Stochastic EM Algorithm for Joint Model of Logistic Regression and Mechanistic Nonlinear Model in Longitudinal Studies

Abstract

We study a joint model where logistic regression is applied to binary longitudinal data with a mismeasured time-varying covariate that is modeled using a mechanistic nonlinear model. Multiple random effects are necessary to characterize the trajectories of the covariate and the response variable, leading to a high dimensional integral in the likelihood. To account for the computational challenge, we propose a stochastic expectation-maximization (StEM) algorithm with a Gibbs sampler coupled with Metropolis–Hastings sampling for the inference. In contrast with previous developments, this algorithm uses single imputation of the missing data during the Monte Carlo procedure, substantially increasing the computing speed. Through simulation, we assess the algorithm’s convergence and compare the algorithm with more classical approaches for handling measurement errors. We also conduct a real-world data analysis to gain insights into the association between CD4 count and viral load during HIV treatment.

Keywords

• logistic regression
• longitudinal binary data
• measurement error
• time-varying covariate
• mechanistc nonelinear model
• stochastic EM