Peter Doshi is an Assistant Professor of Pharmaceutical Health Services Research at the University of Maryland, an Associate Editor at BMJ, and a leading advocate for clinical trial transparency. On 13 June 2013, a paper authored by Peter Doshi, David Healy, and several others appeared in BMJ. The authors noted that they had obtained access to 178,000 ages of previously confidential drug company documents pertaining to clinical trials which had either never been published in the scientific literature, or which had been misreported. They called upon the sponsors of these trials to publish the unpublished studies, and to formally correct or retract the misreported ones. They further stated that if the sponsors failed to do so, the data would be considered “public access data” that others would be allowed to publish.
Series:
Part 1: “I tried killing myself thirty times”
Part 2: “Remarkable efficacy and safety”
Part 3: “An effective drug treatment”
Part 4: The Ghost Writer
Part 5: It's shameful"
This article, titled “Restoring invisible and abandoned trials: a call for people to publish the findings,” amounted to a manifesto demanding a new era of clinical trial transparency. The authors specifically mentioned GSK’s Study 329 of Paxil as an example of a misreported trial in need of restoration. Parts of Study 329 had been published in a 2001 paper in the Journal of the American Academy of Child and Adolescent Psychiatry, with Dr. Martin Keller, Professor of Psychiatry at Brown University, listed as first author.
After GSK made it clear they would not retract or correct the paper, Dr. Healy set about the task himself, along with Dr. Jureidini and several others. Through GSK’s website, the authors had access to five thousand pages of appendices along with 77,000 pages of individual patient-level data – information never before made available to independent researchers.
The re-analysis, published in BMJ on 17 September 2015, actually held few surprises, although the authors uncovered three more instances of suicidal behavior or self-harm in youths taking Paxil. (They also uncovered one additional case of self-harm in the placebo arm.) Of greater significance was the following statement that appeared in BMJ, perhaps the most prestigious medical journal in the world: “[P]ublished conclusions about safety and efficacy should not be read as authoritative.”
In an accompanying editorial, Doctor Doshi blasted Brown University and the American Academy of Child and Adolescent Psychiatry for failing to demand the retraction of the 2001 JAACAP paper. (Karen Wagner, President-Elect of the Academy, is one of the co-authors of the JAACP paper.) Dr. Doshi noted that the Academy received between $500,000 and $1 million a year, or anywhere between five and twenty percent of its total revenues, from the drug companies.
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It’s a cold rainy morning, the first week of October. In his office in downtown Baltimore, Peter Doshi is receiving a visitor. Dr. Doshi, a graduate of both Brown University and MIT, is in his mid-thirties, soft-spoken, with tousled hair and wire-frame glasses, casually attired in jeans and a light blue sweater.
He tells his visitor “Here we have a fundamentally ethical issue about research and scientific integrity, and Brown University – my university, my alma mater – will not confirm or deny whether or not it’s actually looked into the case. And this has been going on for years. It’s shameful, right?” He also noted that Dr. Keller, along with eight of his co-authors of the JAACP paper, had issued a statement, promising to submit a more detailed letter to BMJ. “To my knowledge, we haven’t received that letter yet. I’m very concerned that we are going to see the various actors that have institutional responsibility for this story remain in the positions of potentially stonewalling and not getting involved. That’s my biggest worry.”
In a telephone interview, Dr. Healy summed up matters thusly: “This isn’t a paper about an antidepressant being given to kids. This is a paper about access to data, and in the absence of access to data you have to assume that industry’s mode of operation in this trial is the standard industry approach towards harms, and that it applies to all drugs, for all indications, for all age groups, and at this point in time we will be concluding you cannot trust the academic literature, you cannot trust the clinical study reports, and you can’t trust the FDA. The only way forward from here is demand access to individual patient-level data.”
As for Vickie, she has managed, against all odds, to regain a semblance of normalcy. By the time she reached her early twenties, her condition stabilized somewhat, although she remains dependent on Paxil. She has attempted many times to taper off the drug, but every time she tries she experiences uncontrollable sweating, nausea, vomiting, crushing migraine headaches, horrible vivid nightmares, and terrifying rage.
She now works as a nurse and is raising three children, although her marriage crumbled under the strain of her condition. “I can’t really have a relationship with anybody. As soon as anybody finds out that I have these issues, their views on me change.” Her liver has sustained significant damage, and she believes a transplant is in her future.
“It’s a horrible medication,” she says of GlaxoSmithKline’s blockbuster drug. “Paxil turned me into a monster.”
List of Sources
Peter Doshi, personal interview 2 October 2015.
Doshi, P. et al. 2013. Restoring invisible and abandoned trials: A call for people to publish the findings. BMJ 2013;346:f2865 doi: 10.1136/bmj.f2865.
Noury, J. et al. 2015. Restoring Study 329: Efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015;351:h4320 doi: 10.1136/bmj.h430.
Doshi, P. 2015. No correction, no retraction, no apology, no comment: Paroxetine trial reanalysis raises questions about institutional responsibility. BMJ 2015;351:h4629 doi: 10.1136/bmj.h4629.
