A study in this week's PLoS Medicine suggests that the apparent clinical effectiveness of the newer form of drugs used to treat schizophrenia and other psychotic illnesses (second-generation anti-psychotic drugs) may be enhanced by the selective reporting of trials of these drugs in medical journals – a phenomenon called publication bias. This finding is important as the results of published trials influence clinicians' decisions to prescribe drugs.
The authors, led by Erick Turner from Oregon Health & Science University in Portland, USA, say: "Selective reporting of research results undermines the integrity of the evidence base, which ultimately deprives clinicians of accurate data for prescribing decisions."
The authors reached these conclusions by reviewing 24 FDA-registered premarketing trials for eight second-generation antipsychotics—aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection, and ziprasidone— and then comparing these trials with the results conveyed in subsequent articles in medical journals.
The authors found that four premarketing trials submitted to the FDA remained unpublished and that all of the unpublished trials showed negative results—three showed the new anti-psychotic had no statistically significant advantage over placebo, and in one trial the new drug was statistically inferior to a much less expensive competing drug.
In the published trials, there was some evidence that the journal articles over-emphasised efficacy of the new drug. For example, the FDA review revealed that one of the newer drugs, iloperidone, was statistically inferior to three different competing drugs, but this information was not mentioned in the corresponding journal articles.
On the other hand, when the authors used meta-analysis to combine trial data and compare all eight drugs to placebo, they found that publication bias had little effect on their overall apparent efficacy. Of more concern was that some negative data remain unreported, potentially misleading clinicians.
The authors conclude: "The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently."
They continue: "With further studies investigating publication bias in other drug classes, a more accurate evidence base can emerge. To that end, increased access to FDA reviews has been advocated. At the present time, the FDA is not as transparent with its clinical trial data as it could be."
The authors add: "it is encouraging that the FDA has convened a Transparency Task Force. If the agency fulfills its mission to increase transparency, the public health will surely benefit."
Funding: Grant support: Stanley Medical Research Institute, grant number 08D-1892 (http://www.stanleyresearch.org/dnn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: From 1998 to 2001, ET served as a medical reviewer at the US Food and Drug Administration (FDA). Subsequently, but ending in 2005, ET provided outside consulting to Bristol-Myers Squibb, Eli Lilly, and GlaxoSmithKline. From 2004 to 2005, ET was on the speaker's bureaus of Eli Lilly, AstraZeneca, and Bristol-Myers Squibb. LS is Scorecard Director for the AMSA Pharmfree Scorecard, and a fourth year medical student at Oregon Health & Science University (OHSU). DK is also a fourth year medical student at OHSU and has no competing interests to report.
Citation: Turner EH, Knoepflmacher D, Shapley L (2012) Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database. PLoS Med 9(3): e1001189. doi:10.1371/journal.pmed.1001189
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