Registration of published randomized trials: a systematic review and meta-analysis

Abstract

BackgroundProspective trial registration is a powerful tool to prevent reporting bias. We aimed to determine the extent to which published randomized controlled trials (RCTs) were registered and registered prospectively.MethodsWe searched MEDLINE and EMBASE from January 2005 to October 2017; we also screened all articles cited by or citing included and excluded studies, and the reference lists of related reviews. We included studies that examined published RCTs and evaluated their registration status, regardless of medical specialty or language. We excluded studies that assessed RCT registration status only through mention of registration in the published RCT, without searching registries or contacting the trial investigators. Two independent reviewers blinded to the other’s work performed the selection. Following PRISMA guidelines, two investigators independently extracted data, with discrepancies resolved by consensus. We calculated pooled proportions and 95% confidence intervals using random-effects models.ResultsWe analyzed 40 studies examining 8773 RCTs across a wide range of clinical specialties. The pooled proportion of registered RCTs was 53% (95% confidence interval 44% to 58%), with considerable between-study heterogeneity. A subset of 24 studies reported data on prospective registration across 5529 RCTs. The pooled proportion of prospectively registered RCTs was 20% (95% confidence interval 15% to 25%). Subgroup analyses showed that registration was higher for industry-supported and larger RCTs. A meta-regression analysis across 19 studies (5144 RCTs) showed that the proportion of registered trials significantly increased over time, with a mean proportion increase of 27%, from 25 to 52%, between 2005 and 2015.ConclusionsThe prevalence of trial registration has increased over time, but only one in five published RCTs is prospectively registered, undermining the validity and integrity of biomedical research.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1168-6) contains supplementary material, which is available to authorized users.

More systematic reviews were registered in PROSPERO each year, but few records' status was up-to-date

“…Furthermore, for clinical trials, prospective registration is a condition of consideration for publication by the International Committee of Medical Journal Editors (ICMJE) since 2005 [22] and is lawfully required for clinical trials of drugs, biological products, or devices regulated by the US Food and Drug Administration since 2007 [23], for example. Nevertheless, in a systematic review, Trinquart et al found that the pooled proportion of RCTs that had been prospectively registered was 20% [24], which seems to be rather low compared to the proportion of SRs registered in PROSPERO.…”

A multi-state model analysis of the time from ethical approval to publication of clinical research studies

“…While the presence of missing time-to-event information was an important limitation, it did not appear to have an undue influence on the findings. Since this study was initiated, the proportion of studies which are registered in a clinical trial registry prior to data collection has greatly increased [43], and therefore future investigations of time to publication should have access to more complete information regarding the timing of state transitions. We recommend using modern statistical methods of event history analysis (multistate models) to permit a detailed study of the publication process in medicine, epidemiology, or other areas of research.…”

A review of prospective registration of trials published in nursing science journals in 2017

“…Authors of a systematic review of trial registration in biomedical research identified 24 studies that included 5,529 RCTs (Trinquart, Dunn, & Bourgeois, 2018). The pooled proportion of trials that were prospectively registered was 20%, rates were higher in industryfunded and more extensive trials.…”