Optimal Designs for Two Nested Pharmacokinetic Models with Correlated Observations

Abstract

Two nested pharmacokinetic models are considered in this article. Several observations are taken on the same subject so they are correlated. The covariance function assumed is an exponential covariance function. Optimal exact designs are computed with different criteria, both for discriminating between models and estimating parameters. Compound criteria to estimate the parameters and nonlinear functions of the parameters are used. An iterative algorithm based on T-optimality and an algorithm from Brimkulov et al. (1986) are combined in order to compute T-optimal designs with correlated observations. Finally, compound designs to discriminate between the models and estimate the nonlinear functions are considered. A test power study is performed to adjust the compound parameter.