Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

ABSTRACT:

Background

Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established.

Methods

We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in w

SUBMITTER: Boonstra PS 

PROVIDER: S-EPMC5834117 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature