Analysis of the Cox Model with Longitudinal Covariates with Measurement Errors and Partly Interval Censored Failure Times, with Application to an AIDS Clinical Trial.
Analysis of the Cox Model with Longitudinal Covariates with Measurement Errors and Partly Interval Censored Failure Times, with Application to an AIDS Clinical Trial.
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DOI：
10.1007/s12561-023-09372-y
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发表时间：
2023
影响因子：
1
通讯作者：
Gilbert, Peter B
中科院分区：
文献类型：
--
作者：
Sun, Yanqing;Zhou, Qingning;Gilbert, Peter B
时间依赖性协变量通常是间歇性测量的，并且存在测量误差。受艾滋病临床试验组（ACTG）175试验的启发，本文发展了部分区间删失失效时间和纵向协变量与测量误差的考克斯模型的统计推断。针对有测量误差和右删失数据的考克斯模型的条件评分方法不再适用于区间删失数据。假设一个纵向协变量的加性测量误差模型，我们提出了一个非参数最大似然估计方法，通过推导测量误差引起的风险模型，显示使用插件估计的衰减效应的真实潜在的纵向协变量。EM算法的设计，以促进最大似然估计，占部分区间删失的故障时间。所提出的方法可以适应不同个体和不同时间的不同重复次数。仿真研究表明，所提出的方法具有良好的有限样本性能，忽略测量误差或使用插入估计的朴素方法会产生较大的偏差。提出了测量误差模型的假设检验方法。将所提出的方法应用于ACTG 175试验，以评估治疗组和时间依赖性CD4细胞计数对AIDS或死亡的复合临床终点的相关性。在线版本包含补充材料，可通过10.1007/s12561 - 023 - 09372-y获得。
Time-dependent covariates are often measured intermittently and with measurement errors. Motivated by the AIDS Clinical Trials Group (ACTG) 175 trial, this paper develops statistical inferences for the Cox model for partly interval censored failure times and longitudinal covariates with measurement errors. The conditional score methods developed for the Cox model with measurement errors and right censored data are no longer applicable to interval censored data. Assuming an additive measurement error model for a longitudinal covariate, we propose a nonparametric maximum likelihood estimation approach by deriving the measurement error induced hazard model that shows the attenuating effect of using the plug-in estimate for the true underlying longitudinal covariate. An EM algorithm is devised to facilitate maximum likelihood estimation that accounts for the partly interval censored failure times. The proposed methods can accommodate different numbers of replicates for different individuals and at different times. Simulation studies show that the proposed methods perform well with satisfactory finite-sample performances and that the naive methods ignoring measurement error or using the plug-in estimate can yield large biases. A hypothesis testing procedure for the measurement error model is proposed. The proposed methods are applied to the ACTG 175 trial to assess the associations of treatment arm and time-dependent CD4 cell count on the composite clinical endpoint of AIDS or death. The online version contains supplementary material available at 10.1007/s12561-023-09372-y.