Schall R, Luus H G
Department of Pharmacology, University of the Orange Free State, Bloemfontein, R.S.A.
Stat Med. 1993 Jun 30;12(12):1109-24. doi: 10.1002/sim.4780121202.
In a traditional assessment of the bioequivalence of two formulations of a drug one compares the average bioavailability from the two formulations. Anderson and Hauck argued that in some situations it is not sufficient to demonstrate average bioequivalence, and they proposed a method for the assessment of what they called individual bioequivalence, which essentially is the comparison of the individual responses to the two drug formulations within subjects. In this paper we propose a unified strategy for the assessment of bioequivalence that encompasses new approaches to the assessment of both population bioequivalence, which is the comparison of the marginal or population distributions of bioavailabilities, and individual bioequivalence, which is the comparison of the conditional or within-subject distributions of bioavailabilities. The general idea is to use a comparison of the reference formulation to itself as the basis for the comparison of the test with the reference formulation. The new approaches overcome the main weakness of the current methods for the assessment of bioequivalence by considering the variability of bioavailabilities in addition to their means. The current methods for the assessment of bioequivalence, namely the conventional assessment of average bioequivalence and the proposal by Anderson and Hauck for the assessment of individual bioequivalence, emerge as special cases. One can evaluate the new bioequivalence criteria statistically by use of bootstrap confidence intervals.
在对一种药物的两种制剂进行生物等效性的传统评估中，人们会比较这两种制剂的平均生物利用度。安德森和豪克认为，在某些情况下，证明平均生物等效性是不够的，他们提出了一种评估所谓个体生物等效性的方法，该方法本质上是比较受试者体内对两种药物制剂的个体反应。在本文中，我们提出了一种评估生物等效性的统一策略，该策略包含了评估群体生物等效性和个体生物等效性的新方法，群体生物等效性是生物利用度的边际或总体分布的比较，个体生物等效性是生物利用度的条件或受试者内分布的比较。总体思路是将参比制剂与其自身的比较作为测试制剂与参比制剂比较的基础。这些新方法除了考虑生物利用度的均值外，还考虑了其变异性，克服了当前生物等效性评估方法的主要弱点。当前的生物等效性评估方法，即平均生物等效性的传统评估方法以及安德森和豪克提出的个体生物等效性评估方法，都成为了特殊情况。人们可以通过使用自助法置信区间对新的生物等效性标准进行统计学评估。
