On statistical power for average bioequivalence testing under replicated crossover designs.
In its recent guidance on bioequivalence, the U.S. Food and Drug Administration (FDA) recommends a two-sequence, four-period (2 x 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 x 2m replicated 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 x 2m replicated 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 x 2m replicated crossover design is also provided.
Wan
Hansheng
H
StatPlus, Inc., Heston Hall, Yardley, PA 19067, USA. hwang@statplusinc.com
Chow
Shein-Chung
SC
D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D017408:Guidelines as Topic; D015233:Models, Statistical; D012107:Research Design / Q000706:statistics & numerical data*; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration