The win ratio in contemporary clinical trials: growing adoption and interpretation challenges-a meta-epidemiological...

The win ratio (WR) has been used with increasing frequency in clinical trials with hierarchical composite end points. This meta-epidemiological study aims to systematically evaluate the contemporary use of the WR in clinical trials. Specifically, we sought to (1) describe temporal trends in WR application, (2) quantify its use across therapeutic areas, and (3) examine component directional contributions and conclusion consistency between analyses summarized by the WR and the original analyses.

We conducted a systematic review (PRISMA 2020) of PubMed, Embase, and Web of Science (search date: 26 March 2025). Eligible studies were published clinical trials or reanalyses that summarized treatment effects using the WR based on individual data. Studies were classified by application type (prespecified vs reanalysis) and mapped to International Classification of Diseases (ICD-10) categories. After inclusion, we further screened for studies with comparable data, then performed two comparisons: first, the component directional contribution between end point component and the overall WR result; and second, the conclusion-level consistency between each WR-reported analyses and the conclusions of the original trials.

A total of 90 studies were included: 35 prespecified end point analyses and 55 reanalyses. Circulatory system trials accounted for about 80% of the applications. We included 57 studies for comparison, and discrepancies between component-level results and overall conclusions were common. In prespecified end point analyses, 36 of 139 components (25.9%) had directional discordance or neutrality with the overall WR point estimate, compared with 17.0% in reanalyses, although the difference was not statistically significant (generalized linear mixed-effects model with study as a random effect, P = .114). Among the 35 studies included for conclusion-level comparison, 22 reached WR-reported conclusions that were consistent with those of the original trials. Nearly all observed discrepancies in conclusions were associated with changes in the selection or prioritization of end point components.

The use of the WR in clinical research has steadily increased and is expanding beyond cardiovascular trials. Hierarchical composite end points constructed using the WR may differ from conventional composites in component selection, and directional discordance among components is not uncommon. In WR-reported reanalyses, changes to end point components may influence clinical interpretation. Careful attention to the appropriate use of the analytical framework, end point definition, and result interpretation is essential to ensure the interpretability and validity of WR-reported analyses.