Clinical trial registration was associated with lower risk of bias compared with non-registered trials among trials included in systematic reviews

• Published in: Journal of clinical epidemiology 2022-05, Vol.145, p.164-173
• Main Authors: Lindsley, Kristina, Fusco, Nicole, Li, Tianjing, Scholten, Rob, Hooft, Lotty
• Format: Article
• Language: English
• Subjects: Bias; Clinical trials; Confidence intervals; Data analysis; Data collection; Domains; Epidemiology; Evidence synthesis; Humans; Intervention; Pharmaceuticals; Prospective Studies; Randomized controlled trial; Registration; Regulatory approval; Research methods; Retrospective Studies; Reviews; Risk; Risk of bias; Systematic review; Systematic Reviews as Topic; Trial registration
• ISSN: 0895-4356; 1878-5921; 1878-5921
• DOI: 10.1016/j.jclinepi.2022.01.012

•Less than one-third of trials included in recent systematic reviews had been registered; less than one-third of registered trials were registered prospectively.•Clinical trial registration was associated with low risk of bias for five domains: random sequence generation, allocation concealment, performance bias, detection bias, and reporting bias.•What this adds to what is known.•The design, conduct, and reporting of clinical trials are interwoven and both are necessary for adequately assessing the quality of the evidence.•What is the implication, what should change now.•Clinical trial investigators should include trial registration as part of the process of conducting a trial.•Multi-disciplinary teams should be involved to address both content and methodological aspects of designing and conducting trials. To examine the association between clinical trial registration and risk of bias in clinical trials that have been included in systematic reviews. As a secondary objective, we evaluated the risk of bias among trials registered prospectively vs. retrospectively. Clinical trials published in 2005 or after included in a sample of 100 Cochrane systematic reviews published from 2014-2019. Of 1,177 clinical trials identified, we verified 368 (31%) had been registered, of which 135 (36.7%) were registered prospectively (i.e., before or up to 1 month after enrollment of the first participant). Across the bias domains (one bias assessment for each domain per trial), the percentage of trials at low risk ranged from 29% to 58%; unclear risk ranged from to 26% to 61% and high risk ranged from 2% to 38%. Trials that had been registered had less high or unclear risk of bias in five domains: random sequence generation (univariate risk ratio [RR] 0.69, 95% confidence interval [95% CI] 0.58-0.81), allocation concealment (RR 0.64, 95% CI 0.57-0.72), performance bias (RR 0.65, 95% CI 0.58-0.72), detection bias (RR 0.70, 95% CI 0.62-0.78), and reporting bias (RR 0.62, 95% CI 0.53-0.73). An association between clinical trial registration and high or unclear risk of attrition bias could not be demonstrated nor refuted (RR 1.02, 95% CI 0.89-1.17). It also was observed in terms of overall risk of bias, that registered trials had less high or unclear overall risk of bias than trials that had not been registered (univariate RR 0.29, 95% CI 0.19-0.46). Prospective clinical trial registration was associated with low risks of selection bias due to inadequate allocation concealment,