The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM.

ABSTRACT: The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get "stuck" on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalatio

SUBMITTER: Koopmeiners JS 

PROVIDER: S-EPMC5581285 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature