Bayesian analysis of nonlinear mixed-effects mixture models for longitudinal data with heterogeneity and skewness

Abstract

It is a common practice to analyze complex longitudinal data using nonlinear mixed-effects (NLME) models with normality assumption. The NLME models with normal distributions provide the most popular framework for modeling continuous longitudinal outcomes, assuming individuals are from a homogeneous population and relying on random-effects to accommodate inter-individual variation. However, the following two issues may standout: (i) normality assumption for model errors may cause lack of robustness and subsequently lead to invalid inference and unreasonable estimates, particularly, if the data exhibit skewness and (ii) a homogeneous population assumption may be unrealistically obscuring important features of between-subject and within-subject variations, which may result in unreliable modeling results. There has been relatively few studies concerning longitudinal data with both heterogeneity and skewness features. In the last two decades, the skew distributions have shown beneficial in dealing with asymmetric data in various applications. In this article, our objective is to address the simultaneous impact of both features arisen from longitudinal data by developing a flexible finite mixture of NLME models with skew distributions under Bayesian framework that allows estimates of both model parameters and class membership probabilities for longitudinal data. Simulation studies are conducted to assess the performance of the proposed models and methods, and a real example from an AIDS clinical trial illustrates the methodology by modeling the viral dynamics to compare potential models with different distribution specifications; the analysis results are reported.