Simulating realistically complex comparative effectiveness studies with time-varying covariates and right-censored outcomes

Abstract: Simulation studies are useful for evaluating and developing statistical methods for the analyses of complex problems. Performance of methods may be affected by multiple complexities present in real scenarios. Generating sufficiently realistic data for this purpose, however, can be challenging. Our study of the comparative effectiveness of HIV protocols on the risk of cardiovascular disease -- involving the longitudinal assessment of HIV patients -- is such an example. The correlation structure across covariates and within subjects over time must be considered as well as right-censoring of the outcome of interest, time to myocardial infarction. A challenge in simulating the covariates is to incorporate a joint distribution for variables of mixed type -- continuous, binary or polytomous. An additional challenge is incorporating within-subject correlation where some variables may vary over time and others may remain static. To address these issues, we extend the work of Demirtas and Doganay (2012). Identifying a model from which to simulate the right-censored outcome as a function of these covariates builds on work developed by Sylvestre and Abrahamowicz (2007). In this paper, we describe a cohesive and user-friendly approach accompanied by R code to simulate comparative effectiveness studies with right-censored outcomes that are functions of time-varying covariates.