A generalized phase 1-2-3 design integrating dose optimization with confirmatory treatment comparison

Year: 2024

Type: article

Abstract: A generalized phase 1-2-3 design, Gen 1-2-3, that includes all phases of clinical treatment evaluation is proposed. The design extends and modifies the design of Chapple and Thall (2019), denoted by CT. Both designs begin with a phase 1-2 trial including dose acceptability and optimality criteria, and both select an optimal dose for phase 3. The Gen 1-2-3 design has the following key differences. In stage 1, it uses phase 1-2 criteria to identify a set of candidate doses rather than 1 dose. In stage 2, which is intermediate between phase 1-2 and phase 3, it randomizes additional patients fairly among the candidate doses and an active control treatment arm and uses survival time data from both stage 1 and stage 2 patients to select an optimal dose. It then makes a Go/No Go decision of whether or not to conduct phase 3 based on the predictive probability that the selected optimal dose will provide a specified substantive improvement in survival time over the control. A simulation study shows that the Gen 1-2-3 design has desirable operating characteristics compared to the CT design and 2 conventional designs.

Source: Biometrics

DOI: 10.1093/biomtc/ujad022

Authors: Yong Zang, Peter F Thall, Ying Yuan

Institutions: Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, The University of Texas MD Anderson Cancer Center

Language: English

Topic: Statistical Methods in Clinical Trials

Subfield: Statistics and Probability

Field: Mathematics

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences

OpenAlex ID: W4391900263