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

Abstract

Background: Prospective 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.

Methods: We 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.

Results: We 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.

Conclusions: The 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.

Keywords: Randomized controlled trials; Registration; Reporting bias.

Fig. 1

Flow diagram of study selection

Fig. 2

Combined estimates of the prevalence of trial registration

Fig. 3

Combined estimates of the prevalence of prospective trial registration

Fig. 4

Meta-regression analysis of the prevalence of trial registration in relation to publication year. Each circle represents one study, and the size of each circle represents the weight given to the study in meta-regression. Separate meta-regression models were fitted in 7 studies that reported trial registration data by publication year. The black dashed line corresponds to an overall meta-regression model across these 7 studies with 11 studies that examined RCTs published in a single year. It showed that the proportion of registered trials increased over time, from 23% in 2005 to 52% in 2015 (29% increase, p = 0.03)