A Bayesian Approach to Bioequivalence for the 2 x 2 Changeover Design

Abstract

Bioequivalence trials are carried out to compare two or more formulations of a drug containing the same active ingredient, in order to determine whether the different formulation give rise to comparable blood levels. We consider the 2 x 2 changeover experiment the compares two formulations, one of which is considered the standard. For a single univariate characteristic of the plasma concentration--time curve, a criterion for bioequivalence is proposed based on the posterior probability that the difference in formulation means is less than a specific percentage of the mean of the standard. The sensitivity of this posterior probability to alternative priors is investigated. Differences in carry-over effects can be incorporated within the Bayesian framework without restoring to the "all-or-nothing" approach implied by a preliminary test. The use of sequential experimentation is discussed.