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Notwithstanding theoretical critiques since the concept\u2019s initial proposal, equipoise has remained an important moral consideration. In oncology, many research questions are now pursued via clinical trial designs that diverge in various ways from conventional, fixed-design, two-arm randomised controlled trials. In this article, we outline the challenges that these new designs pose for implementing equipoise. Specifically, we consider challenges posed by trials incorporating seamless designs, \u2018immortal\u2019 trials, and trials incorporating adaptive techniques. While we note that equipoise retains a central role in the ethical evaluation of conventional randomised controlled trials, we contend that its utility as a moral construct is challenged by more recent, \u2018novel randomised controlled trial\u2019 designs. Consequently, other ethical tools become important in considering the different types of risk that trial participants are exposed to in modern clinical trial designs.<\/jats:p>","DOI":"10.1177\/17407745261469887","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:02:36Z","timestamp":1789117356000},"page":"457-468","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncertainty and novel clinical trial designs in oncology \u2013 when should equipoise matter?"],"prefix":"10.1177","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-5320","authenticated-orcid":false,"given":"Sarah","family":"Heynemann","sequence":"first","affiliation":[{"name":"Sydney Health Ethics, Faculty of Medicine and Health, The University of Sydney, NSW, Australia"},{"name":"Department of Oncology, Northern Health, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-657X","authenticated-orcid":false,"given":"Wendy","family":"Lipworth","sequence":"additional","affiliation":[{"name":"Department of Philosophy, Macquarie University, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-0322","authenticated-orcid":false,"given":"Sue-Anne","family":"McLachlan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St Vincent\u2019s Hospital, Melbourne, VIC, Australia"},{"name":"Department of Medicine, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-0645","authenticated-orcid":false,"given":"Jennifer","family":"Philip","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, VIC, Australia"},{"name":"Department of Palliative Care, St Vincent\u2019s Hospital, Melbourne, VIC, Australia"},{"name":"Department of Palliative Care, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"John","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"},{"name":"Sir Peter MacCallum Department of Medical Oncology, The University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Kerridge","sequence":"additional","affiliation":[{"name":"Sydney Health Ethics, Faculty of Medicine and Health, The University of Sydney, NSW, Australia"},{"name":"Department of Philosophy, Macquarie University, Sydney, NSW, Australia"},{"name":"Department of Haematology, Royal North Shore Hospital, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.25.2.107"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5337.1043"},{"key":"e_1_3_4_4_2","volume-title":"Medical experimentation: Personal integrity and social policy","author":"Fried C.","year":"1974","unstructured":"Fried C. 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