中美抗肿瘤新药加速通道审评政策与使用情况的比较分析

Expedited program and utilization for anticancer drug approval in China and the United States

目的系统汇总并比较分析中美加速审评通道发展与设置概况及2012—2021年中美上市抗肿瘤新药加速通道的使用情况。方法基于中国和美国国家药品监督管理部门官网,查阅并整理中美两国新药加速审评通道发展历程和设置现状;针对2012—2021年在中美两国上市的抗肿瘤药物(中国87种,美国118种),查阅并汇总比较抗肿瘤新药加速通道的使用率和变化趋势,包括加速通道总体使用率和各加速通道使用率。采用χ2检验进行组间比较。结果中美两国分别建立了5条加速通道,包括优先审评、附条件批准或加速批准和突破性治疗3条相同通道,中国特有的特别审批、特殊审批,美国特有的快速通道和实时肿瘤审评。与美国相比,中国的加速通道设置起步晚(美国1992年,中国2005年)。2012—2021年获批的抗肿瘤新药中,中美加速通道的总体使用率相近[分别为90.8%(109/118)和92.4%(79/87),P=0.800]。中美两国都是优先审评通道使用率最高(分别为77.0%和82.2%,P=0.381);相对而言,中国附条件批准(分别为31.0%和44.9%,P=0.041)和突破性治疗(分别为2.3%和50.0%,P<0.001)使用率较低。中国有52.9%的抗肿瘤新药使用了特殊审批,美国40.7%的抗肿瘤新药使用了快速通道。中美优先审评的变化波动较小,年平均使用率接近(分别为84.8%和83.7%);美国加速批准和突破性疗法使用率波动幅度较大,2019—2021年趋于稳定。结论中美两国均已建立了较为完善的加速审评体系,总体使用率在90%以上;中国加速审评起步较晚,虽然总体使用率与美国接近,但附条件批准和突破性治疗通道的使用率较低。灵活运用加速通道,获得监管认定使用替代终点、实现滚动审查和实时指导是加速中国新药研发的关键。

Objective To systematically summarize and comparatively analyze the development,establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods Based on National Medical Products Administration(NMPA)and Food and Drug Administration(FDA)websites,the development and current status of the speedy review approaches were consulted and summarized.Approved oncology drugs in China and in the United States(87 in China,118 in the United States)over the past decade were analyzed using chi-square test for group comparison.Results Five speedy approaches have been established in China and in the United States,three of which are the same,priority review,conditional approval or accelerated approval and breakthrough therapy.The rest two are special review and approval,special examination and approval in China,and fast track and real-time oncology review in the United States.Compared to the United States,speedy review approaches in China set up late(1992 vs.2005).The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States(90.8%vs.92.4%,P=0.800)in the previous 10 years,and priority review have highest utilization rates in both China and the United States without significant group difference(77.0%vs.82.2%,P=0.381);relatively low utilization rates of conditional approval(31.0%vs.44.9%,P=0.041)and breakthrough therapy(2.3%vs.50.0%,P<0.001)were seen in China.52.9%of new drugs applied for special examination and approval in China and 40.7%of new drugs applied for fast track in the United States.Overall,the priority review both in China and the United States are stable,with a similar average annual utilization rate(84.8%vs.83.7%);accelerated approval and breakthrough therapies in the United States fluctuate wildly,but the situation is tending towards stability in the last 3 years.Conclusions Both China and the United States have established a relatively complete accelerated review system,with an overall utilization rate over 90%;China's accelerated review started late,although the overall utilization rate is close to that of the United States.The utilization rates of conditional approval and breakthrough therapy are still relatively low.Flexible usage of speedy review approaches,gaining regulatory recognition to use alternative endpoints,achieving real-time review and guidance are keys to accelerate new drug development in China.