Problems of drug research: The case of "Study 329".

Author/s Paolo Migone
Publishing Year 2015 Issue 2015/4
Language Italian Pages 6 P. 589-594 File size 50 KB
DOI 10.3280/PU2015-004003
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On September 16, 2015, the British Medical Journal (BMJ) published the reanalysis, authored by Le Noury et al., of the infamous "Study 329", i.e., the randomized controlled trial (RCT) by Keller et al. of 2001 on the effects of paroxetine and imipramine for major depression in adolescents, that had concluded that paroxetine was «generally well tolerated and effective»ۚ. This reanalysis, instead, on the basis of the same data has reached the opposite conclusion, i.e., that paroxetine is not effective in the treatment of major depression in adolescents, and there is a clinically significant increase in harms, including serious, severe, and suicide related adverse events. The manufacturer of paroxetine, the GlaxoSmithKline (GSK) pharmaceutical company, had in fact been sued for fraud and had to pay a $3 billion fine.

Keywords: Paroxetine, drug research, fraud, pharmaceutical companies, GlaxoSmithKline (GSK)

  1. Chan A.-W. et al. (2013). SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. British Medical Journal (BMJ), 346: e7586. DOI: 10.1136/bmj.e7586
  2. Doshi P. (2015). No correction, no retraction, no apology, no comment: Paroxetine trial reanalysis raises questions about institutional responsibility. BMJ, 351: h4629. DOI: 10.1136/bmj.h4629
  3. Doshi P., Jones M. & Jefferson T. (2012). Rethinking credible evidence synthesis. BMJ, 344: d7898. DOI: 10.1136/bmj.d7898
  4. Doshi P., Dickersin K. & Healy D. (2013). Restoring invisible and abandoned trials: A call for people to publish the findings. BMJ, 346: f2865. DOI: 10.1136/bmj.f2865.
  5. Ebrahim S., Sohani Z.N., Montoya L. & Agarwal A. (2014). Reanalyses of randomized clinical trial data. Journal of the American Medical Association (JAMA), 312, 10: 1024-1032. DOI: 10.1001/jama.2014.9646
  6. Godlee F.(2013a). In praise of informed scepticism.BMJ,346: f3980. DOI: 10.1136/bmj.f3980
  7. Godlee F. (2013b). Editor’s reply to Smith. BMJ, 347: f6859. DOI: 10.1136/bmj.f6859
  8. Godlee F. (2015). Study 329. BMJ, 351: h4973. DOI: 10.1136/bmj.h4973.
  9. Hawkes N. (2013). Independent researchers should have right to publish trial results if original researchers don’t, campaigners say. BMJ, 346: f3857. DOI: 10.1136/bmj.f3857
  10. Hendrick R. (2011). Ghosts in the machine. BMJ, 343: d7860. DOI: 10.1136/bmj.d7860
  11. Henry D. & Fitzpatrick T. (2015). Liberating the data from clinical trials. BMJ, 351: h4601. DOI: 10.1136/bmj.h4601
  12. Hrynaszkiewicz I., Norton M.L., Vickers A.J. & Altman D.G. (2010). Preparing raw clinical data for publication: Guidance for journal editors, authors, and peer reviewers. BMJ, 340: c181. DOI: 10.1136/bmj.c181
  13. Jureidini J.N. & Nardo J.M. (2014). Inadequacy of remote desktop interface for independent reanalysis of data from drug trials. BMJ, 349: g4353. DOI: 10.1136/bmj.g4353
  14. Keller M.B. et al. (2001). Efficacy of paroxetine in the treatment of adolescent major depression: A randomized, controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), 40, 7: 762-772. DOI: 10.1097/00004583-200107000-00010
  15. Le Noury J., Nardo J.M., Healy D., Jureidini J., Raven M., Tufanaru C. & Abi-Jaoude E.
  16. (2015). Restoring Study 329: Efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ, 351: h4320. DOI: 10.1136/bmj.h4320
  17. Loder E. (2013). Sharing data from clinical trials: Where we are and what lies ahead. BMJ, 347: f4794. DOI: 10.1136/bmj.f4794
  18. Loder E., Godlee F., Barbour V. & Winker M. (2013). Restoring the integrity of the clinical trial evidence base. BMJ, 346: f3601. DOI: 10.1136/bmj.f3601
  19. Melander H., Ahlqvist-Rastad J., Meijer G. & Beermann B. (2003). Evidence b(i)ased medicine. Selective reporting from studies sponsored by pharmaceutical industry: Review of
  20. studies in new drug applications. BMJ, 326: 1171. DOI: 10.1136/bmj.326.7400.1171
  21. Migone P. (2005). Farmaci antidepressivi nella pratica psichiatrica: efficacia reale. Psicoterapia e Scienze Umane, XXXIX, 3: 312-322.
  22. Migone P. (2009). Quanto sono efficaci i farmaci antidepressivi? Il Ruolo Terapeutico, 112: 45-56. Internet Migone P. (2010). Evidence-Based Medicine o Evidence-B(i)ased Medicine? Ancora sulla efficacia dei farmaci antidepressivi. Psichiatri Oggi, XII, 3: 15-17.
  23. Migone P. (2013a). La congiura del silenzio. I farmaci antidepressivi sono veramente efficaci? Psicologia Contemporanea, XL, 238 (luglio-agosto): 20-25.
  24. Migone P. (2013b). Scheda: “Irving Kirsch, I farmaci antidepressivi: il crollo di un mito. Dalle pillole della felicità alla cura integrata (2009). Milano: Tecniche Nuove, 2012; Robert Whitaker, Indagine su un’epidemia. Lo straordinario aumento delle disabilità psichiatriche nell’epoca del boom degli psicofarmaci (2010). Roma: Fioriti, 2013”. Psicoterapia e Scienze Umane, XLVII, 3: 526-527. DOI: 10.3280/PU2013-003007
  25. Migone P. (2014). Prefazione. In: Herzberg D., Le pillole della felicità in America. Dal Miltown al Prozac (2009). Roma: L’Asino d’Oro, 2014, pp. IX-XXIV.
  26. Newman M. (2010). The rules of retraction. BMJ, 341: c6985. DOI: 10.1136/bmj.c6985
  27. Prayle A.P., Hurley M.H. & Smyth A.R. (2012). Compliance with mandatory reporting of clinical trial results on Cross sectional study. BMJ, 344: d7373. DOI: 10.1136/bmj.d7373
  28. Rubiales A.S. (2013). Who is responsible for publishing the results of old trials? BMJ, 347: f7199. DOI: 10.1136/bmj.f7199
  29. Schulz K.F. et al. (2010). CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. BMJ, 340: c332. DOI: 10.1136/bmj.c332
  30. Smith R. (1997). Authorship is dying: Long live contributorship. BMJ, 315: 696. DOI: 10.1136/bmj.315.7110.696
  31. Smith R., Gøtzsche P.C. & Groves T. (2014). Should journals stop publishing research funded by the drug industry? BMJ, 348: g171. DOI: 10.1136/bmj.g171
  32. Spagnoli A. (2012). “British Medical Journal (BMJ), 2012, Volume 344, n. 7845 (25 febbraio)”. Psicoterapia e Scienze Umane, XLVI, 2: 312-314. DOI: 10.3280/PU2012-002009
  33. Taylor D., Sparshatt A., Varma S. & Olofinjana O. (2014). Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies. BMJ, 348: g1888. DOI: 10.1136/bmj.g1888
  34. Torjesen I. (2015). Study links SSRIs to violent crime in young adults. BMJ, 351: h4945. DOI: 10.1136/bmj.h4945
  35. Tucker M.E. (2013). How should clinical trial data be shared? BMJ, 347: f4465. DOI: 10.1136/bmj.f4465
  36. Internet: Driessen E., Hollon S. D., Bockting C. L. H., Cuijpers P. & Turner E. H. (2015). Does publication bias in flate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US National Institutes of Health-fundedtrials. PLoSONE, 10,9 DOI: 10.1371/journal.pone.0137864

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Paolo Migone, Problemi della ricerca farmacologica: il caso dello "Studio 329" in "PSICOTERAPIA E SCIENZE UMANE" 4/2015, pp 589-594, DOI: 10.3280/PU2015-004003