English

Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards

Methodology 2026-02-17 v1 Applications Machine Learning

Abstract

The hazard ratio from the Cox proportional hazards model is a ubiquitous summary of treatment effect. However, when hazards are non-proportional, the hazard ratio can lose a stable causal interpretation and become study-dependent because it effectively averages time-varying effects with weights determined by follow-up and censoring. We consider the average hazard (AH) as an alternative causal estimand: a population-level person-time event rate that remains well-defined and interpretable without assuming proportional hazards. Although AH can be estimated nonparametrically and regression-style adjustments have been proposed, existing approaches do not provide a general framework for flexible, high-dimensional nuisance estimation with valid sqrt{n} inference. We address this gap by developing a semiparametric, doubly robust framework for covariate-adjusted AH. We establish pathwise differentiability of AH in the nonparametric model, derive its efficient influence function, and construct cross-fitted, debiased estimators that leverage machine learning for nuisance estimation while retaining asymptotically normal, sqrt{n}-consistent inference under mild product-rate conditions. Simulations demonstrate that the proposed estimator achieves small bias and near-nominal confidence-interval coverage across proportional and non-proportional hazards settings, including crossing-hazards regimes where Cox-based summaries can be unstable. We illustrate practical utility in comparative effectiveness research by comparing immunotherapy regimens for advanced melanoma using SEER-Medicare linked data.

Keywords

Cite

@article{arxiv.2602.13475,
  title  = {Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards},
  author = {Xiang Meng and Lu Tian and Kenneth Kehl and Hajime Uno},
  journal= {arXiv preprint arXiv:2602.13475},
  year   = {2026}
}

Comments

Main paper: 24 pages and 2 figures; Reference and Supplement: 22 pages and 8 Figures