新药临床前致癌性实验设计的关注点

Considerations for the experimental design of the preclinical carcinogenicity study of new drugs

致癌性实验主要用于评价新药的潜在致癌性风险,是创新药物临床前安全性评价和上市风险控制内容的重要组成部分。但致癌性实验由于周期长、花费高、实验设计和结果评价比较复杂,因此需要研究申报者、实施评价机构以及药品审评管理机构等多方面加强沟通。本文简要介绍了致癌性实验设计的关注点,包括动物种属的选择、动物组数以及组容量、饲养条件、供试品给药途径、给药暴露时间、暴露剂量、观察指标、大体剖检及组织病理学检查、结果分析以及统计学分析方法等内容,希望能够对致癌性实验的更好开展提供一定的参考。

The objective of carcinogenicity study is to explore the potential carcinogenicity of new drugs,which is one of the important constituents of nonclinical safety evaluation and the market risk control of innovative drugs.In consideration of the long duration,high costs,complexity of the experimental design and the evaluation of the results of carcinogenicity study,it is better to make good communication among applicants,testing facilities and drug evaluation regulatory agencies.In this paper,the considerations were briefly introduced for the experimental design of the preclinical carcinogenicity study of drugs,such as species and strains of the experimental animals,experimental groups and group size,animal housing,route of administration,dose expose duration,dose levels,in-life observation,gross pathology and histopathology,result analysis and statistical analysis,so as to provide some technical help for the conduct of carcinogenicity studies.