Department of Experimental Therapeutics Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
J Clin Pharm Ther. 2013 Aug;38(4):309-13. doi: 10.1111/jcpt.12064. Epub 2013 Apr 9.
Many drugs fail during development. However, detailed reasons for failure during drug development are almost never disclosed. We focused on the drugs whose clinical development and registration were initially hampered, but which were finally approved to identify reasons that delayed their marketing approval in Japan.
We analysed 727 new drug applications (NDAs) approved in Japan between 2001 and 2011.
Fifty-three NDAs had serious and identifiable problems during drug development. Of these, 43 NDAs had 'problem related to clinical data'. We found that the problems for withdrawal of these NDAs could be ascribed largely to inappropriate clinical data package and study design for supporting the intended indications and usage and to unclear clinical results for defining dosage regimen or efficacy of the drugs.
Our results indicate the importance of careful determination of the optimal dosage regimen and the choice of objective endpoints in clinical trials. Further, it is important to establish a clear strategy for generating the clinical data package, to include careful design of clinical trials on the basis of the nature of the target disease and target population. For drugs marketed in Japan, there is a need to include sufficient numbers of Japanese patients in the trials.
许多药物在开发过程中失败。然而，药物开发过程中失败的详细原因几乎从未被披露过。我们专注于那些临床开发和注册最初受阻但最终获准的药物，以确定在日本延迟其上市许可的原因。
我们分析了 2001 年至 2011 年间在日本批准的 727 份新药申请（NDA）。
53 份 NDA 在药物开发过程中存在严重且可识别的问题。其中，43 份 NDA“与临床数据有关的问题”。我们发现，这些 NDA 的撤回问题主要归因于支持预期适应症和用途的临床数据包和研究设计不当，以及定义药物剂量方案或疗效的临床结果不明确。
我们的结果表明，在临床试验中仔细确定最佳剂量方案和选择客观终点非常重要。此外，重要的是要建立一个明确的策略来生成临床数据包，包括根据目标疾病和目标人群的性质仔细设计临床试验。对于在日本上市的药物，有必要在试验中纳入足够数量的日本患者。
