{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:40:00Z","timestamp":1792600800335,"version":"4.5.0"},"reference-count":7,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biometrical J"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The multi\u2010arm two\u2010stage (MATS) design combines proof\u2010of\u2010concept and dose optimization in a single study, which starts from parallel enrollments of participants across multiple cohorts (indications) at a dose selected from the dose\u2010escalation study, which is usually the maximum tolerable dose (MTD) in traditional oncology dose\u2010escalation studies, followed by randomizing subjects into two dose levels only for those \u201cefficaciously promising\u201d cohorts at the second stage. Here, we communicate a variant of the MATS design by \u201creversing\u201d the two stages so that randomization to two dose levels for each indication\u2010specific cohort precedes potential further enrollment at the dose selected for optimal efficacy\/safety profile based on the randomization stage. This \u201cReversed MATS\u201d (RevMATS) design fits into certain situations when prior data evidence indicates two doses may result in similar activities or there is not enough evidence to favor one dose over the other in terms of preliminary activities, thus justifying earlier randomization of two doses instead of delaying to the second stage. It also fits when one dose has revealed promising early efficacy signals in a heterogenous population and there is reasonable belief of effectiveness across indications (so that a larger upfront investment is justified so that the second stage of MATS may be skipped). The RevMATS design further improves the underlying Bayesian hierarchical model in the MATS design by accounting for broader (potential) efficacy profiles of candidate doses and explicitly incorporating collective data evidence, such as estimated dose\u2013response curves (from dose escalation), to boost efficiency in decision\u2010making.<\/jats:p>","DOI":"10.1002\/bimj.70195","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:40:37Z","timestamp":1791960037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Reversed Multi\u2010Arm Two\u2010Stage (RevMATS) Design in Oncology Dose Optimization"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5625-6826","authenticated-orcid":false,"given":"Yue","family":"Yang","sequence":"first","affiliation":[{"name":"Evidence Generation and Decision Sciences Sanofi Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-954X","authenticated-orcid":false,"given":"Gu","family":"Mi","sequence":"additional","affiliation":[{"name":"Evidence Generation and Decision Sciences Sanofi Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Lin","sequence":"additional","affiliation":[{"name":"Evidence Generation and Decision Sciences Sanofi Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307980"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-026-00947-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2023.107278"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2023-5667"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00310"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1850"},{"key":"e_1_2_8_8_1","unstructured":"U.S. Food and Drug Administration.2024.Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases Guidance for Industry.U.S. Food and Drug Administration.https:\/\/www.fda.gov\/media\/164555\/download."}],"container-title":["Biometrical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70195","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bimj.70195","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70195","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:51:25Z","timestamp":1792597885000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bimj.70195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":7,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bimj.70195"],"URL":"https:\/\/doi.org\/10.1002\/bimj.70195","archive":["Portico"],"relation":{},"ISSN":["0323-3847","1521-4036"],"issn-type":[{"value":"0323-3847","type":"print"},{"value":"1521-4036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70195"}}