Hyslop T, Hsuan F, Holder D J
Biostatistics Section, Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, 132 S. 10th Street, 1170 Main Building, Philadelphia, PA 19107-5244, USA.
Stat Med. 2000 Oct 30;19(20):2885-97. doi: 10.1002/1097-0258(20001030)19:20<2885::aid-sim553>3.0.co;2-h.
The concept of interchangeable pharmaceutical products has been examined in great detail in the literature. Anderson and Hauck proposed a statistical random coefficient model to study 'switchability', and coined the phrase 'individual bioequivalence' which they defined with a probability-based inequality. Since that paper there has been considerable work and discussion. The Food and Drug Administration has recommended the introduction of individual bioequivalence (IBE) and population bioequivalence (PBE) methods in a draft guidance document. The proposal in the draft guidance includes criteria for IBE and PBE and recommends the use of non-parametric bootstrap 95 per cent upper confidence intervals for the conclusion of either IBE or PBE. However, this method requires intensive computations. We have developed an alternative confidence interval procedure to assess IBE by the FDA recommended criteria. This method utilizes Howe's approximation I to a Cornish-Fisher expansion. Our proposed method is applicable to balanced or unbalanced data in a broad class of extended cross-over designs, and can be easily programmed using readily available software.
可互换药品的概念在文献中已得到详细研究。安德森和豪克提出了一个统计随机系数模型来研究“可转换性”，并创造了“个体生物等效性”这一术语，他们用基于概率的不等式对其进行了定义。自那篇论文发表以来，已经有了大量的工作和讨论。美国食品药品监督管理局在一份指导文件草案中建议引入个体生物等效性（IBE）和群体生物等效性（PBE）方法。该指导文件草案中的提议包括IBE和PBE的标准，并建议使用非参数自助法95%上置信区间来得出IBE或PBE的结论。然而，这种方法需要大量计算。我们开发了一种替代的置信区间程序，以根据美国食品药品监督管理局推荐的标准评估IBE。该方法利用了豪对康尼什 - 费希尔展开式的近似I。我们提出的方法适用于广泛的扩展交叉设计中的平衡或不平衡数据，并且可以使用现成软件轻松编程。
