Ahn Chul, Lee Seung-Chun
Department of Clinical Sciences, UT Southwestern Medical Center.
Ungyong Tonggye Yongu. 2011 Jun 1;24(3):495-503. doi: 10.5351/KJAS.2011.24.3.495.
When the patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency (EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.
当一种创新（品牌）小分子药物的专利到期时，如果已证明其与创新药物具有治疗等效性，那么该创新药物的仿制药就可以上市销售。如果两种药物在交叉临床试验中显示出具有相同活性成分的药学等效性以及具有可比药代动力学的生物等效性，那么小分子药物就被认为具有治疗等效性并且可以互换使用。然而，治疗等效性范式不能应用于生物类似药，因为生物类似药的活性成分是具有复杂和异质结构的大分子，而且这些分子很难在每个细节上都进行复制。欧洲药品管理局（EMEA）引入了一条监管生物类似药的途径，该途径要求进行临床试验以证明治疗等效性。在本文中，我们讨论生物类似药癌症临床试验设计和分析中的统计学考虑因素。
