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.
Description
Sequential designs for phase I clinical trials with late-onset toxicities. - PubMed - NCBI
%0 Journal Article
%1 Cheung:2000:Biometrics:11129476
%A Cheung, Y K
%A Chappell, R
%D 2000
%J Biometrics
%K ClinicalTrials DoseFinding SurvivalAnalysis oncology phase1 statistics
%N 4
%P 1177-1182
%T Sequential designs for phase I clinical trials with late-onset toxicities
%U https://www.ncbi.nlm.nih.gov/pubmed/11129476
%V 56
%X 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.
@article{Cheung:2000:Biometrics:11129476,
abstract = {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.},
added-at = {2019-10-13T12:17:00.000+0200},
author = {Cheung, Y K and Chappell, R},
biburl = {https://www.bibsonomy.org/bibtex/2c38382e65f0bb4bb6ec4476b997d480f/jkd},
description = {Sequential designs for phase I clinical trials with late-onset toxicities. - PubMed - NCBI},
interhash = {88529e8ee33e2b6a3175f60633f43f8b},
intrahash = {c38382e65f0bb4bb6ec4476b997d480f},
journal = {Biometrics},
keywords = {ClinicalTrials DoseFinding SurvivalAnalysis oncology phase1 statistics},
month = dec,
number = 4,
pages = {1177-1182},
pmid = {11129476},
timestamp = {2019-10-13T12:17:00.000+0200},
title = {Sequential designs for phase I clinical trials with late-onset toxicities},
url = {https://www.ncbi.nlm.nih.gov/pubmed/11129476},
volume = 56,
year = 2000
}