Om vitenskapelig uredelighet

Industrifinansieret forskning giver positive resultater op til fem gange oftere end offentligt finansieret forskning. (...) Det ville vi ikke acceptere på ret mange andre områder, og det giver naturligvis industrien et problem... (Berlingske Tidende 30.3.2005)

FLERE AV VÅRE mest ærbødige vitenskapelige tidsskrifter har nylig blitt besudlet av beskyldninger om vitenskapelig uredelighet. Sjokkerende? Vi bør være akkurat like sjokkert som inspektør Renault da han oppdaget gambling på Ricks kafé i Casablanca. (Los Angeles Times 7.1.2006)

Konklusjoner. Ufullstendig rapportering av resultater i publiserte artikler fra randomiserte forsøk er vanlig og er forbundet med statistisk ikke-signifikans. Den medisinske litteratur representerer derfor en selektiv og partisk delmengde studieresultater, og forsøksprotokoller bør gjøres offentlig tilgjengelige. (BMJ 2005;330:753 (2 April))

- Metodene eller analysene er manipulert (BMJ 16.11.2007) (BMJ 16.11.2007)

Om sponsorer og regionale komiteer for medisinsk forskningsetikk (REK-er)

- Negative studier kan bli puttet i skuffen fordi resultatet går mot det undersøkerne eller sponsorene ønsket, sier professor Arnold Berstad, leder for Regional komité for medisinsk forskningsetikk i Vest-Norge... (Tidsskr Nor Lægeforen 2005; 125: 2333 (8.9.2005))

- Industrifinansieret forskning giver positive resultater op til fem gange oftere end offentligt finansieret forskning

Industrisponsorerede forskere lyver om lægemidler
videnskab.dk 12.12.2012
Ny omfattende undersøgelse viser, at industrisponsorerede studier både overvurderer lægemidlers effekter og undertrykker deres bivirkninger, uden at læger og patienter har en chance for at opdage det.

Lægemiddelindustrien kan manipulere med deres data på mange måder - lige fra forskningsmetoder over analyser til præsentation af data.

Læger og patienter kan ikke altid stole på de konklusioner, forskere fremsætter, efter at de har afprøvet lægemidler i forsøg finansieret af lægemiddelvirksomheden. De sponsorerede studier er nemlig tit betydeligt mere positive over for industriens produkter, end tilsvarende forsøg der ikke er finansiereret af industrien.

Det viser en ny analyse af hele den videnskabelige litteratur på området – en såkaldt metaanalyse - som forskere fra Det Nordiske Cochrane Center på Rigshospitalet har gennemført. Ved at medtage 48 videnskabelige artikler, der tilsammen vurderer tusindvis af industrisponsorerede studiers resultater og konklusioner, er metaanalysen den største af sin art nogensinde. (...)

(Anm: Legemiddelindustrien (Big Pharma) (mintankesmie.no).)

(Anm: USAs mest beundrede lovbryter. (America's Most Admired Lawbreaker ) I løpet av 20 år utviklet Johnson & Johnson et kraftig legemiddel, promoterte det ulovlig overfor barn og eldre, skjulte bivirkninger og tjente milliarder av dollar. Dette er innsidehistorien. (Over the course of 20 years, Johnson & Johnson created a powerful drug, promoted it illegally to children and the elderly, covered up the side effects and made billions of dollars. This is the inside story.) (huffingtonpost.com 8.10.2015).)

(Anm: Statlig legemiddelkontroll (Statens legemiddelverk etc.) (mintankesmie.no).)

(Anm: Statlig hvitvasking av legemiddelinformasjon (Tidsskr Nor Legeforen 2010; 130:368 (25.2.2010).)

(Anm: Spinn i randomiserte kontrollerte studier (RCT) på angstlegemidler (antidepressiva) med et positivt opprinnelig resultat: en sammenligning av bekymringer uttrykt av den amerikanske legemiddelkontrollen FDA og den publiserte litteratur. (Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.) BMJ Open. 2017 Mar 29;7(3):e012886.)

(Anm: Lederartikler. Båndene som binder. Forfatternes økonomiske bånd kan være en kilde til skjevhet i studieforsøk og må gjøres kjent i sin helhet. (Editorials. The ties that bind. Authors’ financial ties may be a source of bias in trials and must be disclosed in full.) BMJ 2017;356:j176 (Published 17 January 2017).)

- Vanlige magesyrehemmere (syrepumpehemmere) knyttet til høyere risiko for død. (- Resultatene legges til en voksende liste over alvorlige helseproblemer knyttet til bruk av PPI, hvorav noen inkluderer nyreskader, Clostridium difficile-infeksjoner, beinbrudd hos personer med osteoporose og demens.)

(Anm: - Vanlige magesyrehemmere (syrepumpehemmere) knyttet til høyere risiko for død. Bruk av protonpumpehemmere (PPI) - en klasse legemidler tatt av millioner for å behandle halsbrann og redusere magesyre - er knyttet til en høyere risiko for tidlig død. (- Resultatene legges til en voksende liste over alvorlige helseproblemer knyttet til bruk av PPI, hvorav noen inkluderer nyreskader, Clostridium difficile-infeksjoner, beinbrudd hos personer med osteoporose og demens.) (- Kan øke risikoen for vevskader som skyldes oksidativ stress og telomerer som forkortes i celler. (medicalnewstoday.com 4.7.2017).)

(Anm: Protonpumpehemmere (proton pump inhibitors (PPIs) (syrepumpehemmere) (magesyrehemmere) (syrenøytraliserende midler (antacida)). (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

- Forskning bliver farlig, når de negative resultater glemmes. (…) Nyt dansk studie viser problemet. (...) For få negative resultater leder til falske konklusioner.

(Anm: Forskning bliver farlig, når de negative resultater glemmes. (…) Nyt dansk studie viser problemet. (...) For få negative resultater leder til falske konklusioner. (…) Manglende negative resultater har kostet liv. (…) Vores model viser, at vi er nødt til at få publiceret mindst 20 procent af de negative resultater, der produceres inden for hvert forskningsfelt, hvis vi skal undgå at lave falske antagelser om videnskabelig fakta. (videnskab.dk 5.1.2017).)

(Anm: Legemiddelindustriens fortjeneste var nesten det dobbelte av utgifter til forskning og utvikling (FoU-utgifter) i 2013, 2014 og 2015. (Pharmaceutical Industry Profits Are Nearly Double R&D Costs in 2013, 2014 and 2015) (…) En primær unnskyldning som legemiddelindustrien bruker for «prisøkning» er de høye kostnadene for forskning og utvikling (FoU) som disse firmaene betaler for å få nye legemidler på markedet. (citizen.org 27.3.2017).)

- Hemmelig funn avslører frekt "korstog" for å gjøre OxyContin til en blockbuster. (- Donuts-trikset er fremhevet i et av de interne dokumenter innhentet av STAT, som viser hvor langt Abbott gikk for å hanke inn leger for å gjøre OxyContin til en milliard-dollar-blockbuster. Selgerne kjøpte takeaway-middager til leger og møtte dem hos bokhandlere for å betale for deres innkjøp. I notater betegnet salgsteamet markedsføringen av legemidlet som et "korstog", og deres sjef kalte seg selv "Kongen av smerte» (King of Pain).)

(Anm: Hemmelig funn avslører frekt "korstog" for å gjøre OxyContin til en blockbuster. (Secret trove reveals bold ‘crusade’ to make OxyContin a blockbuster) (…) Knepet virket.) (…) I notater betegnet salgsteamet markedsføringen av legemidlet som et "korstog", og deres sjef kalte seg selv "Kongen av smerte» (King of Pain). (…) Donuts-trikset er fremhevet i et av de interne dokumenter innhentet av STAT, som viser hvor langt Abbott gikk for å hanke inn leger for å gjøre OxyContin til en milliard-dollar-blockbuster. Selgerne kjøpte takeaway-middager til leger og møtte dem hos bokhandlere for å betale for deres innkjøp. I notater betegnet salgsteamet markedsføringen av legemidlet som et "korstog", og deres sjef kalte seg selv "Kongen av smerte» (King of Pain).("The doughnut ploy, highlighted in a trove of internal documents obtained by STAT, shows the lengths to which Abbott went to hook in doctors and make OxyContin a billion-dollar blockbuster. The sales force bought takeout dinners for doctors and met them at bookstores to pay for their purchases. In memos, the sales team referred to the marketing of the drug as a “crusade,” and their boss called himself the “King of Pain.”) (statnews.com 23.9.2016)

(Anm: OxyContin (oxycodone hydrochloride) (Oksykodon) (mintankesmie.no).)

(Anm: Begrensninger av legemiddelkonsulenters markedsføringstaktikk endrer legers foreskrivende atferd. (Restricting pharmaceutical reps' marketing tactics changes physician prescribing behavior.) (…) Legemiddelkonsulenters besøk på legekontorer, kjent som "formidling", er den mest fremtredende formen for markedsføring fra legemiddelindustrien. "Formidlingen" involverer ofte små gaver til leger og deres ansatte, for eksempel måltider. Legemiddelfirmaer har mye større utgifter på "formidlings"-besøk enn på direkte markedsføring, eller til og med på forskning og utvikling av nye legemidler. Til tross for utbredelsen av "formidlingen" og de mange programmene for å regulere "formidlingen" var innil nå lite kjent om hvordan nivået på praksisen påvirker den forskrivende lege. (medicalnewstoday.com 4.5.2017).)

- Dette skjoldet av patenter beskytter verdens bestselgende legemiddel.

(Anm: Dette skjoldet av patenter beskytter verdens bestselgende legemiddel. (- Produktet med 16 milliarder dollar i årsomsetning. (...) - Det har dessuten vært tilgjengelig i nærmere 15 år. (…) Den virkelige utfordringen var den tilsynelatende ugjennomtrengelige festningen av patenter som AbbVie metodisk har bygget rundt sin verdsatte pengemaskin. (…) Humira, som står for mer enn 60 prosent av AbbVies inntekter har en listepris på mer enn 50 000 dollar per pasient. (bloomberg.com 7.9.2017).)

(Anm: Myten om mediers åpenhet. Hvorfor er virkelig fordomsfri og frisinnet debatt uvanlig? Hvorfor så få nye, uavhengige meningsytrere? Hvorfor møter mediene dem dels med motstand, dels med taushet? (aftenposten.no 7.9.2006).)

(Anm: Uheldige hendelser underrapporteres i målrettede terapiforsøk (studier). (AEs Are Underreported in Targeted Therapy Trials Copenhagen, Denmark) — Mer enn halvparten av 81 studier som førte til godkjenning av en målrettet terapi ble vurdert å ikke være helt åpen om risikoen for bivirkninger (AES), ifølge en ny studie. Granskerne antydet at underrapportering av bivirkninger kan være hyppigere forekommende ved målrettede behandlinger enn konvensjonelle cytotoksiske kjemoterapier..) (clinicaloncology.com 16.2.2017)

- Er det en reproduserbarhetskrise i vitenskapelig forskning?

(Anm: Er det en reproduserbarhetskrise i vitenskapelig forskning? (Is there a reproducibility crisis in science?) (…) Nyere studier, som undersøkte en rekke publiserte legemiddelstudier, klarte å gjenskape resultatene for mindre enn 25 % av dem - og tilsvarende resultater er blitt funnet i andre vitenskapelige disipliner. Hvordan bekjemper vi denne krisen for vitenskapelig ikke-reproduserbarhet? (ed.ted.com).)

(Anm: Spinn i randomiserte kontrollerte studier (RCT) på angstlegemidler (antidepressiva) med et positivt opprinnelig resultat: en sammenligning av bekymringer uttrykt av den amerikanske legemiddelkontrollen FDA og den publiserte litteratur. (Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.) BMJ Open. 2017 Mar 29;7(3):e012886.)

(Anm: LEGEMIDDELPENGER – FDA er avhengig av industrifinansiering; penger kommer «festet med strikk» (DRUG MONEY. FDA Depends on Industry Funding; Money Comes with “Strings Attached”) (pogo.org 1.12.2016).)

(Anm: LEGEMIDDELPENGER - I FDA-møter er "pasientstemmene" ofte finansiert av legemiddelfirmaer (DRUG MONEY - In FDA Meetings, "Voice" of the Patient Often Funded by Drug Companies) (pogo.org 3.12.2016).)

(Anm: Tjenestemenn anklaget også firmaene for at de i markedsføringen av legemidler til barn hadde unnlatt å opplyse om at Risperdal (risperidone) kan føre til hormonelle ubalanser som kan føre til brystvevutvikling og infertilitet (barnløshet) hos gutter og jenter. I markedsføringen av legemidlet for behandling av eldre mennesker med demens hadde firmaet opprettet et salgsteam for omsorg for eldre, til tross for at data fra en studie finansiert av Janssen som viste at risperidon doblet risikoen for dødsfall blant eldre mennesker, ifølge statlige tjenestemenn. BMJ 2015;351:h7018 (Published 31 December 2015).)

(Anm: - Således ble bruk av antipsykotika knyttet til en doblet risiko for lungebetennelse hos pasienter med AD (Alzheimers sykdom), og til og med en høyere relativ risikoøkning (3,43 ganger) blant dem uten AD. (…) Resultatene indikerer at bruk antipsykotika er knyttet til en høyere risiko for lungebetennelse uavhengig av alder, anvendt studiedesign, behandlingsvarighet, valg av legemidler eller samtidige sykdommer. (dgnews.docguide.com 30.8.2016).)

(Anm: Margaret McCartney: Valgfri offentliggjøring av utbetalinger er meningsløst. (Margaret McCartney: Optional disclosure of payments is pointless.) (- Og åpenhet anskueliggjør problemene: bør de som mottar tusenvis av pund fra industrien som "påtenkte ledere" sitte i paneler for utarbeidelse av nasjonale retningslinjer eller hjelpe til med å stake ut regjeringens politikk?) BMJ 2016;354:i3692 (Published 01 July 2016).)

(Anm: For mange retningslinjer for behandlinger er skrevet av eksperter med finansielle konflikter, viser studien. (statnews.com 22.8.2016).)

(Anm: Naturlig at dette er offentlig. OUS-lege Elisabeth Gulowsen Celius samtykket til offentliggjøring av honorarer. Hun er kritisk til kolleger som ikke har gjort det samme. – Det kan reise spørsmål om det er bindinger som ikke tåler dagens lys. (dagensmedisin.no 12.8.2016).)

(Anm: Resultater publisert i JAMA Internal Medicine antyder at ett enkelt gratis måltid kan øke sannsynligheten for at en lege vil foreskrive et bestemt legemiddel. (Findings published by JAMA Internal Medicine suggest that even a single free meal can boost the likelihood a doctor will prescribe a certain drug) (online.wsj.com 20.6.2016).)

(Anm: FDAs rådgivere på opioider sparket grunnet bånd til industrien, ifølge AP. (FDA's advisers on opioids booted for ties to industry, AP learns. Having been buffeted by controversy over its approval of addictive opioid drugs, the FDA is calling on a panel of experts to help it sort through the thorny issue. But even before the new panel met, it has been tinged by controversy itself, dismissing four advisers because of perceived ties to drugmakers.) (fiercepharma.com 8.7.2016).)

(Anm: Offentliggjøring av verdioverføringer. Legemiddelindustrien offentliggjør i dag alle verdioverføringer til helsepersonell og helseforetak. (lmi.no 30.6.2016).)

(Anm: Leder. Disclosure UK: åpenhet (offentliggjøring) bør ikke lenger være valgfritt BMJ. (Editorials. Disclosure UK: transparency should no longer be an optional extra) BMJ 2016;354:i3730 (Published 06 July 2016).)

(Anm: Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre (Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre) (Disclosure UK website gives “illusion of transparency,” says Goldacre) BMJ 2016;354:i3760BMJ 2016; 354 (Published 06 July 2016).)

(Anm: Reporting of financial and non-financial conflicts of interest by authors of systematic reviews: a methodological survey. (…) Conclusions Although close to half of the published systematic reviews report that authors (typically many) have conflicts of interest, more than half report that they do not. Authors reported individual conflicts of interest more frequently than institutional and non-financial conflicts of interest. BMJ Open 2016;6:e011997.)

- Lundbeck-rival dykker 40 pct efter dødsfald i Parkinsons-studier. (- Ifølge nyhedsbureauet havde selskabet observeret 7 tilfælde af sepsis, også kaldet blodforgiftning, med 5 dødsfald til følge på tværs af en række mellem- og senfasestudier med kandidaten.) (- Studierne med tozadenant vil fortsætte, men Acorda meddeler, at man nu vil øge overvågningen af patienternes blodtal i studierne.)

(Anm: Lundbeck-rival dykker 40 pct efter dødsfald i Parkinsons-studier. Et amerikansk selskab, der ligesom danske Lundbeck udvikler lægemidler mod Parkinsons sygdom, har set sin aktiepris falde med omkring 40 pct. onsdag, efter man meldte om fem dødsfald i kliniske studier med en lægemiddelkandidat. Det amerikanske biotekselskab Acorda Therapeutics meddelte onsdag, at flere forsøgspersoner er gået bort i kliniske studier med en lægemiddelkandidat mod Parkinsons sygdom.Det skriver Reuters.De kliniske problemer, som sendte selskabets aktiepris ned med små 40 pct. til 17 dollars stykket, skete i et fase 3-studie med kandidaten tozadenant. Ifølge nyhedsbureauet havde selskabet observeret 7 tilfælde af sepsis, også kaldet blodforgiftning, med 5 dødsfald til følge på tværs af en række mellem- og senfasestudier med kandidaten. Studierne med tozadenant vil fortsætte, men Acorda meddeler, at man nu vil øge overvågningen af patienternes blodtal i studierne. (medwatch.dk 16.11.2017).)

(Anm: - Legene som deklarerte de høyeste inntektene fra legemiddelfirmaer i Storbritannias nye database uttaler at åpenhet om utbetalingene bør være obligatorisk. (The doctors who declared the most earnings from drug companies in the United Kingdom’s new database have said that being transparent about payments should be mandatory.) BMJ 2016;354:i3716 (Published 04 July 2016).)

(Anm: Leger som mottar de største utbetalingene fra legemiddelfirmaer deklarerer dem ikke på nytt nettsted. (Doctors getting biggest payments from drug companies don’t declare them on new website. BMJ 2016;354:i3679 (Published 01 July 2016).)

(Anm: Association between payments from manufacturers of pharmaceuticals to physicians and regional prescribing: cross sectional ecological study. BMJ 2016;354:i4189 (Published 18 August 2016).)

(Anm: Medisinsk utstyr (mintankesmie.no).)

(Anm: Legemiddelprodusenter og medisinske utstyrsprodusenter betalte i fjor 6,5 milliarder dollar til leger og undervisningssykehus. (Drug and device makers paid $6.5 billion to docs and teaching hospitals last year.) (statnews.com 30.6.2016).)

(Anm: Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective. BMJ 2016;355:i5078 (Published 03 October 2016).)

(Anm: - Hadde medisinerne på et tidligere tidspunkt hatt et evolusjonært perspektiv på sin medisinering, ville vi ikke vært i den kritiske situasjon vi er kommet i med hensyn til resistens. (aftenposten.no 22.8.2016).)

(Anm: Antibiotika associeras med högre risk för tarmcancer. (…) Det här är första studien som visar på sambandet mellan antibiotikaanvändning och utveckling av adenom i tjock- och ändtarmen. Studien publiceras i den vetenskapliga tidskriften Gut. (…) Resultatet visade att långvarig antibiotikaanvändning tidigare i livet, i åldern 20 till 59 år, hade samband med diagnostiserade adenom. (lakemedelsvarlden.se 5.4.2017.)

- Hvorfor begår forskere uredelighet? (- I alle disse tilfellene observerte vi at forskere som arbeider i land hvor publikasjonene er motivert av pengebonuser har større risiko for uredelighet eller skjevhet.)

Why do researchers commit misconduct? A new preprint offers some clues
retractionwatch.com 14.4.2017
“Why Do Scientists Fabricate And Falsify Data?” That’s the start of the title of a new preprint posted on bioRxiv this week by researchers whose names Retraction Watch readers will likely find familiar. Daniele Fanelli, Rodrigo Costas, Ferric Fang (a member of the board of directors of our parent non-profit organization), Arturo Casadevall, and Elisabeth Bik have all studied misconduct, retractions, and bias. In the new preprint, they used a set of papers from PLOS ONE shown in earlier research to have included manipulated images to test what factors were linked to such misconduct. The results confirmed some earlier work, but also provided some evidence contradicting previous findings. We spoke to Fanelli by email.

Retraction Watch (RW): This paper builds on a previous study by three of your co-authors, on the rate of inappropriate image manipulation in the literature. Can you explain how it took advantage of those findings, and why that was an important data set?

Daniele Fanelli (DF): The data set in question is unique in offering a virtually unbiased proxy of the rate of scientific misconduct. Most data that we have about misconduct comes either from anonymous surveys or from retracted publications. Both of these sources have important limitations. Surveys are by definition reports of what people think or admit to have done, and usually come from a self-selected group of voluntary respondents. Retractions result from complex sociological processes and therefore their occurrence is determined by multiple uncontrollable factors, such as the policies of retracting journals, the policies of the country in which authors are working, the level of scrutiny that a journal or a field is subject to, the willingness of research institutions to cooperate in investigations, etc.

DF: Results obtained in this study largely resemble what we found on retractions and corrections (the latter interpreted as a proxy of research integrity) as well as bias in meta-analysis. In all these cases, we observed that researchers that work in countries in which publications are incentivized with cash-bonuses are at greater risk from misconduct or bias. We also consistently observe that the number of years a researcher has been in activity is inversely related to this risk – suggesting that early-career researchers are more likely to engage in misconduct or [questionable research practices (QRPs). A remarkable finding of this new study is that, in secondary analyses in which we focus on first authors working in Western countries, we seem to observe a positive and marginally significant association between first authors’ productivity and risk of data fabrication. This could be a surprising suggestion that, in some contexts, our naive predictions about pressures to publish might indeed be correct. However, these results are exploratory and need to be confirmed. (…)

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

(Anm: Autisme: tidlig dødsrisiko en "skjult krise" (- Den ulikhet i utfall for autistiske mennesker vist i disse data er skammelige. Vi kan ikke akseptere en situasjon hvor mange autistiske mennesker aldri vil oppleve sin 40-årsdag.) (- Alle som er involvert i å støtte folk med autismespekteret fra regjeringen rett ned til lokalt helsepersonell har et ansvar for å stå opp og begynne å redde liv så snart som mulig.) (medicalnewstoday.com 21.3.2016).)

(Anm: Association of anticholinergic burden with adverse effects in older people with intellectual disabilities: an observational cross-sectional study. Conclusions Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation. The British Journal of Psychiatry Dec 2016, 209 (6) 504-510.)

(Anm: New study links autism to mutations in mitochondrial DNA (medicalnewstoday.com 31.10.2016).)

(Anm: Økning i dødsfall blant pasienter med psykiske lidelser må etterforskes, sier parlamentsmedlem. (Rise in deaths of mental health patients needs investigating, says MP.) BMJ 2016;352:i518 (Published 26 January 2016).)

(Anm: Medisinske feil — den tredje største dødsårsaken i USA. Medisinske feil inkluderes ikke i dødsattester eller i rangeringen av dødsårsaker. (...) Medisinske feil "fører til mer enn 250 000 dødsfall i USA årlig". (Medical error—the third leading cause of death in the US. Medical error is not included on death certificates or in rankings of cause of death. (...) Medical error 'causes more than 250,000 deaths in the U.S. annually.) BMJ 2016;353:i2139 (Published 03 May 2016).)

(Anm: Forskere: Medisinske feil nå tredje største dødsårsak i USA (Researchers: Medical errors now third leading cause of death in United States) (washingtonpost.com 3.7.2016).)

(Anm: Legemiddelfirmaer har inngått forlik om påstander om villeding av leger om overlevelsesdata for kreft. (Drug companies settle claim of misleading doctors on cancer survival data) (- Medisinsk svindel sto for mer enn halvparten av 3,5 milliarder dollar som ble utbetalt i erstatninger i fjor. Vanligvis involverte dette beskyldninger om bestikkelser betalt for å generere falske pasienter eller unødvendige behandlinger og resepter som er belastet Medicare.) BMJ 2016;353:i3361 (Published 15 June 2016).)

(Anm: Den britiske regjeringen har drevet lobbyvirksomhet overfor EU-kommisjonen for å få vedtatt en mer avslappet tilnærming til reguleringer av legemidler, medisinsk utstyr og mat, ifølge et brev som BMJ har fått tilgang til. (The UK government has been lobbying the European Commission to adopt a more relaxed approach to regulating drugs, devices, and food, a letter seen by The BMJ has shown.) BMJ 2016;353:i3357 (Published 15 June 2016).)

(Anm: Gruppe (Transparency International) ber om flere tiltak for å takle korrupsjonen innen legemiddelindustrien. (Group calls for more to be done to tackle corruption in the pharmaceutical industry) (…) På begynnelsen av 2016 har én av 10 korrupsjonsundersøkelser i USA involvert legemiddelfirmaer, hvilket ifølge rapporten er et langt høyere antall saker enn det som involverer banksektoren. (BMJ 2016;353:i3099 (Published 02 June 2016).)

(Anm: Finanschef beskyldt for insiderhandel med pharma-tips. (- Sanjay Valvani er anklaget for at have handlet på tips fra en tidligere ansat i den amerikanske FDA-myndighed, som bl.a. godkender lægemidler, samt for at sende informationerne videre til kollegaen Christopher Plaford. (medwatch.dk 16.6.2016).)

(Anm: TEST UTVIKLET FOR Å OPPDAGE FARLIGE BIVIRKNINGER SLIK AT FÆRRE PASIENTER GIS UTRYGGE LEGEMIDLER (Test aims to detect dangerous side effects so that fewer patients are given unsafe drugs) (medicalnewstoday.com 19.12.2014).)

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

(Anm: Når er et synspunkt en interessekonflikt? (When is a point of view a conflict of interest?) BMJ 2016;355:i6194 (Published 23 November 2016).)

(Anm: Høyresiden har størst mistillit til journalistikken. (…) Videre mente 63 prosent at journalister favoriserer kilder som mener det samme som dem. (aftenposten.no 13.2.2017).)

(Anm: Mina Ghabel Lunde, journalist. Når kilder også er venner. Pressen skal unngå bindinger som skaper usikkerhet om lojalitet. Da kan ikke journalister omgås sine kilder privat. (aftenposten.no 8.2.2017).)

(Anm: Ingen gratis lunsj for leger: Sponsede måltider knyttet til flere resepter (No free lunch for docs: Sponsored meals linked to more prescriptions) (mmm-online.com 20.6.2016).)

(Anm: Pasientsikkerhet (rettssikkerhet) (mintankesmie.no).)

(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).)

(Anm: Industry sponsorship and research outcome. Editorial Group: Cochrane Methodology Review Group. The Cochrane Library (Published Online: 12 DEC 2012).)

(Anm: Spøkelsesforfattere (ghostwriters) (mintankesmie.no).)

(Anm: Skiftet fra akademiske til kommersielle legemiddelnettverk (CRO - Kontraktsforskningsorganisasjoner) (mintankesmie.no).)

(Anm: Åpenhet om data (datatransparens) er den eneste måten (Data transparency is the only way) Editor's Choice - Fiona Godlee, editor in chief (BMJ 2016;352:i1261).)

(Anm: Legemidlene virker ikke: en moderne medisinsk skandale. Legene som forskriver legemidler vet ikke at de ikke virker som de er ment å gjøre. Det gjør heller ikke deres pasienter. Produsentene vet det veldig godt, men de forteller det ikke. (The drugs don't work: a modern medical scandal.) (guardian.co.uk 21.9.2012).)

(Anm: Are clinical drug trials more marketing than science? (ER KLINISKE LEGEMIDDELFORSØK MER MARKEDSFØRING ENN VITENSKAP?) (…) Based on what we found, marketing trials probably occur more often than I first thought. Perhaps, because clinicians who are involved in a company-sponsored clinical trial significantly increase their prescribing preferences for the sponsor’s drug, irrespective of international guidelines, which is deeply disturbing when you think about it. (blogs.biomedcentral.com 21.1.2016).)

(Anm: How to use rhetoric to get what you want - Camille A. Langston (ed.ted.com).)

(Anm: Forførende entusiasme: 40 års forskning på Dr. Fox-effekten. (Uniped 02 / 2016 (Volum 9).)

(Anm: Characterisation of trials where marketing purposes have been influential in study design: a descriptive study. (…) CONCLUSIONS: We reached consensus that a fifth of drug trials published in the highest impact general medical journals in 2011 had features that were suggestive of being designed for marketing purposes. Each of the marketing trials appeared to have a unique combination of features reported in the journal publications. Trials. 2016 Jan 21;17(1):31.)

(Anm: Antidepressant Fails Depressed HF Patients. —No impact on depression scores or clinical outcomes in double-blind trial (medpagetoday.com 30.6.2016).)

(Anm: Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012. (…) CONCLUSIONS: Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. BMJ Open. 2015 Nov 12;5(11):e009758.)

(Anm: Statlig legemiddelkontroll (Statens legemiddelverk etc.) (mintankesmie.no).)

(Anm: Statlig hvitvasking av legemiddelinformasjon (Tidsskr Nor Legeforen 2010; 130:368 (25.2.2010).)

(Anm: Forskning bliver farlig, når de negative resultater glemmes. (…) Nyt dansk studie viser problemet. (...) For få negative resultater leder til falske konklusioner. (…) Manglende negative resultater har kostet liv. (…) Vores model viser, at vi er nødt til at få publiceret mindst 20 procent af de negative resultater, der produceres inden for hvert forskningsfelt, hvis vi skal undgå at lave falske antagelser om videnskabelig fakta. (videnskab.dk 5.1.2017).)

(Anm: Legemiddelindustriens fortjeneste var nesten det dobbelte av utgifter til forskning og utvikling (FoU-utgifter) i 2013, 2014 og 2015. (Pharmaceutical Industry Profits Are Nearly Double R&D Costs in 2013, 2014 and 2015) (…) En primær unnskyldning som legemiddelindustrien bruker for «prisøkning» er de høye kostnadene for forskning og utvikling (FoU) som disse firmaene betaler for å få nye legemidler på markedet. (citizen.org 27.3.2017).)

- Undersøgelse rokker ved industriens forskning

Undersøgelse rokker ved industriens forskning
Berlingske Tidende 30.3.2005
Industrifinansieret forskning giver positive resultater op til fem gange oftere end offentligt finansieret forskning. (...)

- Der er en forskydning mellem privat og offentlig forskning. Det har længe været et diskussionsemne, der breder sig til flere og flere områder af den industri-finansierede forskning, siger Annette Winkel Schwarz, der er leder af Danmarks Tekniske Videncenter under Danmarks Tekniske Universitet. (...)

Analyseenheden The Copenhagen Trial Unit på Rigshospitalet står bag undersøgelsen og har analyseret både behandlingseffekt og bivirkninger ved en række lægemidler og sammenlignet sine resultater med producenternes.

Konklusionen er, at der i langt fra alle tilfælde er videnskabeligt belæg for de private forskeres positive konklusioner. Tvært imod, fremgår det af undersøgelsen, og det er symptomet på et alvorligt problem, mener læge og direktør Peter Gøtzsche fra Nordic Cochrane Centre i København:

- Vi ser samtidig, at lægemiddelindustrien tester sine egne produkter. Det ville vi ikke acceptere på ret mange andre områder, og det giver naturligvis industrien et problem, siger han.

Den offentlige forskning er mere innovativ end den industrifinansierede fortæller Peter Gøtzsche. Det er nemlig for nyligt kommet frem, at der er flere penge i at udvikle produkter, der ligner de produkter, der allerede er på markedet, fortæller han.

- Det er belyst i en analyse, at de store gennembrud inden for eksempel lægemidler og medicinsk behandling fortrinsvis er kommet fra den offentligt finansierede forskning, siger Peter Gøtzsche. (...)

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

(Anm: - Reseptbelagte legemidler blir sett på som velsignet av legemiddelkontrollen FDA, mens foreldre og barn oversvømmes av stadig mer aggressiv reklame fra legemiddelfirmaer med meldinger om at disse substansene er trygge, populære, og fordelaktige. (medicalnewstoday.com 27.3.2015).)

(Anm: Peter Gøtzsche: »Én mand kan godt ændre videnskaben«. Han har sammenlignet medicinalindustrien med Hitlerjugend og har fået en stor del af den danske psykiaterstab på nakken, da han for nylig udgav bogen ’Dødelig psykiatri og organiseret fornægtelse’. Mød Peter Gøtzsche; internationalt anerkendt professor, som ikke er bange for at være udiplomatisk. (videnskab.dk 13.11.2015).)

- Studie finner rapportering av resultater fra kliniske forsøk ikke tilfredsstillende, inkonsekvent (ulogisk)

Study finds outcome data in clinical trials reported inadequately, inconsistently
worldpharmanews.com 20.5.2014
Det er et økende offentlig press for å rapportere resultatene av alle kliniske forsøk for å eliminere publikasjonsskjevhet og forbedre offentlig tilgang. Imidlertid har granskere som bruker Verdens helseorganisasjons internasjonale Clinical Trials Registry Platform (ICTRP) til å bygge opp en database over kliniske studier som involverer kronisk smerte støtt på flere utfordringer. De beskriver farene og fallgruver ved bruk av ICTRP og foreslår alternative strategier for å forbedre rapportering fra kliniske studier. Denne viktige og innsiktsfulle studie er publisert i augustutgaven av tidsskriftet PAIN ®. (There is increasing public pressure to report the results of all clinical trials to eliminate publication bias and improve public access. However, investigators using the World Health Organization's International Clinical Trials Registry Platform (ICTRP) to build a database of clinical trials involving chronic pain have encountered several challenges. They describe the perils and pitfalls of using the ICTRP and propose alternative strategies to improve clinical trials reporting. This important and insightful study is published in the August issue of the journal PAIN®.)

Amerikansk lov krever allerede at oppsummerte resultater skal postes på ClinicalTrials.gov, en tjeneste hos National Institutes of Health, i løpet av ett studieåretter etter ferdigstillelse for visse kategorier av industrisponsede forsøk. Lovgivning for mandat på datapublisering innen ett studieår etter ferdigstillelse, uavhengig av resultater er under vurdering hos EU. Så langt er det dårlig samsvar med amerikansk lov . (U.S. law already requires posting summarized results on ClinicalTrials.gov, a service of the National Institutes of Health, within one year of study completion for certain categories of industry-sponsored trials. Legislation mandating data publication within one year of study completion, irrespective of outcome, is under consideration in the European Union. Yet compliance with the U.S. law is poor.)

"Selv om kliniske forsøksregistre letter publikums tilgang til grunnleggende forsøksinformasjon fant vi at tilgang til objektive forsøksresultater fortsatt er mangelfull. Et bekymringsfullt stort antall studier har ingen publiserte resultater i det hele tatt eller er nevnt bare i sponsors pressemeldinger. Nyere analyser har viser at bare 25 - 35 % av de kliniske studier som krever studieresultater lagt ut på ClinicalTrials.gov faktisk gjør det, "sier senior etterforsker Michael C. Rowbotham, MD, vitenskapelig direktør ved California Pacific Medical Center Research Institute i San Francisco. (...) ("Although clinical trial registries facilitate public access to basic trial information, we found that access to unbiased trial results is still inadequate. A distressingly large number of trials have no published results at all or are mentioned only in sponsor press releases. Recent analyses have found that only 25-35% of clinical trials required to post study results on ClinicalTrials.gov actually do so," comments senior investigator Michael C. Rowbotham, MD, scientific director of the California Pacific Medical Center Research Institute in San Francisco.)

- Forsøk på antidepressiva ekskluderer de fleste pasienter med depresjoner "i virkelighetens verden"

Antidepressant trials exclude most 'real world' patients with depression.
medicalnewstoday.com 15.7.2015
More than 80 percent of people with depression in the general population aren't eligible for clinical trials of antidepressant drugs, according to a study in the Journal of Psychiatric Practice. The journal is published by Wolters Kluwer.

At least five patients would need to be screened to enroll just one patient meeting the typical inclusion and exclusion criteria for antidepressant registration trials (ARTs), suggests the new research by Drs. Sheldon Preskorn and Matthew Macaluso of University of Kansas School of Medicine-Wichita and Dr. Madhukar Trivedi of Southwestern Medical School, Dallas. The study highlights some major differences between patients with depression seen in everyday clinical practice and those enrolled in ARTs--the studies of antidepressants that lead to FDA drug approval.

Most Patients with Major Depression Aren't Eligible for ARTs

Antidepressant registration trials use certain inclusion and exclusion criteria to create a group of patients with similar characteristics. These criteria increase the chances of detecting true drug effects, while reducing "false signals" of safety problems or side effects. For example, ARTs commonly exclude patients with other medical problems--if their illness worsened during the study, it might raise inaccurate safety concerns about the drug being studied.

To find out how these inclusion and exclusion criteria affect patient selection for ARTs, the researchers analyzed more than 4,000 patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Funded by the National Institute of Mental Health, STAR*D was the largest and longest study of depression treatment ever conducted. To ensure that the "real world" population of patients with depression was represented, STAR*D used minimal exclusion criteria.

The researchers found that more than 82 percent of STAR*D patients would not be eligible for enrollment in current ARTs, based on a list of "usual" inclusion and exclusion criteria. Fourteen percent would be excluded on the basis of age alone--that's because most ARTs exclude patients older than 65. Another 15 percent would be excluded because their depression was less severe than a commonly used cutoff point.

More than 20 percent of STAR*D patients would be excluded from ARTs because of a "clinically significant or unstable general medical condition." Twenty-one percent of women would be excluded because they were not using birth control to prevent pregnancy during the study.

Because many ARTs use stricter criteria, the true exclusion rate is probably even higher, the authors note. For example, more recent studies have used even higher severity thresholds for enrollment, which would eliminate more than 90 percent of the STAR*D population. The researchers also point out that all of the STAR*D patients had obviously agreed to participate in that research study--which is something many people with depression might be unwilling to do.

The researchers hope their work will help drug developers understand how inclusion and exclusion criteria may affect enrollment in ARTs, and help them in developing an appropriate recruitment plan and timeline. "The timelines in most drug studies are unrealistically short and their recruitment plans are often woefully inadequate, resulting in studies that take longer than expected to complete and frequent budget overruns," Drs. Preskorn, Macaluso, and Trivdei write. Failure to consider the effort needed for ART recruitment might lead to lost revenue, delays in bringing a drug to market, or failure to develop a potentially effective medication.

The findings may also help to explain to healthcare practitioners why ARTs tend to overestimate the benefits of antidepressant treatment in "real world" patients with depression. "Obviously," the researchers add, "the more patients who are excluded from the ARTs, the greater the chances that the results will not generalize to the routine clinical practice." (…)

- Karsten Juhl Jørgensen, seniorforsker og dr.med. på det Det Nordiske Cochrane Center på Rigshospitalet, mener, at kliniske forsøg bør foregå uden for virksomhedernes eget regi.

Pharmadanmark: Stop med kritik – kom med forslag
pharmadanmark.dk 16.10.2015
Karsten Juhl Jørgensen, seniorforsker og dr.med. på det Det Nordiske Cochrane Center på Rigshospitalet, mener, at kliniske forsøg bør foregå uden for virksomhedernes eget regi. Antje Marquardsen, formand for Pharmadanmark efterspørger realistiske og finansieret alternative forslag.

edicinalindustrien manipulerer forskningsresultater til at se bedre ud og dermed gøre deres dyre medicin til nødvendige behandlingsmetoder, lyder kritikken fra Cochrane Center på Rigshospitalet i Orienteringen på P1 i mandags.
Karsten Juhl Jørgensen, seniorforsker og dr.med. på det Det Nordiske Cochrane Center på Rigshospitalet, siger, at der heller ikke er nok kontrol med medicinalmedicinen.

Han mener, at det helt grundlæggende er en fejl, at man lader medicinalindustrien sikkerhedsteste egne produkter.

»Gennemgangen af de studier, som medicinalindustrien producerer er slet ikke grundig nok. Vi ser igen og igen, at når uafhængige forskere får adgang til råmateriale fra kliniske forsøg, så ser virkeligheden meget anderledes ud, end hvordan det ser ud i medicinalindustriens videnskabelige litteratur,« siger Karsten Juhl Jørgensen.

Derfor opfordrer han til, at kliniske forsøg bør foregå uden for virksomhedernes eget regi. Men strukturen er der bare ikke til det i dag.
»Det vil kræve en omlægning af den måde, som man godkender lægemidler på. Jeg tror dog ikke, at vi får et sandfærdigt billede af, hvad de dyre lægemidler kan, ikke kan og hvilke skadevirkninger, der er, før vi får bedømmelser fra en uafhængig instans,« understreger han.

Formand for Pharmadanmark Antje Marquardsen synes, at det er ærgerligt, at hans udtalelser står uimodsagt i programmet. (…)

- Økonomiske bånd som kan binde - Grav dypere for å finne linker

Financial ties that might bind - Delve deeper to find the links (Økonomiske bånd som kan binde - Grav dypere for å finne linker)
BMJ 2008;336:59 (12 January)
Funn av Yank et al om ingen forbindelser mellom resultater i metaanalyser og økonomiske bånd er overraskende gitt de store manglene for rapportering av skadelige konsekvenser i forsøk, som utelukkende var finansiert av industrien (median 56 % per forsøk), enn blant forsøk som ikke var det1 (27 %).2 Det er åpenbart at Oxman-Guyatt mål på vitenskapelig kvalitet på forskninggjennomganger, som er brukt av Yank et al, ikke kan fange opp avvik i opprinnelige forskningsprotokoller og deres publiserte skjemaer og de selektive rapporteringer av resultater, som begge er utbredt i randomiserte forsøk.2 (The finding by Yank et al of no connection between results in meta-analyses and financial ties is surprising,1 given the greater deficiencies for reporting of harm outcomes among trials that were solely funded by industry (median 56% per trial) than among trials that were not (27%).2 Evidently the Oxman-Guyatt measure of scientific quality of research reviews used by Yank et al cannot capture discrepancies in original research protocols and their published form and the selective reporting of outcomes, both of which are prevalent in randomised trials.2 )

For det første handler det om skjevhet (bias) ved rapportering av resultater i tillegg til publikasjonskjevhet som drar i samme retning for hele studier hvilket gir oppblåste anslag over effekter på behandlinger.2 (Firstly, bias in reporting outcomes acts in addition to and in the same direction as publication bias of entire studies to produce inflated estimates of the effects of treatment.2)

For det andre er motgiften å kreve registrering av alle forsøk og protokoller i det offentlige domene (nettsteder) før fullføringen av studien for å sikre at de gjøres tilgjengelige sammen med at ethvert manuskript som gjennomgår fagfellevurdering for tidsskriftspublisering. (Secondly, the antidote is to require registration of all trials and protocols in the public domain before completing the study and to assure that they be made available along with any manuscript undergoing peer review for journal publication.)

For det tredje er tro på at innsamlede rådata liksom er upåvirket av det som går på forskningsdesign, prøvetaking og måling feilaktig. Epsteins avvisning av betydningen av resultatene til Yank et al og hans drøye argumenter for å rettferdiggjøre problematisk praksis for legemidler og produsenter av medisinsk utstyr er basert på slike misforståelser.3 Epsteins påstand om at ingenting i arbeidet med Yank et al antyder at rådata fra legemiddelsponsede studier var ufullstendige 3 ser bort fra bruk av Oxman-Guyatts mål på forskningskvalitet som en statistisk kontrollvariabel. (...) (Thirdly, belief that the collected raw data are somehow unaffected by the artefacts of research design, sampling, and measurement is mistaken. Epstein’s dismissal of the importance of the findings of Yank et al and his strained argument to justify problematic practices of the drug and medical device industry are based on such misunderstanding.3 Epstein’s assertion that nothing in the work of Yank et al suggests that the raw data from the drug sponsored studies were defective3 overlooks the use of the Oxman-Guyatt measure of research quality as a statistical control variable)

(Anm: Pasientsikkerhet (rettssikkerhet) (mintankesmie.no).)

(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).)

- Legemiddelforsøk ikke representative, ifølge forskere

Drug Trials Not Representative, Researchers Charge (Legemiddelforsøk ikke representative, ifølge forskere)
medpagetoday.com 27.12.2011
Few major randomized, controlled clinical trials examine the effects of a drug in patients who have multiple chronic conditions, even though more than one-quarter of all Americans are living with at least two chronic health conditions, researchers reported.

The proportion is even greater for older individuals, two out of three of whom are likely to have at least two chronic health conditions, according to Alejandro Jadad, MD, and colleagues from the Centre for Health, Wellness and Cancer Survivorship at the University Health Network in Toronto.

That means that most trials on which the FDA bases its approval of new drugs are not generalizable to the U.S. population, they wrote in a research letter published in the Dec. 28 issue of the Journal of the American Medical Association. (...)

(Anm: Consideration of Multiple Chronic Diseases in Randomized Controlled Trials. JAMA. 2011;306(24):2670-2672 (December 28).)

(Anm: Legemiddelindustrien (Big Pharma) (mintankesmie.no).)

(Anm: USAs mest beundrede lovbryter. (America's Most Admired Lawbreaker ) I løpet av 20 år utviklet Johnson & Johnson et kraftig legemiddel, promoterte det ulovlig overfor barn og eldre, skjulte bivirkninger og tjente milliarder av dollar. Dette er innsidehistorien. (Over the course of 20 years, Johnson & Johnson created a powerful drug, promoted it illegally to children and the elderly, covered up the side effects and made billions of dollars. This is the inside story.) (huffingtonpost.com 8.10.2015).)

(Anm: Tjenestemenn anklaget også firmaene for at de i markedsføringen av legemidler til barn hadde unnlatt å opplyse om at Risperdal (risperidone) kan føre til hormonelle ubalanser som kan føre til brystvevutvikling og infertilitet (barnløshet) hos gutter og jenter. I markedsføringen av legemidlet for behandling av eldre mennesker med demens hadde firmaet opprettet et salgsteam for omsorg for eldre, til tross for at data fra en studie finansiert av Janssen som viste at risperidon doblet risikoen for dødsfall blant eldre mennesker, ifølge statlige tjenestemenn. BMJ 2015;351:h7018 (Published 31 December 2015).)

(Anm: - Således ble bruk av antipsykotika knyttet til en doblet risiko for lungebetennelse hos pasienter med AD (Alzheimers sykdom), og til og med en høyere relativ risikoøkning (3,43 ganger) blant dem uten AD. (…) Resultatene indikerer at bruk antipsykotika er knyttet til en høyere risiko for lungebetennelse uavhengig av alder, anvendt studiedesign, behandlingsvarighet, valg av legemidler eller samtidige sykdommer. (dgnews.docguide.com 30.8.2016).)

(Anm: Among antidementia drugs, memantine is associated with the highest risk of pneumonia. A recent study from the University of Eastern Finland shows that among users of antidementia drugs, persons using memantine have the highest risk of pneumonia. The use of rivastigmine patches is associated with an increased risk as well. (medicalnewstoday.com 24.11.2016).)

(Anm: Publikum ønsker tøffere straffetiltak mot uansvarlig atferd i næringslivet. (- Resultatene viste en sterk offentlig bekymring for skjevhet i rettssystemet) (theconversation.com 25.7.2016).)

(Anm: Superrike skattesnytarar. (…) Denne verksemda vil ikkje ta slutt før dei som legg til rette for hemmeleghald og skatteunndraging – bankar, advokatar og rådgjevarar – opplever ein reell risiko for å bli straffa for å utføre slike tenester.) (dn.no 3.7.2017).)

(Anm: EU-kommissionen visste om VW-fusket. (- Misstankarna inom kommissionen väcktes till liv när dess experter insåg att luftkvaliteten i städer inte förbättrades som förväntat efter de strängare utsläppskraven för bilar som infördes 2007, enligt Der Spiegel.) (nyteknik.se 15.7.2016).)

(Anm: Volkswagen mistenkt for å ha villedet EUs investeringsbank. Volkswagen er mistenkt for å ha brukt et lån fra Den europeiske investeringsbanken (EIB) til å utvikle teknologi som åpnet for juks med utslippstester. Sjefen for den europeiske investeringsbanken (EIB) Werner Hoyer er skuffet over Volkswagen. (dn.no 2.8.2017).)

(Anm: VW-chef erkänner bedrägeri. En högt uppsatt chef på tyska Volkswagen (VW) i USA, inblandad i avgasskandalen, erkänner bedrägeri, meddelade en talesperson för domstolen i Detroit på tisdagen. (nyteknik.se 26.7.2017).)

(Anm: VW-topp sier seg skyldig – risikerer 169 år i fengsel. Den tidligere VW-toppen i USA, Oliver Schmidt, innrømmer å ha forsøkt å dekke over utslippsjukset. Nå risikerer han mange år bak murene. (tv2.no 28.7.2017).)

(Anm: Tidligere Volkswagen-ingeniør dømt til fengsel. En tidligere ingeniør i Volkswagen får 40 måneders fengsel etter Volkswagen-skandalen. (vg.no 25.8.2017).)

(Anm: Dieselskandalen truer tysk økonomi. Den tyske dieselskandalen utgjør en risiko for landets økonomi, opplyser Tysklands finansdepartement i en rapport mandag. Dieselskandalen oppsto for nesten to år siden, da det ble kjent at Volkswagen jukset med utslippstallene. Her monterer tyske arbeidere dieselmotorer på en Volkswagen-fabrikk i Chemnitz i Tyskland. (dn.no 21.8.2017).)

(Anm: -1200 vil dø av utslipp fra Volkswagens «juksebiler». Amerikanske forskere har undersøkt konsekvensene av utslippsjuks. (…) Det er forskere ved universitetet MIT i USA som har sett nærmere på konsekvensene av Volkswagens utslippsjuks. (dagbladet.no 3.3.2017).)

(Anm: Dieseljuks. Forskere har funnet den skjulte koden i juksebilene til Volkswagen. Gikk langt for å hindre at det var mulig å teste det virkelige utslippet. (…) Nå har de funnet svaret, gjemt i programvaren til bilene, melder University of California San Diego. (…) Resultatene er publisert i en rapport (PDF), som blir lagt frem frem under IEEE Symposium on Security and Privacy i San Francisco denne uken. Under vanlig bruk, slipper bilene ut inntil 40 ganger mer NOx enn tillatt. Utslippsavsløring: Skrur av eksosrensingen allerede ved 17 grader (tu.no 23.5.2017).)

(Anm: Research. The Volkswagen Emissions Scandal Could Shorten Thousands of Lives, Study Says (time.com 3.3.2017).)

(Anm: VW-sjef pågrepet i USA En høytstående sjef i Volkswagen i USA har i kjølvannet av dieselskandalen blitt pågrepet av FBI, mistenkt for bedrageri, ifølge The New York Times. Oliver Schmidt ble ifølge den amerikanske avisa pågrepet lørdag. (nrk.no 9.1.2017).)

(Anm: Volkswagen må betale 36 milliarder kroner etter utslippsjukset. (aftenposten.no 11.1.2017).)

(Anm: Volkswagen trolig spart for milliarder i USA. En dommer i USA har avvist et søksmål mot Volkswagen, noe som kan spare den tyske bilprodusenten for milliarder av dollar i utbetalinger. Avgjørelsen kan avskrekke en rekke amerikanske stater fra å saksøke Volkswagen etter utslippsskandalen som har fulgt bilprodusenten i nesten to år. Den føderale dommeren Charles Breyer avviste søksmålet fra delstaten Wyoming med henvisning til at den aktuelle forurensningsloven må reguleres sentralt og ikke av de amerikanske delstatene. (dn.no 1.9.2017).)

(Anm: Tysk avis: VW-sjefen godkjente dekkoperasjon. Martin Winterkorn, avgått konsernsjef i Volkswagen, godkjente en plan om å holde tilbake informasjon fra amerikanske myndigheter, skriver Bild. (e24.no 26.9.2016).)

(Anm: VW må betale 2,8 milliarder dollar i bot for dieseljuks. Beløpet tilsvarer over 24 milliarder kroner. (dagbladet.no 21.4.2017).)

(Anm: Nobelprisvinner trekker seg fra Panama-gransking. (…) Begrunnelsen er at granskingen vanskeliggjøres av hemmelighold og manglende åpenhet.) (…) Pieth sier det blant annet finnes beviser for hvitvasking av penger fra barneprostitusjon i Panama-dokumentene. (dn.no 6.8.2016).)

(Anm: Margaret McCartney: Valgfri offentliggjøring av utbetalinger er meningsløst. (Margaret McCartney: Optional disclosure of payments is pointless.) (- Og åpenhet anskueliggjør problemene: bør de som mottar tusenvis av pund fra industrien som "påtenkte ledere" sitte i paneler for utarbeidelse av nasjonale retningslinjer eller hjelpe til med å stake ut regjeringens politikk?) BMJ 2016;354:i3692 (Published 01 July 2016).)

(Anm: For mange retningslinjer for behandlinger er skrevet av eksperter med finansielle konflikter, viser studien. (statnews.com 22.8.2016).)

(Anm: Naturlig at dette er offentlig. OUS-lege Elisabeth Gulowsen Celius samtykket til offentliggjøring av honorarer. Hun er kritisk til kolleger som ikke har gjort det samme. – Det kan reise spørsmål om det er bindinger som ikke tåler dagens lys. (dagensmedisin.no 12.8.2016).)

(Anm: Resultater publisert i JAMA Internal Medicine antyder at ett enkelt gratis måltid kan øke sannsynligheten for at en lege vil foreskrive et bestemt legemiddel. (Findings published by JAMA Internal Medicine suggest that even a single free meal can boost the likelihood a doctor will prescribe a certain drug) (online.wsj.com 20.6.2016).)

(Anm: FDAs rådgivere på opioider sparket grunnet bånd til industrien, ifølge AP. (FDA's advisers on opioids booted for ties to industry, AP learns. Having been buffeted by controversy over its approval of addictive opioid drugs, the FDA is calling on a panel of experts to help it sort through the thorny issue. But even before the new panel met, it has been tinged by controversy itself, dismissing four advisers because of perceived ties to drugmakers.) (fiercepharma.com 8.7.2016).)

(Anm: Offentliggjøring av verdioverføringer. Legemiddelindustrien offentliggjør i dag alle verdioverføringer til helsepersonell og helseforetak. (lmi.no 30.6.2016).)

(Anm: Leder. Disclosure UK: åpenhet (offentliggjøring) bør ikke lenger være valgfritt BMJ. (Editorials. Disclosure UK: transparency should no longer be an optional extra) BMJ 2016;354:i3730 (Published 06 July 2016).)

(Anm: Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre (Disclosure UKs nettsted gir en "illusjon av åpenhet", sier Goldacre) (Disclosure UK website gives “illusion of transparency,” says Goldacre) BMJ 2016;354:i3760BMJ 2016; 354 (Published 06 July 2016).)

(Anm: Reporting of financial and non-financial conflicts of interest by authors of systematic reviews: a methodological survey. (…) Conclusions Although close to half of the published systematic reviews report that authors (typically many) have conflicts of interest, more than half report that they do not. Authors reported individual conflicts of interest more frequently than institutional and non-financial conflicts of interest. BMJ Open 2016;6:e011997.)

(Anm: - Legene som deklarerte de høyeste inntektene fra legemiddelfirmaer i Storbritannias nye database uttaler at åpenhet om utbetalingene bør være obligatorisk. (The doctors who declared the most earnings from drug companies in the United Kingdom’s new database have said that being transparent about payments should be mandatory.) BMJ 2016;354:i3716 (Published 04 July 2016).)

(Anm: Leger som mottar de største utbetalingene fra legemiddelfirmaer deklarerer dem ikke på nytt nettsted. (Doctors getting biggest payments from drug companies don’t declare them on new website. BMJ 2016;354:i3679 (Published 01 July 2016).)

(Anm: Association between payments from manufacturers of pharmaceuticals to physicians and regional prescribing: cross sectional ecological study. BMJ 2016;354:i4189 (Published 18 August 2016).)

(Anm: Medisinsk utstyr (mintankesmie.no).)

(Anm: Legemiddelprodusenter og medisinske utstyrsprodusenter betalte i fjor 6,5 milliarder dollar til leger og undervisningssykehus. (Drug and device makers paid $6.5 billion to docs and teaching hospitals last year.) (statnews.com 30.6.2016).)

(Anm: Legemiddelkonsulenter forteller leger lite om sideeffekter, ifølge studie. (Drug Reps Tell Docs Little of Side Effects: Survey) (Journal of General Internal Medicine 2013 (April).)

(Anm: Interessekonflikter vanlig blant forfattere av amerikanske retningslinjer for kreft, ifølge studie. (Conflicts of interest common among US cancer guideline authors, study finds.) BMJ 2016;354:i4660 (Published 25 August 2016).)

(Anm: Selgere i kirurgenes rekker: Relasjoner mellom kirurger og medisinske utstyrsrepresentanter (Salespeople in the Surgical Suite: Relationships between Surgeons and Medical Device Representatives. PLoS ONE 11(8): e0158510).

(Anm: - Nesten ni av 10 leger og forskere som bidro til å utvikle et førende sett med retningslinjer for kreftomsorgen i USA rapporterte finansielle bånd til legemiddelindustrien og medisinske utstyrsfirmaer). (medicalnewstoday.com 30.8.2016).)

(Anm: Ingen gratis lunsj for leger: Sponsede måltider knyttet til flere resepter (No free lunch for docs: Sponsored meals linked to more prescriptions) (mmm-online.com 20.6.2016).)

(Anm: Vioxx - informasjon vs kunnskap og visdom - hvem visste hva? (mintankesmie.no).)

- Oblindade studier ger mer positivt resultat

Oblindade studier ger mer positivt resultat
lakemedelsvarlden.se 14.2.2013
Om läkaren vid kliniska studier vet vilka patienter som får den verksamma substansen påverkar det resultatet. Det visar en analys från Cochrane-institutet.

En ny metaanalys från Cochrane-institutet visar att det har betydelse om studien är blindad när effekten av ett nytt läkemedel eller en ny kirurgisk metod utvärderas. Man har länge antagit att det är bäst med blindade studier, men nu han man för första gången kunnat visa denna observationspartiskhet tydligt, skriver Videnskab.dk.

Analysen visar att oblindade studier gör att effekten av det nya läkemedlet eller kirurgiska metoden i större grad blir positiv jämfört med effekten i blindade studier. Skillnaden var signifikant, däremot varierade den beroende på studierna. Det hade forskarna ingen förklaring till.

Metaanalysen innehöll 16 kliniska studier som innehöll både oblindade och blindade delar. Det, menar forskarna, är analysens styrka eftersom man inte jämför blindade studier som är gjorda på ett sätt i till exempel USA med oblindade studier gjorda i Danmark.

Enligt forskarna finns det bara en lösning på problemet, att använda blindade studier, även om det är dyrare.

- Som med all vetenskap finns det sällan en ultimat sanning, så du kan inte på grund av den här studien säga att alla oblindade studier kommer att innehålla partiskhet. I själva verket visar analysen att vissa studier inte är partiska - men de flesta av dem är det, och därför resultaten måste tas på allvar, säger Asbjörn Hróbjartsson, senior forskare vid Cochrane-institutet, till Videnskab.dk. (...)

(Anm: Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. CMAJ 2013 (January 28).)

- Grassley sier Glaxo hemmeligholdt legemiddeldata

Grassley Says Glaxo Withheld Drug Data (Grassley sier Glaxo hemmeligholdt legemiddeldata)
online.wsj.com 13.7.2010
WASHINGTON—A former Food and Drug Administration official said the maker of diabetes drug Avandia withheld from regulators information suggesting the drug posed an increased risk for serious heart problems, according to people familiar with her statements.

The allegation comes as one of the biggest recent drug-safety fights nears a climax. Starting Tuesday, a panel of FDA experts will debate whether GlaxoSmithKline PLC's Avandia should be pulled from the market after years of controversy over its alleged side effects.

The statements by the ex-FDA official, made in a deposition for lawsuits filed against Glaxo, are included in a letter received Monday by the agency from Sen. Charles Grassley (R., Iowa), the top Republican on the Senate Finance Committee, which has been investigating Glaxo and Avandia. His letter, co-signed by committee chairman Sen. Max Baucus (D., Mont.), includes additional information detailing internal company records about Avandia, according to people familiar with the letter. (...)

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

- Publiserte studier er ofte i konflikt med resultater innrapportert til ClinicalTrials.gov

Author Insights: Published Studies Often Conflict With Results Reported to ClinicalTrials.gov (Forfatters innsikt: Publiserte studier er ofte i konflikt med resultater innrapportert til ClinicalTrials.gov)
JAMA 2014 (March 11, 2014)
Joseph S. Ross , MD , MHS , ved Yale University School of Medicine og hans kolleger fant ulikheter mellom innrapportering av resultater til tidsskrifter og ClinicalTrials.gov. (Joseph S. Ross, MD, MHS, of Yale University School of Medicine and his colleagues found discrepencies between the reporting of results in journals and ClinicalTrials.gov. Image: Yale University.)

Studieresultatene fra denne undersøkelsen som er publisert i store medisinske tidsskrifter er ofte i konflikt med dataene som forfatterne har sendt inn til ClinicalTrials.gov, ifølge en analyse publisert i JAMA i dag. (...) (Study results published in major medical journals often conflict with the data its authors have submitted to ClinicalTrials.gov, according to an analysis published in JAMA.)

- Stans av randomiserte kliniske forsøk vanlig

Discontinuation of randomized clinical trials common (Stans av randomiserte kliniske forsøk vanlig)
medicalnewstoday.com 11.3.2014
Approximately 25 percent of about 1,000 randomized clinical trials initiated between 2000 and 2003 were discontinued, with the most common reason cited being poor recruitment of volunteers; and less than half of these trials reported the discontinuation to a research ethics committee, or were ever published, according to a study in JAMA. (...)

- Østtyskere brukt som prøvekaniner

Østtyskere brukt som prøvekaniner (dagsrevyen 19.5.2013)
nrk.no 17.5.2013
Legemiddelskandalen ryster Tyskland.

Titusener av innbyggere i det tidligere DDR ble brukt som forsøkspersoner av vestlige legemiddelkonserner på 1980-tallet.

Mange døde av forsøkene viser avsløringer i det tyske medier. I noen av tilfellene ga pasientenes familier sitt samtykke, uten å vite hva de var med på.

Hør mer om legemiddelskandalen i Verden på lørdag

Mer enn 50.000 østtyskere deltok i rundt 600 kliniske tester som ble gjennomført ved et femtitall sykehus i det tidligere Øst-Tyskland, skriver Der Spiegel. Regimet skal ha tjent enorme summer på testene.

De nye avsløringene baserer seg på tidligere ukjente dokumenter fra det østtyske helsedepartementet, farmasøytiske institutter og Stasi-arkivet.

Blant legemidlene som ble prøvd ut, var blodtrykksmedisiner og antidepressiva fra store legemiddelprodusenter i Vest-Tyskland, Sveits og USA.

Mange av deltakerne skal ha mistet livet under forsøkene, og legemidler skal også ha blitt testet på spedbarn og deliriske alkoholikere. (…)

(Anm: Deadly Side Effects: New Details Emerge in East German Drug Test Scandal (spiegel.de 14.5.2013).)

- Metodene eller analysene er manipulert

Registration of observational studies (Registrering av observasjonsstudier)
Editorials
BMJ 2010;340:c950 (18 February)
The next step towards research transparency

Observational studies, such as cohort and case-control studies, are an important form of medical research, but they are also vulnerable to bias and selective reporting.1 They often produce large datasets that can be subjected to multiple analyses. Researchers may then craft a paper that selectively emphasises certain results, often those that are statistically significant or provocative. These decisions may reflect strong financial or academic interests and prior beliefs. At present, consumers of observational research cannot easily distinguish hypothesis driven studies from exploratory, post hoc data analyses. Researchers do not routinely disclose the number of additional analyses performed. Nor is there any satisfactory way to know whether the research questions or methods of statistical analysis diverged from those initially planned. It has been observed that there is "little or no penalty" for data dredging and selective reporting. Rather than attracting censure it can "get you into the BMJ and the Friday papers."2 (...)

(4) Some drug studies more likely to have favourable conclusions (Enkelte legemiddelstudier mer sannsynlig å ha gunstige konklusjoner)
British Medical Journal 16.11.2007
(...) Tidligere arbeider har vist at resultatet av en legemiddelstudie, når den er finansiert av det firmaet som utviklet legemidlet, kan være partisk fordi metodene eller analysene er manipulert. (Previous work has shown that, when a drug study was funded by the company that made that drug, the results might be biased in favour of that drug because the methods or analyses were manipulated.)

New research published on bmj.com today shows that, for blood pressure drugs, studies are now much less likely to have biased results but still tend to have overly positive conclusions favouring the company's products.

The authors call on editors and peer reviewers to scrutinise the conclusions of these studies to ensure that they contain an unbiased interpretation of the results. (...)

- 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. (...)

- 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 (...)

- Industry funded trials were reported on time in 52% of cases

FDA disagrees with BMJ study that found clinical trials were not being reported
BMJ 2012;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. (...)

- Professors studie linket til barne-selvmord

Prof’s study linked to child suicide (Professors studie linket til barne-selvmord)
browndailyherald.com 17.11.2011
U. remains silent in face of accusations

Ten years after its publication, a study by Professor of Psychiatry and Human Behavior Martin Keller continues to generate concern in the medical community due to its alleged link to child suicide.

Last month, the global nonprofit Healthy Skepticism wrote to the University requesting support for its efforts to retract Keller's article — commonly known as Study 329 — from the Journal of the American Academy of Child and Adolescent Psychiatry.

Healthy Skepticism expressed concern that the study, which identified the drug Paxil as an effective combatant of depression in children, "seriously misrepresented both the effectiveness and the safety" of the drug. The authors added that the study's continued citation was harmful to children, since some children committed suicide after being prescribed Paxil.

The letter follows several ethical examinations of Study 329, including a BBC documentary, the book "Side Effects" by former Boston Globe reporter Alison Bass and an investigation by the Senate Finance Committee. Those inquiries led to allegations that the authors of the study — who had received funds from Paxil's parent company GlaxoSmithKline — suppressed the findings on the drug's connection to suicidal tendencies because they would adversely affect profits.

Keller, the lead author, was also accused of allowing the study to be ghostwritten by a GlaxoSmithKline affiliate. In June 2009, he stepped down as chair of the psychiatry department, citing personal reasons, but he retained his professorship. Keller did not respond to multiple requests for comment for this story.
Citing confidentiality reasons, Dean of Medicine and Biological Sciences Edward Wing also declined to comment. (...)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Restoring Study 329. Scientific Integrity Through Data Based Medicine (study329.org).)

(Anm: Study 329 continuation phase: Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression. (…) CONCLUSIONS: The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration.Int J Risk Saf Med. 2016 Sep 17;28(3):143-61.)

(Anm: Study 329: Big Risk. Study 329 seems to fit the classic picture. It has Big Pharma ghostwriting articles, hiding data, corrupting the scientific process and leaving a trail of death, disability and grieving relatives in its wake. (davidhealy.org 16.11.2015).)

(Anm: Letters. Restoring Study 329. Retraction of biased journal articles. Study 329 may be the most infamous example of biased reporting within psychiatry, but this practice is widespread. (…) For example, our analysis included trial STL-N/S-95-003 (sertraline for social phobia). A memo in the FDA review stated: “Since the sponsor acknowledged that this was a negative study . . . they needed to submit only a summary report.” However, this trial was published as a success. (…) Although our papers clearly identified biased articles, none has since been retracted. BMJ 2015;351:h5497 (Published 21 October 2015).)

(Anm: Restoring Study 329. Paroxetine and Study 329: what we already knew and when. (…) More disturbing than the results of the Study 329 re-analysis is the continued prescribing of drugs such as paroxetine in populations for which there is no evidence of benefit. BMJ 2015;351:h5411 (Published 14 October 2015).)

(Anm: Study 329: The Timelines (davidhealy.org).)

- Pasientenes manglende stemme ved rapportering av legemiddelsikkerhet

The Missing Voice of Patients in Drug-Safety Reporting (Pasientenes manglende stemme ved rapportering av legemiddelsikkerhet)
healthcarereform.nejm.org 10.3.2010 (New England Journal of Medicine)
En pasient ønsker å bli informert om hvilke symptomer hun kan få av et legemiddel som inntas. Ved å lese avsnittet “Uheldige reaksjoner” i pakningsvedlegget finner hun et vell av data, men hun er ikke oppmerksom på at denne informasjonen, som i hovedsak er samlet inn i løpet av kliniske forsøk, nesten utelukkende er basert på klinikernes inntrykk av pasienters symptomer — ikke på pasienters rapporteringer av egne erfaringer med legemidlet. (A patient wants to know about symptoms she may have from a prescription drug she is taking. Consulting the label’s “Adverse Reactions” section, she finds a wealth of data. Little does she realize that this information, largely collected during clinical trials, is based almost entirely on clinicians’ impressions of patients’ symptoms — not on patients’ own firsthand reports of their experiences with the drug.)

Den nåværende praksis med pakningsvedlegg for uheldige hendelser er stilltiende basert på den forutsetning at en nøyaktig fremstilling av pasientens subjektive erfaringer alene kan fremskaffes gjennom klinikernes dokumentasjon. Selv om det er en betydelig bevismengde som ikke støtter denne antakelsen, viser det seg at klinikere systematisk undervurderer alvorligheten av pasienters symptomer, at pasienters selvrapporteringer ofte påviser sideeffekter som klinikere overser, og at klinikerne svikter når det gjelder å notere denne type symptomer hvilket resulterer i uheldige hendelser som kunne forebygges.1, 2 (...) (The current drug-labeling practice for adverse events is based on the implicit assumption that an accurate portrait of patients’ subjective experiences can be provided by clinicians’ documentation alone. Yet a substantial body of evidence contradicts this assumption, showing that clinicians systematically downgrade the severity of patients’ symptoms, that patients’ self-reports frequently capture side effects that clinicians miss, and that clinicians’ failure to note these symptoms results in the occurrence of preventable adverse events.1, 2)

(Anm: Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists. BMJ 2011; 342:c7153 (6 January).)

- Identifikasjon av bias resultatrapportering i randomiserte forsøk på PubMed: gjennomgåelse av publikasjoner og undersøkelse av forfattere.

Identifying outcome reporting bias in randomised trials on PubMed: review of publications and survey of authors. (Identifikasjon av bias resultatrapportering i randomiserte forsøk på PubMed: gjennomgåelse av publikasjoner og undersøkelse av forfattere)
BMJ 2005;330:753 (2 April)
(...) Resultater: 519 forsøk med 553 publikasjoner og 10 557 resultater ble identifisert. Respondenter på undersøkelsen (responserate 69 %) ga informasjon på ikke-rapporterte resultater, men var ofte upålitelige — for 32 % av de som nektet eksistensen av slike resultater var der bevis på det motsatte i deres publikasjoner. I gjennomsnitt, var over 20 % av resultater målt i en parallell gruppe ufullstendig rapportert. I løpet av et forsøk, hadde et slikt resultat høyere odds for å være statistisk ikke-signifikant sammenliknet med fullt ut rapporterte resultater (odds ratio 2,0 (95 % konfidensintervall 1,6 til 2,7) for effektresultater; 1,9 (1,1 til 3,5) for skaderesultater). De vanligste rapporterte grunner for utelatelse av effektresultater inkluderte plassbegrensning, mangel på klinisk betydning, og manglende statistisk signifikans. (Results 519 trials with 553 publications and 10 557 outcomes were identified. Survey responders (response rate 69%) provided information on unreported outcomes but were often unreliable—for 32% of those who denied the existence of such outcomes there was evidence to the contrary in their publications. On average, over 20% of the outcomes measured in a parallel group trial were incompletely reported. Within a trial, such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes (odds ratio 2.0 (95% confidence interval 1.6 to 2.7) for efficacy outcomes; 1.9 (1.1 to 3.5) for harm outcomes). The most commonly reported reasons for omitting efficacy outcomes included space constraints, lack of clinical importance, and lack of statistical significance.)

Konklusjoner. Ufullstendig rapportering av resultater i publiserte artikler fra randomiserte forsøk er vanlig og er forbundet med statistisk ikke-signifikans. Den medisinske litteraturen representerer derfor en selektiv og partisk delmengde studieresultater, og forsøksprotokoller bør gjøres offentlig tilgjengelige. (...) (Conclusions Incomplete reporting of outcomes within published articles of randomised trials is common and is associated with statistical non-significance. The medical literature therefore represents a selective and biased subset of study outcomes, and trial protocols should be made publicly available.)

- Metaanalyse ved bruk av individuelle deltakerdata fra randomiserte forsøk: muligheter og begrensninger skapt ved tilgang til rå data.

(Anm: Meta-analysis using individual participant data from randomised trials: opportunities and limitations created by access to raw data. Introduction. Meta-analysis using individual participant data (IPD) is becoming increasingly popular, despite being a laborious and resource-intensive method of evidence synthesis compared with a standard review using study-level data.1 It has the potential to overcome the limitations of meta-analyses based on published data through access to raw trial data,1–4 such as standardisation of analysis methods and data across trials1 5 (table 1). Access to IPD can facilitate integrity checks and intention to treat analysis by imputing for missing data. Collation of rarely reported variables for the key outcomes can result in greater precision of the intervention effect and address the problem of selective reporting.1 Evidence-Based Medicine 2017 (Published Online First: 17 August 2017).)

- Bør medisinske tidsskrifter publisere industrifinansierte studier

Should journals publish industry-funded bioethics articles?
The Lancet 2005; 366:422-424 (30 July 2005)
North American bioethics has a growing credibility problem. As the influence of bioethics has grown, so has the willingness of bioethicists to seek out funding from the pharmaceutical and biotechnology industries. These industries have begun to fund bioethics centres, lectureships, consultants, advisory panels, conferences, and private regulatory boards.1-3 The results of this industry-funded work are now making their way into peer-reviewed academic journals. Readers of the medical and bioethics literature have recently seen articles on the ethics of recruiting homeless individuals for research, funded by Eli Lilly;4 on the ethics of biotechnology and the developing world, funded by Glaxo, Merck, and Pfizer;5 on the ethics of stem-cell research, funded by Geron;6 and the ethics of placebo-controlled trials for mood-altering drugs, funded by antidepressant manufacturers.7 They have also seen pharma-funded university bioethicists collaborating on ethics articles with biotech entrepreneurs8 and a medical ethics and humanities journal issue funded by a pharmaceutical lobbying organisation.9 The authors of these articles have disclosed their industry ties, but readers are left to wonder: is an industry-funded bioethicist a bioethicist that we can trust? (...)

- LMI spør om prosess rundt ny mal for pasientsamtykke

LMI spør om prosess rundt ny mal for pasientsamtykke
lmi.no 21.2.2007
LMI ber om å bli inkludert i uformell høring.
LMI har fått kjennskap til at det foregår en prosses mellom blant annet etikk komiteene, personvernombudene og legemiddelverket for å utarbeide ny mal til pasientsamtykker for kliniske studier. En slik mal vil kunne få vesentlig betydning for legemiddelforskningen i Norge, men LMI har ikke vært inkludert i dette arbeidet. LMI har derfor sendt brev til aktuelle aktører der vi ber om å bli inkludert i prosessen. (...)

- Forekomsten av ufullstendig rapportering av studieresultater (rapporteringsbias) er høyt

Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists (Hyppighet og årsaker til rapporteringsbias(rapporteringskjevhet) av resultater i kliniske forsøk: intervju med de som utfører forsøk)
BMJ 2011; 342:c7153 (6 January)
Målsetting Å gi informasjon om hyppigheten og årsakene til rapporteringsbias(rapporteringskjevhet) i kliniske forsøk. (...) (Objectives To provide information on the frequency and reasons for outcome reporting bias in clinical trials.)

Konklusjon Forekomsten av ufullstendig rapportering av forsøksresultater er høyt. De som utfører kliniske forsøk (tester) virket generelt uvitende om konsekvensene for kunnskapsgrunnlaget å ikke rapportere alle resultater og protokollendringer. En generell mangel på enighet om valg av resultater i spesielle kliniske settinger var påtagelig, og påvirker forsøksdesign, gjennomføring, analyse og rapportering. (...) (The prevalence of incomplete outcome reporting is high. Trialists seemed generally unaware of the implications for the evidence base of not reporting all outcomes and protocol changes. A general lack of consensus regarding the choice of outcomes in particular clinical settings was evident and affects trial design, conduct, analysis, and reporting.)

(Anm: Bias [baies] -en, - skjevhet i vitenskapelig undersøkelse el. resultat pga. mangelfull systematikk i innsamlingen av data. Etym.: eng., fr. biais helning, tendens. Kilde: ordnett.no.)

(Anm: Bias; (...) valg og vurderinger som på systematisk måte avviker fra det som er faktisk korrekt. Kilde: Store norske leksikon.)

(Anm: Legemiddeletterlevelse (Tas legemidler som foreskrevet?) (Adherence to Medication.) (…) Legemidler virker ikke på pasienter som ikke tar dem. (Drugs don't work in patients who don't take them.)  (NEJM 2005;353:487-497(August 4).)

- Legemiddelindustriens påvirkning på konklusjoner av metaanalyser som de selv finansierer

Influence of pharmaceutical funding on the conclusions of meta-analyses (Legemiddelindustriens påvirkning på konklusjoner av metaanalyser som de selv finansierer)
Editorials (Leder)
BMJ 2007;335:1167 (16 November 2007)
(...) Yank og kollegaer viser at studier finansiert av et enkelt legemiddelfirma har en 55 % rate for partiske resultater som forvandles til en rate på 92 % for partiske resultater, som representerer et gap på 37 %. Gapet krymper til 21 % (57 % til 79 %) når to eller flere legemiddelfirmaer gir støtte. Men gapet forsvinner helt for studier utført av ikke-profitt institusjoner alene eller selv i samarbeid med legemiddelfirmaer. Den klare konklusjon er at nøytrale studier er mest pålitelige. Hvilken nytte av disse resultater? Og hva skal vi gjøre med dem? (...) (Yank and colleagues show that studies funded by a single drug company have a 55% rate of favourable results that is transformed into a 92% rate for favourable conclusions, representing a 37% gap. The gap shrinks to 21% (57% to 79%) when two or more drug companies provide support. Yet the gap vanishes entirely for studies done by non-profit institutions alone or even in conjunction with drug companies. The clear inference is that impartial studies are more reliable. What accounts for these results? And what should be done about them?)

- Legemiddelindustrien manipulerer forskningsresultater

GlaxoSmithKline distorted trial results for antidepressant Seroxat: BBC (BBC: GlaxoSmithKline forvrenger forsøksresultater for antidepressaet Seroxat)
marketwatch.com 29.1.2007
LONDON (MarketWatch) -- GlaxoSmithKline PLC (GSK) distorted trial results of its antidepressant Seroxat and covered up a link with teenage suicide, the BBC reported Monday on its Web site. (...)

Web sites: http://www.gsk.com
http://news.bbc.co.uk/1/hi/programmes/panorama/6291773.stm (...)

(Anm: Antidepressiva – Løgn, pisspreik (bullshit) eller sannhet? (mintankesmie.no).)

Medicinalindustri pynter på forskning
Ingeniøren 7.11.2005
Forskningsresultater fra forskere betalt af medicinalindustrien er i mange tilfælde ikke det papir værd, de er trykt på, skriver Ugebrevet Mandag Morgen.

Ofte er der mere reklame end videnskab over forskningen. Negative resultater tilbageholdes og produkter anbefales, selvom de ikke er bedre end tilsvarende præparater. (...)

- Negative legemiddelstudier publiseres ikke, ifølge rapport

Lyver om negative legemiddelstudier
helserevyen.no 23.1.2008
I en gjennomgang har den amerikanske legemiddelmyndigheten, FDA, funnet at legemiddelindustrien underslår negative tester på antidepressive midler.

Undersøkelsen tyder på at effekten av antidepressive legemidler er sterkt overdrevet i forhold til testresultatene.

Grunnen er at negative resultat aldri blir offentliggjort, eller at de blir presentert som positive istedenfor negative, ifølge The Wall Street Journal. (...)

Unfavorable drug studies don't see print: report (Negative legemiddelstudier publiseres ikke, ifølge rapport)
reuters.com 17.1.2008
BOSTON (Reuters) - Nearly a third of antidepressant drug studies are never published in the medical literature and nearly all happen to show that the drug being tested did not work, researchers reported on Wednesday.

And in some of the studies that are published, unfavorable results have been recast to make the medicine appear more effective than it really is, said the research team led by Erick Turner of the Oregon Health & Science University. (...)

The idea that unfavorable test results get quietly tucked away so nobody will see them -- sometimes call the "file drawer effect" -- has been around for years. (...)

They could see which experiments approved by the FDA between 1987 and 2004 were ultimately publicized in the medical literature and the main criteria the researchers planned to measure success.

"It tells you where they placed their bets before they saw the data," Turner said in a telephone interview. (...)

REWRITTEN STUDIES
However, when it came to the 36 studies with negative or questionable results, as assessed by the FDA, only three were published and another 11 were turned around and written as if the drug had worked.

"Not only were positive results more likely to be published, but studies that were not positive, in our opinion, were often published in a way that conveyed a positive outcome," said the team.

For example, of the seven negative studies done on GlaxoSmithKline's Paxil, five were never published. The researchers found three studies for GSK's Wellbutrin SR, but the two negative ones never reached print. (...)

"There's an expectation that if you get a positive result, that's what you're supposed to do, and if you get a negative result you have failed," said Turner. "The first impulse is to say, 'I was wrong. Maybe I should move on to something more interesting'" so the results may never get written up. (...)

Researchers Find a Bias Toward Upbeat Findings on Antidepressants
nytimes.com 17.1.2008
The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found. (...)

Web Link
Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy (NEJM)

In published trials, about 60 percent of people taking the drugs report significant relief from depression, compared with roughly 40 percent of those on placebo pills. But when the less positive, unpublished trials are included, the advantage shrinks: the drugs outperform placebos, but by a modest margin, concludes the new report, which appears Thursday in The New England Journal of Medicine. (...)

Antidepressants Under Scrutiny Over Efficacy (Effekt av antidepressiva granskes)
wsj.com 17.1.2008
Sweeping Overview Suggests
Suppression of Negative Data
Has Distorted View of Drugs

The effectiveness of a dozen popular antidepressants has been exaggerated by selective publication of favorable results, according to a review of unpublished data submitted to the Food and Drug Administration.

ACCENTUATE THE POSITIVE

A review of research submitted to the FDA:
• Of 74 studies reviewed, 38 were judged to be positive by the FDA. All but one were published, researchers said.
• Most of the studies found to have negative or questionable results were not published, researchers found.
Source: The New England Journal of Medicine (...)

Five Trials
For example, Pfizer submitted five trials on its drug Zoloft to the FDA, the study says. The drug seemed to work better than the placebo in two of them. In three other trials, the placebo did just as well at reducing indications of depression. Only the two favorable trials were published, researchers found, and Pfizer discusses only the positive results in Zoloft's literature for doctors. (...)

The average effect size of the antidepressant Zoloft rose 64% by the failure to publish negative or questionable data on the drug, the researchers found. (...)

Antidepressants Less Effective Than Doctors Have Been Led to Believe: Study
therapeuticsdaily.com 17.1.2008
TORONTO - Antidepressants are far less effective than doctors have been led to believe, a new study has found.

That's because 88 per cent of clinical trials that showed the drugs didn't work either weren't published in medical journals or were presented as positive findings, says the study in the New England Journal of Medicine. (...)

Snedvriden publicering om antidepressiva
lakemedelsvarlden 17.1.2008
Studier som visar negativa resultat för antidepressiva läkemedel publiceras inte i den vetenskapliga litteraturen. Det visar en jämförelse som forskare gjort mellan de studier som amerikanska läkemedelsverket har tillgång till och de studier som är offentliggjorda i medicinska tidskrifter. (...)

Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy (Selektiv publikasjon av forsøk på antidepressiva og dets innflytese på angivelig effektivitet)
NEJM 2008; 358:252-260 (January 17)
Background Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials — and the outcomes within those trials — can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio. (...)

According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.

Conclusions We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. (...)

Antidepressant Studies Unpublished
nytimes.com 17.1.2008
Eli Lilly, manufacturer of Prozac, was among those criticized.

The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found. (...)

Antidepressant Trial Results Exaggerated (Forsøksresultater på antidepressiva overdrevet)
ivanhoe.com 16.1.2008
(Ivanhoe Newswire) – A new study shows a problem with past reporting of antidepressant research. The analysis finds selective publication in reporting exaggerates the effectiveness of antidepressants. (...)

Turner’s team found that whether and how the studies were published depended on how they turned out. They found 94 percent of the studies had positive results, but the FDA data showed only half of the study were positive. All but one of the positive studies was published. Most of the studies that were not positive were not published or they were published with a positive spin.

“Selective publication can lead doctors and patients to believe drugs are more effective than they really are, which can influence prescribing decisions,” says Turner. “Doctors and patients must have access to evidence that is complete and unbiased when they are weighing the risks and benefits of treatment.” (...)

- Hemmeligholdt dødsrisiko

Hemmeligholdt dødsrisiko
forskning.no 17.4.2008
Et legemiddelfirma hemmeligholdt risikoen ved en ny medisin. Tester som ble fremstilt som uavhengige, var skrevet av selskapet selv. - Trolig ikke et unikt tilfelle, sier en norsk professor. (...)

Siden har det vist seg at flere titalls tusen amerikanere kan ha dødd av Vioxx. I Norge ble dødstallet anslått til et hundretalls personer.

Nå viser det seg at Merck & Co., lenge før legemiddelet ble trukket tilbake i 2004, var klar over den høye dødsrisikoen bruk av legemiddelet medførte. (...)

- Studiene bekrefter noen antakelser om den farmasøytiske industrien, der store pengeinteresser er på spill, sier professor i etikk, Knut W. Ruyter, ved Forskningsetiske komiteer. (...)

Studien viser at vitenskapelige artikler som ble fremstilt som uavhengige, i realiteten var skrevet av ansatte ved Merck & Co. (...)

Spøkelsesforfattere
Fenomenet omtales som "ghostwriting", fordi de som egentlig har skrevet studien, er "usynlige" for offentligheten og helsemyndighetene. (...)

I følge de amerikanske forskerne har det lenge vært mistenkt at en slik praksis med "spøkelsesforfattere" er relativt utbredt innenfor biomedisinsk publisering. (...)

(Anm: Spøkelsesforfattere (ghostwriters). (mintankesmie.no).)

- Tilbakeholdelse av legemiddeldokumentasjon

Medical Journal:
Drug Studies Hide Key Data
(Medisinsk tidsskrift: Legemiddelstudier holder nøkkeldata skjult)
The Wall Street Journal 29.12.2005
Flere store farmasøytiske firmaer tilbakeholder viktige detaljer omkring kliniske legemiddelstudier, til tross for oppfordringer fra statlige kontrollorganer og medisinske tidsskreftsredaktører om å være mer imøtekommende, ifølge en studie publisert i denne ukes utgave av New England Journal of Medicine. (...) (Several major pharmaceutical companies are withholding important details about clinical drug trials, despite urging from federal regulators and medical-journal editors to be more forthcoming, according to a study published in this week's New England Journal of Medicine.)

Registries and Registration of Clinical Trials (Registre og registrering av kliniske forsøk)
New England Journal of Medicine (NEJM) 2005;353:2811-2812 (December 29) (PDF)
Argumentene i favør av registreringen av kliniske forsøk er nå velkjente.1,2,3,4 Viktigst av disse er praksisen med selektiv rapportering, hvorved studier som er negative eller skadelige ikke gjøres tilgjengelig for offentligheten, hvilket eksperter på spørsmålet om kliniske forsøk betrakter som en viktig form for vitenskapelig uredelighet.5 Denne praksis, som illustrert i et antall høyt profilerte eksempler, har økt kravet til påbudt offentlig registrering av kliniske forsøk. Registrering av forsøk bør øke kompletteringen, påliteligheten, og kvaliteten på fortolkningen av klinisk forskning. (The arguments in favor of the registration of clinical trials are now familiar.1,2,3,4 Chief among these addresses the practice of selective reporting, whereby negative or detrimental studies are not brought into the public domain, which experts on the subject of clinical trials consider an important form of scientific misconduct.5 This practice, as illustrated in a number of high-profile examples, have increased the demand for the mandatory public registration of clinical trials. Registration of trials should improve the completeness, reliability, and quality of the interpretation of clinical research.)

Dette behov for registrering tvinger frem spørsmålet om hvor forsøk bør være registrert. Det synes åpenbart at, for å unngå interessekonflikter og å øke publikums tillit, bør enhetene som etablerer og forvalter registre imøtekomme bestemte krav. (...) (This need for registration prompts the question of where trials should be registered. It seems obvious that, to avoid conflicts of interest and to increase the public trust, the entities that establish and manage registries should meet certain requirements.)

Formidling av resultater må spores så vel som finansiering (Dissemination of results needs to be tracked as well as the funding is)
BMJ 2005;331:456 (20 August)
Letter (Brev)
Redaktør — Decullier et al evaluerte noen av de faktorer som påvirker publikasjon av helserelaterte forskningsprosjekt.1 De undersøkte resultater fra forskningsaktiviteter ut fra perspektivet til forskningsetisk godkjennelse. (EDITOR—Decullier et al evaluated some of the factors influencing publication of health related research projects.1 They examined research activity outcomes from the perspective of research ethics approval.)

Registrering av kliniske forsøk er ikke allment krevet, og sponsordatabaser har nødvendigvis begrenset omfang. Imidlertid er godkjenning fra en etisk forskningskomite krevet for alle menneskelige kasus og inkluderer protokoller uten hensyn økonomisk støtte og opprinnelse. Vi var enige om denne tilnærmelse og tror at forskningsetisk godkjenning er det tidligste sammenfall i oppstarten til forskningsprosjekter på mennesker og et ideelt perspektiv for å studere de påfølgende hendelser i et prosjekts livssyklus. (...) (Registration of clinical trials is not universally required, and sponsor databases are necessarily limited in scope. However, approval by a research ethics committee is required for all research on human subjects and includes protocols regardless of funding status and origin. We agree with this approach and believe that research ethics approval is the earliest convergence in the birth of research projects on human subjects and an ideal perspective from which to study the subsequent events in a project's life cycle.)

Unnlatelse å formidle resultater er betraktet som uredelig forskning og er en alvorlig vitenskapelig og etisk bekymring.2 3 Som bekreftet av Decullier et al, forskyver selektiv formidling av forskningsresultater i publikasjonsbias, litteraturen typisk mot rapporter med positive funn. Imidlertid, i sine diskusjoner, synes Decullier et al å integrere spørsmålet om kliniske forsøksregistrering med selektiv formidling, som antyder at registrering vil hjelp mot denne situasjonen. (...) (Failure to disseminate results is considered to be research misconduct and is an urgent scientific and ethical concern.2 3 As confirmed by Decullier et al, selective dissemination of research results in publication bias, typically skewing the literature towards reports with positive findings. In their discussion, however, Decullier et al seem to conflate the issue of clinical trial registration with that of selective dissemination, implying that registration will remedy this situation.)

- Clinical trial results often overstate benefits of treatment

Clinical trial results often overstate benefits of treatment
BMJ 2007;334:1341 (30 June)
Failings in the way that clinical trials are designed and presented may lead doctors to overstate the benefit of treatments, experts warned last week.
The conference on clinical trials, organised by the James Lind Alliance and the Lancet and held at the Royal Society of Medicine in London, also heard that key groups of participants were often excluded from clinical studies and as a result were denied the benefits of evidence based medicine. Stephen Holgate, professor of immunopharmacology at Southampton University, said that children and elderly people were "especially neglected" in this area.
As another example he noted that the routine exclusion of smokers from asthma studies meant that it has only recently been discovered that inhaled steroids do not work in this group—decades after millions of smokers began taking these drugs for their asthma. (...)

(Anm: Evidence based medicine: a movement in crisis? BMJ 2014;348:g3725 (13 June 2014).)

- Influence of drug company authorship and sponsorship on drug trial outcomes

Influence of drug company authorship and sponsorship on drug trial outcomes
The British Journal of Psychiatry (2007) - © 2007 The Royal College of Psychiatrists
(...) Studies of drug treatments are more likely to report favourable outcomes when they are funded by the pharmaceutical industry. We compared drug trials reported in three major psychiatric journals to investigate these influences. Independent studies were more likely to report negative findings than industry-funded studies. However, the involvement of a drug company employee had a much greater effect on study outcome than financial sponsorship alone. (...)

- Korrupt forskning

Korrupt forskning kan skade folkehelsen
Tidsskr Nor Lægeforen 2005; 125: 2672-3 (6.10.2005)
Jeg anbefalte i et innlegg i Dagens Næringsliv i 1998 at staten skulle fullfinansiere et forskningslaboratorium innen hvert medisinske fagområde og bruke dette som referanse i faglige spørsmål (1). Bakgrunnen for innlegget var uro over kommersielle aktørers samarbeid med fagpersoner hvis habilitet kunne bli påvirket. Utviklingen i Norge har dessverre gått i motsatt retning. Universitetene med fakultetene og deres institutter har kvittet seg med sitt demokratiske kontrollapparat (2) og i stedet ansatt ledere og styrer med sterke kommersielle interesser. Dette åpner for økt korrupsjon, på bekostning av faglige prioriteringer. Norges forskningsråd har gått i samme retning, med økt vektlegging av næringspolitiske aspekter. (...)

Nylig ble det rapportert at «medisinske tidsskrifter er en forlengelse av legemiddelfirmaenes markedsføringsavdelinger» (5). Et meget anerkjent tidsskrift er for eksempel blant kolleger lenge blitt kalt Journal of Positive Medical Studies.

Selv har jeg i årevis arbeidet innen et felt der negative konsekvenser ved flere preparater er fremhevet. Det har som regel vært hard kamp å få disse artiklene publisert. Generelt har det i flere tidsskrifter vært motvilje mot å trykke manuskripter som kan ha negative konsekvenser for farmasøytisk industri. Etter min mening har man også sett noe av den samme holdningen innen Norges forskningsråd og fagmiljøene i Norge. Det heter seg i dag at norsk forskning kvantitativt skal bringes opp på et gjennomsnittlig vesteuropeisk nivå. Det hadde kanskje vært bedre for alle dersom vi hadde fortsatt med fri og selvstendig norsk forskning, men i mindre omfang? (...)

Hvorfor bør vi ikke være overrasket?

Drug profits infect medical studies (Legemiddelprofitt infiserer medisinske studier)
Los Angeles Times 7.1.2006
FLERE AV VÅRE mest ærbødige vitenskapelige tidsskrifter har nylig blitt besudlet av beskyldninger om vitenskapelig uredelighet. Sjokkerende? Vi bør være akkurat like sjokkert som inspektør Renault da han oppdaget gambling på Ricks kafé i Casablanca. (...) (SEVERAL OF OUR most venerated scientific journals have recently been besmirched by allegations of scientific misconduct. Shocking? We should be just as shocked as Inspector Renault when he discovered gambling at Rick's Cafe in Casablanca.)

Hvorfor bør vi ikke være overrasket? Fordi over de siste 25 år, har klinisk forskning i stor utstrekning blitt privatisert. Trekvart av kliniske studier publisert i de tre mest respekterte medisinske tidsskrifter (New England Journal of Medicine, Journal of the American Medical Assn. og Lancet) er nå kommersielt finansiert. Som et resultat, vokser ikke vår medisinske kunnskap i den retning som best forbedrer vår helse men mot korporativ fortjeneste, som planter vokser mot sollyset. (Why shouldn't we be surprised? Because over the last 25 years, clinical research has been largely privatized. Three-quarters of the clinical studies published in the three most respected medical journals (the New England Journal of Medicine, the Journal of the American Medical Assn. and the Lancet) are now commercially funded. As a result, our medical knowledge grows not in the direction that best improves our health but toward corporate profits, the way that plants grow toward sunlight.)

Det var ikke alltid slik. Før 1980, var de fleste medisinske studier statlig finansiert, og de fleste akademiske forskere foraktet industriell sponsing. Nå, imidlertid, er det store flertall av kliniske forsøk kommersielt finansiert, og med de finansielle innsats så høy, er der økende bevis for at enkelte forskere og selskaper manipulerer sine resultater. (This wasn't always so. Before 1980, most medical studies were publicly funded, and most academic researchers scorned industry support. Now, however, the vast majority of clinical trials are commercially funded, and with the financial stakes so high, there is mounting evidence of individual scientists and corporations manipulating their findings.)

Selv våre mest betrodde tidsskrifter er avhengig av penger fra legemiddelfirmaer. Legemiddelfirmaer kjøper ikke bare annonsering på deres sider. Ifølge Richard Horton, redaktør for Lancet, betaler de også opp til 1,75 millioner dollar for opptrykk av artikler som favoriserer deres legemidler, som salgsrepresentanter deler ut til leger. (...) (Even our most trusted journals are dependent on drug-company money. Drug makers don't just buy advertising in their pages. According to Richard Horton, editor of the Lancet, they also pay up to $1.75 million for reprints of articles favorable to their drugs, which sales reps then hand out to doctors.)

(Anm: Uredelighet og fusk (juks/forskningsjuks) i medisinsk forskning. (mintankesmie.no).)

- Identifisering av bias

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. (...)

Survival End Point Reporting in Randomized Cancer Clinical Trials: A Review of Major Journals
Journal of Clinical Oncology 2008;26(22):3721-3726 (August 1)
(...) Purpose: Several publications showed that the standards for reporting randomized clinical trials (RCTs) might not be entirely suitable. Our aim was to evaluate the reporting of survival end points in cancer RCTs. (...)

Conclusion: A majority of articles failed to provide a complete reporting of survival end points, thus adding another source of uncontrolled variability. (...)

Systematic review of publication bias in studies on publication bias (Systematisk gjennomgåelse av publikasjonsbias i studier på publikasjonsbias)
BMJ 2005;331:433-434 (20 August)
Vi fant ingen bevis på publikasjonsbias i rapporter på publikasjonsbias. Men, med bare 26 studier, var muligheten til å avdekke asymmetry i en samlet plot lav.5 Videre, forklaringen av betegnelsen "positiv" og "signifikant" er ikke-ensartet og noen ganger nærmest skjønnsmessig i de studier undersøkt på nytt her. For eksempel, Dickersin (se bmj.com) brukte betegnelsen "studier rapportert å ha statistisk signifikante resultater var kombinert med de rapportert å ha resultater av stor viktighet. Sammen referert som "signifikant" og som står i motsetning til den resterende del, som er referert som "ikke signifikant".'" (We found no evidence of publication bias in reports on publication bias. But, with just 26 studies, the power to detect asymmetry in a funnel plot was low.5 Furthermore, the definition of the terms "positive" and "significant" is non-uniform and sometimes rather arbitrary in the studies reinvestigated here. For example, Dickersin (see bmj.com) used the definition "studies reported to have statistically significant findings were combined with those reported to have findings of great importance. Together they are referred to as `significant' and are contrasted with the remainder, which are referred to as `not significant.'")

De fleste data på publikasjonsbias ble registrett retrospektivt og mangler prospektiv registrering, som de presenterte analyser. Fremtidige og registrerte studier på publikasjonsbias er nødvendig. (Most data on publication bias were recorded retro-spectively and lack prospective registration, as does the present analysis. Prospective and registered studies on publikasjonsbias are needed.)

Hva er allerede kjent om dette emnet (What is already known on this topic)

Studier estimert å ha publikasjonsbias synes mer sannsynlig i det hele tatt å være publisert, tidligere, og i tidsskrifter med høyere gjennomslagsfaktor; som en konsekvens er effekter ofte overestimert (Studies estimated to have publication bias seem more likely to be published at all, earlier, and in journals with higher impact factors; as a consequence effects are often overestimated.)

Hva denne studien tilføyer (What this study adds)

Disse resultater indikerer ikke publikasjonsbias i rapporter på publikasjonsbias. (These findings do not indicate publication bias in reports on publication bias.)

(Anm: Bias [baies] -en, - skjevhet i vitenskapelig undersøkelse el. resultat pga. mangelfull systematikk i innsamlingen av data. Etym.: eng., fr. biais helning, tendens. Kilde: ordnett.no.)

(Anm: Bias; (...) valg og vurderinger som på systematisk måte avviker fra det som er faktisk korrekt. Kilde: Store norske leksikon.)

(Anm: Legemiddeletterlevelse (Tas legemidler som foreskrevet?) (Adherence to Medication.) (…) Legemidler virker ikke på pasienter som ikke tar dem. (Drugs don't work in patients who don't take them.)  (NEJM 2005;353:487-497(August 4).)

(Anm: Outcome selection bias in meta-analysis Statistical Methods in Medical Research 2005;14(5):515-524.)

Flaws are found in validating medical studies (Flaws are found in validating medical studies)
Boston Globe 15.8.2005
Many see need to overhaul standards for peer review
WASHINGTON -- They are two of the most widely publicized pieces of medical research in recent years: Reports in prestigious journals declared that women who underwent hormone replacement therapy, and people who ingested large amounts of Vitamin E, had relatively low rates of heart disease. (Many see need to overhaul standards for peer review. (...) (- They are two of the most widely publicized pieces of medical research in recent years: Reports in prestigious journals declared that women who underwent hormone replacement therapy, and people who ingested large amounts of Vitamin E, had relatively low rates of heart disease.)

Doubts raised over cancer vaccine study
BMJ 2001;323:184 (28 July)
A prizewinning German study claiming to have found a safe and effective vaccine for kidney cancer has been heavily criticised by doctors who say that the research data may have been manipulated and that the treatment could even be dangerous.

German doctors press for a national trial register
BMJ 2005;331:178 (23 July)
A task force of German epidemiologists, doctors, and consumer protection campaigners is pressing for the swifter establishment of a national register of clinical trials. (...)

Forskere manipulerer med medicinalforsøg
Berlingske Tidende 13.6.2005
Drømme om ære og formuer i forskningsstøtte får medicinalforskere til at manipulere forskningsresultater. I forskningskredse kender man til snyderiet.

Kampen for at undertrykke negative nyheder i medicinforskning er skærpet så meget til, at forskningsforsøg manipuleres. Enten af forskerne selv eller af medicinalindustrien. (...)

Hiding the Data on Drug Trials
The New York Times 1.6.2005
Any Americans gullible enough to believe that the drug industry can be trusted to report fully on what clinical trials it is sponsoring or what results were found must be sorely disappointed by recent developments. A government survey determined that three of the largest drug companies have effectively reneged on their pledges to list trials in a federal database. A report in yesterday's Times by Alex Berenson reveals that this intransigence also extends to a voluntary industry database. It looks as if demands from researchers and the medical profession for full access to clinical trial data will continue to be frustrated.

Companies already provide the data to the Food and Drug Administration, which is required to keep much of it confidential. A public listing of trials is important to prevent drug makers from hiding results that reflect badly on their drugs while publishing only results that make their drugs look good. By law, the companies are supposed to register important trials with a government Web site. Most manufacturers are complying, but the three big obfuscators - Merck, GlaxoSmithKline and Pfizer - are often getting around the requirement by not naming the drugs they are testing, instead using phrases like "an investigational drug." Merck was the worst offender, failing to provide a drug's name some 90 percent of the time. Glaxo withheld a name 53 percent of the time, and Pfizer 36 percent of the time.

Merck and Pfizer are also the most prominent withholders of trial results from the industry's voluntary database. As Mr. Berenson reported, Pfizer has posted only a few results of clinical trials, and Merck has posted none. That meager contribution appears to satisfy the weak guidelines set by the industry, but it offers a sorry contrast with the record of Eli Lilly. Lilly appears to have been quite scrupulous in listing its current trials with the government site and has posted the results of hundreds of completed clinical trials on the industry site. Surely if one big company can make its trials transparent, other drug makers can do the same.

A coalition of medical editors has just stiffened its announcement that leading journals will soon refuse to publish the results of any clinical trial that has not complied with tough international standards for transparency. That should apply useful pressure to recalcitrant companies. But the best hammer would be federal legislation to compel all companies to provide critical information when a trial is begun and full results when a trial is completed, with stiff penalties for noncompliance. (...)

Journal Editor Blasts Drug Firms' Trial Data
Los Angeles Times 24.5.2005
The editor in chief of the New England Journal of Medicine accused three of the largest drug companies of "making a mockery" of efforts to create transparency in clinical trials, saying that could lead some important medical publications to avoid publishing their studies.

Dr. Jeffrey M. Drazen, the editor, said Pfizer Inc., Merck & Co. and Glaxo-SmithKline were not providing enough useful information on clinical trials they registered with the government. (...)

The three companies "are giving nonsense details," Drazen said Monday. "They are written in a way that they are trying to hide what they are doing."

The editors created the policy after some drug companies were accused of stifling negative data. Last year, New York Atty. Gen. Eliot Spitzer sued Glaxo-SmithKline, accusing it of suppressing unfavorable studies of its antidepressants.

Drazen said some of the problems with the information submitted by the three companies included a failure to state the number of patients in trials and to clearly outline primary and secondary goals of their studies. He noted that most other companies had complied but had started to follow the lead set by the companies he criticized. (...)

- Skader og dødsfall i legemiddelstudier - pasienter som forsøkskaniner

New England journal report describes unique features of adverse reactions in TGN1412 trial
BMJ 2006;333:570 (16 September)
The healthy volunteers who took part in the clinical trial of the anti-CD28 monoclonal antibody TGN1412 had multiple organ failure similar to that seen in septic shock but with several unique features, says a report published last week by Dr Suntharalingam and his colleagues, who cared for the six men after they were transferred to the NHS (New England Journal of Medicine 2006;355:1018-28).

Within 90 minutes of receiving a single intravenous dose of TGN1412 all six volunteers had a systemic inflammatory response characterised by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgia, nausea, diarrhoea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. The patients were given a range of treatments, including steroids. (...)

(Anm: Experimental drug that injured UK volunteers resumes in human trials. BMJ 2015;350:h1831  (Published 02 April 2015).)

Drug firm 'had not tested on humans before'
independent.co.uk 17.3.2006
The German company whose drug trial has left six men fighting for their lives after it went badly wrong had never tested its products on humans before.
Thomas Hanke, the chief scientific officer of TeGenero, based in Wurzburg, said the company was "devastated" by the news. The new medicine, known as TGN 1412, had shown no safety problems in laboratory trials or animal tests, he said.

But it emerged yesterday that the American testing company Parexel, which TeGenero had commissioned to run the trial, had initially been refused permission to test the drug in Germany. The Paul Ehrlich Institute in Germany, which was responsible for overseeing the company's proposed drug-testing programme, sent back its project with a lengthy list of deficiencies which it demanded be corrected before testing was allowed.

Two drug trial men critically ill
bbc.co.uk 15.3.2006
Two men remain critically ill and four others are in a serious condition after suffering a violent reaction while taking part in a clinical drugs trial.
All are still in intensive care in Northwick Park Hospital, north-west London, after falling ill on Monday.

Myfanwy Marshall told BBC News her boyfriend's body was badly swollen and she had been told he could die.

One of the drugs companies involved in the trial said it has apologised to the families of the men.

But relatives are said to be unhappy with the information given from the firm behind the anti-inflammatory drug.

The families had been given "mixed messages" during two meetings with pharmaceutical company TeGenero AG, which manufactures the drug and Parexel, which ran the trial, it was claimed. (...)

Older people are wrongly excluded from drug trials
BMJ 2005;331:1360 (10 December)

Human guinea pigs pay for lax FDA rules
The Seattle Times 6.11.2005
Across the U.S., 3.7 million people have enrolled in drug tests sponsored by the world's largest pharmaceutical companies. The companies have outsourced 75 percent of experimental drug trials to centers such as SFBC, a leader in a $14 billion industry.

At the same time, the U.S. Food and Drug Administration has farmed out much of the responsibility for overseeing safety in these tests to private companies known as institutional review boards. These boards are also financed by pharmaceutical companies.

So, the drug industry is paying the people who do the tests — and most of the people who regulate those tests. And that combination can sometimes be deadly.

"The fundamental problem is a system in which investor-owned businesses have control over the evaluation of their own products," says Marcia Angell, editor in chief of the New England Journal of Medicine from 1999 to 2000. "Oversight of clinical trials is too important to leave in the hands of drug companies and their agents."

Most of the people lining up at SFBC to rent their bodies to medical researchers are poor immigrants from Latin America, drawn to this five-story test center in a converted Holiday Inn motel. (...)

How Safe Are Drug Trials for Participants?
abcnews.go.com 2.11.2005
Bloomberg News Investigates Conditions for Human Guinea Pigs
Nov. 2, 2005 — - Nearly 4 million Americans each year become human guinea pigs when they volunteer to be subjects in drug trials. Universities used to handle most of these trials, but now they're mostly done by private, profit-driven testing centers. Every year, human testers get sick or die during these drug trials, but no one knows how many because nobody tracks that number, explains GMA consumer correspondent Elisabeth Leamy.

Putting clinical trials into context (Å sette kliniske forsøk i en sammenheng)
The Lancet 2005; 366:107-108 (9 July 2005)
(...) Biomedisinsk forskning redder hver dag livene til menn, kvinner, og barn, i alle land over hele verden. Men, biomedisinsk forskning skaper også risiko. (...) (Biomedical research saves the lives of men, women, and children every day, in every nation around the world. However, biomedical research also poses risks.)

En del av farene forbundet med forskning er uunngåelige: noen nye teknikker for diagnostikk og behandlinger vil bli funnet mindre effektive enn de beste alternativer og noen vil bli funnet skadelige. Denne risiko er understreket i samtykkeprosedyrer. Det er prisen som betales for altruismen til deltakerne i kliniske forsøk. Mer bekymrende er farene til forskning som kan unngås men oppstår på grunn av dårlig forskningspraksis. Idet samfunnsmessig forståelse av problemer forbundet med biomedisinsk forskning øker, er der økende erkjennelse at dårlig forskning ikke bare involverer uhensiktsmessig utført forskning, men også unødvendig forskning, forskning som er gjort men som ikke blir publisert, og forskning som er publisert men som ikke på en måte som rettferdiggjør dens eksistens eller relevans. Det er nylig gjort anstrengelser for å registrere visse typer upubliserte kliniske forsøk, eller så raskt som mulig etter oppstart.3,4 Men hva med unødvendig eller dårlig fremlagt forskning? (Part of the danger associated with research is unavoidable: some new diagnostic techniques and treatments will be found to be less effective than the best alternative and some will be found to be harmful. This risk is underlined in consent procedures. It is the price paid for the altruism of participants in clinical research. More troubling are the dangers of research that are avoidable but incurred because of bad research practice. As societal awareness of problems associated with biomedical research grows, there is increasing recognition that bad research involves not only research conducted inappropriately, but also unnecessary research, research which is done but remains unpublished, and research which is published but not in a way that justifies its existence or its relevance. Unpublished research has recently been the focus of efforts to register certain types of clinical trial at, or as soon as possible after, inception.3,4 But what of unnecessary and badly presented research?)

Unødvendig og dårlig presentert klinisk forskning skader frivillige like mye som enhver annen form for dårlig medisin, så vel som sløsing med ressurser og misbruk av tilliten til forskere og deres studiedeltagere. De som sier at systematisk gjennomgåelse og metaanalyser ikke er “riktig forskning” tar feil;8 det er kliniske forsøk utført i fraværet av slike gjennomgåelser og metaanalyser som er utilbørlig, vitenskapelig og etisk. Forskerne og organisasjoner som påta seg samordnede gjennomgåelser og metaananlyser trenger nå den finansieringen og anerkjennelsen de fortjener dersom publikums tillit til biomedisinsk forskning skal opprettholdes og ressurser bli brukt på en effektiv måte. (Unnecessary and badly presented clinical research injures volunteers and patients as surely as any other form of bad medicine, as well as wasting resources and abusing the trust placed in investigators by their trial participants. Those who say that systematic reviews and meta-analyses are not “proper research” are wrong;8 it is clinical trials done in the absence of such reviews and meta-analyses that are improper, scientifically and ethically. Investigators and organisations who undertake and coordinate reviews and meta-analyses now need the funding and recognition they deserve if public trust in biomedical research is to be maintained and resources used in an effective way.)

Guinea Pig Kids
BBC 29.11.2004
Vulnerable children in some of New York's poorest districts are being forced to take part in HIV drug trials. (...)

For months, the BBC tried to get information from the people responsible for the trials, but none would comment.

The companies that supply drugs for the trials are among the world's largest, including Britain's own Glaxo SmithKline (GSK).

GSK responded to BBC programme makers, saying that all trials follow stringent stardards and are compliant with local laws and regulations.

Døde i forsøksprosjekt
VG 30.6.1999
Norske pasienter med blodforgiftning var med i utprøvingen av preparatet 546C88. Men så begynte pasientene å dø. (...)

Unødvendige studier

Nye retningslinjer – kliniske utprøvinger på legemidler
Den nasjonale forskningsetiske komité 31.08.2005
Når et legemiddel har fått markedsføringstillatelse og det settes i gang videre studier, er det da forskning eller markedsføring? Dette er et forskningsetisk dilemma. Den nasjonale forskningsetiske komité for medisin (NEM) har utarbeidet et verktøy til bruk for egne komiteer og andre instanser som vurderer slike forskningsprosjekt. (...)

Problemet er at noen av disse studiene har liten vitenskapelig verdi, og man kan derfor ikke forsvare å sette dem ut i livet. Dette er erfaringer vi har gjort etter mange års arbeid i regionale komiteer for medisinsk forskningsetikk (REK). (...)

Superfluous Medical Studies Called Into Question
washingtonpost.com 2.1.2006
In medical research, nobody is convinced by a single experiment.

A finding has to be reproducible to be believable. Only if different scientists in different places do the same study and get the same outcomes can physicians have confidence the finding is actually true. Only then is it ready to be put into clinical practice.

Nevertheless, one of medicine's most overlooked problems is the fact that some questions keep being asked over and over. Repeated tests of the same diagnostic study or treatment are a waste -- of time and money, and of volunteers' trust and self-sacrifice. Unnecessary clinical trials may also cost lives.

All this is leading some experts to ask a new question: "What part of 'yes' don't doctors understand?"

Two papers dramatically illustrated this problem last year and may have helped nudge the medical establishment toward doing something about it.

Norges forskningsråd (Forskningsrådet)

Adm. dir. Arvid Hallén i Forskningsrådet:
- Forskningsjukset reiser flere problemstillinger

Norges forskningsråd 16.1.2006
- Alle undersøkelser tyder på at fusk i forskning har et begrenset omfang, men det må arbeides permanent med disse spørsmålene, sier administrerende direktør i Forskningsrådet, Arvid Hallén, i en kommentar til jukset som er blitt avdekket rundt kreftforskningen til en forsker ved Rikshospitalet-Radiumhospitalet. (...)

En ansvarlig forskning
aftenposten.no 30.1.2006
Arvid Hallén, administrerende direktør i Norges forskningsråd
Forskningsjuks. Forskningen er i sitt vesen sannhetssøking. (...)

Begrenset omfang. Mediene har spekulert på om det avslørte fusket er toppen av et isfjell. Dette er ikke tilfellet. Alle undersøkelser tyder på at fusk i forskningen har et begrenset omfang. (...)

Legemidler og barn

Små pasienter - en stor utfordring
aftenposten.no 21.1.2005
Nye regler. Aftenposten hevdet fredag 6. januar, i forbindelse med en artikkel om legemidler for barn, at "Legemiddelindustrien mener at EU-kravene til legemiddeltesting vil fordyre utprøving i betydelig grad og argumenterer med at dette derfor kan hindre utvikling av nye legemidler". (...)

Med det nye EU-regelverket får legemiddelindustrien plikt til å utrede alle relevante nye legemidler med hensyn til bruk for barn. En tett dialog mellom legemiddelindustri, klinikere og myndigheter er nødvendig for å sikre en etisk forsvarlig iverksettelse av nytt regelverk. (...)

Pasienter vill vita resultater fra kliniska forsøk

Patienter vill veta resultaten från kliniska prövningar
Läkemedelsvärlden 2006(5) (Mai)
Så många som 98 procent av patienter som deltar i kliniska prövningar vill veta resultaten av prövningen. Men det finns inga krav på att informera dem.

FORSKNING Under den senaste europeiska bröstcancerkongressen EBCC framkom att 98 procent av deltagare i kliniska prövningar vill veta utfallet av prövningen. Men idag finns inget standardiserat sätt att meddela patienterna resultaten.

- Det finns inte heller myndighetskrav på det och det regleras vanligen inte heller i studieprotokollen, säger Jane Ahlqvist-Rastad, informationsläkare på Läkemedelsverket.

- Om det däremot framkommer ny kunskap som kan påverka patientens deltagande i studien så ska patienten informeras.
Det enda som regleras från myndighetshåll är att studier på något sätt ska offentliggöras.

- Därför är det upp till enskilda patienter att själva ta reda på studiens resultat. Följden blir att bara en del gör det, säger Anders Grahnén, Chief Scientific Officer på Quintiles.

Enligt Birgitta Pettersson, specialistläkare på enheten för kliniska prövningar på Läkemedelsverket, finns det inom EU ett intresse att skapa en större öppenhet mot allmänhet och hälso- och sjukvård.
- Det kan vara rimligt att arbeta för att de patienter som vill ska informeras om resultaten.

Ökad öppenhet
Vanligtvis har sponsorn, oftast ett läkemedelsföretag, ansvaret att informera prövaren om studieresultaten. Företagen förväntar sig sedan att prövaren i sin tur informerar patienten.

För att förbättra öppenheten och spridning av resultat har Läkemedelsindustriföreningen LIF tillsammans med de internationella branschföreningarna enats om en global policy om öppenhet kring kliniska studier, tillgänglig via www.lif.se.

Dessutom har International Fedaration of Pharmaceutical Manufacturers & Associations, IFPMA, utvecklat en webbportal för att söka information om pågående och avslutade kliniska prövningar i flera databaser, både allmänna och hos läkemedelsföretag, på www.ifpma.org. (...)

Krav om fuld åbenhed om medicinforsøg i den tredje verden

Krav om fuld åbenhed om medicinforsøg i den tredje verden
pharmadanmark.dk 11.10.2007
De store medicinalvirksomheders brug af forsøgspersoner i den tredje verden får nu Socialdemokratiet til at gøre det lovpligtigt, at offentligheden bliver fuldt orienteret om alle medicinforsøg med mennesker.

- Der skal være fuldstændig gennemsigtighed. Alle forsøg skal registreres, så offentligheden kan følge med. Ideelt set burde der indføres internationale standarder, men Danmark bør her og nu gå forrest med en national ordning, siger socialdemokratiets videnskabs- og forskningsordfører, Rasmus Prehn.

De store medicinalfirmaer bør kunne tvinges til at oplyse offentligheden om alle deres kliniske forsøg på mennesker, mener Prehn. Årsagen til kravet er et stigende fokus på medicinalindustrien, der efterhånden fortager halvdelen af sine medicinske forsøg med mennesker i den tredje verden. Overlæge Christian Gluud fra Copenhagen Trial Unit bakker op omkring Prehns forslag, som han mener, vil gavne både patienter, forsøgsdeltagere og forskningen.

- Vi løber en risiko ved ikke at anerkende det problem - industrien har hidtil prøvet at undgå registreringer af forsøgsprotokoller og -resultater, siger Martin Gluud. (...)

Tette bånd til industrien

Tette bånd til industrien
tv2.no 28.2.2006
Overlege Pål Zeiner er svært positiv til medisinering av ADHD-barn og er samtidig legemiddelindustriens favoritt som foreleser.

Pål Zeiner er overlege på sykehuset Buskerud, i det fylket i landet som bruker mest medisiner i behandlingen av ADHD.

Han har doktorgrad i ADHD-behandling og er en sterk tilhenger av medisinering - en medisinbruk som er tidoblet de siste ti årene og som har sendt Norge i verdenstoppen i bruk av piller mot ADHD.

Pillebruken bekymrer FNs narkotikakommisjon, men ikke Zeiner.
- Det er ikke påvist at terapeutisk bruk ved ADHD har noen sammenheng med misbruk av sentralstimulerende midler for eksempel, sier Zeiner.
Samtidig som Zeiner er behandlende lege for ADHD-pasienter, er han en av legemiddelindustriens mest brukte forelesere.

Brukt på 18 konferanser
Produsenten Lilly, som lager legemiddelet Strattera betalte i fjor Zeiner for å forelese på ikke mindre enn 13 av sine konferanser for helsepersonell. I tillegg jobber Zeiner som rådgiver for selskapet.

Konkurrenten Janssen-Cilag, som lager det sentralstimulerende preparatet Concerta brukte Zeiner fem ganger i fjor.

- Hvor mye fakturerte du?
- Det har jeg ingen oversikt over her og nå

Faren
De sterke båndene mellom en del leger og legemiddelindustrien er noe professor Einar Kringlen lenge har vært kritisk til.

– Faren er jo at når medisinindustrien kobles inn så får man et salg som går utover det som er vitenskapelig riktig, sier Kringlen.

En amerikansk undersøkelse publisert i journal of american medical association viser at hver femte lege som deltar på legemiddelindustriens presentasjoner blir mer positiv til å foreskrive medikamentene som presenteres.

- Forstår du at det stilles spørsmål ved dine tette bånd til industrien?
- Ja, jeg må akseptere at det gjøres det. Jeg må bare svare slik at folk kan skjønne at eg er opptatt av at det drives god pasientbehandling på dette feltet, sier Zeiner. (...)

Forskning eller markedsføring?

Overlege trikset med ADHD-tall
tv2.no 2.3.2006
En norsk overlege lot være å ta med 70 prosent av prøvepersonene i en undersøkelse om ADHD-medisinering.

- Ritalin hjelper voksne med ADHD, konkluderte overlege Nils Olav Aanonsen i 2004.

Men så viste det seg at overlegen lot være å ta med 70 prosent av forsøkspersonene da han trakk sine konklusjoner. Talltriksingen førte i tur til at oppdragsgiverne i Sosial- og Helsedirektoratet ba Aanonsen om å skrive en ny og supplerende rapport.

De påståelige konklusjonene måtte dermed fjernes.
Diskutér ADHD-problematikken på Veggavisen

- Bedre liv
Avdelingsoverlege Nils Olav Aanonsen ved avdeling for voksenrehabilitering ved Ullevål universitetssykehus hevdet i en kunnskapsstudie offentliggjort i 2004 at Ritalin gav voksne med ADHD et bedre liv.

Det ble også konkluderte med at det var få rapporter om betydningsfulle negative effekter ved langtidsbehandling og anbefalte videre bruk av Ritalin, som blant annet inneholder sentralstimulerende narkotikum nesten identisk med amfetamin.

Avdelingsoverlege Nils Olav Aanonsen gikk i 2004 hardt ut og hevdet at Ritalin gav voksne med ADHD et bedre liv.

Kunnskapsstudiet skulle i utgangspunktet ikke være en vanlig vitenskaplig rapport, men hadde som mål å overvåke medisineringen av voksne med ADHD-diagnose. Da prosjektet startet, ble 1328 pasienter godkjent for Ritalin-behandling.

Seks år senere var konklusjonen klar og Aanonsen fikk stor oppmerksomhet i norske medier. I et intervju med Aftenposten fortalte overlegen at 95 prosent av respondentene opplevde at Ritalin hadde god eller svært god effekt.
- Disse pasientene melder også om få komplikasjoner eller uønskede bivirkninger av behandlingen, sa Aanonsen i intervjuet.

Ett år etter den første rapporten var klar, kom Aanonsen med en ny supplerende rapport.

Avslørt
Men så kom avsløringen: Aanonsen hadde valgt å se bort fra rundt 70 prosent av pasientene da han trakk sine konklusjoner. Disse hadde falt fra i løpet av de to første årene av prosjektet.

Årsak: bivirkninger eller ingen virkning av medikamentene.
Konklusjonene om 95 prosent positiv effekt var dermed utelukkende bygget på de 30 prosentene som holdt ut i mer enn to år.

Det var den svenske skribenten Jan Larsson som først kom med anklagene. I en lengre utgreiing adressert til det Internasjonale narkotikakontroll komiteen i Wien plukker Larsson fra hverandre Aanonsens kunnskapsstudie og pekte på at han dreide sine konklusjoner feilaktig til å være positive til medisinering, til tross for at 70 prosent hadde falt fra.

Brevet ble også sendt til norske helsemyndigheter.

Nekter å svare
I dag ønsker ikke Aanonsen å svare på noen av TV 2 Nettavisens spørsmål.
- Jeg er ikke interessert i å snakke med deg, sier overlege Aanonsen når TV 2 Nettavisen ringer.

- Du er ikke interessert i å snakke med meg?
- Nei, svarer Aanonsen og legger på før TV 2 Nettavisen rekker å si hva saken gjelder.

Men da anklagene ble kjent i 2004, sa Aanonsen følgende i et intervju med Dagbladet:
- Vi ble sjokkerte og trodde ikke våre egne ører. Vi synes det er rart at påstander som i våre øyne er uberettiget, avstedkommer alt dette oppstyret. Det oppleves som ytterst ubehagelig, sa Aanonsen.

Denne konklusjonen var blant dem som måtte fjernes i den nye rapporten etter at Sosial- og helsedirektoratet ba om presiseringer.

Fjernet konklusjon
Måneden etter brevet fra Larsson ble mottatt, sendte Sosial- og Helsedirektoratet et brev til Aanonsen hvor de ber hans team av sakkyndige om å utdype og kommentere hvorfor så mange avsluttet behandlingen og hvilke bivirkninger som var rapportert.

Etter det TV 2 Nettavisen erfarer stilte direktoratet seg svært spørrende til Aanonsens positive uttalelser i Aftenposten. De så at rapporten fra 2004 inneholdt en rekke mangler allerede før Larsson kom med sine beskyldninger om juks.

Et knapt år senere kommer en ny versjon av kunnskapsstudien fra Aanonsen som nå inneholder de 70 prosentene han nedtonet i den første utgaven.
Konklusjonen om at voksne med ADHD-diagnoser burde fortsette å bruke sentralstimulerende legemidler var fjernet. (...)

Manglende studier

65 % of Promised Drug Studies Pending (65 % av lovte legemiddelstuier ennå ikke avsluttet)
washingtonpost.com 4.3.2006
Legemiddelfirmaer har igangsatt knapt en tredjedel av de opfølgningsstudier, som de orpliktet seg til å gjennomføre straks deres nye legemiddel var kommet på markedet, opplyste staten i går. (Drug companies have launched barely a third of the follow-up studies they agreed to undertake once their new medications were on the market, the government said yesterday.)

Ofte har legemidler fått fremskyndet godkjennelse fra statlige kontrollorgan på den betingelse at studiene skulle gjennomføres. (Often the drugs received expedited approval from federal regulators on the condition that the studies be carried out.)

Food and Drug Administration uttalte i en årsrapportt, datert 30 september, at 65 prosent av de 1 231 studier "etter markedsføring", som firmaer hadde forpliktet seg til å utføre, ennå ikke var avsluttet. (The Food and Drug Administration said in an annual report that, as of Sept. 30, 65 percent of the 1,231 "post-marketing" studies that companies had pledged to carry out were still pending.)

"Det betyr ikke at de aldri vil bli igangsatt," sa John Jenkins, direktør for FDAs Office of New Drugs, som bemerker at 116 av de 797 studier som var forpliktet i løpet av de 12 måneder avsluttes i september. Han sa at det kan ta seks måneder til et år å designe og introdusere kliniske forsøk. ("That doesn't mean they will never be started," said John Jenkins, director of the FDA's Office of New Drugs, noting that 116 of the 797 studies were committed to during the 12 months ending in September. The clinical trials can take six months to a year to design and launch, he said.)

Noen studier er forplikter tidligere år, men FDA ga ikke noen oppsplitting. (Some studies had been committed to years earlier, but the FDA did not provide a breakdown.)

De 797, som ikke er avsluttet, representerer en ubetydelig nedgang fra 812 i forhold til året før. FDA-leder Kathleen Quinn sa kontrollorganet føler at "disse tall viser at legemiddelfirmaer tar disse tingene alvorligt." (The 797 pending studies represent a slight dip from 812 a year earlier. FDA official Kathleen Quinn said the agency feels that "these numbers show drug companies are taking this thing seriously.")

Jerry Avorn, professor ved Harvard Medical School professor og forfatter av "Powerful Medicines," hvor han kritiserer FDAs system for oppfølging etter markedsføring, sa at antallet viser systemet ikke virker. (Jerry Avorn, a Harvard Medical School professor and author of "Powerful Medicines," in which he criticizes the FDA's post-marketing system, said the numbers show the system is broken.)

"Denne nye informasjon er en pinlig fortsettelse på liknende årlige rapporter publisert av FDA, som går på den hårreisende tilstand med hensyn til legemiddelsikkerhetsstudier som de har "krevd" at legemiddelprodusenter skal gjennomføre. Det er skandaløst at de formodede verserende studier, omtrent to tredjedeler, ennå ikke er startet," sa Avorn. ("This new information is an embarrassing continuation of similar reports issued by FDA each year on the appalling state of the medication safety studies it has 'mandated' drug manufacturers to perform. It is scandalous that of the supposedly active studies, about two-thirds haven't even been started yet," Avorn said.)

Men Alan Goldhammer, hos Pharmaceutical Research and Manufacturers of America, sa at tallene ikke bør "forvrenges." (But Alan Goldhammer, of the Pharmaceutical Research and Manufacturers of America, said the figures should not be "distorted.")

New Drugs Hit the Market, but Promised Trials Go Undone (Nye legemidlere kommer på markedet, men lovte studier utføres ikke)
New York Times 4.3.2006

Uredelig forskning, tilbaketrekking, og opprydding i den medisinsk litteratur: Lærepenger fra Poehlman-saken

Research Misconduct, Retraction, and Cleansing the Medical Literature: Lessons from the Poehlman Case (Uredelig forskning, tilbaketrekking, og opprydding i den medisinsk litteratur: Lærdommen fra Poehlman-saken)
Ann Intern Med (18.4.2006)
MEDICINE AND PUBLIC ISSUES (MEDISIN OG OFFENTLIGE SPØRSMÅL)
Harold C. Sox, MD, Editor, and Drummond Rennie, MD
Den vitenskapelige litteratur er en offisiell opptegnelse av søkingen etter sannhet. Publikasjon av forfalskede data avleder dette søket. Det vitenskapelige samfunn har en plikt å advare mennesker om å ignorere en artikkel som inneholder forfalskede data og må forsøke å forhindre utilsiktet sitering fra den. Det vitenskapelige samfunn iverksetter disse oppgaver ved å publisere en tilbakekalling og å linke den falske artikkelens til siteringer gjort i elektroniske register for medisinsk litteratur, slik som PubMed. Denne mekanisme er langt fra perfekt, som vist vi et tilfelle med vitenskapelig svindel begått av Eric Poehlman, PhD. Hans institusjon viste til tre tidsskrifter der de hadde publisert infiserte artikler. To tidsskrifter mislyktes å trekke tilbake. Det tredje tidssriftet trakk tilbake umiddelbart, men forfatterne fortsatte å sitere de artikler som var trukket tilbake. (The scientific literature is a record of the search for truth. Publication of faked data diverts this search. The scientific community has a duty to warn people to ignore an article containing faked data and must try to prevent inadvertent citation of it. The scientific community accomplishes these tasks by publishing a retraction and linking it to the fraudulent article's citation in electronic indexes of the medical literature, such as PubMed. This mechanism is far from perfect, as shown by a case history of scientific fraud perpetrated by Eric Poehlman, PhD. His institution notified 3 journals that they had published tainted articles. Two journals failed to retract. The third journal retracted immediately, but authors continued to cite the retracted article.)

Another duty of the scientific community is to verify the integrity of other articles published by the author of a fraudulent article. This task falls to the author's institution and requires coauthors to vouch for their article's integrity by convincing institutional investigators that the suspect author could not have altered the raw scientific data from their study. Two universities are currently investigating Poehlman's published research.

Maintaining the integrity of the scientific literature requires governmental institutions that have the authority to investigate and punish guilty scientists and requires that research institutions investigate alleged fraud. It requires journal editors to issue a retraction when they learn that their journal has published a tainted article. It requires research institutions to accept their responsibility to investigate every article published by a scientist who has published even 1 fraudulent article. Finally, it requires authors to take pains to avoid citing retracted articles and to issue a correction when they inadvertently cite a retracted article. (...)

Legemiddelfirmaer offentliggjør flere kliniske data

Drug firms disclose more clinical trial data (Legemiddelfirmaer offentliggjør flere kliniske data)
boston.com 11.1.2007
Responding to public criticism and increased pressure from prestigious medical journals, pharmaceutical companies are publicly disclosing more information about clinical trials they sponsor.

The number of trials with incomplete information listed on clinicaltrials.gov, the National Institutes of Health's registration website, plunged to 8 percent in the first 11 months of 2006, from 26 percent prior to 2006, said an editorial published today in the New England Journal of Medicine.

"Although more can be done, this improvement in registration quality is to be praised," said the editorial's authors, Journal editor Dr. Jeffrey Drazen and Dr. Deborah Zarin, head of clinicaltrials.gov. (...)

Critics say drug makers sometimes attempt to bury negative trial results.

The long-standing issue of clinical-trial disclosure came to a head in 2004 following accusations that British drug maker GlaxoSmithKline suppressed trial results suggesting its antidepressant Paxil provided little benefit to adolescents and may have led some to contemplate suicide. GlaxoSmithKline agreed to pay $2.5 million to settle a lawsuit brought by New York Attorney General Eliot Spitzer over the company's failure to disclose the information.

The New England Journal of Medicine today details a Pfizer Inc. trial of a renal cancer treatment. The editors were prepared to reject an article about the trial because Pfizer didn't disclose what health effects it would measure based on "commercial sensitivity." The journal agreed to publish the manuscript after learning a trial investigator independently registered the study, including information about the health effects to be measured. Pfizer said it is investing millions of dollars in an effort to make sure required information about its drug trials is disclosed. (...)

Åpen tilgang til alle studieresultater

Bill Seeks Access to Tax-Funded Research
washingtonpost.com 3.5.2006
Grant Recipients Would Be Required to Post Findings on Internet (...)

Bill would make drug trials public
duluthsuperior.com 22.3.2006
- Two lawmakers want Minnesota to make up for failures in the federal drug safety system by requiring drug companies to reveal the results of all clinical studies -- good and bad.

State Rep. John Lesch, DFL-St. Paul, and state Sen. John Hottinger, DFL-St. Peter, said Tuesday that drug companies conduct the bulk of the clinical trials on new drugs, but aren't obliged to disclose trials that turn out badly.

"We think it's only fair that doctors and consumers have all the available results to make informed choices about the safety of these drugs," Lesch said.

Kim Witczak of Minneapolis joined lawmakers at a Tuesday morning news conference. Her husband committed suicide shortly after he started taking an antidepressant, Zoloft, for a sleeping disorder. Witczak has lobbied for greater reporting of drug risks since her husband's death in 2003.

In recent months, the U.S. Food and Drug Administration has required greater warnings of suicide risks for people taking antidepressants, but Witczak said the maker of Zoloft has known of this risk since the 1980s. Her lawsuit against the drug company, Pfizer, has unearthed documents proving this early knowledge, she said.

"We the public and even the FDA seem to be the last to know," she said. "The state of Minnesota needs to step in where the federal government has dropped the ball." (...)

Beslutning om å gjøre legemiddelutprøvninger offentlige etterleves ikke

Beslutet att göra läkemedelsprövningar offentliga efterlevs inte
Läkemedelsvärlden 2006(6) (Juni)
Bara tre av tio företag informerar på sin svenska hemsida

Läkemedelsindustrin har åtagit sig att öppet redovisa vilka läkemedelsprövningar som pågår, liksom resultaten. Såväl positiva som negativa. Men det verkar vara lite si och så med publiceringen. Framförallt gör företagen mycket lite för att hjälpa den intresserade att hitta till sajterna.

KLINISKA PRÖVNINGAR För snart ett och ett halvt år sedan enades läkemedelsindustrin om att offentliggöra sina kliniska prövningar i en publik databas. Enligt överenskommelsen ska studier anmälas till en databas senast tre veckor efter att de påbörjats. Avslutade ska senast ett år efter läkemedlets första godkännandet finnas tillgängligt.

Men det visar sig vara lite si och så med publiceringen, kanske främst med tillgängligheten, dryga året efter överenskommelsen.

Av de tio företag som sålde mest i Sverige förra året fann Läkemedelsvärlden bara tre som hade en länk på sina svenska webbplatser till sidor där prövningar presenteras. Och då behövde vi dessutom hjälp av företaget för att finna en av dem. (...)

Legemiddelindustriforeningen om legemiddelutprøvninger og offentlighet

6 av 10 vil teste nye medisiner
orapp.no 18.5.2006
Seks av ti nordmenn vil være med på utprøving av nye medisiner hvis de rammes av en alvorlig sykdom.

Det viser en undersøkelse som Opinion har gjort for Legemiddelindustriforeningen.

94 prosent svarer at utviklingen av nye og bedre medisiner er viktig for et best mulig pasienttilbud. Videre mener nesten halvparten av de spurte, 48 prosent, at legemiddelindustrien er den viktigste bidragsyter, mens 11 prosent mener sykehusene har denne rollen, melder Legemiddelindustriforeningen.

70 prosent av de spurte mener det er nødvendig med kontakt mellom leger og legemiddelindustrien for at legene skal være faglig oppdatert. I en tilsvarende måling for ett år siden var det bare 54 prosent som mente at slik kontakt var nødvendig.

RYDDIG
48 prosent er helt eller delvis enig i at kontakten mellom helsepersonell og legemiddelindustri foregår på en ryddig måte. 38 prosent er helt eller delvis uenig, mens 14 prosent er usikre.

- Dette er likevel oppmuntrende tall for oss. Sammenlignet med en måling for ett år siden er det flere som mener at denne kontakten nå foregår på en ryddig måte. Det tar vi som en kraftig oppmuntring, og tegn på at det arbeidet Legemiddelindustriforeningen gjør for å skape åpne og etterprøvbare relasjoner mellom industri og helsepersonell er riktig, mener administrerende direktør Pål Christian Roland. (...)

LES INDUSTRISTØTTEDE LEGEMIDDELGJENNOMGÅELSER MED FORSIKTIGHET, ADVARER LEGER

Read industry supported drug reviews with caution
BMJ 2006;333 (14 October)
Industry supported meta-analyses are of inferior quality to Cochrane meta-analyses of the same drugs. Jørgensen and colleagues (p 782) systematically compared the methodology and conclusions of 24 Cochrane meta-analyses with industry supported meta-analyses and other meta-analyses that studied the same two drugs in the same disease. Cochrane reviews were more transparent and more often considered the potential for bias than industry supported reviews, which always recommended the drug without reservation. Reviews with no, undeclared, and not for profit support had similarly cautious conclusions to matched Cochrane reviews. (...)

Online First
(Cochrane reviews compared with industry-supported meta-analyses and other meta-analyses of the same drugs: systematic review)
http://bmj.bmjjournals.com/cgi/rapidpdf/bmj.38973.444699.0B

A study published on bmj.com today has found that reviews of drugs which are supported by the pharmaceutical industry are less transparent, and are more likely to reach favourable conclusion on drugs, than independent reviews.

According to the authors, bias in drug trials is common and often favours the trial-sponsor’s product. To balance this effect, independent reviews – which can have a more critical and systematic approach - are essential to ensure doctors and other health professionals have the information they need on drugs. (...)

(Anm: Cochrane reviews compared with industry supported meta-analyses
and other meta-analyses of the same drugs: systematic review

BMJ, doi:10.1136/bmj.38973.444699.0B (published 6 October 2006)
(...) Conclusions
Industry supported reviews of drugs are less transparent than Cochrane reviews and have few reservations about methodological limitations of the included trials; their conclusions should be read with caution.We believe that details of concealment of allocation, blinding, inclusion and exclusion criteria for trials, search strategies, and estimated effects in each included trial need to be reported to allow readers to judge the reliability of reviews. To improve transparency, access to the protocol should be available.
Protocols for Cochrane reviews are published in the Cochrane Library, and protocols for other systematic reviews can be registered free of charge at the UK national research register through the Centre for Reviews and Dissemination in York, UK. (...)

(Anm: Rapid Responses to: Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review BMJ 2006; 333: 782 [Abstract] [Full text].)

- Industry-Supported Drug Research Called Into Question

Industry-Supported Drug Research Called Into Question
healthfinder.gov 6.10.2006
Studies done by nonprofit groups tend to be less biased, review contends.

-- Drug reviews that are supported by the pharmaceutical industry tend to be more biased and rate the drugs more favorably than independent reviews, a new study contends.

As a result, industry-supported reviews of existing drug research need to be taken with a grain of salt, said the authors of the study in the Oct. 7 issue of the British Medical Journal. (...)

All seven of the industry-supported reviews recommended the drug in question without hesitation, while none of the Cochrane reviews did. (...)

"This suggests that the main problem with industry-supported reviews lies in how conclusions are formulated," the authors stated. (...)

- 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. (...)

(Anm: Drug Testing: Undercover Tests Reveal Significant Vulnerabilities in DOT's Drug Testing Program. GAO-08-225T, November 1 http://www.gao.gov/cgi-bin/getrpt?GAO-08-225T
Highlights - http://www.gao.gov/highlights/d08225thigh.pdf

Drug Safety: Preliminary Findings Suggest Weaknesses in FDA's Program for Inspecting Foreign Drug Manufacturers. GAO-08-224T, November 1 http://www.gao.gov/cgi-bin/getrpt?GAO-08-224T
Highlights - http://www.gao.gov/highlights/d08224thigh.pdf.)

- In Defense of Pharmacoepidemiology — Embracing the Yin and Yang of Drug Research

In Defense of Pharmacoepidemiology — Embracing the Yin and Yang of Drug Research
NEJM 2007 357:2219-2221 (November 29)
The past decade has not been kind to observational studies of medications. The damage began in 1998 with the publication of the Heart and Estrogen–Progestin Replacement Study, a randomized controlled trial showing that hormone replacement increased the risk of cardiac events among postmenopausal women with heart disease. Like many physicians, I had been teaching the gospel that estrogen use prevented heart disease — an idea based on observational studies1 showing that postmenopausal women who regularly took estrogen were less likely to have heart disease than apparently similar women who did not take hormones. It now appeared that this had been a misleading conclusion that may have led to drug-induced disease in millions of patients. (...)

- GSK to strip down through outsourcing and offshoring

US Senator seeks probe into pharma outsourcing (Amerikansk senator ber om granskning av legemiddelfirmaers 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 signals vigour for outsourcing
in-pharmatechnologist.com 11.12.2007
11/12/2007 - Eli Lilly is the latest big pharma company to signal plans of a vigorous commitment to outsourcing in a bid to prevent its fortunes fading.

The company said it is intending to take on a new, leaner shape, forming itself into a "network structure" made up of third party service providers and contract firms, in its quest to ensure a rosy bottom line in these turbulent pharma times. (...)

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. (...)

- Pfizer plans more off-shoring and outsourcing

Pfizer flyttar produktion till Asien
lakemedelsvarlden.se 3.12.2007
Pfizer planerar att flytta åtminstone 30 procent av sin produktion utanför USA. Produktionen ska framförallt läggas i Asien. (...)

Pfizer plans more off-shoring and outsourcing
drugresearcher.com 3.12.2007
03/12/2007 - Pfizer is looking to Asia for both R&D and manufacturing outsourcing and to help it cut costs in a bid to mitigate the effects of patent expiries and competition from generic drugs.

Pfizer announced plans to increase its R&D presence in Asia at its Hong Kong investor meeting on Friday, while saying it is also look to double the amount of manufacturing outsourcing to 30 per cent.

The pharma giant has struggled in the past year and the high profile clinical trial failure of its cholesterol-lowering drug Torcetrapib has only matters worse. (...)

- Fattige godt egnet til forsøk

Asia is a growing base for drug trials
BMJ 2008;336:1458 (28 June)
Asia is a growing base for drug trials: Asian countries are now engaged in 18% of the world’s clinical trials and are involved in more trials sponsored by the drug industry than any other region outside North America and Europe, concludes a study by the University of Hong Kong’s Clinical Trials Centre (Clinical Trial Magnifier www.clinicaltrialmagnifier.com). India, South Korea, and Taiwan are the most active countries. (...)

Ny rapport: Omstridt norsk test av AIDS-medisin i u-land
norwatch.no 22.11.2007
Det norske legemiddelselskapet A-Viral testet ut AIDS-medisiner på filippinske forsøkspersoner stikk i strid med etiske anbefalinger i Norge. Dette går fram av en helt ny Norwatch-rapport om norsk testing av legemidler og behandlingsmetoder i u-land. (...)

Norwatch har i dag lagt ut en rapport om hvilke norske selskaper som har foretatt uttesting av legemidler og behandlingsmetoder i Sør. Dette er den eneste rapporten hittil som på en utfyllende måte tar for seg temaet. Last ned rapporten her (1 Mb, pdf).

Rapporten tar særlig for seg det norske selskapet A-Viral som prøvde ut AIDS-medisiner på Filippinene i 2000-2002. Norwatch har besøkt Filippinene og lyktes å spore opp fem av pasientene som deltok i det norske prosjektet.

I tillegg ser rapporten på A-Virals AIDS-tester i Uganda, NorChips livmorhalskreft-undersøkelser i Kongo, Rikshospitalets strupekreft-behandling i Kina og Normedicas AIDS-planer i Thailand.

– Utilstrekkelig pasientinformasjon
Ingen skal delta i kliniske undersøkelser uten at de samtykker. Vanligvis skjer et samtykke ved at pasienten signerer en utfyllende kontrakt, som gjør rede for medikamentet, prosjektet og selskapet. (...)

Fattige godt egnet til forsøk
dagbladet.no 22.11.2007
(Dagbladet.no): Legemiddelindustrien har et uuttømmelig behov for å teste ut nye medisiner, og stadig flere av forsøkene foregår i u-land.

Det er lettere å rekruttere pasienter her enn blant mer skeptiske nordboere.
Fattige pasienter blir sett på som mer egnet. En av grunnene er at pasientene i u-land ofte ikke bruker andre legemidler - de er «rene», slik at det er lettere å måle effekten, ifølge Norwatch - Framtiden i våre henders søkelys på norsk næringsliv i Sør.

De har utarbeidet en rapport om norsk testing av legemidler og behandlingsmetoder i u-land.

Trolig foregår mellom 20 og 30 prosent av all legemiddel-uttesting i u-land. (...)

- Medicinalindustri eksporterer menneskeforsøg til ulande

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).

Medicinalindustri eksporterer menneskeforsøg til ulande
business.dk 4.4.2008
Det er bekymrende, at medicinalvirksomheder flytter deres forsøg på mennesker til u-lande, mener kritikere.

I lighed med den internationale medicinalindustri lægger Novo Nordisk og Lundbeck en stadig større del af deres kliniske forsøg i udviklingslande. Hovedårsagen er de hjemlige myndigheders pres for stadig flere tests, forklarer industrien. (...)

Dermed følger de to danske virksomheder den internationale tendens. Ifølge en ny kritisk rapport fra den hollandske NGO, SOMO, blev 40 pct. af medicinalindustriens test på mennesker gennemført i Asien og Øst- og Centraleuropa. (...)

- GSK dobler kliniske forsøk

GSK doubles clinical trials
thehindubusinessline.com 26.11.2007
‘Product patent regime cause for spurt’

GSK conducts clinical trials in India for its parent company, GSK Plc, across oncology, neuropsychiatry, cardiovascular and metabolic and anti-infectives segments.

Clinical trials in India are estimated to touch about $1.5 billion by 2010, says McKinsey. (...)

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. (...)

Evaluering av løsninger på sponsing og bias

Evaluating solutions to sponsorship bias (Evaluering av løsninger på sponsing og bias)
Journal of Medical Ethics 2008;34:627-630
More than 40 primary studies, and three recent systematic reviews and meta-analyses, have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. Industry sponsorship biases published scientific research in favour of the sponsors, a result of the strong interest commercial sponsors have in obtaining favourable results.

Three proposed remedies to this problem are widely agreed upon among those concerned with the level of sponsorship bias: financial disclosure, reporting standards and trial registries. This paper argues that all of these remedies either fail to address the mechanisms by which pharmaceutical companies’ sponsorship leads to biased results—design bias, multiple trials with predictable outcomes, fraud, rhetorical effects and publication bias—or else only inadequately address those mechanisms. As a result, the policies normally proposed for dealing with sponsorship bias are unable to eliminate it. Only completely separating public clinical research from pharmaceutical industry funding can eliminate sponsorship bias. (...)

Eksperter konkluderer at Pfizer manipulerte studier

Läkemedelsföretag anklagas för manipulation av medicinstudier
dagensmedicin.se 8.10.2008
Läkemedelsföretaget Pfizer anklagas i en rättegång för att ha manipulerat flera studier kring epilepsiläkemedlet Neurontin.

Det hävdar flera experter under den pågående rättegången i en federal domstol i Boston, USA. (...)

Experts Conclude Pfizer Manipulated Studies (Eksperter konkluderer at Pfizer manipulerte studier)
nytimes.com 8.10.2008
The drug maker Pfizer earlier this decade manipulated the publication of scientific studies to bolster the use of its epilepsy drug Neurontin for other disorders, while suppressing research that did not support those uses, according to experts who reviewed thousands of company documents for plaintiffs in a lawsuit against the company.

Pfizer’s tactics included delaying the publication of studies that had found no evidence the drug worked for some other disorders, “spinning” negative data to place it in a more positive light, and bundling negative findings with positive studies to neutralize the results, according to written reports by the experts, who analyzed the documents at the request of the plaintiffs’ lawyers.

One of the experts who reviewed the documents, Dr. Kay Dickersin of the Johns Hopkins Bloomberg School of Public Health, concluded that the Pfizer documents spell out “a publication strategy meant to convince physicians of Neurontin’s effectiveness and misrepresent or suppress negative findings.”

Pfizer issued a statement Tuesday denying that it had manipulated Neurontin data, saying “study results are reported by Pfizer in an objective, accurate, balanced and complete manner, with a discussion of the strengths and limitations of the study, and are reported regardless of the outcome of the study or the country in which the study was conducted.” (...)

Suit Alleges Pfizer Spun Unfavorable Drug Studies
online.wsj.com 8.10.2008
Pfizer Inc. marketers urged the suppression of medical studies that reached unfavorable conclusions about the effectiveness of the company's big-selling drug Neurontin, according to internal Pfizer documents submitted in a lawsuit against the company.

In 2004, Pfizer's Warner-Lambert unit pleaded guilty to felony charges that it promoted Neurontin for uses not approved by the Food and Drug Administration, including bipolar disorder and chronic nerve pain. The FDA originally approved the drug as an antiseizure treatment for epilepsy and in 2002 for one kind of pain related to shingles.

Pfizer paid $430 million to resolve the charges and reimburse state Medicaid (...)

- Publikasjonbias (publikasjonsskjevhet) i forsøk på antidepressiva og antipsykotika

Antipsychotic Clinical Trials & Exaggerated Benefits (Kliniske forsøk med antipsykotika og overdrivelse av nytte)
pharmalot.com 21.3.2012
Nok et tilfelle av påstått publikasjonsskjevhet er dukket opp. For fire år siden fant en gjennomgang av upubliserte studier sendt til FDA av ulike legemiddelprodusenter at mange antidepressiva hadde liten eller ingen effekt på pasienter. Hvorfor? Selektiv rapportering nesten doblet den tilsynelatende andel positive studier, overdrivelse av nytte som formodentlig påvirker pasientbehandlingen (back story). (Yet another instance of alleged publication bias has emerged. Four years ago, a review of unpublished studies submitted to the FDA by various drugmakers found many antidepressants had little or no effect on patients. How so? Selective reporting nearly doubled the apparent proportion of positive trials, exaggerating the benefits and, presumably, influencing patient treatment (back story).)

Nå viser en gjennomgang gjennomført av antipsykotika et lignende funn publisert i PLoS Medicine. Tre forskere fra Oregon Health & Science University undersøkte 24 forsøk før markedsføring registrert hos FDA for Abilify, Fanapt, Zyprexa, INVEGA, Seroquel, Risperdal, Consta og Geodon. Resultatene fra FDA-dokumenter ble deretter sammenlignet med resultatene publisert i medisinske tidsskrifter. (Now, a review was conducted of antipsychotics and a somewhat similar finding is being reported in PLoS Medicine. A trio of researchers from Oregon Health & Science University examined 24 premarketing trials registered with the FDA for Abilify, Fanapt, Zyprexa, Invega, Seroquel, Risperdal, Consta and Geodon. The results from the FDA documents were then compared with results published in medical journals.)

Hva fant de? Forskerne oppdaget at fire studier før markedsføring ble sendt til FDA - to involverer Abilify, som selges av Bristol-Myers Squibb, og en annen som involverer Geodon, som markedsføres av Pfizer - men disse ble aldri publisert. Og tre mislykkes å vise at noen av studielegemidlene hadde en statistisk fordel fremfor placebo. (...) (What did they find? The researchers discovered four premarketing trials were submitted to the FDA - two involving Abilify, which is sold by Bristol-Myers Squibb, and another involving Geodon, which is marketed by Pfizer - but these were never published. And three failed to show either study drug had a statistical advantage over placebo.)

(Anm: Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database. PLoS Med 2012;9(3): e1001189 (March 20).)

(Anm: Bias [baies] -en, - skjevhet i vitenskapelig undersøkelse el. resultat pga. mangelfull systematikk i innsamlingen av data. Etym.: eng., fr. biais helning, tendens. Kilde: ordnett.no.)

(Anm: Bias; (...) valg og vurderinger som på systematisk måte avviker fra det som er faktisk korrekt. Kilde: Store norske leksikon.)

(Anm: Legemiddeletterlevelse (Tas legemidler som foreskrevet?) (Adherence to Medication.) (…) Legemidler virker ikke på pasienter som ikke tar dem. (Drugs don't work in patients who don't take them.)  (NEJM 2005;353:487-497(August 4).)

(Anm: Publication bias is a type of bias occurring in published academic research. It occurs when the outcome of an experiment or research study influences the decision of the researcher whether to publish (or otherwise distribute) it. (en.wikipedia.org).)

Farlige følger av publikasjonsskjevhet
Tidsskr Nor Lægeforen 2004; 124:1499 (3.6.2004)
En analyse som inkluderer upubliserte data, viser at selektive serotoninreopptakshemmere ikke er effektive ved depresjon hos barn. Studien viser hvordan publikasjonsskjevhet kan føre til uriktig informasjon om legemidler.

Depresjon forekommer hyppig hos barn og ungdom, og selvmord er en av de vanligste dødsårsakene i denne aldersgruppen. Derfor er behovet for effektiv behandling stort.

I USA har flere typer selektive serotoninreopptakshemmere (SSRI) vært godkjent ved depresjon hos barn og unge. Også i Norge har slike medikamenter vært brukt på denne indikasjonen.

En reanalyse av tilgjengelige studier viser imidlertid at bare fluoksetin hadde en positiv effekt (1). Ved andre typer selektive serotoninreopptakshemmere, samt for venlafaxin, var risikoen ved bruk av medikamentet større enn nytten. Studien inkluderte upubliserte data fremlagt for amerikanske helsemyndigheters komité for godkjenning av legemidler. (...)

(Anm: Bias [baies] -en, - skjevhet i vitenskapelig undersøkelse el. resultat pga. mangelfull systematikk i innsamlingen av data. Etym.: eng., fr. biais helning, tendens. Kilde: ordnett.no.)

(Anm: Bias; (...) valg og vurderinger som på systematisk måte avviker fra det som er faktisk korrekt. Kilde: Store norske leksikon.)

(Anm: Legemiddeletterlevelse (Tas legemidler som foreskrevet?) (Adherence to Medication.) (…) Legemidler virker ikke på pasienter som ikke tar dem. (Drugs don't work in patients who don't take them.)  (NEJM 2005;353:487-497(August 4).)

(Anm: Publication bias is a type of bias occurring in published academic research. It occurs when the outcome of an experiment or research study influences the decision of the researcher whether to publish (or otherwise distribute) it. (en.wikipedia.org).)

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database (Publikasjonbias i forsøk på antipsykotika: En analyse av effektivitet ved sammenligning av den publiserte litteraturen i databasen til den amerikanske legemiddelkontrollen Food and Drug Administration)
PLoS Med 2012;9(3): e1001189 (March 20)
Background
Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. (...)

Conclusions
The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. (...)

Editors' Summary - Background
People assume that, when they are ill, health-care professionals will ensure that they get the best available treatment. But how do clinicians know which treatment is likely to be most effective? In the past, clinicians used their own experience to make such decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of trials, studies that investigate the efficacy and safety of medical interventions in patients. Evidence-based medicine can guide clinicians, however, only if all the results from clinical trials are published in an unbiased manner. Unfortunately, “publication bias” is common. For example, the results of trials in which a new drug did not perform better than existing drugs or in which it had unwanted side effects often remain unpublished. Moreover, published trials can be subject to outcome reporting bias—the publication may only include those trial outcomes that support the use of the new treatment rather than presenting all the available data. (...)

Newer Anti-Psychotic Drugs May be Less Effective (Nyere antipsykotika kan være mindre effektive)
ivanhoe.com 21.3.2012
(Ivanhoe Newswire) – If you’re in pain, there’s a pill for that! But it may not always be good. A new study shows clinical effectiveness of the newer form of drugs used to treat schizophrenia and other psychotic illnesses may be enhanced by a phenomenon called publication bias.

The study, led by Erick Turner from Oregon Health & Science University in Portland, shows selective reporting of research results undermines the integrity of the evidence base, which ultimately deprives clinicians of accurate date for prescribing decisions.

The authors reached these conclusions by reviewing 24 FDA-registered premarketing trials for eight second-generation antipsychotics – aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, long-acting injection, and ziprasidone – and then comparing these trials with the results conveyed in subsequent articles in medical journals.

They found that four premarketing trials submitted to the FDA remained unpublished and that all of the unpublished trials showed negative results – three showed the new anti-psychotic had no statistically significant advantage over placebo, and in one trial the new drug was statistically inferior to a much less expensive competing drug.

In the published trials, there was some evidence that the journal articles over-emphasized efficacy of the new drug. For example, the FDA review revealed that one of the newer drugs, iloperidone, was statistically inferior to three different drugs, but this information was not mentioned in the corresponding journal articles.

On the other hand, when the authors used meta-analysis to combine trial data and compare all eight drugs to placebo, they found that publication bias had little effect on their overall apparent efficacy. Of more concern was that some negative data remain unreported, potentially misleading clinicians.

"With further studies investigating publication bias in other drug classes, a more accurate evidence base can emerge. To that end, increased access to FDA reviews has been advocated. At the present time, the FDA is not as transparent with its clinical trial data as it could be," the authors were quoted saying.

However, "it is encouraging that the FDA has convened a Transparency Task Force. If the agency fulfills its mission to increase transparency, the public health will surely benefit," they said. (...)

- Forskere stiller spørsmål ved tradisjonell modell for effektstudier

Researchers question traditional efficacy trial model Forskere stiller spørsmål ved tradisjonell modell for effektstudier
outsourcing-pharma.com 6.9.2016
According to a recent study, traditional efficacy trials have limited applicability in everyday clinical practice – an issue which researchers say needs to be amended.

As part of their research, Professors Jorgen Vestbo and Ashley Woodcock from The University of Manchester's School of Biological Sciences conducted an effectiveness and safety trial of fluticasone furoate-vilanterol to manage COPD.

Their report, Effectiveness of Fluticasone Furoate-Vilanterol for COPD in Clinical Practice, was published in the New England Journal of Medicine.

According to the researchers, instead of using a traditional randomized cohort, the new study used representative patients who were already receiving care from a general practitioner (GP). In addition to providing the patient pool, the GPs continued administering the patients’ usual care which was built into the trial – basing the study in a real clinical environment. (…)

(Anm: Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice NEJM 2016 (September 4, 2016).)

- Forskare på Karolinska fälls för forskningsfusk. Artiklarna i bland annat the Lancet som Paolo Macchiarini och medförfattare skrivit baserades på forskningsfusk.

(Anm: Forskare på Karolinska fälls för forskningsfusk. Artiklarna i bland annat the Lancet som Paolo Macchiarini och medförfattare skrivit baserades på forskningsfusk. Det konstaterade Centrala etikprövningsnämnden, CEPN, som idag presenterade sitt yttrande. CEPN har haft i uppdrag att granska redligheten i sex artiklar publicerade i vetenskapliga tidskrifter, två av dem i the Lancet, efter skandalerna med kirurgen Paolo Macchiarini. Artiklarna är de viktigaste som publicerats som handlar om Paolo Macchiarinis forskning i Sverige och transplantationerna av luftstrupar på patienter. (lakemedelsvarlden.se 30.10.2017).)

Diverse artikler

Alle trodde han utviklet verdens første HIV-vaksine, men han bløffet hele tiden
tv2.no 4.7.2015
FENGSEL: Forsker Dong-Pyou Han er dømt til over fire og et halvt års fengsel for å ha jukset med forskningsresultatene til HIV-vaksine.

Dong-Pyou Han (58) var for få år siden en stjerne blant verdens ledende forskere på HIV-viruset.

Som ansatt ved et forskningslaboratorium i Cleveland var han delaktig da teamet hans begynte å teste en eksperimentell HIV-vaksine på kaniner.

Teamet mottok litt offentlig støtte, men da han i 2008 rapporterte at vaksinen var årsaken til at kaninene klarte å utvikle antistoffer mot HIV ble dette sett på som et så stort gjennombrudd at de statlige overføringene økte til mange titalls millioner kroner. (…)

Risikerer å bli utvist for alltid
Påtalemyndigheten mener på sin side at det er viktig å statuere et eksempel slik at andre ikke lar seg forlede til å jukse med offentlige forskningsmidler.

Dong-Pyou Han, som opprinnelig er fra Sør-Korea, ble dømt til 57 måneders fengsel og til å betale tilbake vel 59 millioner kroner i erstatning. (…)

Journals and drug industry funded research
Data from industry funded trials are reliable enough to be published

BMJ 2014;348:g1298 (Published 5 February 2014)
Cite this as: The question whether medical journals should stop publishing drug industry sponsored research is absurd.1 During the past decade the need for transparency and disclosure of all clinical trial data has been universally recognised. However, more than half of all drug trials are sponsored by drug companies. How can the industry be transparent about its trials if journals refuse to publish the results? By not making this information public, journals would contribute greatly to a biased view on the benefits and harms of new drugs. Why would the relatively scarce academia sponsored drug research be more reliable? There is good evidence that potential targets for drug discovery identified by academia could not be replicated by industry.2 (...)

Bioanalyst gets jail sentence for falsifying preclinical trial data
BMJ 2013;346:f2514 (18 April 2013)
A former senior bioanalyst who worked in Scotland for a US based drug discovery and development firm, Aptuit, has become the first person to be successfully prosecuted under the Good Laboratory Practice Regulations 1999 for manipulating data.

Steven Eaton, who worked for Aptuit until 2009, was found guilty at Edinburgh Sheriff Court and sentenced to three months in prison, after a prosecution brought by the Medicines and Healthcare Products Regulatory Agency (MHRA). (...)

Fängelse för forskarfusk
lakemedelsvarlden.se 18.4.2013
En brittisk forskare har fått fängelsestraff efter att ha förfalskat resultat i en studie av ett cancerläkemedel.

Det var 2009 som den brittiske forskaren förfalskade studieresultat för en läkemedelskandidat mot cancer. Anledningen till fusket var att han ville gå vidare och testa medlet på människor men hans verkliga data räckte inte till. Forskaren fabricerade då studieresultat och presenterade för sina dåvarande chefer.

Mannen, som då arbetade vid företaget Aptuit, har nu dömts till tre månaders fängelse av brittisk domstol, rapporterar BBC. Det hela uppdagades när kollegorna började titta närmre på hans dokumentation och konstaterade att allt inte stod rätt till. De avbröt då allt arbete som forskaren var involverad i vid företaget.

Fallet blev känt då han dömdes i mars under en lag som kallas Good Laboratory Practice Regulations. Han är den andra personen som hittills blivit åtalad under lagen men den första som blivit dömd.

Gerald Heddell, chef för det brittiska läkemedelsverkets inspektionsenhet, säger i ett utlåtande att han välkomnar domen och att den är en signal om att de inte tvekar om att åtala personer som på detta vis riskerar allmänhetens säkerhet.

Enligt BBC har den dömda forskaren manipulerat studieresultat sedan 2003. (...)

Scientist Steven Eaton jailed for falsifying drug test results
bbc.co.uk 17.4.2013
Eaton had been selectively reporting research data since 2003

A scientist who faked research data for experimental anti-cancer drugs has been jailed for three months for falsifying test results.

Steven Eaton, from Cambridgeshire, has become the first person in the UK to be jailed under scientific safety laws.

Eaton, 47, was working at the Edinburgh branch of US pharmaceutical firm Aptuit in 2009 when he came up with the scam.

If it had been successful, cancer patients who took the drug could have been harmed, the court was told.

Edinburgh Sheriff Court heard how Eaton had manipulated the results of an experiment so it was deemed successful when it had actually failed.(...)

Man guilty of manipulating drug tests (Mann skyldig i å manipulere legemiddeltester)
ft.com 12.3.2013
A man has been found guilty of manipulating the results of experimental medicine tests on animals to exaggerate their benefits, in the first such prosecution by British regulators.

Steven Eaton, a former employee of Aptuit, a US-based clinical research organisation, was judged at Edinbugh Sheriff’s Court for violating Good Laboratory Practice.

His actions since 2003 had falsely given the impression of successful tests, forcing a review of “many hundreds” of safety studies to ensure they had not been compromised, the Medicines and Healthcare Products Regulatory agency said. It ultimately concluded that the results did not invalidate the trials involved, from companies including AstraZeneca and Roche.

The prosecution comes at a time of growing debate over the data used in drug tests.

Mr Eaton had selectively reported figures on whether analytical methods were working properly and which assess the concentration of the drug in blood. The data manipulation ensured an experiment appeared successful when in fact it had failed.

The regulators said Aptuit had itself identified the problems through an internal audit. His actions triggered “considerable” costs and generated “significant” delays in testing medicines.

Gerald Heddell, director of inspection, enforcement and standards at the agency, said: “Mr Eaton’s actions directly impacted the validity of clinical trials and delayed a number of medicines coming to market, including one to treat depression. This conviction sends a message that we will not hesitate to prosecute those whose actions have the potential to harm public health.” (...)

Former Aptuit LLC Employee Found Guilty of Data Scam
biospace.com 13.3.2013
A former employee of the Aptuit clinical research organization was found guilty of altering pre-clinical trial data that was used to support applications to perform clinical trials, according to the UK’s Medicines and Healthcare products Regulatory Agency. The MHRA noted this was the first instance in which Good Laboratory Practice Regulations were used to pursue such a prosecution. The probe into Steven Eaton began when Aptuit identified serious irregularities in pre-clinical data and informed the agency. Dating back to 2003, he began selectively reporting used to assess whether analytical methods were working properly or to assess the concentration of the drug in blood. The data manipulation ensured an experiment was deemed successful, when it actually had failed, the MRHA notes. (...)

A Clinical Trial and Suicide Leave Many Questions: Part 5: The Case of the Mysteriously Appearing Documents
blogs.scientificamerican.com 12.3.2013
This series uses the story of Dan Markingson’s participation in a clinical trial of anti-psychotics at the University of Minnesota, his ultimate suicide while participating on the study, and subsequent events as a case study in which to explore various aspects of clinical trial conduct. In previous posts, we’ve looked at issues of “good clinical practices” and ethics: consent, investigator responsibilities, and conflicts of interest. In the last post, we examined the University’s response. Now we return to the importance of careful documentation of consent.

Since I last wrote on the lapses in good clinical practices at the University of Minnesota, involving the suicide of a clinical trial participant, Dan Markingson, more disturbing documents have come to light, provided and contextualized by Professor Carl Elliott. Hard to imagine, I know…but this single case can provide a lifetime of lessons on clinical trial conduct, oversight, and ethics. (...)

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).)

Sample size: how many participants are needed in a trial?
BMJ 2013;346:f1041 (15 February 2013)
Researchers investigated the effectiveness of a home based early intervention on children’s body mass index (BMI) at age 2 years. A randomised controlled superiority trial was used. The intervention consisted of eight home visits from specially trained community nurses in the first 24 months after birth; this was in addition to the usual childhood nursing service from community health service nurses. The control group received the usual childhood nursing service alone. Participants were first time mothers and their infants. The primary outcome was children’s BMI at age 2.1 (...)

FDA beskylder biotekselskab for at tilbageholde oplysninger
medwatch.dk 26.6.2012
Amylin har ifølge FDA tilbageholdt vigtige infomationer om bivirkninger forbundet med selskabets diabetesmiddel Bydureon.

De amerikanske sundhedsmyndigheder, FDA, har beskyldt biotekselskabet Amylin for at have tilbageholdt vigtige oplysninger om bivirkninger forbundet med brug af diabetesmidlet Bydureon. Det skriver Financial Times.

I et dokument fra januar, som blev offentliggjort for nyligt, gjorde FDA's ansvarlige for diabetesmedicin opmærksom på forsinkelser, før Amylin fremviste patientresultater relevante både i forhold til diabetesmidlet Byetta og den langtidsvirkende version af samme medicin, Bydureon.

Ifølge FDA har evalueringen fra myndighedernes side været "lang og kompliceret...til dels som følge af, at Amylin har tilbageholdt information om Byetta, som FDA anså for vigtig i sin evaluering af sikkerhed- og effekt af Bydureon". (...)

Problems of stopping trials early (Problemer med å stanse studier tidlig)
BMJ 2012;344:e3863 (15 June)
When interim analyses of randomised trials suggest large beneficial treatment effects, investigators sometimes terminate trials earlier than planned. Gordon H Guyatt and colleagues show how this practice can have far reaching and harmful consequences

In a seminal simulation study published in 1989, Pocock and Hughes showed that randomised control trials stopped early for benefit will, on average, overestimate treatment effects.1 Since then, the warning implicit in this simulation study has been largely ignored.

Fifteen years later, we reported a systematic survey which showed that trials stopped early for benefit—which we will refer to as truncated trials—yield treatment effects that are often not credible (relative risk reductions over 47% in half, over 70% in a quarter), and that the apparent overestimates were larger in smaller trials.2 We subsequently compared effect estimates from all the truncated trials we could identify that had been included in systematic reviews and meta-analyses with the results of non-truncated trials in those same meta-analyses. We found, on average, substantially larger effects in the truncated trials (ratio of relative risks in truncated versus non-truncated of 0.71). Again, we showed an association with the size of the truncated trial: large overestimates were common when the total number of events was less than 200; smaller but important overestimates occurred with 200 to 500 events; and trials with over 500 events showed small overestimates.3

The results of simulation studies and systematic surveys of truncated trials therefore show that when true underlying treatment effects are modest—as is usually the case—small trials that are stopped early with few events will result in large overestimates. Larger trials will still, on average, overestimate effects, and these overestimates may also lead to important spurious inferences. Uncritical belief in truncated trials will often, therefore, be misleading—and sometimes very misleading. (...)

Rapporterte ikke alvorlige bivirkninger
dagensmedisin.no 7.6.2012
Legemiddelfirmaet Roche har tatt i mot et stort antall alvorlige bivirkningsrapporter uten å sende dem videre til helsemyndighetene. Roche i Norge ser svært alvorlig på saken.

Legemiddelfirmaet Roche har tatt i mot et stort antall bivirkningsrapporter uten å sende dem videre til helsemyndighetene, slik reglene er.

Alvorlige bivirkninger ikke meldt
Legemiddelfirmaet, som er sveitsisk, hadde besøk av inspektører fra det britiske legemiddelverket i vinter.

Da alarmerte myndighetene sine kolleger i Europa, ifølge svenske Aftonbladet som fikk tilgang til en e-post sendt til det svenske Läkemedelsverket.

- Det handler om alvorlige bivirkninger som firmaet er pliktige til å rapportere, sier Kerstin Jansson i Läkemedelsverket til avisen.

Bivirkningsrapportene skal ha kommet inn til legemiddelfirmaet fra både pasienter, helsevesenet og kliniske studier.

Bivirkninger fra minst 100 000 pasienter har aldri blitt rapportert videre. (...)

Drug companies and publishers set out 10 steps to enhance credibility of industry sponsored trials
BMJ 2012;344:e3767 (28 May)
A coalition of drug companies and major medical journal publishers has recommended 10 steps to help refurbish the tarnished credibility and enhance the quality and transparency of the reporting of industry sponsored clinical trials. The 10 steps were published in the May issue of the Mayo Clinic Proceedings.1
The Medical Publishing Insights and Practices Initiative (MPIP) was established in 2008 by leading drug companies and medical publishers as an ongoing collaboration (www.mpip-initiative.org). The recommendations grew out of a meeting held in New York in November 2010.

The initiative’s first recommendation is that research should be grounded in the asking and answering of questions of scientific and clinical importance, within the context of regulatory requirements for approval of a drug or device.

“Credibility is compromised when clinical research is intended for marketing purposes rather than advancing scientific and medical knowledge,” the authors wrote. The paper urges sponsors and authors to “enhance transparency and credibility by better explaining . . . the decision-making process underlying the research endeavor.” (...)

Pharma research not always more positive on drugs
reuters.com 24.2.2012
(Reuters Health) - Drugmaker-funded science isn't always more likely to favor new medicines than studies paid for by non-profits, according to a new report on past research in rheumatoid arthritis.

The finding flies in the face of a large body of evidence showing industry studies tend to promote new drugs and downplay potential side effects. (...)

BIAS UNIVERSAL

But Rothman said Khan's team is emphasizing the wrong point.

"The finding is not that industry doesn't have a proclivity to publish positive results. The finding is that not-for-profits also have a proclivity to publish positive results," he said. "The problem may be the journals rather than industry or not-for-profits." (...)

Duke Scientist Suspended Over Rhodes Scholar Claims
nytimes.com 20.7.2011
Duke University School of Medicine has suspended a researcher and stopped patient enrollment in three cancer studies upon learning of reports that the researcher had overstated his academic credentials. (...)

The controversy erupted late last week after an article published in The Cancer Letter, a weekly publication for cancer specialists, reported that Dr. Potti, an assistant professor of medicine, had on occasion exaggerated his credentials. (A spokeswoman at Rhodes House at Oxford confirmed on Tuesday that Dr. Potti had not received the scholarship.)

When questions about Dr. Potti’s credentials became public, the American Cancer Society suspended payments of a five-year, $729,000 grant awarded to Dr. Potti to study the genetics of lung cancer. The society awarded the grant based in part on a résumé from the doctor that included the Rhodes honor, said Dr. Otis W. Brawley, the chief medical officer of the cancer society.

Dr. Potti did not respond to an e-mail message seeking comment. (...)

(Anm: Four Cancer Genomics Papers Retracted From Top Journals (medscape.com 4.3.2011).)

Svindel og humbug: Forskere pillede ved resultater af personlig kræftmedicin
ing.dk 14.7.2011
Løgn om akademisk hædersbevis afslørede, at amerikanske forskere i årevis har givet kræftpatienter virkningsløs behandling med medicin målrettet med gentest.

En sag om videnskabelig uredelighed ryster i øjeblikket amerikanske kræftforskere, efter det er kommet frem, at Doktor Anil Potti fra medicinskolen på Duke Universitet ikke bare øjensynligt har løjet om sine videnskabelige hædersbevisninger, men at han tilsyneladende også har manipuleret med forskningsresultater og behandlet patienter med ubrugelig medicin i årevis.

Blandt andre den amerikanske avis New York Times har dækket skandalen.

Ifølge avisen fik Doktor Anil Potti og hans kolleger i 2006 offentliggjort en videnskabelig artikel i det prestigiøse tidsskrift Nature Medicine. I artiklen beskrev forskerne en metode, de havde udviklet, som kunne hjælpe læger med at vælge den helt rigtige kemobehandling til en bestemt patient på baggrund af genom test, der beskriver kræftsvulstens molekylære opbygning.

En anden kræftforsker, doktor John Minna fra Texas Universitet, forskede også i området. Han bad to statistikere om at se på resultaterne i den offentliggjorte artikel, og statistikerne fandt omgående fejl. Forskerne fra Duke Universitetet affejede dog fejlene som betydningsløse. (...)

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. (...)

Inadequate reporting of research ethics review and informed consent in cluster randomised trials: review of random sample of published trials
BMJ 2011; 342:d2496 (11 May)
Objectives To investigate the extent to which authors of cluster randomised trials adhered to two basic requirements of the World Medical Association’s Declaration of Helsinki and the International Committee of Medical Journal Editors’ uniform requirements for manuscripts (namely, reporting of research ethics review and informed consent), to determine whether the adequacy of reporting has improved over time, and to identify characteristics of cluster randomised trials associated with reporting of ethics practices. (...)

Conclusions Reporting of research ethics protections in cluster randomised trials is inadequate. In addition to research ethics approval, authors should report whether informed consent was sought, from whom consent was sought, and what consent was for. (...)

(Anm: Openness and honesty in gaining fully informed consent will benefit both patients and doctors BMJ 2015;350:h1784 (Published 07 April 2015).)

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. (...)

Special report: Big Pharma's global guinea pigs
reuters.com 6.5.2011
(Reuters) - The Polish port city of Gdansk is famous for its shipyards. Hungary's fifth largest city, Pecs, is known for its ancient architecture and brewery. Neither is particularly renowned for medicine. Yet when AstraZeneca Plc tested its big new drug hope Brilinta on heart attack patients in a major clinical study, it was hospitals in these places that enrolled some of the highest number of patients anywhere in the world. (...)

"The motivation to involve lots of patients is very high in Eastern European countries and also in Asia," says Dr. Ivan Horvath, head of interventional cardiology at the University of Pecs. "There are three factors driving this. Our patients get access to a new drug, which is free during the trial. It is also very important for scientific reasons. And we get paid." (...)

In the United States, the widespread "off-shoring" of research was highlighted in a report last year by the inspector general of the Department of Health and Human Services, which revealed just how reliant the country has become on foreign testing. In 2008, a total of 78 percent of all subjects participating in trials to support drug applications submitted to the Food and Drug Administration (FDA) were enrolled at foreign sites -- and as more experimental medicines move through the pipeline the numbers are set to increase further. (...)

Limitations Of The Evidence Base For Prescribing Aripiprazole In Maintenance Therapy Of Bipolar Disorder
medicalnewstoday.com 3.5.2011
The evidence base for the prescribing of aripiprazole in maintenance treatment of bipolar disorder is limited to a single trial, sponsored by the manufacturer of aripiprazole, according to a rigorous appraisal of the evidence for its use led jointly by Alexander Tsai of Harvard University, Boston USA, and Nicholas Rosenlicht of the University of California San Francisco, USA. In the paper, published in this week's PLoS Medicine, the authors describe key limitations of the trial, which were not identified in most subsequent review articles and guidelines for the treatment of bipolar disorder in which the trial was cited.

Bipolar disorder (also known as manic depression) is a common and serious psychiatric illness. Individuals with bipolar disorder experience mood swings with manic episodes (where they may feel euphoric, restless, and behave impulsively), along with depressive episodes where they may feel low, worthless, and suicidal. Aripiprazole is a second-generation antipsychotic medication and the newest of such drugs to have received approval by the US Food and Drug Administration (FDA) for use both in treatment of acute episodes and, more recently, for maintenance therapy. (...)

Stan Kutcher involved in controversial drug test
thecoast.ca 28.4.2011
Lberal candidate for Halifax co-authored problematic Paxil study

Stan Kutcher, the Liberal candidate for Halifax in Monday’s federal election, is running on his expertise as a doctor.

“I have a lot of experience in the health field,” says Kutcher, “in multiple areas: as a clinician, as a researcher, as associate dean of our medical school and in my work globally in my work with the World Health Organization, as someone who has worked to establish a number of national health institutions.”

But Kutcher’s experience as a clinician and researcher includes his involvement in a controversial drug test known as the Paxil 329 study, which was the subject of multiple lawsuits and explosive allegations of wrongdoing by researchers, and which ultimately changed the way medical research is conducted.

That study started in 1992, when Martin Keller, then the chair of the Psychiatry department at Brown University, proposed to the drug company SmithKline Beechman a study of the use of Paxil for the treatment of adolescent depression. In 2000, SmithKline Beechman merged with Glaxo Wellcome to become GlaxoSmithKline.

The drug trials took place between 1994 and 1997 at 12 research centres across North America, including the Dalhousie Medical School, where Kutcher oversaw the trials. It was a typical “double blind” study, with half the participants taking Paxil, and half taking a placebo. The results were published in 2001, with Kutcher as co-author.

But as documents later made public through the lawsuits demonstrate, the initial outcome measures in the study showed that there was no difference in therapeutic benefits between Paxil and the placebo, but those measures were changed to give Paxil a more favourable result.

“They essentially distorted the outcome measures, and essentially lied,” says Alison Bass, a former science reporter with the Boston *Globe* who broke the story and went on to write *Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial*, which examines the Paxil 329 study. “They also omitted information about adolescents who became suicidal on Paxil and withdrew from the study. And they miscoded those teenagers---they said they were non-compliant when in fact they had been withdrawn from the study because they became suicidal.”

Only in 2003, when a secretary at Brown leaked information to Bass, did the problems with the study became public. Afterwards, New York state attorney general Eliot Spitzer sued GlaxoSmithKline for fraud; that suit was settled out of court, but together with separate suits filed in Canada and California, hundreds of internal GSK documents were released. In Britain, the Committee on the Safety of Medicine found that the incidence of suicidal thoughts in the Paxil group was double that of the placebo group. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

2-Deaths in Pfizer arthritis trial hurt shares
reuters.com 21.4.2011
* 4 patient deaths reported in Pfizer drug study
* Pfizer shares close down 3 percent
* Pfizer says one of four deaths found drug study-related (Adds Pfizer comment)

NEW YORK, April 21 (Reuters) - New data raising safety concerns for Pfizer Inc's (PFE.N) experimental arthritis drug sent its shares down 3 percent, while lifting shares of rival drugmaker Abbott Laboratories (ABT.N), analysts said.

Wells Fargo analyst Larry Biegelsen in a research report on Thursday said four deaths were seen in one late-stage study of tofacitinib, Pfizer's oral drug for rheumatoid arthritis, which has been considered a potential rival to Abbott's big-selling Humira.

It was not clear from a brief description of the study, called an abstract, that the drug caused the deaths, Biegelsen said. But the report of the fatalities spooked investors.
The abstract from a 792-patient study to be presented at a meeting of the European League against Rheumatism said four patients who had been taking the 10-milligram dose of the Pfizer drug had died, including one from heart failure.

Pfizer said in a statement late on Thursday that the investigator reported only one of the four deaths -- the case of respiratory failure -- as study-drug related.

The drugmaker also said that the mortality rate from all causes across its drug development program, including this study, is within the range of rates reported for all biologic therapies for rheumatoid arthritis. (...)

Withdrawal of clinical trials policy by Canadian research institute is a “lost opportunity for increased transparency”
BMJ 2011; 342:d2570 (21 April)
Canadian researchers and academics are puzzled by the Canadian Institute for Health Research’s decision to withdraw its policy on clinical trial registration and results just three months after posting it on its website.

The institute has declined to comment on the decision. A statement on its website says that its policy has been “superseded” by a more general guidance document on the ethics of research involving humans that was prepared for, and approved by, Canada’s three major public funding agencies.

“The CIHR [Canadian Institute for Health Research] policy certainly was leading the drive towards increasing transparency,” said An-Wen Chan, a scientist with the Women’s College Research Institute in Toronto and co-author of the Ottawa Statement on Principles and Implementation of Clinical Trial Registration and Results Reporting (BMJ 2005;330:956-8; doi:10.1136/bmj.330.7497.956). (...)

Consultant is suspended for inventing data for drug trial (Konsulent er suspendert for å dikte opp data i legemiddelforsøk)
BMJ 2011; 342:d2261 (7 April)
A consultant community physician in north London has been suspended from practice for 12 months for research fraud after inventing patients for a clinical trial.
Devasenan Devendra, 41, lied repeatedly to the drug company Novartis after claiming to have recruited 69 patients for a trial comparing drugs for Muslims with diabetes who fast during Ramadan. The actual number was six.

The General Medical Council fitness to practise panel said suspension was necessary to mark the “profound unacceptability” of Dr Devendra’s conduct, which “undermines the trust that both the public and the professional have in medicine as a science.”

But the panel decided not to strike him off the medical register after hearing that he had an “exemplary” past record, did not benefit financially, and had started the research with the best of intentions. His dishonesty arose after he encountered unexpected difficulties, including losing funding for two clinical assistants and being unable to locate patients involved in earlier research he had conducted on the same subject. (...)

Why do clinical trials exclude depressed people?
reuters.com 18.3.2011
NEW YORK (Reuters Health) - When the U.S. Food and Drug Administration announced in 2009 that Pfizer Inc's smoking-cessation drug Chantix would need to carry a restrictive "black box" warning label, the move didn't really surprise the market.

The drug's sales had already been declining. By the end of 2009, they had dropped to $700 million, down from $846 million the previous year.

"When this drug launched, a lot of people expected a blockbuster drug, with over $1 billion in sales, but then the reports of the side effects started coming in," Damien Conover, an analyst with Morningstar, told Reuters Health.

The FDA's response came after hundreds of reports of erratic behavior and several suicides. Now, Pfizer faces a civil lawsuit involving at least 1,200 patient complaints.

In retrospect, experts say all of this could have been avoided -- or at least predicted -- had the company's clinical trials been designed differently. Pfizer tested Chantix on thousands of smokers in order to get FDA approval, but the clinical trials excluded people with depression. (...)

Medical Research Fraud Risks Millions of Patients' Lives in Europe
healthland.time.com 7.3.2011
(...)
The doctor in question, Joachim Boldt, may have forged up to 90 studies on the safety and effectiveness of drugs known as colloids, which are used to boost blood volume in patients undergoing surgery. Boldt, 57, was the chief anesthesiologist at Ludwigshafen Hospital in Rhineland and the leading advocate of colloids. His studies were published in respected British medical journals and led to a wider application of the drugs, even though they had been shown in previous studies to be more dangerous than similar, cheaper drugs. (...)

Officials first became suspicious of Boldt's findings when readers of an article published in the U.S. journal Anesthesia and Analgesia noticed that the patterns of his data were "too perfect to be believed," reported the U.K.'s Daily Telegraph.

Medical guidelines regarding the use of colloids, which were followed by a number of British medical groups, were withdrawn for re-evaluation after it was revealed that four crucial studies on which the recommendations were based would be retracted. "The profession I represent does not want to be associated with potentially fraudulent research," John MacFie, president of the Association of Surgeons, told the Daily Telegraph, urging other doctors to stop using colloids.

German medical authorities are reviewing 92 of Boldt's publications. Meanwhile, allegations that the doctor forged signatures of co-authors on his studies, tested drugs on patients without their consent and claimed payments for operations he had never performed are the subject of a criminal investigation. (More on Time.com: Bruesewitz v. Wyeth: What the Supreme Court Decision Means for Vaccines) (...)

De flesta försökspersoner värvas utanför EU
lakemedelsvarlden.se 16.2.2011
Omkring 60 procent av de patienter som deltog i kliniska prövningar för läkemedel till den europeiska marknaden är från utomeuropeiska länder. Det visar en rapport från läkemedelsmyndigheten EMA.

I rapporten från EMA konstateras att 61 procent av de patienter som ingått i kliniska prövningar mellan 2005 och 2009 och som ligger till grund för ansökningar till det europeiska läkemedelsverket utförs utanför både EU, EFTA och EEA. Dessutom konstateras att av de 44 000 platser där kliniska prövningar utförts har inspektioner gällande GPP, Good Clinical Practice, bara gjorts på 228 stycken sedan 1997.

Enligt EMA kommer omkring 35 av de 61 procent som rekryterats utanför EU från Nordamerika. Resten kommer från vad man kallar övriga världen, främst Mellanöstern, Afrika, Brasilien, Argentina, Mexiko och Indien. Intressant är också att av de patienter som rekryteras inom EU kommer 11 procent från länder som gått med i EU på senare år som Cypern, Tjeckien, Ungern, Rumänien och de baltiska länderna. (...)

Postmarketing studies of drug safety
BMJ 2011; 342:d342 (8 February)
A European initiative could help bring more transparency and rigour to pharmacoepidemiology

In the early days of randomised clinical trials, their results could be manipulated in several ways—protocols could be altered in light of early findings, sponsors could exert undue influence over what could be published, and some “unfavourable” results could be suppressed entirely. In the United States, the creation of the government clinical trials website (www.clinicaltrials.gov) greatly contributed to minimising these threats to honest science.1 But requiring similar consistency, rigour, and transparency has been more difficult with observational studies, because any person or company with modest resources can purchase a large database of health insurance claims and perform a variety of epidemiological analyses with little or no accountability for the transparency, rigour, or visibility of such work. (...)

Two studies, same data source, two answers (To studier, samme data, to svar)
BMJ 2010; 341:c5980 (26 October)
Various studies have used the UK General Practice Research Database (GPRD) to evaluate the same side effects of drugs, often with opposite conclusions. Examples include third generation pills and venous thromboembolism; proton pump inhibitors and fracture1; and oral bisphosphonates and gastrointestinal cancers.2

Only rarely have GPRD data been reanalysed to find out why results vary so much. The judge requested reanalysis during the third generation pill lawsuit, but the results were not published as a scientific paper. The other examples are our reanalysis of statins and fracture risk,3 and our paper on confounding by respiratory disease severity.4 (...)

Når svart blir hvitt
MINILEDER
Tidsskr Nor Legeforen 2010; 130:1997 (21.10.2010)
Spin Doctor er tittelen på en satire som nå spilles på Oslo Nye Teater. Den handler om hvordan politikken styres av kommunikasjonsrådgivere og taleskrivere. Slike spinndoktorer er mest kjent nettopp fra politikkens verden, men mye tyder på at denne type «doktorer» er i ferd med å utvide reviret. I en fersk undersøkelse av 72 randomiserte studier ble det funnet spinn i over halvparten av dem. Det kunne f.eks. innebære at studier med negative funn ble fremstilt som positive, bl.a. ved å legge vekt på ikke-signifikante resultater. Det er forståelig at politikere – og forskere – ønsker å fremstille budskapet sitt på en best mulig måte. Men spinn i forskningen har vi ikke bruk for. (...)

Drug firms hiding negative research are unfit to experiment on people
guardian.co.uk 14.8.2010
Another pharmaceutical giant has settled a big compensation claim. So why are they allowed to go on misleading the public?

This week the drug company AstraZeneca paid out £125m to settle a class action. More than 17,500 patients claim the company withheld information showing that schizophrenia drug quetiapine (tradename Seroquel) can cause diabetes. So why do companies pay out money before cases get to court?

An interesting feature of litigation is that various documents enter the public domain. This is how we know about the tobacco industry's evil plans to target children, the fake academic journal that Elsevier created for Merck's marketing department, and so on.

One of the most revealing documents ever to come out of a drug company emerged from an earlier quetiapine case: an email from John Tumas, publications manager at AstraZeneca. In it, he helpfully admits that they do everything I say drug companies do. (...)

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. (...)

Flere medicinforsøg til Danmark
business.dk 12.4.2010
Danmark skal tage konkurrencen op med Kina, Indien og Østeuropa, når det gælder medicinforsøg. Flere danskere skal deltage i store internationale forsøg, og det skal være lettere for industrien at få godkendt forsøgene. Det fremgår af en række forslag, som sundhedsministeren nu skal føre ud i livet.

Det skal være nemmere for danske patienter at komme med i forsøg med ny medicin og medicinsk udstyr, medicinalindustrien skal have lettere ved at få godkendt deres forsøg med nye lægemidler, og lægerne på hospitalerne skal have mere tid til at forske.

Sådan lyder nogle af de forslag, som sundhedsminister Bertel Haarder (V) skal i gang med at føre ud i livet. (...)

Norge vill sätta stopp för spökskrivare
lakemedelsvarlden.se 15.2.2010
Den senaste tidens avslöjanden att artiklar om läkemedelsstudier allt som oftast författas av andra än de som utfört forskningen och att dessa andra är spökskrivare betalda av läkemedelsföretagen har väckt debatt i Norge. Nu väntar tydligare regler mot spökskriveri i grannlandet. (...)

Anledningen är en amerikansk undersökning som nyligen publicerades i PLos Medicine som visar att få amerikanska forskningsinstitutioner har några regler mot de spökskriverier som läkemedelsföretag visat sig inte på något sätt vara främmande för.

Bara ett fåtal av de akademiska institutionerna hade enligt undersökningen regler som uttryckligen förbjuder detta. Hur spökskriveriet går till och hur utbrett det är beskrivs i senaste numret av Läkemedelsvärlden.

– Den här okulturen som vi nu fått inblick igenom de amerikanska rättstvisterna mot läkemedelsföretag innebär att systematiska kunskapssammanfattningar och begreppet evidensbaserad medicin förorenas, säger Jørund Straand till tidningen.

– Kanske är det dags att sluta tro på resultat från läkemedelsprövningar sponsrade av företagen. (...)

(Anm: Ghostwriting at Elite Academic Medical Centers in the United States
PLoS Med 7(2): e1000230 (February 2)
.)

From Evidence-based Medicine to Marketing-based Medicine: Evidence from Internal Industry Documents (Fra bevisbasert medisin til reklamebasert medisin: Bevis fra interne industridokumenter)
Journal of Bioethical Inquiry 2010;1176-7529 (Print) 1872-4353 (Online) (January 21).
Abstract While much excitement has been generated surrounding evidence-based medicine, internal documents from the pharmaceutical industry suggest that the publicly available evidence base may not accurately represent the underlying data regarding its products. The industry and its associated medical communication firms state that publications in the medical literature primarily serve marketing interests. Suppression and spinning of negative data and ghostwriting have emerged as tools to help manage medical journal publications to best suit product sales, while disease mongering and market segmentation of physicians are also used to efficiently maximize profits. We propose that while evidence-based medicine is a noble ideal, marketing-based medicine is the current reality.

The larger issue is how do we face the outside world when they begin to criticize us for suppressing data... AstraZeneca publications manager in internal
email 6 Dec 1999.(...)

(Anm: Campaign is launched to make patients the focus of evidence based medicine. BMJ 2014;349:g4443 (03 July 2014).)

Forskningssnyd i farmaindustrien
business.dk 10.12.2009
Undersøgelser viser, at medicinalindustrien snyder med forskningsresultaterne. Det sker af hensyn til indtjeningen, siger forsker. (...)

De groveste tilfælde er opdigtede forskningsresultater og forfalskede data, som to procent af alle forskere indrømmer, at de mindst en gang i karrieren har medvirket til. Mere udbredt er det at bedrive diskutabel forskningspraksis.

Det indrømmer 33 procent af forskerne at have været med til, dokumenterer undersøgelse af forskersnyd fra University of Edinburgh, som også påpeger, at forskningssnyd oftere forekommer blandt medicinske- og farmakologiske forskere end blandt andre forskere. (...)

Should drug companies conduct their own clinical trials?
pharmatimes.com 30.11.2009
As new guidance on the standards required for communicating company-sponsored medical research is published, today on bmj.com two experts debate whether drug firms carrying out clinical trials on their own medicines creates an unacceptable conflict of interest.

Vincent Lawton, a healthcare consultant and non-executive director at the UK Medicines and Healthcare products Regulatory Agency (MHRA), argues that having invested billions of pounds in medicine development, it is unrealistic to expect the drug industry to “surrender its intellectual property.” He adds that taking away research from pharmaceutical companies will lead to delays, inefficiency and a lack of innovation. (...)

Pioneering gastroenterologist is accused of faking study results
BMJ 2009;339:b4193 (12 October)
An award winning researcher who pioneered the use of laser scanning confocal endomicroscopy in the United Kingdom to detect and treat early bowel cancer faked the results of a study published in the journal Gut, a General Medical Council panel was told this week. (...)

Bad Drug Test Results Routinely Hidden by Pharmaceutical Companies: Study (Dårlige testresultater for legemidler hemmeligholdes av legemiddelfirmaer)
aboutlawsuits.com 29.9.2009
Drug companies regularly hide the results of bad clinical trials that may have a negative impact on their medications and attempt to only publish studies that show their products in a positive light, according to a new international study.

Researchers from Canada, France and Britain, working with the Ottawa Hospital Research Institute, found that pharmaceutical companies are routinely conducting tests without disclosure that the drug trials are underway, allowing them to cancel studies that may reveal problems with their medications.
According to standard practices for clinical trials, researchers are supposed to announce when any trial is underway and provide information on what the goals are, the researchers pointed out in the Ottawa Citizen.

The examination into drug company practices found that only 50% of drug trials were publicly announced in an appropriate manner, and medical journals are not consistently insisting that the trials first be published on a public register. The researchers concluded that there was a prevalent amount of “selective outcome” reporting of trial results. (...)

Glaxo Official Memo Official Scientists to Withhold Information About Paxil's Risks,... (Offisielt notat viser at Glaxo oppfordret forskere til å hemmeligholde informasjon om risiko ved Seroxat,...)
reuters.com 16.9.2009
Glaxo Official Memo Urged Scientists to Withhold Information About Paxil's
Risks, Trial Hears; Pharmaceutical Industry Today Offers Complete News
Coverage

ASHINGTON, Sept. 16 /PRNewswire-USNewswire/ -- Antidepressant drug Paxil,
which generated about 2.1% of GlaxoSmithKline's total revenue last year, has
been known to cause birth defects, but the world's second-biggest drugmaker
hid its risks to pump up profits, a Philadelphia court has heard.

According to available information, Glaxo failed to properly test the drug and
urged scientists to conceal Paxil's risks. The Philadelphia trial is the first
of more than 600 cases against the London-based company. (...)

Less than half of completed trials are published
BMJ 2009;339:b3739 (15 September)
All you need to read in the other general journals

PLoS Med 2009;doi:10.1371/journal.pmed.1000144

Selective publication of clinical trials distorts the literature and denies doctors, patients, and researchers access to essential information about the safety and effectiveness of treatments. The full extent of selective publication is hard to determine, although a recent study of trials registered on ClinicalTrials.gov suggests it is still widespread.

Among a random sample of 677 trials completed by 2005, only 311 (46%) were published and traceable through Medline. Even fewer (96 out of 311 published trials (31%)) provided a citation on ClinicalTrials.gov to allow easy access to published results. Only 66% of trials reported their primary outcomes and 56% reported their secondary outcome. Trials sponsored by government agencies were no more likely to be published than trials sponsored by the drugs industry (47% (57/122) v 40% (144/357); P=0.22). (...)

NEJM & BMJ editors to challenge pharma conducting its own clinical trials
pharmatimes.com 27.8.2009
The pharmaceutical industry faces an ethical dilemma when it conducts trials on its own drugs, Dr Jeffrey Drazen Editor in Chief of the New England Journal of Medicine and Dr Fiona Godlee, Editor in Chief of British Medical Journal, will argue in the world famous debating chamber at Oxford Union this month alongside Guardian Bad Science columnist Ben Goldacre.

Clinical trials are central to the success of the industry, providing the bedrock of evidence for a medicine’s use. Typically, these studies are conducted and paid for by pharma: in other words, the medicines developed by industry are tested by the industry.

But is this a conflict of interest? Is it acceptable for industry to pay for and run clinical trials of its own medicines – either for the purposes of registration or subsequent use?

Arguing in industry’s favour at the PharmaTimes’ Great Oxford Debate will be Robert Ruffolo, former R&D President of Research at Wyeth, Scott Gottlieb, former FDA senior official and a frequentWall Street Journal columnist, and Vincent Lawton, ex-Managing Director of MSD and President of the Association of the British Pharmaceutical Industry. (...)

Pfizer will make clinical trial networking site
forbes.com 19.8.2009
NEW YORK -- Pfizer Inc. said Wednesday it will team with information technology company Private Access to create a Web site where patients can find out about clinical trials of new drugs, and where physicians, researchers and drug companies can look for test subjects. (...)

European and US agencies will cooperate to ensure ethical conduct of trials
BMJ 2009;339:b3274 (10 August)
The US Food and Drug Administration and the European Medicines Agency (EMEA) have announced that they will work together to ensure that clinical trials "related to drug marketing applications" in the United States and Europe are conducted "uniformly, appropriately, and ethically."

The "good clinical practices initiative" is expected to strengthen safeguards for participants in clinical studies as research becomes increasingly globalised. (...)

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said that resources available to address the global nature of clinical research were limited and thus the joint initiative was "an outstanding opportunity." (...)

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).)

Sjukhusanställda använde forskningspengar till nöjen
dagensmedicin.se 3.8.2009
Anställda vid Universitetssjukhuset Mas i Malmö använder forskningspengar från läkemedelsföretag till middagar och datorer. ”Oacceptabelt”, anser Lif.

Sydsvenskan har granskat den ekonomiska redovisningen från 18 olika läkemedelsstudier som genomfördes på sjukhuset under 2008. Totalt betalade läkemedelsföretagen 5,2 miljoner kronor för studierna. 3,7 miljoner har gått till löner för sjuksköterskor och läkare.

De resterande 1,5 miljoner kronorna har bland annat använts till utlandsresor, datorer, mobiltelefoner, taxiresor och restaurangbesök.

– Det är väl en trevlig grej att samlas runt en påsklunch eller julmiddag, det uppskattar alla. Det är ett sätt att få någonting tillbaka för allt jobb man lagt ner vid en läkemedelsstudie, säger Lennart Minthon, verksamhetschef på neuropsykiatriska kliniken, till Sydsvenskan. (...)

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 (...)

Medicine's Not-So-Silent Killer: Human Guinea Pigs
ivanhoe.com 1.7.2009
COLUMBUS, Ohio (Ivanhoe Newswire) -- There are 40,000 clinical trials going on in the United States right now, and 20 million Americans are recruited into clinical trails annually by universities, medical centers and drug companies. Some have cancer or other illnesses that are threatening their lives, but did you know there is a hot competition for clinical trial recruits who aren’t even sick? It’s an easy but risky way to make money. (...)

Medicine's Not-So-Silent Killer: Studies Under Scrutiny
ivanhoe.com 3.7.2009
PORTLAND, Ore. (Ivanhoe Newswire) -- Each year, $84 billion is spent on drug development. The rush to create better pills and more effective medicine could be costing the people who take them more than their money -- it could cost them their health. Is medicine losing out to the almighty dollar? Are clinical trials rigged? The results skewed?

There's a lot on the line. The prescription drug market is a $162 billion dollar a year business. But some say the studies done to get these drugs to market can -- and are -- being manipulated.

"Negative studies? We don’t hear about them," Peter Lurie, M.D., Deputy Director of Public Citizen's Health Research Group, told Ivanhoe.

“Many medical journals are becoming marketing instruments for the drug companies," Sidney Wolfe, M.D., Director of Public Citizen's Health Research Group, said. (...)

A JAMA study found industry-sponsored research was positive 87 percent of the time compared with 65 percent of non-industry-sponsored research. UCLA professor Jerome Hoffman says it’s not just the companies that profit from positive results.

"The financial success of medical journals, particularly the major journals, is intimately tied to meeting the needs of the companies that sponsor these big studies," Dr. Hoffman told Ivanhoe. (...)

Glaxo Fails To Learn Lesson of Avandia
forbes.com 6.6.2009
Disclose, disclose, disclose. And definitely don't leave out key facts when you publish your clinical trial.

Today, GlaxoSmithKline is unveiling results of a large clinical trial it says exonerates its Avandia diabetes pill of the charge that it raises the risk of heart attack.

But the scientific paper detailing the results is missing a key fact: 40% of patients analyzed in the study were not taking Avandia at the study's end.

The 4,447-patient study, called RECORD, shows no difference in the rates at which patients were hospitalized for or killed by heart disease whether they were on a drug combination that contained Avandia or not. The study is being published in The Lancet and presented at the annual meeting of the American Diabetes Association in New Orleans.

That would seem to conflict with the headline-grabbing analysis published on May 21, 2007 by Steven Nissen of the Cleveland Clinic, which indicated, based on a pooled analysis of Glaxo's data, that patients who took Avandia were 43% more likely to have heart attacks or strokes. (...)

Merck gav ut falsk tidskrift
lakemedelsvarlden.se 8.5.2009
Ett av världens största förlag för vetenskapliga tidskrifter, Elsevir, har gett ut en reklamprodukt gjord av läkemedelsföretaget Merck. Men att tidskriften var en reklamprodukt framgick inte.

FALSK FLAGG Den liknande på alla sätt en klassisk traditionell vetenskaplig tidskrift, The Australasian Journal of Bone and Joint Medicine.

Men har det nu visat sig, det var en reklamprodukt som läkemedelsföretaget Merck finansierade. Företaget har betalat ett av världens största förlag, Elsevir, ett okänt belopp för att ge ut reklamprodukten.

Tidskriften utgav sig för att ha en redaktion och peer-review system, det vill säga att oberoende experter läser artiklarna innan de publiceras. Inget av det visade sig stämma.

Artiklarna var istället hopklipp av gamla artiklar som ofta beskriver Mercks produkter i positiva ordalag.

– Jag har sett mycken kreativitet i läkemedelsföretagens marknadsföring, men detta var ett nytt grepp också för mig, kommenterar Peter Lurie på Public Citizen i reklamprodukten i Scientist. (...)

Pasientene er øverste prioritet
Tidsskr Nor Legeforen 2009; 129:900-1 (30.4.2009)
Sjefredaktøren i JAMA, Catherine D. DeAngelis, mener lesere av vitenskapelige publikasjoner skal ha innsyn i forfatternes eventuelle interessekonflikter og bindinger til legemiddelindustrien. (...)

Penger og medisin
DeAngelis har som redaktør rettet søkelyset mot pengenes innflytelse på medisinsk forskning (2). Hun mener profittinteresser i for stor grad styrer forskningen.

– Firmaer kan øve innflytelse på kunnskapsutviklingen gjennom å kontrollere dataene og de statistiske analysene. Videre kan man ta kontroll over utarbeidingen av manuskriptet. Jeg har selv opplevd å bli spurt om jeg vil stå som forfatter på publikasjoner som rapporterer fra forskning som ikke er min egen.

Hun retter her søkelyset mot problemet med såkalte «ghostwriters», hvor de som har skrevet manuskriptet ikke står oppført som forfattere, men hvor kommersielle aktører inviterer klinikere eller andre med på forfatterlisten for å gi studien legitimitet.

Uavhengige analyser
JAMA stiller krav om at studier som er finansiert av kommersiell virksomhet, skal gjennomgås av en uavhengig, akademisk tilknyttet statistiker. Er ikke dette et strengt krav?

– Vi mener en uavhengig gjennomgang av analysene styrker studiens troverdighet. Hvis det blir reist spørsmål om holdbarheten av studien, vil jeg som sjefredaktør ha et system å forholde meg til. Jeg vil ha noen jeg kan ringe, og da ringer jeg helst til det medisinske fakultetet hvor forskeren er ansatt. Universitetene har prosedyrer for å granske spørsmål om forskningsjuks, men jeg har ikke tillit til at kommersielle aktører vil kunne gjennomføre tilsvarende granskninger.

– Kan ikke et slikt krav resultere i at enkelte lar være å sende manuskripter til dere?

– Vel, har du noe å skjule, vil ikke jeg ha din artikkel på trykk i JAMA. Så enkelt er det – og vi har ikke akkurat registrert en nedgang i antall innsendte manuskripter. Vi får tilsendt i underkant av 6 000 manuskripter hvert år. Nei, jeg tror tvert imot at JAMA er et attraktivt tidsskrift nettopp fordi vi stiller strenge krav. Publikum kjenner til vår redaksjonelle linje og ser denne som et tegn på kvalitet. (...)

News: Merck published fake journal (Nyheter: Merck publiserte falskt tidsskrift)
the-scientist.com 30.4.2009
Merck paid an undisclosed sum to Elsevier to produce several volumes of a publication that had the look of a peer-reviewed medical journal, but contained only reprinted or summarized articles--most of which presented data favorable to Merck products--that appeared to act solely as marketing tools with no disclosure of company sponsorship.

"I've seen no shortage of creativity emanating from the marketing departments of drug companies," Peter Lurie, deputy director of the public health research group at the consumer advocacy nonprofit Public Citizen, said, after reviewing two issues of the publication obtained by The Scientist. "But even for someone as jaded as me, this is a new wrinkle."

The Australasian Journal of Bone and Joint Medicine, which was published by Exerpta Medica, a division of scientific publishing juggernaut Elsevier, is not indexed in the MEDLINE database, and has no website (not even a defunct one). The Scientist obtained two issues of the journal: Volume 2, Issues 1 and 2, both dated 2003. The issues contained little in the way of advertisements apart from ads for Fosamax, a Merck drug for osteoporosis, and Vioxx. (Click here and here to view PDFs of the two issues.)

The claim that Merck had created a journal out of whole cloth to serve as a marketing tool was first reported by The Australian about three weeks ago. It came to light in the context of a civil suit filed by Graeme Peterson, who suffered a heart attack in 2003 while on Vioxx, against Merck and its Australian subsidiary, Merck, Sharp & Dohme Australia (MSDA). (...)

Merck disguised "marketing publication" as medical journal to help promote Vioxx, court hears (I rettsforhandlinger opplyses at Merck maskerte "reklamepubliksajon" som tidsskrift for å promotere Vioxx)
BMJ 2009;338:b1714 (28 April)
The Federal Court in Australia has heard allegations that the drug company Merck produced an entire medical journal as part of its marketing campaign to allay safety fears about Vioxx (rofecoxib), its cyclo-oxygenase-2 inhibitor, which was withdrawn in 2004.

The allegations came during testimony from George Jelinek, an emergency doctor and journal editor. Dr Jelinek was called as an expert witness by lawyers acting for Graeme Peterson, who had a heart attack in 2003 after taking rofecoxib for several years and is lead plaintiff in a class action. (...)

Inquiry into vaccine trial in India suggests ineffective oversight
BMJ 2009;338:b1418 (8 April)
An inquiry by the Indian government into the death of an infant during a clinical trial of an investigational vaccine has indicated deficiencies in the supervision of the trial, rekindling concerns about standards of scrutiny of clinical trials in India.

A two member panel appointed by the drugs controller general of India has determined that the infant who died at the St John’s Hospital in Bangalore had a pre-existing medical condition and should have been excluded from the trial of an investigational pneumococcal vaccine manufactured by Wyeth. (...)

Antidepressant Marketing Tactics Lead to Federal Lawsuit (Salgsteknikk for antidepressiva førte til statlig søksmål)
Psychiatr News 2009;44(7):6 (April 3) (American Psychiatric Association)
Government prosecutors say the maker of citalopram and escitalopram concealed unfavorable clinical trial results from the public and bribed physicians with kickbacks to increase market share.

The U.S. Department of Justice has accused Forest Laboratories of conducting a "fraudulent scheme to market and promote" unapproved indications for its antidepressants citalopram and escitalopram and paying kickbacks to induce physicians to prescribe those medications. (...)

Study conclusions should reflect results
CMAJ 2009; 180 (7). doi:10.1503/cmaj.1080132. (March 31)
(...) The correct conclusion from their data should be that fluoroquinolones are no better than comparator antibiotics in the treatment of community-acquired pneumonia. A secondary conclusion should be that, in blinded and high-quality studies, there is no difference in mortality rate or treatment success for patients who receive fluoroquinolones versus comparator antibiotics. Moreover, it is unclear why the authors chose to include low-quality trials in their meta-analysis and to base their conclusions on such low-quality studies: this runs counter to common sense. (...)

(Anm: FDA: Avoid Cipro, Similar Drugs for Common Infections. —Agency says risks outweigh benefits. WASHINGTON -- Fluoroquinolone antibiotics, the class that includes ciprofloxacin (Cipro), should not be used to treat uncomplicated infections such as sinusitis, bronchitis, and urinary tract infections for which other drug types are effective, the FDA announced Thursday. (medpagetoday.com 12.5.2016).)

GSK steps up commitment to research transparency
pharmatimes.com 25.3.2009
GlaxoSmithKline (GSK) has sought to draw a line under the reputation for data distortion that has plagued the company since its tangles with regulators and the media over the antidepressant Seroxat/Paxil (paroxetine) by announcing a clutch of initiatives to enhance the transparency of its clinical research.

The measures are disclosed in GSK’s latest annual Corporate Responsibility Report, which recognises the company’s “unique and privileged” position. “Continually strengthening our contract with society is vitally important, and this is why we are fully committed to operating to the highest ethical standards,” commented chief executive officer (CEO) Andrew Witty. (...)

Känd narkosläkare anklagas för forskningsfusk
lakemedelsvarlden.se 11.3.2009
Behandlingen av miljontals patienter kan ha påverkats av studier som en amerikansk anestesiolog har publicerat. Nu anklagas läkaren för att ha manipulerat sina resultat och det rör sig om 21 publicerade forskningsartiklar, skriver Scientific American. (...)

Ethical and Scientific Implications of the Globalization of Clinical Research
NEJM 2009; 360:816-823 (February 19)
Economic globalization is an important development of the past half century. Proponents of globalization highlight the benefits of greater economic growth and prosperity; critics point to the exacerbation of economic disparities and the exploitation of workers, particularly in developing (i.e., low- and middle-income) countries.1 2 Pharmaceutical and device companies have embraced globalization as a core component of their business models, especially in the realm of clinical trials. This phenomenon raises important questions about the economics and ethics of clinical research and the translation of trial results to clinical practice: Who benefits from the globalization of clinical trials? What is the potential for exploitation of research subjects? Are trial results accurate and valid, and can they be extrapolated to other settings? In this article, we discuss recent trends in and underlying reasons for the globalization of clinical research, highlight important scientific and ethical concerns, and propose steps for the harmonization of international clinical research. (...)

Wemos: Health for All
Wemos Film on Clinical Drug Trials in Developing Countries
youtube.com (18.12.2008)
Medical experiments are being conducted on soci (...)

Researchers refine in vitro test that will reduce the risk of "first in humans" drug trials
BMJ 2008;337:a3061 (18 December)
UK researchers investigating what went wrong in the drug trial with the immunomodulator TGN1412 in 2006, in which six healthy volunteers became critically ill, have developed an in vitro test that could have predicted the drug’s serious side effects before it was tested in humans.

The six men had catastrophic multiorgan failure when they took part in a "first in humans" trial of TGN1412—a monoclonal superagonist of the CD28 T cell surface receptor, which was being tested for use in autoimmune conditions. The drug triggered a systemic inflammatory response with rapid induction of proinflammatory cytokines; this caused a life threatening "cytokine storm," which had not been predicted from preclinical testing (BMJ 2006;333:570; 10.1136/bmj.333.7568.570). (...)

Fatalt fase 1-forsøg kan føre til strammere lovgivning
dagenspharma.dk 19.1.2016
EU skærpede sidst reglerne for fase 1-forsøg efter TeGenero-katastrofen i London i 2006. Spørgsmålet er, om den aktuelle sag fra Frankrig vil føre til yderligere stramninger

Et fase 1-forsøg i London med proteinmolekylet CD28 udviklede sig i 2006 katastrofalt. Seks raske unge mandlige forsøgspersoner fik livstruende reaktioner og varigt mén efter forsøgsbehandling med CD28 i sagen, der siden er blevet kendt som TeGenero-sagen, navngivet efter det nu lukkede firma, som stod lægemiddelkandidaten. TeGenero-sagen førte i 2007 til en skærpelse af det […]

Scrutiny Grows of Drug Trials Abroad
online.wsj.com 1.12.2008
Western pharmaceutical companies are facing intensifying scrutiny over the conduct of clinical trials in developing countries -- an increasingly important source of patients to test new drugs and get them to the market.

In November, regulatory authorities in India halted a 350-participant study of a new Wyeth vaccine after a baby died. The Drugs Controller General of India is now investigating whether the infant was screened properly and whether the rules were bent to get babies into the study. A conclusion is expected shortly, according to A.B. Ramteke, deputy drugs controller general for India. (...)

Overlæge: DR har ødelagt fremtidig forskning
politiken.dk 28.10.2008
Rigshospitalet har stævnet DR for programmet 'Når lægen ved bedst', der handler om behandling af lungehindekræft.

'Når lægen ved bedst'
DR viste 24 september programmet 'Når lægen ved bedst'.
Programmet blev optaget over et år på rigshospitalet, hvor man dækkede dennes kræftbehandling.

Da programmet blev sendt viste det en overlæge, som undlod at fortælle kræftpatienter om mulig behandlinger, angiveligt for egen vindings skyld. (...)

Programet viste hvordan overlæge Jens Benn Sørensen bevidst lod være med at informere patienterne om den godkendte medicin Alimta, og i stedet henviste dem til forsøgsmedicinen Vinorelbine.

Angiveligt fordi det ville gøre ham berømt eller rig. (...)

Report Examines Cost-Effectiveness of Larger Clinical Trials To Prevent Postapproval Adverse Events
kaisernetwork.org 6.8.2008
"Use of Larger Versus Smaller Drug-Safety Databases Before Regulatory Approval: The Trade-Offs," Health Affairs: In the Web exclusive, Shelby Reed, an associate professor of medicine at the Duke University Clinical Research Institute, and colleagues evaluate the potential benefits and costs of requiring larger sample sizes in preapproval clinical trials for new prescription drugs. The researchers used a hypothetical model to estimate the expected incremental number of adverse drug events that could be avoided after a drug receives FDA approval. The study finds that requiring larger preapproval clinical trials could be a cost-effective way to reduce adverse drug events. A Web exclusive perspective responding to the study also is available online (Health Affairs release, 8/5). (...)

Big drugs companies shift trials from UK
ft.com 26.6.2008
Leading pharmaceutical groups are cutting back on clinical research in the UK, claiming insufficient commitment by the government and the National Health Service to support new drug development.

Pfizer of the US, Roche of Switzerland and Merck-Serono of Germany are among the companies which have told the Financial Times they have, or will, reduce the number of British patients enrolled in trials to test experimental medicines for life-threatening diseases such as cancer. (...)

Exploiting a Research Underclass in Phase 1 Clinical Trials
NEJM 2008;358:2316-2317 (May 29)
In November 1996, the Wall Street Journal reported that Eli Lilly was paying homeless alcoholics from a local shelter to participate in safety testing of new drugs at its trial site in Indianapolis.1"These individuals want to help society," asserted Lilly's director of clinical pharmacology. The subjects, however, said they took part for easy money and free room and board. Although Lilly reportedly offered the lowest per diem in the business, it managed to attract poor subjects from all over the country.1 The medical director of the local Homeless Initiative Program said Lilly had created a "shadow economy" of paid human subjects. (...)

Sen. Grassley Knocks Psychiatrist’s Funding from AstraZeneca
Posted by Sarah Rubenstein
wsj.com 7.4.2008 (Wall Street Journal)
A University of Cincinnati psychiatrist who was the lead author of a 2002 study that concluded kids did well on AstraZeneca’s antipsychotic Seroquel has received hundreds of thousands of dollars from the company since then, according to Sen. Charles Grassley (R-Iowa).

Grassley (pictured) raised the issue in a floor statement last week in support of a bill he’s co-sponsoring that would require drug and device makers with annual revenues of more than $100 million to disclose to the federal government on a quarterly basis anything of value given to physicians, such as payments, gifts, or travel expenses. (...)

Trial participants need to be more representative of patients
BMJ 2008;336:737 (5 April)
A new report is calling for changes in the conduct of clinical trials in the United States to reduce disparities of age, sex, race, and comorbidity. The goal is to give a more representative picture of the benefits and risks of a treatment across the entire population but particularly among those who bear the greatest burden of the morbidity. (...)

Report Claims Clinical Trials Miss Many Populations (Rapport hevder kliniske forsøk utelater mange grupper av befolkningen)
washingtonpost.com 1.4.2008
TUESDAY, April 1 (HealthDay News) -- A new analysis of the American clinical trial process suggests that the system for testing new drugs has routinely excluded or under-represented women, older people, minorities, disabled individuals and rural populations for decades.

"We've got a big problem," said Daniel S. Goldberg, chief policy adviser for the report. "And it's extremely urgent that we fix it. Because we're trying to figure out how to streamline health care and make people healthy, of course. And the fact that we have under-representation in clinical trials undermines both of these goals and undermines the quality of the evidence we come up with." (...)

Clinical trials and the right to information (Kliniske forsøk og rett til informasjon)
Sarah Hiddleston
thehindu.com 25.3.2008
Does putting full sets of clinical trial data in the public domain affect a company’s commercial interest? It might. But does the public interest not outweigh this? Yes, because if the product is useless or harmful, there should be no commerce in it in the first place. (...)

TRIAL AND ERROR
Delays in Drug's Test (Forsinkelser i legemiddeforsøk)
wsj.com 24.3.2008
Fuel Wider Data Debate

In January, Merck & Co. and Schering-Plough Corp. disclosed surprising news: A long-overdue study of their blockbuster cholesterol drug Vytorin found it was no better at fighting heart disease than a far-cheaper generic. Doctors and public officials questioned whether the companies had delayed the results for more than a year to protect billion of dollars in sales. (...)

The Vytorin study has fueled two broad controversies, both likely to be stoked this week as the findings are formally presented for the first time. Its handling has sharpened the debate over how much control sponsors should wield in clinical trials that influence doctors and regulators. And the study's results have led some skeptical doctors to question the value of cholesterol-lowering drugs that have become the front-line medical weapon against heart disease, the Western world's leading killer. (...)

Dutch researcher John Kastelein, the outside scientist who led the study, has called it "a trial from hell." (...)

Jeremy Laurance: The vested interests that conspire to bury bad news (Jeremy Laurance: Egeninteressene som fører til at dårlige nyheter ikke publiseres)
independent.co.uk 26.2.2008
"Publication bias" is not a phrase widely familiar to people outside the world of academic research. Yet it can explain how a drug launched as a safe and effective treatment can later turn out to be useless, or even deadly. (...)

Dr Kendall, a consultant psychiatrist in Sheffield, said: "The doubt the study raises is how much confidence we can have in our current data set, which is much bigger [than in the study] but may not be complete. The drug industry says they are being much more open but I am not convinced we are seeing the data we should see, and we are certainly not seeing what the licensing authorities are seeing." (...)

Study finds 98% of child drug trials lack independent safety checks (Studie viser at 98 % av legemiddelforsøk på barn mangler sikkerhetskontroll)
guardian.co.uk 19.3.2008
• Research highlights adverse effects of tests
• 'Surprise' at lack of monitoring committees

Only a tiny minority of drug trials on children have an independent safety monitoring committee to pick up potentially dangerous side-effects, a study has revealed.

Researchers from Nottingham University found that under 2% of the 739 international drug trials published between 1996 and 2002 had such committees of independent experts who would scrutinise data and warn, if necessary, that it was not safe to carry on.

Among the 2%, six trials had to be stopped early because of toxic effects on the child patients. (...)

The team found that children experienced adverse effects caused by the drugs in a third of the trials - nearly 37%. In 11%, side-effects were moderate or severe and even sometimes life-threatening. Sammons stressed that the point of a trial was to find out whether the benefits of the drug outweighed any side-effects before the drug was used in the population at large. (...)

Only Two Percent Of Child Drug Trials Have Independent Safety Checks (Bare to prosent av legemiddelforsøk på barn har uavhengig sikkerhetsjekker)
fiercebiotech.com 19.3.2008
Only Two Percent Of Child Drug Trials Have Independent Safety Checks (...)

While 74 per cent of the drug trials described how safety monitoring was performed during the study, only two per cent — 13 studies out of 739 — had independent safety monitoring committees.
Lead author Dr Helen Sammons, an Associate Professor of Child Health in the University's Academic Division of Child Health, based at Derbyshire Children's Hospital, said: “We were very surprised by the low level of trials that had independent safety monitoring committees and are urging pharmaceutical companies to include these in all future trials involving children.

“It is essential that drugs are developed for use in children and clinical trials need to continue. They are vital because they increase the chance of picking up adverse reactions before drugs are introduced into general clinical practice.” (...)

Drug giants warned: Tell the truth on medicines (Legemiddelgigant advart: Fortell sannheten om legemidler)
independent.co.uk 27.2.2008
After antidepressant treatments are discredited, fears grow that other products may be ineffective

The pharmaceutical industry came under assault from senior figures in medical research yesterday over its practice of withholding information to protect profits, exposing patients to drugs which could be useless or harmful.
Experts criticised the stranglehold exerted by multinational companies over clinical trials, which has led to biased results, under-reporting of negative findings and selective publication driven by the market, which was worth £10.1bn in the UK in 2006, amounting to 11 per cent of total NHS costs.

The latest attack was triggered yesterday by an analysis of published and unpublished trials of modern antidepressants, including Prozac and Seroxat, showing they offer no clinically significant improvement over placebos (dummy pills) in most patients. But doctors said patients on the drugs should not stop taking them without consulting their GPs. (...)

The drug industry's long and ignoble history of secrecy
independent.co.uk 27.2.2008
Discovering, testing and bringing a new drug to market can take more than a decade and cost as much as £500m. Over the past 30 years, as the costs have mounted, so have the pressures to protect new chemical agents which could become potential blockbusters.

Secrecy became the pharmaceutical industry's watchword as it sought to control publication of trials and even manipulate results. Cancer drugs introduced in the 1990s claimed to offer major benefits which later turned out to be more apparent than real. Evidence published in The Journal of the American Medical Association showed that 38 per cent of independent studies of the drugs reached unfavourable conclusions about them, compared with just 5 per cent of studies funded by the pharmaceutical industry. (...)

Läkemedelsföretag använder fattiga som försökskaniner
lakemedelsvarlden.se 27.2.2008
En ny holländsk rapport hävdar att läkemedelsföretag i allt högre grad utnyttjar patienter i fattiga länder för oetiska studier. Tester med placebo har i praktiken orsakat dödsfall hävdas i rapporten, som nu hamnat hos EU-parlamentariker. (...)

I en ny rapport anklagar de två holländska organisationerna Somo och Wemos, som forskar om multinationella företag, läkemedelsindustrin för att testa sina nya läkemedel mot placebo trots att det finns läkemedel. (...)

Ett exempel som analyseras i rapporten är ett försök med en medicin mot schizofreni. Preparatet testades 2004 och 2005 på 327 sjuka patienter i Indien, Bulgarien, Polen, Ukraina och Ryssland. Preparatet var redan godkänt, men företaget hade utvecklat en ny version som innebar att patienten bara behövde ta läkemedlet en gång om dagen.
En patient tog sitt liv och flera av de andra patienterna som fick placebo måste läggas in för psykiatrisk vård, trots att de var stabila i sin sjukdom innan försöket började.
Enligt rapporten gjordes 2005 nästan 40 procent av läkemedelsförsöken i Asien eller fattigare delar av Europa. (...)

Särskilt tester mot placebo läggs enligt undersökningen ut i fattigare länder. Eftersom det kan vara farligt för försökspersonerna blir sällan sådana placebostudier godkända av kontrollmyndigheten i till exempel Nederländerna.

Men hela ansvaret för detta ligger inte på läkemedelsföretagen. (...)

-EU respekterar Helsingforsdeklarationen, men EMEA följer den inte, säger hon till den danska tidningen Information.
-Enligt. Helsingforsdeklarationen ska det finna tunga skäl för att genomföra ett placebotest på sjuka, medan EMEA vänder på det och istället kräver goda argument för att inte göra det.

Rapporten har nu fått flera EU-parlamentariker att reagera och kräva att EU inte godkänner läkemedel som inte testats enligt Helsingforsdeklarationens regler. (...)

Hasjrøyking fremmer sinnslidelser
nrk.no 22.8.2007
Ny forskning viser at hasjrøyking øker risikoen for alvorlige sinnslidelser som psykose og schizofreni. Professor i sosiologi ønsker nå Frederic Hauge med på laget i en kampanje mot hasjrøyking. (...)

(Anm: 50.000 nordmenn vil utvikle schizofreni i løpet av livet. - De som lider av denne psykoselidelsen har tanker om verden som ikke stemmer, sier ekspert. (…) Uklare symptomer i starten. Symptomer på Schizofreni utvikler seg over tid, og er i starten litt uklare. Ofte blir de mer fremtredende etter hvert. - Da vises blant annet sosial tilbaketrekning, man mister kontakt med virkeligheten, har vrangforestillinger, hallusinasjoner, tap av matlyst og tap av hygiene. Det er store individuelle variasjoner og mange opplever det som en berg- og dalbane, sier Tove Gundersen, som er generalsekretær i Rådet for psykisk helse. (kk.no 26.9.2016).)

(Anm: Katteparasitt kan gi schizofreni og tvangslidelser. Forskere har funnet en sammenheng mellom katteparasitten Toxoplasma gondii og utviklingen av forskjellige psykiske lidelser hos mennesker. (…) En parasitt fra katteavføring, T. gondii, kan sette fast seg i menneskehjernen og føre til schizofreni, manisk depressiv sinnslidelse, avhengighet og tvangstanker. (nrk.no 29.6.2015).)

(Anm: No, Your Cat Isn't a Threat to Your Mental Health. (…) But mental health worries aside, pregnant women should still be cautious about exposure to cat litter boxes, another researcher warned. "There is good evidence that T. gondii exposure during pregnancy can lead to serious birth defects and other health problems in children," said study senior author Dr. James Kirkbride. (medicinenet.com 21.2.2017).)

(Anm: Angstbehandling spres til utlandet. Her er nederlandske psykologer i Bergen for å lære om behandlingen som kan kurere tvangstanker på fire dager. Nå spres behandlingsopplegget til andre sykdommer og utover Norges grenser. (dagensmedisin.no 21.12.2016).)

(Anm: Schizofreni kopplas till TBE-smitta. Det kan finnas en koppling mellan virusinfektioner som TBE och neuropsykiatriska sjukdomar som schizofreni. Det har svenska forskare kommit fram till i en studie som presenterades på en konferens i San Diego på måndagen. (svd.se 6.11.2007).)

(Anm: Scientists find chemical pathway responsible for schizophrenia symptoms. Recent studies have suggested that kynurenic acid (KYNA) plays a key role in the pathophysiology of schizophrenia. People with schizophrenia have been shown to possess higher levels of KYNA than healthy individuals. KYNA helps to metabolize tryptophan - an essential amino acid that, in turn, helps the body to produce the "happiness" neurotransmitter serotonin, and the vitamin niacin. (medicalnewstoday.com 9.2.2017).)

(Anm: Psykose. Alle mennesker kan utvikle psykose. - Balansegangen mellom opplevd stress og ballast til å stå imot, er avgjørende, forteller psykiater. (…) - Stress er et sentralt tema. For eksempel har vi forskjellige måter å takle en belastende hendelse på jobb på. (…) - Man kan kalle det en forvirringstilstand, selv om heller ikke det er helt dekkende. (…) Symptomer ved psykose. Tidlige tegn kan være at man: (…) - Det er en kjempebelastning å ha en psykose. Mange blir redde og opplever ting de ikke forstår. Man vet at noen mennesker kan få tanker og impulser om å ta sitt eget liv, legger hun til. (lommelegen.no 13.6.2016).)

(Anm: Samtaleterapi styrker hjernens forbindelser for behandling av psykose. (Talk therapy strengthens brain connections to treat psychosis. Cognitive behavior therapy is used to help treat a number of mental health conditions, including anxiety, depression, and post-traumatic stress disorder. For the first time, researchers have shown how this type of therapy triggers brain changes to produce long-term benefits for patients with psycosis. Researchers have found evidence to suggest that talk therapy can alter the brain in a way that leads to long-term recovery from psychosis. Lead study author Dr. Liam Mason, of King's College London in the United Kingdom, and colleagues report their findings in the journal Translational Psychiatry.) (medicalnewstoday.com 22.1.2017).)

(Anm: Forskningen på schizofreni og psykose er i dyp krise | Paul Møller, dr. med. og spesialist i psykiatri. Hjernen kan måles, veies og avbildes eksakt og detaljert. Psyken er derimot subjektiv, flytende, flyktig og abstrakt, og derfor langt mer krevende å forske på. (aftenposten.no 26.1.2017).)

(Anm: Fem myter om schizofreni | Bjørn Rishovd Rund, professor, Psykologisk institutt, Universitetet i Oslo Fem myter om schizofreni. Begrepet schizofreni er sterkt belastet. Det skyldes til dels noen myter som er vanskelige å knekke. Bjørn Rishovd Rund professor, Psykologisk institutt, Universitetet i Oslo (aftenposten.no 5.2.2017).)

(Anm: Det vakreste mennesket jeg kjenner, har diagnosen schizofreni. Likevel kaller du ham gal | Karoline Kongshaug (aftenposten.no 29.6.2017).)

(Anm: Probiotics may help treat yeast infections, bowel problems in men with schizophrenia. The findings, published in the May 1 issue of Brain, Behavior, and Immunity, support growing evidence of close links between the mind and the gut. (…) The commercially available probiotic contained over 1 billion colony-forming units of Lactobacillus rhamnosus and Bifidobacterium animalis in each pill. PANSS scores were reassessed every two weeks, and the participants self-reported on the ease of their bowel movements weekly on a scale of 0 to 4. At the end of the study, the researchers collected another blood sample. Using the blood samples, the researchers measured antibody levels to yeast Saccharomyces cerevisiae, known as brewer's yeast, and Candida albicans, known to cause yeast infections, before and after the probiotic treatment. Both types of yeast are elevated in people with schizophrenia. (news-medical.net 5.4.2017).)

(Anm: Psychosis: Link to brain inflammation antibodies raises new treatment hope. For the first time, researchers reveal that some people presenting with a first episode of psychosis have specific antibodies in their blood. The antibodies are the same ones known to cause encephalitis or brain inflammation. The discovery raises the question of whether the removal of these antibodies could be an effective treatment for psychosis as it is for encephalitis. The researchers - led by Belinda R. Lennox, a professor in the department of psychiatry at the University of Oxford in the United Kingdom - report their findings in The Lancet Psychiatry. (…) Previous studies have already fueled discussion about the role antibodies targeting neural proteins may play in psychosis. For example, a study reported in 2015 of children experiencing their first episode of psychosis, also found links to an antibody response to NMDAR. (medicalnewstoday.com 9.12.2016).)

(Anm: Psykose som målestokk for tvungent psykisk helsevern. Sammendrag Abstract  Denne artikkelen handlar om vilkåra for tvungent psykisk helsevern. Det er særleg fokusert på ei drøfting omkring det såkalla hovudvilkåret etter lov om psykisk helsevern (phvl.) § 3-3 (1) nr. 3. I artikkelen vert det drøfta om dagens rettsregel og dei vurderingstema den set opp, gjer ei god avgrensing sett i høve til føremåla med tvungent psykisk helsevern. Det vert òg skissert ei betre løysing for tolking av vilkåret. Kritisk juss03 / 2016 (Volum 2) Side: 217-237DOI: 10.18261/issn.2387-4546-2016-03-03.)

(Anm: Psykose forbundet med lave nivåer av fysisk aktivitet. (Psychosis associated with low levels of physical activity. A large international study of more than 200,000 people in nearly 50 countries has revealed that people with psychosis engage in low levels of physical activity, and men with psychosis are over two times more likely to miss global activity targets compared to people without the illness.) (medicalnewstoday.com 26.8.2016).)

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. (...)

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. (...)

Mandatory disclosure of trial results for drugs and devices
Editorials
BMJ 2008;336:170 (26 January)
New US law will require public posting of all the main results and data on harms (...)

Legemiddelverket kritisk til Ullevål-forskning
vg.no 8.1.2008
Statens Legemiddelverk er kritisk til hjerteforskningsprosjektet som pågår ved Ullevål universitetssykehus. (...)

Non-drug industry funded research
Editorials
BMJ, doi:10.1136/bmj.39416.559942.BE (published 6 December 2007)
High cost and poor availability of drugs mean that important clinical questions remain unanswered (...)

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study
BMJ 2007;335:1202-1205 (8 December)
(...) Results 124 meta-analyses were included in the study, 49 (40%) of which had financial ties to one drug company. On univariate logistic regression analyses, meta-analyses of better methodological quality were more likely to have favourable results (odds ratio 1.16, 95% confidence interval 1.07 to 1.27). Although financial ties to one drug company were not associated with favourable results, such ties constituted the only characteristic significantly associated with favourable conclusions (4.09, 1.30 to 12.83). When controlling for other characteristics of meta-analyses in multiple logistic regression analyses, meta-analyses that had financial ties to one drug company remained more likely to report favourable conclusions (5.11, 1.54 to 16.92).

Conclusion Meta-analyses on antihypertensive drugs and with financial ties to one drug company are not associated with favourable results but are associated with favourable conclusions. (...)

Insider Analysis: Can Outsourced Clinical Trials Also Be The Best?
pharmasianews.com 26.11.2007
The Potential To Harmonize Best Practices in China, India and Globally (Part 2 of 2)

The first part of this two-part column explored the remarkable potential for outsourcing clinical trials to China, India and other developing nations, as well as the challenges that worldwide governments face when establishing and enforcing best practices for such outsourced clinical research. This second part focuses on potential methods for benchmarking outsourced clinical research to internationally-recognized performance standards. (...)

Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review
BMJ 2006;333:782 (14 October)
(...) Conclusions Industry supported reviews of drugs should be read with caution as they were less transparent, had few reservations about methodological limitations of the included trials, and had more favourable conclusions than the corresponding Cochrane reviews. (...)

FDA Has Not Inspected Many Foreign Companies That Manufacture Medications, Medication Ingredients Imported to U.S., GAO Report Finds
kaisernetwork.org 2.11.2007
FDA this year has not visited as many as two-thirds of foreign companies that manufacture medications or medications components imported by the U.S. subject for inspection, according to a report from the Government Accountability Office released on Thursday during a hearing of the House Energy and Commerce Oversight and Investigations Subcommittee. Under current law, FDA must inspect U.S. companies that manufacture medications or medications components at least once every two years, but no such requirement exists for inspections of foreign companies, although an estimated 80% of medication ingredients and 40% of medications sold in the U.S. are imported (Bridges, AP/San Francisco Chronicle, 11/1). (...)

Foreign Drug Makers Face Few Inspections
sfgate.com 1.11.2007
WASHINGTON, (AP) -- Two-thirds of the foreign drug manufacturers subject to inspection by the Food and Drug Administration may never have been visited by agency inspectors, a government watchdog reported to Congress Thursday.

The FDA this year listed 3,249 foreign pharmaceutical manufacturers subject to its inspection — yet the agency cannot determine whether it has ever inspected 2,133 of them, according to a Government Accountability Office report released during a House subcommittee hearing.

While some of the more than 3,000 firms may never have exported prescription drugs or drug ingredients to the United States, others likely have.

Who are those firms and what are they shipping? asked Rep. Bart Stupak, D-Mich., during Thursday's hearing of the House Energy and Commerce subcommittee on oversight and investigations.

"We don't know and we are not certain the FDA knows," Marcia Crosse, director of health care at the GAO, replied. (...)

Adverse Effects of Inhaled Corticosteroids in Funded and Nonfunded Studies
Arch Intern Med. 2007;167:2047-2053 (October 22)
(...) Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33).

Conclusions The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs. (...)

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. (...)

Prescription Drugs: FDA Guidance and Regulations Related to Data on Elderly Persons in Clinical Drug Trials
GAO-07-47R, September 28 (The Government Accountability Office (GAO))
gao.gov (28.9.2007)
Elderly persons use drugs at a higher rate than younger persons,1 in part because elderly persons experience higher rates of certain diseases—such as cancer, Parkinson’s disease, and heart disorders. Elderly persons—those age 65 and older—are also more likely than younger adults to experience complications when taking some prescription drugs.2 For example, because of their decreased liver and kidney functions, elderly persons often lack the ability to eliminate drugs from their bodies as efficiently as younger adults, making elderly persons more likely to experience side effects associated with drugs. As a result, the Food and Drug Administration (FDA) has noted that it is important that drugs be studied for use by elderly persons during the clinical drug trials3 —that is, those drug studies conducted by drug sponsors before they submit an application to have a drug approved for marketing.4 (...)

Time for a quality check before recruiting patients
Letters
BMJ 2007;335:7 (7 July)
Drug trials in general practice
In Norway, through our work in a general practice research committee under the Norwegian Medical Association, we have been involved in a voluntary arrangement with pharmaceutical companies where we evaluate research projects initiated by the industry and recruit general practitioners to find patients.1 Our committee makes recommendations to Norwegian general practitioners about whether a project is a real research project rather than marketing camouflaged as research. (...)

Stricter Regulations Sought for Drug Trials
themoscowtimes.com 3.7.2007
Health officials said Monday that they wanted to introduce tougher rules for clinical drug trials after a scandal involving vaccine tests by GlaxoSmithKline earlier this year. (...)

Clinical Trial Registration
Looking Back and Moving Ahead

JAMA. 2007;298:(doi:10.1001/jama.298.1.jed70037)
(...) Key Summary Points
In addition to accepting registration in any of the 5 existing registries, the ICMJE will accept registration of clinical trials in any of the primary registers that participate in the WHO ICTRP. Registration in a partner register only is insufficient. (...)

Amerikansk forsker:
Homofile lever kortere

vg.no 12.4.2007
Amerikansk forsker mener homofile lever kortere en heterofile. Han baserer forskningen på tall fra Norge. (...)

Det er ikke bare SSB som syns Cameron driver betenkelig forskning. Han har blitt ekskludert av den amerikanske psykiaterforeningen på grunn av sine metoder, og er kjent i USA for sin homohets.

Ikke holdbar statistikk
Cameron har samlet informasjon fra dødsannonser i tidsskrifter som retter seg mot et homofilt publikum. Disse dataene har han kombinert med tall fra Skandinavia for å komme fram til konklusjonen i den kontroversielle rapporten. Tallene han har brukt fra Statistisk Sentral Byrå (SSB) er datert 1997 til 2002. I denne perioden ble det registrert dødsfall av 31 menn og 6 kvinner som levde i homofilt partnerskap. (...)

Study of drug therapy for compulsive buying yields a puzzle
emaxhealth.com 13.3.2007
Compulsive buying
Researchers at the Stanford University School of Medicine say they are puzzled by findings from their new study indicating that an antidepressant, which previously showed promise in treating a behavioral disorder known as compulsive buying, did not result in a sustained benefit for the patients who took it.

The medication is escitalopram, a commonly prescribed antidepressant sold under the brand name Lexapro. In the study, researchers found no difference in the relapse rate of people with compulsive-buying disorder when they continued to take escitalopram compared with those who had been switched to a placebo. Those results are perplexing to lead author Lorrin Koran, MD, professor of psychiatry and behavioral sciences emeritus, because he had done a similar study in 2003 that found compulsive-buying patients improved stably after taking another antidepressant medication, citalopram, in which escitalopram is the active ingredient.

"It was a shock that, when we did the trial again with the active ingredient, it didn't work exactly the same way. It should have," said Koran, who also led the 2003 study. The results of the latest double-blind, placebo-controlled trial will be published in the April issue of the Journal of Clinical Psychopharmacology. (...)

Bias in psychiatric case–control studies (Bias i psykiatriske studier - kontrollstudier)
The British Journal of Psychiatry (2007) 190: 204-209
Background: Case–control studies are vulnerable to selection and information biases which may generate misleading findings. (...)

Conclusions Poor reporting of recruitment strategies threatens the validity of reported results and reduces the generalisability of studies. (...)

Tests of Drug to Block H.I.V. Infection Are Halted Over Safety
Efforts to develop a topical microbicide to prevent H.I.V. infection during sex suffered a surprising setback yesterday when researchers announced that they had stopped two full-scale trials for safety reasons. (...)

Redd for at storebror ser deg?
dagbladet.no 28.6.2006
Folk er ikke alltid like ærlige når det gjelder penger. Når folk skal putte en tier i en kopp for en vaffelplate, eller en femtilapp i en kasse for en middag på en turisthytte, er det ikke alle som er like ærlige.

Nå har forskere fra Newcastle University funnet løsningen for de lokale idrettslagene og for Den norske turistforening: Heng opp et ark med bilde av et øye, skriver BBC. (...)

Harmful impact of EU clinical trials directive
Letter
BMJ 2006;332:666 (18 March)
Trial of alerting drug in fibromyalgia has had to be abandoned...

EDITOR—Hemminki and Kellokumpu-Lehtinen show the impact of the EU Clinical Trials Directive and the resulting additional cost and bureaucratic delays on cancer drug research.1 It has become almost impossible for academic researchers to initiate and conduct pharmaceutical trials without the involvement of a pharmaceutical company, particularly in areas that do not attract much funding or involve a drug that is close to the end of or outwith patent protection. (...)

(Anm: Fibromyalgi: Fibromyalgi rammer over 100.000 norske kvinner. - En del tror sykdommen bare er tøys. Også blant leger er det en del som flirer av den, forteller professor. (…)   Når leger blir bedt om å rangere hvilke sykdommer det er mest prestisje å jobbe med, så havner alltid fibromyalgi nederst, forteller hun. Professor Egil Andreas Fors ved Institutt for samfunnsmedisin og allmennmedisinsk forskningsenhet ved NTNU er blant Norges fremste eksperter på sykdommen. Han bekrefter holdningene Slydal beskriver. (…) Sykdommen kjennetegnes gjerne ved at man har kroniske muskelsmerter, andre symptomer kan være utmattelse, hodepine, stivhet i kroppen, svimmelhet, kvalme, indre frost, depresjoner, angst og søvnproblemer. (kk.no 8.3.2016).)

(Anm: Lettere at diagnosticere fibromyalgi. På University of Colorado har forskere opdaget en speciel hjernesignatur, der med 93 pct. sikkerhed kan fastslå, hvorvidt en person lider af fibromyalgi eller ej. (pharmadanmark.anp.se 27.10.2016).)

Drug firms making more study results public
msnbc.msn.com/ 28.12.2005
But key details of clinical trials still being withheld, new analysis finds

Drug companies are making public more information about medical studies they are conducting, but some still withhold key details, a new analysis of a federal registry finds.

Merck & Co., stung by allegations that it hid information on Vioxx’s dangers, gets somewhat better marks in the new analysis than it did in an earlier one. However, Pfizer Inc., GlaxoSmithKline PLC and Novartis are lagging, according to the report in Thursday’s New England Journal of Medicine.

In May, the journal’s editor-in-chief accused Merck, Pfizer and Glaxo of making a mockery of efforts to increase the transparency of such experiments, called clinical trials. (...)

Drug firms launch Web site to disclose trials data
abcnews.go.com 21.9.2005
- The global pharmaceutical industry launched a new Web site on Wednesday giving details of clinical trials on new medicines in a bid to allay patient fears over drug safety.

The move follows criticism that companies manipulate or suppress results of clinical studies in order to come up with favorable conclusions.

The new portal (http://www.ifpma.org/clinicaltrials.html), established by the International Federation of Pharmaceutical Manufacturers and Associations, links available online information about clinical trials worldwide. (...)

De gikk først - leger som eksperimenterte på seg selv
Tidsskr Nor Lægeforen 2005;125:2388-90 (8.9.2005)
Siden oldtiden har det vært laget regler for forsøk på mennesker. Noen har hevdet at hvis man mener et forsøk innebærer risiko, bør man gjøre forsøket på seg selv først. Det er tallrike eksempler på leger som har gjort dristige forsøk på seg selv. Artikkelen beskriver disse forsøkene, hvorfor de ble gjort og hva de førte til.

Contradicted and Initially Stronger Effects in Highly Cited Clinical Research
JAMA. 2005;294:218-228 (July 13, 2005)
Design All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990-2003 and cited more than 1000 times in the literature were examined.

Results Of 49 highly cited original clinical research studies, 45 claimed that the intervention was effective. Of these, 7 (16%) were contradicted by subsequent studies, 7 others (16%) had found effects that were stronger than those of subsequent studies, 20 (44%) were replicated, and 11 (24%) remained largely unchallenged. Five of 6 highly-cited nonrandomized studies had been contradicted or had found stronger effects vs 9 of 39 randomized controlled trials (P = .008). Among randomized trials, studies with contradicted or stronger effects were smaller (P = .009) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact. Matched control studies did not have a significantly different share of refuted results than highly cited studies, but they included more studies with "negative" results.

Conclusions Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes. The extent to which high citations may provoke contradictions and vice versa needs more study. Controversies are most common with highly cited nonrandomized studies, but even the most highly cited randomized trials may be challenged and refuted over time, especially small ones.

ClinicalStudyResults.org (...)

Websidene er designet og tilrettelagt av Hein Tore Tønnesen © 2009