Bayesian Joint Modeling of Longitudinal Measurements and Time-to-Event Data Using Robust Distributions

Abstract

Distributional assumptions of most of the existing methods for joint modeling of longitudinal measurements and time-to-event data cannot allow incorporation of outlier robustness. In this article, we develop and implement a joint modeling of longitudinal and time-to-event data using some powerful distributions for robust analyzing that are known as normal/independent distributions. These distributions include univariate and multivariate versions of the Student’s t, the slash, and the contaminated normal distributions. The proposed model implements a linear mixed effects model under a normal/independent distribution assumption for both random effects and residuals of the longitudinal process. For the time-to-event process a parametric proportional hazard model with a Weibull baseline hazard is used. Also, a Bayesian approach using the Markov-chain Monte Carlo method is adopted for parameter estimation. Some simulation studies are performed to investigate the performance of the proposed method under presence and absence of outliers. Also, the proposed methods are applied for analyzing a real AIDS clinical trial, with the aim of comparing the efficiency and safety of two antiretroviral drugs, where CD4 count measurements are gathered as longitudinal outcomes. In these data, time to death or dropout is considered as the interesting time-to-event outcome variable. Different model structures are developed for analyzing these data sets, where model selection is performed by the deviance information criterion (DIC), expected Akaike information criterion (EAIC), and expected Bayesian information criterion (EBIC).

Key Words:

• Bayesian approach
• Joint models
• Longitudinal data
• Markov-chain Monte Carlo
• Normal/independent distributions
• Time-to-event data