Shen Meiyu, Russek-Cohen Estelle, Slud Eric V
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, USA.
Pharm Stat. 2015 Mar-Apr;14(2):95-101. doi: 10.1002/pst.1666. Epub 2014 Dec 5.
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.
在药代动力学两期双治疗交叉生物等效性研究中，受试者数量通常较少，多数情况下少于60人。检测生物等效性最常用的方法是双单侧检验程序。尽管基于欧文双变量非中心t分布的特殊情况的精确功效已制成表格并绘制成图，但统计文献中不存在双单侧检验程序背景下功效函数的明确数学公式。此前已发表了几种交叉生物等效性研究双单侧检验程序中拒绝概率的近似方法。本文对这些近似方法及相关样本量公式进行了综述，并与在此推导的精确功效公式针对各种参数组合进行了比较，精确功效公式作为单变量积分进行解析计算，并已通过蒙特卡罗模拟验证。结果表明，在实际参数设置下，功效和样本量的精确公式比先前的近似方法有显著改进。
