Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards
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arXiv
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| Autores principales: | , , , |
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| Formato: | Preprint |
| Publicado: |
2026
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| _version_ | 1866915798276112384 |
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| author | Meng, Xiang Tian, Lu Kehl, Kenneth Uno, Hajime |
| author_facet | Meng, Xiang Tian, Lu Kehl, Kenneth Uno, Hajime |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2602_13475 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards Meng, Xiang Tian, Lu Kehl, Kenneth Uno, Hajime Methodology Applications Machine Learning 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. |
| title | Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards |
| topic | Methodology Applications Machine Learning |
| url | https://arxiv.org/abs/2602.13475 |