Shao, J.; Kübler, J.; Pigeot, Iris
Consistency of the Bootstrap Procedure in Individual Bioequivalence.
Collaborative Research Center 386, Discussion Paper 159
Recently, new concepts have been proposed for assessing bioequivalence of two drug formulations, namely the so-called population and individual bioequivalence. Using moment-based and probability-based measures for evaluating the proposed bioequivalence concepts, criteria have been formulated to decide whether two formulations should be regarded as bioequivalent or not. This decision has of course to be based on an adequate statistical method where the Food and Drug Administration (FDA) guidance (1997) recommends the use of a bootstrap percentile interval. In this paper, we discuss theoretical properties such as consistency and accuracy of the recommended bootstrap intervals. We focus our investigations on the concept of individual bioequivalence and here especially on the scaled versions of the moment-based as well as the probability-based measures as recommended by the FDA. As estimates for the former, we consider those obtained from an according analysis of variance and restricted maximum likelihood estimators under mixed effect models, where an unbiased estimator of the latter can be derived from the corresponding relative frequencies.