{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:13:52Z","timestamp":1788362032934,"version":"build-2803163510"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Sequential multiple adaptive randomized treatment designs can generate registrational-quality evidence for the contribution of phase in perioperative oncology by preserving randomized comparisons and intent-to-treat estimation while improving efficiency relative to traditional three-arm trials, and yet they remain underappreciated. We present a sequential multiple adaptive randomized treatment design framework for perioperative regimens with neoadjuvant and adjuvant phases, motivated by perioperative immunotherapy in resectable non-small-cell lung cancer, where the benefit of neoadjuvant therapy is hypothesized to be greater than that of adjuvant therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We define analyses for perioperative-versus-control, neoadjuvant-only-versus-control, and contribution of phase (incremental adjuvant benefit). We specify intent-to-treat analysis sets and describe unbiased estimation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In a hypothetical trial calibrated to a perioperative setting, a sequential multiple adaptive randomized treatment design increases the number of events for regimen-versus-control comparisons and isolates a randomized comparison for the contribution of phase at the second randomization. Compared with a traditional multi-arm design, simulations demonstrate controlled family-wise type I error (&lt;0.05) and higher power.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Sequential multiple adaptive randomized treatment designs provide a principled, practical approach to within-trial contribution of phase in confirmatory oncology. Sequential multiple adaptive randomized treatment designs offer an efficient approach that addresses regulatory concerns and provides valid and robust inference. Because sequential multiple adaptive randomized treatment designs formalize the iterative nature of clinical decision-making, they are uniquely poised to explicitly answer questions related to overtreatment or undertreatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745261471462","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:40:26Z","timestamp":1788180026000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["How to be SMART in oncology: A practical framework to assess the contribution of phase using sequential multiple adaptive randomized treatment designs"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-3702","authenticated-orcid":false,"given":"Kristine R.","family":"Broglio","sequence":"first","affiliation":[{"name":"Oncology Statistical Innovation, AstraZeneca, Gaithersburg, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-3799","authenticated-orcid":false,"given":"Elizabeth F.","family":"Krakow","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"},{"name":"Department of Medicine, University of Washington, Seattle, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-3977","authenticated-orcid":false,"given":"Erica E. M.","family":"Moodie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_3_2_2_2","unstructured":"Food and Drug Administration. Codevelopment of two or more new investigational drugs for use in combination 2013 https:\/\/www.fda.gov\/media\/80100\/download"},{"key":"e_1_3_2_3_2","unstructured":"European Medicines Agency. Guideline on clinical development of fixed combination medicinal products https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-clinical-development-fixed-combination-medicinal-products-revision-2_en.pdf (2017 accessed 26 January 2026)."},{"key":"e_1_3_2_4_2","unstructured":"Food and Drug Administration. Development of cancer drugs for use in novel combination\u2014determining the contribution of the individual drugs\u2019 effects 2025 https:\/\/www.fda.gov\/media\/187589\/download"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Yang J Kang H Lyu L et al. A target map of clinical combination therapies in oncology: an analysis of clinicaltrials.gov. 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A phase 3 open-label controlled randomized study of newly diagnosed multiple myeloma treatment designed to evaluate the efficacy and safety of the elranatamab-lenalidomide combination as a replacement for chemotherapy followed by autologous stem cell transplant in the consolidation phase and to compare elranatamab with standard of care in the maintenance phase https:\/\/clinicaltrials.gov\/study\/NCT06918002 (2025 accessed 11 February 2026)."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(25)00143-7"},{"key":"e_1_3_2_22_2","unstructured":"Dunleavy K. AZ will face tough questions on Imfinzi application in NSCLC https:\/\/www.fiercepharma.com\/pharma\/ahead-adcomm-fda-raises-questions-about-astrazenecas-trial-imfinzi-nsclc (2024 accessed 26 January 2026)."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304875"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302983"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2311926"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.07.001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00518-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2202170"},{"key":"e_1_3_2_29_2","unstructured":"Meeting of the Oncologic Drugs Advisory Committee Meeting https:\/\/www.fda.gov\/advisory-committees\/updated-agenda-information-july-25-2024-meeting-oncologic-drugs-advisory-committee-meeting (2024 accessed 26 January 2026)."},{"key":"e_1_3_2_30_2","unstructured":"Conti A Wermers J. FDA\u2019s oncologic advisors support multi-arm trials for multi-phase regimens. Agency IQ by Politico 26 July https:\/\/www.agencyiq.com\/blog\/fdas-oncologic-advisors-support-multi-arm-trials-for-multi-phase-regimens\/ (2024 accessed 26 January 2026)."},{"key":"e_1_3_2_31_2","unstructured":"Smith V Coffman C Hudgens M. Interpreting the results of intention-to-treat per-protocol and as-treated analyses of clinical trials. In: Livingston EH Lewis RJ (eds) JAMA guide to statistics and methods. McGraw-Hill 2019 https:\/\/jamaevidence.mhmedical.com\/content.aspx?bookid=2742\u00a7ionid=272161146 (accessed 26 January 2026)."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4020"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1955.10501294"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-01476"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-026-00937-9"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745261471462","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17407745261471462","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745261471462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:20:59Z","timestamp":1788358859000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17407745261471462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":34,"alternative-id":["10.1177\/17407745261471462"],"URL":"https:\/\/doi.org\/10.1177\/17407745261471462","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"article-number":"17407745261471462"}}