Assessment of bioequivalence using a multiplicative model

Abstract

In many bioavailability / bioequivalence studies, the distributions of responses such as AUC and C_max are often positively skewed and exhibit a lack of homogeneity of variances. In this situation, a logarithmic transformation is usually consideredfor reduction of skew-ness and achievement of an additive model with relatively homogeneous variance. In this paper, consideration is given to a multiplicative model based on empirical evidence. A method is proposed using individual subject ratios for assessing the bioequivalence of two different formulations. This method is then subsequently extended to several commonly used crossover experiments.