On recurrent-event win ratio.

Abstract

The win ratio approach proposed by Pocock et al. (2012) has become a popular tool for analyzing composite endpoints of death and non-fatal events like hospitalization. Its standard version, however, draws on the non-fatal event only through the first occurrence. For statistical efficiency and clinical interpretability, we construct and compare different win ratio variants that make fuller use of recurrent events. We pay special attention to a variant called last-event-assisted win ratio, which compares two patients on the cumulative frequency of the non-fatal event, with ties broken by the time of its latest episode. It is shown that last-event-assisted win ratio uses more data than the standard win ratio does but reduces to the latter when the non-fatal event occurs at most once. We further prove that last-event-assisted win ratio rejects the null hypothesis with large probability if the treatment stochastically delays all events. Simulations under realistic settings show that the last-event-assisted win ratio test consistently enjoys higher power than the standard win ratio and other competitors. Analysis of a real cardiovascular trial provides further evidence for the practical advantages of the last-event-assisted win ratio. Finally, we discuss future work to develop meaningful effect size estimands based on the extended rules of comparison. The R-code for the proposed methods is included in the package WR openly available on the Comprehensive R Archive Network.