Dynamic Prediction for Multiple Repeated Measures and Event Time Data: An Application to Parkinson's Disease

Abstract: In many clinical trials studying neurodegenerative diseases such as Parkinson's disease (PD), multiple longitudinal outcomes are collected to fully explore the multidimensional impairment caused by this disease. If the outcomes deteriorate rapidly, patients may reach a level of functional disability sufficient to initiate levodopa therapy for ameliorating disease symptoms. An accurate prediction of the time to functional disability is helpful for clinicians to monitor patients' disease progression and make informative medical decisions. In this article, we first propose a joint model that consists of a semiparametric multilevel latent trait model (MLLTM) for the multiple longitudinal outcomes, and a survival model for event time. The two submodels are linked together by an underlying latent variable. We develop a Bayesian approach for parameter estimation and a dynamic prediction framework for predicting target patients' future outcome trajectories and risk of a survival event, based on their multivariate longitudinal measurements. Our proposed model is evaluated by simulation studies and is applied to the DATATOP study, a motivating clinical trial assessing the effect of deprenyl among patients with early PD.