A joint model of longitudinal and competing risks survival data with heterogeneous random effects and outlying longitudinal measurements.

Abstract

This article proposes a joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model with t-distributed measurement errors for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the survival outcome, and a regression sub-model for the variance-covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. A Bayesian MCMC procedure is developed for parameter estimation and inference. Our method is insensitive to outlying longitudinal measurements in the presence of non-ignorable missing data due to dropout. Moreover, by modeling the variance-covariance matrix of the latent random effects, our model provides a useful framework for handling high-dimensional heterogeneous random effects and testing the homogeneous random effects assumption which is otherwise untestable in commonly used joint models. Finally, our model enables analysis of a survival outcome with intermittently measured time-dependent covariates and possibly correlated competing risks and dependent censoring, as well as joint analysis of the longitudinal and survival outcomes. Illustrations are given using a real data set from a lung study and simulation.