title: The rapid enrollment design for Phase I clinical trials.
abstract: We propose a dose-finding design for Phase I oncology trials where each new patient is assigned to the dose most likely to be the target dose given observed data. The main model assumption is that the dose-toxicity curve is non-decreasing. This method is beneficial when it is desirable to assign a patient to a dose as soon as the patient is enrolled into a study. To prevent assignments to doses with limited toxicity information in fast accruing trials we propose a conservative rule that assigns temporary fractional toxicities to patients still in follow-up. We also recommend always using a safety rule in any fast accruing dose-finding trial. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7420, U.S.A.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.affiliation: Departments of Pediatrics and Biostatistics, George Washington University and Children's National Medical Center, Washington DC, 20010, U.S.A.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 27599, U.S.A.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Foster
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020714:Maximum Tolerated Dose; D008495:Medical Oncology; D018579:Patient Selection; D012107:Research Design
keywords: CRM; Phase I trial; RED; TITE-CRM; mTPI
references.citation: Stat Med. 2003 Jan 15;22(1):69-82
references.pmid: 12486752
references.citation: Leuk Lymphoma. 2012 Jul;53(7):1331-7
references.pmid: 22149206
references.citation: Biostatistics. 2008 Jul;9(3):442-57
references.pmid: 18084008
references.citation: Stat Med. 1998 May 30;17(10):1103-20
references.pmid: 9618772
references.citation: Biometrics. 1989 Sep;45(3):925-37
references.pmid: 2790129
references.citation: Pharm Stat. 2015 Mar-Apr;14(2):102-7
references.pmid: 25408518
references.citation: Biometrics. 2000 Dec;56(4):1177-82
references.pmid: 11129476
references.citation: PLoS One. 2014 Mar 24;9(3):e93070
references.pmid: 24663812
references.citation: J Clin Oncol. 2013 May 10;31(14):1785-91
references.pmid: 23569307
references.citation: Biometrics. 2009 Mar;65(1):307-15
references.pmid: 18479486
references.citation: Biometrics. 1990 Mar;46(1):33-48
references.pmid: 2350571
references.citation: Biometrics. 2002 Sep;58(3):671-4
references.pmid: 12230003
references.citation: Clin Trials. 2004;1(6):499-508
references.pmid: 16279290
references.citation: Clin Trials. 2010 Dec;7(6):653-63
references.pmid: 20935021