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用于检测 Cox 比例风险模型中变化点的信息准则。

Information criteria for detecting change-points in the Cox proportional hazards model.

机构信息

Biometrics Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

Department of Statistical Science, The Graduate University for Advanced Studies, Tokyo, Japan.

出版信息

Biometrics. 2023 Dec;79(4):3050-3065. doi: 10.1111/biom.13855. Epub 2023 Apr 4.

Abstract

The Cox proportional hazards model, commonly used in clinical trials, assumes proportional hazards. However, it does not hold when, for example, there is a delayed onset of the treatment effect. In such a situation, an acute change in the hazard ratio function is expected to exist. This paper considers the Cox model with change-points and derives Akaike information criterion (AIC)-type information criteria for detecting those change-points. The change-point model does not allow for conventional statistical asymptotics due to its irregularity, thus a formal AIC that penalizes twice the number of parameters would not be analytically derived, and using it would clearly give overfitting analysis results. Therefore, we will construct specific asymptotics using the partial likelihood estimation method in the Cox model with change-points, and propose information criteria based on the original derivation method for AIC. If the partial likelihood is used in the estimation, information criteria with penalties much larger than twice the number of parameters could be obtained in an explicit form. Numerical experiments confirm that the proposed criteria are clearly superior in terms of the original purpose of AIC, which are to provide an estimate that is close to the true structure. We also apply the proposed criterion to actual clinical trial data to indicate that it will easily lead to different results from the formal AIC.

摘要

Cox 比例风险模型常用于临床试验,它假设风险比例不变。然而,当治疗效果延迟出现时,这种假设就不再成立。在这种情况下,预计危险比函数会发生急剧变化。本文考虑了带有断点的 Cox 模型,并推导出用于检测这些断点的 Akaike 信息准则(AIC)型信息准则。由于其不规则性,带有断点的模型不允许使用常规的统计渐近性,因此不会通过解析方法推导出惩罚参数数量两倍的正式 AIC,使用它显然会导致过度拟合的分析结果。因此,我们将使用带有断点的 Cox 模型中的部分似然估计方法构建特定的渐近性,并提出基于 AIC 的原始推导方法的信息准则。如果在估计中使用部分似然,那么可以以显式形式获得惩罚远远大于参数数量两倍的信息准则。数值实验证实,所提出的准则在 AIC 的原始目的方面明显更优,即提供接近真实结构的估计。我们还将所提出的准则应用于实际临床试验数据,以表明它将很容易导致与正式 AIC 的不同结果。

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