The impact of non-drug-related toxicities on the estimation of the maximum tolerated dose in phase I trials.

ABSTRACT: The rate of observed dose-limiting toxicities (DLT) determines the maximum tolerated dose (MTD) in phase I trials. There are cases in which non-drug-related toxicities or other-cause toxicities (OCT) are flagged as DLTs, or vice versa, due to attribution errors. We aim to assess the impact of such errors on the final estimate of MTD. We compared the impact of attribution errors using 2 trial designs-the "3+3" dose-escalation scheme and the continual reassessment method (CRM). Two attribution errors are considered: when a DLT is classified as an OCT (type A error) and when an OCT is misclassified as a DLT (type B error). The impact of these errors on accuracy, patient safety, sample size, and study duration was evaluated by varying the probability of occurrence of each error through simulat

SUBMITTER: Iasonos A 

PROVIDER: S-EPMC3463734 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature