Maximizing return on socioeconomic investment in phase II proof-of-concept trials

Area of Science:

• Oncology
• Clinical Trial Design
• Biostatistics

Background:

• Phase II proof-of-concept (POC) trials are critical in oncology drug development for selecting therapies for Phase III testing.
• The increasing number of potential drug targets outstrips available resources, necessitating efficient trial strategies.
• Current resource limitations necessitate optimizing the return on socioeconomic investment in early-phase oncology trials.

Purpose of the Study:

• To propose a design strategy for Phase II POC trials that maximizes socioeconomic return on investment.
• To identify optimal trial parameters (size, power, Go-No Go criteria) for efficient oncology drug development.
• To balance knowledge acquisition with minimal patient exposure in early-phase oncology trials.

Main Methods:

• Comparative analysis of benefit-cost ratios for different Phase II POC trial designs.
• Evaluation of various trial sizes, statistical powering schemes, and Go-No Go (GNG) criteria.
• Modeling to determine optimal Type I and Type II error rates for detecting clinically meaningful effect sizes.

Main Results:

• The most cost-effective strategy involves conducting small POC trials with high Go-No Go bars.
• This approach allows for more trials within socioeconomic constraints, increasing overall knowledge generation.
• Optimal design features approximately 5% Type I error and 20% Type II error (80% power) for detecting effect sizes around 1.5δ, with a 'Go' decision at an observed effect size near δ.

Conclusions:

• Maximizing the number of small POC trials with stringent Go-No Go criteria enhances the return on investment in oncology drug development.
• This strategy is crucial given the expanding landscape of molecular targets and limited resources.
• Prioritizing efficiency in Phase II trials ensures more promising oncology therapies advance to definitive testing.