© 2000 by Biometrika Trust
Consistency of the bootstrap procedure in individual bioequivalence
Z Department of Statistics, University of Wisconsin, 1210 West Dayton Street, Madison, Wisconsin 53706, USA E-mail: shao@stat.wisc.edu ZZ Bayer AG, PH-PD M CDPI/PE, D-42096 Wuppertal, Germany E-mail: juergen.kuebler.jk@bayer-ag.de Y Institute of Statistics, University of Munich, Ludwigstrasse 33, D-80539 Munich, Germany E-mail: pigeot@stat.uni-muenchen.de
Recently, the concepts of population and individual bioequivalence have been proposed for assessing the bioequivalence of two drug formulations. Moment-based and probability-based measures of bioequivalence have led to criteria for deciding whether two formulations should be regarded as bioequivalent or not. The US Food and Drug Administration (1997) guidance recommended the use of bootstrap percentile intervals for this purpose. In this paper, we discuss theoretical properties such as consistency and accuracy of the recommended bootstrap intervals. We concentrate on individual bioequivalence and especially on the scaled versions of the moment-based as well as the probability-based measures as recommended by the US Food and Drug Administration. As estimates for the former, we consider those obtained from an appropriate analysis of variance and restricted maximum likelihood estimators under mixed effect models, whereas an unbiased estimator of the latter can be derived from corresponding relative frequencies.
Key Words: bioequivalence; bootstrap percentile; consistency