[An open letter to Bob Park, author of What's New]
Thanks for another excellent instalment of What’s New. You might be interested to know that the WIRED piece on the placebo effect is seriously flawed. You mentioned that it is likely that we are getting better at designing trials to eliminate bias, and while I think that is true, the main reason antidepressants don’t perform as well as they used to is already well known. The drug companies submitted biased data to the FDA. You can read all about it in the New England Journal of Medicine.
The 2008 NEJM study shows that the drug companies did not publish all their registered trials. Here’s the money quote: “Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.”
In short, publication bias made antidepressants appear much more effective than they really were. There has been no change in the power of placebo. There has been a correction in our understanding based on more complete analysis of the data. This evidence is not obscure. NEJM is one of the elite medical journals and this study and accompanying editorials made world-wide news.
I would not claim that the apparent reduction in efficacy of antidepressants was 100% due to publication bias. There could be other mysterious factors at work. Perhaps mercury in vaccines. But does it not raise concerns about the WIRED article? A cynic might point out that the author only interviewed quoted at length three people, each of whom is being paid by pharmaceutical companies to find out why the placebo effect keeps ruining their studies. (Suggestion: maybe because the drugs don’t work as well as they’d like.) The cynic might wonder why, of all the possible explanations for reduced efficacy of antidepressants, the interviewees fixated on the extremely unlikely mechanism of society-wide placebo effect enhancement while ignoring the documented evidence of publication bias. And the same cynic might even wonder if these researchers are being employed by the drug companies for the purpose of developing new analytic techniques to amplify drug effect over placebo when standard analysis shows little or no benefit.