Shared parameter and copula models for analysis of semicontinuous longitudinal data with nonrandom dropout and informative censoring.

Analysis of longitudinal semicontinuous data characterized by subjects' attrition triggered by nonrandom dropout is complex and requires accounting for the within-subject correlation, and modeling of the dropout process. While methods that address the within-subject correlation and missing data are available, approaches that incorporate the nonrandom dropout, also referred to informative right censoring, in the modeling step are scarce due to the computational intensity and possible intractable integration needed for its implementation. Appreciating the complexity of this problem and the need for a new methodology that is feasible for implementation, we propose to extend a framework of likelihood-based marginalized two-part models to account for informative right censoring. The censoring process is modeled using two approaches: (1) Poisson censoring for the count of visits before dropout and (2) survival time to dropout. Novel consideration was given to the proposed joint modeling approaches for the semicontinuous and censoring components of the likelihood function which included (1) shared parameter, and (2) Clayton copula. The cross-part and within-part correlations were accounted for through a complex random effect structure that models correlated random intercepts and slopes. Feasibility of implementation, and accuracy of these approaches were investigated using extensive simulation studies and clinical application.