Copulas for Covariate Simulation in Pharmacometrics

Patient-specific covariates are commonly incorporated in pharmacometric and quantitative system pharmacology models to predict differences in pharmacokinetic or pharmacodynamic profiles between patients. When simulating new virtual populations of patients, generating realistic covariate sets that accurately reflect the correlation structures among covariates is essential to obtain reliable simulation outcomes. Copulas are joint distribution functions that characterize the dependence structures of patient covariates and enable the simulation of virtual populations. The current tutorial provides a step-by-step guide for understanding the concept of copulas and an overview of applications of copulas in pharmacometric research.