{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:10:30Z","timestamp":1767892230437,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1RR033176"],"award-info":[{"award-number":["UL1RR033176"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000124"],"award-info":[{"award-number":["UL1TR000124"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010582","name":"NCI","doi-asserted-by":"publisher","award":["CA188480-01A1"],"award-info":[{"award-number":["CA188480-01A1"]}],"id":[{"id":"10.13039\/100010582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010582","name":"NCI","doi-asserted-by":"publisher","award":["P01 CA098912-11"],"award-info":[{"award-number":["P01 CA098912-11"]}],"id":[{"id":"10.13039\/100010582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"FDA","doi-asserted-by":"publisher","award":["5R01 FS004099-03"],"award-info":[{"award-number":["5R01 FS004099-03"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>The standard 3 + 3 or \u201cmodified Fibonacci\u201d up-and-down (MF-UD) method of dose escalation is by far the most used design in dose-finding cancer trials. However, MF-UD has always shown inferior performance when compared with its competitors regarding number of patients treated at optimal doses. A consequence of using less effective designs is that more patients are treated with doses outside the therapeutic window. In June 2012, the U S Food and Drug Administration (FDA) rejected the proposal to use Escalation with Overdose Control (EWOC), an established dose-finding method which has been extensively used in FDA-approved first in human trials and imposed a variation of the MF-UD, known as accelerated titration (AT) design. This event motivated us to perform an extensive simulation study comparing the operating characteristics of AT and EWOC. We show that the AT design has poor operating characteristics relative to three versions of EWOC under several practical scenarios. From the clinical investigator\u2019s perspective, lower bias and mean square error make EWOC designs preferable than AT designs without compromising safety. From a patient\u2019s perspective, uniformly higher proportion of patients receiving doses within an optimal range of the true MTD makes EWOC designs preferable than AT designs.<\/jats:p>","DOI":"10.3390\/e17085288","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T02:12:37Z","timestamp":1438049557000},"page":"5288-5303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Escalation with Overdose Control is More Efficient and Safer than Accelerated Titration for Dose Finding"],"prefix":"10.3390","volume":"17","author":[{"given":"Andr\u00e9","family":"Rogatko","sequence":"first","affiliation":[{"name":"Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT, Suite 900C, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen","family":"Cook-Wiens","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT, Suite 900C, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mourad","family":"Tighiouart","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT, Suite 900C, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Piantadosi","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT, Suite 900C, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/sim.4780111011","article-title":"Bayesian Methods for Phase I Clinical Trials","volume":"11","author":"Gatsonis","year":"1992","journal-title":"Stat. 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