Tests for individual and population bioequivalence based on generalized p-values.

Abstract

The U.S. Food and Drug Administration (FDA) has proposed new regulations that address the 'prescribability' and 'switchability' of new formulations of already-approved drugs. These new criteria are known, respectively, as population and individual bioequivalence. Two methods have been proposed in the bioequivalence literature for assessing population and individual bioequivalence that calculate an upper 95 per cent confidence bound for the bioequivalence criterion in question, and then test bio-equivalence by comparing this bound to the limit established by the FDA. In this paper we propose applying the generalized test function (GTF) methodology of Tsui and Weerahandi (Journal of the American Statistical Association 1989; 602-607) to this problem to produce tests based on a generalized p-value (GPV). This methodology allows us to construct hypothesis tests in the presence of nuisance parameters. Using simulation we show that these tests perform well in comparison to the confidence interval methods and have superior power for assessing population bioequivalence.