Title: The Joint Modeling of Longitudinal Covariates and Censored Quantile Regression for Health Applications
Description: The overall theme of this thesis focuses on the joint modeling of longitudinal covariates and a censored survival outcome, where a survival outcome is modeled using a conditional quantile regression. In traditional joint modeling approaches, a survival outcome is usually parametrically modeled as a Cox regression. Censored quantile regressions can model a survival outcome without pre-specifying a parametric likelihood function or assuming a proportional hazard ratio. Existing censored quantile methods are mostly limited to fixed cross-sectional covariates, while in many longitudinal studies, researchers wish to investigate the associations between longitudinal covariates and a survival outcome. The first part considers the problem of joint modeling with a survival outcome under a mixture of censoring: left censoring, interval censoring or right censoring. We pose a linear mixed effect model for a longitudinal covariate and a conditional quantile regression for a censored survival outcome, assuming that a longitudinal covariate and a survival outcome are conditional independent on individual level random effects.

We propose a Gibbs sampling approach as an extension of a censored quantile based data augmentation algorithm, to allow for a longitudinal covariate process. We also propose an iterative algorithm that alternately updates individual level random effects and model parameters, where a censored survival outcome is treated in the way of re-weighting. Both of our methods are illustrated by the application to the LEGACY Girls cohort Study to understand the influence of individual genetic profiles on the pubertal development (i.e., the onset of breast development) while adjusting for BMI growth trajectories. The second part considers the problem of joint modelling with a random right censoring survival outcome. We pose a linear mixed effect model for a longitudinal covariate and a conditional quantile regression for a censored survival outcome, assuming that a longitudinal covariate and a survival outcome are conditional independent on individual level random effects. We propose a Gibbs sampling approach as an extension of a censored quantile based data augmentation algorithm, to allow for a longitudinal covariate process.

Theoretical properties for the resulting parameter estimates are established. We also propose an iterative algorithm that alternately updates individual level random effects and model parameters, where a censored survival outcome is treated in the way of re-weighting. Both of our methods are illustrated by the application to Mayo Clinic Primary Biliary Cholangitis Data to assess the effect of drug D-penicilamine on risk of liver transplantation or death, while controlling for age at registration and serBilir marker.