Covariate Modeling in Population PK/PD Models: an Open Problem

Abstract

Covariate Model selection for population PK/PD models represents a daunting task because of the large variety of possible alternative covariates that can enter a structural model, the different models that can express the relationship parameter/covariates, and the number of alternative models that can be considered. After describing the problem and briefly reviewing the past literature dedicated to the solution of the problem we use simulations to show the limitations of current approaches and propose an alternative based on the sequential use of Bayesian Trans Dimensional Models. Although the alternative mollifies the dimensionality problem associated with covariate selection, we argue that the overall approach to covariate modeling within PKPD models might need to be reconsidered.