Study 329 was a clinical trial conducted in North America from 1994 to 1998 to study the efficacy of paroxetine, an SSRI antidepressant marketed as Paxil and Seroxat, in treating depressed teenagers.
It concluded that paroxetine is “generally well tolerated and effective for major depression in adolescents.” In 2001, the study was published in the Journal of the American Academy of Child and Adolescent Psychiatry.
Study 329 was funded by GlaxoSmithKline (GSK), the drug’s manufacturer.
In the years following that study’s publication, reports of suicidal thoughts and behaviors in teens taking the drug raised concerns about Paxil’s effectiveness and safety. In 2003, the U.S. Food and Drug Administration (FDA) advised doctors not to prescribe the drug to teenagers suffering from depression. The following year, the FDA voted to require manufacturers to add a black box warning to their product labels.
In 2012, GSK pleaded guilty to fraud charges and paid $3 billion in fines – the largest health care fraud settlement in U.S. history – which included a criminal fine of $1 billion. The fine also included an amount for “preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy.”
A recent reanalysis of tens of Study 329 revealed that the antidepressant paroxetine is not only ineffective for teens with depression – the drug is not safe for adolescents. The reanalysis team found that the authors of the original paper “deliberately misrepresented the outcomes of the study” and changed the protocols of the study without following the proper procedures to do so.
Unfortunately, Study 329 is not an outlier: drug studies have long been known to be flawed, mainly because testing is conducted by the very entities that stand to profit from sales of the medications – the drug manufacturers.
Another recent study exposed just how pervasive and serious the problem is.
Because pharmaceutical industry influence is known to permeate research, people who review scientific papers as part of their jobs rely on meta-analyses, which are supposedly thorough reviews that summarize the evidence from multiple trials, rather than trust individual studies.
Meta-analyses are meant to be as comprehensive as possible and to serve as a shortcut to a lot of evidence for busy clinicians who don’t have time to do a full evaluation of each drug on their own.
But as Roni Jacobson of Scientific American explains, a recent analysis casts doubt on that practice as well:
…the vast majority of meta-analyses of antidepressants have some industry link, with a corresponding suppression of negative results.
The latest study, published in the Journal of Clinical Epidemiology, which evaluated 185 meta-analyses, found that one third of them were written by pharma industry employees. “We knew that the industry would fund studies to promote its products, but it’s very different to fund meta-analyses,” which “have traditionally been a bulwark of evidence-based medicine,” says John Ioannidis, an epidemiologist at Stanford University School of Medicine and co-author of the study. “It’s really amazing that there is such a massive influx of influence in this field.”
The researchers considered all meta-analyses of randomized controlled trials for all approved antidepressants including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, atypical antidepressants, monoamine oxidase inhibitors and others published between 2007 and March 2014.
Here’s a list of the findings of the analysis:
- Almost 80 percent of meta-analyses in the review had some sort of industry tie, either through sponsorship, which the authors defined as direct industry funding of the study, or conflicts of interest, defined as any situation in which one or more authors were either industry employees or independent researchers receiving any type of industry support (including speaking fees and research grants).
- About 7 percent of researchers had undisclosed conflicts of interest.
- A third of the papers were written by industry employees; of the majority of authors, 60 percent were independent, university-affiliated researchers with conflicts of interest.
- For the 53 meta-analyses where the author was not an industry employee and did not report any conflicts of interest, 25 percent had unreported conflicts of interest that the researchers identified in their search and included in their evaluation.
- Meta-analyses by industry employees were 22 times less likely to have negative statements about a drug than those run by unaffiliated researchers.
- The rate of bias is similar to what a 2006 study found: industry-sponsored trials reported favorable outcomes 78 percent of the time, compared with 48 percent in independently funded trials.
We knew that the industry would fund studies to promote its products, but it’s very different to fund meta-analyses which have traditionally been a bulwark of evidence-based medicine. It’s really amazing that there is such a massive influx of influence in this field.
Erick Turner, a professor of psychiatry at Oregon Health & Science University who was not associated with the research, told Scientific American he is “very concerned” about the results but is not surprised:
There’s a certain pecking order of papers. Meta-analyses are at the top of the evidence pyramid. Industry influence is just massive. What’s really new is the level of attention people are now paying to it.