Jointly Modeling Event Time and Skewed-Longitudinal Data with Missing Response and Mismeasured Covariate for AIDS Studies

Abstract

In longitudinal studies it is often of interest to investigate how a repeatedly measured marker in time is associated with a time to an event of interest. This type of research question has given rise to a rapidly developing field of biostatistics research that deals with the joint modeling of longitudinal and time-to-event data. Normality of model errors in longitudinal model is a routine assumption, but it may be unrealistically obscuring important features of subject variations. Covariates are usually introduced in the models to partially explain between- and within-subject variations, but some covariates such as CD4 cell count may be often measured with substantial errors. Moreover, the responses may encounter nonignorable missing. Statistical analysis may be complicated dramatically based on longitudinal-survival joint models where longitudinal data with skewness, missing values, and measurement errors are observed. In this article, we relax the distributional assumptions for the longitudinal models using skewed (parametric) distribution and unspecified (nonparametric) distribution placed by a Dirichlet process prior, and address the simultaneous influence of skewness, missingness, covariate measurement error, and time-to-event process by jointly modeling three components (response process with missing values, covariate process with measurement errors, and time-to-event process) linked through the random-effects that characterize the underlying individual-specific longitudinal processes in Bayesian analysis. The method is illustrated with an AIDS study by jointly modeling HIV/CD4 dynamics and time to viral rebound in comparison with potential models with various scenarios and different distributional specifications.

Key words:

• Bayesian analysis
• covariate measurement errors
• Dirichlet process prior
• mixed-effects joint models
• skew-t distribution
• time-to-event

ACKNOWLEDGMENTS

The authors are extremely grateful to the Editor, an Associate Editor, and two anonymous referees for their insightful comments and valuable suggestions that led to significant improvement of the article.

FUNDING

This research was partially supported by University South Florida Internal Grant 18324 to Y. Huang and by National Natural Science Foundation of China under Grant 61174160 to C. Yan.