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纵向数据与生存数据联合建模中的贝叶斯模型评估及其在癌症临床试验中的应用

Bayesian Model Assessment in Joint Modeling of Longitudinal and Survival Data with Applications to Cancer Clinical Trials.

作者信息

Zhang Danjie, Chen Ming-Hui, Ibrahim Joseph G, Boye Mark E, Shen Wei

机构信息

Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, U.S.A.

Department of Statistics, University of Connecticut, 215 Glenbrook Road, U-4120, Storrs, CT 06269, U.S.A.

出版信息

J Comput Graph Stat. 2017;26(1):121-133. doi: 10.1080/10618600.2015.1117472. Epub 2017 Feb 16.

Abstract

Joint models for longitudinal and survival data are routinely used in clinical trials or other studies to assess a treatment effect while accounting for longitudinal measures such as patient-reported outcomes (PROs). In the Bayesian framework, the deviance information criterion (DIC) and the logarithm of the pseudo marginal likelihood (LPML) are two well-known Bayesian criteria for comparing joint models. However, these criteria do not provide separate assessments of each component of the joint model. In this paper, we develop a novel decomposition of DIC and LPML to assess the fit of the longitudinal and survival components of the joint model, separately. Based on this decomposition, we then propose new Bayesian model assessment criteria, namely, ΔDIC and ΔLPML, to determine the importance and contribution of the longitudinal (survival) data to the model fit of the survival (longitudinal) data. Moreover, we develop an efficient Monte Carlo method for computing the Conditional Predictive Ordinate (CPO) statistics in the joint modeling setting. A simulation study is conducted to examine the empirical performance of the proposed criteria and the proposed methodology is further applied to a case study in mesothelioma.

摘要

纵向和生存数据的联合模型在临床试验或其他研究中经常被用于评估治疗效果,同时考虑诸如患者报告结局(PROs)等纵向测量指标。在贝叶斯框架下,偏差信息准则(DIC)和伪边际似然对数(LPML)是比较联合模型的两个著名的贝叶斯准则。然而,这些准则并未对联合模型的每个组成部分进行单独评估。在本文中,我们对DIC和LPML进行了一种新颖的分解,以分别评估联合模型中纵向和生存部分的拟合优度。基于这种分解,我们随后提出了新的贝叶斯模型评估准则,即ΔDIC和ΔLPML,以确定纵向(生存)数据对生存(纵向)数据模型拟合的重要性和贡献。此外,我们开发了一种有效的蒙特卡罗方法,用于在联合建模设置中计算条件预测纵坐标(CPO)统计量。进行了一项模拟研究以检验所提出准则的实证性能,并将所提出的方法进一步应用于间皮瘤的案例研究。

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