Joint modeling of longitudinal continuous, longitudinal ordinal, and time-to-event outcomes

In this paper, we propose an innovative method for jointly analyzing survival data and longitudinally measured continuous and ordinal data. We use a random effects accelerated failure time model for survival outcomes, a linear mixed model for continuous longitudinal outcomes and a proportional odds mixed model for ordinal longitudinal outcomes, where these outcome processes are linked through a set of association parameters. A primary objective of this study is to examine the effects of association parameters on the estimators of joint models. The model parameters are estimated by the method of maximum likelihood. The finite-sample properties of the estimators are studied using Monte Carlo simulations. The empirical study suggests that the degree of association among the outcome processes influences the bias, efficiency, and coverage probability of the estimators. Our proposed joint model estimators are approximately unbiased and produce smaller mean squared errors as compared to the estimators obtained from separate models. This work is motivated by a large multicenter study, referred to as the Genetic and Inflammatory Markers of Sepsis (GenIMS) study. We apply our proposed method to the GenIMS data analysis.