Defining estimand for the win ratio: Separate the true effect from censoring.

The win ratio has been increasingly used in trials with hierarchical composite endpoints. While the outcomes involved and the rule for their comparisons vary with the application, there is invariably little attention to the estimand of the resulting statistic, causing difficulties in interpretation and cross-trial comparison. We make the case for articulating the estimand as a first step to win ratio analysis and establish that the root cause for its elusiveness is its intrinsic dependency on the time frame of comparison, which, if left unspecified, is set haphazardly by trial-specific censoring. From the statistical literature, we summarize two general approaches to overcome this uncertainty-a nonparametric one that pre-specifies the time frame for all comparisons, and a semiparametric one that posits a constant win ratio across all times-each with publicly available software and real examples. Finally, we discuss unsolved challenges, such as estimand construction and inference in the presence of intercurrent events.