Har industrien for stor innflytelse på forskning?

Hvor stor innflytelse har industrien på arbeidet og produkter i forskningssamfunnet? Kan allmennpraktiserende leger stole på den informasjon de mottar om de legemidler som de forskriver? Gir skiftet fra akademisk til kommersiell forskningssektor industrien for mye kontroll over legemiddelstudiene? (N Engl J Med 2000;342:1539-44)

Konklusjon

Akademisk tilhørighet fortsetter å være fremtredende blant forfatterne av den hyppigst siterte medisinske forskning. Slik forskning er stadig oftere finansiert av industrien, ofte utelukkende. Akademikerne kan miste kontrollen på agandaen for klinisk forskning. (BMJ (17 March 2006))

Kommersialisering av kliniske forsøk - Risiko og nytte av CRO-boom But some recent events have raised questions about whether the commercialization of clinical trials, in its current form, is in the best interest of science or the public. (NEJM 2007;357:1365-1368 (October 4))

Om en voksende markedsplass for profitt

For å påskynde undersøkelser, har det vært en dreining bort fra de akademiske institutter til fordel for en voksende markedsplass for profitt, hvor nøkkelspillerne er CRO-er og SMO-er. (N Engl J Med 2000;342:1539-44)

Virkelig uavhengig forskning? (BMJ 2008;337:a1332 (21 August))

Mye høflighet, lite kvalitet Prioriterer anvendt forskning (aftenposten.no 2.11.2006)

- Ubehagelige allianser – kliniske forskere og legemiddelindustrien (den farmasøytiske industri) - kommersielle legemiddelnett

Uneasy Alliance - Clinical Investigators and the Pharmaceutical Industry (Ubehagelige allianser – kliniske forskere og legemiddelindustrien (legemiddelindustrien (den farmasøytiske industri)))
N Engl J Med 2000;342:1539-44
(...) Hvor stor innflytelse har industrien på arbeidet og produkter i forskningssamfunnet? Kan allmennpraktiserende leger stole på den informasjon de mottar om de legemidler som de forskriver? Gir skiftet fra akademisk til kommersiell forskningssektor industrien for mye kontroll over legemiddelstudiene? (...) (How much influence does industry have over the work and products of the research community? Can practicing physicians trust the information they receive about the medications they are prescribing? Does the shift from the academic to the commercial research sector give industry too much control over clinical drug trials?)

De siste 10 år har det vært en oppsiktsvekkende vekst for en ny forskningsmodell. Kommersielt orienterte nettverk av ”kontraktsforskningsorganisasjoner” og ”stedlige styringsorganisasjoner” har endret landskapet når det gjelder legemiddelforsøk, noe som har ført til at akademiske medisinske sentre må tenke nytt når det gjelder deres deltagelse i legemiddelforskning finansiert av industrien. (...) (The past 10 years have seen the spectacular growth of a new research model. Commercially oriented networks of contract-research organizations (CROs) and site-management organizations (SMOs) have altered the drug-trial landscape, forcing academic medical centers to rethink their participation in industry-funded drug research.)

The Shift to Commercial Drug Networks (Skiftet til kommersielle legemiddelnettverk)

(...) For hver dags forsinkelse på oppnåelse av godkjenning hos FDA for et legemiddel, taper produsenten i gjennomsnitt 1,3 millioner dollar. En rask prosess går foran alt annet for farmasøytiske firmaer. (...) (For each day’s delay in gaining FDA approval of a drug, the manufacturer loses, on average, $1.3 million. Speed is paramount for pharmaceutical firms.)

For å påskynde undersøkelser, har det vært en dreining bort fra de akademiske institutter til fordel for en voksende markedsplass for profitt, hvor nøkkelspillerne er CRO-er og SMO-er. (11,12,13) I 1991, gikk 80 prosent av industriens penger til kliniske forsøk ved akademiske institutter; i 1998 hadde tallet stupt til 40 prosent. (14) Beviser tyder på at den kommersielle sektor fullfører forsøk raskere og billigere enn akademiske medisinske sentre. (11) (...) (To expedite trials, industry is turning from academic medical centers to a growing for-profit marketplace whose key players are CROs and SMOs (11,12,13) In 1991, 80 percent of industry money for clinical trials went to academic medical centers; by 1998, the figure had dropped precipitously to 40 percent. (14) Evidence suggests that the commercial sector completes trials more rapidly and more cheaply than academic medical centers. (11))

CRO-er kan bruke både akademiske medisinske sentre og offentlig ansatte leger til å rekruttere pasienter til et forsøk. I den samfunnsmessige gren av legemiddelforsøk, har enda et mellomledd kommet inn i bildet, SMO-ene. CRO-er kan inngå underentrepriser med de profittbaserte SMO-er for å organisere nettverk av offentlig ansatte leger, som sikrer rask innrullering av pasienter, og leverer skjemaer for caserapport til CRO-en. Noen forsøk har fire lag (produsenter, CRO, SMO, og lege-forsker), en situasjon som minner om en “multitiered regulert helsemodell” (arbeidsgiver, helseforbyggende organisasjoner, uavhengige praksisforbindelser, og leger). Tre av de største SMO-ene er Clinical Studies Limited, Hill Top Research, og Affiliated Research Centers. SMO-er skaffer de offentlig ansatte lege-forskerne administrativ støtte og hjelper legemiddelfirmaenes markedsforskerne. (15) De er blitt kritisert for produksjon av data med dårlig kvalitet, utilstrekkelig forskeropplæring, og at de koster mer enn et system med uavhengig stedlige enheter som ikke er assosiert med en SMO. (13,15) (...) (CROs may use both academic medical centers and community physicians to recruit patients for a trial. In the community arm of drug trials, yet another intermediary has entered the picture, the SMO. CROs may subcontract with for-profit SMOs to organize networks of community physicians, ensure rapid enrollment of patients, and deliver case-report forms to the CRO. Some trials have four layers (manufacturer, CRO, SMO, and physician-investigator), a situation reminiscent of the multitiered managed-care model (employer, health maintenance organization, independent practice association, and physician). Three of the largest SMOs are Clinical Studies Limited, Hill Top Research, and Affiliated Research Centers. SMOs provide community-physician investigators with administrative support and help market investigators’ services to pharmaceutical companies. (15) They have been criticized for producing data of poor quality, inadequately training investigators, and costing more than a system of independent sites unassociated with an SMO. (13,15))

(Anm: (13) Henderson L. The ups and downs of SMO usage. Centerwatch 1999;6:4-8); (15) Vogel JR. Maximizing the benefits of SMOs. Appl Clin Trials 1999;8:56-62.)

Publishing the Results (Publisering av resultater)

For akademiske forskere, er det å få publisert et arbeide i et tidsskrift som er fagfellevurdert (ekstern fagvurdering) som å vinne prinsessen og halve kongerike. I kontrast til farmasøytiske firmaer, hvor det essensielle produktet er nye legemiddelsøknader oversendt FDA. Uten FDA-godkjennelse er ingen tidsskriftsartikkel verdt et rødt øre for legemiddelfirmaet. Selv om publisering i prestisjefylte tidsskrift er viktig, for å overbevise leger om å forskrive legemiddelfirmaets produkter. (For academic investigators, publication in peer-reviewed journals is the coin of the realm. For pharmaceutical firms, in contrast, the essential product is the new-drug application to the FDA. In the absence of FDA approval, no journal article is worth a cent to a drug company. Yet publication in prestigious journals is important, to persuade physicians to prescribe the company’s products.)

(Anm: peer-reviewed; fagfellevurdert; dvs. "gransket" av fagfeller (som oftest andre som publiserer medisinske artikler og studier) før publisering i et vitenskapelig tidsskrift.)

(Anm: peer-review; fagfellevurdering, på engelsk peer review, er en metode for å vurdere riktighet og verdi av forskningsrapporter ved budsjettering før forskningsprosjekter får starte og ved publisering av resultater i tidsskrifter. Kilde: wikipedia.org. Tidsskr Nor Lægeforen 2006;126:3327.)

Noen multisenter forsøk har publiseringskomiteer, som kan være dominert av ansatte forskere innen husets fire vegger eller utenforstående, som oppsummerer resultater for publisering. I andre tilfeller skriver firmaet eller CRO rapporter for publikasjon, sirkulerer utkast av manuskriptet til de forskere som vil bli oppført som forfattere. Forfatterskap kan bli bestemt av slike kriterier som hvem som deltok i designet av studien, som innmeldte flest pasienter, og som har et fremtredende navn innen fagfeltet. (Some multicenter trials have publication committees, which may be dominated by in-house or outside investigators, that write up the results for publication. In other cases, the company or CRO writes the reports for publication, circulating draft manuscripts to the investigators who will be listed as authors. Authorship may be determined by such criteria as who participated in designing the study, who enrolled the most patients, and who has a prominent name in the field.)

(Anm: CRO; contract-research organizations; kontraktsforskningsorganisasjoner.)

Control over Publication (Kontroll over publikasjon

(...) Seks intervjuede forskere til denne rapporten omtalte tilfeller hvor publikasjonen ble stoppet eller innhold ble endret av det firmaet som stod bak finansieringen. I et tilfelle, ifølge dr. Cummings, forsinket firmaet gjennomgangsprosessen før publisering i et halvt år, da de anmodet om en detaljert revisjon som ville ha ført til at manuskriptet ville bli mer gunstig for firmaets offisielle markedsposisjon. I løpet av denne forsinkelsen skrev firmaet i hemmelighet en konkurrerende artikkel som omhandlet det samme emne, som favoriserte firmaets synspunkt. (...) (Six investigators interviewed for this report cited cases of articles whose publication was stopped or whose content was altered by the funding company. In one case, according to Dr. Cummings, the company held up the prepublication review process for over half a year, then requested pages of detailed revisions that would have made the manuscript more favorable to the company’s official marketing position. During the delay, the company secretly wrote a competing article on the same topic, which was favorable to the company’s viewpoint.)

I et annet tilfelle virket ikke det legemidlet som ble undersøkt. Forskerne argumenterte for at vitenskapelig integritet krevde publisering av funnene. Firmaet nektet ikke publisering, men de forsinket prosessen inntil forskerne mistet interessen. (...) (In another case, the drug being investigated did not work. The investigator argued that scientific integrity required publishing the findings. The company never refused to publish, but it stalled until the investigator lost interest.)

For en annen forsker, hadde de fleste relasjoner til industrien vært uten problemer, relatert til tilfellet med to forsøk på samme legemiddel, en mer gunstig for firmaet enn den andre. På tross for en protest fra forskeren, ble resultatene fra den minst gunstige undersøkelsen aldri publisert. (...) (Another investigator, most of whose relations with industry have been without problems, related the case of two trials of the same drug, one more favorable to the company. Despite a protest from the investigator, the results of the less favorable trial were never published.)

En fjerde forsker fant at et legemiddel han gransket forårsaket uheldige reaksjoner. Han sendte manuskriptet til det sponsende firmaet for gjennomgåelse. Firmaet sverget aldri å finansiere noe arbeid igjen og publiserte en konkurrerende artikkel hvor de uheldige effekter knapt var nevnt. (...) (A fourth investigator found that a drug he was studying caused adverse reactions. He sent his manuscript to the sponsoring company for review. The company vowed never to fund his work again and published a competing article with scant mention of the adverse effects.)

Dr. Curt Furberg, professor i offentlig folkehelse ved Wake Forest University School of Medicine og ledende forsker for en studie hvor resultater var ugunstige for det sponsende firma, nektet å sette sitt navn på de publiserte resultater i en studie, fordi sponsoren ”forsøkte å bruke utilbørlig innflytelse på karakteren på det sluttlige arbeidet. Dette forsøk var så trykkende at vi følte at det hemmet den akademiske frihet.” (27) (...) (Dr. Curt Furberg, professor of public health sciences at Wake Forest University School of Medicine and principal investigator in a study whose results were unfavorable to the sponsoring company, refused to place his name on the published results of the study, because the sponsor was ”attempting to wield undue influence on the nature of the final paper. This effort was so oppressive that we felt it inhibited academic freedom. (27))

En sjette forsker beretter om to eksempler på fortielser i manuskripter angående negative studier hvor resultater var viktige å publisere. (...) (A sixth investigator recounted two examples of suppressed manuscripts regarding negative studies whose results were sufficiently important to publish.)

(Anm: (27) Applegate WB, Furberg CD, Byington RP, Grimm R Jr. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). JAMA 1997;277:297.)

Imidlertid, som en forsker beskrev det, ”når resultater favoriserer firmaet, er alt kjempeflott. Men når resultater er skuffende, er der vanligvis et forsøk på spin, bagatellisering, eller forandring av resultater. En CRO-leder tilføyde at ”industriens blokkering av publisering er et stort problem. De er nervøse for at dårlige data lekker ut til massemedia. Forskere innen kommersiell sektor er kanskje mindre bekymret enn de akademiske med kontraktsklausuler som garanterer deres rett til publisering, ved å gi industri større kontroll over publikasjonen. (...) (However, as one investigator described it, ”when results favour the company, everything is great. But when results are disappointing, there is commonly an effort to spin, downplay, or change findings. A CRO executive added that ”industry obstruction to publishing is a big problem.” They are nervous if bad data comes out and gets into the mass media. Investigators in the commercial sector may be less concerned than those in academia with contract clauses guaranteeing their right to publish, thereby giving industry greater control over publications.)

(Anm: WHO says Semler Research manipulated data and warns repeat studies may needed. The WHO has accused Semler Research of data fraud and said Mylan, Micro Labs, Lupin and Strides and others may need to repeat bioanalytical trials conducted by the CRO. (outsourcing-pharma.com 25.4.2016).)

(Anm: "Vi tar det säkra före det osäkra". I början av året fick en läkemedelsprövning i Frankrike förödande konsekvenser. Vi besökte en forskningsklinik i Sverige som genomför kliniska prövningar för att ta reda på hur det går till i Sverige. (…) Om CTC: CTC är ett svenskt kliniskt CRO, contract research organisation, som grundades 2011 och har sedan dess varit delaktiga i ett 90-tal studier. Där ingår ungefär 25 fas I-studier, varav sju av dem är first in human-studier. I Uppsala finns en sjukhusbaserad fas I-enhet inne på Akademiska sjukhuset. CTC har även två så kallade SMO-kliniker, en i Uppsala och en i Linköping. Det är en slags professionella forskningskliniker som enbart bedriver kliniska prövningar. CTCs team består främst av läkare, apotekare, forskningssjuksköterskor, projektledare och monitorer. (lakemedelsvarlden.se 31.3.2016).

- Industrien finansierer større andel av medisinsk forskning

Contract Research Organisations (Kontraktsforskningsorganisasjoner)
Truly independent research?
(Virkelig uavhengig forskning?)
BMJ 2008;337:a1332 (21 August)
Research contracted to commercial or academic organisations might sound less biased than that done by industry. But as Jeanne Lenzer reports, influence is hard to avoid

Drug and medical device companies are increasingly outsourcing clinical trials to commercial and academic contract research organisations (CROs). As well as cutting costs, this could potentially put desperately needed distance between sponsor and research product. If achieved, such distancing couldn’t come at a better time: a Harris Interactive poll shows that of the top 11 industry sectors, only tobacco companies had higher negative public opinion ratings than drug companies (76% and 52% respectively).1

Although the literature about the biasing effects of industry sponsorship on medical research is rapidly expanding, little is known about whether studies conducted by CROs are subject to similar biases. This raises the question whether research outsourced to CROs is genuinely independent or subject to influence from corporate sponsors. (...)

(Anm: Outsourcing (no.wikipedia.org).)

(Anm: Fri tilgang til forskningsresultater? (forskningsdata) (mintankesmie.no).)

(Anm: The hidden side of clinical trials | Sile Lane | TEDxMadrid (youtube.com).)

(Anm: Forvaltningsmakt og kunnskapspolitikk. Sammendrag. Helse- og omsorgsdepartementet benekter at de ønsker å styre forskninga i underliggende etater, og ser ingen problemer med at forskninga ligger under forvaltninga. Rus & Samfunn 05 / 2016 (Volum 9) Side: 33-35.)

(Anm: Frie forskere eller maktens lakeier? Abstrakt. Det går et skisma gjennom den samfunnsvitenskapelige rusforskningen. Ved første øyekast er det vanskelig å forstå hvorfor. Rus & Samfunn 05 / 2016 (Volum 9) Side: 36-40.)

(Anm: Nesten halvparten av alle studier som er gjennomført av store sponsorer i det siste tiåret er upublisert (Nearly half of all trials run by major sponsors in past decade are unpublished.) BMJ 2016;355:i5955 (Published 04 November 2016).)

(Anm: Who's not sharing their trial results? (trialstracker.ebmdatalab.net).)

(Anm: Transparency for patients: How much is too much? (pharmafile.com 11.10.2016).)

(Anm: Parlamentsmedlemmer hører at kliniske forsøk er byråkratiske, uklare, og forvirrende for forskere og pasienter. (…) "Det har vært en rekke kjente tilfeller hvor godkjente legemidler er basert på ufullstendig informasjon — og hvor den informasjonen som senere er stilt til rådighet har vist at legemidlet er ineffektivt eller faktisk skadelig.  (Clinical trials are bureaucratic, opaque, and offputting to researchers and patients, MPs hear.) BMJ 2013;346:f1711 (14 March 2013).)

Origin and funding of the most frequently cited papers in medicine: database analysis
BMJ, doi:10.1136/bmj.38768.420139.80 (published 17 March 2006)
Objective To evaluate changes in the role of academics and the sources of funding for the medical research cited most frequently over the past decade.

Design Database analysis.

Data sources Web of Knowledge database.

Methods For each year from 1994 to 2003, articles in the domain of clinical medicine that had been cited most often by the end of 2004 were identified. Changes in authors' affiliations and funding sources were evaluated.

Results Of the 289 frequently cited articles, most had at least one author with a university (76%) or hospital (57%) affiliation, and the proportion of articles with each type of affiliation was constant over time. Government or public funding was most common (60% of articles), followed by industry (36%). The proportion of most frequently cited articles funded by industry increased over time (odds ratio 1.17 per year, P=0.001) and was equal to the proportion funded by government or public sources by 2001. 65 of the 77 most cited randomised controlled trials received funding from industry, and the proportion increased significantly over time (odds ratio 1.59 per year, P=0.003). 18 of the 32 most cited trials published after 1999 were funded by industry alone.

Konklusjon Akademisk tilhørighet fortsetter å være fremtredende blant forfatterne av den hyppigst siterte medisinske forskning. Slik forskning er stadig oftere finansiert av industrien, ofte utelukkende . Akademikerne kan miste kontrollen på agandaen for klinisk forskning. (...) (Conclusion Academic affiliations remain prominent among the authors of the most frequently cited medical research. Such research is increasingly funded by industry, often exclusively so. Academics may be losing control of the clinical research agenda.)

Industry Is Funding Bigger Share of Medical Research
healthfinder.gov 17.3.2006
Dwindling participation of public, academic sectors troubles experts.

-- Industry is paying for more and more medical research, slowly shifting the lion's share of funding away from academia and to the private sector, a new study reveals.

The findings have experts worrying that academia is losing control of the clinical research agenda.

"Our findings suggest that while most highly cited papers in medicine are still authored or co-authored by people with university affiliations, there is a gradual change in the sources of funding," said Dr. John Ioannidis, senior author of the study and professor and chairman of the department of hygiene and epidemiology at the University of Ioannina School of Medicine in Greece.

According to Ioannidis, who also holds an appointment as professor of medicine at Tufts University School of Medicine in Boston, industry is currently funding almost all clinical trials most often cited by other scientists, and is now considered to have a large impact on medicine. In fact, "in half of these [studies] there is absolutely no other source of funding," he said.
The report appears in the March 18 issue of the British Medical Journal. (...)

Eighteen of the 32 most-cited trials published after 1999 were funded by industry, with no other sources of funding listed.

So, what's to be done? One solution would be to make sure all authors declare any and all interests, said the author of the accompanying commentary, Dr. Brendan Delaney, a professor of primary care at the University of Birmingham in England. Delaney said that, like many researchers, he has ties with several pharmaceutical companies, including Astra-Zeneca, Wyeth and Merck.

According to Ioannidis, "Funding for research should be increased, in particular government funding and funding from other public sources. Society should invest more in research."

"It is great to have funding from private sources, including for-profit ones, but it would be a pity if governmental funding for research, especially research that has a direct impact on the lives of people, cannot catch up," he continued. (...)

- Kommersialisering av kliniske forsøk - Risiko og nytte av CRO-boom

Commercializing Clinical Trials — Risks and Benefits of the CRO Boom (Kommersialisering av kliniske forsøk - Risiko og nytte av CRO-boom)
NEJM 2007;357:1365-1368 (October 4)
In a trend that has received surprisingly little attention, contract research organizations (CROs) have gradually taken over much of academia's traditional role in drug development over the past decade. They've been able to do so by offering greater speed and efficiency in conducting clinical trials than academic groups can, but questions have been raised about their qualifications, ethics, accountability, and degree of independence from their pharmaceutical-industry clients.

Annual CRO-industry revenues have increased from about $7 billion in 2001 to an estimated $17.8 billion today; of more than 1000 CROs in operation, the four largest — Quintiles, Covance, Pharmaceutical Product Development (PPD), and Charles River Laboratories — are now billion-dollar companies, and two others — Parexel and MDS Pharma Services — are worth more than $500 million each (see Figure 1).1 This growth reflects the industry's contribution to clinical trials: a study sponsored by the large CROs and conducted by the Tufts Center for the Study of Drug Development showed that 10 of the largest firms had enrolled more than 640,000 subjects in trials in 2004. According to the clinical-trials information company Thomson CenterWatch, CROs played a substantial role in 64% of phase 1, 2, and 3 clinical studies in 2003 (for about $7.6 billion in contracts), as compared with 28% in 1993 (for $1.6 billion) (see Figure 2).2

But some recent events have raised questions about whether the commercialization of clinical trials, in its current form, is in the best interest of science or the public. In 2005, a Bloomberg News report revealed the inadequate conditions and minimal oversight at a phase 1 and 2 clinical-trials unit housed in a converted Holiday Inn in south Florida and owned by the SFBC International CRO. With 675 beds, the site was the largest experimental-drug test center in North America. But SFBC's clinical-trials director was an unlicensed physician, and its Florida research subjects, many of them poor Hispanic immigrants lured by per-trial payments, enrolled without fully comprehending the risk of injury or death and were enticed to stay in trials in some cases by "backloading," in which the largest payments are made near the end of the trial. At an SFBC site in Montreal, a patient was allowed to remain in a trial despite having active tuberculosis; nine other trial participants later tested positive for the disease. The company, now called PharmaNet, shut down its Florida site and settled a resulting shareholder class action lawsuit for $28.5 million in August 2007. (...)

- Penger, matematikk og medisin

Money, Math And Medicine (Penger, matematikk og medisin)
forbes.com 3.11.2010
Quintiles founder Dennis Gillings has made a fortune doing the grunt work for drug companies.

The current state of drug research studies traces back to a 1975 phone call between an executive at what was then the world's largest drug company and a 30-year-old Brit with longish hair and bushy sideburns named Dennis Gillings. (...)

His thinking helped foment a revolution in drug development. Today Quintiles is the leader in a secretive and powerful $20 billion industry--outsourcing clinical trials. Over the past decade Gillings' company has conducted 4,700 trials in 2.7 million patients in over half the countries in the world. But exactly which trials is it doing? Quintiles won't say. It says its Big Pharma clients want this to remain a secret. Clinical research organizations (CROs) now have some role in almost all large clinical trials, compared with about a quarter in 1993. (...)

Quintiles conducted a key safety study of the diabetes drug Avandia that was publicly savaged by a Food & Drug Administration reviewer in July. GlaxoSmithKline ( GSK - news - people ) contended that the trial showed that Avandia did not cause heart attacks. But the reviewer found crucial errors in case report forms. Major heart problems in as many as a dozen Avandia patients had never been counted, he concluded. In the wake of the new evidence an expert committee voted to severely restrict the drug's use. Quintiles points to other FDA reports that did not identify any "systemic or pervasive findings" that would undermine the data. It maintains its monitoring systems were satisfactory.

CROs are "better than anyone" at compiling patient data, says Eric Topol, a Scripps Research Institute cardiologist who served on Quintiles' board of directors in the 1990s. But often "they overstep their bounds," he says. CROs are too beholden to their drug company clients to be trusted with analyzing trial results, as they increasingly have been doing, he says.

Robert Harrington, who directs the Duke Clinical Trial Research Institute, one of the few academic organizations big enough to compete with Quintiles, says that though CROs helped turn clinical trials into a professional medical activity, they aren't independent enough from their Big Pharma clients. He points to Quintiles ads aimed at drug companies that say, "The answer is yes." Harrington's reply: "The answer should not always be yes."

Quintiles says it does turn down drug company trials sometimes. Gillings calls Harrington's complaint "ridiculous" and says his company guards against ethical lapses with "a paranoid approach." "Academic medical centers are primarily focused on advances in medicine. But the logistics of managing a 20,000-patient trial across 50 countries is not their expertise. This is a hugely complex business, which isn't the same business as high-powered medicine."

Quintiles and other big CROs, including Covance (CVD - news - people) and Parexel, have benefited from the trend away from developing drugs for acute infectious diseases toward testing drugs that address chronic medical problems like Alzheimer's. This has led to ever bigger and more complex patient trials. Recent heart disease studies have followed 30,000 patients for years.

Billions of dollars in drug sales can hinge on obscure statistical issues. Put too few patients on a drug trial and you don't get approved. Too many and the competition beats you to market. Companies like Quintiles specialize in getting these answers right. (...)

- Mister samfunnet kontroll med forskningsagendaen?

Is society losing control of the medical research agenda? (Mister samfunnet kontroll med forskningsagendaen?)
BMJ 2006;332:1063-1064 (6 May)
Funding for medical research comes from three sources: government, charities, and industry. Research funded by industry should benefit the public, but as an aside to commercial interests. Patsopoulos et al compared the proportion of the most frequently cited articles in the Institute for Scientific Information database that were funded by public or industry sources over the past decade.1 They found a significant trend towards funding by industry, despite the continued dominance of academics as authors. If we take this as a robust finding, three questions arise: why is this happening; what are its implications; and what, if anything, should be done about it?

Academics may be losing control of clinical research
BMJ 2006;332 (6 May)
Academic affiliations remain prominent among authors of the most frequently cited medical research. However, such research is increasingly funded by industry, often exclusively so. Patsopoulos and colleagues (p 1061) identified the authors' affiliations and funding sources of the 289 most frequently cited articles of the Web of Knowledge database. Sixty per cent of the articles published during 1994-2003 and cited by the end of 2004 were funded by government or public funding, but the proportion of articles funded by industry alone increased over time; 18 of the 32 most cited trials published after 1999 were funded by industry alone. (...)

Diverse artikler

Kæmpe-CRO og medicinalgigant i strategisk samarbejde
medwatch.dk 16.5.2013
Verdens største kontraktforskningsfirma og en af verdens største medicinalselskaber har indgået et femårigt samarbejde, der rækker videre end traditionel outsourcing.

Tyske Merck Serono og amerikanske Quintiles har ifølge FierceBiotech annonceret et fem-årigt, eksklusivt samarbejde om den tyske gigants kliniske forsøg.
Sammen skal de forme og lede Mercks F&U-strategi, mens Quintiles administrerer planlægning af de kliniske forsøg og udførelse fra fase 1 gennem post-marketing-studier.

Ifølge Quintiles er det således en anderledes omfattende aftale i forhold til de gængse outsourcing-aftaler, man har set hidtil i industrien.

"Der er en række unikke aspekter i dette samarbejde, især det faktum, Quintiles vil være et stående medlem af et collaborative clinical operations team, der vil være ansvarlig for beslutninger vedrørende kliniske aktiviteter i tilknytning til Mercks udviklingsportefølje," siger en talsperson fra CRO-selskabet til FierceBiotech. (...)

Outsourced drug trials lack oversight, study says (Outsourcede legemiddelforsøk mangler tilsyn, ifølge studie)
ft.com 28.11.2012
Leading pharmaceuticals companies show no evidence that they adequately supervise the conduct of outsourced clinical drug trials, according to a new analysis released on Wednesday.

The Access to Medicine Index, a Dutch-based initiative that ranks top drug producers based on their activities in the developing world, expressed concern over contracting with third-party clinical research organisations (CROs), through which companies conduct their tests of experimental medicines on patients.

Its findings highlighted continued gaps in the system of drug testing, which is increasingly being outsourced and taking place in poorer countries. Testing in such countries is cheaper but raises ethical issues over treatment of participants if the drugs cause problems, and concerns about whether such communities can gain access to the drugs even if the new medicines work.

“Current industry performance in the area of accountability for CRO behaviour is far from meeting Index expectations for clinical trial participant wellbeing in developing countries,” the Index concluded.

It said few companies report robust monitoring of their conduct or enforced disciplinary action to ensure CROs act ethically and safely, leaving patients “vulnerable to clinical malpractice with little recourse to justice”.

The findings came as part of a broader analysis of companies’ operations and was last conducted in 2010. GlaxoSmithKline retained its top rating among its peers on measures including drug pricing and research and development of products relevant to the world’s poor.

It judged that 17 of the 20 leading companies had improved their ratings, with Johnson & Johnson jumping six places to number two following its acquisition of Crucell, which makes many vaccines for the developing world. Merck of Germany rose most places, while the four Japanese companies were at the bottom of the rankings.

The Index said just four companies – GSK, Merck of the US, Eisai and Sanofi – included evidence of disciplinary action against CSOs. None were transparent about which such contractors they hired.

Three-quarters of the companies now disclose tiered pricing – to offer discounts to patients in poorer countries – and 12 propose discounts even within countries to charge less to the poor without health coverage than to richer patients. But it highlighted no transparency over these prices.

Overall, the Index said there was greater accountability in the boardroom today over access to medicines, with more openness, targets and investment in drugs relevant to the poor. (...)

(Anm: Outsourcing (no.wikipedia.org).)

When Clinical Trials Are Farmed Out
•Books et al.
Science 2011;332(6036):1383 (17 June)
Medical Research for Hire The Political Economy of Pharmaceutical Clinical Trials by Jill A. Fisher (...)

Summary Drawing in part on her own fieldwork, Fisher explores the consequences of the increasing use of private-sector pharmaceutical trials. (...)

How much does the boss earn – CEO pay at CROs 2010
outsourcing-pharma.com 19.4.2011
Outsourcing-Pharma looks at the wages of CEOs at the big five public clinical CROs and how they compare to company earnings.

Following the end of their financial years the big five public clinical CROs (contract research organisations) have detailed executive compensation in regulatory filings. Outsourcing-Pharma has analysed these filings to create the following tables and graphs.

The first table shows the basic salary earned by each CEO. PPD changed leader in 2009 so data for the previous CEO, Fred Eshelman, is used for 2008. The second table shows total pay once bonuses, stock awards and other compensation are factored into earnings. (...)

Putting Contract Research Organisations on the Radar
somo.nl (February 2011)
An exploratory study on outsourcing of clinical trials by pharmaceutical companies to contract research organisations

It is a trend for pharmaceutical companies to contract third parties to conduct their clinical trials in order to test their drugs. This trend is referred to as outsourcing, and the companies that carry out the work are called contract research organisations (CROs). In addition, clinical trials are increasingly conducted in non-traditional trial regions, which are mainly low- and middle income countries. This trend is called offshoring. It is widely agreed that the offshoring of clinical trials to these regions should be scrutinised from an ethical perspective because of the vulnerability of the trial population. What happens when offshoring is combined with outsourcing? Do additional ethical risks arise when clinical trials are contracted out? Virtually all pharma ceutical companies publicly declare that they test their drugs in accordance with the highest ethical guidelines, such as the Declaration of Helsinki. But how do pharmaceutical companies safeguard their commitments when they outsource clinical trial activities to CROs in poor regions? These are the central questions that are addressed in this report. (...)

(Anm: Putting Contract Research Organisations on the Radar (somo.nl).

EMA to revise guidance on GMP tech transfer to CMOs
outsourcing-pharma.com 25.11.2010
The EMA is to develop guidance on transfer of analytical methods to tackle GMP issues arising from globalisation and increased use of CMOs.

Globalisation and outsourcing of manufacturing, as well as the rise of quality-by-design (QbD), have increased technology transfer within and between companies and countries. In light of these changes the European Medicines Agency (EMA) believes its Chapter 6 guidance needs revising.

The EMA is acting after good manufacturing practice (GMP) inspectors identified lack of test method validation, in the context of transfer of analytical methods, as the cause of a number of suspected out-of-specification (OOS) results.

Action to address the situation, which frequently occurs at contract quality control laboratories, has now been initiated by the EMA. A concept paper for the revised Chapter 6 was accepted in September, and published online this week, with a February 2011 deadline for comments. (...)

CRO Investment Opportunities Remain Compelling
seekingalpha.com 11.11.2010
The contract-research-organization industry continues to feel the pain from a host of factors that derailed drug development spending and disrupted the trend toward clinical trial outsourcing over the past two years. Many drugmakers looking to rein-in costs decided to delay development spending and cancel trials outright from late 2008 through 2009. These spending delays were then compounded by large pharmaceutical consolidation, reduction in biotech funding, and uncertainty surrounding health-care reform. Quarterly revenue growth for CROs is highly contingent upon new business bookings in prior quarters, particularly for companies specializing in clinical trials with long durations (late-stage providers). While the financial performance of the CRO industry remains below historical levels, new bookings appear to be back on track and cancellations have moderated compared to the crippling amounts experienced in 2009. (...)

ig Pharma Begins Outsourcing Research and Development
seekingalpha.com 14.10.2010
Big pharmaceutical companies seem to be taking tips from an unlikely source these days.

A decade ago, big mining companies had a big problem on their hands in the form of declining prices. With less incoming funds to spend on finding new deposits, they started thinking creatively… They let small entrepreneurial companies handle early-stage exploration, a difficult task in remote parts of the world. Then, if those operations struck it rich, the big miners swooped in to buy them out.

Drug development might not seem like it has much in common with such ventures. But it involves the same high-risk, high reward discovery efforts.

So the pharmaceuticals are going for the gold as well with this new approach. Cutting back on in-house research and development (R&D), they’re hiring contract research organizations (CROs) like Covance (NYSE: CVD) instead. (...)

Drug-Research Sector Shaking Up As Big Pharma Adjusts Strategy
online.wsj.com 20.9.2010
NEW YORK (Dow Jones)--Things are shaking up in the clinical-research industry as major pharmaceutical companies increasingly establish long-term relationships with a small pool of large contract-research organizations, or CROs.

In a recent example of this trend, GlaxoSmithKline PLC (GSK, GSK.LN) told Dow Jones Friday that it is negotiating contracts to enter "strategic relationships" with Parexel International Corp. (PRXL) and Pharmaceutical Product Development Inc. (PPDI), following the drug maker's announcement in June that it was moving from working with 30 CROs down to just a few.

Other large pharmaceutical companies moving in a similar direction include Merck & Co. (MRK) and (...)

MinTankesmie.no 21.11.2017 - Uke 47

Websidene er designet og tilrettelagt av Hein Tore Tønnesen © 2009