The bioequivalence problem is of practical importance because the approval of most generic drugs in the United States and the European Community (EC) requires the establishment of bioequivalence between the name brand drug and the proposed generic version. The problem is theoretically interesting because it has been recognized as one for which the desired inference, instead of the usual significant difference, is practical equivalence. The concept of intersection-union tests will be shown to clarify, simplify, and unify bioequivalence testing. A test more powerful than the one currently specified by the FDA and EC guidelines will be derived. The claim that the bioequivalence problem defined in terms of the ratio of parameters is more difficult than the problem defined in terms of the difference of parameters will be refuted. The misconception that size-ff bioequivalence tests generally correspond to 100(1 \Gamma 2ff)% confidence sets will be shown to lead to incorrect statistical pract...

A completely nonparametric approach to population bioequivalence in crossover trials has been suggested by Munk and Czado (1999). It is based on the Mallows (1972) metric as a nonparametric distance measure which allows the comparison between the entire distribution functions of test and reference formulations. It was shown that a separation between carry-over and period effects is not possible in the nonparametric setting. However when carry-over effects can be excluded, treatment effects can be assessed when period effects are present or not. Munk and Czado (1999) proved bootstrap limit laws of the corresponding test statistics because estimation of the limiting variance of the test statistic is very cumbersome. The purpose of this paper is to investigate the small sample behavior of various bootstrap methods and to compare it with the asymptotic test obtained by estimation of the limiting variance. The percentile (PC) and bias corrected and accelerated (BCA) bootstrap were compared ...

Bioequivalence trials are usually conducted to compare two or more formulations of a drug. Simultaneous assessment of bioequivalence on multiple endpoints is called multivariate bioequivalence. Despite the fact that some tests for multivariate bioequivalence are suggested, current practice usually involves univariate bioequivalence assessments ignoring the correlations between the endpoints such as AUC and Cmax. In this paper we develop a semiparametric Bayesian test for bioequivalence under multiple endpoints. Specifically, we show how the correlation between the endpoints can be incorporated in the analysis and how this correlation affects the inference. Resulting estimates and posterior probabilities “borrow strength” ’ from one another where the amount and direction of the strength borrowed are deter-