Scientific and medical literature is routinely cited by both plaintiffs and defendants in litigation. Such literature usually comes from scientific and medical journals, and has often gone through a review process, known as “peer review” in which the author’s work is fact-checked and evaluated for scientific merit by other authors in the same field, prior to publication. Such work is generally considered to be credible and reliable, and therefore may often be considered strong scientific evidence in litigation. However, a September 16, 2015 publication has reanalyzed the data from a 2001 study from a different journal, involving the antidepressant Paxil and concluded the opposite result about the safety of the drug. The 2015 publication found that the drug is “neither safe nor effective in adolescents with depression.” The 2001 original publication had been sponsored by a grant from the manufacturer of Paxil. The disparity between what the manufacturer and original study authors claim the trial found and what the 2015 analysis says the data shows should be a reminder that we should all be skeptics regarding manufacturer-sponsored studies and manufacturers’ claims of the safety and efficacy of their products.
The 2001 study had found that the antidepressant Paxil was safe and effective for the treatment of depression in adolescents. However, the September 16, 2015 reanalysis looked at “tens of thousands of pages of original trial documents” from the original study, which had been sponsored by the manufacturer of the drug, and concluded that “the antidepressant paroxetine is neither safe nor effective in adolescents with depression.” This conclusion in 2015, which was drawn by independent researchers, is in direct contrast to that of the trial’s original publication in 2001, which had declared that paroxetine (which is also known by the trade name Paxil) was “generally well tolerated and effective.”
The 2001 study, also known as Study 329, tracked depression scores over eight weeks in three groups of about 90 adolescents each, one taking Paxil, one on placebo pills, and one taking imipramine, an older generic drug for depression. The Paxil group did no better than the other two groups on the study’s primary measure, a depression questionnaire, but did rate higher on other “secondary” measures. The manufacturer of Paxil—SmithKline Beecham, now a part of GlaxoSmithKline (GSK) — submitted the trial and others to the FDA. Questions about this study began soon after its publication, and in the following years such antidepressant drugs were required by the FDA to have strong warning labels citing the potential suicide risk for children, adolescents, and young adults. In 2002, the FDA, after having reviewed the trial, reported that “on balance, this trial should be considered as a failed trial, in that neither active treatment group showed superiority over placebo by a statistically significantly margin.” However, in 2002, according to the New York State Attorney General’s office, which subsequently sued GSK, over two million prescriptions were written for children and adolescents in the United States, after a marketing campaign that characterized Study 329 as demonstrating “Remarkable Efficacy and Safety.” GSK and the authors of the study stood by its conclusions and prescriptions of antidepressants to children, adolescents, and young adults increased by 36 percent between 2002 and 2003, according to one analysis.
The authors of the 2015 reanalysis spent about a year looking at “tens of thousands of pages” of original trial documents and focused on what is known as patient-level data, the detailed descriptions of what happened for each person in the original trial. Among other problems with the data, the authors of the reanalysis noted that some adverse events which had been labeled merely as “emotional liability” in the 2001 study, actually involved suicidal thinking or behavior, but were not presented as such by the authors of the original study.
The publication of the 2015 reanalysis is considered an unusual step, as it is “a break from scientific custom” to “post multiple interpretations of the same experiment.” While the conclusions drawn from the 2001 study have been criticized for years, the 2015 publication of the reanalysis of this study serves as an alarming reminder that widely divergent conclusions about the safety of a drug can be published based on the same data. The 2015 reanalysis of the 2001 Paxil study does show a positive step taken by the scientific community toward correcting an earlier problem, but this process reminds us that we should all be skeptics regarding manufacturers’ claims of the safety and efficacy of their products.
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