Estimating the replicability of highly cited clinical research (2004–2018)

Introduction: Previous studies about the replicability of clinical research based on the published literature have suggested that highly cited articles are often contradicted or found to have inflated effects. Nevertheless, there are no recent updates of such efforts, and this situation may have changed over time. Methods: We searched the Web of Science database for articles studying medical interventions with more than 2000 citations, published between 2004 and 2018 in high-impact medical journals. We then searched for replications of these studies in PubMed using the PICO (Population, Intervention, Comparator and Outcome) framework. Replication success was evaluated by the presence of a statistically significant effect in the same direction and by overlap of the replication’s effect size confidence interval (CIs) with that of the original study. Evidence of effect size inflation and potential predictors of replicability were also analyzed. Results: A total of 89 eligible studies, of which 24 had valid replications (17 meta-analyses and 7 primary studies) were found. Of these, 21 (88%) had effect sizes with overlapping CIs. Of 15 highly cited studies with a statistically significant difference in the primary outcome, 13 (87%) had a significant effect in the replication as well. When both criteria were considered together, the replicability rate in our sample was of 20 out of 24 (83%). There was no evidence of systematic inflation in these highly cited studies, with a mean effect size ratio of 1.03 [95% CI (0.88, 1.21)] between initial and subsequent effects. Due to the small number of contradicted results, our analysis had low statistical power to detect predictors of replicability. Conclusion: Although most studies did not have eligible replications, the replicability rate of highly cited clinical studies in our sample was higher than in previous estimates, with little evidence of systematic effect size inflation. This estimate is based on a very select sample of studies and may not be generalizable to clinical research in general.