MinTankesmie

- Flodbølgen av interessekonflikter

Who watches the watchmen? (Hvem vokter vokteren?)
Nature 2011; 476: 125 (11 August)
Late last month, the US government proposed an overhaul of regulations covering research on human volunteers. It includes a move to allow single institutional review boards (IRBs) to oversee US multi-site clinical trials. Such boards underpin the ethics and safety of a trial, reviewing all research protocols and consent forms before it is launched. Currently, dozens or scores of IRBs — one for each trial site — can separately review and approve a clinical trial and its necessary paperwork, leading to massive duplication of effort and delays. (...)

(Anm: Forskning og ressurser (mintankesmie.no).)

Turning the tide on conflicts of interest (Å snu flodbølgen av interessekonflikter)
Editor's Choice
BMJ 2011; 343:d5147 (10 August)
The US Food and Drug Administration says it may loosen its conflict of interest policies (doi:10.1136/bmj.d5070). A shortage of independent experts means that its current rule—no more than 13% of advisers with industry ties—is delaying the introduction of new drugs, says its commissioner. (...)

Back tracking now on conflicts of interest would send the wrong message, especially to the EMA, which has some catching up to do. It still has a reputation for being more on the industry’s side than the public’s, not helped by its outgoing executive director Thomas Lönngren’s revolving door appointment as an adviser to industry (www.pharmatimes.com/Article/11-01-18/Ex-EMA_chief_joins_new_market_access_business.aspx).

WHO too is vulnerable to criticism on this score. A recent report on its handling of the A/H1N1 influenza pandemic concluded that it had not followed its own rules on conflict of interest and that these needed strengthening (BMJ 2011;342:d3378). Now it is under fire for proposals that would increase industry’s influence on how it sets its priorities (doi:10.1136/bmj.d5012). A word of warning to its director general: back in the 1990s, among those telling WHO to stick to its knitting and focus on infectious diseases in the third world were experts covertly funded by the tobacco industry (BMJ 2000;321:314, doi:10.1136/bmj.321.7257.314).

The FDA should stand firm. Not only is the tide turning in its favour, but strong policies are helping to turn the tide. So here’s a question: should the BMJ repeat the NEJM’s experiment and ban editorials and clinical reviews from authors with ties to industry? I’d welcome your views in rapid responses. (...)

(Anm: Interessekonflikter, bestikkelser og korrupsjon (mintankesmie.no).)

FDA is criticised for hinting it may loosen conflict of interest rules (FDA kritisert for å antyde slakkere krav til interessekonflikter)
BMJ 2011; 343:d5070 (8 August)
The US Food and Drug Administration has come under fire for suggesting that it may loosen conflict of interest rules for its advisers, because of a shortage of experts without ties to the drug and medical devices industry.

The FDA’s commissioner, Margaret Hamburg, said that strict rules on conflict of interest implemented in 2008, which limit the proportion of advisory panellists with industry ties to 13%, may be slowing down approvals of products and hindering innovation.

Dr Hamburg told journalists at a meeting held by the non-profit watchdog Public Citizen in Washington, DC, on 25 July that the agency had to be sure it had “subject-matter experts” “for our important decision making,” reported the online news service Bloomberg News (http://bloom.bg/r2QbrF). (...)

Doctors join protest over change to FDA rules on conflict of interest (Leger slutter seg til protest over FDAs endringer av regler for interessekonflikter)
BMJ 2011; 343:d5269 (18 August)
A doctors’ group has joined a growing number of individuals and organisations protesting against a loosening of rules on conflicts of interest at the US Food and Drug Administration.

The National Physicians Alliance, which represents some 20 000 US medical students and doctors and is based in Washington, DC, sent a strongly worded letter on 7 August to the FDA’s commissioner, Margaret Hamburg, stating that it was “dismayed” to learn of the suggestion of a rule change for its advisers. (...)

Conflict-of-Interest Rules May Be Relaxed in 2012, Hamburg Says (Kan bli slakkere regler for interessekonflikter i 2012, ifølge Hamburg)
bloomberg.com 25.7.2011
Conflict-of-interest rules restricting scientists with financial ties to drug and device-makers from advising U.S. regulators may loosen next year, said Food and Drug Administration Commissioner Margaret Hamburg.

A 2008 policy limiting researchers who were paid by manufacturers from serving on advisory panels may be curtailing feedback the FDA receives, Hamburg told the advocacy group Public Citizen in Washington today. Changes may come through a renewal of the law letting the agency receive fees from companies such as Pfizer Inc. (PFE) for product reviews.

“We have to be sure that FDA has subject-matter experts that we need for our important decision making,” Hamburg said, adding that the agency also must “prevent inappropriate influence or distortion of information” that may compromise reviews. Patient-advocacy groups and academic researchers have expressed “valid concerns” about the conflict-of-interest policy, prompting an agency rules review, she said.

Republicans in Congress and manufacturers have criticized the pace of FDA reviews as too slow, blaming unanticipated requests for safety information from FDA staff and advisers. (...)

- Lobbygrupper ber om offentligjøring av "revolving door" mellom legemiddelkontroller og industrien

Lobby groups call for closure of “revolving door” between drug regulators and industry (Lobbygrupper ber om at "svingdøren" mellom legemiddelkontroller og industrien lukkes)
BMJ 2011;343 (30 December)
The European Commission has been urged to review procedures at the European Medicines Agency (EMA) and the staff regulations that govern the conduct of EU officials, after claims that a former executive director of EMA arranged to become a consultant to the drug industry while still employed by the agency.

Thomas Lönngren, who ran Europe’s drug regulatory agency for 10 years before stepping down at the end of 2010, has already been told by the EMA that he should not provide product related advice to drug companies nor take managerial, executive, or consultative positions in the industry for a period of two years.

But three European activist groups say the agency has done too little to close the “revolving door” through which former regulators become industry advisers paid for their expertise. The Alliance for Lobbying Transparency and Ethics Regulation, Formindep, and Health Action International wrote an open letter last month to John Dalli, the European Commissioner for Health and Consumer Policy, saying that the evidence about Mr Lönngren’s activities demands revisions and tightening of the regulations. (...)

In a letter to the committee from his lawyers, Mr Lönngren said that he would be advising NDA on heath technology assessment and would not be involved in regulatory issues. (...)

Anne Chailleu from Revolving doors, where the regulated become confused with the regulators, are at the core of NDA’s business model.Formindep, a French group that campaigns for independent information and education in healthcare, said: “

“Six out of the ten members of NDA’s advisory board are former regulators at EMA and other regulatory agencies. Industry is exploiting its links to the European regulatory framework. This is damaging the trust that European citizens should place in officials appointed to protect public health.”

The EMA told the BMJ that it was preparing a response to the open letter. (...)

(Anm: NDA (NDA.com).)

(Anm: ALTER-EU The Alliance for Lobbying Transparency and Ethics Regulation. (alter-eu.org).)

(Anm: Formindep (formindep.com).)

- Medisinsk forskning og markedsføring av legemidler og medisinsk utstyr

FDA disagrees with BMJ study that found clinical trials were not being reported
BMJ2012;344:e3277 (8 May)
The US Food and Drug Administration has denied charges made in a study in the BMJ that rules making it mandatory to report clinical trial results are being flouted. The study, published in January by Andrew Prayle and colleagues at the University of Nottingham,¹ calculated that only 22% of the trials that should have reported their results on the ClinicalTrials.gov website had actually done so.

In response to the study Henry Waxman, the Democrat Congressman for part of Los Angeles, wrote to the FDA demanding an explanation. Jeanne Ireland, the FDA’s assistant commissioner for legislation, replied, contesting the figures.

In response to the study Henry Waxman, the Democrat Congressman for part of Los Angeles, wrote to the FDA demanding an explanation. Jeanne Ireland, the FDA’s assistant commissioner for legislation, replied, contesting the figures.

She said that the analysis included some trials that were completed before the law took effect and had not excluded all those, such as uncontrolled trials, that are exempt from the reporting requirements. The list also included some trials of products yet to be approved, which are exempt from the law, and included some for which data had been submitted but not yet vetted by the FDA. In addition, she said, the BMJ authors could not tell from publicly accessible data whether the deadline for reporting had been extended, as the law allows in some cases. She wrote that the FDA was pursuing “individual responsible parties in 15 cases for failure to report on time.”

The FDA’s response to Waxman has not been published but was obtained by Nature under freedom of information legislation.² The BMJ was told by the FDA that it would have to submit a separate freedom of information request of its own to see the letter.

Prayle said that the Nottingham team stands by its findings as the best possible job that could have been done with publicly available information. (...)

The US National Institutes of Health (NIH), jointly responsible with the FDA for enforcing the law, produced an unofficial analysis for Nature of trials that have reported, agreeing with the BMJ analysis that the industry is doing better than government or academia in filing results on time. Industry funded trials were reported on time in 52% of cases, against 21% of those funded by NIH and 14% for NIH funded academic sponsors, the NIH found. The BMJ study found that 40% of industry funded studies reported on time, against 9% of those not solely industry funded. (...)

UK medical device regulation is criticised as both cumbersome and inadequate (Britisk kontroll av medisinsk utstyr kritisert for å være både besværlig og mangelfull)
BMJ 2012;344:e1202 (17 February)
Medical device regulations were criticised last week by manufacturers who make devices and doctors who use them.

At a press briefing on 16 February, manufacturers said the regulations were unnecessarily cumbersome, while doctors criticised them for being inadequate and subject to conflicts of interest. The recent breast implant affair may have brought the issue to public attention, but medical professionals and manufacturers alike say they have been questioning the system for years. (...)

(Anm: The European Medicines Agency (EMA) (tidligere EMEA) (den europeiske legemiddelkontrollen) (mintankesmie.no).)

Partier vil granske Legemiddelverket
aftenposten.no 26.5.2011
Omniscan-saken får etterspill

Høyre, KrF og Frp ber om en uavhengig granskning etter at flere er blitt syke etter bruk av kontrastvæsken Omniscan.

Representanter for samtlige partier i Stortingets helsekomité reagerer på avsløringene i Aftenposten i helgen. Opposisjonen ber om en uavhengig gransking.

I Danmark har helsemyndighetene fått krass kritikk etter at de i 1998 tillot fjerning av en advarsel mot bruk av kontrastmiddelet.

Advarselen ble også fjernet i Norge og en rekke andre land, men advarselen kom tilbake i 2007. Den danske nyreforeningen rapporterer at 80 nyrepasienter er rammet i landet, hvorav ti i dag er døde. På verdensbasis er flere hundre blitt syke. INorge er det registrert åtte ofre. To er døde, hvorav én etter undersøkelse med Omniscan.

Granskes. Nå kan det gå mot en offentlig oppvask i Norge. Leder i helse- og omsorgskomiteen, Bent Høie (H), mener Regjeringen må sørge for en uavhengig undersøkelse av hva som skjedde i Norge. Han fremhever det store antall menneskeskjebner saken angår, men at det også er viktig med en undersøkelse av hensyn til helsevesenets tillit i befolkningen.

Lengst går Fremskrittspartiets nestleder Per Arne Olsen og Kristelig Folkepartis Laila Dåvøy. Begge sier at de vil ha en uavhengig granskning. De vil, som danske politikere, ha svar på hvordan det var mulig å fjerne advarselen. Frps nestleder forbereder et skriftlig spørsmål til helseminister Anne-Grete Strøm-Erichsen (Ap) om dette. (...)

Making raw data more widely available (Å gjøre rådata mer alminnelig tilgjengelig)
BMJ 2011; 342:d2323 (4 May)
New initiative by the Wellcome Trust sets out some guiding principles

Medical investigators routinely refuse to share data from medical studies, seeming to regard such data as private property rather than a public resource for the benefit of medical science and future generations of patients. One survey found that 75% of pharmaceutical researchers were opposed in principle to making raw data available.¹ Two studies have found that only a minority of researchers (10% and 25%) share data when publishing in journals with explicit policies that raw data must be made available.^{2 3} Even in genomics research, where the principle that microarray data should be deposited in a publicly accessible database is widely accepted, many published studies do not have an associated data set publicly available.^{4 5}

The benefits of sharing raw data from medical studies have been widely discussed.^{6 7 8 9} Data sharing ensures reproducibility, allows testing of secondary hypotheses, facilitates development of new statistical methods, provides a resource for teaching, aids design of new studies, simplifies data acquisition for meta-analysis, and helps prevent fraud and selective reporting. (...)

(Anm: Forskning og ressurser (mintankesmie.no).)

Why the FDA can’t protect the public (Hvorfor FDA ikke kan beskytte publikum)
BMJ 2010; 341:c4753 (2 November)
Medical device makers often fail to properly conduct safety studies and the US Food and Drug Administration provides scant oversight. Jeanne Lenzer and Shannon Brownlee look at some of the problems with post approval surveillance of novel devices (...)

Transparency at the Food and Drug Administration (Åpenhet hos Food and Drug Administration (FDA))
healthcarereform.nejm.org 19.5.2010
On his first full day in office, President Barack Obama issued a memorandum calling for “creating an unprecedented level of openness in Government.” The Department of Health and Human Services embraced this goal, and in June 2009, the new commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg, announced a major transparency initiative. The goal of this initiative was to better explain the FDA’s actions by providing information that supports clinical medicine, biomedical innovation, and public health. (...)

Rosiglitazone, marketing, and medical science (Rosiglitazone (Avandia), markedsføring og medisinsk forskning)
BMJ 2010;340:c1848 (7 April)
Feature,doi:10.1136/bmj.c1849 Observations,doi:10.1136/bmj.c1819

Forsøk på å tone ned mulig hjerterisiko for et populært diabeteslegemiddel reiser spørsmål om det trenges fundamentale endringer innen legemiddelkontroll, skriver Ray Moynihan (Attempts to play down the potential cardiac risks of a popular diabetes drug raise questions about the need for fundamental changes in drug regulation, writes Ray Moynihan)

Når du fra sidelinjen følger skjebnen til det storselgende diabeteslegemiddel rosiglitazone (Avandia), kan du ikke unngå å tenke på en Hollywood-thriller. Der er en scene hvor en ledende forsker gjør hemmelige opptak fra et møte med firmaets ledelse, en tung kongressgranskning, og en bitter juridisk kamp som venter i kulissene. Men når du ser nøyere på det er virkeligheten mer underlig enn fiksjon. Det er vist at et nytt og dyrt legemiddel, som øker risikoen for hjertesvikt og er mistenkt for å øke risikoen for hjerteanfall hos millioner av mennesker rundt omkring i verden, holdes på markedet av et industrifinansiert kontrollsystem, til tross for signaler fra ledende sikkerhetseksperter som sier av det bør trekkes fra markedet. Selv benekter legemiddelprodusenten linken til hjerteanfall og peker på bevis som støtter sine påstander. Men detaljene i den virkeligheten som brettes ut tyder nå på en velkjent sammensmeltning av medisinsk forskning og markedsføring av legemidler. (...) (Casually following the fortunes of the blockbuster diabetes drug rosiglitazone (Avandia), you can’t help but imagine a Hollywood thriller. There is the scene where a leading scientist secretly records a meeting with drug company executives, a high powered congressional investigation, and a bitter legal battle waiting in the wings. Yet when you look more closely, the facts are even stranger than fiction. An expensive new drug shown to raise the risk of heart failure and suspected of increasing the chance of heart attacks has been taken by millions of people around the world and is being kept on the market by an industry funded regulatory system, despite calls from senior safety experts to withdraw it. For its part, the drug’s manufacturer strongly denies the link with heart attacks and points to evidence to back its claims. But the details of this unfolding real life drama suggest a now familiar merging of medical science and drug marketing.)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

- EMA anklaget for å sette legemiddelindustriens profitt foran pasienter

EMA accused of putting pharma profits before patients (EMA anklaget for å sette legemiddelindustriens profitt foran pasienter)
pharmatimes.com 11.5.2011
Regulators are "protecting drug company profits rather than the lives and welfare of patients by withholding unpublished trial data", according to researchers in articles published by the BMJ.

They call for full access to full trial reports, both published and unpublished, "to allow the true benefits and harms of treatments to be independently assessed by the scientific community." Peter Gotzsche and Dr Anders Jorgensen from the Nordic Cochrane Centre in Denmark write that despite the existence of hundreds of thousands of clinical trials, "doctors are unable to choose the best treatments because research results are being reported selectively".

They claim that selective reporting can have "disastrous consequences". For example, they say Merck & Co's now-withdrawn painkiller Vioxx (rofecoxib) has "probably caused about 100,000 unnecessary heart attacks in the USA alone, while anti-arrhythmic drugs have probably caused the premature death of about 50,000 Americans each year in the 1980s".

Three-year 'struggle' to get unpublished data
The authors go on to describe what they call a three-year struggle to access unpublished trial reports for two anti-obesity drugs, Sanofi-Aventis now-withdrawn Acomplia (rimonabant) and Roche's Xenical (orlistat), submitted by the manufacturers to the European Medicines Agency.

This information "was important for patients because anti-obesity pills are controversial,” they say, and "people have died from cardiac and pulmonary complications or have experienced psychiatric disturbances, including suicidal events, and most of the drugs have been de-registered for safety reasons".

However, Prof Gotzsche and Dr Jorgensen claim the EMA refused access, arguing that this would undermine "commercial interests and that there was no overriding public interest in disclosure". They also cited the "administrative burden involved and the worthlessness of the data after they had edited them". The authors appealed to the European ombudsman, who criticised the EMA’s refusal to grant access. But only after the ombudsman accused the agency of maladministration did the regulator agree to widen public access to documents.

'Fundamentally wrong'
“There is something fundamentally wrong with our priorities in healthcare if commercial success depends on withholding data that are important for rational decision making by doctors and patients,” say Prof Gotzsche and Dr Jorgensen. They call on other drug regulatory agencies to follow suit and suggest that access should be prompt and that documents should be provided in a useful format to allow for independent scrutiny.

“Drug agencies should get rid of the huge paper mountains and require electronic submissions from the drug companies, including the raw data, which should also be made publicly available,” they conclude.

In an accompanying editorial, researcher Andrew Vickers of the Memorial Sloan-Kettering Cancer Center, New York says "the system is broken and needs fixing". He describes a new initiative by the Wellcome Trust to tackle the problem by developing principles for funders with regard to data sharing, and suggests that the medical research community “get used to it.”

He argues that once medical researchers start publishing their data, and depositing it in data archives, "they will discover not only that it is painless, but that it affords huge advantages to medical science, and to patients present and future." The BMJ added that it believes "systematic efforts are needed to assess this largely unexamined threat to the integrity of evidence-based medicine". (...)

(Anm: Opening up data at the European Medicines Agency. BMJ 2011; 342:d2686 (10 May).)

Opening up data at the European Medicines Agency (Åpn opp for data ved European Medicines Agency)
BMJ 2011; 342:d2686 (10 May)
Widespread selective reporting of research results means we don’t know the true benefits and harms of prescribed drugs. Peter Gøtzsche and Anders Jørgensen describe their efforts to get access to unpublished trial reports from the European Medicines Agency

Doctors cannot choose the best treatments for their patients despite the existence of hundreds of thousands of randomised trials. The main reason is that research results are being reported selectively. Comparisons of published drug trials with unpublished data available at drug regulatory agencies have shown that the benefits of drugs have been much over-rated^{1 2 3} and the harms under-rated.⁴ Comparisons of trial protocols with published papers have also shown widespread selective reporting of favourable results.^{5 6}

Selective reporting can have disastrous consequences. Rofecoxib (Vioxx) has probably caused about 100 000 unnecessary heart attacks in the United States alone,⁷ and class 1 antiarrhythmic drugs probably caused the premature death of about 50 000 Americans each year in the 1980s.⁸ An early trial found nine deaths among patients taking the antiarrhythmic drug and only one among those taking placebo, but it was never published because the company abandoned the drug for commercial reasons.⁹ (...)

- Ute av syne men ikke ute av sinn: hvordan søke etter upubliserte kliniske forsøksbevis

Out of sight but not out of mind: how to search for unpublished clinical trial evidence (Ute av syne men ikke ute av sinn: hvordan søke etter upubliserte kliniske forsøksbevis)
BMJ 2012;344:d8013 (3 January)
A key challenge in conducting systematic reviews is to identify the existence and results of unpublished trials, and unreported methods and outcomes within published trials. An-Wen Chan provides guidance for reviewers on adopting a comprehensive strategy to search beyond the published literature

Summary points (Legemiddelkontroller)
The validity of systematic reviews relies on the identification of all relevant evidence
Systematic reviewers should search for unpublished information on the methods and results of published and unpublished clinical trials
The potential sources of unpublished information on clinical trials have expanded over recent years
Recognition of the strengths and limitations of these key information sources can help to identify areas for further emphasis and improvement

Systematic reviews of randomised trials play a key role in guiding patient care and health policy. Their validity depends to a large extent on reviewers’ ability to retrieve relevant information from all existing trials. Unfortunately, about half of clinical trials remain unpublished after receiving ethics approval—particularly those with statistically non-significant findings.¹ Even when published, most journal articles do not report all of the outcome data or key methodological information.^{2 3} The overall result is that the published literature tends to overestimate the efficacy and underestimate the harms of a given intervention, while providing insufficient information for readers to evaluate the risk of bias. (...)

Regulatory agencies
Regulatory agencies have access to substantially more clinical trial information than the healthcare providers, patients, and researchers who use and evaluate the interventions. Successful attempts to obtain access to regulatory data have previously necessitated litigation and incurred lengthy delays.^{15 16 17} Over recent years, regulatory agencies have recognised the need to address this untenable situation by increasing public access to information from regulatory submissions.^{18 19} (...)

- For å kunne reagere raskt på dødelige sideeffekter trenger FDA interne endringer

To act fast on lethal side effects, FDA needs internal changes (For å kunne reagere raskt på dødelige sideeffekter trenger FDA interne endringer)
GLOBE EDITORIAL (GLOBE-LEDERARTIKKEL)
boston.com 14.6.2010
DERSOM Food and Drug Administration (FDA) håper å få nye legemidler til syke pasienter så raskt som nødvendig, må de nøye overvåke enhver sideeffekt etter opprinnelig testing. Akkurat nå er de mennesker som har ansvaret for overvåkningen de samme som overvåket godkjennelsesprosessen. Denne mangel på kontroll og balanse kan en lett finne et botemiddel mot. Kongressen bør la vaktbikkja som overvåker nylig godkjente legemidler rapportere direkte til lederen for FDA. (IF THE Food and Drug Administration hopes to get new drugs to sick patients as quickly as necessary, it must closely monitor any side effects that might appear after initial testing. Right now, the people overseeing those who monitor the drugs are the same ones who oversaw the approval process. That lack of checks and balances can easily be remedied. Congress should make the watchdogs who oversee newly approved drugs report directly to the FDA commissioner.)

There is reason to believe the FDA acts too slowly when problems appear with recently approved drugs. The agency did not respond promptly to warnings from physicians about the painkiller Vioxx, which the drug company Merck finally pulled from the market in 2004 after it was linked to heart attacks and deaths. Now, critics of GlaxoSmithKline’s diabetes drug Avandia say it should suffer the same fate. In both cases, the FDA failed to heed early warnings from its own staffers responsible for monitoring problems with approved drugs. Those staffers would have a better chance of getting their concerns heard if they reported independently to the commissioner, rather than to the Center for Drug Evaluation and Research. That center handles the initial tests and would be understandably reluctant to second-guess itself.(...)

- Defekte implantater, skumle legemidler og en tannløs vaktbikkje som svikter pasienter

Faulty implants, dodgy drugs and a toothless watchdog that's failing patients (Defekte implantater, skumle legemidler og en tannløs vaktbikkje som svikter pasienter)
dailymail.co.uk 10.1.2012
Just over two years ago consultant plastic surgeon Azhar Aslam became deeply worried — he’d had to remove eight silicone breast implants from women within a few months of each other because they had ruptured prematurely.

It struck him as highly unusual.

‘If implants do rupture, it is normally after seven to ten years, and it is usually caused by an impact, such as the wearer falling over or having a car accident,’ he says.

Last week, the Medicines and Healthcare products Regulatory Agency (MHRA) admitted the safety of breast implants was actually impossible for it to judge
‘But these implants had failed after only two to three years, and the patients had not been involved in any impact.’ (...)

The agency’s initial response to fears over the implants was to say the failure rate was only 1 per cent.

Then, last week, the MHRA admitted the safety of breast implants was actually impossible for it to judge, because an accurate record of the number of procedures has not been kept.

Clinics were blamed for this failing, with Health Secretary Andrew Lansley criticising them for providing ‘poor quality’ data. (...)

Sadly, this is not the first time the agency has been criticised for acting slowly and ineffectually.

In September 2010, for instance, the diabetes drug Avandia was finally banned in Britain after the European Medicines Agency ruled there was a serious risk it could lead to heart attacks or stroke.

Evidence against Avandia had been building since 2007. (...)

The MHRA did not reveal this warning to the public; it simply passed its information on to European authorities.

A few years earlier, media pressure was required to force the MHRA to act over another prescribed-drug danger. Again, it was a GlaxoSmithKline medicine — the antidepressant Seroxat. (...)

Vioxx was withdrawn from the market in the UK four years ago, but only after a 2004 U.S. study found it doubled the risk of heart disease
Then, in 2003, following two BBC Panorama programmes, the drug watchdog mounted its own investigation and discovered the manufacturer had hidden information about the suicide link.

After this, the MHRA said it wanted to require drug makers to share more information about clinical trials — but admitted that, without stronger legislation in place, there was no chance of prosecuting the company for what it called an ‘ethical lapse’.

The watchdog was not only asleep, it was toothless.

Similar problems arose with the arthritis painkiller Vioxx. This was withdrawn from the market in the UK four years ago, but only after a 2004 U.S. study found it doubled the risk of heart disease. Leading cardiologists had been flagging up the risks for years.

After Vioxx’s withdrawal it emerged that data from clinical trials had been ‘fudged’.

The MHRA launched an investigation into whether its maker, Merck, had correctly reported the side-effects of Vioxx to the authorities.

But government prosecutors decided that there was no realistic prospect of a conviction in this case.

The MHRA says the UK laws requiring disclosure of negative drug trial results have since been tightened. No companies have been prosecuted since then.
Yet it’s not just the agency’s supervision of drugs that raises concerns, but medical devices, too.

These include crucial items such as heart pacemakers.

Last May, the British Medical Journal (BMJ) said not enough was being done to check the safety of medical implants.

It says that in 2009 the MHRA received more than 9,000 reports of ‘adverse incidents’ involving medical devices.

More than 1,880 of these involved serious injury and 202 resulted in death. In one case, a patient’s combined pacemaker/defibrillator misfired more than 30 times in one day, delivering huge jolts of 750 volts direct to his heart. ¨

The BMJ has said our regulators are not ‘fit for purpose’ because of their failure to act in patients’ interests.

It is these sorts of problems that have led experts such as Andrew Herxheimer to call for the MHRA to be subjected to ‘root and branch reform’.

Dr Herxheimer is an emeritus fellow of the UK Cochrane Centre and a world leader in examining clinical trials to see how well therapies work.

One problem, says Herxheimer, is that the agency’s role is shrouded in confusion.

‘Its job description has not been defined,’ he says.

‘In fact, it seems to be acting as a rather secretive negotiating agency between the government and the pharmaceutical industry.

‘It is certainly too close to the pharmaceutical industry,’ adds Herxheimer. ¨

‘There appears to be a revolving door with people who have previously worked in the pharmaceutical industry coming to work inside the MHRA. ’

Accusations have long been made that the watchdog is too close to industrial interests, notably when Ian Hudson, who was worldwide safety director of GlaxoSmithKline until 2001, became director of licensing at the MHRA.

Nor have the agency’s actions helped assuage these kinds of concerns. (...)

- Raskere tilgang til nye legemidler?

Speeding up access to new drugs (Raskere tilgang til nye legemidler)
BMJ 2012;344:e999 (17 February)
Plans to cut the time it takes to get innovative treatments into clinical practice are finally to be put out to consultation next month. Nigel Hawkes provides a reminder of the key points

The prime minister promised at the end of last year to give some patients quicker access to new drugs. Was this just an empty aspiration?

No. A lot of thought has been given to a faster access scheme since David Cooksey recommended it in his review of UK health research funding in December 2006. A working group from industry and government produced a plan by November 2009. It sat on a shelf until resurrected two years later.

How would it work?
Medicines that have completed phase III trials (or in exceptional circumstances phase II) and that will treat or prevent life threatening, chronic, or seriously debilitating conditions that lack adequate existing treatments would qualify. Manufacturers would have to apply, and a decision would be promised in 75 days.

How would that be any quicker than licensing, if phase III trials have already been completed?
It usually takes a year or more to get licensing approval after a successful phase III trial. The new process is expected to get these medicines to patients a year earlier than otherwise would be the case.

But doesn’t it mean that proper risk assessment will be skimped?
There’s a danger of that. The burden of risk will be shifted towards the doctor and the patient and away from the manufacturer. Good information will be vital; patients will need to be fully informed and give active consent. Legally, the position will be the same as that for any unlicensed medicine, and the working group believes—but cannot guarantee—that primary care trusts or clinical commissioning groups will not be liable should anything go wrong. And it says that if the decision by a doctor to treat a patient was reasonable in all the circumstances and all relevant information was provided, a successful claim for negligence is unlikely.

If unlicensed medicines can be marketed and sold, what’s the point of licensing?
The medicines under this scheme would be exceptional and few in number, perhaps only one or two a year. The NHS already uses unlicensed or off-label medicines in some cases, on the authority of the prescribing doctor (for example, bevacizumab for age related macular degeneration). Patients consulted by the working group were confident that they were competent to make a proper assessment of the risks. Doctors were not so sure. (...)

- FDA saksøkt for overvåkning av ansatte

FDA staffers sue agency over surveillance of personal e-mail (FDA-medarbeidere saksøker kontrollorganet for overvåkning av personlig e-post)
washingtonpost.com 30.1.2012
The Food and Drug Administration secretly monitored the personal e-mail of a group of its own scientists and doctors after they warned Congress that the agency was approving medical devices that they believed posed unacceptable risks to patients, government documents show.

The surveillance — detailed in e-mails and memos unearthed by six of the scientists and doctors, who filed a lawsuit against the FDA in U.S. District Court in Washington last week — took place over two years as the plaintiffs accessed their personal Gmail accounts from government computers. (...)

Copies of the e-mails show that, starting in January 2009, the FDA intercepted communications with congressional staffers and draft versions of whistleblower complaints complete with editing notes in the margins. The agency also took electronic snapshots of the computer desktops of the FDA employees and reviewed documents they saved on the hard drives of their government computers. (...)

FDA is sued for allegedly violating privacy of employees (FDA er saksøkt for angivelig brudd på personvern for ansatte)
BMJ 2012;344:e784 (1 February)
Six current and former employees of the US Food and Drug Administration (FDA) have sued that agency for allegedly violating their right to privacy by secretly monitoring their personal email activity. The doctors and scientists reviewed medical devices for the agency as part of the approval process.

Among the monitored activity were complaints to congressional staff members about the safety and efficacy of medical devices the agency approved, over objections from the employees.

The employees say they were harassed, terminated, or did not have their contracts as outside consultants renewed because of their contacts with those staff members. They claim they are covered under the Whistleblower Protection Act of 1989 that protects federal employees who report misconduct.
The FDA Center for Devices and Radiological Health began its internal investigation into the employees over concern for the potential release of confidential information. Its request for a formal investigation by the inspector general of the Department of Health and Human Services was twice denied. The FDA has a policy of not commenting on ongoing litigation.

“Who would have thought they [FDA] would have the nerve to be monitoring my communications to Congress?” Robert C Smith, MD, JD, told the Washington Post. “How dare they?” (www.washingtonpost.com/world/national-security/fda-staffers-sue-agency-over-surveillance-of-personal-e-mail/2012/01/23/gIQAj34DbQ_story.html).

Dr Smith is one of the litigants suing the agency. The radiologist was earlier employed by Cornell University and Yale University where he was “forced out” of his position in 1999. [legal document www.ctd.uscourts.gov/Opinions/021006.PCD.Smith.pdf ]. He sued both universities. He also serves on the board of directors of the National Whistleblowers Center.

But it is not clear whether Dr Smith is correct in his assertion of privacy. US law says that employers have the right to monitor electronic communications that are conducted using property owned by the employer, such as computers and cell phones. Government computers have a standard opening screen reminding the user that they have “no reasonable expectation of privacy” on that machine.

It is alleged that the FDA investigation used “screen capture” software to record everything that the user viewed while on the job, including personal email. It did not access the hard drive of personal computers at home.

The software is the same tool the FDA used to gain information and prosecute former employees who made millions of dollars on stock trades based on insider information of the devices they were reviewing. Insider trading is illegal.

An outside expert with knowledge of the situation, who would talk only on background, said the dispute was more of a personnel issue than a policy matter. The agency needs better procedures and processes on how internal disagreements are resolved.

Last summer the Institute of Medicine recommended legal changes in the way devices are reviewed and regulated by the Food and Drug Administration. www.iom.edu/Reports/2011/Medical-Devices-and-the-Publics-Health-The-FDA-510k-Clearance-Process-at-35-Years.aspx. (...)

- Leger krever uhildet viten om legemidler

Læger kræver uvildig viden om medicin (Leger krever uhildet viten om legemidler)
b.dk 28.11.2011
Lægemiddelindustrien driver og finansierer lægernes vigtigste opslagsværk om medicin. Det vil lægerne stoppe.

Læger skal have nem adgang til uvildig information om lægemidler, som ikke kan mistænkes for at være styret af lægemiddelindustrien.

Lægeforeningen opfordrer nu sundhedsminister Astrid Krag (SF) til at etablere et nationalt videncenter, som sikrer sundhedspersonale adgang til de nødvendige oplysninger.

I dag er lægers primære kilde til viden om medicin opslagsværket promedicin.dk, som ejes og drives af medicinalindustrien.

- Det er fagligt stærkt og brugervenligt, men signalet er simpelthen forkert. Det er uholdbart, at medicinalindustrien ejer det mest benyttede opslagsværk om lægemidler, siger Lægeforeningens formand, Mads Koch Hansen, og fortsætter:

- Det er afgørende, at patienter og læger har tillid til, at de får uvildig rådgivning. Det sikres bedst, hvis en offentlig myndighed er garant for informationen.

Lægeforeningen opfordrer derfor sundhedsministeren til at etablere et videncenter, der samler ekspertisen fra flere myndigheder og råd, som i dag vurderer lægemidler.

Mads Koch Hansen peger på, at finansloven afsætter midler til at lave faglige retningslinjer for bedste behandling af de enkelte sygdomme. Det betyder også, at eksperter skal fordybe sig i brugen af lægemidler.

- Derfor håber vi på sundhedsministerens forståelse for, at retningslinjerne kan kobles sammen med en uvildig medicininformation, siger Mads Koch Hansen.
I en undersøgelse for nylig blandt praktiserende læger sagde 9 ud af 10 nej til industribetalte oplysninger om medicin og bivirkninger. 85 procent ønskede, at det offentlige overtager driften af promedicin.dk.

Undersøgelsen kom i kølvandet på afsløring af, at promedicin.dk var et år om at opdatere opslagsværket med vigtige oplysninger om, at gravides ufødte børn risikerede alvorlige bivirkninger ved en række lykkepiller. (...)

- GAO (Government Accountability Office): FDA trenger bedre planer for å beskytte folkehelsen

GAO: FDA Needs Better Plans To Protect Public Health (GAO: FDA trenger bedre planer for å beskytte folkehelsen)
online.wsj.com 23.3.2010
WASHINGTON (Dow Jones)--Den amerikanske legemiddelkontrollen (U.S. Food and Drug Administration) møter betydelige utfordringer når det gjelder planlegging og forvaltning som kan påvirke dets evne til å beskytte folkehelsen, ifølge en rapport som ble publisert tirsdag av Government Accountability Office. (The U.S. Food and Drug Administration is facing significant planning and management challenges that could affect its ability to protect the public health, according to a report to be released Tuesday by the Government Accountability Office.)

The report says the FDA needs to do a better job of recruiting employees, modernizing its information systems and keeping pace with scientific (...)

FDA Needs A Decade To Rebuild: Chief Scientist (FDA trenger et tiår for å gjenoppbygges ifølge ledende forsker)
By Ed Silverman
pharmalot.com 25.3.2010
Dersom du er bekymret over FDAs problemer er du er ikke alene. Kontrolloganets ledende forsker, Jesse Goodman, forteller en kongresskomite at FDA trenger et tiår for å kunne gjenopprette tapt ære. (If you were concerned there are problems at the FDA, you’re not alone. The agency’s chief scientist, Jesse Goodman, tells a Congressional committee that the FDA needs a decade to restore itself to its past glory.)

“I think what FDA really needs is a 5- to 10-year building effort/re-building effort. And it’s not just rebuilding to what it was. I think it’s being a part of building the science of the future,” Goodman told a Capitol Hill briefing on the FDA’s scientific progress, according to The Pink Sheet. (...)

Risker med Vioxx kända tidigt
lakemedelsvarlden.se 24.11.2009
Redan fyra år innan det antiinflammatoriska Vioxx togs av marknaden fanns data som visade på risker med läkemedlet. Efter en analys av 30 studier av preparatet menar forskare att tydliga tecken visade att risken för hjärt-kärlrelaterade problem ökade med behandlingen.

Det är amerikanska forskare som har gått igenom 30 randomiserade placebokontrollerade studier av rofecoxib, den aktiva substansen i läkemedlet Vioxx. (...)

Menforskarna bakom den nya analysen, som publicerats i Archives of Internal Medicine, en av JAMA-publikationerna, menar att riskerna med läkemedlet var kända redan flera år tidigare. Analysen innefattar totalt 20 152 patienter och studierna har varat från fyra veckor till fyra år. De doser som getts har varit mellan 12,5 till 50 mg. (...)

(Anm: Bringing the FDA's Information to Market. Arch Intern Med. 2009;169(21):1985-1987 (November 23).)

Lost in Transmission — FDA Drug Information That Never Reaches Clinicians (pdf) (Borte på veien - FDA-informasjon som aldri når frem til leger)
NEJM 2009 (October 21st)
(...) The most direct way that the FDA communicates the prescribing information that clinicians need is through the drug label. Labels, the package inserts that come with medications, are reprinted in the Physicians’ Desk Reference and excerpted in electronic references. To ensure that labels do not exaggerate benefits or play down harms, Congress might have required that the FDA or another disinterested party write them. But it did not. Drug labels are written by drug companies, then negotiated and approved by the FDA. (...)

Information Lost Between Review and Drug Label
medpagetoday.com 21.10.2009
Want to know if the FDA really really liked a new drug? Or if the agency's reviewers held their noses and approved it despite reservations? (...)

FDA approval doesn't mean a drug works well, they reported online in the New England Journal of Medicine: "It only means the agency deemed its benefits to outweigh its harms."

But that determination can be hard to make, and the "nature -- or even existence -- of reviewer uncertainty is not addressed in the (drug) label," Schwartz and Woloshin argued.

At least part of the problem, they said, is that drug labels and package inserts are typically written by the drugmakers, not the FDA, with final language arrived at through negotiation with the agency. (...)

Pfizer's $2.3 Billion-Dollar Settlement (Pfizers 2,3 milliarder dollar forlik)
forbes.com 9.9.2009
Et rekordstort krav reiser enkelte alvorlige spørsmål om FDA. (...) (A record-breaking claim raises some serious questions about the FDA.)

Scientists and doctors ask Obama to investigate "wrongdoing" at the FDA (Forskere og leger ber Obama granske "ulovligheter" innen FDA)
BMJ 2009;338:b1483 (14 April)
Nine doctors and scientists at the US Food and Drug Administration (FDA) sent a letter to President Barack Obama on 2 April, saying they wanted "to draw your attention to the frustration and outrage that FDA physicians and scientists, public advocacy groups, the press, and the American people, have repeatedly expressed over the misdeeds of FDA officials."

They sent a copy of the letter to Senator Charles Grassley, a Republican from Iowa, who posted it on his committee’s website with the names of the signatories blacked out. The letter is similar to one that nine people sent to President Obama’s transition team in January before he took office. (...)

The letter from the scientists can be seen at http://grassley.senate.gov/news/press_releases.cfm (...)

A To-Do List for the New FDA Commissioner
NEJM 2009 (March 14) (10.1056/NEJMp0810755)
A week before President Barack Obama's inauguration, the departing commissioner of the Food and Drug Administration (FDA), oncologist Andrew von Eschenbach, compared the agency he has led for the past 3 years to a person with cancer. (...)

Testifying last year before a House subcommittee, Science Board chair Gail Cassell said, "We conclude that American lives are at risk and that there is an urgent need to address the deficiencies." A series of high-profile incidents — related to the FDA's handling of information about the risks associated with drugs such as rofecoxib and antidepressants; the adulteration or contamination of imported ingredients in heparin, pet food, and other products; the agency's politically motivated delay in approving over-the-counter access to "Plan B" emergency contraception; and a series of major food-poisoning outbreaks — have damaged the FDA's credibility. It is perceived as slow to act, secretive, and subject to influence by political and corporate interests. (...)

Dissident US FDA scientists tell Obama: “we’re under criminal investigation” (Forskere med avvikende meninger forteller Obama: "vi etterforskes")
pharmatimes.com 30.1.2009
Nine scientists at the US Food and Drug Administration (FDA) who claimed to Congress that illegal activities were ongoing at the agency have written to President Barack Obama, telling him they believe they are now under criminal investigation.

In early January, the group of scientists wrote to the Obama Administration’s transition team describing their concerns, which specifically relate to the agency’s scientific review process for medical devices. Staff working on the reviews were being forced by their managers to manipulate data, thus endangering patient safety, said the scientists, who claimed the system had been “corrupted and distorted by current FDA managers, thereby placing the American people at risk."

"Ifølge forskerne frykter ærlige ansatte stemningen innen FDA, og beskriver systemet som "fundamentalt ødelagt". (“There is an atmosphere at the FDA in which the honest employee fears the dishonest employee,” they said, and described the FDA as “fundamentally broken.”) (...)

- Rapport: FDA utøver for lite oppsyn med forskernes interessekonflikter

Report: FDA Exerts Too Little Oversight of Researchers’ Conflicts of Interest (Rapport: FDA utøver for lite oppsyn med forskernes interessekonflikter)
JAMA. 2009;301(7):709-710. (February 18)
The US Food and Drug Administration (FDA) is doing too little to identify and mitigate the impact of financial conflicts of interest among researchers who conduct clinical trials of experimental drugs, biologics, and medical devices, according to a report released in January by the Department of Health and Human Services' Office of Inspector General (OIG).
Despite a 1999 regulation that requires a drug or device manufacturer to disclose the financial interests of clinical trial investigators when the company submits an application to market a product, nearly 42% of the 118 applications approved by the FDA in 2007 lacked complete financial information, the report said (http://www.oig.hhs.gov/oei/reports/oei-05-07-00730.pdf). Even when such information was disclosed, FDA reviewers often did not document that they had investigated the potential impact of such conflicts on trial data. (...)

(Anm: THE FOOD AND DRUG ADMINISTRATION’S OVERSIGHT OF CLINICAL INVESTIGATORS’ FINANCIAL INFORMATION. Office of Inspector General (OIG). (OEI-05-07-00730) (January 2009).)

- Sikkerheten settes på sidelinjen — FDAs mangelfulle respons til IOM

GAO: FDA Yet to Make Safety Changes post-Vioxx
pharmpro.com 9.12.2009
WASHINGTON (AP) — The Food and Drug Administration still hasn't restructured its staff to better monitor drug safety, more than three years after experts recommended key changes in the wake of the Vioxx scandal.

That's according to congressional investigators who found that the FDA has yet to follow through on changes suggested in 2006 to help the agency detect problems with drugs taken by millions of Americans. Those recommendations came after the embarrassing and dangerous episode with Vioxx, a blockbuster pain drug the FDA approved in 1999, only to pull from the market in 2004 after linking it to heart attack and stroke.

Agency officials have made some changes to drug oversight, according to a Government Accountability Office report, but the FDA continues to give the bulk of its decision-making power to scientists who approve new drugs, rather than those who monitor the side effects of drugs on the market. (...)

FDA kritiseras för dålig kontroll
lakemedelsvarlden.se 28.10.2008
FDA får skarp kritik i en rapport till amerikanska kongressen. Övervakningen av fabriker som tillverkar läkemedel är undermålig och de som varnats följs inte upp.

KRITIK Den amerikanska läkemedelsmyndigheten, FDA, klarar inte övervakningen av de fabriker som tillverkar läkemedel till den amerikanska befolkningen. Kritiken kommer från GAO (Government Accountability Office) som i sin rapport detaljerat visar hur FDA misslyckats med sina inspektioner. (...)

F.D.A. to Expand Scrutiny of Risks From Drugs After They’re Approved for Sale
nytimes.com 23.5.2008
(...) The new system, called the Sentinel Initiative, will allow officials from the Food and Drug Administration for the first time to monitor almost immediately how drugs affect health. As it stands now, months or even years must pass before officials learn of unexpected side effects that can cost dozens or even thousands of lives. (...)

Americans Confused About FDA and Drug Safety (Amerikanere forvirret over FDA og legemiddelsikkerhet)
healthfinder.gov 21.9.2007
Poll finds many mistrust the job the agency is doing. (Meningsmåling avdekker mistillit til hvordan byrået arbeider.)

(SOURCES: James Thurber, Ph.D., director, Center for Congressional and Presidential Studies, American University, Washington, D.C.; A. Mark Fendrick, M.D., professor, internal medicine, University of Michigan School of Medicine, and professor, health management and policy, University of Michigan School of Public Health, Ann Arbor; Peter Lurie, M.D., deputy director, Public Citizen's Health Research Group, Washington, D.C.; Sept. 19, 2007, news release, Consumers Union; Sept. 20, 2007, Prescription Drug Safety: National Survey)

THURSDAY, Sept. 20 (HealthDay News) -- Although millions of Americans depend on prescription medicines for health, many are confused and distrustful of government's role in keeping those medicines safe, a new survey finds.

In fact, many of those polled said they didn't understand how the U.S. Food and Drug Administration approves drugs, and almost half judged the agency's performance as poor. (...)

In the meantime, however, Americans remain unsure about drug safety and the FDA's record so far. Some key findings from the new survey, which was funded by by a grant from pharmaceutical giant Pfizer:
• Most Americans (64 percent) believe that the U.S. health care system is "broken."
• More than three-quarters believe a candidate's position on drug safety is "somewhat important" in choosing the next president.
• A vast majority of Americans (88 percent) are confident that prescription drugs made in the United States are safe. In contrast, only 56 percent think that drugs made in Canada and Europe are safe, and only 14 percent think that drugs made in China and India are safe. Many of the drugs sold in the United States are made in China and India, Thurber noted.
• Eighty-two percent of those polled said they trust the FDA when it comes to overseeing prescription drugs, 74 percent trust patient-advocate groups, 67 percent trust pharmaceutical companies, and 53 percent trust Congress.
• A full 50 percent of Americans are skeptical of the ability of Congress to pass "common-sense" laws on how the FDA approves drugs, however. "Only 6 percent trust Congress to do the right thing," Thurber said. (...)

Sidelining Safety — The FDA's Inadequate Response to the IOM (Sikkerheten settes på sidelinjen — FDAs mangelfulle respons til IOM)
Sheila Weiss Smith, Ph.D.
NEJM 2007;357:960-963 (September 6)
Having been commissioned by the Food and Drug Administration (FDA) to evaluate the U.S. drug-safety system, the Institute of Medicine (IOM) published a report, The Future of Drug Safety, in September 2006 identifying weaknesses in the laws, regulations, resources, and practice of ensuring drug safety.¹ Some of the IOM's recommendations were directed toward Congress, which it believed should increase FDA funding and regulatory authority. Some outlined ways in which other federal agencies could work in partnership with the FDA for the public good. But most of the report outlined deficiencies that the FDA itself — or the Department of Health and Human Services (DHHS), to which it belongs — should correct.

In general, the IOM implored the agency to "embrace a culture of safety" by increasing the priority accorded to the safety of patients. Such an emphasis could have ramifications for medical care that would be as broad and positive as those that the 1999 IOM report on medical error, To Err Is Human,² has had for the health care system. Sadly, the FDA's official response falls far short of what the American public expects and deserves.³ Indeed, it highlights the very reason that the agency — with which I have had some firsthand experience — is in need of monumental change: its philosophy is no longer aligned with its regulatory mandate. (...)

FDA stands accused of giving safety too low a priority (FDA er anklaget for å gi sikkerhet lav prioritet)
pharmatimes.com 7.9.2007
Just shy of a year since the US Institute of Medicine implored the Food and Drug Administration to “embrace a culture of safety”, an article in the latest New England Journal of Medicine says that the agency’s response shows a lack of understanding of the problems. (...)

- FDA-forskere anklager tilsynsledere for tjenesteforsømmelse (ber Obama granske "ulovligheter")

F.D.A. Scientists Accuse Agency Officials of Misconduct (FDA-forskere anklager tilsynsledere for tjenesteforsømmelse)
Nytimes.com 17.11.2008
WASHINGTON — Top federal health officials engaged in “serious misconduct” by ignoring concerns of scientists at the Food and Drug Administration and approving for sale unsafe or ineffective medical devices, the scientists have written in a letter to Congress.

“These allegations are deeply concerning,” said the committee chairman, Representative John D. Dingell, Democrat of Michigan, “and we intend to uncover whether any F.D.A. activity has compromised the health and safety of American consumers.”

Heidi Rebello, an agency spokeswoman, said, “The F.D.A. will respond directly to the committee’s concerns.”

The letter to Congress, dated Oct. 14, is part of a growing chorus of dissent from what had long been a tight-lipped agency. In decades past, scientists rarely disagreed publicly with their agency’s decisions, and any concerns they had about important decisions were whispered among veterans. (...)

- FDA avdekker at amerikansk firma som driver legemiddelforskning forfalsket dokumenter

FDA finds U.S. drug research firm faked documents (FDA avdekker at amerikansk firma som driver legemiddelforskning forfalsket dokumenter)
reuters.com 26.7.2011
(Reuters) - Drug companies that had medicines tested by contractor Cetero Research might have to reevaluate results, U.S. regulators warned after the firm was found faking documents and manipulating samples.

The Food and Drug Administration said on Tuesday two 2010 inspections, an internal company investigation and a third-party audit uncovered "significant instances of misconduct and violations" at a Cetero facility in Houston.

The Cary, North Carolina-based firm does early-phase clinical research and bioanalytics for a number of drugmakers. The pharmaceutical companies can then use those studies as supporting evidence in drug approval applications to the FDA.

"The pattern of misconduct was serious enough to raise concerns about the integrity of the data Cetero generated during the five-year time frame," the FDA said, warning drugmakers they might have to repeat or confirm any studies Cetero did in support of their applications between April 2005 and June 2010.

It remains unclear which drugmakers have used Cetero's services to apply for regulatory approvals and the FDA is asking companies to identify such instances. The regulators said the measure is precautionary and the safety and efficacy of drugs already on the market are unlikely to be affected.

The FDA inspected Cetero in May and December last year and found falsified records about studies.

Specifically, in at least 1,900 instances between April 2005 and June 2009, laboratory technicians identified as conducting certain studies were not actually present at Cetero facilities at that time, the FDA said in its May report.

The FDA also said at the time that Cetero might have "fixed" studies to get the desired result, or did not include failed results in their report.

"Cetero's May 2010 and December 2010 responses are inadequate because the scope of their internal investigation was far too narrow to identify and adequately address the root cause of these systemic failures," the regulators said.

Cetero was not immediately available for comment. (...)

- Den britiske legemiddelkontrollen ødelegger alle bevis etter 15 år

UK drug regulator destroys all evidence after 15 years (Den britiske legemiddelkontrollen ødelegger alle bevis etter 15 år)
BMJ 2011; 343:d4203 (5 July)
Jørgensen and I recently gained access to clinical study reports and trial protocols of placebo controlled trials at the European Medicines Agency (EMA).¹ Some drugs, however, have not been approved centrally, and in such cases the EMA advises contacting the relevant national drug agencies.

For the antidepressant drug fluoxetine, the United Kingdom acts as Reference Member State according to the Mutual Recognition Procedure in the European Union. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has, however, informed us that it no longer holds the requested reports:

Under MHRA record management policy, all application files and data for licences are held for 15 years. After this period, files are destroyed unless there is a legal, regulatory, or business need to keep them, or unless they are considered to be of lasting historic interest.

Legal or historic interest? How ironic. Court cases have shown serious scientific misconduct in placebo controlled industry sponsored trials of antidepressant drugs including fluoxetine—for example, recoding suicidal events as “emotional lability,” “hospital admission,” “lack of effect,” or “drop-out” while patients were taking the drugs and adding suicides to the placebo group that had not occurred while the patients were taking placebo.^{2 3}

Despite these manipulations, selective serotonin reuptake inhibitors as a drug class increase the risk of suicide in children and adolescents.^{2 3} But the action of the MHRA may mean that it is impossible for independent researchers to correct the seriously flawed publication record on fluoxetine, which, ironically, is the only drug approved for use in childhood depression.

I have asked the UK Department of Health and the EMA how we can obtain the data the MHRA has destroyed, and I suggest legislation be introduced to prevent the MHRA from destroying the evidence in future. Lack of space is no excuse because the documents can be scanned. (...)

- TGA told to open up and get on front foot

TGA told to open up and get on front foot
theaustralian.com.au 21.7.2011
AUSTRALIA'S medicines watchdog is set for a shake-up after an inquiry criticised its secrecy and inefficiency.

An eight-month investigation into the Health Department's Therapeutic Goods Administration has called on the industry-funded regulator to publish the results of all its safety investigations, and improve the way it gathers and reports the side-effects of medicines and vaccines.

The inquiry's report, released yesterday, says the TGA should investigate putting a new "black triangle" logo on the packets of all new medicines, to warn the public that the safety of newly approved drugs has yet to be proven in the marketplace.

It concludes that Australians know more about US regulator the Food and Drugs Administration than their own TGA.

"It's a worry," said the head of the inquiry, former commonwealth ombudsman Dennis Pearce. (...)

- Health Affairs sier at FDA bør offentliggjøre sikkerhetsdata

FDA Should Release Safety Data, Health Affairs Commentary States (Health Affairs sier at FDA bør offentliggjøre sikkerhetsdata)
kaisernetwork.org 7.3.2007
FDA should release more detailed information about clinical trial data so that it can be used by independent researchers for further safety study, according to a commentary published on Tuesday in Health Affairs, Dow Jones reports. The authors, Aaron Kesselheim of Brigham & Women's Hospital and Michelle Mello of Harvard School of Public Health, dispute the belief that releasing more detailed safety data would jeopardize corporate secrets, and in the commentary they recommend "placing a heavier burden of proof on companies to show competitive harm if data are released." Currently, FDA releases a summary of safety issues associated with clinical trials of approved drugs but withholds the raw data over concerns that more detailed information "could enable competitors to more easily copy ... drugs or create similar versions," Dow Jones reports (Brickates Kennedy, Dow Jones, 3/6). (...)

An abstract of the commentary is available online. (...)

Researchers say FDA increases public risks by delaying safety data release (Forskere sier FDA øker folks risiko ved å forsinke frigivning av sikkerhetsdata)
boston.com 6.3.2007
WASHINGTON -- Heart problems that pushed the painkillers Bextra and Vioxx off the market could have come to light earlier had federal regulators given outside researchers speedier access to raw safety data, according to a commentary written by Boston researchers. (...)

Analysis: New call for FDA openness
UPI Senior Medical Correspondent
upi.com 6.3.2007
WASHINGTON, March 6 (UPI) -- Two researchers Tuesday urged a change in U.S. Food and Drug Administration policies to allow the scientific community access to pharmaceutical manufacturers' clinical trial data in order to help reveal safety issues with new drugs. (...)

Taking the Wraps Off Drug Safety Data From Clinical Trials
docguide.com 6.3.2007
BOSTON, MA -- March 6, 2007 -- For years, pharmaceutical companies have sought to restrict public access to drug safety data collected in clinical trials on the basis that it is proprietary information, arguing that competitors could use that information in the development of their own products. However, a number of recent cases of drugs found to have dangerous side effects after coming to market, such as the anti-inflammatory drug rofecoxib (Vioxx), have raised concerns about safety data being treated as confidential. (...)

FDA fails public, doctor says
cleveland.com 14.2.2007
Washington - A prominent Cleveland Clinic cardiologist on Tuesday accused the Food and Drug Administration of making inappropriate concessions to the pharmaceutical industry that put dangerous drugs on the market and let sales continue after safety questions were raised. (...)

U.S. Lawmakers Blast FDA Drug Safety Oversight
medscape.com 13.2.2007
WASHINGTON (Reuters) Feb 13 - U.S. lawmakers criticized the Food and Drug Administration's monitoring of the risks of a Sanofi-Aventis antibiotic and some other prescription drugs on Tuesday. (...)

F.D.A. Widens Safety Reviews on New Drugs
nytimes.com 31.1.2007
The Food and Drug Administration announced changes yesterday that were intended to ensure that marketed drugs are as safe as advertised, including the first effort to do a comprehensive assessment of the safety of drugs 18 months after introduction. (...)

FDA Reinforces Commitment to Drug Safety
fda.gov 30.1.2007
Progress Underway, New Initiatives Announced in Response to Institute of Medicine Recommendations (...)

Stor reform av läkemedelskontrollen på väg i USA
Läkemedelsvärlden 2006(11) (November)
(...) Alla har gått och väntat på vad Institute of Medicine skulle föreslå. Kanske en klyvning av FDA, med en myndighet för godkännande av nya läkemedel, en annan del för övervakning? (...)

Blueprint for a Stronger Food and Drug Administration
N Engl J Med 2006;355:1821 (October 26)
Over the past 5 years, a series of recalls of high-profile prescription medications has aroused serious concern about the safety of the nation's drug supply. Faced with a crisis of confidence, the Food and Drug Administration (FDA) in 2004 called on the Institute of Medicine (IOM) of the National Academies to conduct a comprehensive review of the safety of prescription drugs. The IOM assembled a distinguished review committee, and after nearly a year and a half of deliberations, a draft of the committee report became public on September 21, 2006 (www.iom.edu/CMS/3793/26341/37329.aspx). The committee recommends a number of specific reforms that we believe should serve as a blueprint for a stronger system of drug regulation. The reforms are discussed by Psaty and Burke in this issue of the Journal.¹ (...)

Protecting the Health of the Public — Institute of Medicine Recommendations on Drug Safety
B.M. Psaty and S.P. Burke
Free Full Text
An audio interview with Dr. Bruce M. Psaty (...)

FDA isn't keeping Americans safe
Editorial
roanoke.com 11.10.2006
Serious steps need to be taken to force the agency to undergo serious reform. (...)

FDA under fire again on drug safety
pharmatimes.com 11.10.2006
Five leading clinicans have added their voice to criticism of the US Food and Drug Administration's record on drug safety in an editorial published in the journal Archives of Internal Medicine.

The critics say the FDA lacks authority to fulfil its function because it cannot order drugs off the market, required label changes or issue sanctions against pharmaceutical companies that fall foul of its recommendations. (...)

Report Faults FDA on Drug Safety (Rapport finner feil ved FDAs legemiddelsikkerhet)
washingtonpost.com 10.10.2006
Five experts who have advised the Food and Drug Administration on drug safety yesterday threw their weight behind mounting criticism that the agency does not adequately protect the public from unsafe drugs. (...)

"The FDA has for the past decade been aware of these problems; they've done very little to fix them," said Curt D. Furberg, a professor of medicine at Wake Forest University and a member of the drug safety advisory panel.

Joining Furberg in the critical paper were current panelists Robyn S. Shapiro and Arthur A. Levin, and former members Peter A. Gross and Brian L. Strom. (...)

FDA Should Implement IOM Recommendations on Prescription Drug Safety NEJM, Editors Say
kaisernetwork.org 10.10.2006
FDA should implement recommendations from a recent Institute of Medicine report on the safety of new prescription drugs in the U.S., New England Journal of Medicine editors Gregory Curfman, Stephen Morrissey and Jeffrey Drazen write in an editorial in the journal, the Newark Star-Ledger reports. (...)

According to Curfman, Morrissey and Drazen, a series of safety issues with prescription drugs in the past several years has created "a crisis of confidence" among the public and requires "definitive action" on the part of federal leaders. In addition, the editors in a statement said, "The committee recommends a number of specific reforms that we believe should serve as a blueprint for a stronger system of drug regulation." They said the IOM report is "a crucial starting point" and urged Congress "to implement its recommendations and give them the highest priority." Bruce Psaty, an author of the IOM report and a physician-researcher at the University of Washington, in an NEJM "Perspective" piece said, "The key point is the ongoing effort to assess risk and to acquire information in a timely manner so that we can be informed and respond appropriately." (...)

Expert Critique Says FDA Does Not Adequately Protect Consumers From Unsafe Drugs, Calls for Agency Changes
kaisernetwork.org 10.10.2006
FDA-mandated studies on prescription drugs can miss serious safety issues before and after a drug's approval, according to five current and former members of the agency's Drug Safety and Risk Management Advisory Committee, the Washington Post reports. (...)

Blueprint for a Stronger Food and Drug Administration
EDITORIAL
New England Journal of Medicine (NEJM) (2006 October 9)
Over the past 5 years, a series of recalls of highprofile prescription medications has aroused serious concern about the safety of the nation’s drug supply. Faced with a crisis of confidence, the Food and Drug Administration (FDA) in 2004 called on the Institute of Medicine (IOM) of the National Academies to conduct a comprehensive review of the safety of prescription drugs. The IOM assembled a distinguished review committee, and after nearly a year and a half of deliberations, a draft of the committee report became public on September
21 (www.iom.edu/CMS/3793/26341/37329.aspx). The committee recommends a number of specific reforms that we believe should serve as a blueprint for a stronger system of drug regulation. (...)

Protecting the Health of the Public -- Institute of Medicine Recommendations on Drug Safety
New England Journal of Medicine (NEJM) (2006 October 9)
(...) According to the 2003 report of the Office of Inspector General of the Department of Health and Human Services,³ a survey of CDER reviewers revealed that 66% lacked confidence in the FDA’s safety monitoring of marketed prescription drugs, and 18% had felt pressure to approve a drug despite reservations about its quality, efficacy, or safety. In 2006, the Government
Accountability Office found that the “FDA lacks clear and effective processes for making decisions about, and providing management oversight of, postmarket
safety issues.”⁴ (...)

Los Angeles Times Examines FDA Funding Levels
kaisernetwork.org 10.10.2006
An FDA study on the cardiovascular risks of attention deficit hyperactivity disorder drugs might be "halted in midstream" because the "agency doesn't have the money to finish it," the Los Angeles Times reports. According to the Times, the "threat to the study ... stems from chronic shortchanging of the nation's drug safety program" and "is one symptom of a federal agency increasingly constrained by a budget that has failed to keep up with costs." FDA has earmarked $1.6 million this year for postmarket drug safety studies, with funding expected to drop to $900,000 next year. Experts estimate that FDA needs $20 million to $100 million annually to conduct such studies. A recent report from an Institute of Medicine panel found that FDA funding for drug safety is "especially inadequate, [and] resource limitations have hobbled the agency's ability to improve and expand this essential component of its mission." (...)

(Anm: FDA Budget Malnourished. latimes.com 7.10.2006.)

Eroding faith in the FDA
EDITORIAL
journalonline.com 26.9.2006
Restore funding, focus for strict drug-safety testing

It should be unthinkable that a medication prescribed to heal could do more harm than good. Drugs have always had side effects, but what patient would consent to take a drug for a relatively minor condition -- say, acne -- if he knew the medication could be fatal?

At the very least, patients should know what they're taking, and what the possible dangers are. And at one time, they could have confidence that the Food and Drug Administration was the strictest drug safety agency in the world. (...)

IOM Report Calls on FDA To Improve Consumer Safety; Recommendations Include Restrictions on Prescription Drug Advertisements, Increased Post-Market Drug Reviews
kaisernetwork.org 25.9.2006
Committee Member Comments
Committee Chair Sheila Burke, deputy secretary and chief operating officer of the Smithsonian Institution, said, "We found an imbalance in the regulatory attention and resources available before and after approval. (...)

Report says FDA needs overhaul
pharmatimes.com 25.9.2006
World News | The US Institute of Medicine said on Friday that there are serious deficiencies in the way the safety of medicines is overseen and regulated once they reach the market, and that the Food and Drug Administration needs new funding and powers to get the situation back on track. (...)

Panel: FDA hasn't learned from Vioxx
suntimes.com 24.9.2006
WASHINGTON -- Two years after the withdrawal of the pain-killer Vioxx, the Food and Drug Administration still can't adequately track the safety of new drugs and respond quickly to problems, a panel of experts said Friday. (...)

Drug Safety Overhaul Is Urged
latimes.com 23.9.2006
The FDA spends far more time on approvals than on follow-ups, a review finds. Calls for reform include warning labels and limits on ads.

— The government's drug safety system is seriously out of balance, devoting too much attention to approving new medications and not enough follow-up to uncovering risky side effects, a blue-ribbon scientific panel concluded in a major report released Friday. (...)

Study Condemns F.D.A.’s Handling of Drug Safety
By GARDINER HARRIS
nytimes.com 23.9.2006
— The nation’s system for ensuring the safety of medicines needs major changes, advertising of new drugs should be restricted, and consumers should be wary of drugs that have only recently been approved, according to a long-anticipated study of drug safety.

Related
Text of the Report (nap.edu) (...)

FDA Told U.S. Drug System Is Broken (FDA har fått beskjed om at legemiddelsystem ikke fungerer)
washingtonpost.com 23.9.2006
Expert Panel Calls For Major Changes
By Shankar Vedantam
Washington Post Staff Writer
Saturday, September 23, 2006; Page A01
The federal system for approving and regulating drugs is in serious disrepair, and a host of dramatic changes are needed to fix the problem, a blue-ribbon panel of government advisers concluded yesterday in a long-awaited report. (...)

"FDA's credibility is its most crucial asset, and recent concerns about the independence of advisory committee members . . . have cast a shadow on the trustworthiness of the scientific advice received by the agency," the report said.

To reduce turnover and political interference, the institute said, the FDA commissioner should be appointed to a fixed six-year term. Currently, the commissioner serves at the pleasure of the president. (...)

Drug Safety System Still Lacking In The USA
medicalnewstoday.com 23.9.2006
The Food and Drugs Administration (FDA) doesn't yet have the necessary resources and clout to monitor the safety of new medications and respond effectively when something goes wrong, said a panel of experts from The Institute of Medicine in a new report, called The Future of Drug Safety. The FDA needs more resources - money, staff and powers - to effectively monitor and ensure the safety of medications. (...)

The Future of Drug Safety. Action Steps for Congress
Click here to download the report

Panel: FDA needs more power, funds
boston.com 23.9.2006
Report urges revamp to improve drug safety
-- The Food and Drug Administration lacks clear regulatory authority and is chronically underfunded, shortcomings hindering its ability to evaluate the safety of drugs used by millions of Americans, according to outside scientists the agency asked to critique its performance.

The assessment from the independent panel comes nearly two years after the painkiller Vioxx was pulled from the market, a move that prompted thousands of liability lawsuits and a series of congressional hearings on the safety of drugs approved by the FDA. (...)

FDA needs to monitor new drugs on market
seattlepi.nwsource.com 23.9.2006
Congress urged to provide greater funding for agency

-- The Food and Drug Administration has neither the funds nor the authority to adequately monitor licensed prescription drugs and ensure that they are safe, a committee of the Institute of Medicine declared Friday. (...)

Calling the Vioxx incident a "dead canary in a coal mine," Sen. Charles Grassley, R-Iowa, one of the FDA's most vocal critics in Congress, said the report should speed reforms of the agency. (...)

Panel says new steps needed to ensure drug safety
seattletimes.nwsource.com 23.9.2006
(...) Key proposals
Major recommendations of the Institute of Medicine report:

Put a symbol on packages for new drugs to denote that benefits and risks may not be fully understood. It would be used for two years.

Ban advertising directed at patients during those two years.

Review the risks and benefits of all new drugs after five years.

Increase the Food and Drug Administration's (FDA's) safety staff and give it an integral role in drug approval.

Modernize and extend the FDA's databases for tracking serious reactions to prescription drugs.

Create an Internet registry to post results of clinical drug trials.

Adopt stronger policies to minimize conflicts of interest among outside advisers who serve on the panels that guide much of the FDA's work.

Establish a six-year term for the FDA commissioner to provide stable leadership for the agency.

Los Angeles Times (...)

F.D.A. Is Faulted for Drug-Safety Process
nytimes.com 22.9.2006
WASHINGTON, Sept. 22 — The nation’s system for approving and monitoring the safety of medicines is inadequate and needs far-reaching reforms, and the Food and Drug Administration is plagued with poor management and persistent internal squabbling, according to a long-anticipated study of the agency.

Small Business
Go to Special Section »
The report by the Institute of Medicine is likely to intensify a debate about the safety of the nation’s drug supply and the adequacy of the F.D.A.’s oversight. The debate began in earnest in September 2004 when Merck withdrew its popular arthritis drug, Vioxx.

The Institute of Medicine, a nonprofit organization created by Congress to advise the federal government on health issues, conducted the study at the request of the F.D.A. (...)

Drug Safety Monitoring in U.S. Needs Improvement (Update6)
bloomberg.com 22.9.2006
Sept. 22 (Bloomberg) -- Widespread changes are needed in how U.S. regulators monitor the safety of prescription drugs after they're on the market, including a reassessment of potential risks after five years, a report said.
The report, released today by the U.S. Institute of Medicine, also suggested new drug packaging include warning symbols indicating the medications may not be safe, and that consumer advertising be limited. (...)

"This report should be a watershed moment for FDA reform,'' said Grassley, chairman of the Senate Finance Committee, in a statement that called for quick congressional action. "Public safety is at stake, along with the credibility of our nation's drug-safety agency.'' (...)

Reports cite cardiovascular risks of COX 2 inhibitors and NSAIDs
BMJ 2006;333:565 (16 September)
Cyclo-oxygenase-2 (COX 2) inhibitors and some other non-steroidal anti-inflammatory drugs (NSAIDs) may present cardiovascular and renal risks, say two papers published online ahead of print publication in JAMA. (...)

Dr David Graham: The FDA's concerns should now be "focused on patient safety rather than corporate profitability" (...)

The researchers found that naproxen did not lower the risk of myocardial infarction, as had been indicated by an earlier study (New England Journal of Medicine 2000;343: 1520-8[Abstract/Free Full Text]). (...)

Group raps FDA panels as 'rubber stamps'
chron.com 28.8.2006
Bloomberg News
The U.S. Food and Drug Administration's outside advisory panels typically serve as "rubber stamps" for companies seeking approval of drugs and medical devices, according to a nonprofit research group. (...)

Eleven randomly selected FDA advisory committees recommended approval in 79 percent of their votes on applications between 1998 and 2005, according to the study released Monday by the Washington-based National Research Center for Women & Families. The committees considered 89 products during that period. (...)

(Anm: "rubber stamps"; godkende helt automatisk; godkende uden videre... Kilde: ordbogen.com.)

Report Criticizes Lack of FDA Oversight
JAMA. 2006;296:920-922
A small cloud hovered over the June 30 celebration of the US Food and Drug Administration's (FDA) 100th anniversary in the form of a report, released 4 days earlier, that took the FDA to task for the agency’s lackluster enforcement of laws protecting the nation's food and medical products.

The report, issued by Rep Henry A. Waxman (D, Calif), said that during the past 5 years, the number of warning letters (a notice of violation of federal law) issued by the FDA to companies decreased by more than 50%. Waxman's report also said that officials at FDA headquarters routinely rejected the enforcement recommendations of the agency’s field staff and that the agency's recordkeeping and case tracking practices were inadequate. (...)

FDA to clarify rules on advisory committee members
BMJ 2006;333:278 (5 August)
The US Food and Drug Administration announced last week that it is to develop guidelines to clarify the relationships between members of its advisory committees and pharmaceutical companies. The aim is to make advisory committee processes more effective and to reassure the public about the integrity of the process.

There will be a period for public comment on the proposed new rules. (...)

Rules Planned for Industry Ties on F.D.A. Boards
nytimes.com 24.7.2006
WASHINGTON, July 23 — The Food and Drug Administration is expected to announce Monday an effort to write guidelines detailing the kind of industry ties that are permitted for those who serve on its powerful advisory boards.

The agency is hoping the move will appease some of its critics who have complained for years that those who sit on its boards often have such deep financial ties to drug makers that their advice is tainted. Advisory boards recommend drugs for approval, and their votes can have enormous influence on drug company stock prices. (...9

FDA to spell out rules on outside advisers
chron.com 23.7.2006
WASHINGTON — Outside experts who advise the government on drugs and other regulated products often have financial ties to industry, creating the potential for conflicts of interest.

Bar these scientists from review panels, say some members of Congress and critics of the Food and Drug Administration. Not possible, the agency says, because so many scientists whose expertise the government relies on have ties to industries under FDA regulation.

But pressured by Congress, the agency is trying to bring its decision-making more into the open, by spelling out how and why it grants waivers for outside experts that allow them to serve as FDA advisers.

Eventually, new guidelines _ plans for which are being announced Monday _ should clarify its actions when an expert might have a conflict of interest, said Dr. Scott Gottlieb, the FDA's deputy commissioner for Medical and Scientific Affairs. Few details were available about the proposed guidelines.

The FDA says that simply eliminating all outside reviewers with potential conflicts would deny the FDA access to advisers with the expertise and experience it seeks.

"We probably couldn't recruit department chairmen. It would hinder us from recruiting all but junior faculty members," Gottlieb said.

A congressional critic called that claim "absolutely untrue," adding that anything action short of barring advisers with conflicts would be a "charade."

"It just doesn't make any sense to me. When you have this problem _ conflicts of interest on critical panels _ the solution is eliminate the conflict. It's simple and easy to do," said Rep. Maurice Hinchey, D-N.Y.

That blanket approach is too restrictive, while the FDA's is too permissive, said Dr. Peter Lurie, author of a recent study on the issue that appeared in The Journal of the American Medical Association.

"They should literally beat the bushes to find people with as few conflicts as possible. One thing is to look harder," Lurie said. (...)

Criticism of FDA resurfaces in survey of agency scientists
baltimoresun.com 21.7.2006
WASHINGTON // More than a third of Food and Drug Administration scientists who responded to a survey said that agency officials cared more about speeding new drugs and medical devices to market than assuring they're safe, and about the same number said the agency wasn't adequately protecting the public health, according to results released yesterday by an advocacy group.

The findings, in a survey by the Union of Concerned Scientists, were the latest iteration of criticism of the FDA's integrity. Whistleblowers, members of Congress and interest groups have for several years attacked the agency, saying it has been weakened by industry and political influence at the expense of sound science and the public health. (...)

Survey says scientists feel pressured, which FDA denies
nj.com 21.7.2006
WASHINGTON -- Food and Drug Administration scientists are often subjected to inappropriate political and commercial interfer ence that compromises their mission to protect public health and safety, according to the findings of a survey released yesterday by two public interest groups.

The Union of Concerned Scientists and Public Employees for Environmental Responsibility said their survey of 997 FDA staff members suggests the "culture of science is under attack and struggling at the FDA."

"Science must be the driving force for decisions made at the FDA. These disturbing survey re sults make it clear that inappropriate interference is putting people in harm's way," said Francesca Grifo, a senior scientist with the Union of Concerned Scientists. (...)

Among the survey's other findings:

• Only half (51 percent) of the scientists felt FDA was acting effectively to protect public health.
• Two in five (40 percent) said they could not publicly express concerns about public health for fear of retaliation.
• Nearly 70 percent said they do not believe the FDA has suffi cient resources to effectively perform its mission.
• Forty percent described morale as poor or extremely poor, and only 32 percent said the agency is moving in the right direction.

Susan Wood, a former FDA assistant commissioner for women's health, said the survey reflects longstanding concerns within the agency. But Wood, who quit last year after charging political interference with the emergency contra ceptive case, said "some things have gotten worse" under the Bush administration.

Sen. Charles Grassley (R-Iowa), a vocal critic of the FDA, said the survey echoes views and allegations scientists report to Congress on a regular basis.

Full clinical trial disclosure needed: expert
CMAJ 2006; 175 (2) (July 18)
Legislation is required to force pharmaceutical companies to disclose clinical trial information to Canadians, says Dr. Andreas Laupacis of the Canadian Expert Drug Advisory Committee (CEDAC).

Laupacis, who emphasized that he was speaking as an individual, told attendees at a recent Centre for Health Services and Policy Research conference that he is "enormously frustrated" by how long it is taking to bring more transparency to the system.

Pharmaceutical companies don't make complete information about the original trial protocols and outcomes available, he noted. "We see only a few outcome measures from a trial. Are we getting all the information about harm?" (...)

Can we tame the monster?
Editor's choice
BMJ 2006;333 (8 July)
What can we learn from the New England Journal of Medicine's correction last week of its study on rofecoxib (BMJ 2006;333: 12, 1 Jul[Free Full Text])? The simple message is that increased cardiovascular risks were visible as early as four months into treatment, rather than the 18 months that Merck had claimed. But rofecoxib was withdrawn two years ago, so why all the fuss?

Well, reputations are at stake. The journal wants to show that it had made no mistakes in peer reviewing the study. And Merck, having already incurred financial loss, needs to protect its share price. But the stand-off between journal and drug company is just one symptom of a wider disease: an overpowerful, under-regulated drug industry and a research establishment and publishing industry in its thrall.

Between the interests of the public and the commercial interests of drug companies stand two potential safeguards—journal peer review and drug regulation. The pressures on journals to publish drug industry trials include the need for newsworthy content and revenues from reprint sales. These pressures are intensifying, and recent examples of selective reporting and data manipulation have made clear that peer review in its current form is unequal to the task. Writing in PLoS Clinical Trials (2006;1: e6)[CrossRef] in May, Richard Smith and Ian Roberts proposed a different model for disseminating the results of clinical trials. Protocols and analyses would be prespecified and posted for discussion, and full datasets would be uploaded on completion of the trial. The role of journals would be limited to providing commentaries. Is this feasible? Is it the answer? (...)

Watchdogs 'too close to drug firms'
guardian.co.uk 7.7.2006
Drugs regulators and manufacturers are "too close", meaning they ignore warning signs over potentially dangerous medications, a doctor has said.
David Healy, Professor of Psychiatry at Cardiff University, said bodies like the Medicines and Healthcare products Regulatory Agency (MHRA) do not always act in the best interest of patients.

In a paper in the British Medical Journal, Prof Healy points to the increased suicide risk from taking some anti-depressants, such as Seroxat.

Its manufacturer, GlaxoSmithKline (GSK), caused controversy from 2002 onwards over claims about the potential side effects of the drug.

The US medicines regulator, the Food and Drug Administration (FDA), ordered a review of its clinical evidence, leading GSK and the MHRA to concede that there was an increased risk of adults feeling suicidal.

Previously, the MHRA had said there was no evidence to back up a claim of suicide risk in adults. The drug is not recommend for use in people under the age of 18.

Prof Healy said the MHRA was obsessed with "statistically significant data" and is too much in the pocket of drug manufacturers.

An original campaigner on the issue, he said evidence on the side effects of anti-depressants first appeared in the mid to late 1980s.
Trials in children from the mid-1990s onwards showed a doubling of the risk of suicidal acts, leading to a warning on their use in youngsters.
But trials showing a similar risk for adults did not lead to a warning for adults until May this year, Prof Healy argued.

Report Raises New Concerns About Antidepressants-Suicide Link
forbes.com 7.7.2006
-- Doctors and their patients need a more balanced picture of the risks and benefits of the popular antidepressants known as selective serotonin reuptake inhibitors (SSRIs), a new report contends. (...)

According to the BMJ report, GlaxoSmithKline, which makes Paxil, recently sent a letter to doctors saying the drug caused a six-fold increase in the risk of suicidal behavior. This was in sharp contrast to a 2004 report by British health authorities, and to previous pronouncements from the company, Healy said. (...)

Conflicts cause FDA to review advisory committees
CMAJ 2006;175 (1) (July 4)
Critics have lately cast the US Food and Drug Administration (FDA)'s scientific advisory panels as little more than partially owned subsidiaries of the pharmaceuticals industry. In fact, one influential US Congressman is so outraged by the degree to which panels are replete with scientists who sport financial conflicts of interest that for the second consecutive year, he has successfully attached a rider to the FDA budget that would prohibit the agency from using panelists so conflicted. (...)

FDA’s enforcement arm 'tied behind its back'
in-pharmatechnologist.com 3.7.2006
- A report on the US Food and Drug Administration’s (FDA) enforcement record by US Democratic lawmakers has highlighted a plunge in the number of warning letters the agency has sent to drug manufacturers since 2000, citing several examples where violations spotted in site inspections were not followed through.

The investigation found that officials at the FDA headquarters routinely rejected the recommendations of field officers, resulting in fewer enforcement actions.
The number of warning letters issued by the agency for violations of federal requirements has fallen by over 50 per cent, from 1,154 in 2000 to 535 in 2005, a 15-year low according to the report. (...)

Study Cites Marked Drop In FDA's Warning Letters
ashingtonpost.com 27.6.2006
The number of serious "warning letters" sent by the Food and Drug Administration to drug, device and food companies has dropped by half over the past five years, leading to a situation where the agency's ability to ensure that products are being made properly has been "significantly compromised," according to a study by the Democratic staff of the House Government Reform Committee.

In addition to a drop of almost 50 percent in the number of on-site inspections at manufacturing plants, the 15-month probe found that in some cases, FDA headquarters rejected the enforcement recommendations of agency field offices despite inspectors' findings that violations had led to deaths or serious injuries. (...)

Senators Prepare to Unveil New Drug Safety Proposals
nytimes.com 21.6.2006
WASHINGTON, June 20 — After more than a year of quiet negotiations, two influential senators are expected within weeks to introduce a legislative proposal that could drastically change how drugs are tested and approved in the United States.

The senators, Michael B. Enzi, Republican of Wyoming and chairman of the Health, Education, Labor and Pensions Committee, and Edward M. Kennedy of Massachusetts, the ranking Democrat on the committee, still refuse to speak about the proposal, representatives for both said.

But committee staff members have for weeks been showing legislative talking points to drug industry representatives, scientists and others on Capitol Hill to help tailor the proposed legislation and build support for it.

In broad terms, the bill would require that drug makers disclose the results of all large human tests of their drugs, known as Phase 3 and Phase 4 trials; create a detailed risk management plan to uncover and control any safety problems that arise after a drug is approved; and pay penalties if they fail to follow through with this plan, according to four experts who were briefed on the proposals.

The experts spoke on condition that their names not be used because they had told members of the senators' staffs that they would not talk publicly about the proposals. (...)

(Anm: Big Pharma Research Racket Is Killing People. sierratimes.com (24.6.2006).)

Congress slow to act on FDA reforms
nj.com 11.6.2006 (The Star Ledger)
WASHINGTON -- The recall of popular pain medicine Vioxx because of links to deaths and heart attacks prompted congressional hearings, harsh criticism of the Food and Drug Administration and proposals for stronger drug safety procedures.

Yet almost two years later, neither the House nor the Senate has taken any legislative action on drug safety, and neither is likely to do so any time soon.
"This Congress has refused to consider any of the proposals to reform the FDA, and that refusal comes about because members are comfortably obliged to the pharmaceutical industry," said Rep. Maurice Hinchey (D-N.Y.), the sponsor of one of the drug-safety bills.

"We expected more urgency and we wanted more urgency," said Diana Zuckerman of the National Research Center for Women and Families, a nonprofit public interest group. "There has been a lot of talking, but that's all."
Lawmakers and officials from consumer and industry groups predict the drug safety issue won't come to the front burner until at least a year from now, when Congress must renew the law authorizing payment of pharmaceutical company user fees to the FDA to cover the costs of drug reviews.

For the drug industry, the go-slow congressional approach is welcome.
"We have been very cautious as we have reviewed legislative initiatives over the past year," said Alan Goldhammer, an associate vice president of the Pharmaceutical Research and Manufacturers of America, the major industry trade group.

"There is a tendency to react to the news of the day, but these are all complex issues, and one doesn't want to make dramatic policy changes without a thorough examination," Goldhammer said.

During the past two years, the FDA has been criticized for its handling of Vioxx and other heavily marketed pain medications that studies have linked to deaths, heart attacks and strokes.
Merck, Whitehouse Station, pulled its Vioxx painkiller from the market in 2004, and the FDA, under close scrutiny, later ordered Pfizer to withdraw its Bextra arthritis medicine and required more warnings on pain pills.

The FDA also has been faulted for not moving quickly enough to deal with the potential link between suicidal tendencies and antidepressants in children and for failing to closely regulate direct-to-consumer drug advertising.

A Wall Street Journal Online/Harris Interactive poll released last month found only 36 percent of the public thinks the FDA is doing a good job, down from 56 percent in 2004. The poll also found that 80 percent of the public has concerns about the FDA's ability to make independent decisions to make sure patients are getting safe and effective medicines.

A year ago, Sen. Charles Grassley (R-Iowa), who held a public hearing exploring missteps by the FDA and Merck in the handling of Vioxx, introduced legislation to create an independent drug safety center within FDA.

Under his bill, if a drug turned out to have safety problems, the unit could restrict distribution, require labeling changes or even withdraw its approval. Currently, the FDA center that approves drugs also reviews safety and must negotiate recalls or labeling changes with the drug companies.

The measure would give the FDA authority to mandate that manufacturers create a registry of all clinical trials and conduct additional clinical studies if questions about safety arise after a drug is on the market. It also would impose more direct-to-consumer advertising rules.
Hinchey introduced a similar bill in the House.

Sen. Mike Enzi (R-Wyo.), chairman of the committee with jurisdiction covering the FDA, and Sen. Edward Kennedy of Massachusetts, the ranking Democrat, are drafting their own bill that will be introduced this summer.

Details aren't available, but some interest groups briefed about the legislation said it is likely to seek more transparent and complete dissemination of pre-market clinical trial data, and better FDA oversight procedures once a drug has been approved for use.

The bill, however, isn't expected to recommend creation of a powerful drug safety center within the FDA.

Hoping to head off congressional action, the FDA last year created a board inside the agency to oversee management of drug safety issues.
But in April, the Government Accountability Office, the congressional investigating agency, said the FDA still lacks a reliable system for keeping track of emerging drug safety problems.

Capitol Hill Watch | Newark Star-Ledger Examines Prospects of Congressional Reform of FDA
kaisernetwork.org 13.6.2006
Daily Health Policy Report

Ex-Head of F.D.A. Faces Criminal
nytimes.com 29.4.2006
WASHINGTON, April 28 — Dr. Lester M. Crawford, the former commissioner of food and drugs, is under criminal investigation by a federal grand jury over accusations of financial improprieties and false statements to Congress, his lawyer said Friday. (...)

The FDA Awaits a Cure for Its Malaise
latimes.com 30.4.2006
Problems pile up in the absence of a permanent chief and political disputes over ideology.

WASHINGTON — The Food and Drug Administration has been without a permanent leader for more than two-thirds of President Bush's tenure, and major unresolved problems are piling up at the federal agency in a time of huge medical and scientific change.

With the FDA stuck in the bureaucratic equivalent of slow gear, critics as well as supporters — in a rare point of agreement — say the agency is in danger of losing its standing in setting regulatory policy in the rapidly evolving medical and scientific fields. (...)

Congressional Investigators Are Critical of F.D.A.'s Efforts to Detect Drug Dangers
nytimes.com 24.4.2006
— Disorganization, bureaucratic infighting and an inability to force drug makers to conduct needed safety tests have undercut efforts at the Food and Drug Administration to uncover drug dangers, government auditors say.

When drug safety specialists raise alarms about certain medicines, they sometimes feel that their recommendations fall "into a 'black hole' or 'abyss' " at the agency, according to a report to be released Monday by the Government Accountability Office, the auditing arm of Congress.

Top agency officials sometimes excluded drug safety specialists from presenting findings at public hearings, and tensions between officials who approve drugs and those who ensure that they are safe are common, the report said.

"F.D.A. lacks clear and effective processes for making decisions about, and providing management oversight of" issues involving the safety of popular medicines, the report states.

The F.D.A. told the accountability office that its conclusions were "reasonable," the report said. (...)

(Anm: Drug Safety: Improvement Needed in FDA's Postmarket Decision-Making and Oversight Process. GAO-06-402, March 31. http://www.gao.gov/cgi-bin/getrpt?GAO-06-402 Highlights: http://www.gao.gov/highlights/d06402high.pdf.)

Expert View: The world needs drugs companies to get well soon
independent.co.uk 11.12.2005
Regulators are too often on the back foot in crises

Big pharma is in a state of crisis. Public trust is at an all-time low. Recent polls show that drugs companies are no more trusted than the insurance, tobacco or oil industries. These days the public views the sector as greedy, putting profits before people's wellbeing and ignoring warnings about the safety of some drugs. (...)

So what went wrong and what can the sector do about it?

Big pharma's reputation is intertwined with that of its regulators, and here in particular I refer to the US Food and Drug Administration, the largest pharmaceutical regulator in the world. For many years the FDA was perceived as tough but fair. It had rescued the American public from the thalidomide disaster (which was largely averted in the US, though not in the UK) and had promoted strict scientific standards for drugs testing.

However, more recently, cracks have begun to appear in the FDA's reputation, caused primarily by the increased number of drug recalls and by concerns about a runaway rate of health scares involving prescription drugs. Legislators and politicians became worried and started inquiries into the conduct of the regulator. This process was made more complicated and drawn out because, during these inquiries, the FDA has remained de facto leaderless.

UK government fails to tackle weaknesses in drug industry (Britiske myndigheter mislykkes å ordne opp i svakheter innen legemiddelindustrien)
BMJ 2005;331:534 (10 September)
De britiske myndigheter har mislykkes å ordne opp i svakheter i farmasøytisk industri i sin respons på en rapport publisert tidligere i år på industrien rolle og innflytelse, sier en ledende kritiker. (The UK government has failed to tackle the weaknesses in the pharmaceutical industry in its response to a report published earlier this year on the industry’s role and influence, says a leading critic.)

- Interessekonflikter er vanlig hos FDA

FDA Issues Revised Procedures for Panel Conflict Disclosures
kaisernetwork.org 16.11.2007
FDA on Thursday issued proposed guidelines to increase transparency regarding potential conflicts of interest of members on its advisory panels, Dow Jones reports. Advisory panels -- convened to offer recommendations to FDA on health policy issues, and new drugs and medical devices -- are made up of external academic, medical and federal experts (Corbett Dooren, Dow Jones, 11/15). Under the new proposed rules, experts on advisory panels would be required to disclose any financial ties to the industry being considered, and they also would be asked to detail the reasons that they still should be allowed to serve, AP/Long Island Newsday reports. If FDA issues a waiver, the disclosure form then would be posted on the agency's Web site about two weeks before the panel convenes for a meeting, AP/Newsday reports. (...)

Conflicts of interest are common at FDA (Interessekonflikter er vanlig hos FDA)
BMJ 2006;332:991 (29 April)
Members of drug advisory committees at the US Food and Drug Administration often have financial conflicts of interest and those conflicts affect voting patterns, says a study in JAMA (2006;295: 1921[Abstract/Free Full Text]). (...)

The researchers studied three categories of conflicts of interests: "index conflicts" (those with financial interest in the drug under discussion); "competitor conflicts," and "any conflict." In all three categories, voting margins would have been less favourable to the index drug if panellists with conflicts had been excluded. Panellists with competitor conflicts sometimes exhibited the widest margin in favour of a drug, something the authors suggested might be due to a general "pro-industry" position among those with any industry ties. (...)

Many FDA Experts Have Drug Industry Ties
healthfinder.gov 25.4.2006
But votes on drug approvals wouldn't change much if they withdrew from advisory panels, study finds. (...)

Financial Conflict of Interest Disclosure and Voting Patterns at Food and Drug Administration Drug Advisory Committee Meetings
JAMA. 2006;295:1921-1928.
Context In January 2002, the US Food and Drug Administration (FDA) issued a draft guidance requiring more detailed financial conflict of interest disclosure at advisory committee meetings.

Objectives To characterize financial conflict disclosures at drug-related meetings, and to assess the relationship between conflicts and voting behavior at meetings that considered specific products.

Design and Setting Cross-sectional study using agendas and transcripts from all FDA Drug Advisory Committee meetings (2001-2004) listed on the FDA Web site.

Main Outcome Measures Conflict rates, type, and size. The relationship between having a conflict and voting in favor of the index drug was described for each voter using Mantel-Haenszel relative risks and Monte Carlo simulations; Spearman rho was used for a meeting-level analysis comparing rates of conflict with voting patterns. The impact of the removal of persons with conflicts of interest on the vote margins was also evaluated.

Results A total of 221 meetings held by 16 advisory committees were included in the study. In 73% of the meetings, at least 1 advisory committee member or voting consultant disclosed a conflict; only 1% of advisory committee members were recused. For advisory committee members (n = 1957) and voting consultants combined (n = 990), 28% (n = 825) disclosed a conflict. The most commonly specified conflicts were consulting arrangements, contracts/grants, and investments. Nineteen percent of consulting arrangements involved over $10 000, 23% of contracts/grants exceeded $100 000, and 30% of investments were over $25 000. The meeting-level analysis did not show a statistically significant relationship between conflict rates ("index conflict," "competitor conflict," or "any conflict") and voting patterns, but a weak, statistically significant positive relationship was apparent for competitor conflict and any conflict in the Mantel-Haenszel analyses. The Monte Carlo analyses produced similar findings in the competitor conflict analysis only. In all 3 conflict categories, the exclusion of advisory committee members and voting consultants with conflicts would have produced margins less favorable to the index drug in the majority of meetings, but this would not have changed whether the majority favored or opposed the drug.

Conclusions Disclosures of conflicts of interest at drug advisory committee meetings are common, often of considerable monetary value, and rarely result in recusal of advisory committee members. A weak relationship between certain types of conflicts and voting behaviors was detected, but excluding advisory committee members and voting consultants with conflicts would not have altered the overall vote outcome at any meeting studied. (...)

- Lovgivning krever at FDA gradvis avvikler interessekonflikter

FDA considers reforming use, selection of advisory panels (FDA vurderer å reformere utvelgelsen til rådgivende paneler)
boston.com 22.9.2007
(...) The Food and Drug Administration is considering a top-to-bottom reshaping of how it picks and uses the outside scientists who serve on the agency's advisory panels. (...)

The FDA's move toward internal reform comes even as Congress this week passed sweeping drug safety reform legislation. The bill, which awaits President Bush's signature, includes a compromise that would place new conflict-of-interest restrictions on advisory panel participants. It would require the FDA to decrease the number of participants with conflicts by 5 percent a year. (...)

"When members of the advisory committee have conflicts of interest, it not only hurts the public, but it also destroys the credibility of the committee's recommendations," said US Representative Edward Markey, Democrat of Malden. "The FDA should not allow individuals with conflicts of interest to vote on decisions and the FDA should significantly limit conflicted individuals' participation, in order to preserve the integrity of the process." (...)

"Even if you concede some very large proportion of the qualified scientists and physicians out there do have financial conflicts of interests, all FDA needs is less than 500 people," she said.

"It may take outreach. It may take a more active and engaged FDA," Wood said. "There truly are people out there who are unconflicted - if we just look."

Wood and others who share her view say limiting the number of advisers with conflicts could boost public confidence in FDA decision-making. (...)

But Dr. Steve Nissen, a prominent cardiologist at the Cleveland Clinic, said the FDA can skew advisory recommendations by selecting certain scientists to serve on panels, and through the way it compiles background documents used to brief panels. (...)

Bill calls for FDA to end all conflicts of interest (Lovforslag krever at FDA setter en stopper for interessekonflikter)
boston.com 7.8.2007
Agency faces pressure on advisers who have financial ties to firms

WASHINGTON -- The Food and Drug Administration could face a tough new assignment from Congress: Eliminate all conflicts of interest on outside advisory panels whose votes heavily guide the agency's decision-making.

US Representative Maurice Hinchey, Democrat of New York, attached such language to an agriculture appropriations bill passed by the House last week. The funding measure next moves to the Senate, where the FDA conflicts section faces a tough fight; opponents include Senator Edward M. Kennedy, Democrat of Massachusetts. (...)

Capitol Hill Watch | FDA Provision in Spending Bill Would Eliminate Conflicts on Advisory Committees
kaisernetwork.org 7.8.2007
A provision included in the fiscal year 2008 Agricultural appropriations bill (HR 3161) passed last week by the House would require FDA to eliminate all conflicts of interest on its advisory committees, the Boston Globe reports. (...)

Bill calls for FDA to end all conflicts of interest (Lovforslag krever at FDA setter en stopper for interessekonflikter)
boston.com 7.8.2007
Agency faces pressure on advisers who have financial ties to firms

WASHINGTON -- The Food and Drug Administration could face a tough new assignment from Congress: Eliminate all conflicts of interest on outside advisory panels whose votes heavily guide the agency's decision-making.

US Representative Maurice Hinchey, Democrat of New York, attached such language to an agriculture appropriations bill passed by the House last week. The funding measure next moves to the Senate, where the FDA conflicts section faces a tough fight; opponents include Senator Edward M. Kennedy, Democrat of Massachusetts. (...)

Capitol Hill Watch | FDA Provision in Spending Bill Would Eliminate Conflicts on Advisory Committees
kaisernetwork.org 7.8.2007
A provision included in the fiscal year 2008 Agricultural appropriations bill (HR 3161) passed last week by the House would require FDA to eliminate all conflicts of interest on its advisory committees, the Boston Globe reports. (...)

- Rapport angriper FDAs tilsyn med kliniske forsøk

Report Assails F.D.A. Oversight of Clinical Trials (Rapport angriper FDAs tilsyn med kliniske forsøk)
nytimes.com 27.9.2007
WASHINGTON, Sept. 27 — The Food and Drug Administration does very little to ensure the safety of the millions of people who participate in clinical trials, a federal investigator has found.

In a report due to be released Friday, the inspector general of the Department of Health and Human Services, Daniel R. Levinson, said federal health officials did not know how many clinical trials were being conducted, audited fewer than 1 percent of the testing sites and, on the rare occasions when inspectors did appear, generally showed up long after the tests had been completed.

The F.D.A. has 200 inspectors, some of whom audit clinical trials part time, to police an estimated 350,000 testing sites. Even when those inspectors found serious problems in human trials, top drug officials in Washington downgraded their findings 68 percent of the time, the report found. Among the remaining cases, the agency almost never followed up with inspections to determine whether the corrective actions that the agency demanded had occurred, the report found.

“In many ways, rats and mice get greater protection as research subjects in the United States than do humans,” said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania.

Animal research centers have to register with the federal government, keep track of subject numbers, have unannounced spot inspections and address problems speedily or risk closing, none of which is true in human research, Mr. Caplan said.

Because no one collects the data systematically, there is no way to tell how safe the nation’s clinical research is or ever has been.

The drug agency oversees just the safety of trials by companies seeking approval to sell drugs or devices. Using an entirely different set of rules, the Office for Human Research Protections oversees trials financed by the federal government.

Privately financed noncommercial trials have no federal oversight.
“It’s crazy that we have all these different sets of rules,” said Dr. Ezekiel J. Emanuel, chairman of the bioethics department at the National Institutes of Health. “It would facilitate things a lot if we had one agency overseeing things.”
Dr. Janet Woodcock, chief medical officer at the drug agency, acknowledged that it needs to put more “teeth” in its enforcement. “We are working to address these problems very aggressively,” Dr. Woodcock said. (...)

- Denne farsen har pågått lenge nok

Glukosamin - den store sukkerpillebløffen
Tidsskr Nor Lægeforen 2007; 127: 2121-2
(...) Glukosamin burde aldri ha vært godkjent som legemiddel, og nå må man i det minste ta til fornuft og reversere denne feilaktige avgjørelsen. Snuoperasjonen bør omfatte kvalitetssikring av anbefalings- og godkjenningsprosedyrene i Statens legemiddelverk, og arbeid med retningslinjer bør ekskludere aktører med interessekonflikter, anvende anerkjente metoder og graderes med hensyn til evidensstyrke. Denne farsen har pågått lenge nok. (...)

- Amerikanske forskere oppfordrer til gjennomgang av kliniske forsøk for å gjenreise tillit

US scientists urge overhaul of clinical trials to restore confidence (Amerikanszke forskere opfordrer til gjennomgang av kliniske forsøk for å gjenreise tillit)
BMJ 2006;332:991 (29 April)
The US government's top biomedical scientists have called for an overhaul of clinical trials to protect the public and to restore trust in medicine. After a summit at the National Institutes of Health (NIH), in Maryland, the institutes' director, Elias Zerhouni, warned that failure to spot serious side effects of drugs quickly enough was gradually eroding public trust. He announced an eight point plan designed to improve clinical trials and reduce the likelihood of side effects being swept under the carpet.

A key recommendation is for equal weight to be given to determining the safety as well as the efficacy of medicines. The NIH committee cited the scandal surrounding the painkiller Vioxx (rofecoxib) as evidence that safety needed to be stepped up. Merck withdrew the drug in 2004 after it emerged that users were at increased risk of heart disease and stroke. Earlier this month, a jury in New Jersey ordered the company to pay $13.5m (£7.6m; 10.9m) in damages to a 77 year old man after Vioxx was found to have contributed to his heart attack, and Merck had failed to warn about the dangers of taking the drug (BMJ 2006;332: 927, 22 Apr[Free Full Text]). The company is facing thousands of other lawsuits in the United States. (...)

- The advisory panels often vote unanimously to recommend approval even after members express doubts about the product or say the evidence submitted is insufficient...

Group Says FDA, Advisory Panels Show Bias Toward Drug Approvals
washingtonpost.com 29.10.2006
The panels of experts assembled by the Food and Drug Administration to advise it on whether to approve new drugs and medical devices are often biased in favor of recommending approval, according to a consumer group's analysis released yesterday.

The advisory panels often vote unanimously to recommend approval even after members express doubts about the product or say the evidence submitted is insufficient, said the report by the National Research Center for Women & Families, a policy research and advocacy group. The FDA has recently come under fire over drug safety issues, including its decisions to approve the popular arthritis pain medications Vioxx and Celebrex that were later associated with an increased risk of heart attacks and strokes. (...)

FDA Oversight Board Should Become More Transparent, Official Says
Kaiser Daily Health Policy Report
kaisernetwork.org 13.2.2006
Peter Gross, chair of the FDA Drug Safety and Risk Management Advisory Committee, on Friday said the agency's Drug Safety Oversight Board must become more open and transparent, the Wall Street Journal reports. According to Gross, who also chairs the internal medicine department at Hackensack University Medical Center , FDA should consider the addition of outside experts to the board, which was established in 2005 in response to criticism related to the market withdrawal of the COX-2 inhibitor Vioxx in September 2004. The board currently includes FDA employees and representatives from NIH and the Department of Veterans Affairs . Sandra Kweder, deputy director of the FDA Office of New Drugs, said that the addition of outside experts to the board would require legislation, adding that the board was not established to replace the advisory committee (Corbett Dooren, Wall Street Journal, 2/12). (...)

- Uavhengighet hos Food and Drug Administration

Independence at the US Food and Drug Administration
The Lancet 2006; 367:1630 (20 May 2006)
If confirmed, Andrew von Eschenbach, President George W Bush's choice to lead the US Food and Drug Administration (FDA), will bring considerable expertise and experience to the post. He is a respected cancer researcher, an experienced administrator, and has been a cancer patient himself. This background no doubt served him well as Director of the US National Cancer Institute (NCI), a position he held until he resigned last month. But are these qualifications enough for the job of FDA commissioner?

At the NCI, von Eschenbach led an agency that conducts intramural and funds extramural research programmes to develop new ways to prevent and treat cancer. Through its oversight and guidance, the FDA, which celebrates its centenary this year, also works to help researchers and industry move new discoveries from bench to bedside. But the FDA is also charged with making sure new drugs are safe and effective, to act as the “cop on the beat”—a tough, but fair, guardian of patients' and consumers' safety.

To do that job, the FDA must be led by a commissioner willing to take independent stands, following the best judgment of his expert staff and scientific advisers, even when that means incurring the wrath of patients' groups, industry, Congress, and the White House. (...)

- Styrking av FDAs myndighet på legemiddelsikkerhet

Bolstering the FDA's Drug-Safety Authority (Styrking av FDAs myndighet på legemiddelsikkerhet)
NEJM 2007 357:2217-2219 (November 29)
The modern era of drug development began with the 1962 Kefauver-Harris Drug Amendments, which required that drugs be tested for efficacy as well as safety and gave the Food and Drug Administration (FDA) the authority to require sophisticated clinical trials before approving drugs.¹ Today, we can be confident that an approved drug will be effective for its labeled uses. The same cannot be said of the drug's safety. At the time of approval, a drug has typically been tested in several thousand patients, in studies powered to identify only relatively common adverse reactions. For example, a study that includes 3000 subjects will identify adverse reactions that occur at rates of 1 in 500 to 1 in 1000. Yet if the drug is used by 1 million people, a serious adverse event affecting only 1 in 10,000 people would occur 100 to 200 times. Such rare reactions can be identified only after wide use. (...)

Nasjonalt kunnskapssenter for helsetjenesten (FHI)

Hvilke spørsmål bør prioriteres?
dagensmedisin.no 19.10.2007
- Vi vil ta til orde for å evaluere ordningen med foretrukket legemiddel - og hva denne har ført til av bedret legemiddelbruk eller innsparinger. Vi vil også selv vurdere hvilke oppdrag vi bør prioritere på legemiddelområdet i fremtiden, fastslår artikkelforfatterne. (...)

Troverdighet
Kunnskapssenterets informasjon skal, sammen med informasjon fra myndighetene, Statens legemiddelverk og Sosial og helsedirektoratet (SHdir), utgjøre en motvekt til informasjon fra legemiddelindustrien - produsentene. (...)

Uavhengig legemiddelinformasjon - hvem gjør hva og hvordan?
Nasjonalt kunnskapssenter for helsetjenesten (19.9.2005)
Fagmiljøer som utvikler og formidler informasjon om legemidler har hatt møte i Kunnskapssenteret for å få oversikt over forventninger, hvem som gjør hva i dag og hvordan aktørene kan samarbeide fremover.

Les presentasjonene fra møtet...|
Les om Kunnskapssenterets satsing på legemiddelfeltet...

Informasjon, refusjonsstatus og bivirkningsforhold (pdf, 0,1MB)

Statens legemiddelverk - (SLV)

Nasjonalt kunnskapssenter for helsetjenesten
Rundebordskonferanse 29.august 2005: Informasjon om nye legemidler, refusjonsstatus og bivirkningsforhold
Steinar Madsen - Avdeling for legemiddelbruk - Statens legemiddelverk

Ifølge SLV er legemiddelverkets hovedoppgaver:

•Godkjenne nye legemidler
•Legemiddelovervåking
•Fastsette pris
•Forvaltning av blåreseptordningen

Irritert på statlig hemmelighold
dagensmedisin.no 7.4.2006
Røntgenlege Arne Høiseth irriterer seg kraftig over at Legemiddelverket hemmeligholder forskningsresultater på generiske legemidler - og krever et åpnere Legemiddelverk.

Lege Arne Høiseth ved Sentrum Røntgeninstitutt i Oslo har bedt om innsyn i studier som ligger til grunn for at Legemiddelverket har godkjent kopimidler av bisfosfonatet alendronat, med merkenavnet Fosamax.
Legemiddelverket har imidlertid avslått søknaden med begrunnelse om at dette er forretningshemmeligheter. - Vi vurderer studier som ligger til grunn for godkjenning av legemidler som forretningshemmeligheter etter legemiddel- og offentlighetsloven. Dette regelverket har vi praktisert i flere år, opplyser jurist Hilde Holme i Statens legemiddelverk. (...)

Høiseths klage er oversendt Helse- og omsorgsdepartementet (HOD) for endelig avgjørelse. Legemiddelverket opprettholder avslaget, men Holme opplyser at EU vurderer om det skal gis innsyn i bioekvivalensstudier og om Legemiddelverket vil følge EUs standpunkt for lignende saker i fremtiden.

Storbritannia (Medicine and Healthcare Products Regulatory Agency - MHPRA)

Did regulators fail over selective serotonin reuptake inhibitors?
BMJ 2006;333:92-95 (8 July)
Controversy over the safety of antidepressants has shaken public confidence. Were mistakes made and could they have been avoided? (...)

UK drug regulatory body describes attempts to ensure independence
BMJ 2005;331 (8 October)
On page 834, Breckenridge and Woods from the Medicine and Healthcare Products Regulatory Agency discuss the relation between the UK drug regulatory system and the pharmaceutical industry. They describe the steps being taken to ensure that the regulatory agency is independent in its assessment even though it is funded entirely by user fees. Members of staff must disclose any potential competing interests (such as having shares in a pharmaceutical company), and other measures are used to increase transparency while protecting commercial confidentiality and secrecy.

Medicines regulation and the pharmaceutical industry
BMJ 2005;331:834-836 (8 October)
Education and debate
Medicines regulation and the pharmaceutical industry
Alasdair Breckenridge, chairman1, Kent Woods, chief executive1
1 Medicines and Healthcare Products Regulatory Agency, London SW8 5NQ
Correspondence to: A Breckenridge alasdair.breckenridge@mhra.gsi.gov.uk
How does an agency funded by user fees make impartial decisions about the safety of new and licensed drugs? (...)

Agency staff are civil servants and must abide by standard rules of conduct and impartiality. Because of the nature of the agency's work, its policy on conflicts of interest goes further than that pertaining generally in the civil service. In addition, from November 2005, European regulations will require that staff have no financial or other interests that could affect their impartiality. At present, all members of staff complete a declaration of interest (shareholding, or other interest in the pharmaceutical industry) and their managers ensure that they do not perform any task that might be compromised by any interests. Under the new code, the agency is creating a comprehensive register of all current interests of agency staff, and they were required to dispose of all such interests by July 2005. The regulations do not apply to pensions accruing from previous employment in industry or to pooled investments where individuals cannot influence investment strategy—for example, in unit trusts.

Conflict of interest is also relevant for members of the agency's advisory committees. Chairs of advisory committees such as the Medicines Commission and the Committee on Safety of Medicines are not allowed to hold personal financial interests (such as shareholdings or paid consultancies) in the pharmaceutical industry. Members of these committees have been allowed to hold such interests, but they must declare them, both in an annual submission to the agency and at each meeting that discusses a relevant product. Anyone with such an interest must leave the room and take no part in the discussion and recommendations of the committee. Furthermore, if a member's department is being paid to work on a specific product, this must also be declared and the member will normally leave the committee while the discussion is taking place.

Another potential interest arises when a member's department is involved in work with a company on products other than those under discussion (with any fees going to their university or department). Most academic departments in the UK collaborate with pharmaceutical companies in this way and are encouraged by government and universities to do so. All members must declare such non-personal, non-specific interests annually and at meetings when any of the company's products are debated. However, they can take full part in the discussion and decision making. All these interests are published in the agency's annual report. (...)

How and when clinical trial data submitted to a regulatory agency for licensing purposes should be made public is provoking much debate.1 The agency supports recent moves by the associations representing the pharmaceutical industry in Europe, the United States, and Japan to ensure the registration of all clinical trials and to allow that information to be placed in the public domain. It also supports making the results of all clinical trials publicly accessible. Issues such as where such a register of clinical trials should be held, where the results of these trials should be deposited, and when such results should be made publicly available must be resolved. (...)

The agency is committed to greater transparency of its activities. It has already shown this by starting to publish the minutes of its advisory committees and disclose the evidence underpinning its decisions in areas of public concern. For example, the agency published the data from clinical trials that it used in its reviews of selective serotonin reuptake inhibitors in 2003-5 and hormone replacement therapy in 2004.3 4 (...)

- Safer Drugs for the American People

Safer Drugs for the American People
EDITORIAL
NEJM 2007; 357:602-603 (August 9)
By wide margins, both the House and the Senate have now passed bills that aim to ensure the safety of the drug supply in the United States.^{1 2} Given the serious safety problems that have arisen with drugs taken by millions of Americans, this legislation is long overdue. It is now up to both houses of Congress to resolve the differences between the two versions and agree on a strong final bill to send to the President. (...)

In the wake of the landmark report on drug safety issued by the Institute of Medicine almost a year ago,³ Congress is now poised to pass the most important drug-safety legislation in a century. (...)

USA (Food and Drug Administration - FDA)

FDA Advises Researchers on Drug Evaluating
washingtonpost.com 12.1.2006
WASHINGTON -- Concerned by a system in which more than nine out of 10 experimental drugs fail when tested in humans, the Food and Drug Administration issued suggestions Thursday on how researchers can more efficiently evaluate the promise of new laboratory discoveries.

The vast majority of drug candidates fail once they're tested on humans, invariably for safety or efficacy reasons difficult to predict based on initial experiments done in test tubes and on animals. That can waste significant amounts of time and money, slowing the process of developing new drugs.

The goal of the new approaches being floated by the FDA is to guide researchers on methods of identifying early-on those drug candidates that are most likely to succeed once early testing in humans gets under way. Those so-called exploratory investigational new drug studies typically involve very limited numbers of subjects given small amounts of a drug for brief periods.

AAMC comments on FDA drug safety communication
Information: Go to http://www.aamc.org/advocacy/library/research/corres/2005/122005.pdf
This week, the AAMC submitted a comment letter to the U.S. Food and Drug Administration (FDA) on the effectiveness of the agency's communication tools for delivering information about drug safety to patients and physicians. In the letter, the association noted the strengths of the FDA's existing communication tools, particularly their thoroughness. The letter also noted the primary weaknesses of the communication tools: the information is cumbersome for physicians due to a lack of prioritization, and difficult for patients due to the use of medical and technical language. The AAMC listed the obstacles hampering effective communication, as well as potential steps the FDA might take to overcome them. For example, the point at which physicians prescribe and patients first receive their medication often represents the only opportunity to convey clear and simple, limited-length safety alerts and information; this opportunity must be better used to meet patients' needs.

Lessons from Vioxx
The Boston Globe 19.12.2005
MERCK PHARMACEUTICAL company took the pain reliever Vioxx off the market more than a year ago, after a clinical study found that it caused heart attacks. And now instead of helping people with chronic pain, it is the subject of thousands of lawsuits contending that it helped to kill them. (...)

In hindsight, the New England Journal's staff should have been especially vigilant about the Vioxx article. Journal editors did vet it with outside experts, as is customary, but greater scrutiny is needed when the article deals with a drug with great profit-making capabilities. In September, the Journal and other prestigious medical publications decided to insist that all the data from clinical trials mentioned in articles be available for verification. That's an important improvement if journal editors make sure companies clearly disclose any problems with the drugs.

The real problem, however, is the FDA and the entrepreneurial atmosphere that surrounds the introduction of many new drugs. Prescription medicine, aided by massive marketing and the absence of price controls in the United States, is considered a major growth industry by Wall Street. With billions of dollars at stake, corners may be cut.

The Journal said its investigation benefited from information obtained by subpoena in one of the 6,400 lawsuits filed by aggrieved Vioxx users or their families. It shouldn't take court proceedings to reveal damaging information about prescription drugs, but that's going to happen again unless the FDA toughens its approval process.

Senator Charles Grassley, the Iowa Republican who heads the Finance Committee, and Senator Christopher Dodd have bills to do just that, but they have languished since February in the Senate Health, Education, and Labor Committee. This is headed by Mike Enzi of Wyoming; the ranking Democrat is Edward Kennedy.

Grassley's proposal would mandate that information from clinical trials be put in publicly available data bases. This would compel the drug companies to provide the data that the journal editors are seeking.

Grassley also wants to establish a separate drug safety office within the FDA. This ought to provide an institutional check on FDA inclination to approve drugs too quickly. Both of Grassley's proposals seem to be sensible improvements in the status quo, but perhaps Enzi and Kennedy can come up with some that are better. A plan to improve the approval process needs to get out of committee and win congressional approval next year.

Other proposals range from limiting television advertising to reverting back to the system in which the government, not the drug companies, defrayed the cost of approving a drug. It's hard to envision Congress giving up a source of revenue when the federal budget is many billions of dollars in the red. But Congress ought to ban consumer advertising, which the FDA did not allow until 1997. Prescription drugs should not be the object of a consumer marketing frenzy.

Vioxx is held in such low regard that a jury deadlocked on a verdict last week even though the patient, a man with a heart condition who later died, had only taken the drug for a month. Vioxx probably didn't cause all the heart attacks for which it will be blamed in court, but because Merck portrayed it as a safe drug for so long, many jurors are loath to give the company the benefit of the doubt.

No one wants to return to the days when FDA sluggishness delayed the approval of life-sustaining medicine, but there has to be a middle way between long delays and an approval process that makes millions of pain sufferers into unknowing guinea pigs. Tighter regulations may lessen company profits, but they will ensure that the medicines Americans take are once again considered the safest on Earth.

Vioxx scares FDA into 'black-box' safety blitz
The Times timesonline.co.uk/ 12.12.2005
THE number of drugs given so-called “black box” warnings by the US Food and Drug Administration (FDA) has more than doubled in the past year as concerns over the safety of everyday medicines continues to mount.

FDA seeks to improve drug safety alerts
Financial Times 8.12.2005
The Food and Drug Administration is exploring ways to improve the way it communicates risks, such as dangerous side effects, associated with prescription drugs.

The US medicines regulator opened a two-day public hearing on Wedmesday to gather input on its drug risk communication – a subject of intense legal, political and medical scrutiny in the past year.

F.D.A. Official Becomes 3rd to Quit Agency Since Summer
The New York Times 7.12.2005
A Food and Drug Administration official whose office was involved in a recent controversial application for drug approval said yesterday that he was resigning to join private industry.

Dr. David Orloff, a division director who oversees the review of drugs to treat metabolic and endocrine disorders, is set to join Medpace, a contract research organization based in Cincinnati that runs clinical drug trials.

Dr. Orloff was in charge of the F.D.A.'s review of Pargluva, a diabetes drug from Bristol-Myers Squibb that was recommended for approval by an F.D.A. advisory panel in September. The drug has since been postponed indefinitely as a result of cardiovascular safety concerns.

Dr. Orloff said his decision to leave after 11 years at the F.D.A., with 5 of them as a division director, was not related to any problems or frustrations but reflected a new opportunity.

"I wasn't looking to leave, and I've been very happy here," he said.

How Vioxx is changing US drug regulation (Hvordan Vioxx forandrer amerikansk legemiddelregulering)
The Lancet 2005; 366:1763-1764 (19 November 2005)
Merck and Co now faces more than 6000 lawsuits involving the COX2 inhibitor rofecoxib, marketed as Vioxx. But no matter how these legal battles are resolved, the cases are already having an impact on how the pharmaceutical industry and government regulators do business. Todd Zwillich reports. (Merck and Co now faces more than 6000 lawsuits involving the COX2 inhibitor rofecoxib, marketed as Vioxx. But no matter how these legal battles are resolved, the cases are already having an impact on how the pharmaceutical industry and government regulators do business. Todd Zwillich reports.)

Merck and Co celebrated victory earlier this month after a New Jersey jury ruled that the company's anti-inflammatory drug rofecoxib (Vioxx) did not cause the heart attack of a 60-year-old postal worker. The verdict evened the score for the pharmaceutical giant, which in August lost a similar trial in Texas and was asked to pay US$253 million compensation. (Merck and Co celebrated victory earlier this month after a New Jersey jury ruled that the company's anti-inflammatory drug rofecoxib (Vioxx) did not cause the heart attack of a 60-year-old postal worker. The verdict evened the score for the pharmaceutical giant, which in August lost a similar trial in Texas and was asked to pay US$253 million compensation.)

The August case is under appeal, and Texas law will cut the award by 90%. But the company is just at the beginning of a series of Vioxx-based legal battles, which are expected to continue for years to come. (…) (The August case is under appeal, and Texas law will cut the award by 90%. But the company is just at the beginning of a series of Vioxx-based legal battles, which are expected to continue for years to come.)

Merck's overall liability in the lawsuits could reach $20–35 billion, according to analysts. (Merck's overall liability in the lawsuits could reach $20–35 billion, according to analysts.)

The company has vowed not to make any settlements, and instead promises to fight every case in court. It has already set aside $675 million for the effort. (The company has vowed not to make any settlements, and instead promises to fight every case in court. It has already set aside $675 million for the effort.)

But Vioxx's fallout goes well beyond Merck and its ledgers. Manufacturers facing mounting political pressure have now agreed to scale back advertising—an activity once staunchly defended by the industry. Meanwhile, the US Food and Drug Administration (FDA) has taken what some see as a defensive posture designed to avoid another safety debacle. (…) (But Vioxx's fallout goes well beyond Merck and its ledgers. Manufacturers facing mounting political pressure have now agreed to scale back advertising—an activity once staunchly defended by the industry. Meanwhile, the US Food and Drug Administration (FDA) has taken what some see as a defensive posture designed to avoid another safety debacle.)

But the lawsuits reflect concerns over prescription-drug safety that go well beyond the courtroom. Other manufacturers are also reacting to allegations that they were too cavalier with safety in the rush to get promising new drugs to market. (But the lawsuits reflect concerns over prescription-drug safety that go well beyond the courtroom. Other manufacturers are also reacting to allegations that they were too cavalier with safety in the rush to get promising new drugs to market.)

As the Texas jury was nearing judgment against Merck in August, the Pharmaceutical Research and Manufacturers of America, the industry's main trade group, committed companies to withhold consumer advertisements of new drugs until physicians have been sufficiently educated about risks and benefits. (As the Texas jury was nearing judgment against Merck in August, the Pharmaceutical Research and Manufacturers of America, the industry's main trade group, committed companies to withhold consumer advertisements of new drugs until physicians have been sufficiently educated about risks and benefits.)

“They've clearly gotten the message and tried to back away from (consumer advertising) discreetly”, says Alistair Wood, a professor of medicine and pharmacology at Vanderbilt Medical School in Nashville, TN, who chaired a 3-day series of hearings on COX2 safety in February. (…) (“They've clearly gotten the message and tried to back away from (consumer advertising) discreetly”, says Alistair Wood, a professor of medicine and pharmacology at Vanderbilt Medical School in Nashville, TN, who chaired a 3-day series of hearings on COX2 safety in February.)

The agency has vastly increased the amount of safety-report information it shares with the press and the public, regularly publicising minor drug-label changes and other safety information. An independent review of how the agency monitors drugs already on the market is underway, and over the summer the agency created a new board to help monitor drug safety. (The agency has vastly increased the amount of safety-report information it shares with the press and the public, regularly publicising minor drug-label changes and other safety information. An independent review of how the agency monitors drugs already on the market is underway, and over the summer the agency created a new board to help monitor drug safety.)

Legemiddelstyrelsen

Næsespray kan give nerveskader
netdoktor.com 7.4.2006
Almindelige næsespray som Otrivin er under mistanke for at være årsag til nervebetændelse.

Mistanken kommer, efter at en patient, der gennem flere år dagligt har brugt næsespray mod forkølelse og stoppet næse, har fået konstateret polyneuropati, en nervebetændelse, der sætter sig i hænder og fødder.

Novartis, der producerer næseprayen Otrivin, bekræfter, at et ekstremt overforbrug gennem længere tid kan føre til nerveskader. Derfor står der også på indlægssedlen, at produktet ikke bør bruges mere end otte dage.

Lægemiddelstyrelsen mener, at der er indberettet for få bivirkningsrapporter om næsesprayen, til at forbrugerne skal have besked.
Forbrugerrådet er uenige og mener ikke, at det er antallet af indberetninger, der skal afgøre, om en bivirkning skal med på en indlægsseddel.

- Tidligere sjef i FDA dømt for løgn om interessekonflikter

Former FDA commissioner is fined $90 000 for failing to disclose conflicts of interest (Tidligere FDA-leder er idømt 90 000 dollar i bot for å unnlate å offentliggjøre interessekonflikter)
BMJ 2007;334:492 (10 March)
Lester Crawford, former commissioner of the US Food and Drug Administration, was last week fined $89 377 (£45 800; € 67 000), sentenced to three years of supervised probation, and required to do 50 hours of community service by Judge Deborah Robinson of the US District Court for the District of Columbia.
Last October Dr Crawford pleaded guilty to two charges: failing to report that he and his wife owned shares in companies regulated by the agency and filing false financial reports. The reports are required by US law. The companies included Pepsico, Kimberly-Clark, and Sysco. At the time Dr Crawford was head of the FDA's obesity working group (BMJ 2006; 333:874, doi: 10.1136/bmj.333.7574.874-a). (...)

FDA ex-chief spared jail time
washingtontimes.com 28.2.2007
A judge yesterday sentenced Lester Crawford, former Food and Drug Administration commissioner, to three years of supervised probation with fines of roughly $90,000 for lying about stocks he owned in companies regulated by his agency.

Magistrate Judge Deborah A. Robinson's sentence spares Crawford jail time but is stiffer than the punishment of $50,000 proposed by federal prosecutors and his defense attorney.

"While the total fine exceeds what the parties agreed to, the fine is well below the maximum under the statute," Judge Robinson said in a 90-minute hearing in which she sometimes questioned the extent of Crawford's remorse. (...)

Former FDA Commissioner Crawford Sentence Includes Supervised Probation, $90K in Fines
kaisernetwork.org 28.2.2007
(...) During a 90-minute sentencing hearing, Crawford said, "I want to assure you that I accept responsibility for what I've done." He declined to comment after the hearing. Attorney Barbara Van Gelder, who represented Crawford, said that he should have received a lesser sentence because he did not intend to defraud or misuse his position at FDA for personal financial gain. (...)

Former FDA Chief Crawford's Fraud Case Sentencing Postponed
foxnews.com 23.1.2007
WASHINGTON — Former FDA Commissioner Lester Crawford's sentencing on charges he lied about his stock holdings was delayed Tuesday over questions about sentencing guidelines.

Under a deal worked out between his attorney and federal prosecutors, Crawford had agreed earlier to a $50,000 fine and probation.

Magistrate Judge Deborah A. Robinson asked the attorneys to explain why they didn't use certain federal sentencing guidelines in recommending a penalty.
Sentencing was rescheduled for Feb. 27. (...)

Former FDA commissioner pleads guilty to two charges
BMJ 2006;333:874 (28 October)
Lester Crawford, the former commissioner of the US Food and Drug Administration, pleaded guilty in a district court in Washington, DC, last week to two charges: conflict of interest and failing to disclose financial holdings in companies that the FDA regulated. Each charge carries a maximum penalty of a year in prison and a fine. Dr Crawford will be sentenced on 22 January 2007. (...)

Ex-FDA chief admits conflicts (Tidligere FDA-sjef innrømmer interessekonflikter)
boston.com 18.10.2006
(...) Crawford admitted to falsely reporting that he had sold or did not own stock when he continued holding shares in the firms governed by rules of the Food and Drug Administration. Beginning in 2002, Crawford filed seven incorrect financial reports with a government ethics office and Congress, leading to the charges. (...)

Former F.D.A. Chief Is Charged With Conflict (Tidligere sjef i FDA anklaget for interessekonflikter)
nytimes.com 17.10.2006
Lester M. Crawford, former chief of the Food and Drug Administration, was charged yesterday with conflict of interest and lying about stock he and his wife owned in companies the agency regulates. (...)

Former FDA Chief Crawford Pleads Guilty To Not Disclosing Financial Ties to Agency-Regulated Companies
kaisernetwork.org 17.10.2006
Lester Crawford, who resigned as FDA commissioner last year, is expected to plead guilty on Tuesday to federal charges that he failed to disclose his and his wife's ownership of stock in companies regulated by the agency, according to his attorney, Barbara Van Gelder, the Washington Post reports (Kaufman, Washington Post, 10/17). Crawford left FDA in September 2005, two months after his Senate confirmation. At the time, some reports indicated that a failure to disclose financial holdings led Crawford to leave. (...)

(Anm: Former FDA Chief Illegally Held Stocks. washingtonpost.com (17.10.2006).)

Ex-FDA chief to plead guilty (Tidligere FDA-sjef erklærer seg skyldig)
boston.com 15.10.2006
In this Feb. 15, 2005, file photo, Lester M. Crawford talks to FDA employees in Rockville, Md. Crawford, the former FDA chief, was charged Monday with lying about his ownership of stock in companies regulated by his agency. (...)

The Justice Department accused the former head of the Food and Drug Administration in court papers of falsely reporting that he had sold stock in companies when he continued holding shares in the firms governed by FDA rules. (...)

Former FDA Chief Joins Lobby Shop
washingtonpost.com 8.2.2006
Former Food and Drug Administration commissioner Lester M. Crawford, whose sudden resignation last fall after less than three months in office remains a mystery, has joined a lobbying firm that specializes in food and drug issues.

Crawford is listed as "senior counsel" to the firm Policy Directions Inc. Among the companies and organizations listed as clients are Altria Group Inc. (formerly Philip Morris Companies), Merck & Co. Inc., the Pharmaceutical Research and Manufacturers of America (PhRMA,) the Grocery Manufacturers of America and the American Feed Industry Association. A spokesman for the firm said neither Crawford nor anyone else wished to discuss his appointment.

Ex-Head of F.D.A. or Wife Sold Stock in Regulated Area
New York Times 27.10.2005
Dr. Lester M. Crawford, the former commissioner of the Food and Drug Administration, or his wife sold shares in companies regulated by the agency in 2004, according to financial disclosure forms.

The sales may have played a role in Dr. Crawford's sudden resignation from the agency last month after only two months as its leader.

F.D.A. Chief Quit Over Financial Disclosure Form, His Wife's Brother Says (Lederen for FDA sier opp grunnet formularer om økonomiske opplysninger, sier hans kone og bror)
New York Times 28.9.2005
Lester M. Crawfords kone har fortalt familiemedlemmer at en utilsiktet forsømmelse å opplyse om verdipapirer, foranlediget sist uke hans plutselige avgang som kommisær for mat og legemidler, sa hans bror i går. (...) (Lester M. Crawford's wife has told family members that an unintentional failure to disclose financial holdings prompted his sudden resignation as commissioner of food and drugs last week, her brother said yesterday.)

FDA to Probe Chief's Departure
Washington Post 26.8.2005
Crawford Denies Conflict of Interest
Lawmakers concerned and mystified about last month's sudden retirement of Food and Drug Administration Commissioner Lester M. Crawford may get some answers.

At the time, they requested an investigation, and this week the inspector general who monitors the FDA said he has begun a review.

"This office is currently reviewing the circumstances regarding Dr. Crawford's resignation. Depending upon the results of the review, we will determine the next appropriate action," Department of Health and Human Services Inspector General Daniel R. Levinson wrote to members of Congress.

Editorial
Selling Safety Lessons From Muraglitazar
JAMA (20 October 2005)

Effect of Muraglitazar on Death and Major Adverse Cardiovascular Events in
Patients With Type 2 Diabetes Mellitus
JAMA (20 October 2005)

Crawford's hasty exit from FDA raises concerns about vetting
The Hill 4.10.2005
The abrupt and mysterious resignation of Lester Crawford as commissioner of the Food and Drug Administration (FDA) has prompted questions from a Senate committee about the Bush administration’s vetting process.

Senate Health, Education, Labor and Pensions (HELP) Committee Chairman Mike Enzi (R-Wyo.) and ranking member Edward Kennedy (D-Mass.) are concerned that reports about information missing from Crawford’s financial disclosure forms might be a sign the administration is not being careful enough when it OKs nominees for high-profile positions such as FDA chief, an Enzi aide said.

The committee leaders are seeking information to explain what prompted Crawford to walk away from a job he waited several years to lock up, but they are also eyeing answers to broader questions, according to Enzi’s aide.

What is going on at the FDA?
The Lancet 2005; 366:1137 (1 October 2005)
The scene at the US Food and Drug Administration (FDA) headquarters last week, after the sudden resignation of Commissioner Lester Crawford on Sept 23, was depressingly familiar: a leaderless FDA was plunged into organisational uncertainty, while persistent claims of political meddling in scientific decisions rumbled on.

FDA chief resigns without warning
BMJ 2005;331:713 (1 October)
After only two months as commissioner, but 30 years at the organisation, Lester Crawford, head of the Food and Drug Administration, abruptly resigned last Friday. He sent an email message to FDA staff members saying, "It is time, at the age of 67, to step aside."

President Bush immediately named Andrew von Eschenbach, director of the National Cancer Institute, as temporary commissioner. Dr von Eschenbach said he would continue to hold both jobs. (...)

Dr Crawford's resignation comes after a difficult year for the, FDA, in which it has been criticised for refusing to allow availability over the counter of the emergency contraceptive Plan B (BMJ 2005;331: 596 [Free Full Text], 17 Sep) and for failing to act quickly enough on evidence indicating that the cyclo-oxygenase-2 inhibitor rofe-coxib (Vioxx) had serious side effects (Lancet 2005;365:449-51 [ISI][Medline]. The drug was withdrawn by its manufacturer Merck last year (BMJ 2004;329: 816 [Free Full Text]7 av 10 anmelder ikke økonomisk kriminalitet
dagbladet.no 4.7.2010
- De fleste mener det ikke er noen vits, sier Dag Ellingsen i SSB.

(Dagbladet): Bare tre av ti anmelder økonomisk kriminalitet til politiet. Det kommer fram i en ny undersøkelse Statistisk sentralbyrå (SSB) har utført blant 1800 virksomheter i Norge.

- De fleste sier at det ikke er noen vits i å anmelde forholdene. Det gir ikke noen resultater, det er vanskelig å bevise, og man har gjort opp med gjerningspersonen, sier seniorrådgiver Dag Ellingsen i SSB til Dagbladet. (...)

The agency has also had to contend with criticism arising from malfunctions in implanted cardiac defibrillators, a shortfall in flu vaccine because of problems with a British supplier (BMJ 2004;329: 876 [Free Full Text]), and delay in warning about an increased risk of suicide in children and adolescents taking antidepressants (BMJ 2004;329: 702 [Free Full Text]).

Faces In The News
Former FDA Chief Denies Financial Conflicts
Forbes 28.9.2005
Lester M. Crawford, who resigned as commissioner of the Food and Drug Administration last Friday, told Forbes.com that he decided to leave the agency because he was tiring after three years at the agency. He denies that financial conflicts of interest had anything to do with his decision to resign.

"I thought it was time for somebody else to do it," Crawford says. "I didn't think it was possible to be very effective anymore." (...)

In addition, the Government Accountability Office was going to start routine investigations into financial conflicts, and Crawford says he did not want to go through that process again. Crawford's tenure has been marked by controversy, extending not only to issues of reproductive health but also drug safety, including the firestorm that surrounded the safety of Vioxx--the withdrawn Merck (nyse: MRK - news - people) painkiller--and similar medicines made by Pfizer (nyse: PFE - news - people).

Crawford says he did not want to be a "lame-duck" commissioner, and that he wanted to start looking for his next job--something he couldn't do while he was still heading up the FDA.

"Another year of that stuff," he says, "I didn't think I was up to it."

Leader of the F.D.A. Steps Down After a Short, Turbulent Tenure (Lederen for FDA går etter et kort, turbulent tjenesteforhold)
New York Times 24.9.2005
- Lester M. Crawford, ansvarlig leder for mat og legemidler, som sa opp med umiddelbar virkning på fredag, forårsaket ytterligere virvar i det kaos som har rådet i kontrollorganet i mer enn et år (- Lester M. Crawford, the commissioner of food and drugs, resigned abruptly on Friday, causing further upheaval at an agency that has been in turmoil for more than a year.)

Dr. Crawford, som ble innsatt for bare to måneder siden, den 18.juli, etter å ha fungert som leder i mer enn et år, opplyste ikke hvorfor han gikk av. (Dr. Crawford, who was confirmed just two months ago, on July 18, after serving as acting commissioner for more than a year, did not say why he was stepping down.)

Seniorledere hos Food and Drug Administration sa de var forskrekket over å bli opplyst om oppsigelsen i en e-post fra dr. Crawford, som også sendte et brev til president Bush om at hans oppsigelse var "gjeldende med øyeblikkelig virkning." (...) (Senior officials at the Food and Drug Administration said they were stunned to learn of the resignation in an e-mail message from Dr. Crawford, who also sent a letter to President Bush stating that he was resigning "effective immediately.")

I de siste uker har talsmenn for forbrukerne og forskere innenfor og utenfor kontrollorganet sagt at politikk har fordreid vitenskapelige beslutninger. (In recent weeks, consumer advocates and scientists inside and outside the agency had said scientific decisions were being warped by politics. )

I en kommentar i New England Journal of Medicine torsdag heter det under tittelen "En trist dag for vitenskap hos FDA" at "nylige handlinger til lederskapet hos FDA har latterliggjort evalueringsprosessen av vitenskapelige bevis," har desillusjonert mange vitenskapsmenn, "skuslet bort publikums tillit og skadet kontrollorganets profil." (On Thursday, a commentary in The New England Journal of Medicine titled "A Sad Day for Science at the F.D.A." said that "recent actions of the F.D.A. leadership have made a mockery of the process of evaluating scientific evidence," disillusioned many scientists, "squandered the public trust and tarnished the agency's image.")

FDA Leader Steps Down
CBS 23.9.2005
(...) His resignation came just two months after the Senate, in a long-delayed move, elevated the longtime agency deputy and acting commissioner to the top job.

Crawford's three-year tenure at FDA was marked by increasing criticism, as the painkiller Vioxx was pulled off the market for safety problems, recalls of malfunctioning heart devices mounted and controversy grew over wider access to emergency contraception.

- Public Citizen’s Health Research Group

Von Eschenbach is Not Qualified to Lead the U.S.Food and Drug Administration
Public Citizen 15.3.2006
Statement of Sidney M. Wolfe, M.D., Director of Public Citizen’s Health Research Group
If confirmed by the U.S. Senate to be the next commissioner of the Food and Drug Administration (FDA), Dr. Andrew von Eschenbach will become yet another Bush appointee whose main reason for being selected is that he is a family friend, someone who has been warmly embraced by the regulated industries – especially the pharmaceutical industry – and someone who has been and will continue to be loyal to the White House agenda.

Von Eschenbach continues to exhibit extraordinarily bad judgment, a lack of being in touch with reality and insensitivity to the hopes and fears of other cancer patients and their friends and families, as evidenced by his oft-stated “plan” to eliminate the suffering and death from cancer by 2015. Eradicating cancer within 10 years is not realisitic, and by making this statement, von Eschenbach is cruelly raising people’s hopes.

He is a very poor choice to head this critical agency, and his nomination must be defeated. Otherwise, the FDA will be further weakened and the public health further damaged by someone who is so unqualified.

- Transparent regulering av legemiddelindustrien

Regulating the drugs industry transparently
Editorial
BMJ 2005;331:528-529 (10 September)
The UK government has not gone far enough in responding to a critical inquiry

Over the past 10-15 years, drug regulatory authorities in the United Kingdom and elsewhere have streamlined and accelerated the review of new drugs in response to claims by the pharmaceutical industry that over-regulation was stifling innovation.^{1 2} Despite these policies, the number of new molecular entities—a standard measure of innovation in the industry—submitted to regulatory authorities in the European Union or United States or launched on the world market has fallen overall during the past decade.³-⁵

Issues of secrecy, transparency, and public accountability in the drug regulatory system pervaded almost every aspect of the inquiry. The government agrees that the regulatory system should be as transparent as possible. It has promised to provide public access to information on licensing applications for individual drugs, to the data supporting authorisation for marketing, and to assessments of medicines on which regulatory action is taken. This is a considerable and welcome shift in thinking and policy, but these commitments must also be implemented in practice.

The committee recommended that the MHRA should make public the material it receives from drug companies along with its assessments as soon as they are complete. This would enable scientists and doctors to scrutinise and engage with the agency's decision making processes and would ensure that drug regulation was publicly defensible and hence more robust. The government, however, insists on reaching regulatory decisions about applications for new drug licences before allowing any public access to such information. At least, though, the government has agreed that the MHRA should be independently reviewed every four or five years.

Rapid Response

Open label extension studies: research or marketing?
BMJ 2005;331:572-574 (10 September) (...)

As with any research method, there are good and bad examples. However, open label extension studies seem particularly prone to the pressures of marketing over good research methods and research ethics. We revisit some of these issues and argue that we need to change our approach to the ethical review of such studies. (...)

Use of open label studies after phase III trials is relatively common. In 2004, the multicentre research ethics committee for Wales reviewed three open label extension studies compared with 19 phase III studies of new drugs, a ratio of just over 6:1. However, a recent Medline search for studies between 2000 and 2004, produced only 86 open label studies but over 2000 phase III studies, a ratio of 23:1. This suggests that many open label studies are never published. (...)

The validity of data from open label extension studies raises further questions. Open label extension studies are commonly used to assess long term tolerability of a new drug. However, a proportion of the participants eligible for the study will have already taken the study drug. Those who are unable to tolerate it are therefore unlikely to take part in the extension study. The absence of this group of potential participants will introduce bias and increase the apparent tolerability of the new drug. Analysis strategies need to be developed and implemented to provide unbiased estimates of safety and tolerability. (...)

FDA Standards — Good Enough for Government Work? (FDA Standarders — Gode nok for myndighetenes arbeid?)
New England Journal of Medicine (NEJM) 2005;353:969-972 (September 8)
Klisjéen "godt nok for staten" innebærer at lavere standarder er akseptabelt for en jobb sponset av et offentlig kontor. Men i biomedisinsk forskning, gjelder vanligvis det motsatte. National Institutes of Health har alltid hatt robuste standarder; dets nye framtvungne finansiering fører til en enda strengere gjennomgangsprosess, slik at nesten perfekt score fra evalueringen er nå krevd for å få støtte. Liknende strenge kriterier gjøres gjeldende hos National Science Foundation. Likevel er der et område innen biomedisin hvor staten tillater — til og med forsvarer — en minstestandard som ville være uakseptabel noen andre steder innen forskning. Det er de samlede kravene til bevismateriale håndhevet av Food and Drug Administration (FDA) for godkjennelsen av nye legemidler. (The cliché "good enough for government work" implies that lower standards are acceptable for a job sponsored by a public agency. But in biomedical research, the opposite is usually true. The National Institutes of Health has always had tough standards; its newly constrained funding is leading to an even more stringent review process, so that near-perfect evaluation scores are now required to win support. Similarly stringent criteria prevail at the National Science Foundation. Yet there is one area of biomedicine in which the government allows — even defends — a minimal standard that would be unacceptable anywhere else in research. It is the set of evidentiary requirements maintained by the Food and Drug Administration (FDA) for the approval of new drugs.)

Wall Street biotech insider gets No. 2 job at the FDA
Seattle Times 24.8.2005
Only a month ago, Dr. Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors.

Now Gottlieb holds the No. 2 job at the Food and Drug Administration (FDA), the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted.

Wall Street likes the appointment of Gottlieb, 33, who believes in faster drug approval and fewer news-release warnings to the public about potential side effects of drugs. But some medical experts are shocked by his July 29 appointment, coming at a time when the public is increasingly concerned about the safety of popular medicines. In addition, the federal government has just begun scrutinizing the growing financial ties between Wall Street firms and doctors researching new drugs.

Gottlieb's new job "further impedes the independence of the FDA," said Dr. Jerome Kassirer, former editor of The New England Journal of Medicine. "Gottlieb has an orientation which belies the goal of the FDA."

"I've never heard of anything like this," said Merrill Goozner, a director at the liberal Center for Science in the Public Interest. "If he's had dealings regarding companies whose products are up for review at the agency, it strikes me as a potential conflict of interest. You want a barrier between the regulated and the regulators. It's fundamental," Goozner said

A half-dozen current or former officials at the FDA say they do not know of anyone from Wall Street moving directly into such a high-level job at the agency.

Until last month, Gottlieb was editor of a popular biotechnology investor newsletter, Forbes / Gottlieb Medical Technology Investor. Forbes touted Gottlieb's stock-picking success on its Web site in mid-May: "Special Offer: In the last few months, Dr. Scott Gottlieb recommended two cancer cure stocks to subscribers that have already climbed 38%.
Click here for the latest report from Forbes / Gottlieb Medical Technology Investor, 'Three Biotech Stocks To Buy Now.' "

Now, as one of three deputy commissioners, Gottlieb will help oversee such major policies as the FDA's fast-track approval process for drug and biotech products, a priority for many Wall Street funds and the pharmaceutical industry.

Gottlieb said he has cut his ties to Wall Street and discontinued his newsletter. He doesn't see a conflict between that work and his new role as a high-ranking regulator......

.....When the FDA announced Gottlieb's hiring last month, it noted Gottlieb had been a practicing physician, a scholar at AEI and correspondent for the British Medical Journal. The agency did not mention Gottlieb's stints as editor of the two popular biotech investment newsletters or his work with Wall Street firms.

U.S. drug makers up in arms over info on FDA "Drug Watch" web page
News-Medical.Net 9.8.2005
Pharmaceutical companies in the United States are up in arms over plans by U.S. regulators to release preliminary information, about the potential side effects of drugs.

The drug manufacturers say that the action could lead to unnecessary confusion and "irrational fears" about drugs.

The proposed "Drug Watch" Web page by the Food and Drug Administration (FDA), would apparently list safety concerns about drugs being evaluated by the agency.

According to the drug industry's U.S. lobbying group,the Pharmaceutical Research and Manufacturers of America (PhRMA) , the information the FDA is aiming to publicize "is too vague and preliminary", to be of value in making informed treatment and prescribing decisions, and is unlikely to accomplish anything other than create more confusion among physicians and the public.

PhRMA is arguing that the release of early information may violate a law requiring data released by federal agencies to be useful, and it also suggests the plan may exceed the FDA's authority.

PhRMA President Billy Tauzin says they are concerned that bad information gets into the system, and people stop using drugs they need.

The FDA is yet to comment.
The Web page was proposed by regulators after charges that FDA officials suppressed concerns by staff scientists concerning drugs such as Merck's arthritis pill Vioxx. The company were forced to recall Vioxx in September 2004 amid mounting evidence of links to heart attacks and strokes.

At the time the FDA promised in future to release information sooner, including posting it on the Drug Watch page.

PhRMA has also voiced it's concern that the FDA may not provide companies with sufficient notice of new information for the Web site, or give them the opportunity to make an input.

According to the FDA's Web site, www.fda.gov, it wants to make sure patients "have quick access to the most up-to-date and emerging product information" for making treatment decisions.

The Lessons of Vioxx — Drug Safety and Sales

FDA urged to hold off on approving silicone gel implants
USA TODAY 9.8.2005
WASHINGTON — A coalition of health advocacy groups urged the Food and Drug Administration on Tuesday to refrain from approving silicone-gel breast implants until the manufacturer provides long-term data about the devices' safety.

F.D.A. Will Not Release Some Data on Heart Devices
New York Times 6.8.2005
The Food and Drug Administration said yesterday that it would not release information that it receives annually from the makers of heart devices detailing how often and why products fail. The agency called such data a corporate trade secret.

The F.D.A. took its position in response to a Freedom of Information Act request from The New York Times, which had sought annual reports filed by the Guidant Corporation in connection with a defibrillator, the Ventak Prizm 2 DR. From 2000 to 2002, Guidant made thousands of the devices, some of which had electrical flaws that caused them to short-circuit. In March, a college student with a flawed device died of cardiac arrest.

Independence at the top p442
Nature
The US Food and Drug Administration badly needs some strong and stable leadership.
10.1038/436442a
Full Text | PDF

"We can't risk another Dalkon shield," said Cindy Pearson, executive director of the National Women's Health Network. The Dalkon shield intrauterine contraceptive device, or IUD, came on the U.S. market in 1971 and was pulled in 1974 amid claims that it caused pelvic inflammatory disease, which can leave women infertile.

F.D.A. Responds to Criticism With New Caution
New York Times 6.8.2005
Stung by a series of drug safety scandals, the Food and Drug Administration has in recent months issued a blizzard of drug-safety warnings and approval times for new drugs are slower.

The agency is issuing twice the number of public advisories about drug risks as it did a year ago and adding five times as many black box warnings - its most serious alert - to drug labels. And drugs approved in the first half of this year took almost twice as long to get that approval as drugs approved in the same period last year.

This new conservatism, a response to fierce recent criticism from Congress that the F.D.A. has failed to protect the public against drug dangers, has upset some doctors and drug makers.

FDA chief answers his critics in House
The Boston Globe 27.7.2005
WASHINGTON -- Food and Drug Administration commissioner Lester Crawford rebuffed critics by testifying yesterday before Congress that the FDA was deemed among the best agencies within the Department of Health and Human Services, a designation that allowed additional money. That added funding was one reason bonuses tripled under Crawford's tenure.

FDA Was Told of Viagra-Blindness Link Months Ago
Washington Post 1.7.2005
"More than 13 months before a scientific journal reported that Viagra had been linked to a rare form of blindness in some men, a Food and Drug Administration safety officer made the same observation from monitoring adverse event reports and told her supervisors that doctors and patients should be warned of the findings.

Her recommendation was well received, she told congressional investigators, but nothing happened. The FDA issued no public notice or proposed changes to the Viagra label. That came only following widespread publicity last month about the journal article and public concerns about the possible blindness-Viagra link."

What ails the FDA
Boston Globe 10.3.2005
LET'S FACE it. The FDA is doing a poor job of ensuring that prescription drugs are safe and effective. It approves drugs that offer only minimal benefit, and then sometimes leaves them on the market long after they've been shown to be dangerous.

Give the FDA more help on drug safety (Gi FDA mer hjelp til legemiddelsikkerhet)
The Hill 16.2.2005
Den amerikanske legemiddelkontrollen FDA gir godkjennelsesprosessen høy prioritet og bruker store ressurser på å få nye produkter på markedet, men lite på å sikre at de legemidler som faktisk brukes, har nytteverdi uten å innebære unødvendig risiko. (...) (Today, the FDA pharmaceutical approval process gives high priority and abundant resources to putting new products on the market but does little to ensure that drugs — as actually used — deliver their benefits without imposing undue risk.)

Fixing The FDA
Five Ways To Fix The FDA
Forbes 12.1.2005
The U.S. Food and Drug Administration may have the world's toughest job.
Forbes
A quarter of every dollar Americans spend annually--some $1 trillion in total--is regulated by the FDA. From the start, the safety of medicines has been the agency's most sacrosanct calling. The FDA was founded after a 1937 incident in which a poisonous medicine killed 107 people, most of them children. (...)

FDA Fix 1: Pay Up
How do we expect to police a $216 billion industry on $300 million per year?

FDA Fix 2: Power Up The FDA
Give the FDA powerful sticks and carrots to compel drug companies to test their medicines more thoroughly.

FDA Fix 3: Track Side Effects
In order to make sure that medicines are safe, we need to find new ways to track existing drugs.

FDA Fix 4: Fund Drug Studies
Right now, we depend entirely on companies to test the drugs they sell us. That's not smart medicine, and it's bad economics too.

FDA Fix No. 5: Forget Labels
Adding warnings to drugs has a limited effect. Does the FDA need its own ad agency?

Legemiddelkontroll

Psychiatric Drugs' Use Drops for Children
Suicide Warnings Raise Bigger Fears On Testing Process
Washington Post 8.10.2005
Warnings that drugs such as Prozac, Paxil and Effexor can increase suicidal behavior in some children have resulted in a nearly 20 percent drop in U.S. pediatric prescriptions of the widely used antidepressants and have triggered deep concerns about the quality of current data on psychiatric drugs, doctors and regulators said.

The unprecedented fall of what were once considered wonder drugs comes as a series of taxpayer-funded analyses have systematically undermined the claims of industry-funded drug trials, raising thorny questions about the ways in which psychiatric drugs are being tested, marketed and used. (…)

Senior FDA officials say they are weighing whether companies should be required to conduct longer trials to reveal the true risks and benefits of the drugs.

Pharmaceutical makers say that profound change would increase the time and expense of bringing new medications to market.
Although the agency does ask that companies pursue long-term trials after drugs are approved, few do. At a meeting this month, Laughren said, regulators will debate whether long-term trials "should be asked for at initial approval." (…)

In the absence of long-term data, however, doctors, parents and patients have been confused by a steady stream of concerns that have recently emerged:

• An FDA review last year found that newer antidepressants increase suicidal behavior among some children, and the agency ordered that a "black box" warning be placed on them.
• British authorities last month went even further, telling doctors there never to prescribe medications to depressed children without first trying multiple alternatives, and never to prescribe drugs without also providing psychotherapy. Doctors were also warned not to prescribe the antidepressants Paxil and Effexor to depressed children under any circumstances.
• On Sept. 28, the FDA announced that the drug Strattera, prescribed widely to children with attention deficit disorder, had also been found to increase the risk of suicidal behavior in some, and told manufacturer Eli Lilly and Co. to add a black-box warning.
• Also last month, a major government analysis of antipsychotic medications found newer, expensive drugs were neither safer nor more effective than an older generic medication that doctors rarely use. The drugs had never been systematically compared in a long-term trial. Another study in older patients, paid for by Canadian health authorities, found the newer drugs "are not necessarily safer" when it came to causing uncontrolled movements; for years, doctors have believed the newer drugs were significantly less likely to cause that side effect.

Reflecting the confusion caused by the lack of good data, FDA regulators have drawn the ire both of critics who say the agency has not gone far enough to protect patients who take the drugs and of many psychiatrists who say the agency is going too far.

Antidepressant prescriptions for children fell nearly 20 percent in the last year, according to a recent report by the American Psychiatric Association and data from NDCHealth, a health care information company. Experts at the association worry that patients have been scared into thinking the drugs are dangerous, when the bigger danger of suicide lies in untreated depression.

- Public needs vs. company secrets

Safety mission in a haze
newsday.com 15.2.2006
FDA board, created to monitor drug problems, wrestles over public needs vs. company secrets

A need to protect business secrets balanced against an obligation to inform the public about the risks of prescription medicines has created a dilemma for government drug regulators.

Last February, the Food and Drug Administration promised a new openness after reports of more than 1,000 deaths linked to the arthritis drug Vioxx.

Citing an "emboldened vision," FDA officials unveiled plans for a new board that would monitor drug safety issues and inform the public about possible dangers.

By the time the FDA announced the creation of its new Drug Safety Oversight Board, the agency already had received about 28,000 complaints concerning patients' adverse reactions to Vioxx, made by Merck & Co. The adverse event reports included 1,282 deaths and almost 3,000 heart attacks, strokes or blood clots. The drug was taken off the market in September 2004.

During the past eight months the drug safety board has been trying to find its way - determining its role within the FDA and providing input on certain drugs.

But as concerns about prescription drug safety have escalated, the oversight board has met only five times - always in private.

- Questions about the fast tracking

FDA to ID Research for Drug Development
newsday.com 14.3.2006
WASHINGTON -- Federal regulators, working with patients, academics and pharmaceutical companies, are listing dozens of potential research projects they believe would help shorten the time it takes for new drugs to reach patients.

Lessons for clinical trials from natalizumab in multiple sclerosis
bmj.bmjjournals.com 18.2.2006
BMJ 2006;332:416-419 (18 February)
Analysis and comment (...)

The approval of natalizumab and its recall after three months raises questions about the fast tracking of new drugs by the Food and Drug Administration for commercial licensing.

Alarm over drugs fast-tracking
dehavilland.co.uk 17.2.2006
(...) Dr Chaudhuri suggests: "The approval of natalizumab and its recall after three months raises questions about the fast tracking of new drugs by the FDA for commercial licensing.

"It also highlights the potential risks for patients in trials of new drugs where knowledge of long term efficacy, outcome measures, and safety is lacking."

Natalizumab was licensed for use in relapsing MS patients based on short term results from two unpublished trials, ahead of the publication of final trial and cumulative safety data.

- Vitenskapen er der i virkeligheten ikke ennå

FDA head supports quicker drug OKs
baltimoresun.com 7.3.2006
Stance part of push on fatal-disease treatments

WASHINGTON -- The nation's top drug regulator pledged his agency's support yesterday for research to develop the next wave of tools for preventing and treating fatal diseases like cancer.

Dr. Andrew C. von Eschenbach, acting commissioner of the Food and Drug Administration, said his agency is taking steps to encourage the development of safe and effective medical treatments tailored to a patient's particular condition.

"We can improve the processes by which that developmental process occurs, is regulated and is approved," von Eschenbach told the Personalized Medicine Coalition, an industry group.

Von Eschenbach also vowed to make faster drug approval "one of my highest priorities," however long he leads the agency.

The idea behind "personalized medicine" is that doctors will be able to prevent and treat serious diseases more effectively with genetic tests telling them which patients are at high risk of falling ill and which therapies will best treat those already sick, supporters say.

But some scientists caution that quick approvals of the treatments may come at the expense of a thorough understanding of possible side effects. They are especially concerned about the FDA allowing use of drugs without putting them through random testing.

Vera Hassner Sharav, president of the liberal Alliance for Human Research Protection in New York, said the acting commissioner and supporters of personalized medicine were moving too quickly and might harm patients.

"Vitenskapen er der i virkeligheten ikke ennå," sa hun. (...) ("The science isn't really there yet," she said.)

- F.D.A. lacks the regulatory authority and the money needed to detect and protect against drug dangers

F.D.A. Says Bayer Failed to Reveal Drug Risk Study
nytimes.com 29.9.2006
WASHINGTON, Sept. 29 — Bayer A.G., the German pharmaceutical giant, failed to reveal to federal drug officials the results of a large study suggesting that a widely used heart-surgery medicine might increase the risks of death and stroke, the Food and Drug Administration announced Friday.

Bayer scientists even appeared at a public meeting called by the F.D.A. on Sept. 21 to discuss the possibility that the drug, Trasylol, might have serious risks. But they did not mention the study or its worrisome results.

In a highly unusual move, the food and drug agency released a public health advisory saying it had learned of the study’s existence only on Wednesday. Preliminary results of the study demonstrate “that use of Trasylol may increase the chance for death, serious kidney damage, congestive heart failure and strokes,” the advisory said. (...)

The disclosure comes exactly two years after Merck announced it was withdrawing its arthritis drug, Vioxx, after a study showed that it doubled the risks of heart attacks. Since then, members of Congress and even top scientific advisers have concluded that the F.D.A. lacks the regulatory authority and the money needed to detect and protect against drug dangers. (...)

- A new prescription

A new prescription
fortwayne.com 2.10.2006
(...) Imagine if government regulators spent years testing the safety of new cars before they went on sale, then virtually ignored what happened after they were purchased.

Suppose that car tests were conducted only by automakers themselves, using a handful of the best and safest drivers, and nobody paid attention to how safe cars were in real driving conditions with all sorts of drivers. And, finally, imagine that when problems cropped up, regulators had only limited authority to order fixes. That wouldn't be a good way to protect Americans from unsafe cars. So why would anyone think it was a good way to protect Americans from unsafe drugs?

The U.S. Food and Drug Administration has been under increasing criticism for allowing unsafe drugs to stay on the market. The problem stretches back for years.

This month, a prestigious group of scientists came down firmly on the side of the critics. The Institute of Medicine, part of the National Academy of Sciences, released a sweeping report last week calling for major changes at the FDA. (...)

Legemiddelfirmaet og legemiddelkontrollen (Food and Drug Administration) forsvarer hverandre

Suit: Vioxx maker liable for mom' death
news-journalonline.com 4.12.2006
"Despite the risks, Merck continued to conceal or minimize the cardiovascular risks associated with Vioxx," said Bill Ogle, an attorney in Daytona Beach for the Golin family.

The company and the Food and Drug Administration have defended their actions in numerous lawsuits brought since the drug introduced in 1999 was withdrawn from the market in late 2004

The company and the Food and Drug Administration have defended their actions in numerous lawsuits brought since the drug introduced in 1999 was withdrawn from the market in late 2004. Merck has won four of the seven cases to reach verdicts, including one for $50 million this summer, but still faces more than 21,000 Vioxx lawsuits like Golin's, up sharply from the 14,200 lawsuits reported in June. (...)

- FDA bør ikke søke mer penger fra legemiddelfirmaer, men få all finansiering fra statskassen

FDA Should Not Seek More Drug Company Money, Should Get All Funding From U.S.Treasury (FDA bør ikke søke etter mer penger fra legemiddelfirmaer, men få all finansiering fra statskassen)
citizen.org 11.1.2007
Statement of Dr. Sidney M. Wolfe, Director of Public Citizen’s Health Research Group

The Food and Drug Administration (FDA) is proposing that the Prescription Drug User Fee Act (PDUFA) be reauthorized by Congress this year and that under the act, drug companies give the agency nearly $400 million a year. The FDA’s crucial drug regulatory functions are too important to be tainted and compromised by direct funding from the very companies whose drugs the agency reviews for safety.

All the better ideas that have been discussed for improving FDA functions of reviewing new drugs, post-market safety studies and advertising should be included in the agency’s upcoming budget proposal to the congressional appropriations committees. The agency should request these additional funds through the same process that funded the agency from 1906 through 1992 – that is, the money should come from the federal Treasury, not the pharmaceutical industry.

Ironically, the entire annual amount of funds now sought from industry under PDUFA is equivalent to fewer than two days of the current expenditures for the disastrous war in Iraq. Where are the congressional priorities? (...)

FDA Proposes 29% Increase in User Fees Paid by Pharmaceutical Companies
kaisernetwork.org 12.1.2007
FDA on Thursday proposed a 29% increase in the annual user fees paid to the agency by pharmaceutical companies to improve oversight of prescription drug safety, reduce approval times for new medications and monitor direct-to-consumer television advertisements for treatments, the Newark Star-Ledger reports (Cohen, Newark Star-Ledger, 1/12). (...)

Manglende tilsyn og oppfølging av legemiddelstudier

Report: FDA struggles to track foreign drug trials (Rapport: FDA sliter med å holde oversikten over utenlandske legemiddelforsøk)
pharmpro.com 22.6.2010
The Food and Drug Administration is reviewing only a fraction of foreign drug trials, as companies increasingly move drug testing overseas to reduce costs, a report by agency overseers said Tuesday.

The FDA inspected about one percent of foreign drug testing sites in fiscal year 2008, according to a report issued Tuesday by the Inspector General for the Department of Health and Human Services. The FDA is responsible for looking out for the safety of patients enrolled in studies of all drugs destined for the U.S. market.

However, the inspector found that the FDA was often unaware of early-stage trials conducted in developing countries in South and Central America. (...)

FDA's Foreign Inspection Budget Lean (FDAs budsjett for utenlandsk inspeksjon er magert)
washingtonpost.com 1.11.2007
Although the volume of prescription drugs and drug ingredients coming into the country from foreign manufacturers in developing nations such as India and China has exploded in recent years, the Food and Drug Administration's budget for foreign inspections has not kept pace and will be lower in 2008 than it was in 2002, according to congressional investigators.

As a result, foreign drug and drug ingredient makers are inspected on average once every eight to 12 years, while American-based manufacturers must be inspected at least once every two years. (...)

In addition, the investigators reported, FDA officials generally do not bring their own translators, and so in countries such as China they rely on company-supplied translators to conduct inspections. They also have to tell foreign manufacturers in advance that they are coming, while FDA inspectors can go into American plants at any time unannounced. (...)

"China alone has more than 700 firms making drug products for the U.S., yet the FDA has resources to conduct only about 20 inspections a year in China," he said. "This is dangerously inadequate." (...)

A bipartisan group of inspectors from the committee's oversight and investigations subcommittee accompanied FDA inspectors on an August trip to India and China -- two nations that have become major players in supplying the U.S. drug market. Neither country has a strong drug regulatory agency, and the committee inspectors concluded that setting up permanent FDA offices could solve many inspection problems. They reported that Indian officials supported the idea, while the Chinese officials' position was unclear. (...)

- GSK to strip down through outsourcing and offshoring

US Senator seeks probe into pharma outsourcing (Amerikansk senator ber om granskning av legemidelfirmaers outsourcing)
in-pharmatechnologist.com 16.6.2008
- A US senator has asked the Food and Drug Administration (FDA) for a probe into outsourcing of production for pharmaceuticals, as well as ways to make drugmakers accountable for products which fail to meet quality standards.
Senator Sherrod Brown (Democrat -Ohio) is particularly concerned about cases where elements of production have been outsourced to overseas companies, noting: "In recent testimony to the Senate Committee on Health, Education, Labor, and Pensions (HELP), an FDA official acknowledged that American drug companies outsource operations to take advantage of weak drug safety standards abroad." (...)

Draft legislation has also been proposed - the FDA Globalisation Act of 2008 - which would require the FDA to inspect foreign manufacturing plants every four years. (...)

GSK to strip down through outsourcing and offshoring (GSK skjærer ned gjennom outsourcing og offshoring)
in-pharmatechnologist.com 26.10.2007
- GlaxoSmithKline (GSK) is planning to strip itself down closer to the bare bones of the business through further outsourcing and offshoring, with hopes of making itself into a lean, mean, pharma machine.

The pharma heavyweight announced a sweeping restructuring plan in the form of an 'Operational Excellence' programme, designed to achieve savings of up to £700m (€1bn) by 2010 - 40 per cent of which will come from cutting down on manufacturing sites and simplifying production processes and activities to reduce over capacity.

The cornerstones of this new programme are "persistent focus across all functions; a reduction in complexity, to be achieved by standardisation, consolidation, outsourcing and offshoring; and the exploitation of global opportunities,in regard to procurement, skills, labour cost and arbitrage," indicated GSK's CEO Dr J.P. Garnier.

As with most pharm firms in today's tough business climate, GSK has already been embracing outsourcing and offshoring to a certain extent in order to tighten its purse strings, however, as more parts of the business are seeing the fruits of this strategy, the firm is stepping up its resolve in this regard. (...)

Eli Lilly planlegger mer legemiddelutvikling i Kina

Eli Lilly plans more drug development in China (Eli Lilly planlegger mer legemiddelutvikling i Kina)
reuters.com 8.11.2007
SHANGHAI, Nov 8 (Reuters) - U.S. pharmaceutical firm Eli Lilly & Co (LL.N: Quote, Profile, Research), maker of antidepressant Prozac and erectile dysfunction drug Cialis, said on Thursday it plans to develop more drugs in China because of lower costs and an ample pool of talent.

"We need to find a way to establish leadership in China, not only by selling drugs," Darren Carroll, senior managing director of Lilly Asian Ventures, said in an interview.

The cost for a researcher in China is as little as 20 percent of the cost in the United States, where one out of five of Lilly's researchers is Chinese, Carroll said. (...)

Ufarlig?

Legemiddeltestene du ikke får høre om
vg.no 21.2.2008
Mange legemiddelprodusenter unnlater å publisere negative resultater av antidepressive midler, viser ny rapport. (...)

Testene du ikke får høre om
dinside.no 20.2.2008
Mange legemiddelprodusenter unnlater å publisere negative resultater av antidepressive midler, viser ny rapport. (...)

(...) Nå er det jo slik at antidepressive legemidler virker, men effekten er trolig overdrevet, sier forsker og psykiater Jørgen G. Bramness ved Folkehelseinstituttet til DinSide Helse.

Han kjenner til at det foregår en selektiv publisering av kliniske studier, og mener det er uheldig. (...)

Ifølge Bramnes er det grunn til å tro at denne skjevpubliseringen kan skyldes for nær kontakt mellom markeds- og forskningsavdelinger innen firmaene. (...)

- Plikter å dokumentere
- Når det gjelder kliniske legemiddelstudier som legges til grunn for godkjenning av nye legemidler, så kjenner jo legemiddelverket til studiene. Ved godkjenning av nytt legemiddel plikter firmaet å sende inn all dokumentasjon, så om det er publisert eller ikke, spiller sånn sett ingen rolle. Men det er jo slik at firmaene gjerne publiserer de studiene som har vist de beste resultatene for egen markedsføring, sier avdelingsdirektør for legemiddelbruk i Statens legemiddelverk, Ivar Vollset, til DinSide Helse. (...)

- Ufarlig
- Det viktige poenget er uansett at myndighetene kjenner til alle kliniske legemiddelstudier, og alle slike studier som gjøres i Norge skal meldes til legemiddelverket.

Vollset understreker at det ikke er noen fare forbundet med godkjenningen av legemidler i Norge.

- Men når preparatet er kommet på markedet er det selvsagt viktig for legemiddelfirmaet å selge mest mulig, så der er det opp til myndighetene å sørge for en balansert informasjon, sier han. (...)

Lukrative legemidler, faresignaler og FDA

Lucrative Drug, Danger Signals And the F.D.A. (Lukrative legemidler, fareseignaler og FDA)
The new York Times 10.6.2005
ABSTRAKT - Nylig offentliggjorte firmadokumenter og statlige dokumenter for Johnson & Johnsons medisin mot halsbrann, Propulsid, gir en dypere innsikt i farmasøytiske firmaer som forsøker å beskytte lukrative legemidler hvor de møter økende bevis for skadelige sideeffekter; historien har spesiell gjenklang nå, idet de problematiske smertestillende artrittlegemidler Vioxx, Celebrex og Bextra retter oppmerksomheten på hva kritikere sier er Food and Drug Administrations udugelighet når det gjelder effektivt å kunne overvåke og regulere farmasøytika straks de er på markedet; dokumenter fra søksmål mot Johnson & Johnson viser at firmaer ikke utfører sikkerhetsstudier anbefalt av statlige kontrollører og egne konsulenter; Propulsids historier har slående paralleller til omstridte smertestillende artrittlegemidler; som med dem, dusinvis av studier sponset av Johnson & Johnson som kunne advart leger mot bruk ble aldri publisert, og firmaet klarte å forsinke noen foreslåtte forandringer av pakningsvedlegg; Johnson & Johnson trakk Propulsid fra markedet i 2000 etter rapporter om dødsfall steg før statlige høringer, som truet å trekke oppmerksomhet mot legemidlets lenge, i hovedsak skjulte, problemstatistikk; detaljerte undersøkelser av Propulsids-saken; foto; tabell (L)" (ABSTRACT - Newly obtained corporate and government documents on Johnson & Johnson's heartburn medicine Propulsid provide in-depth view of pharmaceutical company trying to save lucrative drug in face of growing evidence of harmful side effects; story has particular resonance now, as troubled arthritis painkillers Vioxx, Celebrex and Bextra focus attention on what critics say is Food and Drug Administration's inability to monitor and regulate pharmaceuticals effectively once they are on market; documents from lawsuits against Johnson & Johnson show company did not conduct safety studies urged by federal regulators and their own consultants; Propulsid's history has striking parallels with controversial arthritis painkillers; as with them, dozens of studies sponsored by Johnson & Johnson that might have warned doctors away were never published, and company was able to delay and soften some proposed label changes; Johnson & Johnson pulled Propulsid from market in 2000 after reports of deaths mounted and before government hearing that threatened to draw attention to drug's long, largely hidden, record of trouble; detailed examination of Propulsid case; photo; chart (L)")

FDA kurerer seg selv?

We're curing ourselves (FDA kurerer seg selv)
Av Steven Galson
Editorial/Opinion Inside News (Leder/Meninger Innsidenyheter)
usatoday.com 26.4.2006
Hos Food and Drug Administration, er beskyttelse og promotering av landets helse vår topp prioritet. Denne ukes rapport fra Government Accountability Office hilser arbeidet med retningslinjer, som er underveis, velkommen for å bedre vår evne til å identifisere, og ta hånd om og kommuniserer sikkerhetsspørsmål. (At the Food and Drug Administration, protecting and promoting the nation's health is our top priority. This week's report by the Government Accountability Office provides welcome guidance to the work underway at the FDA to advance our ability to identify, manage and communicate safety issues.)
OUR VIEW: FDA ill on tracking pills (VÅRT SYNSPUNKT: FDA ill on tracking pills.)

Examples of some initiatives include: (Eksempler på noen initiativer omfatter:)

Skjerpet oppsyn med legemiddelsikkerhet. Vi har sentralisert vår politiske beslutningsprosess på legemiddelsikkerhet, tilsyn og kommunikasjon med utnevnelsen av ny assosiert senterdirektør for Safety Policy and Communication. Vi har etableret et Drug Safety Oversight Board ledet av interne og eksterne eksperter for å gi ekstra input. For ytterligere å øke identifikasjonen av risikoer forbundet med reseptbelagte legemidler, FDA har signert kontrakter med eksterne partnere for å øke vårovervåkingsevne etter at legemdler er godkjent. (Enhanced drug safety oversight. We have centralized our drug safety policymaking, oversight and communication with the appointment of a new associate center director for Safety Policy and Communication. We have established a Drug Safety Oversight Board led by internal and external experts to provide additional input. To further enhance the identification of risks associated with prescription medications, the FDA has signed agreements with external partners to increase our surveillance capabilities after drugs are approved.)

Nye pakningsvedlegg for reseptbelagte legemidler. Som annonsert i år, dette nye format gir klar og konsis informasjon om et legemiddels nytte og risiko. I kompaniskap med National Library of Medicine, annonserte FDA et nytt standardisert elektronisk pakningsvedlegg som gir den mest oppdaterte informasjon om reseptbelagte legemidler. Disse verktøy vil føre til bedre helse resultater for pasienter og mer rettidig informasjon for helsepersonell. (New prescription drug label. Announced this year, this new format gives clear and concise information about a medicine's benefits and risks. In partnership with the National Library of Medicine, the FDA announced a new standardized electronic drug label that gives immediate access to the most up to date information about prescription medicines. These tools will lead to better health outcomes for patients and more timely information for health care providers.)

Kritisk metode for legemiddeloppdagelse. FDA arbeider for å modernisere de vitenskapelige verktøy brukt til å utvikle og evaluere medisisnske produkter. Vi arbeider for å skape mer effektive og pålitelige måte å overvåke sikkerheten for legemidler straks de er goskjent for bruk. Et eksempel er FDAs samarbide med Duke Clinical Research Institute, National Institutes of Health, og andre for å utvikle bedre metoder for å forutsi hjerterelaterte sideeffekter fra legemidler. (Critical path of drug discovery. The FDA is working to modernize the scientific tools used in developing and evaluating medical products. We are working to create more efficient and reliable ways for monitoring the safety of medicines once they are approved for use. One example is the FDA's collaboration with the Duke Clinical Research Institute, the National Institutes of Health, and others to develop better methods for predicting heart side effects from drugs.)

Alle legemidler har risiko. Alle beslutninger om å bruke et medisinsk produkt krever omhyggelig balansering av disse risikoer mot mulig nytte. Hver beslutning om å bruke et medisinsk produkt krever en omhyggelig balansering av disse risikoer mot mulig nytte. Vi er forpliktet til å forbedre vår vitenskapelige prosess for å identifisere og kommunisere informasjon om legemiddelsikkerhet, slik at helsepersonell og deres pasienter og familier har betimelig, pålitelig informasjon som rettesnor for sine medisinske beslutninger. (All drugs have risks. Every decision to use a medical product requires a careful balancing of these risks with the potential for benefits. We are committed to improving our scientific process for identifying and communicating drug safety information so that health care professionals and their patients and families have timely, reliable information to guide their medical decisions.)

Steven Galson er direktør for FDAs Center for Drug Evaluation and Research. (Steven Galson is director of the FDA's Center for Drug Evaluation and Research.)

Hvem regulerer hvem: "FDA møtte farmasøytisk industri 112 ganger for å utarbeide reautorisasjon av brukeravgift for reseptbelagte legemidler"

FDA Met With Pharmaceutical Industry 112 Times To Develop Prescription Drug User Fee Reauthorization Proposal (FDA møtte farmasøytisk industri 112 ganger for å utarbeide reautorisasjon av brukeravgift for reseptbelagte legemidler)
kaisernetwork.org 12.6.2007
FDA officials over 15 months met 112 times with pharmaceutical industry representatives and only five times with consumer and patient advocacy groups to discuss the development of a proposal for legislation to reauthorize the Prescription Drug User Fee Act, according to data released on Monday by the House Appropriations Committee, USA Today reports. According to the committee, two officials from the Biotechnology Industry Organization and two officials from the Pharmaceutical Research and Manufacturers of America attended at least half of the 112 meetings, which occurred between October 2005 and December 2006 (Rubin, USA Today, 6/12). (...)

Hvordan det amerikanske system for legemiddelsikkerhet bør endres

How the US Drug Safety System Should Be Changed
Commentary (Hvordan det amerikanske system for legemiddelsikkerhet bør endres)
Brian L. Strom, MD, MPH
JAMA. 2006;295:2072-2075 (May 3)
If the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind, and all the worse for the fishes.—Oliver Wendell Holmes, Sr¹ (Dersom hele materia medica, som nå brukes, kunne senkes på havets bunn, ville det være et gode for menneskeheten, men desto verre for fiskene.— Oliver Wendell Holmes, Sr¹)

Nylig lesning av en avis minner en kanskje på ovennevnte sitat. Et av spørsmålene som landet for nærværende står overfor er hva som bør gjøres for å adressere legemiddelsikkerhet. I denne kommentar, er det nåværende system for overvåkning av legemiddelsikkerhet beskrevet og begrensninger for det nåværende system uthevet. En mulig løsning er foreslått som vil kreve implementering av lover. (Reading a recent newspaper might remind one of the above quote. One of the questions the nation is currently confronted with is what should be done to address the safety of drugs. In this Commentary, the current system of drug safety monitoring will be described and the limitations of the current system will be highlighted. A potential solution will then be proposed that will require legislation to implement.)

Current System of Drug Safety Monitoring (Nåværende system for sikkerhetsovervåkning)

Det nåværende system for sikkerhetsovervåkninginkluderer preklinisk testing fulgt av 3 faser av kliniske studier (Figur). Legemiddelgodkjennelse er i noen tilfeller fulgt opp med studier etter markedsføring. Vanligvis, er bare 500 til 3 000 pasienter studert før markedsføring. Derfor, ved . . . [Full Text of this Article] (The current system of drug safety monitoring includes preclinical testing followed by 3 phases of clinical studies (Figure). Drug approval is sometimes followed by postmarketing studies. Usually, only 500 to 3000 patients are studied before marketing. Therefore, by . . . [Full Text of this Article])

Farmasøytiske firmaer har siden 2001 betalt 3,5 milliarder dollar i bøter for lovovertredelser i sin markedsføring av reseptbelagte legemidler

Two newspapers recently examined issues involving the marketing of prescription drugs. Summaries appear below. (To aviser undersøkte nylig spørsmål som involverer markedsføringen av reseptbelagte legemidler. Oppsummeringer nedenfor.)
kaisernetwork.org 8.5.2006
Baltimore Sun: Farmasøytiske firmaer har siden 2001 betalt 3,5 milliarder dollar i bøter for overtredelse av den statlige lov mot falske påstander (False Claims Act), en borgerkrigslov (Civil War-era law) som inntil 1990-tallet bare hadde vært anvendt på militære anskaffelser, rapporterer Sun. Legemiddelindustriens overtredelser har omfattet markedsføring av legemidler utenfor preparatomtale, gaver til leger og salg av legemidler til leger uten å opplyse om rabatter. Aktor har brukt False Claims Act i 16 forlikede saker med firmaer som AstraZeneca, Bayer, GlaxoSmithKline, Schering-Plough og Pfizer, og ytterligere 150 saker er forestående, ifølge Taxpayers Against Fraud. "En grunn til at loven er trådt i kraft" er at varslere (whistle-blowers) er berettiget til 15 % til 30 % av bøter mot et firma, rapporter Sun. Advokater for farmasøytiske firmaer har sagt at de rettslige forutsetninger for bruk av False Claims Act kanskje ikke holder i retten, men de har ikke utfordret loven fordi firmaer "risikerer å miste lukrative statlige godtgjørelser for sine legemidler," rapporterer Sun. I mellomtiden, "hyrer legemiddelfirmaer medarbeidere som skal sikre at eksisterende lovgivning overholdes, omskolerer selgerne og oppretter hot line" for å forebygge overtredelser av loven, ifølge Sun (Rockoff, Baltimore Sun, 5/7). (Baltimore Sun: Pharmaceutical companies have paid $3.5 billion in fines since 2001 for violations of the federal False Claims Act, a Civil War-era law that until the 1990s had been applied only to military acquisitions, the Sun reports. Drug industry violations have included marketing drugs for off-label uses, giving gifts to doctors and selling drugs to doctors at undisclosed discounts. Prosecutors have used the False Claims Act in 16 settled cases with such companies as AstraZeneca, Bayer, GlaxoSmithKline, Schering-Plough and Pfizer, and an additional 150 cases are pending, according to Taxpayers Against Fraud. "One reason the law has been effective" is that whistle-blowers are eligible for 15% to 30% of penalties against a company, the Sun reports. Lawyers for pharmaceutical companies have said the legal premise for using the False Claims Act might not stand up in court, but they have not challenged the law because companies "risk losing lucrative government reimbursement for their drugs," the Sun reports. Meanwhile, "drug companies are hiring compliance officers, retraining sales staff and creating hot lines" to prevent violations of the law, according to the Sun (Rockoff, Baltimore Sun, 5/7).)

Knight Ridder/Miami Herald: Svarkuponger, trygghetsgarantier, tilbakebetalinger og "annen supermarked-vennlig markedsføring" er blitt markedsføringsverktøy for mange merkevarer innen reseptbelagte legemidler, rapporterer Knight Ridder/Herald. Tjuefire støttegrupper spurte nylig FDA om å forby reklamefremstøt, de sier de urettmessig påvirker legers forskrivningspraksis og oppmuntrer pasienter til å bruke dyre legemidler. Reklame rettet mot barn -- slik som promotering av kvisemiddel med gratis nedlasting av musikk -- "har vakt spesiell bekymring," rapporterer Knight Ridder/Herald. FDA-kontrollører sa i en nylig meddelelse at "reseptbelagte legemidler promotert med svarkuponger eller gratis tilbud kan indikere at behandlinger er utbredt, mer velegnet og/eller mindre risikofylt enn de i virkeligheten er." FDA planlegger å utføre en studie på hvordan reklame påvirker forbrukerens synspunkter på risikoer for reseptbelagte legemidler. Ann Richardson Berkley, visepresident for PR hos McKesson -- en legemiddeldistributør som har hjulpet pasienter å løse inn 14,2 millioner svarkuponger -- skriver i et brev til FDA, "Ved å gi en pasient mulighet til å bruke et legemiddel på forsøksbasis før det gjøres en investering i en ny legemiddelterapi, kan svarkuponger være en verdifull tilgang til dagens økende legemiddelkostnader " (Pugh, Knight Ridder/Miami Herald, 5/5). (Knight Ridder/Miami Herald: Coupons, money-back guarantees, rebates and "other supermarket-friendly promotions" have become marketing tools for many brand-name prescription drugs, Knight Ridder/Herald reports. Twenty-four advocacy groups recently asked FDA to ban the promotions, saying they improperly influence doctors' prescribing practices and encourage patients to use costlier drugs. Promotions aimed at children -- such as an acne drug promotion with free music downloads -- "have drawn particular concern," Knight Ridder/Herald reports. FDA regulators in a recent filing said that "prescription drugs promoted with coupons or free trial offers may be seen as more widely indicated, more appropriate and/or less risky than they really are." FDA plans to conduct a study on how the promotions affect consumers' views on the risks of prescription drugs. Ann Richardson Berkley, vice president for public affairs at McKesson -- a drug distributor that has helped patients redeem 14.2 million coupons -- in a letter to FDA said, "[B]y enabling a patient to use a drug on a trial basis prior to making an investment in a new drug therapy, coupons can be a valuable asset in the face of today's increasing drug costs" (Pugh, Knight Ridder/Miami Herald, 5/5).)

Diverse lederartikler og innlegg som adresserer spørsmål relatert til FDA

Editorial, Opinion Pieces Address Issues Related to FDA (Lederartikler, innlegg som adresserer spørsmål relatert til FDA)
kaisernetwork.org 27.4.2006
Opinion (Mening)
En leder og to innlegg publisert på torsdag adresserer spørsmål relatert til FDA. Oppsummeringer er vist nedenfor. (An editorial and two opinion pieces published on Thursday addressed issues related to FDA. Summaries appear below.)

Bill Maher, Los Angeles Times: "Det synes som hver gang jeg slår på TV-nyhetene i disse dager, ser jeg reklame for enkelte legemidler jeg aldri har hørt om," skriver Maher i et innlegg i Times, og legger til "Problemet er at profitten for magiske piller er så enorm at legemiddelfirmaer finner opp pillen først og deretter tryller frem noe som kan behandles." Ifølge Maher, "Bare de to siste årene, har legemidler som har preget overskriftene under kategorien "Reseptbelagte legemidler som skader mennesker" inkludert Vioxx og Ambien. Likevel erklærte FDA sist uke at marihuana hadde ingen kjent medisinsk verdi." Han tillegger, "I virkeligheten, hva marihuana har er ingen kjent lobbyverdi." Maher spør, "Er der noe mer latterlig enn tanken om at FDA ikke beskytter annet enn overskuddet til legemiddelfirmaer?" Han skriver, "Legemiddelfirmaer er pushere, og Kongressen og FDA er hardt pressede politibetjenter som er betalt for å se den annen vei. Nye legemidler pleide å gå igjennom en streng testprosess. Nå gir de det bare til Courtney Love, og, dersom hun overlever, er det godkjent" (Maher, Los Angeles Times, 4/27).(Bill Maher, Los Angeles Times: "It seems as if every time I turn on the TV these days, I see some ad for some drug I never heard of," Maher writes in a Times opinion piece, adding, "The problem is, the profits are so enormous for magic pills that drug companies invent the pill first and then conjure up something it can treat." According to Maher, "Just in the last two years, the drugs that have made the headlines under the category 'Prescription Medicine That Hurt People' have included Vioxx and Ambien. And yet it was marijuana last week that was declared by the FDA to have no known medical value." He adds, "Actually, what marijuana has is no known lobbying value." Maher asks, "Is there anything more laughable than the thought that the FDA is protecting anything but the profit margins of pharmaceutical companies?" He writes, "Drug companies are pushers, and Congress and the FDA are the cop on the beat who's been paid off to look the other way. New drugs used to have to go through a rigorous process of testing. Now they just give it to Courtney Love, and, if she lives, it's approved" (Maher, Los Angeles Times, 4/27).)

USA Today: En rapport publisert på mandag av Government Accountability Office konkluderte at FDA er "preget av indre stridigheter, dårlig ledelse og likegyldighet når det gjelder å spore uheldige legemiddelreaksjoner," og byrået, som "erkjenner problemet," mangler en "klar, konsekvent holdning omkring hva som bør gjøres," ifølge en lederartikkel i USA Today. Lederartikkelen konstaterer, "Oppgaven er langt større enn de ressursene som er satt av for å få utrettet noe," delvis fordi FDA "årlig mottar 400 000 rapporter om bivirkningsreaksjoner." Ifølge lederartikkelen, "snarere enn aggressivt å spore opp slike hendelser, venter byrået på at rapporter drypper inn fra leger og farmasøytiske firmaer," og "at informasjon skusles bort fordi FDA mangler klare strategier for hurtig å handle på klager." I tillegg, har ikke FDA "makt til å kreve studier" etter at legemidler er kommet på markedet, har stor gjennomtrekk i viktige stillinger og mangler adekvat kommunikasjon mellom Office of New Drugs og Office of Drug Safety, konstaterer lederartikkelen. Lederartikkelen konkluderer, "Å balansere risiko og nytteverdi for ethvert legemiddel er utfordrende. Men, som et minimum, trenger FDA å gi sikkerhet topp prioritet og å insistere på at dets egne forskere arbeider som medspillere i stedet for rivaler" (USA Today, 4/27). (USA Today: A report released on Monday by the Government Accountability Office concluded that FDA "is hobbled by turf battles, poor management and passivity in tracking adverse drug reactions," and the agency, which "acknowledges the problem," lacks a "clear, consistent approach about what should be done," according to a USA Today editorial. The editorial states, "The task far outstrips the resources committed to achieve it," in part because FDA "receives 400,000 reports of reactions to drugs each year." According to the editorial, "Rather than aggressively tracking such events, the agency waits for reports to trickle in from doctors and pharmaceutical firms," and "that information is squandered because the FDA lacks clear policies to act swiftly on complaints." In addition, FDA does not have "clout to demand studies" after medications reach the market, has high turnover in important positions and lacks adequate communication between the Office of New Drugs and the Office of Drug Safety, the editorial states. The editorial concludes, "Balancing the risks and benefits of any drug is challenging. But at a minimum, the FDA needs to make the tracking of safety its top priority and to insist that its own scientists work as teammates instead of rivals" (USA Today, 4/27).)

Steven Galson, USA Today: FDA betrakter "beskyttelse og promotering av landets helse" som "topp prioritet," og GAO-rapporten "hilser arbeidet med retningslinjer, som er underveis, velkommen for å bedre vår evne til å identifisere, og ta hånd om og kommuniserer sikkerhetsspørsmål," skriver Galson, direktør for byrået Center for Drug Evaluation and Research, i et innlegg i USA Today. Ifølge Galson, har FDA begynt å forbedre "politisk beslutningsprosess for legemiddelsikkerhet, oppsyn og kommunikasjon"; revisjon av pakningsvedlegg for resepter; og utvikle "mer effektive og pålitellige måter å overvåke sikkerheten for legemidler straks de er godkjent for bruk." Han tillegger, "Alle legemidler har risiko. Alle beslutninger om å bruke et medisinsk produkt krever omhyggelig balansering av disse risikoer mot potensialet for nytte." Galson konkluderer, "Vi er forpliktet til å forbedre vår vitenskapelige prosess for å identifisere og kommunisere informasjon om legemiddelsikkerhet, slik at helsepersonell og deres pasienter og familier har betimelig, pålitelig informasjon som rettesnor for sine medisinske beslutninger" (Galson, USA Today, 4/27). (Steven Galson, USA Today: FDA considers "protecting and promoting the nation's health" a "top priority," and the GAO report "provides welcome guidance to the work underway at the FDA to advance our ability to identify, manage and communicate safety issues," Galson, director of the agency Center for Drug Evaluation and Research, writes in a USA Today opinion piece. According to Galson, FDA has begun to improve "drug safety policymaking, oversight and communication"; revise prescription drug labels; and develop "more efficient and reliable ways for monitoring the safety of medicines once they are approved for use." He adds, "All drugs have risks. Every decision to use a medical product requires a careful balancing of these risks with the potential for benefits." Galson concludes, "We are committed to improving our scientific process for identifying and communicating drug safety information, so that health care professionals and their patients and families have timely, reliable information to guide their medical decisions" (Galson, USA Today, 4/27).)

(Anm: Report Abstract. Drug Safety: Improvement Needed in FDA's Postmarket Decision-making and Oversight Process GAO-06-402 March 31, 2006
Highlights-PDF PDF Accessible Text.)

(Anm: F.D.A. Dismisses Medical Benefit From Marijuana. New York Times (20.4.2006).)

Drug Safety Panel Is Criticized (Panel for legemiddelsikkerhet kritisert)
The Washington Post 8.6.2005
Forsøk å beskytte forbrukere som er utsatt for risiko, uttalte senator, FDA-leder (Efforts to Protect Consumers at Risk, Say Senator, FDA Official)

Det nye styret for legemiddelsikkerhet etablert av Food and Drug Administration forn å gjenopprette tilliten til landets legemiddelleveranser vil i virkeligheten forsinker anstrengelser for å forbedre sikkerheten for legemidler som amerikanere inntar og vil ikke gjøre det noe lettere å fjerne farlige legemidler fra markedet, sa en FDA-varsler og en sentral senator. (The new drug safety board established by the Food and Drug Administration to restore confidence in the nation's drug supply will actually set back efforts to improve the safety of the medications Americans take and will not make it any easier to take dangerous drugs off the market, an FDA whistle-blower and a key senator said.)

David Graham, sikkerhetsleder hos FDA , konkluderte etter å ha gjennomgått sammensetning og struktur for Drug Safety Oversight Board, at panelet er "voldsomt skjevt i favør av industri" og at "FDA ikke er til å stole på når det gjelder å beskytte publikum eller forbedre seg selv." (FDA safety officer David Graham said that after reviewing the makeup and structure of the Drug Safety Oversight Board, he concluded that the panel is "severely biased in favor of industry" and that "the FDA cannot be trusted to protect the public or reform itself.")

- The Vioxx story really highlights the difference between marketing and informing

Vioxx Problems Known Years Before Recall
healthday.com 23.11.2009
Study points up weaknesses of drug approval process in United States, researcher says (...)

In a statement released Tuesday, Merck officials said this: "Merck believes the article published in The Archives of Internal Medicine in today's issue related to Vioxx used unreliable methods and reached incorrect conclusions."

"The first time Merck observed a difference in a placebo-controlled study was when it learned the results of the APPROVe study in September 2004. We voluntarily withdrew Vioxx from the market within a week of those results," the statement continued.

"Merck acted responsibly -- from researching Vioxx prior to approval in studies with approximately 10,000 patients to monitoring the medicine while it was on the market -- to voluntarily withdrawing the medicine when it did," the statement said. "Our decisions were based on the data from well-controlled clinical trials."
But the authors of the new study believe the Vioxx saga points to a larger problem, one that involves the drug approval process in the United States.

"One of the challenges in health care is to recognize these safety risks early," said lead researcher Dr. Joseph S. Ross, an assistant professor of geriatrics and palliative medicine at Mount Sinai School of Medicine in New York City. (...)

Bringing the FDA's Information to Market (Formidling av FDAs informasjon til markedet)
Arch Intern Med. 2009;169(21):1985-1987 (November 23)
Here is a challenge: Imagine you are asked to turn a new prescription drug into a blockbuster. The drug is approved by the US Food and Drug Administration (FDA) to treat arthritis pain. That is good news because the arthritis market is huge. But you face some big challenges. First, there are several over-the-counter drugs available that treat pain equally well and at one-fiftieth of the cost. Your only comparative advantage is that your drug causes less gastrointestinal tract (GI) bleeding than other arthritis pain medicines. But this reduction is not very big and only applies to a very small slice (probably <5%) of the market—people at high risk for GI bleeding. And, oh yes, your drug may triple the chance of myocardial infarction.

Do you think you could get physicians to prescribe your drug to over 20 million Americans? Could you achieve over $2 billion in annual sales? Well, the makers of Vioxx (Merck & Co Inc, Whitehouse Station, New Jersey) did just that—until the drug was pulled from the market.

Ross et al show how a cumulative meta-analysis might have led the FDA to halt sales of Vioxx in 2001, 3 years before Merck voluntarily stopped selling it. Doing so might have prevented thousands of myocardial infarctions. We applaud this study and hope that independent investigators will apply the same methods to other drugs to help answer important safety questions. But the article left us wondering, just how did Vioxx get so big and stay so big for so long?

-Vioxx-historien fremhever virkelig forskjellen mellom makedsføring og informasjon. Dersom leger og pasienter hadde hatt fakta hadde de hatt behov for en alkymist for å gjøre denne gråstein til gull, ikke en markedsføringsavdeling. (The Vioxx story really highlights the difference between marketing and informing. If physicians and patients had had the facts, it would have taken an alchemist, not a marketing department, to turn this lemon into gold.)

The problem is that when it comes to prescription drugs, a lot more effort goes into marketing than informing. It has been estimated that drug companies spend $30 billion to $50 billion a year on drug promotion (advertising, detailing visits, free samples, and other promotion techniques).1 That means that the industry can really get its message out. (...)

- Når er et legemiddel for farlig til å være på markedet?

When is a drug too risky to stay on the market? (Når er et legemiddel for farlig til å være på markedet?)
forbes.com 30.6.2010
Artritis-pillen Vioxx ble trukket fra markedet men menopause hormoner ble ikke, selv om de begge var knyttet til hjerterisiko. Et legemiddel mot multippel sklerose ble trukket fra markedet og senere tillat å komme tilbake på markedet . (The arthritis pill Vioxx was withdrawn but menopause hormones were not, even though both were tied to heart risks. A multiple sclerosis medicine was pulled and later allowed back on.)

Så, når er et legemiddel for farlig til å være på markedet? (So, when is a drug too risky to stay on the market?)

Spørsmål om legemiddelsikkerhet ble stilt nok engang denne uken, idet flere ber om at Avandia, et legemiddel mot diabetes, trekkes fra markedet. Det overraskende er at legemiddelkontrollen Food and Drug Administration (FDA) ikke har noen regler for å avgjøre slike saker – bare en grumsete retningslinje som sier "når risiko overgår nytten." (...) (Drug safety questions arose again this week, as calls mount for the diabetes pill Avandia to be withdrawn. Surprisingly, the Food and Drug Administration has no firm rules for deciding such cases - just a murky guideline of "when the risks exceed the benefits.")

Risky drugs pulled from the market in recent years (Farlige legemidler trukket fra markedet de senere år)
forbes.com 30.6.2010
When a drug's risks exceed its benefits, the federal Food and Drug Administration may ask or order a company to withdraw it from the market, or a company may do so on its own. Here are some drugs withdrawn in recent years. (...)

Medical Flops Of The Decade (Medisinske flopper det siste tiår)
Drug Safety
forbes.com 1.7.2010
Sometimes medical innovation goes badly wrong. Here are some of the biggest recent drug recalls and market failures. (...)

While small trials can detect severe toxicities, the only way to gauge safety and efficacy in the broad population is to perform big studies in which thousands of patients are randomly given one treatment or another. Sometimes rare but very serious problems emerge only after a drug is on the market and used by hundreds of thousands of people. (...)

Når et legemiddel feiler (FDA kritiserer bruk av Avastin mot bryskreft)

When a Drug Fails (Når et legemiddel feiler)
EDITORIAL (LEDER)
nytimes.com 25.7.2010
Nedturen til et enormt dyrt legemiddel for behandling av fremskreden kreft er en kritisk test for Food and Drug Administration. Vil tilsynet ha mot til å reversere kursen når en medisinsk behandling, som de godkjente basert på forløpige bevis, kraftig mislykkes i oppfølgingsstudier? (...) (The flameout of an enormously expensive drug to treat advanced breast cancer will pose a critical test for the Food and Drug Administration. Will the agency have the courage to reverse course when a medical treatment that it approved based on preliminary evidence flops badly in follow-up studies?)

Two years ago, the F.D.A. gave Avastin, which is made by the Genentech unit of Roche, “accelerated approval” as a treatment for breast cancers that have spread to other parts of the body. Such cancers are essentially incurable so the best that current treatments can do is extend a patient’s life. (...)

FDA advisors reject Avastin for breast cancer (FDA-rådgivere vraker Avastin for brystkreft)
pharmatimes.com 21.7.2010
Shares in Roche have fallen this morning after advisors to the US Food and Drug Administration recommended that the firm’s oncology blockbuster should no longer be approved as a treatment for breast cancer.

The FDA’s Oncologic Drugs Advisory Committee has voted 12 to one that use of Avastin (bevacizumab) in combination with paclitaxel for previously-untreated (first-line) advanced HER2-negative breast cancer be removed from the drug’s US label. Avastin received a conditional thumbs-up in 2008 for the aforementioned indication under the FDA’s accelerated approval programme, a decision which saw the agency reject advice from its panellists. (...)

FDA: Breast-cancer drug Avastin does not extend lives (FDA: Legemidlet Avastin mot brystkreft forlenger ikke livet)
seattletimes.nwsource.com 16.7.2010 (The Associated Press)
Federal health scientists said Friday that follow-up studies of a Roche breast-cancer drug showed that it failed to extend patient lives...

WASHINGTON — Federal health scientists said Friday that follow-up studies of a Roche breast-cancer drug showed that it failed to extend patient lives, opening the door for the drug to be potentially withdrawn for use in treating that disease.

The Food and Drug Administration approved Roche's blockbuster Avastin in 2008 based on a trial showing it slowed growth of tumors caused by breast cancer. The decision was controversial because drugs for cancer patients who have never been treated before must usually show evidence they extend lives.
Avastin's so-called "accelerated approval" was based on the condition that later studies would show a survival benefit.

But in briefing documents posted online, FDA reviewers said two follow-up studies recently submitted by Roche failed to show that Avastin significantly extended lives compared to chemotherapy alone.

Additionally, the FDA said that in follow-up studies the drug did not slow tumor growth to the same degree as in earlier studies.(...)

New York Times Examines Benefits, Costs of Cancer Drug Avastin (New York Times gransker nytte, kostnader for kreftlegemidlet Avastin)
kaisernetwork.org 7.7.2008
The New York Times on Sunday examined how the Genentech cancer drug Avastin "signifies both the hopes and dilemmas of modern medicine" because while it offers incremental benefits for cancer patients, the drug is costly and concerns have been raised about its safety and efficacy. The drug, which is seen as a "wonder drug" for its ability to cut off blood supply to tumors, costs as much as $100,000 annually and had sales of $3.5 billion last year. Research shows that the drug prolongs the lives of patients with colon, lung or breast cancer by "only a few months, if that," and some recent studies suggest that it could be less effective than FDA believed it to be when approving the drug, the Times reports. Some patients and physicians say Avastin improves the quality of life, allowing patients to perform daily functions without exhaustion, but such benefits are difficult to confirm, according to the Times. (...)

F.D.A. Criticizes Avastin Use for Breast Cancer (FDA kritiserer bruk av Avastin mot bryskreft)
nytimes.com 4.12.2007
Genentech’s drug Avastin did not help women with breast cancer live meaningfully longer, and it caused significant side effects, including a few deaths, the Food and Drug Administration said yesterday in a review of the drug.

The analysis by the agency’s staff appeared to dim the prospects that Avastin would win a approval as a treatment for breast cancer. Genentech’s stock fell $2.75, or 3.6 percent, yesterday, closing at $73.50.

An advisory committee to the F.D.A. will meet tomorrow to discuss whether Avastin, already a blockbuster drug for colon and lung cancer, will win an additional approval for breast cancer. The drug had $1.7 billion in United States sales in the first nine months of the year. Roche Holding, which owns a majority of Genentech, sells it overseas. (...)

Diverse artikler

Top adviser at the European Medicines Agency quits suddenly (Topprådgiver hos European Medicines Agency slutter plutselig)
BMJ2012;344:e2641 (11 April)
The European Medicines Agency (EMA) announced on 4 April the immediate resignation of the chair of its Committee for Medicinal Products for Human Use (CHMP) in a short press release, which gave no reasons for his departure.

The document stated that the agency’s, director Guido Rasi, had accepted the resignation of Eric Abadie “with immediate effect,” and that the committee’s vice chair, Tomas Salmonson, would take over meanwhile to ensure continuity. (...)

FDA says focused on tracking drugs after approval
reuters.com 21.4.2012
Janet Woodcock, Director of the Center for Drug Evaluation and Research at FDA, speaks during the Reuters Health Summit in New York, May 9, 2011.

(Reuters) - The U.S. Food and Drug Administration said on Saturday it now spends as much effort and resources on surveilling a drug after it is approved as it does in the pre-approval process.

The FDA was responding to critics who say the agency is toothless when it comes to tracking the safety of drugs already on the market, when industry funds that supported pre-approval reviews tend to dry up.

"We think we've really balanced this," Dr. Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, told reporters attending the Association of Healthcare Journalist meeting in Atlanta.

In a report released on Saturday, the FDA says it has required companies to do 385 post-market studies since 2008, and to change the label based on new safety information 65 times.

Before 2008 the FDA could not compel label changes or require additional safety trials and had to rely on voluntary action from drugmakers, she said.
The FDA's focus on post-market drug safety comes after the agency was sharply criticized as being slow to respond to drug side effects, notably Vioxx, a painkiller that Merck & Co Inc pulled five years after approval because of a link to heart attacks and strokes. (...)

But critics question how often the agency actually follows through on penalties.

In 2008 the FDA also launched Sentinel, a computer tracking system designed to help identify problems with drugs and medical devices already on the market by searching various databases for possible side effects - rather than just relying on voluntary reports from companies and patients.

The FDA said it used the system to see if there were negative drug interactions for Chantix, the smoking cessation drug manufactured by Pfizer Inc, but did not find any.

Last November U.S. researchers said Chantix carried too many risks and should only be tried when other treatments fail. (...)

Legemiddelbruk i Norge – for lite, for mye eller passe?
Madsens blogg - Steinar Madsen er medisinsk fagdirektør ved Statens legemiddelverk. Han er utdannet lege og har arbeidet ved Bærum sykehus og Rikshospitalet. Ved siden av Legemiddelverket har han deltidsstilling som privatpraktiserende spesialist i indremedisin og hjertesykdommer.
dagensmedisin.no 17.4.2012
(...) Legemiddelbruken i Norge er lav sammenlignet med mange vestlige land, uansett målestokk: Andel av helsebudsjettet, andel av totaløkonomien, antall tabletter eller kostnad per innbygger. Er dette bra eller ikke bra? Det er det vanskelig å svare på, men det er utvilsomt et område det burde forskes på. (...)

Forleden hadde jeg en pasient til utredning. Det var en 74 år gammel mann med høyt blodtrykk, diabetes type 2, KOLS og forkammerflimmer. Det nedslående resultatet av mine undersøkelser var: Blodtrykket var ikke godt behandlet, hans diabetes var ute av kontroll, medisinen han fikk for KOLS var kke den beste og han fikk ikke blodfortynnende behandling til tross for at etningslinjene sier han skulle hatt det. Han kom med fire legemidler og gikk med sju. (...)

Som hjertespesialist er jeg glad for at det kolesterolsenkende legemidlet simvastatin nå er så billig at det kanskje ville være samfunnsøkonomisk lønnsomt å helle det i drikkevannet. Forebygging av tidlig død av hjerte- og karsykdom har vært svært vellykket de siste 20-30 årene. (...)

Og for å svare på mitt eget spørsmål til slutt – jeg tror legemiddelbruken i Norge er omtrent passe. (...)

Medicines regulators agree confidential information
hospitalpharmacyeurope.com 2.4.2012
The Heads of Medicines Agencies and the European Medicines Agency have adopted a joint guidance document that for the firsts time clearly clarifies commercially confidential information and personal data in marketing authorisation applications.

The move promptly follows discussion of the pharmacovigilance legislation and the response of the EFPIA, which pushed for trade secrets to be protected.
This is a major step for transparency, the coverage on the EMA website states. (...)

European medicines regulators agree a common, Europe-wide approach for the identification of commercially confidential information and personal data
pharmanews.eu 28.3.2012
European Medicines Agency (EMA)
The Heads of Medicines Agencies (HMA) and the European Medicines Agency (EMA) have adopted a joint guidance document, providing for the first time for a consistent Europe-wide approach to the identification of commercially confidential information and personal data in a marketing authorisation application. This is a major step for transparency. In future, regulatory authorities in the European Economic Area (EEA) will apply the same principles to identify which parts of an application dossier can or cannot be released in response to access to documents requests. This is regardless of whether the medicine concerned has been authorised using the centralised, mutual recognition or decentralised procedures.

The guidance document limits the scope of what information regulators will consider to be commercially confidential in a marketing authorisation application. The exceptions mainly relate to information about quality and manufacturing of a medicine, as well as information about facilities or equipment and some contractual arrangements between companies.

In addition, the guidance document sets out how personal data as defined by the EU Directive 95/46/EC will be protected if it can lead to the identification of a person. The document gives further guidance on how to identify personal data relating to experts, staff or patients that should be redacted. (...)

Speeding up access to new drugs (Raskere tilgang til nye legemidler)
BMJ 2012;344:e999 (17 February)
Plans to cut the time it takes to get innovative treatments into clinical practice are finally to be put out to consultation next month. Nigel Hawkes provides a reminder of the key points

The prime minister promised at the end of last year to give some patients quicker access to new drugs. Was this just an empty aspiration?

No. A lot of thought has been given to a faster access scheme since David Cooksey recommended it in his review of UK health research funding in December 2006. A working group from industry and government produced a plan by November 2009. It sat on a shelf until resurrected two years later.

How would it work?
Medicines that have completed phase III trials (or in exceptional circumstances phase II) and that will treat or prevent life threatening, chronic, or seriously debilitating conditions that lack adequate existing treatments would qualify. Manufacturers would have to apply, and a decision would be promised in 75 days.

How would that be any quicker than licensing, if phase III trials have already been completed?
It usually takes a year or more to get licensing approval after a successful phase III trial. The new process is expected to get these medicines to patients a year earlier than otherwise would be the case.

But doesn’t it mean that proper risk assessment will be skimped?
There’s a danger of that. The burden of risk will be shifted towards the doctor and the patient and away from the manufacturer. Good information will be vital; patients will need to be fully informed and give active consent. Legally, the position will be the same as that for any unlicensed medicine, and the working group believes—but cannot guarantee—that primary care trusts or clinical commissioning groups will not be liable should anything go wrong. And it says that if the decision by a doctor to treat a patient was reasonable in all the circumstances and all relevant information was provided, a successful claim for negligence is unlikely.

If unlicensed medicines can be marketed and sold, what’s the point of licensing?
The medicines under this scheme would be exceptional and few in number, perhaps only one or two a year. The NHS already uses unlicensed or off-label medicines in some cases, on the authority of the prescribing doctor (for example, bevacizumab for age related macular degeneration). Patients consulted by the working group were confident that they were competent to make a proper assessment of the risks. Doctors were not so sure. (...)

Lægemiddelstyrelsen: Det er op til os at stramme krav til industrien
medwatch.dk 10.2.2012
Det er op til sundhedsmyndighederne selv at udstikke nye, skrappere retningslinjer for, hvordan medicinalselskaberne kan få godkendt deres nye lægemidler, siger chefen i Lægemiddelstyrelsen – medicinalselskaberne følger de spilleregler, der er.

Når medicinalselskaber skal have godkendt lægemidler ved Lægemiddelstyrelsen, vælger de sommetider at sammenligne præparaterne med stoffer, der ikke er de bedste på markedet. Og det skal Lægemiddelstyrelsen tage med i vurderingen, når et lægemiddel står over for godkendelses-folkenes domsfældelse, påpeger Steffen Thirstrup, chef for Godkendelsesafsnittet i Lægemiddelstyrelsen.

”Af og til bliver der i industrien tænkt meget over, hvilket stof man sammenligner sine produkter med. Det er i ikke kun i ansøgninger, der rammer nationalt, men også noget, vi ser, når virksomheder søger markedsføringstilladelse i hele Europa,” siger han.

Angreb på branchen
Kommentaren kommer i kølvandet på en artikel i Information, hvor læger angriber industrien for at fifle med de kliniske forsøg ved at vælge at sammenligne deres nye lægemidler med forældede eller ringeste alternativer på markedet. Det gøres, ifølge kilderne i artiklerne, så virksomheders resultater fremstår stærkere.

Læs også: Avis: Medicinalindustrien sammenligner ny medicin med gamle lægemidler

For at undgå, at nogle virksomheder spekulerer i at sammenligne deres nye lægemidler med forældede produkter, skal der strengere krav til, mener han.
”Det er os, der laver de her guidelines til industrien. Guidelines, der fortæller dem, hvordan de udvikler produkterne” siger Steffen Thirstrup og tilføjer:
”Det kan gøres bedre, det er der ingen tvivl om. Man kan tydeliggøre kravene om at lave sammenligning med et andet aktivt stof og være meget eksplicitte om, hvilket eller hvilke af dem, man som myndighed kunne forestille sig.” (...)

Appetite suppressant was probably responsible for 1300 deaths, study shows (Apetittdempende legemiddel var sannsynligvis skyldig i 1300 dødsfall, ifølge studie )
BMJ 2012;344:e996 (9 February)
A research study into the drug benfluorex (marketed as Mediator), which was withdrawn from the French market in 2009 because of side effects, shows that its use in France during 1976-2009 was probably responsible for around 1300 deaths and 3100 hospital admissions.

The study, published in Pharmacoepidemiology and Drug Safety, was carried out by Agnès Fournier and Mahmoud Zureik, two epidemiologists from the Institut National de la Santé et de la Recherche Medical (Inserm) (2012, doi:10.1002/pds.3213).

They warn that these figures may be underestimates. Patients who took the appetite-suppressant drug experienced valvular insufficiency.

“We have worked with available data from hospitals activity monitoring and from Social Security reimbursements,” Dr Zureik explains. “The population we have studied consisted of 303 336 patients who had taken 78 million boxes of Mediator.” About 5 million people took the drug in the 33 years it was on the market.

The results are published at a difficult time for its manufacturer Servier, because the founder of the company Jacques Servier and his collaborators are due to appear in court in Nanterre, from 14 May to 6 July, to face charges of deception.

Monsieur Servier, and several other executives from his firm, are accused of knowingly hiding the side effects of benfluorex, a fenfluramine derivative drug marketed as an adjunct in the treatment of hyperlipidaemia.

This is only one of two legal cases facing the company. In the second case, which is underway in Paris, the company faces charges of “deception” and “unintentional injuries and manslaughter.” (...)

No need to loosen conflict rules, U.S. FDA head says
reuters.com 1.2.2012
(Reuters) - Congress should not loosen conflict of interest rules to expand the pool of potential U.S. government health advisers, the head of the Food and Drug Administration said on Wednesday.

Lawmakers had proposed bills that would change the rules to make it easier to find more qualified people and speed the review of drugs or devices.

The head of the FDA's drugs division testified in August that the agency was struggling to recruit highly qualified people for its advisory panels. (...)

Lægemiddelstyrelsen bliver nedlagt
dagenspharma.dk 1.2.2012
Sundhedsministeriet vil i morgen offentliggøre, at Lægemiddelstyrelsen skal lægges ind under Sundhedsstyrelsen. Det erfarer Dagens Pharma fra flere kilder. (...)

Det er uklart, hvorfor sammenlægningen af de to store styrelser kommer på nuværende tidspunkt. Lægemiddelstyrelsens renommé er stækket af en række uheldige sager det seneste år, mens økonomien i kraft af en stor brugerfinansiering er relativt solid. Omvendt er Sundhedsstyrelsens renommé relativt intakt, mens økonomien er nødlidende.

Forklaringen på, at sammenlægningen kommer nu, skal måske snarere findes i, at ministeriets nye stærke mand, departementschef Per Okkels, skal udvise handlekraft internt i ministeriet, og i forhold til Folketingets udmeldte genopretningsplan. (...)

Antibiotics
FDA Needs to Do More to Ensure That Drug Labels Contain Up-to-Date Information
gao.gov (GAO-12-218, Jan 31, 2012)
What GAO Found
FDA has not taken sufficient steps to ensure that antibiotic labels contain up-to-date breakpoints. FDA designates certain drugs as “reference-listed drugs” and the sponsors of these drugs play an important role in ensuring the accuracy of drug labels. (...)

(Anm: ANTIBIOTICS - FDA Needs to Do More to Ensure That Drug Labels Contain Up-to-Date Information (GAO-12-218, Jan 31, 2012).)

New Analysis Challenges Tamiflu Efficacy (Nye analyser utfordrer Tamiflus effektivitet)
medpagetoday.com 17.1.2012
A new review of the influenza drug oseltamivir (Tamiflu) has raised questions about both the efficacy of the medication and the commitment of its maker to supply enough data for claims about the drug to be evaluated by independent experts.

It also raises questions about the entire process of systematic review. (...)

Questions remain over safety and effectiveness of oseltamivir (Fortsatt spørsmål om sikkerhet og effektivitet for oseltamivir (Tamiflu))
BMJ 2012;344:e467 (17 January)
Two years after the pharmaceutical giant Roche promised the BMJ that it would release key trial data on oseltamivir (Tamiflu) for independent scrutiny, the safety and effectiveness of this anti-influenza drug remain uncertain, a new meta-analysis by the Cochrane collaboration says.

Cochrane researchers set out to test Roche’s claim that the drug prevented complications and reduced the number of people needing hospital treatment. Their report says that Roche’s refusal to provide full access to all its data leaves critical questions about how well the drug works unresolved (BMJ 2012;344:d7898, doi:10.1136/bmj.d7898).

Roche maintains that it provided the Cochrane researchers with enough information to conduct their evaluation, but the Cochrane team says that this is not the case. (...)

How clinical and research failures lead to suboptimal prescribing: the example of chronic gout
BMJ 2011;343 (1 December)

Despite the existence of several effective drugs for chronic tophaceous gout, management is often neither rational nor effective. Wendy Lipworth and colleagues examine the possible reasons

An evidence based or “rational” approach to prescribing is thought to maximise the benefit and minimise the harm from prescription drugs. Unfortunately, prescribing often does not meet this ideal despite clinicians’ best intentions. We use treatment of chronic tophaceous gout to show how apparently irrational prescribing arises from several interacting “failures” in both clinical practice and drug development. (...)

Failure of drug development?
But suboptimal treatment of chronic gout is not only the result of failure in clinical practice. Given that prescribing is only as rational as the evidence on which it based, we also need to consider the role of the drug development process.

The development of new drugs, although providing benefits for a small subset of patients, might not contribute much to the overall disease burden of chronic tophaceous gout and might carry considerable cost. One such example is febuxostat, a non-purine xanthine oxidase inhibitor approved by the European Medicines Agency in 2008 and by the FDA in 2009. On the face of it, there is nothing wrong with developing additional drugs for people who cannot use existing treatments. But new drugs like febuxostat (which is considerably more expensive than allopurinol) can easily become preferentially prescribed without a robust rationale or sufficient knowledge of long term safety—a concern with febuxostat, for which further data are needed on cardiovascular safety and hypersensitivity. (...)

The F.D.A. Ups Its Numbers
EDITORIAL
nytimes.com 8.11.2011
The Food and Drug Administration recently reported that in the last fiscal year it had approved 35 new drugs, a near-record for the decade, of which 24 were approved here before they were approved in any other country. The new report is consistent with a similar finding in June by independent analysts that new cancer drugs were approved in greater numbers and faster times in the United States than in Europe between 2003 and 2010. (...)

If more patients get access to life-saving drugs, it could be very good news. Of the 35 approvals in the last fiscal year, seven provided major advances in cancer treatment, including two that were approved with a diagnostic test that helps identify which patients are most likely to be helped. There are also important new treatments for hepatitis C, lupus, drug-resistant skin infections and pneumonia and other serious or life-threatening diseases.

The agency will now need to vigilantly monitor how these new drugs affect patients. In the mid-1990s, the F.D.A. approved much larger numbers of new drugs only to find that some had to be withdrawn from the market for safety reasons. Congress must also be careful not to threaten this progress by depriving the agency of sufficient appropriations and user fees to carry out its reviews. (...)

Styrelse erkender fejl
ekstrabladet.dk 24.10.2011
Sundhedsstyrelsen erkender, at læger og gravide skulle have været informeret om bivirkninger ved lykkepiller

Lægemiddelstyrelsen hemmeligholdte i flere år overfor landets patienter og læger, at der havde været dødsfald og andre alvorlige bivirkninger hos danske babyer som følge af deres mødres brug af lykkepiller.

Og Styrelsen erkender nu, at lægerne skulle have været informeret. Det skriver Ekstra Bladet.

Læs også: Heidis søn døde

Lægemiddelstyrelsen vidste allerede i 2007, at der havde været mindst 48 indberetninger om alvorlige bivirkninger og dødsfald hos danske spædbørn.

Alligevel kom den information først ud til lægerne i 2011, og det skulle være sket tidligere, erkender overlæge i afdeling for forbrugersikkerhed, Doris Stenver.

- Det er væsentligt information for lægerne, og det må vi erkende i dag, siger hun.

Læs også: Gravide proppet med livsfarlige lykkepiller

Lægemiddelstyrelsen er nu i gang med at se på, hvordan kommunikationen kan blive bedre. (...)

Human Genome Sciences falls on UK drug concern
businessweek.com 30.9.2011
Shares of Human Genome Sciences Inc. fell Friday after a British agency said the country's National Health Service shouldn't cover Benlysta, Human Genome Sciences' new lupus drug.

THE SPARK: The National Institute for Clinical Excellence, a unit of the U.K.'s publicly funded National Health Service, recommended Wednesday that the NHS not cover Benlysta because the cost of the drug did not justify the expense. If the National Health Service adopts the recommendation, it will not pay for treatment with Benlysta and patients.

GlaxoSmithKline PLC, Human Genome Science's marketing partner, called the recommendation "very disappointing."

"Many current treatments available on the NHS can have undesirable effects, either from chronic use, or side effects associated with immunosuppression," the British drugmaker said in a statement. "A significant number of patients with advanced lupus do not respond to current treatments, even at high doses."

THE BIG PICTURE: Human Genome Sciences, of Rockville, Md., has said that in the U.S., a year of treatment with Benlysta will cost $40,000 for the first year and $35,000 per year after that.

Benlysta was approved in the U.S. in March and in the European Union in July. Analysts have predicted billions of dollars in annual revenue for the drug, but sales have not been as strong as Human Genome Sciences and GlaxoSmithKline expected. (...)

FDA Backpedaling on Plan to Withdraw Drug for Low Blood Pressure?
JAMA 2011 (September 30)
Fifteen years after granting provisional approval for midodrine hydrochloride, a drug prescribed for orthostatic hypotension, the US Food and Drug Administration’s efforts to obtain evidence to confirm the drug’s clinical effectiveness remain mired.

Efforts by the US Food and Drug Administration (FDA) to withdraw from the market a drug to treat low blood pressure that received approval 15 years ago through the agency’s accelerated-approval process appear stalled. The drug, midodrine hydrochloride, was approved with the understanding that its manufacturer would provide solid evidence of its benefit to patients, but such evidence has not been forthcoming. (...)

In January, the agency proposed 2 clinical trial designs that could determine efficacy of the drug and established a 6-month comment period—which ended July 11—for interested parties to express their opinions. Last week, Shire issued a press release saying that although the company was working with the FDA to design trials to confirm efficacy, they had reached an impasse. Shire suggested that final approval by the FDA should come not through new clinical trials but rather through a public hearing at which the company would present its data. An FDA spokesperson said the agency could not comment on the nature of the impasse and that Shire’s request for a hearing is under review. The spokesperson added that a key priority for the agency as the regulatory process moves forward is to make sure patients continue to have access to midodrine.

But some critics suggest the agency’s chief priority should be ensuring that an approved drug is clinically effective. “Once a drug is given accelerated approval, it is out there, and people use it in the absence of data and become convinced of its benefits,” said Rita Redberg, MD, MSc, a professor of medicine at the University of California, San Francisco, and editor of Archives of Internal Medicine. “That seems to be happening with midodrine. We have people saying it helps, but there is no clinical trial data supporting that. The disturbing thing is, it could be hurting them—we really don’t know.” (...)

– USAs syfiliseksperiment i Guatemala var umenneskelig
nrk.no 30.8.2011
USAs president har personlig beklaget et makabert syfiliseksperiment USA utførte i 1940-åren overfor Guatemalas nåværende myndigheter.

Minst 83 personer døde som menneskelige forsøkskaniner i et makabert forskningsprosjekt USA utførte i Guatemala i 1940-årene, fastslår en Obama-oppnevnt granskingskommisjon.

– Forskerne må ha visst at de brøt etiske standarder da de med overlegg smittet guatemalanske fanger og psykiatriske pasienter med syfilis, er kommisjonens soleklare hovedfunn.

Mer enn 1.300 guatemalanere ble i det statsstøttede eksperimentet mellom 1946 og 1948 eksponert for den seksuelt overførbare sykdommen syfilis. Rundt 700 av dem ble smittet, viser granskernes undersøkelser.

– I den gruppen mener vi å ha avdekket at 83 døde, sa kommisjonsmedlem Stephen Hauser mandag. (...)

Dårlig beskyttet
Forskningen på førtitallet skjedde med godkjenning fra amerikanske helsemyndigheter, og var ment å øke kunnskapen om antibiotikamedisinen penicillin.

Etter at det kontroversielle eksperimentet ble avdekket i fjor høst, gikk dagens helsemyndigheter i USA ut og avviste at noe lignende kunne ha skjedd i dag. Men eksperter på bioetikk er mindre overbevist. Spesielt er det grunn til å se på reglene for private forskningsprosjekter som reiser til utlandet for å foreta kliniske studier, sier professor i bioetikk på Universitetet i Minnesota, Mary Faith Marshall.

Deltakere i medisinsk forskning skal gi såkalt informert samtykke, men mange eksperter mener regelverket gir liten grad av kontroll med hvordan dette praktiseres i områder med mange analfabeter, mye korrupsjon og fattigdom. (...)

FDA aims to boost innovation through regulatory science overhaul
pharmatimes.com 22.8.2011
The US Food and Drug Administration (FDA) has a released a new Strategic Plan for Regulatory Science which outlines a sweeping modernisation of the science used in developing and evaluating the products over which it has oversight.

"The core responsibility of FDA is to protect consumers by applying the best possible science to its regulatory activities - from pre-market review of efficacy and safety to post-marketing product surveillance to review of product quality," according to the Strategic Plan.

"In the last few years, rapid advances in innovative science have provided new technologies to discover, manufacture and assess novel medical products," it says, adding: "FDA must both keep pace with and utilise these new scientific advances in order to accomplish its mission to protect and promote the health of our nation." (...)

Deal in Place for Inspecting Foreign Drugs
nytimes.com 13.8.2011
More than 80 percent of the active ingredients for drugs sold in the United States are made abroad, mostly in a shadowy network of facilities in China and India that are rarely visited by government inspectors, who sometimes cannot even find the plants.

But after decades of failed attempts, the federal government and the generic drug industry have reached an agreement that is almost certain to pass Congress and that will lead to routine inspections of these overseas plants, potentially transforming the enormous global medicine trade.

Under the landmark agreement, expected to be completed within weeks, generic drug companies — which make 75 percent of the prescription medicines sold in the United States — would pay $299 million in annual fees to underwrite inspections of foreign manufacturing plants every two years, the same frequency required of domestic plants. (...)

FDA needs better recall monitoring, says GAO (FDA trenger bedre overvåkning av tilbaketrekking, ifølge GAO)
in.reuters.com 23.6.2011
(Reuters) - Congressional auditors have faulted U.S. health regulators for failing to track unsafe medical devices after they are recalled, opening the door to further risks to patients.

The Government Accountability Office (GAO) found 21 high-risk recalls between 2005 and 2009 where companies were unable to correct or remove faulty devices. Its report, dated June 14, was released to the public on Wednesday.

"The FDA can't tell if recalls of high-risk devices were carried out successfully because it lacks criteria for assessing device recalls and doesn't routinely review recall data," said Senator Charles Grassley in a statement, referring to the U.S. Food and Drug Administration.

"It looks like the FDA is missing an opportunity to proactively identify and address risks presented by unsafe devices," he said.

High profile recalls include last year's massive recall of artificial hips from Johnson & Johnson's DePuy unit. Some 93,000 patients worldwide had that line of hip implant.

Medtronic had to recall heart defibrillator leads several years ago, while the FDA recently expanded a recall of coronary imaging catheters from Boston Scientific Corp.

The FDA has already issued seven high-risk device recalls this month. The agency said on Wednesday it had taken steps to improve the recall process with a program launched last November. (...)

(Anm: Medical Devices: FDA Should Enhance Its Oversight of Recalls. GAO-11-468 June 14, 2011 (pdf).)

New FDA Regulation to Improve Safety Reporting in Clinical Trials (Ny FDA-regulering for å forbedre sikkerhetsrapportering i kliniske forsøk)
NEJM 2011 (June 8)
As part of an initiative designed to modernize the clinical trial enterprise, the Food and Drug Administration (FDA) recently published a regulation establishing a new safety-reporting paradigm for drugs being studied under investigational new drug applications (INDs).¹ This rule — published last September and effective as of March 28, 2011 — is one in a series of steps the FDA is taking to enhance the protection of human subjects and improve trial conduct by streamlining the regulatory procedures for clinical trials. (...)

Device Approval
JAMA. 2011;305(22):2280 (June 8)
A commitment by the Food and Drug Administration (FDA) to require a more stringent approval process for high-risk medical devices remains unfulfilled, said the Government Accountability Office (GAO) in a report presented in an April 13 hearing of the Senate Special Committee on Aging (http://1.usa.gov/hB8QDG).

The GAO had previously reported that the FDA should take steps to ensure that high-risk devices undergo the most stringent premarket review process (http://1.usa.gov/jQlfL5). The FDA has issued a final rule for only 1 type of high-risk device, the GAO testified at the hearing. The remaining 26 types of high-risk devices, such as automated external defibrillators and implantable hip joints, can still enter the US market through a less stringent process.

“The drive toward getting new technologies to market shouldn't be done at the risk of patient safety,” said Committee Chairman Sen Herb Kohl (D, Wis), in a statement. “Faulty medical devices, especially those implanted in the body, can have a disastrous impact on the health of those who use them.” (...)

Styrelse overhørte lægers advarsler om farlig medicin
dagensmedicin.dk 24.5.2011
I næsten et år havde Lægemiddelstyrelsen kendskab til, at brugen af SSRI-præparater under graviditet kunne føre til aborter, fosterdød og spædbørnsdød, før den vigtige viden blev givet videre til de praktiserende læger.

Trods adskillige indberetninger om alvorlige bivirkninger forbundet med brugen af SSRI-præparater under graviditet skulle der gå næsten et år, før Lægemiddelstyrelsen advarede landets praktiserende læger mod at udskrive medicinen. Det skriver Ekstra Bladet.

Allerede i 2009 viste to danske forskningsresultater, at gravides brug af antidepressiv medicin kunne skade fosteret, og i juni 2010 konkluderede professor Ebba Holme Hansen og lektor Lise Aagaard fra Institut for Farmakologi og Farmakoterapi på Københavns Universitet i en undersøgelse, at der på daværende tidspunkt var registeret 48 indberetninger om alvorlige bivirkninger forbundet med antidepresiva under graviditet.

Men først i marts 2011 – de indberetningerne var steget til 51, herunder 12 tilfælde af abort og fosterdød samt fire dødsfald hos spædbørn – advarede Lægemiddelstyrelsen de praktiserende læger mod at udskrive antidepressiv medicin til gravide. (...)

Head to head comparisons are missing from half of new drug approvals
BMJ 2011; 342:d2841 (11 May)
All you need to read in the other general journals

JAMA2011;305:1786-9 [Abstract/Full text]
Doctors prescribing a new drug need to know how it compares with established alternatives. Regulators approving new drugs for market don’t always insist on head to head trials, however, so comparative effectiveness data can be hard to find in the crucial few years after the launch of a new drug. Preapproval documentation submitted to regulators is a potential source of information, although it was patchy in one recent study from the US.

Researchers analysed packages of documents submitted to the Food and Drug Administration for new drug approvals between 2000 and 2010. Just over half the packages (100/197) contained one or more studies that compared the new drug with an active alternative. The regulator’s decision was based on comparative efficacy data for just 59 out of 197 drugs.

So some data are available, some of the time. The researchers weren’t able to say whether the head to head studies found on the FDA’s website were good enough to be useful to doctors, other prescribers, or decision makers in charge of formularies. But they do think the source has potential and should be more accessible and easier to use. They would also like to see more comparative studies before drugs are approved. The findings of this US analysis are broadly in line with a study of approval decisions made by the European regulator between 1999 and 2005. (...)

Data from medical trials 'withheld'
hospitalpharmacyeurope.com 11.5.2011
Researchers from the Nordic Cochrane Centre in Denmark said that the profits of drug companies were being prioritised over patient welfare by holding back the information.

The team has called for full access to published and unpublished full trial reports in a bid to allow the scientific community to make an independent assessment of what treatments have to offer.

Peter Gotzsche and Dr Anders Jorgensen said: "Doctors are unable to choose the best treatments because research results are being reported selectively."

The researchers said: "There is something fundamentally wrong with our priorities in healthcare if commercial success depends on withholding data that are important for rational decision making by doctors and patients."

The research, published by the BMJ, suggested that selective reporting can have "disastrous consequences".

The report said: "Anti-arrhythmic drugs have probably caused the premature death of about 50,000 Americans each year in the 1980s." (...)

Public Citizen: Key data left out of Alzheimer's study (Public Citizen: Nøkkeldata utelatt i Alzheimer-studie)
reuters.com 10.5.2011
* Group claims accuracy data excluded from medical journal

* Public Citizen says raises risk of unreliable results

CHICAGO May 10 (Reuters) - A U.S. consumer group alleged on Tuesday that researchers with ties to Eli Lilly and Co (LLY.N) withheld important information from a medical journal in their study of an imaging drug for Alzheimer's disease.

In a letter published in the Journal of the American Medical Association, Public Citizen criticized a Jan. 19 study that assessed the effectiveness of brain scans using Lilly's Amyvid, an experimental dye to detect brain abnormalities.

They said the study authors excluded data on how accurately the scans were interpreted from one physician to the next. (...)

Läkemedelsverkets ledning tappar förtroende
lakemedelsvarlden.se 9.5.2011
Bland de anställda på Läkemedelsverket sjunker förtroendet för verksledningen. Däremot är de betydligt nöjdare med sina närmaste chefer än 2009. Det visar årets medarbetarundersökning. (...)

FDA’s approval of depot naltrexone undermines scientific, regulatory, and ethical standards, say critics
BMJ 2011; 342:d2755 (4 May)
All you need to read in the other general journals

Lancet 2011; doi:10.1016/S0140-6736(11)60358-9

A group of international experts has criticised the US Food and Drug Administration (FDA) for approving a depot form of naltrexone for heroin addiction after a single placebo controlled trial conducted in Russia. The new formulation worked, but a linked comment (doi:10.1016/S0140-6736(10)62056-9) charges the FDA with undermining scientific and ethical standards by accepting evidence from a placebo controlled trial that denied participants an active comparator, such as methadone maintenance. Accepted comparator treatments are available in the US (where depot naltrexone is now licensed) but not in Russia, where the new drug’s manufacturers chose to conduct their trial. “The testing of depot naltrexone in Russia is akin to finding a location with no access to antiretrovirals and then testing a new HIV drug against placebo,” they write. (...)

Making raw data more widely available (Å gjøre rådata mer alminnelig tilgjengelig)
BMJ 2011; 342:d2323 (4 May)
New initiative by the Wellcome Trust sets out some guiding principles

Medical investigators routinely refuse to share data from medical studies, seeming to regard such data as private property rather than a public resource for the benefit of medical science and future generations of patients. One survey found that 75% of pharmaceutical researchers were opposed in principle to making raw data available.¹ Two studies have found that only a minority of researchers (10% and 25%) share data when publishing in journals with explicit policies that raw data must be made available.^{2 3} Even in genomics research, where the principle that microarray data should be deposited in a publicly accessible database is widely accepted, many published studies do not have an associated data set publicly available.^{4 5}

The benefits of sharing raw data from medical studies have been widely discussed.^{6 7 8 9} Data sharing ensures reproducibility, allows testing of secondary hypotheses, facilitates development of new statistical methods, provides a resource for teaching, aids design of new studies, simplifies data acquisition for meta-analysis, and helps prevent fraud and selective reporting. (...)

(Anm: Forskning og ressurser (mintankesmie.no).)

Supreme Court To Weigh Drug Confidentiality Laws
kaiserhealthnews.org 25.4.2011
The New York Times: A Fight Over How Drugs Are Pitched

Marketing to doctors using prescription records bearing their names is an increasingly contentious practice, with three states, Maine, New Hampshire and Vermont, in the vanguard of enacting laws to limit the uses of a doctor’s prescription records for marketing. On Tuesday, the Supreme Court will hear arguments in a case, Sorrell v. IMS Health, that tests whether Vermont’s prescription confidentiality law violates the free speech protections of the First Amendment (Singer, 4/24).

Meanwhile, news outlets also reported on several other drug-related issues. (...)

A Fight Over How Drugs Are Pitched
nytimes.com 24.4.2011
Before pharmaceutical company marketers call on a doctor, they do their homework. These salespeople typically pore over electronic profiles bought from data brokers, dossiers that detail the brands and amounts of drugs a particular doctor has prescribed. It is a marketing practice that some health care professionals have come to hate.

“It’s very powerful data and it’s easy to understand why drug companies want it,” said Dr. Norman S. Ward, a family physician in Burlington, Vt. “If they know the prescribing patterns of physicians, it could be very powerful information in trying to sway their behavior — like, why are you prescribing a lot of my competitor’s drug and not mine?”

Marketing to doctors using prescription records bearing their names is an increasingly contentious practice, with three states, Maine, New Hampshire and Vermont, in the vanguard of enacting laws to limit the uses of a doctor’s prescription records for marketing.

On Tuesday, the Supreme Court will hear arguments in a case, Sorrell v. IMS Health, that tests whether Vermont’s prescription confidentiality law violates the free speech protections of the First Amendment. (...)

FDA's 'Bad Ad' Program Generates One Warning Letter in First Year (FDAs "Dårlig reklame"-program genererer en advarsel det første året)
commercialalert.org 19.4.2011
Nearly a year into the Food and Drug Administration’s “Bad Ad” program, only one pharmaceutical company has received a warning letter that stemmed from the initiative and the recipient called it a “joke.”

“This program,” said Jerry Roth, president of Sanford, Fla.-based Hill Dermaceuticals, “is the phoniest thing I’ve ever seen.”

The “Bad Ad” program, launched in May 2010 by the FDA’s Division of Drug Marketing, Advertising and Communication, enlists the aid of medical professionals and health-care providers to help an understaffed FDA police the pharmaceutical community by anonymously reporting ads and sales pitches that violate FDA rules.

According to the FDA, it has received 239 complaints to the Bad Ad program from its launch in May through January of this year. Of these complaints, 129 (54%) have come from health-care providers, 73 (31%) from consumers, and the remainder from other sources. Of the 239 complaints, approximately 135 were deemed to have sufficient merit for further investigation, with approximately 50% falling within DDMAC oversight and the rest being referred to other centers within FDA.

One of the fears of the Bad Ad plan when it was first announced was that those opposed to direct-to-consumer advertising or competing companies in the same industry could manipulate the program by lodging an anonymous complaint. (...)

FDA Takes Slow Road Toward Withdrawal of Drug Approved With Fast-Track Process
JAMA. 2011;305(10):982-984 (March 9)
The US Food and Drug Administration (FDA) is apparently continuing to slow its withdrawal procedure for a drug that was granted access to the market through the agency's accelerated approval process.

The accelerated approval process for prescription drugs remains a problem for the US Food and Drug Administration, some observers say. For such approval, the FDA expects the drug maker to conduct postmarket studies to evaluate the drug's clinical benefits and adverse events, but companies often do not do such studies in a timely manner.

At issue is midodrine hydrochloride, which received accelerated approval in 1996 for the treatment of symptomatic orthostatic hypotension. The approval was based on studies showing an improvement in the surrogate end point of 1-minute standing systolic blood pressure—a marker considered likely to correspond to clinical benefits, chiefly relief of symptoms and improved ability to perform activities of daily living. In granting accelerated approval, the FDA expects the manufacturer to conduct postmarket studies of clinical benefits and to determine adverse events. (...)

Withdrawing FDA Approval of Midodrine After Marketing
JAMA. 2011;305(8):781-782 (February 23)
To the Editor: Drs Dhruva and Redberg¹​ urged the Food and Drug Administration (FDA) to remove midodrine from the market after it was granted accelerated approval but the manufacturer did not complete confirmatory trials. We doubt that their recommendations will force drug companies to adhere to postmarketing commitments in return for accelerated premarket approval. Failure to conduct the requisite studies to prove “a benefit in clinical outcomes,”¹ or to withdraw a drug when no clinical benefit is found, should carry financial penalties. Moreover, the public, including health professionals, needs to know which companies that have received accelerated approval have violated the FDA's postmarketing requirements. If the FDA is receiving “powerful pressure from many sources”¹​ to ignore its own requirements, the public, including health professionals, needs to know the sources. Two of the citations used by Dhruva and Redberg indicated companies in violation of FDA rules and sources of pressure on the FDA,^2,3​ but their Commentary did not reveal them. In addition, any group or individual (including patients) that appeals to the FDA not to withdraw a drug should be required to provide empirical data on the proportion of patients benefiting from the drug. (...)

FDA processes 'impede US public health, investment, innovation'
pharmatimes.com 21.2.2011
The US Food and Drug Administration's "increasingly unpredictable" approval processes are negatively impacting the nation's public health, economy, job creation, competitiveness and innovation, a new report claims.

The most recent review times for drugs and biologics at the agency have increased 28% compared with average levels for 2003-27, says the study, which is published by the California Healthcare Institute (CHI) and The Boston Consulting Group (BCG). Mounting criticism and pressure from Congress, the media and consumer advocates have resulted in an FDA that is hindered by a growing focus on potential risks of new products, as opposed to benefits, the author claim. (...)

More Outsourcing Planned for FDA Overseas Factory Inspections
Bloomberg.com 10.2.2011
U.S. regulators plan to outsource more inspections of overseas factories within the next decade after criticism from Congress about a lack of oversight for food and drugs made in other countries.

The Food and Drug Administration aims to increase its reliance on third-party inspectors and has started reaching out to industry trade groups about the change, John Taylor, the agency’s acting principal deputy commissioner, said today. The agency will work more closely with other countries and share findings, potentially reducing the number of inspections plants would undergo each year, he said. (...)

FDA issues electronic trial data guidance to support accuracy
outsourcing-pharma.com17.1.2011
Related topics: Clinical evolution, Clinical Development, Data management, Phase I-II, Phase III-IV, Regulatory affairs

The FDA has issued guidance on electronic data in clinical trials to help eliminate duplication, reduce transcription errors and promote real-time entry.

Increased computer use in clinical trials creates problems because data can be easily copied, transferred, changed or deleted without obvious evidence. To help ensure accurate, original and attributable data is available for clinical review and site inspection guidance has been issued .

The US Food and Drug Administration (FDA) draft guidance breaks handling electronic clinical trial data down into three phases: entry; review; and processing and transmission. An FDA chart showing how data might flow between the three phases is pictured below. (...)

US FDA pledges better communication with industry
pharmatimes.com 10.1.2011
Administration (FDA) has launched a new web resource, FDA Basics for Industry, which aims to help companies save time and resources in their interactions with the agency.

The site is one of 19 action items contained within the 46-page FDA Transparency Initiative report, launched by the agency late last week.

FDA Basics for Industry will provide basic information about the FDA’s regulatory processes, including information frequently requested by industry. (...)

Medisinsvikt
Leder
aftenposten.no 20.12.2010
I over 30 år har Efedrin vært den vanligste medisinen norske babyer og småbarn har fått mot hoste. I fjor ble det skrevet ut drøyt 46 000 resepter på medisinen som hvert år brukes av hvert femte barn i Norge. Over halvparten av dem er under to år. Nå har et forskerteam, under ledelse av professor Ansgar Berg, kommet til at medikamentet ikke bør brukes av barn under to år i det hele tatt. Efedrin er et sentralstimulerende middel, og faren for alvorlige bivirkninger er for stor. I utlandet er det registrert dødsfall.

Medisinen brukes aldri på barneavdelinger på sykehus, fremgår det av en reportasje i A-magasinet. Men den er en populær medisin blant legevaktleger som ofte konfronteres med pårørendes ønsker om behandling av småsyke barn.

Reportasjen avslører flere kritikkverdige forhold. Om Efedrin i det hele tatt har noen positiv effekt, er ikke dokumentert. Ingen vet hvor stor dose en liten barnekropp egentlig tåler, ifølge Berg. Nycomed har markedsføringstillatelse for Efedrin, men har ikke undersøkt om det faktisk virker. Begrunnelsen er at det har vært på markedet så lenge.

Efedrinsaken avslører hull i systemet for godkjenning av legemidler. At en medisin er gammel, er ikke noe argument for at den er god. Når leger på sykehusenes spesialavdelinger unnlater å bruke Efedrin, burde dette være retningsgivende for andre leger også. Det er kritikkverdig at Nycomed har unnlatt å teste produktet. Men det endelige ansvaret er det Legemiddelverket som har. Publikum må kunne stole på at godkjente legemidler holder god kvalitet. (...)

AstraZeneca Feels Big Pharma's Pain
online.wsj.com 18.12.2010
AstraZeneca looks vulnerable. A delay in U.S. regulatory approval for one of its most promising new treatments caught the market by surprise Friday. The subsequent drop in the share price of the U.K. pharmaceuticals group reflects a worst-case scenario for the drug.

But the news comes a day after regulators said they plan to revoke approval of rival Roche Holding's best seller Avastin for treatment of advanced breast cancer. Fears about rising regulatory hurdles will (...)

EMA inspects fewer than 1% of clinical trial sites
outsourcing-pharma.com13.12.2010
Related topics: Globalisation, Patient safety, Clinical Development, Phase III-IV, Regulatory affairs

The EMA inspects fewer than 1% of trial sites. Outsourcing-Pharma visualises this data and details the GCP-compliance sampling and collaboration strategies used by the EMA.

Fewer than one per cent of trial sites included in marketing authorisation applications (MAA) were inspected by the European Medicines Agency (EMA) from 2000 to 2009. This is, at least in part, because of lack of resources and the EMA explained how it works around these limitations.

“The key to the process is therefore to test, by sampling, the processes and systems for different regions/regulatory frameworks, companies, therapeutic areas, population types, orphan product, commercial or academic sponsor etc rather than validating sites per se”, writes the EMA. (...)

Regulation is flawed (Regulering er mangelfull)
BMJ 2010; 341:c7016 (7 December)
Something is fundamentally wrong with a drug regulatory system that makes it increasingly difficult to do independent pragmatic trials of widely used but unproven drugs yet licenses a ridiculously expensive drug with no randomised evidence that it improves clinical outcomes over the cheap unlicensed preparation.^{1 2} (...)

FDA is gold standard of review (FDA er gullstandard for saksbehandling)
BMJ 2010; 341:c7004 (7 December)
Brownlee and Lenzer had clearly made up their minds about the Food and Drug Administration (FDA) and medical device community before writing their article.1 It is unfortunate that they didn’t acknowledge the cutting edge advances and improvements to patient care medical devices provide every day.

Today, with such medical advances, the average American can expect to live to 78, a 65% increase over the past 100 years. The medical device industry is perhaps one of the greatest unsung contributors to increased life expectancy. Research has shown that since 1980 death rates have declined 16% and Americans spend 56% fewer days in hospital, partly because of medical devices. (...)

Lægechefer begik »alvorlig fejl« i Omniscan-sag
berlingske.dk 7.12.2010
Lægemiddelstyrelsen erkender, at man ved en fejl fjernede advarslen mod kontraststoffet Omniscan.

Da Lægemiddelstyrelsen i 1998 fjernede advarslen mod at bruge kontraststoffet Omniscan på nyrepatienter, begik man en "alvorlig fejl".

Det erkender Lægemiddelstyrelsens direktør Jytte Lyngvig i et svar til indenrigs- og sundhedsminister Bertel Haarder (V).

- Vi er dybt berørte af den ulykkelige situation og de lidelser, som brug af Omniscan har påført både patienter og pårørende, skriver Jytte Lyngvig i et følgebrev til Lægemiddelstyrelsens notat.

Svar på kritik
Notatet fra Lægemiddelstyrelsen er et svar på den skarpe kritik af Lægemiddelstyrelsen, som er blevet rejst i en uafhængig advokatrapport fra advokatfirmaet Kromann Reumert.

Rapporten konkluderer blandt andet, at tre navngivne chefer i Lægemiddelstyrelsen, heriblandt Jytte Lyngvig, har forsøgt at fortie væsentlige oplysninger om den mangelfulde sagsbehandling, da der blev stillet spørgsmål til sagen i Folketinget.

Det har fået politikere fra flere partier til at kræve de tre chefer afskediget.

Lægemiddelstyrelsen afviser imidlertid, at man har tilbageholdt oplysninger i besvarelsen af Folketingsspørgsmål.

- Vi har svaret korrekt og koncist på de stillede spørgsmål, hedder det i følgebrevet fra Jytte Lyngvig. (...)

Independent drug review group in Canada is squeezed out (Uavhengig gruppe som vurderer legemidler skviset ut)
BMJ 2010; 341:c7009 (6 December)
The British Columbian government is terminating its contract for drug reviews with an independent drug watchdog organisation, instead allowing drug manufacturers and people with financial ties to the industry to advise. The move comes after years of pressure from the industry group Canada’s Research-Based Pharmaceutical Companies for a more “open” process for reviewing drugs.

The watchdog group, Therapeutics Initiative, is based at the University of British Columbia, Vancouver. Its website says that it provides “independent assessments of evidence on drug therapy to balance the drug industry sponsored information sources.”

The decision by the provincial government comes after a closed meeting of “stakeholders” on 24 November, comprising largely representatives of drug companies and patients’ groups. Media representatives and the public were not allowed to attend. (...)

French doctors demand to know why drug stayed on the market for so long (Franske leger krever å få vite hvorfor legemiddel ble værende på markedet så lenge)
BMJ 2010; 341:c6882 (3 December)
French doctors, the public, and the media are asking how a drug that, it is claimed, might have had a role in an estimated 500 deaths was able to stay on the market for 33 years.

The ministry of health announced on 16 November that it was launching a public investigation into the regulation of benfluorex (Mediator) from Servier, France’s second largest drug company. The same day, the French medicines agency (Afssaps, Agence Française de Sécurité Sanitaire des Produits de Santé), stated that, on the basis of epidemiological studies, around 500 deaths might be attributable to the use of benfluorex, which was available in France as an adjuvant for type 2 diabetes from 1976 to November 2009. (...)

FDA Official Retires Amid Inquiry (Leder i FDA fratrer under granskning)
online.wsj.com 24.11.2010
WASHINGTON—The Food and Drug Administration's top criminal investigator is stepping down after a whistleblower made allegations about the alteration of internal agency reports and other misconduct.

Terry Vermillion set up the FDA's Office of Criminal Investigations in 1992 after retiring as a Secret Service agent. The office has been at the center of the current probe into alleged doping by cyclist Lance Armstrong. The anonymous whistleblower complaint, sent to Sen. Chuck Grassley (R., Iowa), doesn't involve the Armstrong case.

According to a September letter by Mr. Grassley, the whistleblower alleged that Mr. Vermillion has been running his office from his home near Virginia Beach and inappropriately hired a certain contractor against the advice of other criminal-division officials.

The whistleblower also said Mr. Vermillion "directed that reports prepared by OCI's Office of Internal Affairs be changed to sanitize them of derogatory information about his fellow U.S. Secret Service retirees now working at FDA/OCI," according to the Grassley letter. (...)

(Anm: Letter From Sen. Grassley Outlining Allegations of Misconduct.)

(Anm: FDA Criminal Division to Increase Prosecutions (03/04/2010.)

Danske fejl og svigt skyld i tusinder af invalide i Europa
dagensmedicin.dk 19.11.2010
Det var stærkt kritisable fejl og forsømmelser i Lægemiddelstyrelsens håndtering af sagsbehandlingen, da advarslen mod at bruge Omniscan til nyrepatienter blev fjernet i 1998, viser uvildig advokatundersøgelse.

En række alvorlige fejl og forsømmelser i Lægemiddelstyrelsens sagsbehandling har afgørende betydning for, at et større antal danske nyrepatienter i dag enten er afgået ved døden eller er blevet stærkt invaliderede. Uden at foretage nogen medicinsk vurdering accepterede Lægemiddelstyrelsen i marts 1998 producenten Nycomeds ønske om at få mr-kontrastmidlet Omniscan frigivet til undersøgelse af patienter med nedsat nyrefunktion. Det fremgår af den længe ventede uafhængige advokatundersøgelse vedrørende Omniscan, som Indenrigs- og Sundhedsministeriet offentliggjorde i sidste uge. (...)

Watchdog Says FDA Risked Integrity
online.wsj.com 8.11.2010
WASHINGTON—Congress's watchdog arm has criticized the Food and Drug Administration for creating the appearance of favoritism toward a Boston company that won lucrative first rights to sell a generic drug after providing free consulting work to the agency.

On Tuesday, a congressional committee plans to release a report by the Government Accountability Office that says the FDA risked giving the appearance that it had compromised its integrity because of its dealings with the company, Momenta Pharmaceuticals Inc. (...)

Congress panel probes FDA office in Puerto Rico
forbes.com 8.11.2010
SAN JUAN, Puerto Rico -- Congressional investigators announced Monday they will probe whether the U.S. Food and Drug Administration's office in Puerto Rico has failed to adequately oversee pharmaceutical plants that dot the U.S. island.

House Oversight and Government Reform Committee Chairman Edolphus Towns, a New York Democrat, and Darrell Issa, a California Republican who is in line to head the panel, questioned whether FDA staff are up to the regulatory job on an island with one of the world's highest concentrations of drug makers.

"It appears that FDA's Puerto Rico district office may be having difficulty exercising oversight on the numerous pharmaceutical manufacturing facilities on the island," the lawmakers wrote in a letter to FDA Commissioner Margaret Hamburg.

They asked the FDA chief for a list of current and past employees in Puerto Rico, inspection records and warning letters issued in the last decade "to better understand whether FDA Puerto Rico is fulfilling its regulatory responsibility."¨(...)

Grassley quizzes FDA chief on conflicts
startribune.com 22.10.2010
A U.S. senator has asked the head of the Food and Drug Administration whether the agency monitors medical device companies' payments to doctors who are involved in clinical studies of the companies' products.

In a letter to FDA Commissioner Margaret Hamburg sent Friday, Sen. Charles Grassley cites information about Medtronic Inc. that surfaced in a separate inquiry.

That query discovered that of 50 clinical investigators studying Medtronic products, "almost all ... received significant payments" from the Fridley-based medical technology company.

In some cases, doctors also had a "proprietary interest in the product being tested and a financial arrangement where the value of compensation could be influenced by the outcome of the study," Grassley said. (...)

Senator: Feds should probe high prescribing docs (Senator: Staten bør granske leger med høy forskrivning)
business.dk 21.10.2010
A key U.S. Senator is asking federal officials to investigate after reviewing data that shows doctors across the country prescribing alarmingly high numbers of powerful mental health drugs paid for by Medicare and Medicaid.

U.S. Sen. Charles Grassley of Iowa studied Medicare and Medicaid prescription rates from doctors around the country, revealing few consequences for doctors with high prescription rates. The findings include a Miami doctor who wrote nearly 97,000 prescriptions in 18 months for mental health drugs for Medicaid patients and an Ohio physician who wrote about 102,000 prescriptions in two years.

A Texas doctor wrote 14,170 prescriptions for the anti-anxiety drug Xanax in 2009, far exceeding other high prescribers in that state. The 10th highest prescriber in Texas for Xanax wrote 1,696 prescriptions in 2009, according to Grassley. (...)

FDA adverse event revisions a positive step, says CEO
outsourcing-pharma.com 21.10.2010
Revision to FDA guidance on adverse event reporting is a positive step and forms part of a welcome increased focus on safety, says the CEO of Prism Ideas.

At the end of September the US Food and Drug Administration (FDA) issued a final rule and draft guidance to revise its stance on the reporting of safety information arising in trials. Making the revisions was intended to speed review of safety information and protect trial participants. (...)

FDA Reviews Use of Controversial Clinical Trials Design
Psychiatr News 2010;45(20):1 (October 15) (American Psychiatric Association)
A report released by the Government Accountability Office (GAO) in August regarding the Food and Drug Administration's (FDA) oversight of new drug applications concluded that the “FDA has limited the indications” for which a certain type of clinical trial known as “an inferiority trial” can be used.

The GAO report was issued in response to a request from Congress, which makes policy and funding decisions based on information provided in these reports.

Noninferiority trials are intended to determine that the effect of a new drug is not worse than that of an approved (reference) treatment. Most clinical trials, in contrast, are set up to demonstrate that one intervention (that is, drug treatment) is superior to another. (...)

FDA to Focus on 'Science' of Drug Regulation
medpagetoday.com 6.10.2010
WASHINGTON -- The FDA announced a plan on Monday to create a network of centers that will help promote its new "regulatory science" agenda.

The agency defines regulatory science as the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products.

The plan was released in a 20-page white paper called "Advancing Regulatory Science for Public Health," which broadly outlines how the agency plans to begin creating a network of Centers of Excellence in Regulatory Science, as well as increase its relationship with academia, industry, and other government agencies.

The Centers would be housed in academic institutions, said FDA Commissioner Margaret Hamburg, MD, who was at the National Press Club on Wednesday to speak about the agency's goal to beef up its approach to regulatory science.

One aspect of how the FDA regulates new drugs, biologics, and devices that might be updated under the new plan is the use of surrogates and biomarkers in clinical trials, Hamburg told MedPage Today. (...)

Reviving the FDA
NEJM 2010 (October 6)
Approaching the end of her first year as commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg remarked that, despite past experience with government bureaucracies, she is struck by how hard it is to make her agency act quickly. “You feel it differently at the FDA — how long it takes to move things through the system,” she told an audience at the Institute of Medicine (IOM) in February. “The process of regulation does not allow you to respond in a timely way to emerging science or to other important emerging concerns.” The FDA’s principal deputy commissioner, Dr. Joshua Sharfstein, put it more bluntly in a recent interview: “I keep a list of things that I wish were moving faster and a list of things moving at just the right speed, and there’s nothing on the second list.” (...)

Drug Safety: FDA Has Conducted More Foreign Inspections and Begun to Improve Its Information on Foreign Establishments, but More Progress Is Needed
fda.gov 30.9.2010 (GAO-10-961 September 30, 2010)
Highlights Page (PDF) Full Report (PDF, 43 pages)
Globalization has placed increasing demands on the Food and Drug Administration (FDA), an agency within the Department of Health and Human Services (HHS), in ensuring the safety and effectiveness of drugs marketed in the United States. Drugs manufactured in more than 100 countries were offered for entry into the United States in fiscal year 2009. FDA inspects drug manufacturing establishments in order to ensure that the safety and quality of drugs are not jeopardized by poor manufacturing practices. In 1998 GAO identified weaknesses in FDA's foreign drug inspection program. In 2008 GAO found, among other things, that from fiscal years 2002 through 2007, FDA inspected relatively few foreign establishments each year. GAO also determined that, because of inaccurate information in its databases, FDA did not know how many foreign drug establishments were subject to inspection. In 2008 GAO recommended that FDA increase inspections of foreign drug establishments and improve information it receives to manage the foreign drug inspection program. This report examines FDA's progress since 2008 in (1) conducting more foreign drug inspections, and (2) improving its information on foreign drug establishments. GAO analyzed information from FDA databases, reviewed documents related to FDA's efforts to both improve these databases and supplement its existing information on foreign drug establishments, examined staffing and funding information, and interviewed FDA officials. (...)

Food and Drug Administration: Overseas Offices Have Taken Steps to Help Ensure Import Safety, but More Long-Term Planning Is Needed
fda.gov 30.9.2010 (GAO-10-960 September 30, 2010)
Highlights Page (PDF) Full Report (PDF, 52 pages) Accessible Text Recommendations (HTML)
Summary
An increasing volume of food and medical products marketed in the United States are produced in foreign countries. This globalization has challenged the Food and Drug Administration (FDA), which is responsible for ensuring the safety of these products. In late 2008 and early 2009, FDA established overseas offices comprised of 42 total staff covering particular countries or regions--China, Europe, India, Latin America, and the Middle East. The offices are to engage with foreign stakeholders to develop information that FDA officials can use to make better decisions about products manufactured in foreign countries, among other activities. GAO examined (1) the steps overseas offices have taken to help ensure the safety of imported products and (2) the extent to which FDA has engaged in long-term strategic and workforce planning for the overseas offices. GAO reviewed documentation of overseas office activities and planning. GAO also visited offices in China, India, and Latin America to interview FDA officials, officials from other U.S. (...)

FDA Sets New Rules for Reporting Adverse Trial Events
medpagetoday.com 29.9.2010
WASHINGTON -- The FDA has finalized new procedures aimed at speeding up reporting and analysis of potential safety problems encountered in clinical trials while cutting down on adverse-event filings the agency considers useless.

Under a final rule that will go into effect in March, reportable events are redefined as "any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related." Such events must be reported to the FDA within 15 days, although serious unexpected events should be reported immediately. (...)

New F.D.A.: Transparence and Flexibility
nytimes.com 24.9.2010
WASHINGTON — During the Bush administration, the Food and Drug Administration was mostly a place of black-and-white decisions. Drugs were approved for sale or they were not, and the agency’s staff was expected to publicly support those decisions.

But as Thursday’s landmark decision on the controversial diabetes medicine Avandia makes clear, things have changed under the Obama administration. Certainty, staff unanimity and even the approval status of big-selling medicines are no longer so black and white. (...)

The End Of Drug Withdrawals?
blogs.forbes.com 24.9.2010
If the Food and Drug Administration won’t withdraw marketing approval for GlaxoSmithKline’s diabetes pill Avandia, will it ever yank any drug?

Sure, some side effects will make a medicine too dangerous to keep around. But the decade-long age of mass-market drug recalls – in which an average of one medicine a year has been withdrawn from the U.S. market – looks to be ending thanks to new powers the FDA was granted by a 2007 law, the Food and Drug Administration Amendments Act (FDAAA). Big, headline-grabbing drug withdrawals that affect millions of patients, like those of Baycol, Vioxx, and Zelnorm, could become a thing of the past. (...)

Regulatory Action on Rosiglitazone by the U.S. Food and Drug Administration
NEJM 2010 (September 23)
There have been ongoing concerns about the safety of the diabetes drugs containing rosiglitazone (Avandia, Avandaryl, and Avandamet) — a thiazolidinedione antidiabetic agent indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (...)

MHRA under pressure to withdraw rosiglitazone
pulsetoday.co.uk 7.9.2010
The UK drug regulator has come under fire for failing to act on an expert recommendation to withdraw the type 2 diabetes drug rosiglitazone.

A Freedom of Information Act request by the BMJ has uncovered a report from July from the Commission on Human Medicines, an advisory group to the Medicines and Healthcare Products Regulatory Agency, saying the drug’s risks ‘outweigh its benefits and it no longer has a place on the UK market.’ (...)

Rosiglitazone: what went wrong?
BMJ 2010; 341 (6 September)
(...) The FDA meeting was held in the open, in front of a packed audience including the world’s media. Ahead of the meeting, the FDA published the 765 page report circulated to panel members.

This is far removed from the secrecy shrouding proceedings at Europe’s regulator, the EMA. The BMJ has talked to a range of experts close to the European regulatory process and submitted a series of Freedom of Information requests to the EMA, but we still have no clear picture of why, after initial rejection in October 1999, the EMA gave market authorisation to rosiglitazone in July 2000 in the absence of new evidence. Neither have doctors and patients been told that in July the UK’s Commission on Human Medicines— in an unanimous vote— advised the Medicines and Healthcare products Regulatory Agency (MHRA) to withdraw the drug. In a statement, the MHRA has confirmed that the evidence now suggests that the risks associated with rosiglitazone outweigh the benefits and “that it no longer has a place on the UK market.” But a “dear doctor” letter sent to UK doctors in July advised doctors to “consider alternative treatments where appropriate.”2 The MHRA said that it used the information provided by the Commission on Human Medicines to push for a UK withdrawal as part of the Europe-wide review by the European Medicines Agency. (...)

After Avandia: Does the FDA Have a Drug Problem? (Etter Avandia: Har FDA et legemiddelproblem?)
time.com 12.8.2010
Five days before a 2007 article in the New England Journal of Medicine showed that the diabetes drug Avandia was linked to a 43% increase in heart attacks compared with other medications or placebos, a group of scientists and executives from the drug's maker, GlaxoSmithKline (GSK), gathered in a conference room at the offices of the Food and Drug Administration in White Oak, Md. The GSK goal: to convince regulators that the evidence that the company's $3 billion-a-year blockbuster drug caused heart problems was inconclusive. To do that, the GSK officials focused not on heart-attack data but on a broader, less well defined category of heart problems called myocardial ischemia. The most recent studies of Avandia, the GSK officials told the FDA, had "yielded information that is inconsistent with an increased risk of myocardial ischemic events," according to sealed court proceedings obtained by TIME. (...)

FDA Asks HHS To Probe Avandia Panel Member
pharmalot.com 26.7.2010
Remember David Capuzzi? He was a member of the recent FDA advisory committee on Avandia who, as it turns out, has also been a speaker for GlaxoSmithKline, which sells the controversial diabetes pill. The FDA, apparently, was not aware of this relationship until it was disclosed last week (see here).

Capuzzi, who is a professor of medicine and biochemistry at Thomas Jefferson University in Philadelphia was paid a total of $14,750 over the past several years, mostly for talking about Lovaza, including at least one engagement earlier this year. But there was once instance in which he spoke about Avandia, according to a Glaxo spokesman. When asked about this last week, the FDA issued a statement saying the agency “takes these allegations very seriously and is investigating the matter.” (...)

FDA joins with federal agencies for toxicology research
in-pharmatechnologist.com 20.7.2010
The FDA has joined with other US federal agencies to collectively research methods for predicting the toxicity of chemicals.

Joining the Tox21 programme, which began in 2008, will help the US Food and Drug Administration (FDA) further development of methods used to evaluate the toxicity of substances it regulates.

“The addition of FDA to this effort allows biomedical researchers and regulatory scientists to work together side by side to more rapidly screen chemicals and find more effective ways to protect the health of the public”, said Linda Birnbaum, director of the National Toxicology Program (NTP).

As well as developing models to better predict human response to chemicals, the FDA will work with the other federal agencies to prioritise chemicals that need more extensive toxicological evaluation.

There are tens of thousands of chemicals in commerce and current testing methods can be expensive and time consuming. Consequently, improving methods and prioritising potentially harmful chemicals will help federal agencies cope with the load they face. (...)

FDA OPENS UP: CAN INDUSTRY LIVE WITH GREATER TRANSPARENCY?
SIS.WINDHOVER.COM 1.7.2010
EXECUTIVE SUMMARY
IN VIVO -- Drug sponsors are finding little to like about FDA's transparency initiative - especially proposals that would allow the agency to disclose more about products still in development. But given the public interest in greater transparency - and FDA's interest in avoiding another Avandia - industry needs to decide whether this is a fight worth having. This article was originally published in the July/August 2010 issue of The RPM Report. (...)

Läkemedelsverket får ny tung roll för bättre svensk läkemedelsanvändning
lakemedelsverket.se 27.5.2010
Nu är det klart att Läkemedelsverket kommer att leda samordning och samarbete mellan alla viktiga aktörer i Sverige inom läkemedelsområdet. Läkemedelsverkets generaldirektör Christina Åkerman ställer sig mycket positiv till uppdraget som innebär att Läkemedelsverket nu ytterligare breddar sitt samhällsansvar. (...)

Drug regulation: a sometimes unhealthy coalition
BMJ 2010;340:c2613 (19 May)
(...) Regulation of drugs in the European Union (and elsewhere) relies, in effect, on a coalition between the pharmaceutical industry and the drug regulators. Far from an antagonistic relationship of the governors and the governed, it’s better thought of as an interdependent union that ostensibly serves (the public and healthcare professionals) through exerting power (decisions on whether and when products get to and stay on the market).

The need for this sort of set up isn’t seriously questioned. And the close and essentially harmonious working relations between what are two very different groups tell their own story. The overall impression is of orderly governance that reliably strikes the right balance between facilitating the advent of innovative drugs and safeguarding public health. (...)

Transparency at the Food and Drug Administration
healthcarereform.nejm.org (May 19th, 2010)
On his first full day in office, President Barack Obama issued a memorandum calling for “creating an unprecedented level of openness in Government.” The Department of Health and Human Services embraced this goal, and in June 2009, the new commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg, announced a major transparency initiative. The goal of this initiative was to better explain the FDA’s actions by providing information that supports clinical medicine, biomedical innovation, and public health. (...)

FDA needs new tools to check food, drugs: experts
reuters.com 12.5.2010
(Reuters) - The Food and Drug Administration is stuck using crude tools to measure the benefits of food, drugs and supplements and needs a whole new set of standards, a panel of experts said on Wednesday.

Relying on so-called biomarkers is confusing the entire process of drug development, the public and doctors alike, they said.

The FDA also needs to use the same strict standards for assessing health claims of food and supplements as it does for drugs, said the panel appointed by the Institute of Medicine, which advises the federal government.

The committee recommended a new framework the FDA could use for judging studies that companies provide to support health and safety claims for their products.

"Congress may need to strengthen FDA authority to accomplish this goal," the institute's report reads. (...)

EMA rapped over access to adverse drug action reports (EMA skarpt kritisert over tilgang til rapporter for uheldige legemiddelvirkninger)
pharmatimes.com 11.5.2010
The European Ombudsman has urged the European Medicines Agency (EMA) to reconsider its refusal to provide access to documents relating to suspected adverse drug reactions (ADRs), stating that its failure to do so “constitutes an instance of maladministration.”

The case concerns an Irish citizen who in April 2008 had asked the EMA for reports on suspected ADRs relating to a nationally-authorised drug used in the treatment of severe forms of acne, such as those reactions which give rise to suicidal tendencies. The EMA refused such access, arguing that European Union (EU) transparency rules do not apply to ADR reports.

In September 2008 the complainant brought his case before the European Ombudsman, Nikiforos Diamandouros, who yesterday announced that he disagreed with the EMA’s argument and that, in his view, EU transparency rules apply to all documents held by the Agency.

Given that the EMA’s work has a direct impact on the health of European citizens, it is “of the utmost importance” for the EMA to give “the widest possible access to documents and also to pursue a pro-active information policy for the benefit of citizens,” said Mr Diamandouros. (...)

Tilbakekaller babymedisiner
nrk.no 4.5.2010
Legemiddelprodusenten Johnson & Johnson tilbakekaller over 40 forskjellige typer medisiner for små barn på grunn av produksjonsfeil.

Feilen ble avdekket da det amerikanske mattilsynet (FDA) inspiserte firmaets anlegg i Fort Washington i Philadelphia. (...)

Nettstedet McNeil Consumer Healthcare har lagt ut en liste med detaljer om alle produktene som tilbakekalles. (...)

WSJ: FDA may stop clinical trial on GlaxoSmithKline diabetes drug Avandia (WSJ: FDA kan stoppe klinisk forsøk på GlaxoSmithKlines diabeteslegemiddel Avandia)
news.moneycentral.msn.com 19.4.2010
The U.S. Food and Drug Administration is considering cutting short trials on GlaxoSmithKline’s diabetes treatment Avandia, The Wall Street Journal is reporting.

The drug has been linked to increased risk of heart attack, and some experts have questioned whether it is ethically responsible to test the drug on humans given the potential side effects, The Wall Street Journal reports. The trial was testing the safety of Avandia compared to Takeda’s Actos, another diabetes drug.

Calls to GSK (NYSE: GSK) were not immediately returned Monday morning

If the FDA cuts short the drug trials, it is likely the regulatory agency also would ask GSK to stop selling Avandia, the Journal said in a blog entry Monday. (...)

US FDA “must test new drugs against current therapies, not placebo”
pharmatimes.com 19.4.2010
The US Food and Drug Administration (FDA) has been told to test new drugs against currently-available treatments rather than placebo.

“It is past time to transition to a new system in which drugs and devices are tested against the currently-approved best practice,” William Vaughan, health policy analyst at Consumers’ Union (CU), told a public meeting conducted by the FDA last week as the first step in what is expected to be at least a two-year process of reauthorising the Prescription Drug User Fee Act (PDUFA) programme.

PDUFA authorizes user fees for FDA product reviews - currently funding 65% of new drug review costs - and was first enacted in 1992. It has been reauthorized three times, most recently in September 2007. The current version, PDUFA IV, expires in September 2012.

The FDA held the meeting before its begins discussions with industry in June on the Act’s reauthorization, in order to gather views on what changes should be made to the current legislation before Congress votes on PDUFA V, it is hoped in early 2012. (...)

Moments of truth (Sannhetens øyeblikk)
BMJ 2010;340:c2042 (15 April)
(...) Silvio Garattini and Vittorio Bertele’ think that responsibility and accountability in drug regulation are best fostered by transparency, and they argue in their Analysis article that the move of the European Medicines Agency from the EU’s Industry Directorate to the Directorate for Health is just the opportunity for the EMA to become more transparent (doi:10.1136/bmj.c1578). The data they want to see are not commercially confidential, they say; patients and taxpayers have contributed to the data, and transparency is a means of reducing bias and improving accountability. They include a revealing little table showing that the types of data the EMA so carefully guards are routinely available from the FDA. (...)

Criminal Investigations (Etterforskning)
JAMA. 2010;303(14):1358 (April 14)
US Food and Drug Administration (FDA) Commissioner Margaret Hamburg, MD, vowed that her agency is committed to improving the oversight and effectiveness of its Office of Criminal Investigations (OCI).

Hamburg's vow came in a March 4 letter to Sen Chuck Grassley (R, Iowa), who had requested a review in 2009 by the Government Accountability Office (GAO) into allegations of lax standards and poor responsibility in the FDA's criminal division. The GAO report (http://www.gao.gov/new.items/d10221.pdf) found the FDA's oversight of its OCI was limited, noting that 24 assessments of field offices, intended to ensure compliance with investigative policy, should have been completed by August 2009, but only 7 were finished. One office had not been assessed in more than 10 years. The OCI investigates a wide variety of criminal activities outside of the FDA, including the manufacture and sale of counterfeit drugs and illegal marketing of drugs.

Grassley, in a press release, indicated he was encouraged by the FDA commissioner's response. "Having the FDA leadership focused on fixing what's broken is the first, very important step needed." (...)

Groups urge drug safety steps with industry fees
reuters.com 12.4.2010
(Reuters) - Consumer and patient groups urged U.S. drug regulators on Monday to push for timely advertising reviews, clearer drug labels and other safety measures as they negotiate new fees with manufacturers.

The Food and Drug Administration is gathering input before it starts private talks with drugmakers on the renewal of industry fees that help speed reviews of new medicines. The current fees expire in September 2012. (...)

Too Much Radiation? The FDA Wants to Know (For mye stråling? FDA ønsker å vite)
usnews.com 30.3.2010
Agency set to open two days of public comment on risks from scans (...)

In February, the FDA noted that the benefits of medical imaging were considerable because they've led to disease being diagnosed earlier, allowing better treatment options, including "image-guided therapies that help save lives every day."

But to keep radiation exposure to a minimum, the agency asked that doctors and patients keep two principles in mind: that each procedure must be justified and that the radiation be given at the minimum dose required. (...)

Staffer: FDA suppressed imaging safety concerns (Ansatt: FDA unnlot å informere om sikkerhetsbekymringer ved bildebehandling)
boston.com 30.3.2010
A former Food and Drug Administration scientist said Tuesday his job was eliminated after he raised concerns about the risks of radiation exposure from high-grade medical scanning.

Dr. Julian Nicholas told an audience of imaging specialists that he and other FDA staffers "were pressured to change their scientific opinion," by managers in the agency's medical device division.

Nicholas, now a physician at the Scripps Clinic in San Diego, said he and eight other staffers raised their concerns with the division's top director last September.

"Scientific and regulatory review process for medical devices was being distorted by managers who were not following the laws," Nicholas said. A month later Nicholas' position was "terminated," he said.

The allegations about suppression of scientific dissent within FDA are not the first, and come at an inopportune time for the agency. (...)

(Anm: Computertomografi (CT), magnetisk resonanstomografi (MR), ultrasonografi (ultralyd) og kontrastmidler (mintankesmie.no).)

Europe’s opportunity to open up drug regulation (Europas mulighet for å åpne opp legemiddelkontroll)
BMJ 2010;340:c1578 (30 March)
Among the priorities for the European health directorate, DG Sanco, as it takes control of the agency in charge of drug regulation should be to end the secrecy surrounding approval decisions, say Silvio Garattini and Vittorio Bertele’

Questions about the benefits of the flu drug oseltamivir in otherwise healthy people^{1 2} have fuelled debate about the secrecy surrounding the documentation submitted for marketing authorisation of new medicines. Greater transparency would open drug dossiers to evaluation by the scientific community and help independent interested parties define the benefit-risk profile of new medicines before they are allowed on to the market. The recent movement of the European Medicines Agency (EMA) to the Health and Consumer Policy Directorate (DG Sanco) rather than the Enterprise and Industry Directorate presents an opportunity to introduce more openness. (...)

Scientists Say F.D.A. Ignored Radiation Warnings (Forskere sier at FDA ignorerte advarsler mot stråling)
nytimes.com 28.3.2010
WASHINGTON — Urgent warnings by government experts about the risks of routinely using powerful CT scans to screen patients for colon cancer were brushed aside by the Food and Drug Administration, according to agency documents and interviews with agency scientists.

After staying quiet for a year, the scientists say they plan to make their concerns public at a meeting of experts on Tuesday called by the F.D.A. to discuss how to protect patients from unnecessary radiation exposures. The two-day meeting is part of a growing reassessment of the risks of routine radiology. The average lifetime dose of diagnostic radiation has increased sevenfold since 1980, driven in part by the increasing popularity of CT scans. Such scans can deliver the radiation equivalent of 400 chest X-rays. (...)

Researchers Find Link between Avandia Defenders and Drug Companies (Forskere finner link mellom Avandia-forsvarere og legemiddelfirmaer)
lawyersandsettlements.com 21.3.2010
Rochester, MN: Forskergruppes resultater viser at eksperter som forsvarte Avandia mot negativ publisitet hadde økonomiske forbindelser til legemiddelfirmaet GlaxoSmithKline. Resultatene reiser spørsmål om etikken til studieforfattere med forbindelser til legemiddelindustrien. (...) (Rochester, MN: A team of researchers has found that many of the experts who defended Avandia against negative publicity actually have financial ties to drugmaker GlaxoSmithKline. The findings raise questions over the ethics of study authors who have ties to the pharmaceutical industry.)

The study, published in the British Medical Journal on 3/18/10, concludes, "Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors' expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies." (...)

(Anm: Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010;340:c1344 (18 March).)

(Anm: Sakkyndige legers integritet, partiskhet og habilitet versus løgn i rettssalen (sakkyndighet) (mintankesmie.no).)

Many Avandia defenders have drug co. ties: study (Mange forsvarere av Avandia hadde forbindelser til legemiddelfirmaer)
reuters.com 18.3.2010
(Reuters) - Praktisk talt alle eksperter som skrev fordelaktig om GlaxoSmithKline Plcs kriseramte diabeteslegemiddel Avandia hadde økonomiske forbindelser til legemiddelfirmaer, et resultat som viser behovet for å reformere slike forbindelser, uttalte amerikanske forskere torsdag. (Virtually all of the experts who wrote favorably about GlaxoSmithKline Plc's troubled diabetes drug Avandia had financial ties to drug makers, a finding that shows the need for reform of such relationships, U.S. researchers said on Thursday.)

A team at the Mayo Clinic in Rochester, Minnesota, pored through more than 200 scientific studies and commentaries that offered positive opinions about the drug after a May 2007 study suggested Avandia significantly increased the risk of heart attacks.

De fant at 94 prosent av forfattere som forsvarte legemidlet, kjent under det generiske navnet rosiglitazone, hadde forbindelser til legemiddelfirmaer, og nesten halvparten hadde økonomiske forbindelser som representerte interessekonflikter. (...) (They found that 94 percent of the authors who defended the drug, known generically as rosiglitazone, had ties to drug companies, and nearly half had financial ties that presented a conflict of interest.)

(Anm: Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010;340:c1344 (18 March).)

(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

Grassley Questions FDA on Med Device Approval (Grassley stiller spørsmål om godkjenning av medisinsk utstyr)
dotmed.com 22.2.2010
Senator Charles Grassley (R-IA), Senate Finance Committee Ranking Member, has asked the U.S. Food and Drug Administration (FDA) for updates on new guidelines for medical device makers in the marketing and use of modified devices under the FDA's 510(k) system. (...)

Does FDA Need More Power?
blogs.forbes.com 22.2.2010
Is the controversy over Avandia further proof that the way we approve new drugs needs to change?

That's what Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles, says. Kaul, cardiology's statistical nitpicker, sees little new in the science released by investigators working for Senators Baucus and Grassley. But he says the continuing debate over the safety of Avandia, like the arguments over the effectiveness of Merck's cholesterol drug Zetia, is evidence that the Food and Drug Administration should be given new and different powers. (...)

New studies question FDA's medical approval process (Nye studier stiller spørsmål ved FDAs medisinske godkjennelsesprosess)
examiner.com 31.12.2009
The US Food and Drug Association (FDA) has come under fire once again this week. Two independent studies were published that are critical of the agency's approval process for medical devices. These findings may prove to have long lasting effects in the US justice system. A court case decided in 2008, Riegel versus Medtronic, concluded that approval from the FDA grants companies that produce medical devices free and clear of lawsuits resulting in injuries from their products. (...)

The other study, conducted by researchers from the FDA and Boston’s Beth Israel Deaconess Medical Center, will be published in the upcoming issue of the American Journal of Therapeutics, indicating that about 40% of the studies used to decide what devices are approved lack clear definitions of safety requirements."

These studies follow hot on the heels of other lawsuits with dire consequences that involved FDA approved drugs. Recent headlines featuring tragic birth defects caused by FDA approved antidepressants such as Zoloft and Paxil have shaken consumer confidence in the agency's standards. Even seemingly benign medicine with the FDA's seal of approval is causing grave concern. A good example is the popular denture creams, Fixodent and Poligrip, which are currently facing litigation for zinc poisoning. (...)

FDA corruption in question (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

FDA to study safety of drugs taken during pregnancy (FDA skal granske sikkerhet for legemidler tatt under svangeskap)
reuters.com 30.12.2009
WASHINGTON (Reuters) - U.S. health officials plan to study the safety of medications taken during pregnancy with an eye toward using the data in future regulations and medical practice, the U.S. Food and Drug Administration said on Wednesday.

Citing a lack of clinical trials to determine how medications affect mothers and unborn children, the FDA said it will collaborate with other researchers in the new study, called the Medication Exposure in Pregnancy Risk Evaluation Program.
The agency said data shows that about two-thirds of women who deliver a baby have taken at least one prescription medication during pregnancy. (...)

FDA, Health Plans Begin Study of Drug Effects in Pregnancy
medpagetoday.com 31.12.2009
A massive new database-driven study of effects of prescription drugs during pregnancy, called the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP), is getting under way under FDA sponsorship, the agency announced.
The FDA will collaborate with the HMO Research Network's Center for Education and Research in Therapeutics, based at Harvard Medical School in Boston and Vanderbilt University in Nashville, to collate data from 11 health plan-affiliated research sites.

About half of these sites are part of the Kaiser Permanente system. Others include the research arms of the Harvard Pilgrim and Fallon Community health plans in Massachusetts, the Lovelace Clinic Foundation in New Mexico, the Group Health Research Institute of Seattle, the HealthPartners system in Minnesota, and the Tennessee Medicaid program. (...)

Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices
JAMA. 2009;302(24):2679-2685 (December 23/30)
Context Medical devices are common in clinical practice and have important effects on morbidity and mortality, yet there has not been a systematic examination of evidence used by the US Food and Drug Administration (FDA) for device approval. (...)

Conclusion Premarket approval of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias. (...)

F.D.A. to Seek New Standards on Human Test Data
nytimes.com 29.12.2009
The Food and Drug Administration is developing guidelines that will set tougher scientific standards for data from tests on humans that makers of medical devices submit when seeking approval of their products, a top agency official said. (...)

In recent years, the agency has come under criticism from lawmakers, researchers and patient advocates for the standards it uses in approving medical devices. The issue of F.D.A. oversight has also taken on particular significance because of a recent United States Supreme Court decision that has shielded makers of high-risk devices from patient lawsuits if their product was approved by the agency. (...)

Medical Device Studies Lack Scientific Rigor, Researchers Find
businessweek.com 29.12.2009
Dec. 29 (Bloomberg) -- Cardiac pacemakers, stents and other medical devices implanted each year in hundreds of thousands of U.S. heart patients often are approved by government regulators based on insufficient scientific review, researchers said.

About two of three cardiovascular devices approved by the U.S. Food and Drug Administration from 2000 to 2007 were tested in a single clinical trial rather than multiple studies, said scientists at the University of California, San Francisco. Eighty-eight percent of the studies failed to include, as a primary goal, a direct clinical measure of whether patients felt better, their heart function improved or they lived longer, the researchers found.

Senator Charles Grassley, a Republican from Iowa, has criticized the FDA’s device review process as too friendly to the industry. The agency said in a Sept. 24 report that its approval of a knee implant made by Hackensack, New Jersey-based ReGen Biologics Inc. was flawed and needed to be re-examined. The FDA asked the Institute of Medicine, an advisory body, to review the approval procedure used for most medical devices, though not for the majority of cardiovascular devices. (...)

GAO: FDA Needs Deadline to Increase OSE Postmarket Surveillance Authority
fdanews.com 10.12.2009
Despite significant increases in staff and use of external advisory committees to conduct drug safety reviews, the FDA’s Office of New Drugs (OND) and Office of Surveillance and Epidemiology (OSE) remain unable to fulfill their responsibilities for postmarket drug safety reviews, a Government Accountability Office (GAO) report says. (...)

Missing in action: An FDA plan for postmarket drug safety
dailyfinance.com 9.12.2009
"There have been long-standing concerns regarding the Food and Drug Administration's (FDA) oversight of postmarket drug safety." So begins a Government Accountability Office (GOA) report released on Wednesday that examines the steps the FDA has taken since making its own 2006 recommendations on the matter. In the eyes of many, the GAO's finding may be an understatement. (...)

FDA Has Only 2 Inspectors Watching Drug Factories in China
industry.bnet.com 4.12.2009
The FDA has only two inspectors for medical products in China, the country to which much of the drug industry is moving its manufacturing and R&D facilities. The FDA confirmed the number at the request of BNET, following reports that Pfizer (PFE), AstraZeneca (AZN), Eli Lilly (LLY) and Novartis (NVS) were moving a variety of functions to the country. (...)

FDA Criticized for Lax Drug-Safety Monitoring
Psychiatr News 2009;44(23):6 (December 4) (American Psychiatric Association)
FDA officials tell GAO auditors that reviewing and monitoring postmarketing studies are considered low priorities, while a GAO report cites multiple cases that have fallen through the regulatory cracks.

The Food and Drug Administration (FDA) has not provided effective oversight for drugs approved on the basis of indirect measurements of efficacy, according to a recent report by the Government Accountability Office (GAO). (...)

In this report, released in September, the GAO reviewed drugs approved based on indirect endpoints from 1992 to December 2008 and concluded that the FDA has not been diligently tracking postmarketing studies the agency itself had requested. (...)

Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes (Er interessekonflikter uakseptable når legemiddelfirmaer utfører forsøk på sine egne legemidler? Ja)
BMJ 2009;339:b4949 (29 November)
Ben Goldacre argues that the financial interests of drug companies lead to distorted evidence, but Vincent Lawton (doi:10.1136/bmj.b4953) believes that adequate safeguards exist to keep bias in check

The practice of medicine is based on evidence. We need this evidence base to be complete, and of the highest quality, so that we can make the right decisions, but at present, drug companies produce most of the evidence we use. There is no doubt that these companies have a conflict of interest when they conduct trials: they want to sell their products, and so naturally they want a positive result from the trials they sponsor. But there is now good evidence from systematic reviews, meta-analyses, and case studies that this conflict of interest results in bad evidence, which distorts medical decision making and so harms patients. (...)

Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? No (Er interessekonflikter uakseptable når legemiddelfirmaer utfører forsøk på sine egne legemidler? Nei)
BMJ 2009;339:b4953 (29 November)
Ben Goldacre (doi:10.1136/bmj.b4949) argues that the financial interests of drug companies lead to distorted evidence, but Vincent Lawton believes that adequate safeguards exist to keep bias in check

The drug industry is sometimes accused of finding it difficult to reconcile the difference between the strict disciplines of ethical science and its responsibility to its shareholders to return a healthy profit. Proposals to move control of this critical process in drug development into the hands of an "objective" third party need to be critically examined. Clinical trials are properly managed by a rigorous system of regulatory scrutiny throughout. Potential for conflict of interest, when clearly identified and controlled, is not unacceptable. (...)

Improving Access to FDA Reviews and Documents
JAMA. 2009;302(20):2204 (November 25)
To the Editor: The Commentary by Dr O’Connor1 highlighted the importance of using publicly available US Food and Drug Administration (FDA) review documents in conducting independent assessments of the therapeutic value of new drugs. Many trials submitted to the FDA were recently found to be unpublished 5 years after new drug approvals.2 Accordingly, the information that is easily available in the published medical literature is incomplete and potentially biased. (...)

FDA: Flush Certain Unused Medications
JAMA. 2009;302(19):2082 (November 18)
Because of safety concerns, certain prescribed medications no longer needed for treatment, including several opioids and other controlled substances, should be flushed down the sink or toilet, said US Food and Drug Administration (FDA) officials during the launching of a new consumer Web site.

This Web site, http://www.fda.gov/ currently lists 26 medications that consumers should dispose of by flushing. The list will be updated as needed based on future safety risk evaluations of other medications by the FDA. (...)

Drug industry presses FDA to allow more online ads
forbes.com 11.11.2009 (Associated Press)
WASHINGTON -- As federal regulators take their first tentative steps toward policing the wild west of medical information online, pharmaceutical companies are pressing their case to market drugs via Google, Twitter and other Web sites.
The Food and Drug Administration will convene a two-day meeting beginning Thursday to hear the drug industry's position on Internet marketing. The agency has agreed to consider developing rules for online advertising after companies complained that the current guidelines for traditional media - which require a detailed list of possible side effects - have left them hamstrung on the Web. (...)

US FDA slammed over post-marketing studies
pharmatimes.com 28.10.2009
The US Food and Drug Administration (FDA) fast-track approval process for drugs to treat serious and life-threatening conditions requires makers to conduct post-marketing studies on their products, but a new study has found that some such studies have still not been completed more than eight years after the drugs were approved for marketing. (...)

FDA Oversight of Postmarketing Studies Slammed
medpagetoday.com 28.10.2009
The FDA has allowed drug manufacturers to wriggle out of postmarketing study commitments for drugs approved with surrogate endpoints, the Government Accountability Office charged.

In a report released Monday, the GAO accused the drug regulator of failing to routinely review manufacturers' annual submissions or otherwise supervise their postmarketing research.

The FDA "does not consider such oversight a priority," the GAO report said.
It noted that never in the FDA's history has it forced a drug off the market because its sponsor failed to confirm its clinical efficacy. (...)

Bristfällig redovisning av biverkningar i studier
lakemedelsvarlden.se 27.10.2009
Biverkningar rapporteras inte på ett tillfredsställande sätt i kliniska studier. Det visar en färsk genomgång av artiklar i världens mest inflytelserika medicinska tidskrifter. (...)

Franska forskare har granskat samtliga randomiserade, placebokontrollerad och dubbelblinda kliniska studier som jämför två behandlingar och publicerats i någon av världens sex mest inflytelserika vetenskapliga tidskrifter mellan 1 januari 2006 och 1 januari 2007. Resultatet publiceras i veckan nummer av Archives of internal medicine.

Visserligen nämndes biverkningar i närmare nio av tio artiklar. Men rapporteringen är allt annat än tillfredsställande, menar forskarna.
I hälften av artiklarna framgick det inte om patienter avbrutit behandlingen på grund av biverkningar och i tre av tio artiklar saknades information om allvarliga biverkningar. (...)

I en ledarkommentar i samma nummer av tidskriften poängteras att de flesta nya behandlingar endast har en liten, om ens någon, fördel i effekt jämfört med redan befintliga behandlingar. Därför är skillnader i biverkningar självklart en viktig faktor vid valet av behandling.

FAKTA: TIDSKRIFTERNA SOM UNDERSÖKTES:
• New England Journal of Medicine (NEJM)
• Lancet
• JAMA
• BMJ
• Annals of Internal Medicine
• PLoS Medicine (...)

Industry Years Behind on Testing Approved Drugs
nytimes.com 26.10.2009
WASHINGTON — Federal drug officials have long been criticized for failing to force drug makers to complete studies proving that their drugs work as hoped, and Congressional investigators on Monday released yet another report pointing out that some of these studies remain undone many years after being promised.
The result is that doctors and patients remain unsure whether some critical medicines used to treat illnesses like cancer and heart disease are actually beneficial. (...)

FDA lets unproven drugs stay on shelves
northjersey.com 26.10.2009
WASHINGTON — The Food and Drug Administration has allowed drugs for cancer and other diseases to stay on the market even when follow-up studies showed they didn't save lives, say congressional investigators.

And the agency has never pulled a drug off the market due to a lack of required follow-up about its actual benefits — even when such information is more than a decade overdue, according to a report due today from the Government Accountability Office.

When pressed about that policy, agency officials said they have no plans to get more aggressive.

The GAO found that the FDA does little to track whether drugs approved based on preliminary results actually have lived up to their promise. (...)

Experts: Key drug facts often left off FDA labels (Eksperter: Nøkkelfakta for legemiddel ofte utelatt fra FDA-pakningsvedlegg)
seattletimes.nwsource.com 21.10.2009
Did you know that Lunesta will help you fall asleep just 15 minutes faster? Or that a higher dose of the osteoporosis drug Zometa could damage a cancer patient's kidneys and raise their risk of death? (...)

If drug labels sometimes exaggerate benefits and play down drug risks, the authors say there's a very good reason: they are written by drugmakers.

While FDA must approve the final labeling, the actual language is drafted by the manufacturer, with input from FDA scientists.

The labeling is based on results from company studies, which generally compare results for patients taking the drug versus those taking placebo.

If FDA decides the drug's ability to treat or prevent a disease outweighs its side effects, the agency is obligated to approve it. But Schwartz and Woloshin point out that benefits may be slim and potential harms may not be fully understood. (...)

The Big Government-Big Pharma Complex: Disease Mongering for Fear and Profit (Big Government-Big Pharma komplekset: Sykdomssalg for frykt og profitt)
by Karen De Coster
lewrockwell.com 10.10.2009
Ronit Ridberg has given the world a marvelous look into the fraudulent, Big Government-Big Pharma complex with his documentary film, Big Bucks, Big Pharma: Marketing Disease and Pushing Drugs. It's a bit dated, from 2006, but certainly, that is no hindrance to the message of the film. It's an hour long, but worth every minute of your time. Below, I have compiled a list of some interesting points from the film. I have also included a lot of my own thoughts from my research on issues brought up in the film, so not all of the material I have presented is contained within the documentary.

Big Pharma is a monster that’s long been out of control, and that is due to its chief enabler, big government, whose bureaucrats profit immensely from promoting Big Pharma’s agenda to grow and protect its profits. In spite of what Michael Moore would say, this arrangement is not capitalism, or as he means it, the free market. It is state capitalism, or, as some may call it, socialist corporatism. (...)

The U.S. Government Accountability Office (GAO). Drug Safety: FDA Has Begun Efforts to Enhance Postmarket Safety, but Additional Actions Are Needed.
GAO-10-68 (9.11.2009) (The U.S. Government Accountability Office (GAO))
Summary
There have been long-standing concerns regarding the Food and Drug Administration's (FDA) oversight of postmarket drug safety. In 2006, GAO reported that FDA had not clearly defined the roles of two offices involved in making decisions about postmarket safety--the Office of New Drugs (OND) and the Office of Surveillance and Epidemiology (OSE). GAO and others reported additional concerns such as limitations in the data FDA relies on to identify postmarket drug safety issues and the systems it uses to track such issues. At that time, GAO made recommendations, including that FDA improve the independence of its program for resolving scientific disputes related to postmarket drug safety. In 2007, legislation further expanded FDA's postmarket responsibilities. This report examines the steps that FDA is taking to (1) enhance its processes for making decisions about the safety of marketed drugs, (2) improve access to data that help the agency identify drug safety issues, and (3) build its capacity to fulfill its postmarket drug safety workload. GAO reviewed FDA policies and planning documents, and interviewed FDA officials. (...)

FDA spotlights drug safety issues
pharmatimes.com 8.10.2009
The FDA's latest quarterly report from its Adverse Event Reporting System has spotlighted a number of drugs with a potential safety issue or that have had new safety information attributed to them between January and March of this year.

According to the list, the US regulator is looking at incidents of liver failure in patients treated with Pfizer's new kidney cancer drug Sutent (sunitinib), and is also investigating gastrointestinal perforation among users of Wyeth and Progenics' opioid-induced constipation treatment Relistor (methylnaltrexone). (...)

More drug firms doing follow-ups than thought—FDA
reuters.com 3.9.2009
WASHINGTON (Reuters) - More pharmaceutical companies have completed studies required by U.S. health regulators after their products were allowed on the market than previously thought, according to an analysis released on Thursday.

But the study found that FDA database errors had obscured the issue, and critics said the post-approval studies, even when completed, still did not necessarily provide useful long-term information about the safety and effectiveness of the drugs.

Often, the Food and Drug Administration approves drugs and devices for sale on condition that companies keep studying the products for possible additional side effects or other issues. (...)

NEW DRUG APPROVAL
FDA Needs to Enhance Its Oversight of Drugs Approved on the Basis of Surrogate Endpoints
gao.gov (September 2009)
What GAO Found
FDA approved 90 applications for drugs based on surrogate endpoints through its accelerated approval process from the creation of the process in 1992 through November 20, 2008, and about two-thirds of postmarketing studies have been closed. FDA created the accelerated approval process to expedite the approval of drugs which are designed to treat serious or life-threatening illnesses and are expected to provide meaningful therapeutic benefits compared to existing treatments. Under this process, 79 of the 90 applications were approved for drugs to treat cancer, HIV/AIDS, and inhalation anthrax. Because of the need to expedite approval, FDA approves drugs under this process based on surrogate endpoints which are not yet proven substitutes for clinical endpoints, but does require that drug sponsors complete postmarketing studies to confirm the drug’s clinical benefit. FDA had required drug sponsors to conduct 144 postmarketing confirmatory studies associated with these 90 applications, and as of December 19, 2008, classified 64 percent as closed—meaning that drug sponsors had met FDA’s requirements for these studies or FDA determined the studies were no longer needed or feasible. However, several of the remaining studies have been classified by FDA as open for an extended period. (...)

FDA Goes Paperless for Adverse Event Reporting
medpagetoday.com 20.8.2009
WASHINGTON -- The FDA has proposed a mandatory switch to digital postmarket reporting of adverse effects of drug and medical devices to streamline and hasten its investigations.

The agency's plans would not change what is reported but rather how it is reported, leading to a more rapid analysis of potential safety hazards. Currently, most reports are filed on paper and must be entered manually into a database for further analysis.

A switch to digital submission would save money and improve communication with the FDA and other regulators, said Gerald J. Dal Pan, MD, director of the Center for Drug Evaluation and Research's Office of Surveillance and Epidemiology, in a prepared statement. (...)

FDA WILL MOVE FASTER TO BAN BAD ACTORS FROM CLINICAL TRIALS
“The Gray Sheet” 2009;35(33):7 (August 17)
Recent changes will speed FDA’s process for barring non-compliant clinical trial investigators from future product research, agency staffers say. FDA has developed new procedures for disqualification and debarment that set timeframes and assign responsibility for each step of the process to specific areas within the agency. FDA has also centralized the disqualification
process in its Good Clinical Practices Office. (...)

New, but Not Improved? Incorporating Comparative-Effectiveness Information into FDA Labeling
healthcarereform.nejm.org August 12th
New technologies, including prescription drugs and medical devices, are a major driver of increases in U.S. health care expenditures, which have grown by an estimated 71% since 2000.1 The U.S. market for drugs and devices is regulated by the Food and Drug Administration (FDA), which scrutinizes clinical trial data for evidence of safety and efficacy. Although the FDA has been criticized for missteps and inefficiencies in its approval process, these are not the causes of increasing health care expenditures. More relevant is FDA oversight of the labeling and promotion of medical products. (...)

Managing Drug-Risk Information — What to Do with All Those New Numbers
healthcarereform.nejm.org July 27th
(...) Despite the increasing availability of information on medication use and clinical outcomes in tens of millions of patients, the Food and Drug Administration (FDA) has relied primarily on analysis of individual case reports submitted by health care professionals or pharmaceutical manufacturers to assess side effects of approved drugs. Critics, including the Institute of Medicine and the Government Accountability Office, argued that this method was inadequate for systematic postmarketing safety surveillance, and in 2007 Congress passed a law instructing the FDA to develop a system to make use of the terabytes of data on drug exposure and clinical events that the health care system generates. Nearly 2 years later, the FDA requested proposals to build such a “Sentinel” system, to be restricted to private-sector U.S. health insurers and funded at a level somewhere between $7 million and $120 million over 5 years. (...)

The New Sentinel Network — Improving the Evidence of Medical-Product Safety
healthcarereform.nejm.org July 27th
In 2007, Congress directed the Food and Drug Administration (FDA) to create a new postmarketing surveillance system that will, by 2012, be using electronic health data from 100 million people to prospectively monitor the safety of marketed medical products.¹ This new system is intended to complement existing systems of “spontaneous” adverse-event reporting. In May 2008, the FDA announced the Sentinel Initiative, which would “access the capabilities of multiple, existing data systems (i.e., electronic health record systems, medical claims databases).”² The network of data systems is intended both to detect signals (i.e., higher-than-expected rates of adverse outcomes) and to confirm signals, including those suggested by other sources, and to do so rapidly and quantitatively. At a recent Senate hearing before her confirmation, FDA Commissioner Margaret Hamburg stated that close postmarketing monitoring of medical-product safety would remain a high priority during her tenure.³ (...)

FDA device chief resigns following complaints (FDAs utstyrsjef går av etter klager)
businessweek.com 11.8.2009
The head of the Food and Drug Administration's medical device division is stepping down, months after staff scientists alleged they were pressured to approve certain products.

In a letter to agency staffers, Daniel Schultz says he and FDA Commissioner Margaret Hamburg agreed his resignation "would be in the best interest of the center and the agency."

FDA's device division, which Schultz led for five years, has been under scrutiny since earlier this year when nine scientists wrote to the Obama administration transition team complaining they were pressured to approve medical devices against their professional judgment.

Lawmakers are investigating the complaints. (...)

Merck, Schering-Plough in $42M Vytorin settlement
pharmpro.com 6.8.2009
NEW YORK (AP) — Merck and Schering-Plough say they will pay $41.5 million to settle class-action lawsuits filed by patients taking the cholesterol drugs Vytorin and Zetia.

The lawsuits claim that the companies purposefully delayed the release of study results showing the cholesterol treatments were no more effective than older, less expensive medications. The companies do not acknowledge any wrongdoing or liability as part of the settlement.

The settlement deal comes while Whitehouse Station, N.J.-based Merck & Co. is in the process of buying Kenilworth, N.J.-based Schering-Plough Corp. for $41.1 billion. (...)

Merck, Schering-Plough Reach Vytorin Settlement With State AGs
Thompson.com 17.7.2009
Merck & Co., Schering-Plough Corp. and their cholesterol joint venture Merck/Schering-Plough Pharmaceuticals reached a civil settlement with the attorneys general (AGs) of 35 states and the District of Columbia concerning the companies’ promotion of the drugs Vytorin and Zetia and the alleged delay in releasing the results of a related clinical trial.

According to the state enforcement officials, a nearly two-year delay in the release of the full results of the so-called ENHANCE clinical trial violated state consumer protection laws. The trial determined that Vytorin, a cholesterol-lowering drug consisting of a combination of the drugs Zetia and Simvastatin, was no more effective in reducing the formation of plaque in carotid arteries than the cheaper, generically available Simvastatin alone. During the delay in the release of the trial results, the companies heavily promoted Vytorin in direct-to-consumer (DTC) advertisements. (...)

Data About Zetia Risks Was Not Fully Revealed (Data for Ezetrol (Zetia) ble ikke fullstendig offentliggjort)
nytimes.com 21.12.2007
New evidence shows that the drug makers Merck and Schering-Plough have conducted several studies of their popular cholesterol medicine Zetia that raise questions about its risks to the liver, but the companies have never published those results.

Partial results of the studies, alluded to in documents on the Food and Drug Administration’s Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

Most of the millions of people who use Zetia take it along with a statin like Lipitor, Crestor or Zocor. Or they take it in a single pill, Vytorin, that combines Zetia with Zocor. (...)

(Anm: Zetia (ezetimibe); markesføres i Norge under handelsnavnet Ezetrol (Zetia i i USA.)

(Anm: Vytorin (ezetimibe and simvastatin); Vytorin er en kombinasjon av Schering-Ploughs Zetia (ezetimibe; fornorsket ezetimib) og Mercks Zocor (simvastatin).)

Merck, Schering-Plough Reach Vytorin Settlement With State AGs
Thompson.com 17.7.2009
Merck & Co., Schering-Plough Corp. and their cholesterol joint venture Merck/Schering-Plough Pharmaceuticals reached a civil settlement with the attorneys general (AGs) of 35 states and the District of Columbia concerning the companies’ promotion of the drugs Vytorin and Zetia and the alleged delay in releasing the results of a related clinical trial.

According to the state enforcement officials, a nearly two-year delay in the release of the full results of the so-called ENHANCE clinical trial violated state consumer protection laws. The trial determined that Vytorin, a cholesterol-lowering drug consisting of a combination of the drugs Zetia and Simvastatin, was no more effective in reducing the formation of plaque in carotid arteries than the cheaper, generically available Simvastatin alone. During the delay in the release of the trial results, the companies heavily promoted Vytorin in direct-to-consumer (DTC) advertisements. (...)

Data About Zetia Risks Was Not Fully Revealed (Data for Ezetrol (Zetia) ble ikke fullstendig offentliggjort)
nytimes.com 21.12.2007
New evidence shows that the drug makers Merck and Schering-Plough have conducted several studies of their popular cholesterol medicine Zetia that raise questions about its risks to the liver, but the companies have never published those results.

Partial results of the studies, alluded to in documents on the Food and Drug Administration’s Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

Most of the millions of people who use Zetia take it along with a statin like Lipitor, Crestor or Zocor. Or they take it in a single pill, Vytorin, that combines Zetia with Zocor. (...)

(Anm: Zetia (ezetimibe); markesføres i Norge under handelsnavnet Ezetrol (Zetia i i USA.)

(Anm: Vytorin (ezetimibe and simvastatin); Vytorin er en kombinasjon av Schering-Ploughs Zetia (ezetimibe; fornorsket ezetimib) og Mercks Zocor (simvastatin).)

Auditors criticise FDA for failing to track adverse events and workload
BMJ 2009;339:b3031 (24 July)
The US medical regulation and safety body, the Food and Drug Administration, has been criticised by auditors for failing to track its workload, which has rendered it unable to estimate what resources it needs to fulfil its responsibilities.

A report by the US Government Accountability Office says, "The FDA reports that it cannot do all that is asked of it and our analysis of the agency’s activities confirm this." (...)

US clears Eli Lilly's blood thinner Effient
forbes.com 11.7.2009 (Associated Press)
WASHINGTON -- The Food and Drug Administration has approved a highly anticipated blood thinner from Eli Lilly after more than 18 months of review.

The FDA delayed its decision on Effient multiple times as reviewers weighed the drug's benefits versus its risks.

A study of over 13,000 patients conducted by Lilly found that Effient prevents more heart attacks than Plavix, but also causes more internal bleeding.

The FDA says Effient will carry a boxed warning to alert physicians to the risks of potentially fatal bleeding. (...)

The Need for Improved Access to FDA Reviews (Behovet for bedre tilgang til FDA-gjennomganger)
JAMA. 2009;302(2):191-193. (July 8)
The medical literature is expanding rapidly, with thousands of new studies published each year. Increasingly, clinicians and scientists rely on rigorous syntheses of the scientific literature, such as high-quality systematic reviews and meta-analyses, which the Oxford Centre for Evidence-Based Medicine considers the highest level of scientific evidence available.¹ However, systematic reviews and meta-analyses are typically based on the published literature, which is known to be biased,^2-4 creating an important question: can we trust the highest level of evidence available in MEDLINE? (...)

FDA Performance Goals for Approving Drugs and Biologics
JAMA. 2009;302(2):189-191. (July 8)
The omnibus spending bill for fiscal year (FY) 2009 that President Obama signed on March 11 contains a milestone for the US Food and Drug Administration (FDA): it is the first time Congress has appropriated $1 billion for the FDA to regulate human drugs and biologics.¹ The total amount Congress appropriated for the FDA in FY 2009, including user fees from industry, is $2.62 billion, which is an increase of $224.3 million, or 9%, from the amount Congress appropriated for the FDA in FY 2008 (including a special supplemental appropriation of $150 million in June 2008). The proposed budget for FY 2010 that President Obama sent to Congress on May 7 would provide the FDA with an additional $511 million (including user fees) for a total budget of $3.2 billion—an increase of 19% from FY 2009. If enacted, this would be the largest annual budget increase in the FDA's history.² (...)

FDA Tells Drug and Device Makers to Give Balanced Picture of Risks in Ads, Labels
JAMA. 2009;301(24):2541. (June 24)
The US Food and Drug Administration (FDA) is advising the makers of medications and medical devices to avoid misleading consumers with marketing strategies that deemphasize the risks of these products.

Promotional materials that omit or minimize risk information are the most frequent reason the agency issues enforcement letters to companies, and the FDA says it has received requests from industry for clarification about what it considers a violation. In the new guidance (http://www.fda.gov/cder/guidance/7427dft.pdf), the agency emphasizes that simply including risk information is not enough to satisfy its requirements; rather, the agency weighs whether marketing materials leave consumers or clinicians with a balanced impression of a product's risks and benefits. (...)

Groups urge FDA to release info on rejected drugs
reuters.com 24.6.2009
WASHINGTON (Reuters) - The U.S. Food and Drug Administration should make more information available to the public, even on drugs and devices that never make it to the U.S. market, consumer advocates told the health agency on Wednesday.

But industry representatives cautioned that findings or data containing confidential company information could harm competition if made widely available.
While the FDA often provides public details on products that win its approval, doctors and consumers could benefit from similar disclosure on those it rejects, several advocates and former FDA staff reviewers said at a public meeting to discuss ways the agency can make its regulatory decisions clearer. (...)

Enhancing FDA Inspections
JAMA. 2009;301(22):2318. (June 10)
Legislation introduced in the Senate on April 23 would give the US Food and Drug Administration (FDA) more resources to inspect domestic and foreign-made prescription drugs and devices. (...)

The bill also calls for an Institute of Medicine (IOM) study to examine the FDA's system for approving devices. Grassley, in a floor statement, said the IOM report was needed because of recent serious allegations raised by scientists within the FDA regarding the agency's handling of medical device reviews. Grassley added that the bill "is an opportunity for Congress to help the FDA do a better job of ensuring that our increasingly foreign-produced drug and device supply is safe and effective." (...)

F.D.A.’s Secret Files (FDAs hemmelige arkiver)
EDITORIAL
nytimes.com 3.6.2009
The Food and Drug Administration has created a task force to recommend ways to reveal more information about how the agency makes decisions about the safety and efficacy of drugs and medical devices. Any move in the direction of greater transparency is bound to help both patients and their doctors better understand the risks and benefits they face. (...)

FDA to Study Ways to Be More Open With Public
healthfinder.gov 2.6.2009
Agency hopes to better explain its decisions to regain lost trust.

TUESDAY, June 2 (HealthDay News) -- The U.S. Food and Drug Administration, an agency long criticized for not informing the public about its inner workings, announced Tuesday that it has created a task force to study how to be more transparent.

"This is an agency-wide effort to try and figure out how to make FDA and its processes more transparent to the public," FDA Commissioner Dr. Margaret A. Hamburg said during a morning news conference.

The move is part of a larger effort by the Obama administration to make all federal government agencies more open to the public, Hamburg said. In addition, the FDA is reacting to criticisms that have shaken the agency's credibility. In the past, an area of particular concern has been the release of unpublished clinical data on new drugs.

"Over the years, there have been complaints made about FDA's lack of transparency," Hamburg said. "The agency has been referred to as a 'black box' that makes important decisions without explaining them. The agency can and should communicate with the public in a way that provides more clarity about agency activity and processes, not less." (...)

FDA Tries to Decide What Should, Shouldn’t Be Kept Secret (FDA prøver å bestemme seg for hva som bør, og hva som ikke bør hemmeligholdes)
blogs.wsj.com 2.6.2009
FDA er anklaget for å være en "sort boks,” ifølge direktør Margaret Hamburg. (The FDA has been accused of being a “black box,” Commissioner Margaret Hamburg says.)

The FDA is pushing to provide more “transparency” to the public on how and why it makes decisions. For now, though, it’s not shedding a lot of light on what it’s likely to be more open about.

The agency for years has been criticized, as FDA Commissioner Margaret Hamburg put it today, as a “black box that makes important decisions without explaining them.”

For an example of the mystery behind the FDA’s decisions, look back no farther than last week, when the agency went against an advisory panel’s recommendation and didn’t approve a Johnson & Johnson anti-clotting drug. As usual, onlookers had to depend on what the company and analysts said for a guess at why the FDA made that decision.

The FDA said today it’s forming an internal task force that will look at what information to provide to public and what to continue to keep behind a veil. There will be two public meetings, one on June 24 and the second in the fall, with a report due near the end of the year. The agency also hopes to solicit feedback from the public and stakeholders during the process. (...)

Drug Agency May Reveal More Data on Actions
nytimes.com 1.6.2009
WASHINGTON — For years, the Food and Drug Administration has withheld information about drugs and medical devices from the public when their makers cite trade secrecy — even in cases where the agency suspects that the products are causing serious illness or death. (...)

Interactive map of FDA registered pharma facilities
in-pharmatechnologist.com 22.5.2009
in-PharmaTechnologist presents an exclusive interactive map of all the FDA registered facilities of 30 of the pharmaceutical industry’s major players, giving a unique geographical oversight.

The US Food and Drug Administration (FDA) is having to contend with pharma’s global supply chain but the map, which is based on the latest data from the FDA, shows that the major players in-house operations are still centered in North America and Western Europe.

You can zoom in and out using the plus and minus buttons, move around the world by pressing the left mouse button and dragging the screen and discover details of each facility by clicking on individual markers. (...)

U.S. Public Lacks Confidence in FDA: Poll
health.yahoo.com 30.4.2009
- THURSDAY, April 30 (HealthDay News) -- Although the American public feels a little better about the job the U.S. Food and Drug Administration is doing now than a year ago, about half still believes the agency isn't doing enough to safeguard the country's food and drugs, a new Harris Interactive/HealthDay poll finds.

When it comes to monitoring the safety and effectiveness of new prescription drugs, 47 percent of respondents believe the agency does a poor job -- an improvement over the 58 percent disapproval rating noted in a similar poll last year.

As for food safety, 49 percent of Americans have a negative view of the job the FDA is doing, while 48 percent have a positive assessment.

Imported food safety, in particular, appears a focus of concern, with only 6 percent of respondents saying that the FDA's oversight of imported foods is "excellent" and 21 percent saying it is "poor."

Similarly, there's doubt about the FDA's ability to ensure the safety of prescription drugs manufactured abroad. (...)

Does the FDA have the authority to trump the Declaration of Helsinki?
Editorials
BMJ 2009;338:b1559 (21 April)
A new rule seems to be more about imperialism than harmonisation
The Food and Drug Administration (FDA) of the United States has ruled that clinical trials performed outside the US no longer have to conform to the Declaration of Helsinki if used to support applications for registration of products in the US.¹ Instead, the International Conference on Harmonisation Good Clinical Practice (GCP) has been designated as the new regulatory standard. This suggestion met considerable opposition from scientists, ethicists, and consumer groups before and during the consultations.¹²³ (...)

FDA puts restrictions on an institutional review board after secret investigation
BMJ 2009;338:b1618 (20 April)
The US Food and Drug Administration said last week that Coast Institutional Review Board, of Colorado Springs, Colorado, had agreed to stop some aspects of its operations in oversight of clinical trials because of "serious concerns about the company’s ability to protect human subjects participating in clinical trials."

The FDA issued a warning letter to the company (www.fda.gov/cder/warn/2009/Coast_IRB_letter.pdf), and the company subsequently agreed that no new studies subject to certain requirements would be approved, and no new participants would be added to some ongoing studies. (...)

Is the FDA Bipolar?
By Martha Rosenberg (Op-Ed Contributor)
newsblaze.com 16.4.2009
In February the Justice Department charged Forest Laboratories with illegally marketing antidepressants Celexa and Lexapro to younger patients and burying a study that showed suicidal side effects in children. But the next month the FDA approved Lexapro for depression in adolescents 12 to 17. (...)

Can a Bad Drug Get a Fair Hearing at the FDA? Seroquel Hearings Begin
opednews.com 8.4.2009
Many question the FDA's approval last month of Lilly's Zyprexa/Prozac combo, Symbyax for Treatment Resistant Depression. (What do you get when you cross Zyprexa with Prozac? Someone who gains 100 pounds and feels great about it.)

While "TRD" is such a new pharma invention it googles Toyota Racing Development and Teacher Recruitment Days it will soon move script like GAD (general anxiety disorder), MDD (major depressive disorder) ADD (attention deficit disorder) RLS (restless legs syndrome) GERD (gastroesophageal reflux disease) and PMDD (Premenstrual dysphoric disorder)--and for the same reasons.

But equally as appalling is this week's consideration of the antipsychotic drug, Seroquel, for "everyday" depression and anxiety.

London-based AstraZeneca who makes Seroquel has been on a roll lately. (...)

Fattige er prøvekaninar for medisin
nrk.no 22.3.2009
Praksisen byt med menneskerettane, seier president Sven Mollekleiv i Noregs Røde Kors.

Norske ekspertar tordnar mot legemiddelindustrien som utnyttar folk i u-land.

Legemiddelindustrien flyttar testinga av medisinar til land i den tredje verda og til Aust-Europa for å spare pengar. Det er billigare og mindre byråkrati i fattige land enn i Vesten.

- Har alt å tape
Menneske i fattige land blir dermed prøvekaninar for medisinar som skal brukast i rike land, viser ein ny forskingsrapport frå Duke University i North Carolina, USA.

- Menneska forsøka blir utførte på har alt å tape. Dei blir utsette for all risiko og ingen vinning, seier professorar ved Duke University.

Professor Eric Peterson er redd forskinga i fattige land ikkje fylgjer den same etiske standarden som i Vesten. Han meiner norske styresmakter må sørgje for snu utviklinga. (...)

Drug industry advocates join chorus to split FDA
forbes.com 22.3.2009 (Associated Press)
As momentum builds to rework the nation's food-safety system after a salmonella outbreak linked to peanuts, the drug industry is hoping for a happy side effect: faster approvals for new medicines.

Drug industry advocates are quietly allying with some of their longtime critics pushing to split the Food and Drug Administration into two agencies, one for food safety and one for medical products. (...)

Medicinalfirmaer betaler til Lægemiddelstyrelsen
dr.dk 12.3.2009
Samtidig med at Lægemiddelstyrelsen får penge af medicin-producenterne - så skal styrelsen også kontrollere dem.

Men det, mener styrelsen ikke, er noget problem.

Siden 2002 har læger advaret mod kontrastmidlet Omniscan, men først i 2007 frarådede Lægemiddelstyrelsen brugen af stoffet.

Konsekvenserne af styrelsens tøven er alvorlige. Mindst seks nyrepatienter er døde, og yderligere 60 mennesker lever i dag med så alvorlige bivirkninger fra stoffet, at mange af dem ikke kan leve et normalt liv. (...)

Obama Taps New FDA Leaders
forbes.com 14.3.2009
White House seeks to bolster food and drug safety.

WASHINGTON, D.C. - President Obama took a significant step toward revamping the country’s public health regulations Saturday, naming new leadership at the Food and Drug Administration and creating a group charged with recommending changes in food safety laws.

In his weekly video address, Obama tapped Margaret “Peggy” Hamburg, a former New York City health commissioner, to lead the FDA, which has been criticized in recent years for being ineffective, overstretched and too lenient in approving pharmaceutical products. (...)

Political Lobbying Drove FDA Process (Politisk lobbying drev FDA-prosess)
online.wsj.com 6.3.2009
WASHINGTON -- Den nylige godkjennelsen av nytt utstyr for behandling av kneskader fulgte en lobbykampanje, som ifølge dokumenter, seiret over gjentatte avslag fra forskere innen FDA. (The recent approval of a new device to treat knee injuries followed a lobbying campaign that overcame repeated rejections by scientists within the Food and Drug Administration, agency documents show.)

FDAs interne uenighet om Menaflex, som brukes ved de mest vanlige kneskader som rammer alt fra unge idrettsutøvere til eldregenerasjonen, setter press på et statlig tilsynsorgan som har ansvaret for en fjerdedel av den amerikanske økonomien. Det fremgår at enkelte seniorledere hos FDA i dokumenter klaget over håndteringen av Menaflex, produsert av ReGen Biologics Inc., som viser hvordan politisk press fra industrien kan påvirke vitenskapelige konklusjoner. (...) (The FDA's internal dissent over Menaflex, which targets the most-common knee injury afflicting everyone from high-school athletes to baby boomers, is straining a government agency that oversees a quarter of the U.S. economy. Some senior FDA staff members complained in documents that the handling of Menaflex, made by ReGen Biologics Inc., shows how political and industry pressure can influence scientific conclusions.)

Spørsmålet går ikke bare på utstyrets effektivitet -- som fortsatt er omstridt -- men måten FDA gjennomfører egen godkjenningsprosess.(...) (At issue isn't just the efficacy of the device -- that remains in dispute -- but the nature of the FDA's own approval process.)

 

Drug Approval Is No Legal Shield, Justices Rule (Legemiddelgodkjenning er ikke rettslig skjold mot søksmål, ifølge domstolkjennelse)
nytimes.com 4.3.2009
WASHINGTON — In a major setback for business groups that had hoped to build a barrier against injury lawsuits seeking billions of dollars, the Supreme Court on Wednesday said state juries may award damages for harm from unsafe drugs even though their manufacturers had satisfied federal regulators. (...)

FDA Commissioner Lays Out Plans To Ensure Quality
kaisernetwork.org 26.2.2009
Acting FDA Commissioner Frank Torti on Tuesday at a meeting with the agency's Science Board presented a series of plans intended to ensure the quality of science at the organization, Dow Jones reports. According to Dow Jones, Torti's plans in part are based on ongoing efforts to strengthen the agency's staff with more qualified people through a fellowship program and other initiatives. Torti said that while 1,300 regulatory, support and scientific positions have been filled over the past year at the agency, new hiring efforts must continue. He noted FDA also is focused on launching new clinical trial concepts that would help regulators make optimal evaluations on the safety of drugs and other medical products. FDA also hopes to develop new ways of quickly detecting the ingredients that have contributed to contaminated food and pharmaceutical products, according to Torti. (...)

Läkemedelssuccéerna är förbi
va.se 20.2.2009
I en exklusiv intervju för VA:s Jill Bederoff uttrycker läkemedelsmyndighetens chef Janet Woodcock en oro för läkemedelsbolagen och att tiden för verkligt storsäljande preparat är förbi. (...)

Charles Grassley and the FDA
philly.com 8.2.2009
(...) Hearings he held on Merck & Co. Inc.'s Vioxx and its heart problems helped get the drug pulled from the market. Grassley's revelations about prominent psychiatrists who failed to disclose large payments from drug companies have fueled investigations into conflicts of interest.

In late 2007, his staff's research revealed how GlaxoSmithKline P.L.C. allegedly bullied a scientist who identified heart problems associated with its diabetes drug Avandia. A follow-up report may be in the works. The London company, which has major operations in the Philadelphia area, has continued to say Avandia's benefits outweigh its risks.

But anyone expecting a firebrand will find that the stereotype of the stubborn, "aw shucks" Iowa farmer fits 75-year-old Grassley better.

His crusading seems populist, but his opposition to abortion and gun control has won him high marks from conservative groups. He is a teetotal Baptist with a sly sense of humor. (...)

FDA lists drugs under review for safety issues
reuters.com 5.2.2009
WASHINGTON (Reuters) - U.S. health regulators said on Wednesday they were reviewing dozens of products for potential safety problems, including some popular antidepressants, a widely used schizophrenia therapy and a well-known weight-loss drug.

The drug list was released on the U.S. Food and Drug Administration's website as part of the agency's ongoing review of potential drug side effects and complications, and is supposed to be updated every three months. (...)

Big Pharma Won't Police Itself
huffingtonpost.com 27.1.2009
"FDA Criticized on Device Approvals"
"FDA Is Lax on Oversight During Trials, Inquiry Finds"
"In FDA Files, Claims of Rush to Approve Devices"
"Financial Disclosures on Drug Studies Found Lacking"
"Glaxo's Emails on Avandia Reveal Concern"
"FDA rule makes it easier for drugmakers to distribute scientific articles on off-label uses"

The headlines above paint a startling picture of the Food and Drug Administration and pharmaceutical industry.

You know what's even scarier?

Those stories are just from the last two weeks. (...)

FDA “must no longer regard drug trial data as proprietary,” Obama is told
pharmatimes.com 21.1.2009
While the US Food and Drug Administration (FDA) is regarded by many as a failed agency, the Obama Administration has the opportunity to reinvigorate it, but only through efforts to protect it from undue influence and promoting transparency, says a controversial front-runner to be the new FDA Commissioner.

To insulate the agency from political influence, the next commissioner should serve a fixed six-year term, according to Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic in Ohio. He also calls for a re-evaluation of the system by which drugmakers fund a large portion of the agency’s budget through the Prescription Drug User fee Act (PDUFA). (...)

Frank Torti tar över FDA
lakemedelsvarlden.se 20.1.2009
När Andrew von Eschenbach idag lämnar sin tjänst som chef på amerikanska Food and Drug Administration blir det Frank Torti som tar över ledarskapet. Torti kommer att leda myndigheten under en övergångsperiod till dess att senaten valt en ny chef. (...)

Flera namn har figurerat i debatten om vem som kommer att ta över ledarskapet på FDA och Frank Torti är en av dem som nämnts. Genom att nu lyfta fram honom och inte förhandstippade Janet Woodcock, som under många år arbetat på FDA, verkar det troligt att Woodcock nu är borta från Obamas lista.

F.D.A. Criticized on Device Approvals (FDA kritisert for godkjenninger av utstyr)
NYTIMES.COM 15.1.2009
WASHINGTON — Nearly two decades after Congress mandated that all high-tech medical devices be thoroughly reviewed before being approved for sale, the Food and Drug Administration still approves most such devices after minimal testing and perfunctory review. (...)

Citizen's Sidney Wolfe Taking on Larger Role at FDA; Drugmakers Express Concerns
kaisernetwork.org 9.1.2009
The Wall Street Journal on Friday examined how, to "the consternation of the drug industry," the appointment of "[d]rug-safety crusader" Sidney Wolfe to FDA's Drug Safety and Risk Management Committee could give one of the leading critics of the pharmaceutical industry "the ear of several health leaders and members of Congress expected to influence FDA policy in the Obama administration." As head of Public Citizen's Health Research Group, Wolfe has "helped push 16 drugs off the market and slap restrictions on several multibillion-dollar products," according to the Journal. (...)

- Fant fullt av feil i medisindatabase for leger
vg.no 9.1.2009
Allmennlegeforeningen: - Kan være meget alvorlig

(VG Nett) Legemiddelindustrien reagerer overfor Statens Legemiddelverk etter at en søkebase for medisiner viser seg å inneholde en rekke feilaktige opplysninger. (...)

FDA Commissioner Eschenbach to Resign
online.wsj.com 15.12.2008
Food and Drug Administration Commissioner Andrew von Eschenbach has told his staff that he plans to resign effective Jan. 20, 2009.

In an internal message sent Monday to FDA officials, Dr. von Eschenbach said he would work closely with President-elect Barack Obama's transition team "to ensure a seamless change in political leadership at the agency. As with any transition, there will likely be changes for other senior managers as well, although all current Deputy Commissioners and the Chief of Staff are career civil servants who have served me and FDA well." (...)

FDA To Post Public Health Advisories, Consumer Updates, Safety Information on Dedicated WebMD Web Page
kaisernetwork.org 4.12.2008
FDA and WebMD on Wednesday announced an agreement that will allow the agency to post public health advisories, consumer updates and safety information on food, medications and cosmetic products on a dedicated WebMD Web page, CongressDaily reports (CongressDaily, 12/3). Under the agreement, FDA will post the information on a dedicated Web page separate from the main WebMD site that includes no advertisements. The Web page also will feature FDA user polls. In exchange, FDA will publish consumer updates in a bimonthly print magazine produced by WebMD. Neither FDA nor WebMD will receive payments under the agreement, agency spokesperson Scott McFarland said. (...)

Personalized Medicine Will Lead to Changes in FDA Approval Process for New Medications von Eschenbach Says
kaisernetwork.org 10.11.2008
Personalized medicine -- the ability to predict how patients will react to certain medications based on their genetic profiles -- will lead to changes in clinical trials and the business model for the pharmaceutical industry, as well as the FDA approval process for new treatments, agency commissioner Andrew von Eschenbach said on Friday during a speech to business students at St. Joseph's University, the Philadelphia Inquirer reports.

According to von Eschenbach, rather than focus on the positive and negative effects of new medications, trials in the future will seek to determine how medications work in the body and in patients with certain genetic profiles. He added that more cooperation will be needed among pharmaceutical, biotechnology and medical device companies in the future as a result of personalized medicine and that FDA will have to revise the agency approval process. (...)

FDA Advisory Committees: Process for Recruiting Members and Evaluating Potential Conflicts of Interest
gao.gov 30.9.2008
GAO-08-640 September 30, 2008
Highlights Page (PDF) Full Report (PDF, 61 pages) Accessible Text
Summary
The Department of Health and Human Services' (HHS) Food and Drug Administration (FDA) has been criticized about how it recruits individuals to become members of its advisory committees and how it grants some determinations that allow members with conflicts of interest to participate in committee meetings. Advisory committee meetings can include both standing and temporary members. Temporary members only serve for a particular meeting. GAO was asked to examine FDA's advisory committee processes. GAO reported on (1) how FDA recruited individuals for membership and evaluated candidates for potential conflicts of interest, (2) barriers that were reported to recruiting qualified individuals to serve on committees, and (3) the proportion of standing and temporary members, and the frequency with which members with conflict of interest determinations participated in meetings. GAO reviewed FDA advisory committee policies and analyzed meeting records for FDA's Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER), and Center for Devices and Radiological Health (CDRH). GAO also interviewed individuals familiar with FDA's committee member recruiting process. GAO did not examine the effects of changes in FDA's advisory committee processes resulting from the FDA Amendments Act of 2007 and 2007 FDA policy revisions as it was too soon to assess them. (...)

Internal Documents Indicate Two FDA Officials Objected To Rules Aimed at Pre-Empting Lawsuits
kaisernetwork.org 30.10.2008
Two FDA officials objected to rules recently issued by the agency that sought to limit the ability of consumers to file product liability lawsuits against pharmaceutical companies in state courts, according to internal documents released on Wednesday by House Oversight and Government Reform Committee Chair Henry Waxman (D-Calif.), the Wall Street Journal reports (Mundy, Wall Street Journal, 10/30). (...)

According to the documents, two FDA officials in memos said that FDA approval of medication labels are not completely reliable or based on full disclosure of safety risks by pharmaceutical companies. The "internal documents also revealed that the White House played a significant role in drafting the industry-friendly rules" in support of pre-emption, CongressDaily reports (CongressDaily, 10/29). (...)

Congressional Report Lays to Waste Bush Administration’s Pre-emption Claims
citizen.org 29.10.2008 (Public Citizen)
A report issued today by the House Oversight and Government Reform Committee is proof that the Bush administration has pulled out the stops to shield drug companies from liability for dangerous drugs while leaving patients out in the cold. The report, based on documents obtained from the Food and Drug Administration (FDA), concludes that the agency’s efforts to protect drug companies delayed the dissemination of important safety information to the public. The documents reveal that top FDA officials who deal with drug safety on a day-to-day basis do not believe that lawsuits undermine consumer safety, but their views were overridden by political appointees who lacked any empirical support for their views.

It’s bad enough that politics consistently trumps science with this administration. But here we have clear documentation of how the White House hijacked an agency and forced it to undermine its own mission, which is to protect patients. (...)

Change pharmacovigilance reporting rules, govt is told
pharmatimes.com 28.10.2008
The law needs to be changed to make it clearer to drugmakers when they should report new information which might influence the evaluation of a medicine’s risks and benefits to the Medicines and Healthcare products Regulatory Agency, the government has been told. (...)

The consultation was launched to discover if the current law – The Medicines For Human Use (Marketing Authorisations, etc) Regulations 1994 – needed to be changed, following the MHRA’s report earlier this year of its investigation into whether GlaxoSmithKline had failed to inform it in a timely manner about information which it had on the safety of its antidepressant Seroxat (paroxetine) when used in patients aged under 18. (...)

Better Data Management and More Inspections Are Needed to Strengthen FDA’s Foreign Drug Inspection Program
The Government Accountability Office (GAO)
gao.gov 22.9 2008

Drug Safety: Better Data Management and More Inspections Are Needed to Strengthen FDA's Foreign Drug Inspection Program. GAO-08-970, September 22 http://www.gao.gov/cgi-bin/getrpt?GAO-08-970
Highlights - http://www.gao.gov/highlights/d08970high.pdf (...)

Tennessean Editorials, Opinions Discuss FDA Investigation Drug List
kaisernetwork.org 10.10.2008
The Tennessean on Thursday published an editorial and two opinion pieces about an FDA decision to publish online a quarterly list of drugs being investigated for potential safety risks. Summaries appear below. (...)

FDA anställer 1 300
lakemedelsvarlden.se 17.9.2008
Det amerikanska läkemedelsverket, FDA, har på kort tid rekryterat över 1 300 läkare och forskare. Ökningen i personalstyrkan är ett led i att hänga med i den snabba utvecklingen som sker på det farmacevtiska området. (...)

FDA Web Site on Drug Ads Developed by Drug Industry PR Firm (FDA-nettsted for legemiddelreklame utviklet av PR-firma som tilhørerer legemiddelindustrien)
cspinet.org 15.9.2008
Should Pharma PR Pros Write the Government’s Advice to Consumers?
WASHINGTON—Drug ads can be confusing and often deceptive, so it makes sense that the Food and Drug Administration would develop a web site aimed at helping consumers separate fact from fiction. But to develop such a site the FDA turned to a nonprofit front group erected by Shaw Science Partners, a public relations firm that specializes in launching new drugs such as Viagra, Celebrex, Zoloft, Cymbalta and the now-withdrawn Rezulin. (...)

FDA Tapped Pharma Consultant For DTC Web Site
pharmalot.com 15.9.2008
The agency hired a non-profit that is run by Michael Shaw, an advertising consultant to the pharmaceutical industry, to help design a new consumer campaign about direct-to-consumer advertising, Integrity in Science Watch reports. (Here is the press release). (...)

Prescription Drug Advertising Subject of New FDA Web Site for Consumers
reuters.com 5.9.2008
ATLANTA, Sept. 5 /PRNewswire/ -- EthicAd, a nonprofit organization devoted
to improving public health through consumer education, announces the launch of a new FDA Web site created to help the general public better understand
direct-to-consumer (DTC) advertising of prescription medications. The site,
"Be Smart About Prescription Drug Advertising," is hosted by the FDA's Center
for Drug Evaluation and Research and was developed by the FDA in partnership
with EthicAd. For details, visit www.FDA.gov/CDER/ethicad/index.htm or link
to the site via FDA's homepage, www.fda.gov. (...)

FDA Posts Names of Prescription Drugs Being Investigated for Potential Safety Problems
kaisernetwork.org 8.9.2008
FDA officials on Friday said the agency will begin publishing quarterly a list of drugs being investigated for potential safety risks, the Washington Post reports. The list, available on the FDA Web site, names the drug and the nature of the related "adverse event" but does not address the severity or the number of such events reported. Appearing on the list does not mean a drug has been found to be unsafe, according to the Post. The new policy is required under legislation passed last year.

Only drugs submitted to the agency's Adverse Events Reporting System will be included on the list. AERS received 482,154 unsolicited reports of potential drug reactions last year but the "vast majority were false alarms," the Post reports. The agency also investigates drugs based on data from clinical trials and other studies, but such drugs will not appear on the list. (...)

Editorial Addresses NEJM Commentary on Pre-Emption
kaisernetwork.org 25.8.2008
A Las Vegas Sun editorial agrees with the editors of the New England Journal of Medicine "who say that taking away consumers' right to sue would also take away a strong incentive for the FDA and the pharmaceutical industry to be open about a drug's potential for causing harm." According to the editorial, the NEJM editors "state the obvious" that FDA and the pharmaceutical companies "haven't always been completely open or correct in their labeling, even when the risk of lawsuits has been present." The editorial concludes, "Preserving the right of consumers to sue will keep federal agencies and manufacturers more honest -- and the public more protected" (Las Vegas Sun, 8/23). (...)

Sun Editorial:
Protecting the consumer
lasvegassun.com 23.8.2008
Federally approved labels should not serve as legal immunity for manufacturers

Many of the recent criticisms of the Food and Drug Administration have been directed toward one of the agency’s most important responsibilities: determining whether prescription drugs are safe before they are allowed on the market.

It is within this context that a case to be heard by the U.S. Supreme Court in November is attracting attention, including from the editors of the New England Journal of Medicine. (...)

New FDA labeling rule could be lawsuit shield (Nye FDA regler for preparatomtaler kan være skjold mot søksmål)
money.cnn.com 22.8.2008
FDA rule on drug labeling attracts praise from drugmakers, ire from lawyers

NEW YORK (Associated Press) - Government regulators have issued new rules designed to keep drug warning labels clear and concise, though some say the new guidelines would also shield drugmakers from lawsuits.

The regulations from the Food and Drug Administration, which were released Thursday and take effect next month, explain when drug and medical device companies are responsible for rushing out safety updates on their products.

The Pharmaceutical Research and Manufacturers of America welcomed the announcement, saying it provides much-needed clarity. But trial lawyers who represent consumers said it will provide legal protection to companies that withhold information on their products' risks. (...)

Drug regulation terms -- a dictionary
latimes.com 18.8.2008
"Black box" warnings. "Dear Doctor" letters. Confused yet? Read on for an insider's guide to drug regulation lingo.

Professional label:Such alabelfor a prescription drug is not the label consumers see on the vial they bring home from the pharmacy. The professional label comprises many pages of information about the drug and how it should be prescribed and used, its side effects, any warnings the Food and Drug Administration has issued about it and results of clinical studies. (...)

Lawsuits Help Ensure Drug Safety, NEJM Editors Say (Søksmål hjelper til med å sikre legemiddelsikkerhet)
kaisernetwork.org 18.8.2008
FDA by itself cannot guarantee drug safety and state-level lawsuits are "a vital deterrent" to help protect consumers against drugmakers that do not disclose all risks associated with a treatment, editors of the New England Journal of Medicine wrote in a friend-of-the-court brief on Thursday, the AP/Orlando Sentinel reports (Alonso-Zaldivar, AP/Orlando Sentinel, 8/15). The brief is related to an upcoming Supreme Court case involving Wyeth.

In the case, Wyeth v. Levine, Diana Levine, a Vermont musician who lost her arm after receiving the nausea drug Phenergan, claims that the drugmaker did not adequately disclose the drug's risks. A Vermont court ruled in her favor, awarding her $6.8 million. Wyeth has appealed the ruling and argues that because FDA weighed the risks and benefits of the drug and approved it, the company is not liable -- a legal doctrine known as pre-emption. The Supreme Court case will "test this legal doctrine ... for prescription drugs," the Wall Street Journal's "Health Blog" reports (Mundy, "Health Blog," Wall Street Journal, 8/15). (...)

Doctors: Lawsuits help guarantee drug safety (Leger: Søksmål bidrar som garantist for legemiddelsikkerhet)
usatoday.com 15.8.2008
WASHINGTON (AP) — Top doctors who run one of the most influential U.S. medical journals are giving the U.S. Supreme Court some unsolicited legal advice about a major case.

Lawsuits can serve as "a vital deterrent" and protect consumers if drug companies do not disclose risks to the U.S. Food and Drug Administration before it approves medicines for use, the editors of the New England Journal of Medicine said in a friend-of-the-court brief. The FDA "is in no position" to guarantee drug safety, the brief said.

At issue is Wyeth v. Levine, a case expected to be heard late this year that could have far-reaching implications for litigation over allegedly harmful drugs, such as the painkiller Vioxx. (...)

FDA Funding Boost
JAMA 2008;300(6):645 (August 13)
Sen Arlen Specter (R, Pa) said the White House is delaying the swift provision of an additional $275 million to the US Food and Drug Administration (FDA) by requesting that the funds be included in the fiscal year 2009 budget rather than the FDA's current budget. The money is intended to help the agency protect the nation's food supply, ensure safer drugs, and modernize its facilities. (...)

Grassley, Dingell Lead Calls
For Overhauling FDA
online.wsj.com 30.7.2008
WASHINGTON -- Powerful members of Congress want to remake the Food and Drug Administration by giving it broad powers to levy fines, order drug recalls and restrict drug-industry advertising. (...)

Controversies over the popular prescription drugs Chantix, an antismoking pill, and cholesterol treatment Vytorin have added to pressure on the FDA, as critics suggest the agency was too lax in pursuing safety or efficacy concerns. (...)

FDA officials "are too cozy with the companies they regulate," Mr. Grassley said, adding that new leadership must "fix the culture." (...)

Grassley, Dingell Call for Overhaul of FDA, Say Agency Should Be Able To Levy Fines, Order Recalls, Limit Drug Industry Advertising
Kaisernetwork.org 30.7.2008
Sen. Chuck Grassley (R-Iowa) and Rep. John Dingell (D-Mich.) have led an effort to restructure FDA by "giving it broad powers to levy fines, order drug recalls and restrict drug industry advertising," and a "series of crises during the past year ... have given ammunition to the lawmakers, both longtime critics" of the agency, the Wall Street Journal reports. According to the Journal, Congress likely will not "enact major changes to the agency this year because it has only a brief fall session before the November elections," but "2009 may bring the most significant overhaul at the FDA in a generation." (...)

Drug Approval Trends at the FDA and EMEA
globalbusinessinsights.com (Business Insights)
(...) Drug safety has become a major industry concern following the market withdrawal of Merck’s Vioxx in 2004 and several other discontinuations of COX-2 inhibitors. Although adverse reactions were previously considered a relatively minor risk compared to a drug’s wider benefit, both newly approved and established drugs are now under intense scrutiny. Drug approvals in the US and Europe have become subject to approval delays, rising requests for further clinical data, and greater chances of rejection. Regulators are currently attempting to reconfigure review processes in order to minimize delays in recognition of the potential mass benefit of new applications. (...)

From FDA to GSK: The Dangerous Partnership between Government and Big Pharma
huffingtonpost.com 26.7.2008
(...) The press release explains the reason for such a celebration at the pharmaceutical giant: "Dan was formerly Chief Counsel for the US Food and Drug Administration (FDA), where he served as a primary liaison to the White House ... " (...)

FDA chief counsel soon on GSK payroll
fiercepharma.com 23.7.2008
In a move that is likely to make industry watchdogs wag their tales, Daniel Troy, formerly chief counsel at FDA from 2001 to 2004, has just signed on to be a senior vice president and general counsel at GlaxoSmithKline.

Famous (and perhaps infamous) for being a good friend to the industry while at the FDA, Troy has been representing pharmaceutical companies and trade associations in their interactions with the agency. For example, the preemption ball began rolling under his tutelage, when FDA began filing amicus briefs in support of pharma companies and medical device makers to protect them from state-based lawsuits, if the products already had met approval and labeling standards. In the fall, the U.S. Supreme Court will determine if it remains possible for patients to sue either once a product receives FDA approval. Troy also is known for telling subordinates to issue fewer warning layers while at FDA. (...)

GSK definitely has a current need for Troy's services, as the U.K. company faces continuing issues regarding its famous antidepressant Paxil and some questionable marketing practices, including federal and congressional investigations.

Between his tenure at FDA and assuming his new role on September 2, Troy's been a partner at the Washington law firm Sidley Austin LLP. In addition, rumor has it that today, Andrew Witty, the new chief executive of GSK, will spill the beans about his strategic review. (...)

Lawmakers probe FDA approval of Ranbaxy drugs (Lovgivere gransker FDA-godkjenning av Ranbaxy-legemidler)
reuters.com 22.7.2008
WASHINGTON (Reuters) - Two leading U.S. Democrats said on Tuesday they are investigating whether Food and Drug Administration knowingly allowed the sale of Ranbaxy drugs that may have been backed by fraudulent data.

The congressional investigation stems from information released as part of a probe by U.S. law enforcement authorities into whether the Indian drugmaker submitted false data to support generic drug applications and tried to hide manufacturing violations, the lawmakers said. (...)

The motion, which was seeking to enforce subpoenas for documents, stated that the FDA was aware of allegations of fraudulent conduct by Ranbaxy for at least 18 months but did nothing to remove suspect products from the market, the lawmakers said.

"If true, these statements would call into serious question whether the leadership of the agency ... have met even the minimum requirements of due diligence," the lawmakers said.

FDA spokesman Christopher Kelly said the agency had received the lawmakers' letter and would respond directly to them. (...)

The lawmakers, in a letter to the FDA, asked for documents relating to its inspections of Ranbaxy facilities and its suppliers, plus other information. (...)

DA reviewers and inspectors to forge closer links
in-pharmatechnologist.com 21.7.2008
21-Jul-2008 - The US Food and Administration says that a new project examining the interaction between its review and facilities inspection arms will help improve inter-departmental communication, particularly during pre-approval inspections (PAI) (...)

Drug Testing
forbes.com 13.7.2008
The Great Drug Debate

The battle between the drug industry and its critics over exactly how much companies must do to prove medicines are safe played out in microcosm at a two-day Food and Drug Administration meeting this week. (...)

Heart attacks and suicides... yet the dangers were all kept so quiet. So how CAN you trust your medicine?
dailymail.co.uk 7.7.2008
A dose of bad medicine? Critics say drugs watchdogs are failing

Few of us would think to question the safety of our prescription drugs. After all, they’ve been developed to make us better.

But just how safe are they really — and is the official drug watchdog doing enough to protect us?

Last month, for instance, it was revealed that the number of powerful anti-psychotic drugs being prescribed to children had almost doubled in past six years.

Yet despite the growing evidence that these drugs can seriously harm children — causing excessive weight gain, a rise in blood pressure, severe lethargy and even lactation — the Medicines and Healthcare Products Regulatory Agency is powerless to limit their use. (...)

FDA tears up approvable, non-approvable letter system
pharmatimes.com 10.7.2008
The US Food and Drug Administration is changing the way it tells drugmakers whether their marketing applications are likely to get a regulatory thumbs-up.

The agency’s Center for Drug Evaluation and Research says it will no longer issue ‘approvable’ or ‘not approvable’ letters but will inform firms through a ‘complete response’ letter at the end of the review period to let them know of the FDA's decision on an application. (...)

Janet Woodcock, director of the CDER, said the new regulations, which will come into force on August 11, will help the FDA “adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form," She added that these “new processes will make our communications with sponsors of applications more consistent”. (...)

Clash Over Drug Approvals
JAMA 2008;300(2):160
Sen Chuck Grassley (R, Iowa) strongly defended himself from an accusation that his investigation into the Food and Drug Administration (FDA) drug approval process will delay getting effective medicines to market, thereby possibly resulting in thousands of preventable cancer deaths. (...)

The investigation "is an effort to strengthen postmarket surveillance by the FDA, to make the relationship between the FDA and drug makers less cozy . . . ," said Grassley in a statement he released May 30. He also noted that the Wall Street Journal identified Thornton as a former FDA officer but failed to mention Thornton is currently a senior vice president of product development at GenVec, Inc, a company developing cancer therapies. (...)

Glaxo Seeks Guidance
From Health Systems
online.wsj.com 7.7.2008
British pharmaceutical giant GlaxoSmithKline PLC is taking the unusual step of giving government health-care systems a say in deciding which drugs advance in its research pipeline, a move it hopes will result in more products these customers will pay for.

Glaxo's new chief executive, Andrew Witty, said the effort is part of his drive to help the world's second-largest drug maker adapt to a tough pharmaceutical market. In recent years, soaring health-care costs have led insurers, governments and other drug buyers to tighten their belts.

"I'm going to deal with the pharmaceutical realities of the next 10 years, and they're very different from those of the 1990s," Mr. Witty said in an interview at a company townhouse here. (...)

Revised Study Maintains Link Between FDA Approvals Made Soon Before Deadlines, Safety Risks
kaisernetwork.org 3.7.2008
Harvard University professor Daniel Carpenter has made revisions to a study published in March that found prescription drugs hurried through the FDA approval process are more likely to later be linked to safety risks, but he maintains that the study's conclusions are still accurate, the Wall Street Journal reports. In a letter published in the New England Journal of Medicine, Carpenter acknowledges mistakes FDA pointed out in the original study, also published in NEJM, but he says FDA's own records also contain errors. (...)

Why Doctors Should Worry about Preemption
NEJM 2008;359: 1-3 (July 3)
A leading drug company may be poised to win a landmark legal victory next fall. If the drug manufacturer, Wyeth, prevails in a case soon to be argued before the U.S. Supreme Court (Wyeth v. Levine),1 drug companies could effectively be immunized against state-level tort litigation if their products that have been approved by the Food and Drug Administration (FDA) are later found to be defective. (...)

Pharmaceutical Companies Say New Approach by FDA Has Led to Decrease Approvals of New Medications
kaisernetwork.org 30.6.2008
An "intensifying focus on safety and a diminished tolerance for side effects" by FDA have "dramatically lowered" the chances that experimental medications will reach the market and have led to a recent decrease in approvals of new treatments, according to pharmaceutical companies, the Wall Street Journal reports.

Last year, FDA approved 19 new medications -- the fewest in 24 years -- and announced about 75 new or revised "black box" warnings, twice the number announced in 2004, according to a division of Sagient Research Systems. In addition, the number of approvable letters, which in most cases require pharmaceutical companies to submit additional clinical data before FDA will make a decision on whether to approve experimental medications, increased by 40% last year. (...)

Drug Makers Say FDA Safety Focus Is Slowing New -Medicine Pipeline
online.wsj.com (30.6.2008
Nearly four years after Merck & Co. yanked the painkiller Vioxx off the market, beleaguered pharmaceutical-industry executives say they are facing a tough new regulatory climate that is altering the landscape of drug development.

Over the past 16 months, Schering-Plough Corp. Chief Executive Fred Hassan and his top scientists have pulled the plug on two drug-development projects -- one for obesity and the other for cholesterol -- that had the potential to produce big sellers. And they're considering scrapping a third. (...)

As FDA Focuses on Safety, Fewer New Drugs Are Approved
blogs.wsj.com 30.6.2008
Why are new drug approvals tapering off?

For one, there’s the industry’s research labs, which have produced a leaky pipeline of promising products lately. Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, notes that new drug applications submitted to the FDA by the industry dropped 33% in 2006. “You can’t approve drugs you don’t get applications for,” she told the WSJ in this front-page story about the changing drug-approval climate. (...)

Personalised medicine requires regulatory change, former FDA head says
BMJ 2008;336:1461 (28 June)
Regulatory changes are needed in the way that drugs are developed, approved, and paid for so that the potential of genetic and molecular personalised medicine can be realised, a former head of the US Food and Drug Administration said at a forum in Washington, DC, last week.

"The goal is a more solid model of disease progression and a more solid understanding of when treatments are having an impact on particular patients," said Mark McClellan, the commissioner of the FDA from 2002 to 2004 and later head of the Medicare system. Under legislative changes passed last year the FDA is moving towards a targeted development process and more effective post-marketing surveillance. (...)

Lægemiddelstyrelsen finansieres af medicinalindustrien
business.dk 18.6.2008 (Berlingske Tidende)
Både den danske Lægemiddelstyrelse og EUs lægemiddelagentur, EMEA, går medicinalindustriens ærinde. Det betyder ringere og dyrere medicin til befolkningen, lyder kritikken fra udenlandske og danske eksperter.

Medicinalindustrien i Danmark betaler for 80 pct. af Lægemiddelstyrelsens aktiviteter. Ud af styrelsens 2008-budget på godt 350 mio. kr. kommer de 275 mio. kr. fra medicinalindustrien. Samtidig er EUs centrale lægemiddelagentur placeret under EU-Kommissionens industri-direktorat, DG Entreprise.

Denne nærhed til medicinalindustrien er årsag til, at myndighederne er industrivenlige og ofte godkender nye lægemidler, som ikke er undersøgt ordentligt, inden de markedsføres.

Dertil kommer, at langt de fleste nye lægemidler er »me-too«-medicin, som ikke virker bedre end eksisterende produkter samtidig med, at de ofte er mangefold dyrere.

Denne sønderlemmende kritik af Danmarks og EUs centrale sundhedsmyndigheder, som er øverste instans ved godkendelse af ny medicin i Europa, fremføres af flere europæiske forskere, herunder Silvio Garattini fra det anerkendte italienske forskningsinstitut, Mario Negri Instituttet i Milano.

»Medicinalindustrien udvikler ikke nye lægemidler, fordi der er behov for dem, men fordi industrien vil have en bid af markedet. EMEA stiller ikke krav om, at nye lægemidler skal være bedre end eksisterende – formentlig fordi EMEA hører under EUs industridirektorat og ikke under sundhedsdirektoratet,« lyder kritikken fra Silvio Garattini. (...)

The FDA Wants to Stop You from Protecting Yourself Against Drug Companies
Dr. Peter Breggin
huffingtonpost.com 14.6.2008
Without the right to sue pharmaceutical companies, not only will individuals fail to obtain justice, sealed company data about the harmful effects of drug will remain secret. That can become a public health problem when serious adverse reactions are hidden from view. The Wall Street Journal has released data indicating that GlaxoSmithKline (GSK) may have manipulated research in order to hide that its antidepressant Paxil was causing people to attempt suicide. In the weekend edition of June 14-15, 2008, the newspaper described how the drug manipulated its figure to disguise the frequency of Paxil-induced suicide attempts. (...)

To this day, the FDA continues to act as if drug company data can be trusted, including GSK's invalid manipulation of the Paxil suicide studies. The FDA has also ignored data that I discovered in product liability suits against Prozac and Eli Lilly. Eli Before Prozac went on the market, Lilly knew that patients taking their drug had a hugely increased rate of suicide attempts compared to similar or the same patients taking placebo. Even after the British medical journal BMJ released this data, the FDA has continued to ignore it. (...)

Certainly drug companies have done a great deal to improve the health of people around the world. But they also have a bad record for hiding harmful and even lethal side effects of their products. If the Supreme Court supports preemption and hampers or stops product liability suits, it will be a bad day for people who use prescription drugs or prescription devices. That's pretty much all of us. Everybody's health will be put at risk when drug companies can no longer be monitored and scrutinized by product liability litigation. (...)

Congress Presses FDA on Investigations
online.wsj.com
WASHINGTON -- The criminal-investigations wing of the Food and Drug Administration is in hot water with Democrats and Republicans in both the Senate and the House.

The Office of Criminal Investigations, or OCI, has operated largely autonomously in recent years, emphasizing a crackdown on illegal abuse of drugs such as Oxycontin. Its budget doubled to $42.8 million from fiscal 2000 to fiscal 2009, even as FDA officials were conceding that funds for assuring the quality of imported drugs weren't adequate. Monday, the Bush administration announced it would ask Congress for an extra $275 million to beef up FDA inspections. (...)

Ny chef på Läkemedelsverket
dagensmedicin.se 5.6.2008
Christina Rångemark Åkerman blir Läkemedelsverkets nya generaldirektör. Det beslutade regeringen i dag. (...)

Innan dess var hon vice vd och chef för teknologi- och produktutveckling på läkemedelsföretaget Orexo. Hon har även en lång historia på olika befattningar inom Astra Zeneca. (...)

FDA Plans Near-Instantaneous Sentinel for Safety of Drugs and Devices
medpagetoday.com 22.5.2008
WASHINGTON, May 22 -- The FDA revealed plans today to develop a system that will allow nearly real-time monitoring of drug and device safety.

The so-called Sentinel initiative will permit "proactive surveillance of medical products on the market," Mike Leavitt, the secretary of Health and Human Services, said at a press conference.

The initiative is a response to last year's Food and Drug Administration Amendments Act, which called for active post-market surveillance of medical products. (...)

Trials on trial
Editorial
Nature 453, 427-428 (22 May 2008) | doi:10.1038/453427b; Published online
The Food and Drug Administration should rethink its rejection of the Declaration of Helsinki.

Later this year, the US Food and Drug Administration (FDA) will adopt new standards for human clinical trials conducted without its advance sign-off in foreign countries. The rules will govern whether data from such trials can be used in applications to market the drug in question in the United States. Although these new standards specify how to run such trials to meet US requirements, they are worryingly silent on key issues relating to human rights, in contrast with the rules currently in effect. As a result, they could open the way to some ethically fraught decisions. (...)

‘We have to spot side effects earlier,’ GSK chief ("Vi må påvise sideeffekter tidligere," ifølge GSK-sjef)
pharmatimes.com 16.5.2008
Outgoing head of GlaxoSmithKline Jean-Pierre Garnier does not foresee the US Food and Drug Administration softening its stance on medicine approvals, he has told the Financial Times in an interview before he steps down at the company’s annual meeting next week. “This is not a pendulum,” he says, “society wants to avoid risk. We have to tease out rare side effects earlier.” (...)

GSK sees tough US regulation
ft.com 15.5.2008
US regulators have permanently raised the bar for approving new medicines in a way that will force companies to change how they develop drugs, the outgoing head of GlaxoSmithKline has warned.

In an interview with the FT before he steps down at the annual meeting next Wednesday, Jean-Pierre Garnier predicted: “The hurdle rate has gone up. It is not going to come down. This is not a pendulum. Society wants to avoid risk. We have to tease out rare side-effects earlier.” (...)

Confidence in FDA Hits New Low, According to WSJ.com/Harris Interactive Study
pharmpro.com (7.5.2008) (Pharmaceutical Processing)
Majorities of U.S. adults give negative ratings for FDA on a number of measures, such as ensuring new drugs come to market quickly (60% negative) and managing recalls or withdrawals when safety concerns arise (53%). The perception that the FDA does a good job ensuring the safety and efficacy of new prescription drugs (35% positive) has declined from 45 percent in 2007 and 56 percent in 2004, even though the general population considers this to be the most important task for the FDA to focus on (61%).

Further, only 26 percent think the FDA does a good job ensuring the safety of prescription drugs that are manufactured outside the U.S. This is no surprise, particularly coming on the heels of the recent Heparin contamination incident, which stemmed from materials made in China. (...)

The FDA, Preemption, and the Supreme Court
NEJM 2008;358:1883-1885 (May 1)
Everyone would like to be immune from lawsuits. Legislatures sometimes provide immunity in order to advance important social policy goals. For example, by providing health care professionals with immunity under Good Samaritan statutes, legislatures hope to encourage voluntary medical assistance in emergencies. Similarly, Congress provided immunity to vaccine manufacturers who claimed they could not economically manufacture vaccines with the threat of liability hanging over them. (...)

The preemption doctrine plays a constructive role in the allocation of regulatory authority over national industries. But its purpose has never been to grant broad legal immunity to private industry. The solution lies not in the courts but in Congress, which is the ultimate creator of preemption. (...)

Drug Safety Agency to Hire More Than 1,300 People (Update2) (Legemiddelkontroll leier inn mer enn 1 300 personer)
bloomberg.com 30.4.2008
April 30 (Bloomberg) -- The U.S. Food and Drug Administration said it will fill more than 1,300 positions by the end of September, triple the number hired by the agency during the past two years.

The agency will add 600 new jobs, including chemists, biologists, and statisticians. It will also fill more than 700 posts that are open, the FDA said today in a statement on its Web site. About 500 of the positions will be funded by user fees that are paid to the agency by drugmakers filing applications to market new products, said FDA spokesman Christopher Kelly. (...)

Pharma "must take more responsibility for quality:" FDA
pharmatimes.com 27.4.2008
The US Food and Drug Administration will never have sufficient resources to be “the quality-control unit of the world,” and drugmakers will have to assume more responsibility for the quality of their products, a senior agency official has told US legislators.

The FDA is not the industry’s quality system, and the agency is holding companies accountable, Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, warned after addressing a hearing convened on April 24 by Democratic Senator Edward Kennedy, chairman of the Senate Education, Labor, Health and Pensions (HELP) Committee to discuss the contaminated heparin supply. “Any legislative fixes that do not address quality by design will fail,” she added. (...)

NEJM Perspectives Look at Problems Faced by FDA
kaisernetwork.org 24.4.2008
"Trying Times at the FDA -- The Challenge of Ensuring the Safety of Imported Pharmaceuticals," New England Journal of Medicine: In the NEJM perspective, Stuart Schweitzer of the University of California-Los Angeles School of Public Health discusses challenges FDA has faced in recent years in ensuring the safety of the country's medical devices and drugs, particularly its inability to effectively inspect foreign manufacturing plants. Schweitzer also examines possible ways to improve FDA inspections, including boosting the agency's efficiency through increased federal funding and reconsidering its responsibilities (Schweitzer, NEJM, 4/24). (...)

Trying Times at the FDA — The Challenge of Ensuring the Safety of Imported Pharmaceuticals
NEJM 200;358:1773-1777 (April 24)
In recent years, the Food and Drug Administration (FDA) has faced three serious challenges to its ability to ensure the safety of the country's medical devices and drugs. (...)

Playing "Kick the FDA" — Risk-free to Players but Hazardous to Public Health
NEJM 2008;358:1774-1775 (April 24)
The Food and Drug Administration (FDA) is responsible for regulating $1 trillion worth of consumer products, or 25% of the U.S. consumer economy — the food we eat, the cosmetics we use, the medical devices implanted in our bodies or used in our care, and the drugs we take. (...)

Public opinion polls show that confidence in the FDA fell from 80% in the 1970s to 36% in 2006¹— ratings usually reserved for tobacco companies and used-car dealers. (...)

Watchdog critical of FDA foreign drug oversight
reuters.com 21.4.2008
WASHINGTON (Reuters) - U.S. authorities increased inspections of foreign drug plants last year but still checked only a fraction of sites that supply medicine ingredients to the U.S. market, a government watchdog is set to tell Congress on Tuesday.

Concern about Food and Drug Administration oversight of foreign drug manufacturers has risen since the finding of a contaminant in some batches of blood-thinner heparin that were made with raw ingredients from China. (...)

(Anm: Preliminary Findings Suggest Recent FDA Initiatives Have Potential, but Do Not Fully Address Weaknesses in Its Foreign Drug Inspection Program (GAO (United States Government Accountability Office (April 22, 2008).)

Draft Legislation Aimed at Overhauling FDA Would Require More Inspections, Change User Fees
kaisernetwork.org 18.4.2008
(...) Medications, Medical Devices, Cosmetics
Under the legislation, the HHS secretary would determine the amount of the registration fee for pharmaceutical companies (CQ Today, 4/17). The amount of the registration fee for medical device companies remains undetermined (CongressDaily, 4/18). Under the bill, FDA would inspect all facilities that manufacture medications every two years (Schmit, USA Today, 4/18). Pharmaceutical companies would have to list the country of origin of active ingredients of their medications on labels. Medical device companies also would have to list the country of origin of their products on labels (AP/San Jose Mercury News, 4/17). (...)

Data Safety Monitoring Committees Often Caught in a Squeeze
medpagetoday.com 10.4.2008
BETHESDA, Md., April 10 -- With problematic clinical trials becoming the more the rule than the exception, the role of data safety monitoring committees is taking center stage for investigators and regulators alike, researchers here said. (...)

A key problem is when to share blinded data with investigators and sponsors if trends show signs of threatening the safety of patients and the integrity of the study, they wrote in a commentary in the April 9 issue of the Journal of the American Medical Association.

In the best of all worlds, the committee never has to act. But sometimes -- on the basis of data not known to investigators or sponsors -- monitoring committees stop trials or call for changes to the way they're being run.
The problem, Dr. Borer said in an interview, is that principles and guidelines governing those actions are "in a state of flux."

Indeed, "people keep having to re-invent the wheel" as they decide what rules a data committee should follow, noted Dr. Gordon on an interview.

He said the JAMA commentary wasn't tied to any specific cases, but is "generally timely because data safety monitoring committees are widely used in clinical trials." (...)

(Anm: When Should Data and Safety Monitoring Committees Share Interim Results in Cardiovascular Trials? JAMA 2008;299(14):1710-1712.)

Suicide Warning Suits Pre-Empted; Makers of Paxil, Zoloft Win
law.com 10.4.2008
In a significant victory for drug manufacturers, the 3rd U.S. Circuit Court of Appeals has ruled that the makers of Paxil and Zoloft cannot be sued for failing to warn of a risk of suicide because the Food & Drug Administration has explicitly refused to order such warnings.

Voting 2-1 in a pair of cases where the lower courts issued conflicting rulings, the 3rd Circuit found that such lawsuits must be pre-empted because they directly conflict with action already taken by the FDA. (...)

Appeals Court Backs Drugmakers in Antidepressant Suicides
blogs.wsj.com/health 9.4.2008
A federal appeals court yesterday sided with drugmakers in a case brought by the families of two people who committed suicide while taking antidepressants. The ruling is important because it turns on the concept of preemption, likely to be the most important legal topic in the drug world this year.

In this case, the families sued the drugmakers under state law, arguing that the warning labels on the drugs weren’t strong enough. (...)

FDA told: “TV drug ads must include side effects info”
pharmatimes.com 7.4.2008
US legislators have asked the Food and Drug Administration to require all television advertisements for prescription drugs to include information on how consumers can report any serious side effects with the advertised drug to the agency, including a toll-free phone number.

The FDA is currently “failing to serve its most vital supervisory responsibility” by not providing this information, said the legislators, Democratic Representatives Rosa DeLauro and Jan Schakowsky, who have both sponsored legislation aimed at placing curbs on direct-to-consumer advertising.

They also point out that a recent survey by Consumers Union (CU) found that only 35% of the public were aware that they could report serious drug side effects to the FDA, while just 7% of respondents named the agency as somewhere to which they could report such a problem. (...)

Drug Makers Near Old Goal: A Legal Shield (Legemiddeprodusenter nær gammelt mål: Et rettslig skjold)
nytimes.com 6.4.2008
(...) The Bush administration has argued strongly in favor of the doctrine, which holds that the F.D.A. is the only agency with enough expertise to regulate drug makers and that its decisions should not be second-guessed by courts. The Supreme Court is to rule on a case next term that could make pre-emption a legal standard for drug cases. The court already ruled in February that many suits against the makers of medical devices like pacemakers are pre-empted. (...)

US and Chinese pharmacopoeias expand working relationship
in-pharmatechnologist.com 3.4.2008
03-Apr-2008 - The pharmacopoeias of the US and China will work more closely together in future in a bid to improve the quality of medicines available in both countries.

To that end, the US Pharmacopoeial Convention and the Chinese Pharmacopoeia Commission have signed a memorandum of understanding (MoU), to tighten up the physical and documentary standards applied to pharmaceutical ingredients and establish processes to update existing monographs in both countries. (...)

Medications Approved by FDA Under Deadlines Set by Congress More Likely To Have Safety Problems Later, NEJM Study Finds
kaisernetwork.org 27.3.2008
Prescription drugs that receive FDA approval shortly before the deadline for deciding on new drug applications are more likely to have safety issues than those that are given additional time and scrutiny, according to a study published Thursday in the New England Journal of Medicine, the Wall Street Journal reports.

Currently, FDA promises to reach a decision on 90% of new drugs within 10 months after an application is submitted, and within six months for so-called priority drugs. (...)

According to the study -- led by Daniel Carpenter, a professor of government at Harvard University -- of the 313 drugs FDA approved between 1993 and 2004, 97 were approved within two months of the deadline. Those 97 drugs had a 14% rate of severe safety problems, compared with 3% of the other 216 drugs. (...)

Steven Nissen of the Cleveland Clinic called the analysis a "wake-up call," saying, "It puts the FDA in a very difficult situation when they're trying to make complex decisions under these very, very tight deadlines." He added, "We've got to re-evaluate now whether that's good public policy" (Neergaard, AP/Philadelphia Inquirer, 3/27). (...)

(Anm: Drug-Review Deadlines and Safety Problems. NEJM;2008;358:1354-1361 (March 27).)

Observational evidence for determining drug safety
Editorials
BMJ 2008;336:627-628 (22 March)
Is no substitute for evidence from randomised controlled trials
Drug regulators are constantly criticised for their handling of drug safety. Comment on the activities of the US Food and Drug Administration with regard to drug safety has become particularly loud and damning. A recent article that proposed sweeping changes to the system criticised the FDA for lacking relevant expertise, being too close to the drug industry, and failing to ensure that companies deliver on their safety commitments with new drugs.¹ The main practical recommendation was that systems of monitoring and reporting adverse events should be enhanced, highlighting a perceived role for observational studies. Drug safety is also an important concern in Europe, and the European Commission Enterprise and Industry Directorate General is consulting with stakeholders on changes of legislation to strengthen and rationalise pharmacovigilance in Europe.² It describes a strategy that also focuses on observational studies of drug safety. But can observational studies alone improve judgments on drug safety? (...)

FDA expanderar till Kina
lakemedelsvarlden.se 18.3.2008
Amerikanska läkemedelsverket, FDA, ska skicka åtta heltidsanställda inspektörer till amerikanska ambassaden i Kina. Det är det första steget i FDA:s plan för att expandera sin verksamhet utanför USA:s gränser. (...)

Expansionen till Kina är ett första steget i det så kallade ”Beyond our borders initiative”, som innebär att FDA de kommande åren ska stärka samarbetet med andra läkemedelsmyndigheter runt om i världen. (...)

Daniel Troy's Poison Pill
motherjones.com 16.3.2008
WASHINGTON DISPATCH: How a former Bush appointee has the high court poised to wipe out consumer suits over dangerous medical products—and possibly much more.

When it comes to notorious Bush political appointees, Daniel Troy's name doesn't usually make the top-10 list, overshadowed as he is by more high profile cronies such as FEMA's Michael Brown. But for three years in the president's first term, Troy served as the chief counsel to the Food and Drug Administration (FDA), where he quietly advanced a legal revolution that is playing out in earnest in the U.S. Supreme Court this year. This revolution has the potential to affect the health and safety of the nation's citizens for years to come, all while making Troy a rich man. In fact, his career is an illustration of how the Bush administration's revolving door has allowed industry lawyers to radically reshape regulatory agencies to benefit the big businesses they once represented and then profit from those changes when they return to the private sector. (...)

Under Troy's leadership, the FDA started showing up in state courts, offering briefs in civil cases on the side of drug companies being sued by people who'd been injured by dangerous prescription drugs and other medical devices. In an unprecedented move, agency lawyers argued that because those products had been approved by the FDA, such lawsuits were "preempted" by federal law and should be dismissed. (...)

Congress asks for investigation of FDA resources and staffing (Kongressen ber om granskning av FDA-ressurser og bemanning)
BMJ 2008;336:525 (8 March)
Congressional committees have made two requests for investigations to determine whether the US Food and Drug Administration (FDA) has the resources and staff to do its job of protecting the US public. (...)

Congress Daily reported that the accountability office will undertake the investigation. Marcia Crosse, the office’s healthcare director, said that the investigation would involve several teams, but she did not give a time schedule (www.CongressDaily.com, 26 Feb, "Probe of FDA gets support from key lawmakers"). (...)

FDA's Review Process Under Investigation (FDAs evalueringsprosess granskes)
forbes.com 4.3.2008
WASHINGTON - The government's watchdog agency is investigating whether the Food and Drug Administration's drug-review process cleared two blockbuster medications without sufficient proof of their safety or effectiveness.

Sen. Charles Grassley said Tuesday the Government Accountability Office has agreed to study a much-debated method for approving drugs used to clear GlaxoSmithKline PLC's diabetes pill Avandia and Merck & Co. Inc. and Schering-Plough's cholesterol drug Vytorin.(...)

Patients' ability to sue at risk
latimes.com 3.3.2008
Justices could shield FDA-backed drugs from suits, as they did for devices. Critics say the agency is fallible.

Years of high-profile court battles over drugs such as Vioxx and Celebrex, along with billion-dollar settlements and jury verdicts, could soon be a thing of the past.

The U.S. Supreme Court, in an 8-1 decision, ruled last month that patients injured by most medical devices can't sue their manufacturers. And this fall, a similar case could extend the same legal protection to the much larger pharmaceutical industry -- a frequent target of lawsuits. (...)

Los Angeles Times Examines Product Liability Lawsuits, Potential for Court To Shield Drug Makers
kaisernetwork.org 3.3.2008
The Los Angeles Times on Monday examined how "high-profile court battles," like those over drugs such as Vioxx and Celebrex, "could soon be a thing of the past" after the U.S. Supreme Court last month ruled that patients injured by most medical devices cannot sue manufacturers. According to the Times, a similar case that will be heard this year could extend the same legal protection to the pharmaceutical industry. In the medical device lawsuit against Medtronic, the Supreme Court ruled that FDA adequately regulates the drug and device industries and that the agency's authority should not be questioned by the courts. In October, the Supreme Court will hear arguments in a lawsuit against Wyeth, "in which it might decide whether FDA approval bars personal-injury lawsuits involving drug companies," the Times reports.

Opponents of the decision in the medical device case "say such an argument would make more practical sense if the FDA were doing a better job," the Times reports. According to the Times, FDA "faces growing challenges and some of its most withering criticism in years, some from within its own walls," as several recent reports have raised serious questions about the agency's performance.

Proponents of the decision "say it is overdue," according to the Times. The drug and medical device industries have "contended for years that the legal environment around their products has grown too restrictive and is stymieing innovation," the Times reports.

However, some legal experts say that without such lawsuits, regulators and the public might never hear of evidence that manufacturers knowingly marketed products they knew were unsafe, according to the Times. David Vladek, a law professor at Georgetown University, asked, "Without the tort system, what reasonable assurance do we have we will learn about the bad actors?" He added, "A lot is lost without these lawsuits" (Costello, Los Angeles Times, 3/3). (...)

FDA Needs More Inspectors, Updated Databases, According to FDA Official (FDA trenger flere inspektører, oppdaterte databaser, ifølgeFDA-leder)
kaisernetwork.org 28.2.2008
FDA needs to hire more inspectors and update its database that tracks approved prescription drugs, Janet Woodcock, the agency's deputy commissioner for scientific affairs and chief medical officer, said on Wednesday, CongressDaily reports. Woodcock testified at House Appropriations Subcommittee on Agriculture, Rural Development, FDA and Related Agencies hearing (Edney, CongressDaily, 2/27). (...)

What the drug giants WON'T tell you (Hva legemiddelgigantene IKKE VIL fortelle deg)
dailymail.co.uk 27.2.2008
(...) Richard Ley, of the Association of the British Pharmaceutical Industry, says all its member companies now make the results of their clinical trials that have been conducted in the UK available to the public on the ABPI website or their own.

Indeed, this week's study looked at data collated before the registers were set up.

But transparency is only one issue.
Another question that arose at the time of the Spitzer case was how the industry was able to keep drugs on the market once their safety had been challenged. (...)

It was revealed in one U.S. Congressional hearing that the industry spends more than $5.5 billion to promote drugs to doctors — which was more than all U.S. medical schools combined spend to educate doctors. (...)

FDA plans new post-approval drug safety effort
reuters.com 26.2.2008
The plan, called "Safety First," includes creation of a new database of possible side effects from medicines, plus clear schedules for following up on concerns about them.

The effort was first reported by the Wall Street Journal. FDA spokesman Christopher DiFrancesco confirmed the information in the Journal's story. (...)

FDA chief is urged to resign (FDA-sjef bedt om å fratre)
latimes.co 15.2.2008
Problems with 2 drugs reveal trouble at the top, a Democrat says.

WASHINGTON -- -- A key House Democrat said Thursday that the head of the Food and Drug Administration should resign in light of a probe over an antibiotic and news of a blood thinner linked to allergic reactions and four deaths.

Rep. Bart Stupak (D-Mich.), who heads an investigative panel overseeing the agency, said FDA Commissioner Andrew C. von Eschenbach should step down because "it's just a total lack of leadership." (...)

Rep. Stupak Calls for FDA Commissioner To Resign Amid Recent Prescription Drug Safety Issues
kaisernetwork.org 15.2.2008
House Energy and Commerce Oversight and Investigations Subcommittee Chair Bart Stupak (D-Mich.) on Thursday called on FDA Commissioner Andrew von Eschenbach to resign, saying that he had lost confidence in officials over the handling of investigations and oversight by the agency, the AP/Los Angeles Times reports (Thomas, AP/Los Angeles Times, 2/15). Stupak said his call for von Eschenbach to resign was spurred in part by the recall of the blood thinner heparin, manufactured by Baxter International, which has been linked to 350 reports of adverse events since the end of last year. According to Stupak, Baxter announced the recall on Jan. 25, 2007, but FDA did not send out its own notice until Monday (Edney, CongressDaily, 2/15). (...)

FDA “failures allowing criminals into drug approval process” (FDA "svikt gir kriminelle adgang til godkjenningsprosess")
pharmatimes.com 15.2.2008
Failure to act by the US Food and Drug Administration has increased the risk that criminals are operating in, and undermining, the drug regulatory process, Congress has been warned.

The agency has neither the will nor the authority to debar companies or individuals convicted of crimes such as bribery, fraud, perjury, blackmail or extortion, according to a report prepared for Representative Joe Barton, ranking (Republican) member of the House Committee on Energy and Commerce. (...)

22,000 died amid delayed Bayer drug recall: doctor (Lege: 22 000 døde under forsinket tilbaktrekking)
reuters.com 15.2.2008
NEW YORK (Reuters) - The lives of 22,000 patients could have been saved if U.S. regulators had been quicker to remove a Bayer AG drug used to stem bleeding during open heart surgery, according to a medical researcher interviewed by CBS Television's 60 Minutes program.

The drug Trasylol was withdrawn in November at the request of the FDA after an observational study linked the medicine to kidney failure requiring dialysis and increased death of those patients. (...)

Bush Administration Fails To Comply With Subpoena for Documents on Testimony About FDA Approval of Ketek
kaisernetwork.org 13.2.2008
Members of the House Energy and Commerce Oversight and Investigations Subcommittee on Wednesday said that the Bush administration has failed to comply with a subpoena for documents used to prepare testimony from FDA Commissioner Andrew von Eschenbach about the antibiotic Ketek, manufactured by Sanofi-Aventis, Bloomberg/Philadelphia Inquirer reports (Blum, Bloomberg/Philadelphia Inquirer, 2/13). In response, leaders of the Energy and Commerce Committee might hold HHS Secretary Mike Leavitt in contempt (Edney, CongressDaily, 2/12).

During a hearing held by the subcommittee in March 2007, von Eschenbach testified about issues related to FDA approval of Ketek, which reports have linked with a number of serious side effects (Bloomberg/Philadelphia Inquirer, 2/13). The committee "has tried to pry the briefing book from FDA since shortly after the hearing, in which von Eschenbach was accused of misleading lawmakers on more than a dozen points concerning the agency's approval" of Ketek, CongressDaily reports. The committee issued a subpoena for the documents earlier this month (CongressDaily, 2/12). (...)

FDA Has Not Appropriately Debarred Individuals, Pharmaceutical Companies Convicted of Crimes, Report Finds (FDA har ikke i tilstrekkelig grad utestengt mennesker og farmasøytiske firmaer dømt for kriminalitet, ifølge rapport)
kaisernetwork.org 12.2.2008
FDA has not appropriately debarred a number of individuals and pharmaceutical companies convicted of crimes from participation in the agency approval process for medications, according to a report presented on Monday by House Energy and Commerce Committee Republicans, Bloomberg/New York Times reports (Bloomberg/New York Times, 2/12). FDA for the past 15 years has had the authority to issue mandatory or permissive debarments, based on the severity of the crimes involved.

The report, drafted by Republican committee staff members, lists 40 individuals convicted of crimes between fiscal years 2003 and 2005 who they maintain FDA should have debarred. According to the report, FDA has debarred a total of 71 individuals but has taken such action against only 13 individuals in the past five years. FDA has never debarred a generic pharmaceutical company and does not have the authority to take such action against brand-name pharmaceutical or medical device companies, according to the report.

The report said, "It is doubtful that this is simply a matter of resources," as "other agencies have been able to start and complete debarments promptly." The report attributed the problem in part to the five-year period that FDA has to issue debarments after convictions. The report indicated that the five-year period might "give the agency an incentive to be lax," according to CongressDaily.

Committee ranking member Joe Barton (R-Texas) said, "This staff report shows in great detail the record of weaknesses in FDA's ability and authority to carry out its duties and to protect its own integrity." Barton has asked his staff to begin to draft legislation to address the problem, an aide said. In the event that FDA does not take action to address the problem, Barton said that he will seek to reduce the agency budget (Edney, CongressDaily, 2/12). (...)

FDA is failing to inspect drug and device makers, government reports say (FDA svikter i sin kontroll av legemiddel- og utstyrsprodusenter, ifølge statlig rapport)
BMJ 2008;336:297 (9 February)
The US Food and Drug Administration has not met its legal requirements to inspect US and foreign medical drug and device manufacturers, and it has not provided effective oversight of domestic and imported food, according to two reports by the General Accountability Office, the independent investigative arm of Congress.

The reports, both released on 29 January, said that the FDA’s science base, scientific workforce, and information technology infrastructure were weak and inadequate.

In November the FDA’s subcommittee on science and technology found "substantial weaknesses across the agency." (...)

Vanlige legemidler gir selvmordstanker
aftenposten.no 8.2.2008
Legemidler mot epilepsi og bipolare lildelser kan øke risikoen for selvmord. Nå advarer Det amerikanske legemiddelverket mot vanlige medisiner. (...)

En ny studie viser at elleve vanlige medisiner mot epilepsi og bipolare lidelser kan øke risikoen for selvmord og selvmordstanker. (...)

Håper norske leger vet
Morten Ingvar Lossius er overlege ved Statens senter for epilepsi ved Rikshospitalet. Han kjenner til at antiepileptikum kan medføre depresjon og andre psykiske bivirkninger.

- Denne undersøkelsen tilfører likevel nyttig og viktig tilleggsinformasjon. Selv om depresjon står oppført som mulig bivirkning på flere av disse preparatene, burde selvmordstanker og selvmordsforsøk også være nevnt. Vi får bare håpe at alle leger som skriver ut disse preparatene er bevist dette, sier Lossius. (...)

Manglende opdatering af bivirkninger kan koste liv
netdoktor.com 4.2.2008
En lang række lægemidler er forsynet med forældede oplysninger om deres bivirkninger. I 1990erne eksisterede en anden praksis for angivelse af bivirkninger, og det har betydet, at nogle sjældne, men potentielt dødelige bivirkninger ikke er blevet oplyst.

”Systemet har i alt for mange år bygget på et gammeldags, arrogant forhold til patienterne, hvor det er systemet, industrien og lægerne, som foretog beslutningen på patientens vegne. Det er helt utidssvarende,” siger dr. med. Christian Gluud fra Copenhagen Trial Unit.

Ifølge Christian Gluud ønsker patienterne i dag selv at sætte sig ind i medicinen og herefter tage stilling. Men det kan blive svært, da de såkaldte produktresumeer og indlægsssedler, som er en brugsanvisning på lægemidlet til henholdsvis lægen og patienten, først vil være ført ajour ved udgangen af i år. (...)

Patientklagenævnet behandler i øjeblikket en sag, hvor en 15-årig pige døde af bivirkningerne af medicinen Solu-Medrol, fremstillet af medicinalfirmaet Pfizer.

Både Pfizer og Lægemiddelstyrelsen kendte til bivirkningerne, men havde ikke oplyst lægerne eller patienterne om dem. (...)

Experts, Lawmakers Call for Increased FDA Funding To Address Agency Problems
kaisernetwork.org 30.1.2008
FDA lacks adequate funds and organization to meet an increased number of responsibilities and ensure public health, witnesses and lawmakers said on Tuesday at a hearing of the House Energy and Commerce Oversight and Investigations Subcommittee, CQ HealthBeat reports. During the hearing, lawmakers heard testimony from members of the FDA Science Board, which recently released a report that found "lives are at risk" because of problems at the agency. (...)

Budget boost suggested to help fix FDA troubles
chron.com 29.1.2008
Report criticizes low morale and quality of science

WASHINGTON — If Congress offered the head of the Food and Drug Administration billions more to upgrade his embattled agency, he should be ecstatic, right?

But that wasn't quite the way FDA Commissioner Andrew C. von Eschenbach sounded Tuesday at an unusual hearing before the House Subcommittee on Oversight and Investigations. (...)

F.D.A. Plans to Post Inspectors Overseas
nytimes.com 25.1.2008
WASHINGTON — The Food and Drug Administration intends to post inspectors to embassies and consulates throughout the developing world in hopes of improving the quality of the food and medicines increasingly flowing to the United States, a top official said Thursday.

The agency’s commissioner, Dr. Andrew C. von Eschenbach, said that he wanted to have “boots on the ground” in nations like India and China and regions like Central and South America and the Middle East. (...)

(Anm: Legemiddelstudier, åpenhet, uredelighet og kvalitet (mintankesmie.no).

The FDA and the IOM Report
NEJM 2007;357:2520-2522 (December 13)
To the Editor: In her Perspective article on the response of the Food and Drug Administration (FDA) to a report by the Institute of Medicine (IOM) on the U.S. drug-safety system, Weiss Smith (Sept. 6 issue)¹ presents an unfair and uninformed portrayal of the FDA's commitment to drug safety and the many ways the agency is implementing major changes to further improve its drug-safety approach.

The FDA commissioned the IOM report, takes the report very seriously, and developed a comprehensive action plan on the basis of the report. In fact, our January 2007 response garnered praise from the IOM. (...)

FDA Oversight Questioned (Spørsmålstegn ved FDA-tilsyn)
JAMA 2007;298(22):2611
The Food and Drug Administration (FDA) is not adequately inspecting foreign manufacturing plants where medicine and ingredients for pharmaceuticals are made for importation to the United States, raising safety concerns, Congressional investigators said. (...)

Editorial | What the FDA Doesn't Know
philly.com 8.12.2007
This could kill you

A scathing report of the Food and Drug Administration concludes that the agency is woefully understaffed and underfunded and its technology is outdated.

The report comes in the wake of recent recalls of drugs, contaminated food and toxic toothpaste. It's getting to be that consumers aren't sure what products are safe anymore.

Unless something changes, the problems are going to get worse.
The report found that the FDA can't keep pace with the latest scientific advances. As a result: "American lives are at risk," the report said.
More troubling, many of the FDA's problems aren't new. (...)

Market Spotlight: Pharma & Drug Safety
forbes.com 4.12.2007
NEW YORK - Drug developers are just beginning to grapple with recent FDA oversight reforms, but already industry and consumer advocates disagree on how well the overhaul will be able to prevent future drug safety scandals. (...)

But safety scares in recent years sparked closer scrutiny of both drugmakers and the FDA, along with big changes. (...)

FDA science dearth puts public health at risk (FDAs kunnskapsmangel utsetter publikum for risiko)
reuters.com 3.12.2007
WASHINGTON (Reuters) - Lives are at risk because the U.S. Food and Drug Administration is woefully behind in the latest scientific advances and is under funded, a panel of advisers to the agency said at a public meeting on Monday.

Inadequate staffing, poor retention, out-of-date technology and a lack of resources mar the FDA's ability, the report by a subcommittee of the agency's Science Board said.

(A copy of the 60-page report, FDA Science and Mission at Risk, can be found at www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_00_index.html.)

"FDA's inability to keep up with scientific advances means that American lives are at risk," the report said. (...)

FDA Needs More Money and Staff, Report Finds
washingtonpost.com 30.11.2007
American lives are at risk because the Food and Drug Administration lacks the funding to keep up with scientific advances, agency advisers said.

The FDA suffers from a "plethora of inadequacies," including an "appallingly low" rate of food inspections and a lack of scientists who understand new technologies, a subcommittee of an outside panel said in a report posted yesterday on the agency's Web site. The full panel, known as the Science Board, will discuss the findings Monday. (...)

Drug firm execs to help lead FDA foundation
msnbc.msn.com 24.11.2007
Some say public-private partnership lets businesses cozy up to regulators (...)

The law creating the center required that at least four board members come from industries regulated by FDA. (...)

FDA still too chummy with pharmaceutical industry, critics say
seattletimes.nwsource.com 22.11.2007
(...) Two doctors — one a veteran FDA epidemiologist, the other a noted cardiologist at the University of Washington — said they have doubts.

"I'm thinking there are not huge advances between 10 years ago and today," said Dr. Bruce Psaty, of UW. "[But] I am hopeful some new changes are possible."

Dr. David Graham, of the FDA, is less sanguine. "The FDA remains stuck in a view that gives the companies and drugs a free pass," he said. (...)

FDA damned if it does, damned if it doesn't
money.cnn.com 9.11.2007
Stung by criticism that it was too cozy with the industry, the agency got tougher after Vioxx. Now who's upset? Big Pharma. Fortune's John Simons examines an embattled regulator. (...)

New FDA Research Center Rife With Risks
washingtonpost.com 14.10.2007
WASHINGTON -- The Food and Drug Administration is moving with unprecedented speed to launch a drug research center to be paid for by companies it regulates. (...)

New FDA Center Rife With Risks
forbes.com 14.10.2007
WASHINGTON - The Food and Drug Administration is moving with unprecedented speed to launch a drug research center to be paid for by companies it regulates.

The goal of the Reagan-Udall Foundation, approved by Congress and signed into law late last month, is to streamline and improve the development of drugs and medical devices, a goal long sought by regulators and the biggest players in the industry, such as Merck & Co., Pfizer Inc., Wyeth, GlaxoSmithKline PLC, and Johnson & Johnson. (...)

FDA is failing to oversee human clinical trials, report says
BMJ 2007;335:691 (6 October)
Problems in the systems and management processes of the US Food and Drug Administration are hindering its ability to oversee clinical trials and to protect trial participants, says a highly critical report by the Office of the Inspector General at the Department of Health and Human Services, the FDA's parent agency.

The report, by Daniel Levinson, the inspector general, was first publicised in a front page story in the New York Times last week (www.nytimes.com, "Report assails FDA oversight of clinical trials," 28 Sep). (...)

Prescription Drugs | Concerns Raised About New Private-Public Research Partnership to Support FDA
kaisernetwork.org 4.10.2007
(...) Critics are concerned that if drug makers gain too much influence on the foundation, the resulting criteria established for evaluating products could be excessively industry-friendly. Merrill Goozner, head of the Center for Science in the Public Interest's Integrity in Science Project, said, "The last thing you want is an industry-run board in which they create a science-sounding rationale before they put the FDA rubber stamp of approval on something that hasn't been proven." Diana Zuckerman, president of the National Research Center for Women & Families, said, "You have a situation where most of the money will be from (industry groups) -- they're going to control the board and therefore they're going to control the executive director, staff and the research." (...)

Open Clinical Trials
Published at www.nejm.org October 3, 2007 (10.1056/NEJMe0706501)
On September 27, 2007, President Bush signed into law the Food and Drug Administration Revitalization Act, which aims to improve the FDA's ability to ensure the safety of the nation's drugs and medical devices. The legislation not only reauthorizes the user-fee mechanism that has been part of the agency's funding since 1992, but also increases the agency's overall financial resources. Although the user-fee approach to funding has been controversial because the fees are paid by the pharmaceutical industry, which the FDA is charged with regulating, legislators believed that user fees provide a stable monetary base that is crucial to the effectiveness of the agency. (...)

FDA Officials Sued Over Conflicts of Interests Part I
lawyersandsettlements.com 30.9.2007
Washington, DC: A lawsuit recently filed in a federal court in Ohio against FDA officials on behalf of terminal cancer patients provides a rare window into the inner workings of an agency hijacked by pharmaceutical industry giants and stacked with insiders by President George Bush to guard against any threat to the profits of his top campaign contributors. (...)

Report: Safety of drug testing gets little FDA scrutiny (Rapport: FDA fører i liten grad tilsyn med uttesting av legemidler)
usatoday.com 28.9.2007
WASHINGTON (AP) — Clinical trials that enroll millions of patients in tests of experimental drugs and medical devices get scant government oversight, according to a watchdog report released Friday.

Over a six-year period, the Food and Drug Administration inspected just one of every 100 trial sites, raising questions about the agency's ability to ensure the safety of study participants, according to the report by Health and Human Services Department inspector general Daniel Levinson.

Hampered by the lack of a comprehensive catalog of clinical trials, the FDA is unable to even identify all trials, the estimated 350,000 study sites and the institutional review boards that oversee each study to ensure they meet scientific, ethical and legal obligations, the report says. (...)

Drug trials go unwatched, study says
news.yahoo.com 28.9.2007
WASHINGTON - Clinical trials that enroll millions of patients in tests of experimental drugs and medical devices get scant government oversight, according to a report released Friday. (...)

Flyter av usikre legemidler på markedet
p4.no 27.9.2007
P4 (Oslo): Over en halv million nordmenn bruker medikamenter som kan gi svært alvorlige bivirkninger.

Stadig flere medikamenter står på en overvåkingsliste hos Statens Legemiddelverk. Og avdelingsoverlege Steinar Madsen mener brukerne må være mer på vakt.

- Det er stadig flere legemidler som blir trukket fra markedet på grunn av bivirkninger, og det er snakk om til dels store legemidler.

Selvmordsadferd, hjerte- og karsykdommer og kreft er blant bivirkningene som mistenkes av medikamenter som blir gitt til norske pasienter. Madsen mener allikevel det er umulig å gjennomteste legemidler før de kommer på markedet.

- En viss risiko
- Vi kan ikke kreve at denne utprøvingen skal være hundre prosent sikker, for da ville vi aldri fått legemidler på markedet. Det er alltid en viss risiko med nye legemidler, det kan man ikke komme fra.

Madsen benekter at over 500.000 nordmenn er prøvekaniner, men sier allikevel at det er noen problemer man ikke kan se før produktene er ute på markedet.

Legemidlene som er under mistanke finner du på hjemmesiden til Statens Legemiddelverk. (...)

The Biggest FDA Reform In A Decade (Den største reform av FDA dette tiåret)
forbes.com 24.9.2007
You wouldn't know it from the lack of fanfare, but the Food and Drug Administration is getting its biggest overhaul in a decade in a dramatic coda to Merck's withdrawal of the blockbuster painkiller Vioxx three years ago. (...)

Another change: The FDA will be able to force drug makers to do clinical trials even after a medicine is approved and fine them if they don't follow through. Previously, many big clinical trials regulators asked for weren't finished. And there will be more money to study side effects of new medicines post-approval. Companies will pay more in fees when they submit drug applications, increasing the amount of money the FDA gets from industry by 25% to $400 million. (...)

Rough-and-ready analyses of existing data set off the Vioxx controversy and the recent kerfluffle over the diabetes drug Avandia. Such analyses, where researchers try to combine different studies to get a better idea of what kinds of side effects emerge in incredibly large groups, also linked antidepressants like GlaxoSmithKline's (nyse: GSK - news - people) Paxil to suicide risk and the Johnson & Johnson (nyse: JNJ - news - people) heart failure medicine Natrecor to kidney problems. In both cases, there are still debates about how real the risks are, but they put a squeeze on sales. (...)

Congress acts to improve drug safety
baltimoresun.com 21.9.2007
FDA gets sweeping powers to better protect consumers

WASHINGTON - Congress overhauled the government's drug-safety system yesterday, giving the Food and Drug Administration sweeping new powers in a bid to better protect patients from harm caused by drugs such as the painkiller Vioxx. (...)

New authority
Legislation passed yesterday by the Senate gives the Food and Drug Administration new authority to:

• Order warnings on drug labels

• Review drug ads before they air on television

• Make results of drug clinical trials available publicly

• Reduce the number of expert advisers with industry ties

• Require studies of new drugs' performance

• Probe patient databases for early signs of side effects (...)

China calls for one-day recall deadline for dangerous drugs - 21/09/2007
pharmatimes.com 21.9.2007
Drugmakers in China may be set a 24-hour deadline to recall dangerous medicines or lose their licences, according to a proposal from the country’s healthcare regulator. (...)

"It means this history of never showing studies that show safety problems will end," said Dr. Steven E. Nissen, a Cleveland Clinic heart specialist whose identification of heart problems caused by the diabetes drug Avandia sparked criticism of the FDA's drug-safety program this year.

"It's not a perfect bill -- no legislation is -- but in the key areas, the bill moves us forward toward safer and more effective drugs," Nissen said. (...)

House Passes Bill Giving More Power to the FDA
nytimes.com 20.9.2007
WASHINGTON, Sept. 19 — The House overwhelmingly passed legislation on Wednesday that is expected to give federal drug regulators significantly more money and power to ensure the safety of the nation’s drug supply. (...)

Drug makers would be required to post publicly the results of all clinical trials involving approved medicines. This provision is in response to controversy about a set of clinical trials kept secret by the industry that revealed that antidepressants increased the risks of suicide in teenagers while doing little to treat their depression.

The bill would also grant the agency the power to require drug makers to undertake clinical trials of medicines that the agency has already approved and to fine those who fail to do so. Few drug makers have followed through on past promises to undertake such trials, and the drug agency has done almost nothing about these failures.

The legislation would also grant the agency the authority to force drug makers to change the labels on their products, and it would give the agency the power to limit the distribution of certain drugs.

It would require the agency to reduce the number of conflict-of-interest waivers it grants to experts who serve on its advisory boards. (...)

FDA launches its first 'drug safety newsletter'
pharmatimes.com 19.9.2007
The US Food and Drug Administration has sent out its first ‘drug safety newsletter’, part of the agency’s response to criticism that it had taken its eye off the ball particularly when it comes to checking on marketed drugs. (...)

As such, the role of the newsletter “is to keep our medical community posted…about selected postmarketing drug safety reviews, important emerging drug safety issues, and recently approved pharmaceutical products,” he said, noting that it will be published quarterly and e-mailed for free to all subscribers. (...)

Bad Medicine?
msnbc.msn.com 11.9.2007
A new report reveals an alarming rise in fatal or debilitating prescription drug-related side effects and raises serious questions about basic medical safety practices. (...)

“We’re not disputing the findings,” says Food and Drug Administration spokeswoman Sandy Walsh. “The numbers are consistent with FDA’s report tracking, but they don’t tell us why.” That data includes more than 15,000 prescription drug-related deaths in 2005--up from around 5,000 in 1998.

According to Thomas Moore, a researcher at the Institute for Safe Medication Practices, a nonprofit group in Huntingdon Valley, Pa., and the study’s lead author, the findings represent widespread failures. “There’s enough blame to go around,” Moore says. “Nobody wants to think about drug safety. Drug companies want to focus on the benefits, doctors don’t want to even consider the possibility that they may be hurting someone, because it makes them uncomfortable, and patients just want to get better.” (...)

Burden of proof
boston.com 10.9.2007
Pointing to risks linked to FDA-approved drugs, a researcher argues that the agency should require more testing, a route some say could keep life-saving medication off the market for years (...)

FDA to Study TV Drug Advertising Methods
forbes.com 21.8.2007
WASHINGTON - Associated Press Federal regulators plan to study whether relaxing, upbeat images featured in TV drug ads distract consumers from warnings about the drugs' risks.

The announcement, posted Tuesday to the Food and Drug Administration's Web site, comes a week after a study published in the New England Journal of Medicine suggested the agency's drug-ad enforcement has steadily declined.

The FDA says it plans to study how 2,000 people react to television drug ads to determine whether they have an overwhelmingly positive impression of products despite audio warnings about potential side effects. (...)

Läkemedelsverket väljer reklambyrå
dagensmedia.se 21.8.2007
Läkemedelsverket har valt reklambyrå, efter en stor upphandling. Tre byråer slogs om uppdraget i upphandlingens slutskede. (...)

FDA Takes Caution on Approving New Drugs
baltimoresun.com 17.8.2007
TRENTON, N.J. - Under growing scrutiny since the blockbuster painkiller Vioxx was pulled from the market, the Food and Drug Administration in recent months has rejected a slew of experimental drugs or delayed their approval and required more data. (...)

FDA needs more funding, NEJM says, amid questions about antidiabetes drug
BMJ 2007;335:322 (18 August)
The US Food and Drug Administration needs more funding to do its job, say two articles in the New England Journal of Medicine (NEJM) related to reports of an increased cardiovascular risk associated with rosiglitazone (marketed as Avandia), used to treat type 2 diabetes. (...)

End conflicts on FDA approvals
A New Haven Register Editorial
nhregister.com 14.8.2007
In the coming weeks, the U.S. House and Senate will have to reconcile bills they passed that give the Food and Drug Administration more money and authority to guarantee the safety of prescription drugs. The legislation is needed. There have been repeated instances where unsafe drugs have remained on the market and safety concerns of FDA scientists have been ignored. (...)

FDA and Defense Dept to share medical protect safety data
pharmatimes.com 7.8.2007
The US Food and Drug Administration and the Department of Defense have announced a partnership under which they will share data and expertise related to the review and use of FDA-regulated drugs, biological products and medical devices. (...)

FDA's Retention Bonuses Rise to the Top
washingtonpost.com 2.8.2007
Critics Say Money Goes to Managers, Not Scientists Coveted by Drug Firms

Before paying $48,823 in cash bonuses to its chief of regulatory affairs in 2005, the Food and Drug Administration asked her to sign a simple declaration: "If I am unable to receive a retention allowance, I am likely to leave the federal government for a higher paying position in the private sector," wrote Margaret O'K. Glavin.

Glavin's statement did not detail a specific job offer, but that did not impede the payment. Over the past 4 1/2 years, she has collected more than $178,000 in cash bonuses -- on top of her $159,840 annual salary. (...)

House passes drug safety overhaul
latimes.com 12.7.2007
The measure, which aims to protect patients by boosting FDA powers, is similar to legislation passed by the Senate in May.

WASHINGTON — The House on Wednesday approved a sweeping overhaul of the nation's drug safety system, as Congress moved swiftly to send President Bush a bill that significantly improves patient protections. (...)

Drug safety concerns rise as FDA dips deeper into pharma's pocket for funds
news.medill.northwestern.edu 2.7.2007
WASHINGTON – Nearly 20 years ago, AIDS activists got fed up with the time it was taking for the federal government to approve potentially life-saving drugs. They stormed the headquarters of the U.S. Food and Drug Administration, effectively shutting down the agency that decides when new medicine is ready for the market. And they demanded medication – fast.

The FDA responded to the public outcry with new regulations to speed up its drug review process. But lack of money continued to stifle the agency’s abilities over the next four years. (...)

The FDA and the industry’s primary trade associations, Pharmaceutical Research and Manufacturers of America and Biotechnology Industry Organization, defend the user fee system. They say user fees came to the rescue when federal funding faltered in the early 1990s and helped to streamline drug reviews and bring life-saving drugs to the market. (...)

“There are a lot of people now at the agency, managers, who view the agency’s job as promotion of drug development, rather than regulation,” said Dr. David Ross, who quit the FDA November 2006 after a dispute over the approval of an antibiotic called Ketek, which he said was unsafe. “People are so anxious to get new drugs out there that the regulation part of it gets put last.” (...)

FDA called 'cozy' with drugmakers (FDA betegnet som "hyggelige" i sin omgang med legemiddelprodusenter)
usatoday.com 12.6.2007
While revising their drug-review policy last year, Food and Drug Administration officials met 112 times with industry representatives but only five times with consumer and patient groups, according to data out Monday from the House Appropriations Committee.

The FDA provided the data in response to questions submitted in March by Rep. Maurice Hinchey, D-N.Y.

The meetings occurred between October 2005 and December 2006 and focused on the Prescription Drug User Fee Act, under which manufacturers help pay for the review of their new drugs. (...)

FDA and EMEA keen to expand cooperation arrangement
pharmatimes.com 19.6.2007
European and US health regulators have agreed to expand their present cooperation plans to cover areas such as paediatric treatments and orphan drugs. (...)

Ahead of the Bell: FDA Hearing
forbes.com 12.6.2007
House lawmakers will discuss legislation Tuesday that would expand the government's regulation of drugs after they reach the market. (...)

FDA Might Lack Balance Between Speed, Safety in Prescription Drug Reviews
kaisernetwork.org 11.6.2007
Several recent problems with prescription drug safety has "led many on Capitol Hill to question" whether FDA has "failed to strike the right balance between speed and safety" in reviews of medications, the New York Times reports. While "immediate access to breakthrough medicines" is important to patients, they "also want to believe the drugs are safe," according to the Times. (...)

Potentially Incompatible Goals at F.D.A.
nytimes.com 11.6.2007
(...) A series of drug-safety scandals has led many on Capitol Hill to question whether the Food and Drug Administration has failed to strike the right balance between speed and safety. A clear sign of this imbalance, these critics say, is the increasing number of F.D.A. drug-safety officers who say they have been punished or ignored after uncovering dangers of popular medicines. (...)

China to Revise Rules on Food and Drug Safety
nytimes.com 7.6.2007
SHANGHAI, June 6 — Responding to growing international concerns about tainted food and counterfeit drugs, China said late Tuesday that it was overhauling its food and drug safety regulations and would introduce nationwide inspections. (...)

FDA Lacks Personnel, Funding To Adequately Inspect Prescription Drug Imports, According to CongressDaily
kaisernetwork.org 5.6.2007
FDA has insufficient personnel and funding to adequately inspect the safety and effectiveness of prescription drugs manufactured at foreign-owned firms and imported to the U.S., according to a CongressDaily investigation. FDA's staff of drug inspectors and biologists is "stretched so thin now" that "the breadth and frequency" of inspections "cover only a fraction of the numbers needed to ensure the purity and safety of the products and to adequately ensure compliance with drug-manufacturing processes," CongressDaily reports. "Also at risk is the monitoring of foreign manufacturers and producers put on watch lists for previous questionable practices or lapses," according to CongressDaily. (...)

FDA Needs Increased Ability To Conduct Postmarket Reviews, Editorial States
kaisernetwork.org 4.6.2007
Recent evidence that GlaxoSmithKline's diabetes drug Avandia can significantly increase the risk of heart problems "makes the case" for legislation (S 484) by Sens. Edward Kennedy (D-Mass.) and Mike Enzi (R-Wyo.) that would allow FDA to order post-approval reviews if "the regulator got a whiff of undocumented risks," a Washington Post editorial states. According to the Post, the "most potent criticism of FDA in the Avandia case is that it hasn't moved fast enough to quantify the drug's dangers." (...)

Balancing Medical Risks
washingtonpost.com 4.6.2007
The FDA needs more authority to monitor drugs following their approval. (...)

FDA offers safety reforms to skeptical lawmakers
fiercebiotech.com 31.5.2007
(...) The FDA has outlined new steps aimed at improving the way new drugs are monitored following approval. In response to a highly critical report from the Institute of Medicine, the FDA will begin to issue report cards 12 to 18 months after approval to highlight any safety problems that could come to light. (...)

Over the years the FDA has been held up to harsh criticism that it is too close to drug companies and is too focused on the approval process while ignoring the safety issues that arise after a drug is OK'd for marketing. A member of the IOM panel, R. Alta Charo (photo), told the Washington Post that the FDA had taken steps in the right direction, but that drug safety experts still didn't have the clout they needed. And members of Congress quickly swooped on FDA Commissioner Andrew von Eschenbach (photo), saying that the agency had far more work to do and offering new bills to force developers to publicly reveal all trial data.

- check out the FDA's release
- here's the article from The New York Times (...)

Congressional Hearings on Prescription Drug Safety Could Highlight 'Dissention' Among FDA Officials (Kongresshøringer om reseptbelagte legemidler kan rette oppmerksomhet på "dissens" mellom ledere i FDA)
Capitol Hill Watch
kaisernetwork.org 31.5.2007
A House hearing on June 6 to examine FDA's regulation of prescription drugs in the wake of recent safety concerns "may highlight the growing internal dissension between officials who approve drugs and those who track the safety" of approved drugs, the New York Times reports. The Times notes that tension between the drug approval office and drug safety office "has long been common, but in recent months it has erupted into sniping," particularly during an advisory committee hearing last month on Merck's arthritis drug Arcoxia. (...)

F.D.A. Still Unsettled in Wake of New Questions
nytimes.com 31.5.2007
ROCKVILLE, Md., May 30 — When Dr. Andrew C. von Eschenbach took over the Food and Drug Administration in 2005, the agency had a crisis over drug approvals that had missed or ignored dangerous side effects in Vioxx, antidepressants and other prominent medications.

Dr. von Eschenbach promised improvements, and agency officials said they would no longer be caught flatfooted on drug safety. (...)

FDA must upgrade reviews of new pharmaceuticals
courierpostonline.com 29.5.2007
Consumers should be able to rely on the Food and Drug Administration to protect them from unsafe medicines (...)

FDA move doesn't inspire confidence
news-herald.com 29.5.2007
"Do you have any questions?" It's a question anyone who's had a prescription filled at a pharmacy has most surely heard.

It's a rare occasion when one is actually posed.

Once the package is opened later, the patient might note the drug's side effects. (...)

Editorial: FDA needs more police power
redbluffdailynews.com 19.5.2007
(...) Under current law, the FDA must negotiate with drugmakers but cannot compel them to remove drugs from the market after they receive government approval.

Before the pain medication Vioxx was voluntarily removed by its maker, Merck, in 2004, the FDA negotiated with the drug company over label changes for 14 months. After FDA approval, Vioxx was discovered to have increased the risk of heart attacks. Rezulin, a diabetes drug found to cause liver failure, was withdrawn from the market after it had caused more than 500 deaths. To get a drug on the market under current law, it must go through four phases of clinical trials. Larger numbers of people are tested in each phase. But once the FDA approves the drug, the drugmaker has almost full control over its marketing and, if need be, its withdrawal. The only recourse consumers have is lawsuits.
(...)

Will Pharma Pay to Prevent the Next Vioxx? Ted Kennedy Thinks So
motherjones.com 15.5.2007
WASHINGTON DISPATCH: Senate's new drug legislation gives FDA some power to go after dangerous drugs after they're approved—but lets industry pick up the tab.

Last week was a good week for Big Pharma. Wednesday's passage in the Senate, 93 votes to 1, of a bill sponsored by Ted Kennedy has been heralded by some for strengthening the Food and Drug Administration. In fact, it only serves to tighten the drug companies' grip on the FDA by allowing the industry to pay for the testing of its own products, setting up potentially huge conflicts of interest. At the same time, the Senate helped tighten the drug companies' grip on the market, blocking the importation of low-cost drugs from Canada. (...)

Editorial: Prescribing a tougher FDA
sptimes.com 15.5.2007
When the U.S. Food and Drug Administration made news in recent years, it was usually for its incompetence. In particular, the agency's deficiencies in providing timely protection from dangerous prescription drugs was exposed by the Vioxx scandal. That reputation could be changing, thanks to a bill recently passed by the Senate that would give the FDA more authority to identify dangerous drugs and get them off the market sooner. (...)

The Senate bill, though not perfect, would strengthen the FDA's authority in key areas. The agency would:

- Track drugs long beyond their initial approval for adverse effects.
- Order, rather than ask, drug manufacturers to change labels or conduct more testing of their products.
- Establish a public database of clinical trials, so that drug companies couldn't hide safety concerns.
- Double its fines of violators to a maximum $2-million.
- Provide financial incentives for manufacturers to study a drug's effects on children, not just adults.
- Require drug advertisements to describe risks in a "clear" and "neutral" manner.

Unfortunately, some important fixes were left out of the bill. It doesn't speed up the availability of generic versions of expensive biological drugs often used in cancer treatment. The Senate vows to do that separately, but it remains to be seen if lawmakers will stand up to the pharmaceutical industry on that one. Senators also rejected an attempt to legalize imported drugs from Canada, which are often much cheaper than the same drugs sold here. (...)

DANGEROUS WARNINGS
By MARC K. SIEGEL
nypost.com 12.5.2007
May 12, 2007 -- CONGRESS may soon increase the Food and Drug Administration's oversight of pharmeceuticals. I certainly don't think we should simply trust what drug companies tell us, but I have my worries about the FDA, too. (...)

Lagförslag skärper kontrollen i USA
Läkemedelsvärlden 2007(5) (Maj)
Höga böter och krav på uppföljning ska öka de amerikanska patienternas förtroende för nya läkemedel. Amerikanska senaten röstade i onsdags igenom ett lagförslag som kraftigt stärker FDA:s kontrollmöjligheter.

Med 93 röster mot 1 röstade senaten ja till lagförslaget som går under namnet ”The Food and Drug Administration Revitalization Act”. Lagförslaget innehåller en rad förändringar som ger det amerikanska läkemedelsverket, FDA, många utökade befogenheter. Enligt amerikanska medier är syftet med lagförslaget dels att förnya den rätt som FDA idag har att ta betalt av läkemedelsföretagen för godkännandeprocessen, och dels att återge det amerikanska folket förtroendet för nya läkemedel. Ett förtroende som varit urholkat sedan Vioxx drogs tillbaka från marknaden efter svåra biverkningar. (...)

Bill granting more powers to the FDA evokes mixed reactions
themoneytimes.com 11.5.2007
(...) Reactions have, not surprisingly, been mixed to the proposed bill. While the drug manufacturers’ association has welcomed the provisions, consumer organizations have expressed discontent that the bill would increase the collaboration between the agency and the industry because of the dependence on user fees for conducting drug reviews. (...)

Senate backs bill giving FDA more powers on drug safety
pharmatimes.com 10.5.2007
Following a week of sometimes fraught negotiations, the US Senate has overwhelmingly approved a bill which is designed to increase the authority of the Food and Drug Administration and is being seen as a victory for 'big pharma'.

The Food and Drug Administration Revitalization Act (S 1082), which re-authorises the Prescription Drug User Fee Act, was passed by 93 votes to one. Its underlying purpose is to renew, up to 2012, the PDUFA programme that sees drugmakers pay annual fees of around $400 million to the FDA to defray the cost of reviewing new medicines but the bill also deals with much larger issues of safety. (...)

Drug Safety Reform at the FDA — Pendulum Swing or Systematic Improvement?
NEJM 2007;356:1700-1702 (April 26)
Every 5 or 10 years, Congress enacts major legislation addressing pressing issues at the Food and Drug Administration (FDA). This year, the biggest reforms since at least 1997 are expected. A decade ago, reform was motivated by the perception that the agency wasn't getting new medicines to patients as efficiently as possible. Today, a leading concern is that it isn't protecting the public from drugs' risks as effectively as it might. (...)

PDUFA Reauthorization — Drug Safety's Golden Moment of Opportunity?
NEJM 2007;356:1703-1704 (April 26)
"This [is] a golden moment of opportunity to improve fundamentally the way FDA regulation considers and responds to the evolving understanding of risks and benefits of drugs." So claims the September 2006 Institute of Medicine (IOM) report entitled The Future of Drug Safety, which paints a dismal picture of the U.S. system for ensuring the safety of drugs after they have been approved by the Food and Drug Administration (FDA).¹ (...)

FDA Advisor Conflicts
JAMA. 2007;297:1764
The Food and Drug Administration (FDA) proposed a new, tougher approach to conflicts of interest among advisors to the agency in March. (...)

Drug safety bill progresses in U.S. Senate
reuters.com 18.4.2007
WASHINGTON (Reuters) - A U.S. Senate committee approved on Wednesday a bill meant to bolster the government's oversight of prescription drug side effects and extend industry fees that help speed reviews of new medicines and devices.

The measure would give health officials new powers to fine companies that fail to do post-approval studies and to ban advertising of a new drug to consumers for two years. The safety of new medicines would be reviewed 18 months and three years after they reach the market. (...)

NEJM Publishes Several Perspectives on FDA User Fee Reauthorization, Prescription Drug Safety
kaisernetwork.org 26.4.2007
(...) "PDUFA Reauthorization -- Drug Safety's Golden Moment of Opportunity?" NEJM: In the perspective, Sean Hennessy and Brian Strom, special government employees of FDA, write that FDA's postmarket monitoring of drug safety is underfunded and FDA recommendations for user fee reauthorization are inadequate for improving safety (Hennessy/Strom, NEJM, 4/13). (...)

Critics of FDA User Fees Shoot for Reform by Congress
medpagetoday.com 13.4.2007
BOSTON, April 13 -- Hefty user fees from pharmaceutical companies account for some 40% of the FDA's budget for new-drug reviews, but this scheme that spurs speedier approvals worries safety watchdogs. (...)

Debate Builds Over Drug Companies' Fees to FDA
healthfinder.gov 13.4.2007
Critics say agency shouldn't take funds from industry it's supposed to police. (...)

Robert Goldberg: Congress ignores basic science on drug regulations
unionleader.com 7.4.2007
Ever since the voluntary withdrawal of Vioxx, the Food and Drug Administration has faced a storm of criticism from Congress over drug safety. Hardly a day passes now without some politician making an impassioned speech about keeping patients safe. (...)

Analysts puzzle over plan to sell a Vioxx-like drug
boston.com 30.3.2007
Furor over the Merck product spurred push to tighten FDA rules

WASHINGTON -- Some analysts are scratching their heads at the move Merck & Co. is planning : The drug maker wants to sell a new painkiller that is just like Vioxx , the blockbuster drug it pulled from the market in 2004 because the treatment doubled heart risks. (...)

Fundamental Improvements in Drug Safety for the 21st Century
aei.org 29.3.2007
Time for a Systematic, Electronic Infrastructure (...)

Reflection and refocus: Former FDA commissioners meet to discuss current agency woes
ama-assn.org 26.3.2007
An increase in funding could go a long way toward helping the agency, but they offered advice: Be wary of the source. (...)

Repeal law that puts "FDA on the payroll of the industry," says former NEJM editor
BMJ 2007;334:447 (3 March)
The law that requires drug companies to pay "user fees" to the US Food and Drug Administration for every drug they submit for approval should not be renewed when it comes before Congress later this year, says a former editor of the New England Journal of Medicine.

Writing an open editorial in the Boston Globe, Marcia Angell, who worked for the journal between 1979 and 2000, most recently as editor in chief, said that the Prescription Drug User Fee Act has, in effect, "put the FDA on the payroll of the industry it regulates" (www.boston.com, 26 Feb, "Taking back the FDA").
The act, which was passed by Congress in 1992, "put the fox in the chicken coop" and has changed the focus of the agency, which now serves the industry rather than the public, says Dr Angell. (...)

Taking back the FDA
MARCIA ANGELL
boston.com 26.2.2007
IT'S TIME to take the Food and Drug Administration back from the drug companies.

Before a prescription drug can be sold, the manufacturer must conduct clinical trials to prove to the FDA that the drug is safe and effective. Without that, doctors have no way of knowing how good or bad a drug is. Just trying it out would be not only risky, but unreliable, since individual experience can be misleading. The scrutiny that this agency exists to provide is vital to our health. (...)

The FDA also refuses to release unfavorable research results in its possession without the sponsoring company's permission. Here again, it contends not to have the authority to do so, but providing evidence of side-effects or negative results would seem to be an integral part of its job. It's no wonder that serious safety concerns about drugs such as Vioxx, Paxil, and Zyprexa have emerged very late in the day -- years after they were in widespread use. (...)

At $300 million to $400 million a year, the equivalent of about a day in Iraq, Congress can easily afford to buy this vital agency back for the public, and it should. (...)

Former FDA Commissioners Suggest Changes for Agency
kaisernetwork.org 23.2.2007
Recent problems at FDA can be attributed to the lack of consistent, long-term leadership; insufficient resources; and not enough authority to address safety issues, according to four former FDA commissioners who participated Wednesday in a panel discussion at the George Washington University School of Public Health and Health Services, the Newark Star-Ledger reports. David Kessler, who served as commissioner from 1990 to 1997, criticized the pharmaceutical industry's use of mass-marketing techniques and direct-to-consumer advertising. "The notion that you can come up with a new drug and millions and millions of people take it safely -- the blockbuster -- that is what got us in trouble," Kessler said. He believes limits should be placed on DTC advertising for prescription medications. (...)

Former New England Journal of Medicine Editor Angell Criticizes Pharmaceutical Companies at Event in Tennessee
kaisernetwork.org 23.2.2007
Prescription Drugs | Daily Health Policy Report
Former New England Journal of Medicine Editor Marcia Angell of Harvard Medical School in Memphis, Tenn., on Thursday "continu[ed] her public criticism" of pharmaceutical companies, the Memphis Commercial Appeal reports. (...)

F.D.A. Requires Guides With Certain Drugs
nytimes.com 22.2.2007
Companies that make drugs to treat attention-deficit hyperactivity disorder must alert patients to possible cardiovascular and psychiatric risks, the Food and Drug Administration says. The agency said it told the drug makers to develop guides that explain the risks and to hand them out with the medications, which already carry label warnings about the risks. (...)

- Må få munnkurv
aftenposten.no 11.2.2007
Bransjerådet for naturmidler er så opprørt over uttalelsene fra avdelingsoverlege Steinar Madsen i Legemiddelverket at de krever at han får munnkurv. (...)

"De ulovlige midlene som brukes i naturmidler og kosttilskudd er ikke godkjent av legemiddelverket. De er ofte urene og kan gi ukjente bivirkninger. De kan føre til sykdom og i verste fall død", sa Madsen den gangen.

Sterk kost.
Dette ble for sterk kost for Bransjerådet for naturmidler. Under overskriften "personalklage" ber de om at avdelingsoverlegen blir omplassert eller får forbud mot å uttale seg til mediene på vegne av Statens legemiddelverk. (...)

FDA Efforts To Improve Prescription Drug Safety 'Encouraging'
kaisernetwork.org 5.2.2007
FDA is "making encouraging moves to strengthen its regulation of drugs that are already on the market," but the "changes fall far short of what's needed to protect millions of unsuspecting patients whose adverse effects may show up only after years of use," a New York Times editorial states. (...)

Moving Toward Greater Drug Safety
EDITORIAL
nytimes.com 5.2.2007
The Food and Drug Administration is making encouraging moves to strengthen its regulation of drugs that are already on the market. But the changes fall far short of what’s needed to protect millions of unsuspecting patients whose adverse effects may show up only after years of use. (...)

FDA has work ahead to regain public's trust
EDITORIALS
masslive.com/editorials/republican/index.ssf
If one were designing a system meant to ensure that drugs brought to market were safe for human consumption, a rigorous testing process would surely be at the top of the list. A drug manufacturer would have to prove beyond any reasonable doubt that the new medicine it was looking to sell would not be harmful to those who used it.

Such a program, at least in a sense, has been in place for years. Before a new drug hits the market, it has been tested and reviewed by the Food and Drug Administration. Only after the FDA has given the green light can a pharmaceutical company begin to sell a new drug. (...)

Vioxx outcry spurs FDA to raise scrutiny of drugs
indystar.com 31.1.2007
WASHINGTON -- The public outcry over the withdrawal of the painkiller Vioxx is leading to closer government scrutiny of new drugs to identify and disclose late-developing safety problems. (...)

Bush Directive Increases Sway on Regulation
nytimes.com 30.1.2007
WASHINGTON, Jan. 29 — President Bush has signed a directive that gives the White House much greater control over the rules and policy statements that the government develops to protect public health, safety, the environment, civil rights and privacy. (...)

Bush Order Grants White House More Authority Over Guidance Issued by Federal Agencies To Regulated Industries
Daily Health Policy Report
kaisernetwork.org 30.1.2007 (...)

FDA proposes higher fees for drug approvals to cover postmarketing surveillance
BMJ 2007;334:177 (27 January)
The US Food and Drug Administration has agreed with pharmaceutical manufacturers on an almost 30% increase in the "user fees" that drug makers pay to the FDA to expedite approval of new drugs. The FDA has also consulted patient advocates, consumer groups, health professionals, and academic researchers about the new rules.

User fees are annual fees paid by pharmaceutical manufacturers. The FDA wants them to increase by $87.4m to $392.8m (£199.0m; 303.7m). The FDA now gets more than half of its funding from user fees. (...)

FDA Feeling The Heat
by Evelyn Pringle
opednews.com 18.1.2007
Over the past year, the Bush administration's FDA has been the focus of non-stop investigations and with the Democrats in control of Congress, a long overdue overhaul of the agency is in the cards.

The Government Accountability Office has identified serious problems within the FDA. In an April 21, 2006, report, the GAO found the FDA's performance "disorganized," "bureaucratic," and undermined by infighting between drug evaluation administrators whose allegiance is with the pharmaceutical industry, and the Office of Drug Safety. (...)

The Bush Administration's FDA
by Evelyn Pringle
opednews.com 16.1.2007
Since the Bush administration took control of the FDA, editorial pages in the major newspapers, along with respected medical journals, have broadcast outrage over the agency's failure to protect the public from an industry focused on profits only.

According to a May 2006, poll conducted by the Wall Street Journal and Harris Interactive, the majority of adults in the U.S. think the FDA's most important function is to ensure the safety and efficacy of new prescription drugs.

However, the poll found that the public has come to doubt the FDA's ability to do its job, with 7 out of 10 adults giving the agency a negative rating and a large majority saying the FDA's decisions are influenced more by politics than science. (...)

FDA: Pay To Be Watched
forbes.com 11.1.2007
In the wake of the withdrawal of Vioxx and other drug safety scandals, the U.S. Food and Drug Administration hopes to compel drug companies to pay to monitor the safety of already approved medicines. (...)

FDA Runs Protection Racket For Big Pharma
by Evelyn Pringle
opednews.com 10.1.2007
Why would Americans trust the FDA to regulate the pharmaceutical industry? Since the Bush administration took office the FDA has become the industry's partner in crime.

The most notorious protection scheme put in place by the FDA and Big Pharma is the preemption policy that bans private lawsuits against drug companies in state courts once a drug and its label have been approved by the FDA. (...)

FDA Makes 'Suboptimum' Use of Advisory Committees, Group Says
kaisernetwork.org 4.1.2007
FDA is "making suboptimum use of its drug advisory committee system," according to a letter from the Health Research Group at Public Citizen published in the current issue of the Lancet, USA Today reports. (...)

FDA Approved 17 New Prescription Drugs in 2006, Lowest Approval Rate Since New Drug Approvals Peaked at 53 a Decade Ago
kaisernetwork.org 4.1.2007
FDA approvals of new medications, which have decreased in recent years, by 2010 likely will increase as pharmaceutical and biotechnology companies seek approval for about 2,000 compounds currently in early stage clinical trials, according to a study released on Wednesday by the Tufts Center for the Study of Drug Development, the Newark Star-Ledger reports. (...)

FDA drug approval at lowest rate
nj.com 4.1.2007
Since Vioxx withdrawal, only 37 treatments received federal OK
As the American pharmaceuti cal industry grapples with layoffs and spending cuts, newly released statistics show drugmakers continue to struggle with the discovery of blockbuster medicines.

The Food and Drug Administration approved only 17 new drugs last year, matching the lowest number of newly approved compounds since the peak of 53 approvals a decade ago. (...)

Family tie helps win FDA contract
latimes.com 19.12.2006
Federal work goes to the client of an official's husband. The couple say they acted properly.
WASHINGTON — The concerns at the office surfaced not long after their Las Vegas wedding. (...)

Los Angeles Times Examines Potential Conflict of Interest After FDA Official Granted Contracts to Husband's Firm
kaisernetwork.org 19.12.2006
The Los Angeles Times on Tuesday examined potential conflict-of-interest issues that arise when spouses or relatives of government officials work for companies that stand to benefit from government contracts. The Times profiles the case of Margaret Burnette, a senior FDA information technology official, and her spouse, Mark Boster, a consultant who later became chief operating officer and an executive vice president of a company that held a contract with Burnette's office. (...)

FDA Oversight
cbsnews.com 14.12.2006
(CBS/60 Minutes)
No matter how you slice it Wednesday was not a great day for the FDA.

In back-to-back stories on our Evening News broadcast we detailed widespread concerns about possible links between teenage suicide and anti-depressant drugs followed by my piece based upon a scathing Senate Committee report that raised troubling questions about a relatively new antibiotic, Ketek, and its links to serious liver damage.

Both the sale and use of Ketek has skyrocketed since its approval on April Fools Day 2004. Last year alone, 3.3 million prescriptions were written, all for a drug that, despite assurances from both the manufacturer and FDA of its safety, has some “serious data integrity problems,” to quote Senator Charles Grassley’s detailed report. (...)

Økt tilgjengelighet til reseptfrie legemidler
legemiddelverket.no 13.12.2006
Evalueringen av ordningen med salg av legemidler utenom apotek (LUA) er nå klar. Målet med evalueringen har vært å undersøke om ordningen har gitt en økt tilgjengelighet til viktige reseptfrie legemidler for befolkningen. (...)

Last ned LUA rapportenPDF (...)

Drugs may win faster approval
baltimoresun.com 1.12.2006
FDA spearheading effort to speed up the process

WASHINGTON -- Federal health officials want to alter the foundations of the system entrusted with making sure new drugs are safe and effective.

By streamlining the way scientists determine a new drug's safety and effectiveness, advocates say, new cures can be delivered to dying patients much more quickly. (...)

Kennedy will push for overhaul of FDA
boston.com 16.11.2006
He says agency is swayed by politics (...)

Six Ways Congress Could Hurt Big Pharma
forbes.com 16.11.2006

Has the drug industry's fabled political lobbying machine finally met its match? (...)

Learning from Vioxx
boston.com 14.11.2006
THE RECALL in 2004 of Vioxx after the arthritis pain reliever was found to cause heart attacks and strokes is just one example of a drug that the Food and Drug Administration approved but then failed to monitor closely enough after it was on the market. Providing the agency with the resources and the authority needed to better ride herd on drugs in the marketplace should be high on the to-do list of the new Congress. (...)

FDA may change handling of safety issues
yahoo.com 9.11.2006
The Food and Drug Administration plans to revamp how it handles safety issues with the stents, pacemakers, implantable defibrillators and other medical devices it regulates.

As it does so, it plans to utilize data-mining techniques that could give the agency early warning of potential problems. (...)

Strengthening the FDA
JAMA. 2006;296:2194.
As the growth in the Food and Drug Administration's (FDA’s) budget continues to lag behind appropriations for other public health agencies, a new advocacy group will try to reverse the trend. The Coalition for a Strong FDA (http://fdacoalition.org) began operation on September 25 under the leadership of the last 3 secretaries of the Department of Health and Human Services—Tommy G. Thompson, Donna E. Shalala, and Louis Sullivan, MD. (...)

‘Opportunity for Improvement'
msnbc.msn.com 12.10.2006
A top FDA official responds to new concerns about the agency's drug safety practices. (...)

New Sense of Caution at F.D.A.
nytimes.com 29.8.2006
A federal advisory group last week derided the Food and Drug Administration as a feckless watchdog unable to protect consumers from unsafe medicines. But try telling that to drug company executives, investors and analysts.

Many of them say the F.D.A. has already responded to a barrage of criticism over the last two years by quietly becoming more assertive about keeping new drugs off the market or refusing to approve new uses for existing medications. (...)

New coalition urges more money for FDA
usatoday.com 25.9.2006
Industry, consumer and patient groups and the last three secretaries of the Health and Human Services department are joining forces to lobby for more money for the Food and Drug Administration. (...)

Hundreds of unapproved drugs sold by prescription
usatoday.com 18.9.2006
hey have official-sounding names, like Lodrane XR Suspension and Cortane B.

They're listed in the Physician's Desk Reference and advertised in medical journals.

You can buy them in drugstores, in person or online, but only if you have a doctor's prescription. They even have generic competitors.

Yet, what looks like a Food and Drug Administration-approved drug and sounds like an FDA-approved drug might not really be an FDA-approved drug. And that little-known fact means consumers — not to mention doctors and pharmacists, who are often as ignorant of the drugs' status as patients are — should beware, the FDA says. (...)

FINDINGS
washingtonpost.com 24.8.2006
The Food and Drug Administration is proposing a new system for tracking what drugs are on the market after a study found that more than 9,000 products were missing from its master listing.

Companies would have to give electronic updates every six months on where their prescription and nonprescription medications are made and whether they are on the market. Currently, the FDA has 15 workers who manually enter paper registrations that companies file when they start or stop selling a drug.
A report Aug. 14 from the Department of Health and Human Services inspector general said the government's ability to enforce drug safety laws was hampered by a lack of information. The FDA's current list of 120,000 medications is missing 9,187 products and includes 34,257 that are no longer available, the report says. (...)

Probe faults prescription drug directory
chron.com 14.8.2006
WASHINGTON — A federal prescription drug directory fails to list more than 9,000 medications but catalogs tens of thousands more that are no longer on the market, according to a report Monday.

The Food and Drug Administration directory is neither complete nor accurate, according to the inspector general of the Department of Health and Human Services.

The omissions and errors limit the usefulness of the directory, which is meant to help the FDA and other government agencies in handling recalls, identifying medication errors and controlling imports, the IG's report said.

The FDA said it generally agreed with the report and is working to fix the problems it identified, including by making it easier for companies to submit listing information.

Federal law requires pharmaceutical companies to list with the FDA the prescription drugs they make. As of February 2005, the FDA's National Drug Code Directory listed 123,856 prescription drug products.

However, the review found it missed about 9,200 prescription drugs, while continuing to include about 34,200 other drugs either no longer sold or listed in error. (...)

Drug makers lobby US to hike FDA funds
boston.com 13.7.2006
Firms say taxpayers should pay bigger part of bill for safety tests

James C. Greenwood, a former congressman now paid by the biotechnology industry to influence legislators, stood before an audience at the Massachusetts Biotechnology Council's annual meeting recently and outlined his next challenge: getting Congress to increase Food and Drug Administration funding.

Greenwood displayed a chart indicating zero growth in congressional appropriations to the FDA from fiscal years 1986 through 2006. (...)

Regulators 'may have delayed' SSRI warnings
pharmatimes.com 7.7.2006
World News | Warnings about the safety of the SSRI class of antidepressants may not have been issued in a timely manner because of the drug approvals process, Professor David Healy of Cardiff University has argued in this week's issue of the British Medical Journal.

Concerns over a link between selective serotonin reuptake inhibitors and an increased risk of suicidal thoughts and behaviour first arose in 1990 after a published article spotlighted that GlaxoSmithKline's Seroxat/Paxil (paroxetine) could trigger suicidal acts. Further trials pointed to a doubling in the suicide rate between placebo and active treatment but, says Prof Healy: "It was only in a recent study reviewing over 700 trials that this difference became significant." (...)

Adds Prof Healy: "Trials in children conducted in the mid-1990s show a doubling of the risks of suicidal acts with SSRIs. These results have recently formed the basis of warnings about the use of SSRIs in children. Trials in adults show a similar risk ratio, yet, until May 2006, no warnings were issued for adults. This trend should have been seen by both companies and regulators as something that required investigation."

Instead, he notes, the finding was obscured by the way in which results were presented to the regulators, as well as the regulators' "rigid interpretation" of the data, which may have delayed warnings over their use. (...)

Statliga pengar till läkemedelsindustrin
dagensmedicin.se 2.5.2006
Regeringen skjuter till statliga pengar för att stärka forskning och utveckling inom läkemedel och bioteknik.

I slutet av 2005 presenterade regeringen tillsammans med industrin och fackliga organisationer ett strategiprogram för branschen. Nu presenterar regeringen en inledande satsning utifrån de åtgärder man enats om i strategiprogrammet.

- Tillsammans med industrin genomför vi nu en omfattande satsning för att stärka näringen. Bioteknik och läkemedel är en framtidsbransch med stor betydelse för svensk export och välfärd, säger näringsminister Thomas Östros i ett pressmeddelande.

Regeringen vill stärka samarbetet mellan högskola och industri, underlätta för forskare att komma in på företagen, och stärka affärskompetensen på universiteten. På så vis ska utvecklingen av nya produkter stimuleras.

Verket för innovationssystem, Vinnova, har fått i uppdrag att ta fram ett underlag. Genomförandet av åtgärderna bygger på gemensam finansiering mellan staten och industrin.

Amerikanska läkemedelsmyndigheten och svenska Läkemedelsverket i nytt avtal
lakemedelsverket.se 28.4.2006
Den amerikanska läkemedelsmyndigheten The Food and Drug Administration (FDA) och svenska Läkemedelsverket har undertecknat ett ömsesidigt avtal om utbyte av information. Avtalet börjar gälla från april 2006 och tillåter de två läkemedelsmyndigheterna att utbyta information som ännu inte offentliggjorts. Det kan till exempel handla om information om införande av lagar eller interna beslutsunderlag.

- Avtalet är en viktig milstolpe, säger det svenska Läkemedelsverkets generaldirektör Gunnar Alvan. Processen för godkännande av nya läkemedel och säkerhetsuppföljningen av läkemedel blir alltmer internationell.
Överenskommelsen kan till exempel användas vid utbyte av produktsäkerhetsinformation som skulle kunna resultera i regulatoriska åtgärder som behöver vidtas samtidigt i USA och Europa. De svårigheter på grund av tidsskillnaden mellan Nordamerika och Europa som tidigare har upplevts har därmed övervunnits. (...)

MS patients urge FDA to reapprove controversial drug
seattletimes.nwsource.com 8.3.2006
WASHINGTON — Multiple-sclerosis patients pleaded with the Food and Drug Administration Tuesday to again allow sales of a drug they described as a "miracle" for the disabling disease, while the family of a woman who died taking it warned of devastating side effects.

The drug, Tysabri, was withdrawn from the market in February 2005 after three patients unexpectedly developed a rare brain infection usually seen in AIDS patients and others with weak immune systems. Two of them died. Now the manufacturers are asking the FDA to allow Tysabri to be prescribed again, with a series of limitations on its use. (...)

(Anm: Tysabri (natalizumab)
fda.gov 27.2.2008
[Posted 02/27/2008] Biogen Idec, Elan and FDA notified healthcare professionals of reports of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose of Tysabri. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Physicians should inform patients that Tysabri may cause liver injury. (...)

How can we regulate medicines better? (Hvordan kan vi regulere legemidler bedre?)
BMJ 2007;335:803-805 (20 October)
Current European licensing regulations give precedence to the interests of drug companies. Silvio Garattini and Vittorio Bertele' suggest changes to ensure they meet the needs of patients and doctors

Despite the undoubted advantages of the establishment of the European Medicines Agency (EMEA)w¹ criticisms have been made, mostly about its independence and transparency and the evaluation criteria.^{1 2 3} The 2004 European Commission law expanded the agency's remit but did not significantly changes the methods of regulation.w2 We offer a few proposals aimed at bettering the work of the agency. These may require important changes in current law regulating the pharmaceutical system. (...)

Legemiddelverkets krig
Aftenposten 3.10.2005
Kosttilskudd. I programmet PULS på NRK nylig ble det tatt opp problemet med at effektive kosttilskudd fjernes fra helsekostmarkedet, nettopp på grunn av at de virker. Konkret gjaldt det glukosamin, et naturlig stoff som bygger opp brusk i leddene, og som dermed er virksomt for personer med slitasjegikt. Begrunnelse fra Legemiddelverket: Befolkningen må beskyttes! (...)

Man kan mistenke Legemiddelverket for å ha en annen agenda: Å beskytte legemiddelindustrien, at folks helse er underordnet. Og politikerne, som skal lage lover og regler på området, aner ikke hvilken galskap som rår. (...)

Høring: Fjerning av ordning med merking av legemidler med varseltrekant
Norges Apotekerforening (NAF) 03.10.2005
Fra NAFs høringsbrev datert 30.09.2005:
Statens legemiddelverk foreslår i høringen å fjerne dagens ordning med merking av legemidler med varseltrekant. Statens legemiddelverk ønsker i stedet mer nyansert informasjon og en tettere oppfølging av hver pasient fra lege og apotek, hvor man i hvert enkelt tilfelle vurderer om legemidlet vil påvirke pasientens evne til å føre motorkjøretøy eller betjene maskiner.

NAFs vurdering er at den røde varseltrekanten nå er godt innarbeidet i Norge, og at befolkningen assosierer symbolet med behov for å være forsiktig med å kjøre bil etter inntak av trekantmerkede legemidler. NAF er av den oppfatning at fjerning av et slikt innarbeidet varslings- og informasjonssystem vil være uheldig.

Det fremgår av høringsnotatet at merkesystemet ikke har vært vurdert vitenskapelig i større grad. Videre skriver legemiddelverket at systemet med varseltrekanter er ressurskrevende å vedlikeholde og i praksis ikke har vært tilstrekkelig vedlikeholdt.

At myndighetene ikke har fulgt opp og evaluert ordningen med trekantmerking er, etter NAFs syn, ikke noe godt argument for å fjerne merkeordningen. Statens legemiddelverk er i disse dager i ferd med å revitalisere og legge grunnlaget for en bedret informasjon om legemidler til pasientene.

Høringssvar fra LMI til Statens legemiddelverk
Legemiddelindustriforeningen (LMI) 12.10.2005 (...)