Repeated measures dose-finding design with time-trend detection in the presence of correlated toxicity data.

ABSTRACT:

Background

Phase I trials are designed to determine the safety, tolerability, and recommended phase 2 dose of therapeutic agents for subsequent testing. The dose-finding paradigm has thus traditionally focused on identifying the maximum tolerable dose of an agent or combination therapy under the assumption that there is a non-decreasing relationship between dose-toxicity and dose-efficacy. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades experienced in the first cycle. More recently, this was extended to a repeated measures design based on the total toxicity profile to account for longitud

SUBMITTER: Yin J 

PROVIDER: S-EPMC5714674 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature