A phase I/II seamless dose escalation/expansion with adaptive randomization scheme (SEARS).

ABSTRACT:

Background

Standard drug development conducts phase I dose finding and phase II dose expansion sequentially and separately. Information between the two phases is rarely shared. Administratively, such a sequential process is time-consuming and burdensome.

Purpose

We propose seamless dose escalation/expansion with adaptive randomization scheme (SEARS), a seamless design that combines phase I dose escalation based on toxicity with phase II dose expansion and dose comparison based on efficacy. SEARS allows extension from phase I to phase II under one design with no gap in between and employs a dynamic and parallel procedure involving simultaneous dose escalation, dose graduation, and adaptive randomization.

Methods

SEARS integrates three components into a seamless scheme.

SUBMITTER: Pan H 

PROVIDER: S-EPMC4281526 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature