生物等效性评价的统计分析方法

Statistical approaches to establishing bioequivalence

生物等效性试验用于评价试验药 (T)与注册药物 (R)的生物等效性 ,以确定其效应相当。目前生物等效性平均、群体、个体生物等效性三种。平均生物等效性只评价观察指标的平均水平 ,而不考虑个体间的变异 ;而群体生物等效性既考虑了平均水平 ,又考虑了个体间的变异 ;个体生物等效性除考虑平均水平和个体变异 ,还考虑个体与药物间的交互作用。本文介绍了评价三种生物等效性的统计学原理 ,准则 ,等效性界值的确定 ,以及应用中的注意事项。并以实例说明。

The purpose of bioequivalence (BE) trial is to show that the test (T) and the reference (R) products can produce similarity bioavailability, and then show therapeutically equivalence. There are three types of bioequivalence, namely, average bioequivalence (ABE), population bioequivalence (PBE) and individual bioequivalence (IBE). The ABE approach focuses only on the comparison of population averages of a BE measure of interest and not on the variances of the measure for the T and R products. In contrast, the approaches to establish PBE and IBE include the comparisons of both averages and variances of the measure. The PBE approach assesses total variability of the measure in the population. While the IBE approach assesses within-subject variability for the T and R products, as well as the subject-by-formulation interaction, that is, the variation in the average T and R difference among individuals. In present paper, the principle of the statistical approaches to establish BE, the way to predetermine criterions and BE limits were introduced, and an example were illustrated.