对单臂试验支持抗肿瘤药物上市策略的再思考

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported

单臂试验是指在临床试验设计时, 不设立平行对照组, 并采用开放设计, 不涉及随机与盲法的一种临床试验设计。单臂试验的特征一方面加速了临床试验的进程, 缩短了药品的上市时间, 使晚期恶性肿瘤患者更快获得治疗药物, 但同时也具有试验结果不够稳定的局限性。2021年4月, 美国食品药品监督管理局召开肿瘤药物咨询委员会会议, 对6项已通过单臂加速批准上市的肿瘤适应证进行讨论, 再次引发了各界对单臂试验的讨论。单臂试验所支持的药品加速上市, 实际是在评估了获益风险后, 对循证医学证据级别要求进行了一定程度的妥协, 因此, 研发单位应严格把握单臂试验支持抗肿瘤药物附条件上市的适用条件, 并科学开展单臂试验, 同时, 及早开展上市后确证性研究, 以确保患者获益。文章基于单臂试验的特点, 结合国家药品监督管理局发布的《单臂试验支持上市的抗肿瘤药进入关键试验前临床方面沟通交流技术指导原则》和《单臂试验支持上市的抗肿瘤药上市许可申请前临床方面沟通交流技术指导原则》, 对单臂试验支持抗肿瘤药物上市策略提出思考与总结。

Single-arm trial refers to a clinical trial design that does not set up parallel control group,adopts open design,and does not involve randomization and blind method.These features,on the one hand,speed up the process of clinical trials,significantly shorten the time to market and meet the needs of patients with advanced malignancies,but also lead to the uncertainty of single-arm clinical trials themselves.Recently,the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved,which once again triggered the discussion of single-arm trials.The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk.Therefore,the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically.Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients.Based on the characteristics of single-arm trial,combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently,this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.