Operating Characteristics of Hierarchical Composite Endpoints in Noninferiority Settings

Music City Center 

The Win Ratio (WR) is a hierarchical composite endpoint which has been used in controlled trials in order to compare efficacy of two treatments across multiple components ordered by clinical priority (Pocock, 2012). Pairwise comparisons are performed between all patients in the treatment and control arms, and the total number of "treatment wins" may be divided by the number of "treatment losses" to calculate the WR. The non-parametric nature of this statistic, as well as its ability to incorporate clinical endpoints of varying modalities (time-to-event, continuous, dichotomous) has made it popular for superiority trials, but the operational characteristics of this statistic have not been adequately investigated when the goal of the trial is to declare noninferiority (NI). Due to suboptimal performance of the WR in the event of a large number of ties, another statistic, the Win Odds (WO) has been proposed as an alternative (Peng 2020) This simulation study examines a hypothetical NI trial where the hierarchical composite endpoint has three levels. Operating characteristics for WR and WO will be compared across multiple choices of NI boundary and event rate in order to demonstrate utility of these statistics in NI trials.

Win Ratio

Noninferiority