A Bayesian Population Model with Hierarchical Mixture Priors Applied to Blood Count Data

Abstract

Abstract Population pharmacokinetic and pharmacodynamic studies require analyzing nonlinear growth curves fit to multiple measurements from study subjects. We propose a class of nonlinear population models with nonparametric second-stage priors for analyzing such data. The proposed models apply a flexible class of mixtures to implement the nonparametric second stage. The discussion is based on a pharmacodynamic study involving longitudinal data consisting of hematologic profiles (i.e., blood counts measured over time) of cancer patients undergoing chemotherapy. We describe a full posterior analysis in a Bayesian framework. This includes prediction of future observations (profiles and end points for new patients), estimation of the mean response function for observed individuals, and inference on population characteristics. The mixture model is specified and given a hyperprior distribution by means of a Dirichlet processes prior on the mixing measure. Estimation is implemented by a combination of various Markov chain Monte Carlo schemes, including a novel independence chain scheme for a logistic regression. The discussion is motivated by a pharmacodynamic case study; however, the concepts are more generally applicable to the wider class of population models.