Chiang Chieh, Hsiao Chin-Fu
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Stat Med. 2017 Mar 30;36(7):1068-1082. doi: 10.1002/sim.7202. Epub 2017 Jan 9.
In 1992, the US Food and Drug Administration declared that two drugs demonstrate average bioequivalence (ABE) if the log-transformed mean difference of pharmacokinetic responses lies in (-0.223, 0.223). The most widely used approach for assessing ABE is the two one-sided tests procedure. More specifically, ABE is concluded when a 100(1 - 2α) % 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 half-life of a drug is long, a parallel design for the bioequivalent study may be preferred. In this study, a two-sided interval estimation - such as Satterthwaite's, Cochran-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 achieves sufficient empirical power. A real example is provided to illustrate the proposed method. Copyright © 2017 John Wiley & Sons, Ltd.
1992年，美国食品药品监督管理局宣布，如果药代动力学反应的对数转换平均差异在（-0.223, 0.223）范围内，则两种药物具有平均生物等效性（ABE）。评估ABE最广泛使用的方法是双单侧检验程序。更具体地说，当平均差异的100(1 - 2α)%置信区间落在（-0.223, 0.223）内时，可得出ABE的结论。众所周知，生物等效性研究通常采用交叉设计。然而，在药物半衰期较长的情况下，生物等效性研究可能更倾向于采用平行设计。在本研究中，使用双侧区间估计——如萨特思韦特近似法、 Cochr an - Cox近似法或豪近似法——来评估平行ABE。我们表明，下限和上限置信限的渐近联合分布是二元正态分布，因此可以根据渐近功效计算样本量，以使置信区间落在（-0.223, 0.223）内。模拟研究还表明，所提出的方法具有足够的经验功效。提供了一个实际例子来说明所提出的方法。版权所有© 2017约翰威立父子有限公司。
