A Note on Power and Sampling Schedule in Population Pharmacokinetic Studies

Abstract

Population pharmacokinetic studies with a single sampling design such as single-trough sampling have been frequently conducted in Japan, often with little statistical consideration to the sampling design as well as to the sample size. When pharmacokinetic parameters obtained by population pharmacokinetic analysis are used for comparing pharmacokinetic profiles between regions/populations, the difference may be overlooked for lack of power. To point out such problems in the current practice of population pharmacokinetic studies in Japan, we investigated the relationship between the sampling schedule and the necessary sample size to detect a difference of parameters between regions/populations with predefined power by simulation using a simple pharmacokinetic model. The result indicates that it is difficult to obtain enough power in studies with a single sampling design even when the number of subjects is 300 per group because the variances of the estimated parameters are too large. Also, the power is influenced by the sampling schedule as well as the kind of pharmacokinetic parameters for evaluation. In designing population pharmacokinetic studies, especially for those that are conducted to obtain confirmative information on pharmacokinetic parameters, it would be crucial to examine prospectively the suitable sampling design as well as the necessary sample size.