{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T18:26:59Z","timestamp":1773858419068,"version":"3.50.1"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NIH\/NCI 2U10CA180899\u201006"],"award-info":[{"award-number":["NIH\/NCI 2U10CA180899\u201006"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH KL2 TR002379"],"award-info":[{"award-number":["NIH KL2 TR002379"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biometrics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As diseases like cancer are increasingly understood on a molecular level, clinical trials are being designed to reveal or validate subpopulations in which an experimental therapy has enhanced benefit. Such biomarker\u2010driven designs, particularly \u201cadaptive enrichment\u201d designs that initially enroll an unselected population and then allow for later restriction of accrual to \u201cmarker\u2010positive\u201d patients based on interim results, are increasingly popular. Many biomarkers of interest are naturally continuous, however, and most existing design approaches either require upfront dichotomization or force monotonicity through algorithmic searches for a single marker threshold, thereby excluding the possibility that the continuous biomarker has a nondisjoint and truly nonlinear or nonmonotone prognostic relationship with outcome or predictive relationship with treatment effect. To address this, we propose a novel trial design that leverages both the actual shapes of any continuous marker effects (both prognostic and predictive) and their corresponding posterior uncertainty in an adaptive decision\u2010making framework. At interim analyses, this marker knowledge is updated and overall or marker\u2010driven decisions are reached such as continuing enrollment to the next interim analysis or terminating early for efficacy or futility. Using simulations and patient\u2010level data from a multi\u2010center Children's Oncology Group trial in Acute Lymphoblastic Leukemia, we derive the operating characteristics of our design and compare its performance to a traditional approach that identifies and applies a dichotomizing marker\u00a0threshold.<\/jats:p>","DOI":"10.1111\/biom.13550","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T11:49:40Z","timestamp":1629460180000},"page":"1441-1453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bayesian adaptive trial design for a continuous biomarker with possibly nonlinear or nonmonotone prognostic or predictive effects"],"prefix":"10.1093","volume":"78","author":[{"given":"Yusha","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Kairalla","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Florida Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-1896","authenticated-orcid":false,"given":"Lindsay A.","family":"Renfro","sequence":"additional","affiliation":[{"name":"Division of Biostatistics University of Southern California and Children's Oncology Group Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3559"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5541"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.472"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4462"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6272"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1761"},{"key":"e_1_2_8_8_1","first-page":"1","article-title":"Adaptive randomized phase II design for biomarker threshold selection and independent evaluation","volume":"3","author":"Renfro L.A.","year":"2014","journal-title":"Chinese Clinical Oncology"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.03.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2013.12.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.300"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-842X.2008.00507.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.7250"}],"container-title":["Biometrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/biom.13550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/biom.13550","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/biom.13550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T18:12:57Z","timestamp":1706292777000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biometrics\/article\/78\/4\/1441-1453\/7460102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/biom.13550"],"URL":"https:\/\/doi.org\/10.1111\/biom.13550","archive":["Portico"],"relation":{},"ISSN":["0006-341X","1541-0420"],"issn-type":[{"value":"0006-341X","type":"print"},{"value":"1541-0420","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]},"assertion":[{"value":"2020-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}