Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs.
Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs.
复制标题
2004年至2019年日本新抗肿瘤药物审批监管途径的改革以及随之而来的关键临床试验设计的变化。
DOI：
10.1007/s10637-021-01165-8
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Matsuura M.
中科院分区：
文献类型：
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作者：
Hirai T;Suzuki A;Yamori T;Matsuura M.
背景日本药品医疗器械管理局（PMDA）成立于2004年。此后，各种立法、通知、指南相继出台，国产药的监管审批路径也呈现多元化。然而，这些措施的效果尚未得到充分审查。我们研究了这些措施的影响，对批准的PMDA药物和设计的关键临床试验的疗效评估由PMDA.MethodsWe收集的PMDA批准的PMDA药物在2004-2019财政年度的数据。我们从PMDA审查报告中提取了批准审查途径和关键临床试验设计，并对其进行了分析，以确定patterns.ResultsIn total，肿瘤学中的387个适应症在2004-2019财年由PMDA批准，或365个适应症排除多个监管途径。批准的适应症数量普遍逐年增加（p< 0.001）。最大数量的批准适应症是孤儿药指定（31%，114/365），并且这一数字继续增加（p< 0.001）。2006年修订后，在提交临床试验数据进行审查的288个适应症中，关键临床试验设计发生了显著变化（p< 0.001）。结论在过去的16年中，随着监管途径的变化，PMDA批准的肿瘤适应症数量一直在增加。2006年的临床评价指南对关键临床试验设计产生了特别的影响。
BackgroundThe Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA.MethodsWe collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004–2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns.ResultsIn total, 387 indications in oncology were approved by the PMDA in fiscal years 2004–2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p< 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p< 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p< 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006.ConclusionThe number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs.