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Exact calculation of power and sample size in bioequivalence studies using two one‐sided tests
Author(s) -
Shen Meiyu,
RussekCohen Estelle,
Slud Eric V.
Publication year - 2014
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1666
Subject(s) - bioequivalence , univariate , sample size determination , mathematics , monte carlo method , crossover , statistics , context (archaeology) , bivariate analysis , power function , power (physics) , multivariate statistics , computer science , mathematical analysis , pharmacokinetics , medicine , paleontology , artificial intelligence , biology , physics , quantum mechanics
The number of subjects in a pharmacokinetic two‐period two‐treatment crossover bioequivalence study is typically small, most often less than 60. The most common approach to testing for bioequivalence is the two one‐sided tests procedure. No explicit mathematical formula for the power function in the context of the two one‐sided tests procedure exists in the statistical literature, although the exact power based on Owen's special case of bivariate noncentral t ‐distribution has been tabulated and graphed. Several approximations have previously been published for the probability of rejection in the two one‐sided tests procedure for crossover bioequivalence studies. These approximations and associated sample size formulas are reviewed in this article and compared for various parameter combinations with exact power formulas derived here, which are computed analytically as univariate integrals and which have been validated by Monte Carlo simulations. The exact formulas for power and sample size are shown to improve markedly in realistic parameter settings over the previous approximations. Copyright © 2014 John Wiley & Sons, Ltd.