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Sequential Designs for Phase I Clinical Trials with Late‐Onset Toxicities
Author(s) -
Cheung Ying Kuen,
Chappell Rick
Publication year - 2000
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/j.0006-341x.2000.01177.x
Subject(s) - duration (music) , clinical trial , medicine , computer science , maximum tolerated dose , biometrics , term (time) , artificial intelligence , art , physics , literature , quantum mechanics
Summary. Traditional designs for phase I clinical trials require each patient (or small group of patients) to be completely followed before the next patient or group is assigned. In situations such as when evaluating late‐onset effects of radiation or toxicities from chemopreventive agents, this may result in trials of impractically long duration. We propose a new method, called the time‐to‐event continual reassessment method (TITE‐CRM), that allows patients to be entered in a staggered fashion. It is an extension of the continual reassessment method (CRM; O'Quigley, Pepe, and Fisher, 1990, Biometrics 46 , 33–48). We also note that this time‐to‐toxicity approach can be applied to extend other designs for studies of short‐term toxicities. We prove that the recommended dose given by the TITE‐CRM converges to the correct level under certain conditions. A simulation study shows our method's accuracy and safety are comparable with CRM's while the former takes a much shorter trial duration: a trial that would take up to 12 years to complete by the CRM could be reduced to 2–4 years by our method.