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

Abstract

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 framework. We evaluated whether replications were successful by the presence of a statistically significant effect in the same direction and by overlap of their effect sizes confidence intervals (CIs) with those of the original studies. We also analyzed evidence of effect size inflation and potential predictors or replicability. Results: We found a total of 89 eligible studies, of which 24 had valid replications. 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 83%. When comparing effect sizes, there was little evidence of systematic inflation in these highly cited studies. Due to the small number of contradicted results, our analysis was underpowered 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 previous estimates, with little evidence of systematic effect size inflation.