|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|
|Keywords||Algorithms, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Medical Oncology, Research Design|
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.
|Alternate Journal||J Biopharm Stat|
|Original Publication||Selection of the initial design for the two-stage continual reassessment method.|
|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.