Title | Selection of the initial design for the two-stage continual reassessment method. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Jia, Xiaoyu, Anastasia Ivanova, and Shing M. Lee |
Journal | J Biopharm Stat |
Volume | 27 |
Issue | 3 |
Pagination | 495-506 |
Date Published | 2017 |
ISSN | 1520-5711 |
Keywords | Algorithms, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Medical Oncology, Research Design |
Abstract | In the two-stage continual reassessment method (CRM), model-based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. This is appealing to clinicians because it allows a sufficient number of patients to be assigned to each of the lower dose levels before escalating to higher dose levels. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose-escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifying cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose-finding study for which clinicians explicitly stated their desire to assign at least one patient to each of the lower dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided. |
DOI | 10.1080/10543406.2017.1290650 |
Alternate Journal | J Biopharm Stat |
Original Publication | Selection of the initial design for the two-stage continual reassessment method. |
PubMed ID | 28300466 |
PubMed Central ID | PMC5383510 |
Grant List | P01 CA142538 / CA / NCI NIH HHS / United States P30 CA196521 / CA / NCI NIH HHS / United States |
Selection of the initial design for the two-stage continual reassessment method.
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