{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:29Z","timestamp":1786480349987,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"10-12","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011723","name":"Myeloma UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every stage until a final sample size is reached or the trial stopped early. This work applies a Bayesian decision\u2010theoretic approach to the problem, proposing a new utility function based on both efficacy and toxicity and grounded in von Neumann\u2010Morgenstern (VNM) utility theory. Our proposed framework seeks to better capture real clinical judgments by allowing attitudes to risk to vary when the judgments are of gains or losses, which are defined with respect to an intermediate outcome known as a reference point. We call this method Reference Dependent Decision Theoretic dose finding (R2DT). A simulation study demonstrates that the framework can perform well and produce good operating characteristics. The simulation results demonstrate that R2DT is better at detecting the optimal dose in scenarios where candidate doses are around minimum acceptable efficacy and maximum acceptable toxicity thresholds. The proposed framework shows that a flexible utility function, which better captures clinician beliefs, can lead to trials with good operating characteristics, including a high probability of finding the optimal dose. Our work demonstrates proof\u2010of\u2010concept for this framework, which should be evaluated in a broader range of settings.<\/jats:p>","DOI":"10.1002\/sim.70547","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T11:03:58Z","timestamp":1777547038000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining Utility as a Measure of Preference Under Uncertainty in Phase I\u2013\n                    <scp>II<\/scp>\n                    Oncology Dose Finding Trials"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7009-571X","authenticated-orcid":false,"given":"Andrew","family":"Hall","sequence":"first","affiliation":[{"name":"Institute of Clinical Trials Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-8718","authenticated-orcid":false,"given":"Duncan","family":"Wilson","sequence":"additional","affiliation":[{"name":"Institute of Clinical Trials Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-7219","authenticated-orcid":false,"given":"Stuart","family":"Barber","sequence":"additional","affiliation":[{"name":"School of Mathematics University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute of Clinical Trials Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00371"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199359011.001.0001"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2012.43.4233"},{"key":"e_1_2_11_5_1","volume-title":"The Emperor of All Maladies: A Biography of Cancer","author":"Mukherjee S.","year":"2011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.02049"},{"key":"e_1_2_11_7_1","unstructured":"FDA \u201cProject Optimus\u2014fda.gov \u201d2023 https:\/\/www.fda.gov\/about\u2010fda\/oncology\u2010center\u2010excellence\/project\u2010optimus."},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2307\/2530393"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197\u20102456(94)90003\u20105"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1541\u20100420.00029"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2018.01.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1081\/bip\u2010200035471"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2201"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1864"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2001.01018.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(01)00205-7"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006\u2010341x.2004.00218.x"},{"key":"e_1_2_11_19_1","volume-title":"Bayesian Designs for Phase I\u2010II Clinical Trials (Chapman & Hall\/CRC Biostatistics Series)","author":"Yuan Y.","year":"2016"},{"key":"e_1_2_11_20_1","volume-title":"Statistical Decision Theory: Kendall's Library of Statistics 9","author":"French S.","year":"2000"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511779237"},{"key":"e_1_2_11_22_1","volume-title":"Theory of Games and Economic Behavior","author":"Von Neumann J.","year":"1947"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543409808835252"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2012.676586"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2303"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543400903280613"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2015.05.014"},{"key":"e_1_2_11_28_1","unstructured":"J. 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