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

TL;DR

This paper reviews design strategies for dose optimization trials, emphasizing the importance of selecting appropriate methods to identify the optimal biological dose, and discusses practical considerations and software tools for implementation.

Contribution

It provides a comprehensive overview of dose optimization trial designs, practical guidance for planning, and introduces software tools, addressing complexities beyond traditional dose-finding approaches.

Findings

Comparison of phase I/II and II/III design strategies

Discussion of advantages and disadvantages of various designs

Illustration with real-world examples

Abstract

The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards 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 I/II and II/III designs, and highlights their respective advantages and disadvantages. Additionally, 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.