{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:23:51Z","timestamp":1770963831500,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences (NCATS) UCLA CTSI","award":["UL1 TR001881-01"],"award-info":[{"award-number":["UL1 TR001881-01"]}]},{"name":"National Center for Advancing Translational Sciences (NCATS) UCLA CTSI","award":["P01 CA233452-02"],"award-info":[{"award-number":["P01 CA233452-02"]}]},{"name":"National Center for Advancing Translational Sciences (NCATS) UCLA CTSI","award":["U01 grant CA232859-05"],"award-info":[{"award-number":["U01 grant CA232859-05"]}]},{"name":"National Center for Advancing Translational Sciences (NCATS) UCLA CTSI","award":["3U01CA232859-05S1"],"award-info":[{"award-number":["3U01CA232859-05S1"]}]},{"name":"NCI","award":["UL1 TR001881-01"],"award-info":[{"award-number":["UL1 TR001881-01"]}]},{"name":"NCI","award":["P01 CA233452-02"],"award-info":[{"award-number":["P01 CA233452-02"]}]},{"name":"NCI","award":["U01 grant CA232859-05"],"award-info":[{"award-number":["U01 grant CA232859-05"]}]},{"name":"NCI","award":["3U01CA232859-05S1"],"award-info":[{"award-number":["3U01CA232859-05S1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>We present a Bayesian adaptive design for dose finding in oncology trials with application to a first-in-human trial. The design is based on the escalation with overdose control principle and uses an intermediate grade 2 toxicity in addition to the traditional binary indicator of dose-limiting toxicity (DLT) to guide the dose escalation and de-escalation. We model the dose\u2013toxicity relationship using the proportional odds model. This assumption satisfies an important ethical concern when a potentially toxic drug is first introduced in the clinic; if a patient experiences grade 2 toxicity at the most, then the amount of dose escalation is lower relative to that wherein if this patient experienced a maximum of grade 1 toxicity. This results in a more careful dose escalation. The performance of the design was assessed by deriving the operating characteristics under several scenarios for the true MTD and expected proportions of grade 2 toxicities. In general, the trial design is safe and achieves acceptable efficiency of the estimated MTD for a planned sample size of twenty patients. At the time of writing this manuscript, twelve patients have been enrolled to the trial.<\/jats:p>","DOI":"10.3390\/e26080687","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T06:23:05Z","timestamp":1723616585000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose Finding in Oncology Trials Guided by Ordinal Toxicity Grades Using Continuous Dose Levels"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-5690","authenticated-orcid":false,"given":"Mourad","family":"Tighiouart","sequence":"first","affiliation":[{"name":"Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90069, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-8890","authenticated-orcid":false,"given":"Andr\u00e9","family":"Rogatko","sequence":"additional","affiliation":[{"name":"Independent Researcher, 2765-399 Monte Estoril, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1001\/jama.292.17.2130","article-title":"Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials","volume":"292","author":"Roberts","year":"2004","journal-title":"J. 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