高变异药物生物等效性评价的几种解决方法初探

实现生物等效是仿制药一致性评价工作中的重要结论性评判标准，近年来得到国家食品药品监督管理总局药品审评中心高度重视。然而，由于通常需要更大的样本量或更多的试验周期，高变异药物生物等效性评价仍有难度，尤其是试验设计和统计方法存在较多争论，困扰着众多医药工作者。为此，本文将针对这些争论焦点问题，分析总结几种目前国际上基于节省样本量和试验周期数的对高（或超高）变异药物生物等效性的评价技术和方法，旨在为降低我国高变异药物的仿制风险提供可借鉴的参考。

The investigation of the methods for bioequivalence evaluation of highly variable drugs

To achieve bioequivalence is an important and conclusive standard to evaluate the uniformity of generic drug with innovator drug. Center For Drug Evaluation (CFDA) nowadays highlights the importance of evaluation of bioequivalence. However, the evaluation of bioequivalence for highly variable drugs (HVD) has always been in dispute among medical professionals or biostatisticians since that the design of trial for HVD usually needs larger sample size or more study periods compared with that of non-HVD. This article reviews several approaches proposed in published international literature to deal with the bioequivalence issues of highly variable drugs. This methodological investigation aims to provide potential solutions using limited sample size that may provide practical reference to the generic drug producer.