by Erick H. Turner, Annette M. Matthews, Eftihia Linardatos, Robert A. Tell, and Robert RosenthalNew England Journal of Medicine. 2008 358:252-260.
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.
Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Databaseby Erick H. Turner, Daniel Knoepflmacher, and Lee ShapleyPLoS Medicine. 2012 9:e1001189.
Methods and Findings: FDA Drug Approval Packages for eight second-generation antipsychotics—aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection [risperidone LAI], and ziprasidone—were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four [17%] were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest [8%] and not statistically significant. On the other hand, the effect size for unpublished trials [0.23, 95% confidence interval 0.07 to 0.39] was less than half that for the published trials [0.47, 95% confidence interval 0.40 to 0.54], a difference that was significant.
by Christopher W Jones, Lara Handler, Karen E Crowell, Lukas G Keil, Mark A Weaver, and Timothy F Platts-MillsBritish Medical Journal. 2013 347:f6104.
Objective To estimate the frequency with which results of large randomized clinical trials registered with ClinicalTrials.gov are not available to the public.Setting Trials with at least 500 participants that were prospectively registered with ClinicalTrials.gov and completed prior to January 2009.Data sources PubMed, Google Scholar, and Embase were searched to identify published manuscripts containing trial results. The final literature search occurred in November 2012. Registry entries for unpublished trials were reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database.Main outcome measures The frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in the ClinicalTrials.gov database.Results Of 585 registered trials, 171 (29%) remained unpublished. These 171 unpublished trials had an estimated total enrollment of 299 763 study participants. The median time between study completion and the final literature search was 60 months for unpublished trials. Non-publication was more common among trials that received industry funding (150/468, 32%) than those that did not (21/117, 18%), P=0.003. Of the 171 unpublished trials, 133 (78%) had no results available in ClinicalTrials.gov.Conclusions Among this group of large clinical drug trials, non-publication of results was common and the availability of results in the ClinicalTrials.gov database was limited. A substantial number of study participants were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results.