Dr. Ben Goldacre is an entertaining speaker [something of value…, another Ben/TED talk…], a journalist [Bad Science: The Guardian], and the author of several books [Bad Science: Quacks, Hacks, and Big Pharma Flacks, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients]. He’s a major force behind AllTrials [upper left], the petition calling for full data transparency in ALL Clinical Trials. On this blog, I’ve focused my attention on the ways in which the scientific data in Clinical Trials has been manipulated to distort both efficacy and safety in the service of commercial gain within the non-ethic of plausible deniability. And while Dr. Goldacre is a master-sleuth at exposing that kind of sheenanigans, which he calls dodgy studies, he’s also on another tack that I haven’t sufficiently emphasized – studies gone missing. He uses an example that goes something like this: "If I flip a coin a hundred times and withhold half the data, I can convince you that I have a two-headed coin." He calls this method of distorting science publication bias. It’s simple, just publish the positive studies. It gets around the tool of meta-analysis, since the negative studies simply aren’t available to be vetted. So the AllTrials campaign is not just asking for the raw data in published Clinical Trials to look at the hanky-panky used to create dodgy studies, they are asking that All Trials be published as a check on publication bias – eliminating the gone missing phenomena.
Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy
by Erick H. Turner, Annette M. Matthews, Eftihia Linardatos, Robert A. Tell, and Robert Rosenthal
New England Journal of Medicine. 2008 358:252-260.
[full text on-line]
Background: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials — and the outcomes within those trials — can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio.Methods: We obtained reviews from the Food and Drug Administration [FDA] for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set.Results: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.Conclusions:We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.