Covariate-adjusted win statistics in randomized clinical trials with ordinal outcomes (2508.20349v1)

Abstract: Ordinal outcomes are common in clinical settings where they often represent increasing levels of disease progression or different levels of functional impairment. Such outcomes can characterize differences in meaningful patient health states that are directly relevant to clinical researchers and frequently represent composite outcomes that include absorbing states such as death. To compare different intervention strategies in clinical trials, the direct use of ordinal logistic regression models may not be ideal for analyzing ranked outcomes due to non-collapsibility, lack of estimation and clarity, or failure of the common underlying proportional odds assumption. In this article, we focus on representing the average treatment effect for ordinal outcomes via intrinsic pairwise outcome comparisons captured through win estimates, such as the win ratio and win difference. We first develop propensity score weighting estimators, including both inverse probability weighting (IPW) and overlap weighting (OW), tailored to estimating win parameters. Furthermore, we develop augmented weighting estimators that leverage an additional ordinal outcome regression to potentially improve efficiency over weighting alone. Leveraging the theory of U-statistics, we establish the asymptotic theory for all estimators, and derive closed-form variance estimators to support statistical inference. Through extensive simulations we demonstrate the enhanced efficiency of the weighted estimators over the unadjusted estimator, with the augmented weighting estimators showing a further improvement in efficiency except for extreme cases. Finally, we illustrate our proposed methods with the ORCHID trial, and implement our covariate adjustment methods in an R package winPSW to facilitate the practical implementation.