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带有随机断点的生存分析。

Survival analysis with a random change-point.

机构信息

Department of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong.

Department of Applied Mathematics, Hong Kong Polytechnic University Shenzhen Research Institute, Hong Kong.

出版信息

Stat Methods Med Res. 2023 Nov;32(11):2083-2095. doi: 10.1177/09622802231192946. Epub 2023 Aug 10.

DOI:10.1177/09622802231192946
PMID:37559549
Abstract

Contemporary works in change-point survival models mainly focus on an unknown universal change-point shared by the whole study population. However, in some situations, the change-point is plausibly individual-specific, such as when it corresponds to the telomere length or menopausal age. Also, maximum-likelihood-based inference for the fixed change-point parameter is notoriously complicated. The asymptotic distribution of the maximum-likelihood estimator is non-standard, and computationally intensive bootstrap techniques are commonly used to retrieve its sampling distribution. This article is motivated by a breast cancer study, where the disease-free survival time of the patients is postulated to be regulated by the menopausal age, which is unobserved. As menopausal age varies across patients, a fixed change-point survival model may be inadequate. Therefore, we propose a novel proportional hazards model with a random change-point. We develop a nonparametric maximum-likelihood estimation approach and devise a stable expectation-maximization algorithm to compute the estimators. Because the model is regular, we employ conventional likelihood theory for inference based on the asymptotic normality of the Euclidean parameter estimators, and the variance of the asymptotic distribution can be consistently estimated by a profile-likelihood approach. A simulation study demonstrates the satisfactory finite-sample performance of the proposed methods, which yield small bias and proper coverage probabilities. The methods are applied to the motivating breast cancer study.

摘要

当代变化点生存模型的研究主要集中在整个研究人群共享的未知通用变化点上。然而,在某些情况下,变化点很可能是个体特有的,例如与端粒长度或绝经年龄相对应的情况。此外,基于最大似然的固定变化点参数推断非常复杂。最大似然估计的渐近分布是非标准的,通常使用计算密集的自助技术来获取其抽样分布。本文的动机来自一项乳腺癌研究,假设患者的无病生存时间受绝经年龄的调节,而绝经年龄是不可观测的。由于绝经年龄在患者之间存在差异,固定变化点生存模型可能不适用。因此,我们提出了一种具有随机变化点的新比例风险模型。我们开发了一种非参数最大似然估计方法,并设计了一种稳定的期望最大化算法来计算估计值。由于模型是正则的,我们基于欧几里得参数估计的渐近正态性,采用常规似然理论进行推断,并且可以通过似然轮廓方法一致地估计渐近分布的方差。模拟研究表明,所提出方法在有限样本情况下表现良好,具有较小的偏差和适当的覆盖概率。这些方法应用于激发乳腺癌研究。

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