Sample Size Determination for The Assessment of Average Bioequivalence

Abstract

The 1992 US Food and Drug Administration (FDA) indicates that two drugs are said to be average bioequivalent (ABE) if the log-transformed mean difference of pharmacokinetic (PK) responses lies in (-0.223, 0.223). To assess ABE, the most widely used approach is the two one-sided test (TOST) procedure. More specifically, ABE is concluded when a?? confidence interval for mean difference falls within (-0.223, 0.223). As known, bioequivalent studies are usually conducted by crossover design. However, in the case that the hale-life of a drug is longer, a parallel design for the bioequivalent study may be preferred. In this study, the two-sided interval estimation such as Satterthwaite's, Cocharn-Cox's or Howe's approximations is used for assessing parallel ABE. We show that the asymptotic joint distribution of the lower and upper confidence limits is bivariate normal, and thus the sample size can be calculated based on the asymptotic power so that the confidence interval falls within (-0.223, 0.223). Simulation studies also show that the proposed method achieve sufficient empirical power. A real example is provided to illustrate the proposed method. Key Words: Average bioequivalence; Confidence Interval; Sample size determination.