Outcome reporting bias in randomized-controlled trials investigating antipsychotic drugs

Abstract

Recent literature hints that outcomes of clinical trials in medicine are selectively reported. If applicable to psychotic disorders, such bias would jeopardize the reliability of randomized clinical trials (RCTs) investigating antipsychotics and thus their extrapolation to clinical practice. We therefore comprehensively examined outcome reporting bias in RCTs of antipsychotic drugs by a systematic review of prespecified outcomes on ClinicalTrials.gov records of RCTs investigating antipsychotic drugs in schizophrenia and schizoaffective disorder between 1 January 2006 and 31 December 2013. These outcomes were compared with outcomes published in scientific journals. Our primary outcome measure was concordance between prespecified and published outcomes; secondary outcome measures included outcome modifications on ClinicalTrials.gov after trial inception and the effects of funding source and directionality of results on record adherence. Of the 48 RCTs, 85% did not fully adhere to the prespecified outcomes. Discrepancies between prespecified and published outcomes were found in 23% of RCTs for primary outcomes, whereas 81% of RCTs had at least one secondary outcome non-reported, newly introduced, or changed to a primary outcome in the respective publication. In total, 14% of primary and 44% of secondary prespecified outcomes were modified after trial initiation. Neither funding source (P=0.60) nor directionality of the RCT results (P=0.10) impacted ClinicalTrials.gov record adherence. Finally, the number of published safety endpoints (N=335) exceeded the number of prespecified safety outcomes by 5.5 fold. We conclude that RCTs investigating antipsychotic drugs suffer from substantial outcome reporting bias and offer suggestions to both monitor and limit such bias in the future.