Registered trials report less beneficial treatment effects than unregistered ones: A meta-epidemiological study in orthodontics

Abstract Objectives Clinical trial registration is widely recommended because it allows tracking of trials that helps ensure full and unbiased reporting of their results. The aim of the present overview was to provide empirical evidence on bias associated with trial registration via a meta-epidemiological approach. Study Design and Settings Six databases were searched in September 2017 for randomized clinical trials and systematic reviews thereof assessing the effects of orthodontic clinical interventions. After duplicate study selection and data extraction, statistical analysis included a two-step meta-epidemiological approach within- and across-included meta-analyses with a Paule-Mandel random-effects model to calculate differences in standardized mean differences (ΔSMD) between registered and unregistered trials and their 95% confidence intervals (CI), followed by subgroup and sensitivity analyses. Results A total of 16 meta-analyses with 83 trials and 4,988 patients collectively were finally included, which indicated that registered trials reported less beneficial treatment effects than unregistered trials (ΔSMD = −0.36; 95% CI = −0.60, −0.12). Although some small-study effects were identified, sensitivity analyses according to precision and risk of bias indicated robustness. Conclusion Signs of bias from lack of trial protocol registration were found with nonregistered trials reporting more beneficial intervention effects than registered ones. Caution is warranted by the interpretation of nonregistered randomized trials or systematic reviews thereof.