A joint model for mixed and truncated longitudinal data and survival data, with application to HIV vaccine studies.

Abstract

In HIV vaccine studies, a major research objective is to identify immune response biomarkers measured longitudinally that may be associated with risk of HIV infection. This objective can be assessed via joint modeling of longitudinal and survival data. Joint models for HIV vaccine data are complicated by the following issues: (i) left truncations of some longitudinal data due to lower limits of quantification; (ii) mixed types of longitudinal variables; (iii) measurement errors and missing values in longitudinal measurements; (iv) computational challenges associated with likelihood inference. In this article, we propose a joint model of complex longitudinal and survival data and a computationally efficient method for approximate likelihood inference to address the foregoing issues simultaneously. In particular, our model does not make unverifiable distributional assumptions for truncated values, which is different from methods commonly used in the literature. The parameters are estimated based on the h-likelihood method, which is computationally efficient and offers approximate likelihood inference. Moreover, we propose a new approach to estimate the standard errors of the h-likelihood based parameter estimates by using an adaptive Gauss-Hermite method. Simulation studies show that our methods perform well and are computationally efficient. A comprehensive data analysis is also presented.