Algorithms, software and sequential optimal sampling schedule designs for pharmacokinetic and physiologic experiments

The problem of designing optimal blood sampling protocols for kinetic experiments in pharmacology, physiology and medicine is briefly described, followed by a presentation of several interesting results based on sequentially optimized studies we have performed in more than 75 laboratory animals. Experiences with different algorithms and design software are also presented. The overall approach appears to be highly efficacious, from the standpoints of both laboratory economics and resulting model accuracy. Optimal sampling schedules (OSS) have a number of different time points equal to the number of unknown parameters for a popular class of models. Replication rather than distribution of samples provide maximum accuracy when additional sampling is feasible; and specific replicates can be used to weight some parameter accuracies more than others, even when a D-optimality criterion is used. Our sequential experiment scheme often converged in 1 step and resulting optimal sampling schedules were reasonably robust, allowing for biological variation among the animals studied.