参比制剂标定的生物等效性研究例数估算

Estimation of sample size in the reference-scaled average bioequivalence study

目的对高变异药物,在进行参比制剂标定的生物等效性试验(RSABE)设计时,就例数的选择提供一种估算方法。方法建立了数据模拟的方法,按照参比制剂标定的计算方法,估算在不同几何均值比值(GMR)、个体内变异(CVw)的情况下,达到一定的把握度时所需要的样本量。结果通过模拟计算,获得了在几何均值比值0. 85～1. 20,个体内变异30%～80%,在80%和90%把握度下所需要的例数。结论所建立的数据模拟方法求算的例数结果可用于开展RSABE的例数设计。针对高变异药物,使用参比制剂标定的三交叉试验可显著提高研究的效率。

Objective To provide a method for the estimation of sample size in the performing of reference-scaled average bioequivalence( RSABE). Methods Numerical simulation method was constructed for the estimation of sample size at specific geomean ratio( GMR),within-subject variation( CVw) and power. Results The numeral simulation method provided sample sizes at 0. 85-1. 20 range of GMR,30%-80% of CVw,80% and 90% of power. Conclusion Sample sizes calculated with present method could be used for the design of RSABE. With high variable drugs,3-period crossover RSABE is more efficient than the 4-period crossover RSABE.