{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T14:18:11Z","timestamp":1788013091084,"version":"build-2784847793"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Globalization of oncology drug development has accelerated the adoption of multiregional clinical trials (MRCTs) as pivotal evidence for regulatory approvals in major markets, including Japan. While MRCTs enhance efficiency and generalizability, they introduce challenges related to inter-ethnic variability and data extrapolation. Japan\u2019s regulatory framework, guided by pharmaceuticals medical devices agency (PMDA) principles and the \u201cGuideline for Clinical Evaluation Methods of Anticancer Drugs,\u201d emphasizes patient efficacy, safety and relevance, historically requiring local data to supplement global findings. This review analyzed the approvals of oncology drugs in Japan over 5 years, focusing on the role of Japanese subgroup data and overall survival (OS) outcomes in pivotal trials. Among 165 approvals for oncology drugs, OS in pivotal trials was set as a sole primary endpoint in 9.1% (15\/165) and as co-primary\/dual primary endpoints in 10.3% (17\/165); alternative endpoints such as progression-free survival were accepted when OS was impractical. In 7.9% (13\/165) of all approvals, Japanese subpopulation results diverged from trends of overall population (hazard ratio [HR]\u2009&gt;\u20091 in Japanese subpopulation), and 4.2% (7\/165) of the approvals involved trials in which the primary endpoint of OS (including a sole, co-primary or dual primary endpoint) was not achieved. The PMDA decisions reflected holistic evaluation, considering trial design integrity, secondary endpoints, and qualitative consistency rather than rigid HR thresholds. Differences in efficacy in Japanese subgroup rarely impacted labeling, underscoring reliance on global evidence with local scientific considerations. These findings highlight the PMDA\u2019s pragmatic approach to endpoint flexibility and extrapolation, reinforcing the importance of early regulatory engagement and strategic alignment in MRCT design for oncology drug development in Japan.<\/jats:p>","DOI":"10.1007\/s43441-026-00970-8","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T14:43:13Z","timestamp":1778596993000},"page":"1398-1418","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Japanese Subpopulation Data and Overall Survival in Pivotal Trials on Oncology Drug Approvals in Japan"],"prefix":"10.1007","volume":"60","author":[{"given":"Takanobu","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"issue":"12","key":"970_CR1","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1111\/cts.13660","volume":"16","author":"M Hideki","year":"2023","unstructured":"Hideki M, Asuka H, Momoka O, et al. Trends in oncology drug lags in Japan from 2001 to 2020: a cross-sectional study. Clin Transl Sci. 2023;16(12):2665\u201374.","journal-title":"Clin Transl Sci"},{"issue":"10","key":"970_CR2","doi-asserted-by":"publisher","first-page":"e70336","DOI":"10.1111\/cts.70336","volume":"18","author":"K Hitoshi","year":"2025","unstructured":"Hitoshi K, Kotone M. Trends in and determinants of approval lag for anticancer drugs in Japan and the US: role of multi - regional trials and concurrent approvals. Clin Transl Sci. 2025;18(10):e70336.","journal-title":"Clin Transl Sci"},{"key":"970_CR3","unstructured":"Basic Principles on Global Clinical Trials. Ministry of Health, Labour and Welfare: PFSB\/ELD Notification 0928010, September 28, 2007. https:\/\/www.pmda.go.jp\/files\/000153265.pdf"},{"key":"970_CR4","unstructured":"Basic Principles on Global Clinical Trials (Reference Cases). Ministry of Health, Labour and Welfare: PSEHB\/PED Administrative Notice, September 5, 2012. https:\/\/www.pmda.go.jp\/files\/000152969.pdf"},{"key":"970_CR5","unstructured":"Amendment to. Basic Principles on Global Clinical Trials (Reference Cases). Ministry of Health, Labour and Welfare: PSEHB\/PED Administrative Notice, September 5, 2012. https:\/\/www.pmda.go.jp\/files\/000246184.pdf"},{"key":"970_CR6","unstructured":"ICH E17: Guidelines on General Principles for Planning and Design of Multi-Regional Clinical Trials. Ministry of Health, Labour and Welfare: PSEHB\/PED Administrative Notice, December 10. 2021. https:\/\/www.pmda.go.jp\/int-activities\/int-harmony\/ich\/0022.html"},{"key":"970_CR7","unstructured":"Basic principles for conducting. phase 1 studies in Japanese prior to initiating multi-regional clinical trials including Japan for drugs in which early clinical development is preceding outside Japan. Ministry of Health, Labour and Welfare: PSB\/PED Notification 1225-2, dated December 25, 2023. https:\/\/www.pmda.go.jp\/files\/000266773.pdf"},{"issue":"7","key":"970_CR8","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1111\/cas.14967","volume":"112","author":"M Hironobu","year":"2021","unstructured":"Hironobu M, Naomi K, Shiro K, et al. Guidelines for clinical evaluation methods of anticancer drugs. Cancer Sci. 2021;112(7):2563\u201377.","journal-title":"Cancer Sci"},{"key":"970_CR9","unstructured":"Pharmaceuticals and Medical Devices Agency. List of Approval new drugs. https:\/\/www.pmda.go.jp\/review-services\/drug-reviews\/review-information\/p-drugs\/0010.html"},{"key":"970_CR10","unstructured":"Pharmaceuticals and Medical Devices Agency. Medical product information search. https:\/\/www.pmda.go.jp\/PmdaSearch\/iyakuSearch\/"},{"key":"970_CR11","unstructured":"Pharmaceuticals and Medical Devices Agency. New drugs (prescription drugs). https:\/\/www.pmda.go.jp\/review-services\/drug-reviews\/about-reviews\/p-drugs\/0021.html"},{"key":"970_CR12","unstructured":"Japanese Law Translation. Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Last Version: Act No. 50 of 2015) https:\/\/www.japaneselawtranslation.go.jp\/ja\/laws\/view\/3213"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-00970-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-00970-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-00970-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T13:47:12Z","timestamp":1788011232000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-026-00970-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["970"],"URL":"https:\/\/doi.org\/10.1007\/s43441-026-00970-8","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"28 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests related to this work. The opinions and interpretations presented herein are those of the author alone and do not represent the official views or positions of the author\u2019s employer or any associated institution.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}