On statistical power for average bioequivalence testing under replicated crossover designs.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wan, H; Chow, S-C

Published Date

  • August 2002

Published In

Volume / Issue

  • 12 / 3

Start / End Page

  • 295 - 309

PubMed ID

  • 12448572

Pubmed Central ID

  • 12448572

International Standard Serial Number (ISSN)

  • 1054-3406

Digital Object Identifier (DOI)

  • 10.1081/bip-120014560

Language

  • eng

Conference Location

  • England