| Abstract: | In its recent guidance on bioequivalence, the U.S. Food and Drug Administration (FDA) recommends a two-sequence, four-period (2×4)replicated crossover design be used for assessment of population and individual bioequivalence FDA. Guidance for Industry on Statistical Approaches to Establishing Bioequivalence; Center for Drug Evaluation and Research, Food and Drug Administration: Rockville, MD, 2001]. The recommended replicated crossover design not only allows estimates of both the inter-subject and the intra-subject variabilities and the variability due to subject-by-formulation interaction, but also provides an assessment of average bioequivalence (ABE). In this article, power function for assessment of ABE under a general replicated crossover design (i.e., a 2×2mreplicated crossover design) based on the traditional analysis of variance model and the mixed effects model as suggested by the FDA are studied. It is found that the power of a 2×2mreplicated crossover design depends upon the variability due to subject-by-formulation interaction and the number of replicates. Based on the derived power function, formula for sample size calculation for assessment of ABE under a 2×2mreplicated crossover design is also provided. |
