STEIN: A simple toxicity and efficacy interval design for seamless phase I/II clinical trials

Area of Science:

• Oncology
• Clinical Trial Design
• Biostatistics

Background:

• Phase I/II trials are crucial for early drug development in oncology.
• Existing dose-finding methods often rely on complex, untestable models, hindering practical application.
• There is a need for simplified, robust methods for dose-finding in early-phase oncology trials.

Purpose of the Study:

• To extend the Bayesian optimal interval design for maximum tolerated dose finding to optimal biological dose finding in seamless phase I/II trials.
• To simplify the practical implementation of dose-finding methods in early-phase oncology drug development.
• To develop a model-free design suitable for various dose-response relationships.

Main Methods:

• Extended the Bayesian optimal interval design to incorporate both toxicity and efficacy.
• Derived optimized intervals by minimizing probabilities of incorrect classifications.
• Proposed a dose allocation rule based on maximizing posterior probability within a desired efficacy interval while controlling toxicity.

Main Results:

• The proposed interval design is model-free, allowing flexibility for diverse dose-response relationships.
• Extensive simulations demonstrated favorable small- and large-sample performance across various scenarios.
• The method showed desirable and robust operating characteristics compared to existing designs.

Conclusions:

• The novel Bayesian interval design offers a practical and effective approach for optimal biological dose finding in phase I/II oncology trials.
• The model-free nature and simplified implementation make it suitable for real-world clinical settings.
• The design provides robust performance and balances efficacy with toxicity control.