{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:40:02Z","timestamp":1792600802726,"version":"4.5.0"},"reference-count":10,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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>In oncology, clinical trials are a cornerstone of evaluating new treatments. However, traditional designs face significant challenges, particularly when assessing multiple treatment options. The emergence of multi\u2010arm multi\u2010stage (MAMS) designs, such as the drop\u2010the\u2010losers (DtL) approach, offers innovative solutions by combining multiple hypotheses within a single trial. This work evaluates the DtL approach. We extend the design to binary and survival endpoints. The statistical performance (Type I error control, statistical power, and biases) of the DtL design was assessed using a simulation study. Results demonstrated that the DtL design effectively balances statistical rigor and efficiency. The design strongly controls Type I error while ensuring high power in detecting drug effects. Scenarios with ineffective treatments highlighted the advantage of eliminating suboptimal options early. One limitation identified is that long\u2010term survival endpoints may not be mature enough to support early treatment selection. Early decision\u2010making is a key aspect of adaptive designs to support futility analysis or early efficacy analysis. It is critical to define properly the decision thresholds for such early analyses. Updating the endpoint of interest over time also aligns with clinical practices, starting with ORR, transitioning to benefit\u2013risk scores or progression\u2010free survival (PFS), and concluding with overall survival (OS) at the final analysis. Such an approach requires handling of correlations between drug effects across these endpoints. This work provides a comprehensive framework for implementing DtL design, demonstrating its potential to accelerate treatment evaluation in oncology.<\/jats:p>","DOI":"10.1002\/bimj.70174","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:15:57Z","timestamp":1790399757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extended Multi\u2010Stage Drop\u2010the\u2010Losers Design for Multi\u2010Arm Clinical Trials Using Binary and Survival Endpoints"],"prefix":"10.1002","volume":"68","author":[{"given":"Manuel","family":"Pfister","sequence":"first","affiliation":[{"name":"Department of Biostatistics University of Zurich, Epidemiology, Biostatistics and Prevention Institute  Zurich Switzerland"},{"name":"Swiss Paraplegic Research  Nottwil, Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Colin","sequence":"additional","affiliation":[{"name":"Data Quantitative Sciences Bristol Myers Squibb Boudry Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.2168"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2673"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010024\u201002247\u2010w"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2022.06.009"},{"key":"e_1_2_12_6_1","volume-title":"Group Sequential Methods With Applications to Clinical Trials","author":"Jennison C.","year":"2000"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/70.3.659"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8086"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.200410119"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3436"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280214550759"}],"container-title":["Biometrical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70174","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bimj.70174","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70174","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:51:32Z","timestamp":1792597892000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bimj.70174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":10,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bimj.70174"],"URL":"https:\/\/doi.org\/10.1002\/bimj.70174","archive":["Portico"],"relation":{},"ISSN":["0323-3847","1521-4036"],"issn-type":[{"value":"0323-3847","type":"print"},{"value":"1521-4036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"2025-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70174"}}