Estimation and Inference for Win Measures with Multiple Ordinal Endpoints Subject to Missingness

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Main Authors: Liu, Yi, Barnhart, Huiman, O'Brien, Sean, Lokhnygina, Yuliya, Matsouaka, Roland A.
Format: Preprint
Published: 2026
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author Liu, Yi
Barnhart, Huiman
O'Brien, Sean
Lokhnygina, Yuliya
Matsouaka, Roland A.
author_facet Liu, Yi
Barnhart, Huiman
O'Brien, Sean
Lokhnygina, Yuliya
Matsouaka, Roland A.
contents Win measures, including the win ratio (WR), win odds (WO), net benefit (NB), and desirability of outcome ranking (DOOR), are increasingly used in randomized clinical trials with multiple hierarchical ordinal endpoints. In practice, however, one or more component endpoints may have missing data. The standard pairwise-comparison approach, which treats pairs with missing outcomes as ties, can produce biased estimates, even if the data are missing completely at random (MCAR). Although inverse probability of censoring weighting (IPCW) methods have been developed for censored survival endpoints, corresponding methods for addressing missing hierarchical ordinal endpoints are not yet available. To address this gap, we develop inverse probability weighting (IPW) and augmented IPW (AIPW) estimators for win measures with hierarchical ordinal endpoints subject to missing data, allowing missingness to depend on treatment assignment and baseline covariates. The IPW estimator corrects bias by reweighting complete observed outcomes using joint non-missingness probabilities involved in estimating the joint cell probabilities that define the win measures. The AIPW estimator additionally incorporates outcome modeling, improving efficiency and achieving double robustness. For inference, we derive closed-form variance estimators for both methods based on influence functions. Simulation studies show that the standard approach can be substantially biased, whereas the proposed IPW and AIPW estimators remain consistent with near-nominal coverage. Furthermore, the AIPW estimator is generally more efficient than IPW estimator. Applications to the SCOUT-CAP and ACTT-1 trials illustrate the practical utility of the proposed methods. An R package, WinMO, is provided for implementation.
format Preprint
id arxiv_https___arxiv_org_abs_2605_27085
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Estimation and Inference for Win Measures with Multiple Ordinal Endpoints Subject to Missingness
Liu, Yi
Barnhart, Huiman
O'Brien, Sean
Lokhnygina, Yuliya
Matsouaka, Roland A.
Methodology
Statistics Theory
Applications
Win measures, including the win ratio (WR), win odds (WO), net benefit (NB), and desirability of outcome ranking (DOOR), are increasingly used in randomized clinical trials with multiple hierarchical ordinal endpoints. In practice, however, one or more component endpoints may have missing data. The standard pairwise-comparison approach, which treats pairs with missing outcomes as ties, can produce biased estimates, even if the data are missing completely at random (MCAR). Although inverse probability of censoring weighting (IPCW) methods have been developed for censored survival endpoints, corresponding methods for addressing missing hierarchical ordinal endpoints are not yet available. To address this gap, we develop inverse probability weighting (IPW) and augmented IPW (AIPW) estimators for win measures with hierarchical ordinal endpoints subject to missing data, allowing missingness to depend on treatment assignment and baseline covariates. The IPW estimator corrects bias by reweighting complete observed outcomes using joint non-missingness probabilities involved in estimating the joint cell probabilities that define the win measures. The AIPW estimator additionally incorporates outcome modeling, improving efficiency and achieving double robustness. For inference, we derive closed-form variance estimators for both methods based on influence functions. Simulation studies show that the standard approach can be substantially biased, whereas the proposed IPW and AIPW estimators remain consistent with near-nominal coverage. Furthermore, the AIPW estimator is generally more efficient than IPW estimator. Applications to the SCOUT-CAP and ACTT-1 trials illustrate the practical utility of the proposed methods. An R package, WinMO, is provided for implementation.
title Estimation and Inference for Win Measures with Multiple Ordinal Endpoints Subject to Missingness
topic Methodology
Statistics Theory
Applications
url https://arxiv.org/abs/2605.27085