POPED, a software for optimal experiment design in population kinetics.

Abstract

Population kinetic analysis is the methodology used to quantify inter-subject variability in kinetic studies. It entails the collection of (possibly sparse) data from dynamic experiments in a group of subjects and their quantitative interpretation by means of a mathematical model. This methodology is widely used in the pharmaceutical industry (where it is termed "pharmacokinetic population analysis") and recently it is becoming increasingly used in other areas of biomedical research. Unlike traditional kinetic studies, where the number of subjects can be quite small, population kinetic studies require large numbers of subjects. It is, therefore, of great interest to design these studies in the most efficient manner possible, to maximize the information content provided by the data. In this paper we propose an algorithm and a computer program, POPED, for the optimal design of a population kinetic experiment. In particular, the number of samples for each subject and the design of the individual sampling strategies, i.e. the number and location of the time points at which the output variable is sampled, will be considered. Among the various criteria proposed in the literature, D and ED optimality are the ones implemented in our software program, since they are the most widely used. A brief description of the techniques employed to perform design optimization is given, together with some details on their actual implementation. Some examples are then presented to show the program usage and the results provided.