生物类似药临床相似性比较试验设计和评价的思考

Considerations for Design and Evaluation of Clinical Similarity Comparison Trial of Biosimilars

目的探讨生物类似药临床相似性比对试验设计的关键考虑要素及结果评价标准。方法检索、调研国外生物类似药指导原则及临床相似性评价相关文献进展,通过案例分析并与生物制药行业研发者、临床及统计学专家共同研讨等方法,形成对生物类似药临床相似性评价的思考。结果与结论生物类似药临床相似性评价的标准应基于产品特异性制定。对于不同的生物制品,在充分了解原研产品质量、有效性、安全性特征的基础上,找到合适的研究人群、终点及等效/非劣效界值至关重要。临床相似性评价标准中应考虑引入参照药自身临床应答变异、受试者临床疗效变异等因素设定界值,并在临床相似性比对试验中进行直接对比评估,从而全面评价临床相似性。

OBJECITVE： To discuss the key considerations and evaluation criteria in designing a clinical comparison study to assess the clinical similarity of biosimilars. METHOD Relevant guidelines and literatures on clinical similarity evaluation were reviewed,the cases were analyzed,discussions were carried out with biotech industry sponsors and clinical and statistical experts,the key considerations and evaluation criteria were proposed for assessing the clinical similarity of biosimilars. RESULTS AND CONCLUSION The clinical similarity criteria should reflect the characteristics of the biological products. It is critical to select right patient population,clinical endpoints and equivalence / non-inferiority margin for development of different biosimilar products on the basis of fully understanding the quality,efficacy and safety profile of the original biological products. To set up the clinical similarity criterion and selection of the equivalence / non-inferiority margin,the consistency of the therapeutic effect of the reference product and subject variability need to be taken into consideration for robust evaluation of clinical similarity.