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arXiv · 2608.06774

Bridging Balancing Weights and Augmentation in Covariate-adjusted Analyses with Time-to-Event Endpoints: Theory and Practical Recommendations

Abstract

Covariate adjustment improves the efficiency of treatment-effect analyses in randomized clinical trials, provided the adjustment targets the correct quantity. For time-to-event endpoints, two marginal targets are of primary interest: the log-rank test for the presence of a treatment effect and the marginal hazard ratio for its magnitude. Existing covariate adjustment approaches reach these targets by different ways. Augmentation adjusts the log-rank score by regressing derived outcomes on the baseline covariates within each arm. Weighting instead reweights the two arms to balance the covariates before the survival comparison is formed: inverse probability weighting does so through a fitted propensity model, while calibration weighting solves directly for weights that match covariate means. In this manuscript, we first develop balancing weighting for time-to-event endpoints, covering both calibration weights (stable balancing weights and entropy balancing) and propensity score weights, and prove that any balancing-regular weighting is first-order equivalent to the augmented log-rank score and to the root of the marginal Cox score. All three routes therefore deliver the same estimator to first order, and calibration reaches it without fitting any model. The weighted procedures thereby inherit the validity and guaranteed efficiency gain of the augmentation approach. In addition, we show that the efficiency gain grows with the prognostic strength of the adjustment covariates, while the practical caveat lies in variance estimation, for which we give recommendations to guard against finite-sample Type I error inflation. We further confirm our results through simulation studies and an analysis of the REWIND cardiovascular trial.

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BibTeXRIS

Baoshan Zhang, Yi Chen, Yu Du, Tuo Wang. 2026-08-07. Bridging Balancing Weights and Augmentation in Covariate-adjusted Analyses with Time-to-Event Endpoints: Theory and Practical Recommendations. https://arxiv.org/abs/2608.06774

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