A review of the original trial data investigating the antidepressant drug paroxetine finds it is neither safe nor effective.
This is the first time a randomized-controlled trial of this kind has been reanalyzed in this way.
This new research, using previously confidential trial documents, is published by The BMJ under the RIAT (Restoring Invisible and Abandoned Trials) initiative, which seeks to have abandoned or misreported studies - such as this one involving paroxetine - published or formally corrected.
The research team, led by Prof. Jon Jureidini of the University of Adelaide in Australia, felt that this study had been misreported in the past.
In the original study - funded by SmithKline Beecham, now GlaxoSmithKline (GSK) - Martin Keller, a former professor of psychiatry at Brown University in Providence, RI, and colleagues compared the effectiveness of paroxetine and higher dose antidepressant imipramine with a placebo in adolescents with depression.
The researchers claimed paroxetine was safe and effective for adolescents. Known as Study 329, the findings were published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2001.
The US Food and Drug Administration (FDA) stated in 2002 that "on balance, this trial should be considered as a failed trial." In the same year, over 2 million prescriptions for paroxetine were written for children and adolescents in the US.
Reanalysis finds paroxetine, imipramine 'no clinically different from placebo'
The main purpose of the new study was to compare paroxetine and imipramine with placebo for effectiveness and safety in treating adolescents with unipolar major depression. The original study had looked at 275 adolescents from 12 North American academic psychiatry centers from April 1994 to February 1998.
The revised results show that paroxetine and imipramine were neither statistically nor clinically significantly different from placebo. They also show that there were clinically significant increases in harms, including thoughts of suicide.
In an accompanying article to this new research, Peter Doshi, associate editor for The BMJ, says "for those who have been calling for a retraction of the Keller paper for many years, the system has failed."
Doshi then runs through a series of revelations concerning the errors made by the original investigators, the drug company staff and Keller's home academic institution.
The original manuscript was not written by any of the 22 named authors, he points out, but by a writer from the drugs company.
What is more, Keller had been the focus of an investigation into the under-reporting of financial ties to drug companies.
In 2012, GSK were fined a record $3 billion - in part for fraudulently promoting paroxetine.
Authors of the reanalysis of Study 329 say that this "illustrates the necessity of making primary trial data and protocols available to increase the rigor of the evidence base."
Dr. Fiona Godlee, The BMJ editor-in-chief, says the publication of the reanalyzed data from Study 329 "sets the record straight" and "shows the extent to which drug regulation is failing us."
Independent reanalysis of a clinical trial is rare
The BMJ call for independent clinical trials rather than trials funded and managed by industry. Dr. Godlee says that this is to:
"[...] ensure that the results of all clinical trials are made fully available and the individual patient data are available for legitimate independent third party scrutiny."
It is argued, in an accompanying editorial to the new research, that "liberating the data" from clinical trials has the potential to benefit patients, prevent harm and correct misleading research.
"Substantial added value [...] can be derived from sharing of trial data as part of a wider open data movement," says Prof. David Henry, of Dalla Lana School of Public Health, Institute for Health Policy Management and Evaluation at the University of Toronto in Canada.
The "broadening open data movement in health" has support from major funding organizations in the US, UK, Europe and Australia.
Medical News Today recently reported on a study linking social media pressure to increased risk of depression and anxiety in teenagers.