Statistical and Practical Considerations in Planning and Conduct of Dose-Optimization Trials

Authors

Ying Yuan
Heng Zhou
Suyu Liu

Publication Date

6-1-2024

Journal

Clinical Trials

Abstract

The U.S. Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection toward identifying the optimal biological dose that offers the best balance between benefit and risk, rather than the maximum tolerated dose. However, achieving dose optimization is a challenging task that involves a variety of factors and is considerably more complicated than identifying the maximum tolerated dose, both in terms of design and implementation. This article provides a comprehensive review of various design strategies for dose-optimization trials, including phase 1/2 and 2/3 designs, and highlights their respective advantages and disadvantages. In addition, practical considerations for selecting an appropriate design and planning and executing the trial are discussed. The article also presents freely available software tools that can be utilized for designing and implementing dose-optimization trials. The approaches and their implementation are illustrated through real-world examples.

Keywords

Humans, Research Design, Maximum Tolerated Dose, Dose-Response Relationship, Drug, Software, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, United States, United States Food and Drug Administration, Clinical Trials, Phase III as Topic, Optimal dose, benefit–risk trade-off, Project Optimus, adaptive design

DOI

10.1177/17407745231207085

PMID

38243399

PMCID

PMC11134987

PubMedCentral® Posted Date

1-19-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes