Doubly robust win statistics for hierarchical survival endpoints in individual- and cluster-randomized trials
Abstract
Prioritized composite endpoints compare trial participants according to a prespecified clinical hierarchy, and the win estimands are increasingly used to summarize treatment effects. When the component event times are right-censored, a pairwise comparison may remain unresolved, and treating unresolved pairs as ties yields a win statistic whose value depends on the censoring distribution. We define win, loss, and tie probabilities at a fixed restriction time for prioritized time-to-event outcomes in individual-randomized trials and extend them to cluster-randomized trials, where cluster-average and individual-average estimands assign equal weight to clusters and to participants, respectively. We propose doubly robust estimators that combine inverse probability of censoring weighting with joint outcome models to incorporate information recorded before censoring. Under covariate-dependent censoring, the resulting U-statistics are consistent when either the censoring models or joint outcome models are correctly specified for both treatment arms, but not necessarily both. We establish asymptotic normality and derive analytic variance estimators for computationally efficient inference. Simulation studies under both designs evaluate bias, precision, and confidence interval coverage under working model misspecification. Applications to two real-world studies demonstrate the use of the proposed methods under individual- and cluster-randomized trials.