Cecily’s doctor was hardly alone in prescribing Paxil that year. A year before, in 2001, a much-publicized paper described a clinical trial that showed Paxil to be safe and effective in teenagers as well as adults. Study 329, as it became known, helped spur a huge increase in Paxil prescriptions. In 2002 alone, over 2 million prescriptions were written for children and teens, and many more for adults. (As a 25-year-old, Cecily Bostock was, from a neurophysiological perspective, on the cusp between adolescence and adulthood.) Did Cecily’s psychiatrist choose Paxil because of Study 329? It’s hard to believe the answer is not at least partly yes.
The study is now again in the news, as a new reanalysis of the its original data—including about 77,000 pages of formerly inaccessible patient records—shows that Paxil was neither effective nor safe. The reanalysis, published in the scientific journal BMJ, found that the study, underwritten by the drug’s maker, GlaxoSmithKline (or GSK), created a false picture of safety partly by misclassifying suicidal acts (such as taking 80 Tylenol) as less-alarming behavior or side effects. Other researchers who have looked at Study 329’s data have concluded likewise.
Count this as shocking but unsurprising, for GSK has been admonished and fined many times since 2001, including once for $3 billion, for exaggerating Paxil’s safety and marketing it improperly for use in adolescents. Yet this BMJ study deals an especially sharp blow, for it’s only rarely that researchers are able to crack open the tightly sealed file cabinets of drugmakers and look at raw trial data. This illustrates why they want to do so: It appears to be a direct demonstration of how a company and researchers can misinterpret the data to make a bad drug look good.
Benedict Carey covers this story well in yesterday’s New York Times, though I disagree with his assertion that this reexamination of original data is something novel. Reexamining important data is part of science. It was delayed here, as it has been for most drug-trial studies, because drug companies are often allowed to keep their raw data secret. Even when outside researchers can get to the data —and it’s a wonder they managed to do so in this case—it’s both hard to find money for independent examination and hard to conduct that examination well. The BMJ study happened because of a special program called RIAT (for restoring invisible and abandoned trials) to spearhead such efforts.
Perhaps the most essential read, aside from the study itself, is the BMJ’s feature examining the study’s history. The article is deeply reported, sad, riveting, and damning. It condemns not just the company and the original study but an entire ecosystem of researchers, journals, and universities that have resisted the sort of correction the BMJ paper seems to offer. The most chilling part is that even though GlaxoSmithKline has been found to have acted questionably again and again in its promotion of Paxil, many of the institutions and researchers involved in the study and subsequent promotion of the product have remained unapologetic and are silent or unresponsive to efforts to have the original paper retracted or the record otherwise corrected.