The ratio of the hazard functions of two populations or two strata of a single population plays an important role in time-to-event analysis. Cox regression is commonly used to estimate the hazard ratio under the assumption that it is constant in time, which is known as the proportional hazards assumption. However, this assumption is often violated in practice, and when it is violated, the parameter estimated by Cox regression is difficult to interpret. The hazard ratio can be estimated in a nonparametric manner using smoothing, but smoothing-based estimators are sensitive to the selection of tuning parameters, and it is often difficult to perform valid inference with such estimators. In some cases, it is known that the hazard ratio function is monotone. In this article, we demonstrate that monotonicity of the hazard ratio function defines an invariant stochastic order, and we study the properties of this order. Furthermore, we introduce an estimator of the hazard ratio function under a monotonicity constraint. We demonstrate that our estimator converges in distribution to a mean-zero limit, and we use this result to construct asymptotically valid confidence intervals. Finally, we conduct numerical studies to assess the finite-sample behavior of our estimator, and we use our methods to estimate the hazard ratio of progression-free survival in pulmonary adenocarcinoma patients treated with gefitinib or carboplatin-paclitaxel.
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Debiased inference for a covariate-adjusted regression function
In this article, we study nonparametric inference for a covariate-adjusted regression function. This parameter captures the average association between a continuous exposure and an outcome after adjusting for other covariates. Under certain causal conditions, it also corresponds to the average outcome had all units been assigned to a specific exposure level, known as the causal dose–response curve. We propose a debiased local linear estimator of the covariate-adjusted regression function and demonstrate that our estimator converges pointwise to a mean-zero normal limit distribution. We use this result to construct asymptotically valid confidence intervals for function values and differences thereof. In addition, we use approximation results for the distribution of the supremum of an empirical process to construct asymptotically valid uniform confidence bands. Our methods do not require undersmoothing, permit the use of data-adaptive estimators of nuisance functions, and our estimator attains the optimal rate of convergence for a twice differentiable regression function. We illustrate the practical performance of our estimator using numerical studies and an analysis of the effect of air pollution exposure on cardiovascular mortality.
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- Award ID(s):
- 2113171
- PAR ID:
- 10520179
- Publisher / Repository:
- Taylor and Francis
- Date Published:
- Journal Name:
- Journal of the Royal Statistical Society Series B: Statistical Methodology
- ISSN:
- 1369-7412
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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