Joint models for longitudinal and survival data

Abstract

Epidemiologic and clinical studies routinely collect longitudinal measures of multiple outcomes. These longitudinal outcomes can be used to establish the temporal order of relevant biological processes and their association with the onset of clinical symptoms. In the first part of this thesis, we proposed to use bivariate change point models for two longitudinal outcomes with a focus on estimating the correlation between the two change points. We adopted a Bayesian approach for parameter estimation and inference. In the second part, we considered the situation when time-to-event outcome is also collected along with multiple longitudinal biomarkers measured until the occurrence of the event or censoring. Joint models for longitudinal and time-to-event data can be used to estimate the association between the characteristics of the longitudinal measures over time and survival time. We developed a maximum-likelihood method to joint model multiple longitudinal biomarkers and a time-to-event outcome. In addition, we focused on predicting conditional survival probabilities and evaluating the predictive accuracy of multiple longitudinal biomarkers in the joint modeling framework. We assessed the performance of the proposed methods in simulation studies and applied the new methods to data sets from two cohort studies.