Abstract

Joint modeling of longitudinal outcomes and time-to-event data has been extensively used in medical studies because it can simultaneously model the longitudinal trajectories and assess their effects on the event-time. However, in many applications, we come across heterogeneous populations and the subjects need to be clustered for a powerful statistical inference. We consider multivariate binary longitudinal outcomes for which we use Bayesian data-augmentation to get latent continuous outcomes. These latent outcomes are clustered using Bayesian Consensus Clustering after which we perform a cluster-specific joint analysis. Longitudinal outcomes are modeled by generalized linear mixed models, and we use proportional hazards model for time-to-event data. Our work is motivated by a clinical trial conducted by Tata Translational Cancer Research Center, Kolkata, where 184 cancer patients were treated for the first two years, and then were followed for the next three years. Three biomarkers (lymphocyte count, neutrophil count and platelet count), categorized as normal/abnormal, were measured over time during the treatment, and the relapse time (if any) was recorded for each patient. Our analysis finds three latent clusters for which the effects of the covariates and the median non-relapse probabilities substantially differ. Through a simulation study, we illustrate the effectiveness of the proposed simultaneous clustering and joint modeling.