Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Clin Transl Sci. 2019 Jul;12(4):408-415. doi: 10.1111/cts.12631. Epub 2019 Apr 23.
Recent International Conference on Harmonization (ICH) guidelines provide pharmaceutical companies with regulatory justifications to pursue various global drug-development pathways, in some of which "local" dose-ranging and/or pivotal phase III studies are skipped. We examined the association between the clinical development pathway and postmarketing safety in Japan for 177 new molecular entities approved between 2004 and 2013 focusing on dose setting histories for each drug. The risk of drug-related deaths was higher when companies did not conduct local (i.e., Japanese) dose-ranging studies and/or pivotal studies. Even when local dose-ranging studies were conducted, the risk remained higher in some drugs for which the approved dose in Japan was set equal to that in the United States. Drugs developed under a bridging strategy tended to show lower risks. These results suggested that local clinical studies may play a substantial role in achieving optimization of postmarketing drug use in each local target population.
最近的国际协调会议（ICH）指导原则为制药公司提供了监管依据，以寻求各种全球药物开发途径，其中一些途径跳过了“局部”剂量范围和/或关键的 III 期研究。我们研究了 2004 年至 2013 年间批准的 177 种新分子实体在日本的临床开发途径与上市后安全性之间的关系，重点关注每种药物的剂量设定历史。当公司不进行局部（即日本）剂量范围研究和/或关键研究时，与药物相关的死亡风险更高。即使进行了局部剂量范围研究，对于某些在日本批准的剂量与在美国相同的药物，风险仍然较高。采用桥接策略开发的药物往往风险较低。这些结果表明，局部临床研究可能在实现每个当地目标人群上市后药物使用的优化方面发挥重要作用。
