Improving safety of the continual reassessment method via a modified allocation rule.

ABSTRACT: This article proposes a novel criterion for the allocation of patients in phase I dose-escalation clinical trials, aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach, the next patient is allocated to the dose with the toxicity estimate closest (in terms of the absolute or squared distance) to the maximum acceptable toxicity. This approach, however, ignores the uncertainty in point estimates and ethical concerns of assigning a lot of patients to overly toxic doses. In fact, balancing the trade-off between how accurately the MTD can be estimated and how many patients would experience adverse events is one of the primary challenges in phase I studies. Motivated by recent discussions in the theory of estimation in restricted parameter spaces, we propo

SUBMITTER: Mozgunov P 

PROVIDER: S-EPMC7064916 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature