Division of Medical Oncology and Hematology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Cancer Center, Kobe University Hospital, Kobe, Japan.
Cancer Sci. 2021 Jul;112(7):2563-2577. doi: 10.1111/cas.14967. Epub 2021 Jun 8.
Clinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti-cancer drugs in Japan were established in 1991 and amended in 2006 after molecular-targeted drugs were introduced. Recent progress in the development of drugs acting on the immune system and cancer genomic medicine targeting rare but important molecular subtypes have altered the strategy for development of anti-cancer drugs. It is often difficult to conduct a confirmatory randomized controlled study using overall survival as the primary endpoint in rare molecular subtypes, and the primary evaluation of the efficacy of some drugs and subsequent approval is based on the tumor response. As conducting clinical studies for rare subtypes solely within Japan is difficult, drug development needs to be conducted within a global study. However, this requires robust monitoring to detect possible ethnic differences in pharmacokinetics and drug efficacy. Development using the conditional approval system for drugs enforced in 2020 may be considered, when clinical utility is evaluated based on surrogate endpoints. Because of these changes, we have revised the guidelines for the clinical evaluation of anti-cancer drugs in Japan. To promote global development of anti-cancer drugs involving Japan, the guidelines have been translated into English.
临床研究旨在为监管审批提供支持，必须在目标人群中证明药物的临床获益。药物的临床开发是通过逐步的临床研究进行的；在评估了安全性和药代动力学，并确定了推荐剂量和给药方案后，以探索性方式评估疗效和安全性，最后将临床获益与传统标准疗法进行比较。日本于 1991 年制定了抗癌药物临床评价指南，并在 2006 年引入分子靶向药物后进行了修订。近年来，作用于免疫系统的药物和针对罕见但重要分子亚型的癌症基因组医学的发展改变了抗癌药物的开发策略。在罕见的分子亚型中，使用总生存期作为主要终点进行确证性随机对照研究通常很困难，一些药物的主要疗效评估和随后的批准是基于肿瘤反应。由于在日本单独开展罕见亚型的临床研究较为困难，药物开发需要在全球范围内开展研究。然而，这需要进行强有力的监测，以检测药代动力学和药物疗效方面可能存在的种族差异。当根据替代终点评估临床实用性时，可能会考虑使用 2020 年开始实施的有条件批准制度进行开发。由于这些变化，我们对日本抗癌药物临床评价指南进行了修订。为了促进涉及日本的抗癌药物的全球开发，指南已被翻译成英文。
