茚达特罗上市剂量选择的论战:美国FDA定量药理学审评的故事  

Dose selection of indacaterol for marketing approval: a FDA story in pharmacometrics review

作　　者：尹芳[1] 王玉珠 郑青山[1] YIN Fang;WANG Yuzhu;ZHENG Qingshan(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]上海中医药大学药物临床研究中心,上海201203 [2]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国临床药理学与治疗学》2018年第9期1031-1039,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：长效β_2受体激动剂(LABA)一直存在安全性争议,此类药物上市的剂量选择至关重要,定量药理学方法成为关键评价工具。茚达特罗在上市审评过程中,美国食品药品管理局(FDA)与企业的定量药理学家们针对相同的试验数据,分别建模获得不同的上市剂量决策,相互反驳,在学术刊物上论战,甚至刊物也发表述评,显然FDA的模型更有说服力。本例堪称定量药理学在新药审评决策中的精彩案例,充分展示了定量药理学优势,即在缺少头对头研究时,整合多个试验数据,通过建模和模拟,确定了最终上市剂量。同时也展示了定量药理学特性,如多学科交叉、专业性极强、分析过程复杂、对经验的要求,可以大胆假设,但务必小心求证。The safety of long-acting β2 agonist （LABA） has always been controversial, and the dose selection of this type of drugs becomes very important issue. Pharmacometrics is a key evaluation tool for the dose selection. In the process of review of indacaterol for marketing approval by US FDA, the pharmacometric scientists from FDA and an en- terprise, respectively conduct modeling ＆ simulation based the data from the same trials, and they found different doses for marketing with refuting each other and debating in academic journals, even the journal published the commentary. Apparently, FDA~ mod- el is more persuasive. This is an excellent case of pharmacometrics in the new drug review of dose formarketing, which fully demonstrates the advantages of pharmacometrics, that is, when the head-to-head study is lacking, many trial data are integrated, and the final marketing dose is determined by modeling and simulation. At the same time, pharmacometric characteristics, such as muhidisciplinary, highly professional, complex analytical process and the requirements of experience, are also showed. Be bold- ly hypothesized but must be carefully verified.

关 键 词：定量药理学 建模与模拟 剂量选择 长效Β2受体激动剂 

分 类 号：R969.1[医药卫生—药理学]