title: Sample size determination for individual bioequivalence inference.
abstract: Statistical criterion for evaluation of individual bioequivalence (IBE) between generic and innovative products often involves a function of the second moments of normal distributions. Under replicated crossover designs, the aggregate criterion for IBE proposed by the guidance of the U.S. Food and Drug Administration (FDA) contains the squared mean difference, variance of subject-by-formulation interaction, and the difference in within-subject variances between the generic and innovative products. The upper confidence bound for the linearized form of the criterion derived by the modified large sample (MLS) method is proposed in the 2001 U.S. FDA guidance as a testing procedure for evaluation of IBE. Due to the complexity of the power function for the criterion based on the second moments, literature on sample size determination for the inference of IBE is scarce. Under the two-sequence and four-period crossover design, we derive the asymptotic distribution of the upper confidence bound of the linearized criterion. Hence the asymptotic power can be derived for sample size determination for evaluation of IBE. Results of numerical studies are reported. Discussion of sample size determination for evaluation of IBE based on the aggregate criterion of the second moments in practical applications is provided.
authors.affiliation: Division of Biometry, Department of Agronomy, National Taiwan University, Taipei, Taiwan; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chieh
authors.initials: C
authors.lastname: Chiang
authors.affiliation: Division of Biometry, Department of Agronomy, National Taiwan University, Taipei, Taiwan; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.affiliation: Division of Biometry, Department of Agronomy, National Taiwan University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Jen-Pei
authors.initials: JP
authors.lastname: Liu
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D010600:Pharmacology / Q000379:methods; D018401:Sample Size; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D059451:Biosimilar Pharmaceuticals; D016568:Drugs, Generic