From Meaningful Outcomes to Meaningful Change Thresholds: A Path to Progress for Establishing Digital Endpoints

Area of Science:

• Digital Health Technologies
• Clinical Trial Design
• Biostatistics

Background:

• Digital health technologies (DHTs) are increasingly used in drug development, offering patient-centric trial designs and sensitive data capture.
• Digital endpoints (DEs) derived from DHTs show promise for detecting changes more effectively than traditional methods.
• Transitioning DEs to primary endpoints for labeling claims necessitates robust validation and reproducible, population-specific values.

Purpose of the Study:

• To examine the determination of meaningful change thresholds (MCTs) for digital endpoints (DEs).
• To explore existing methodologies for establishing MCTs and their application in DE development.
• To emphasize aligning DEs with patient-important health concepts and overall endpoint strategy.

Main Methods:

• Review of existing approaches for determining meaningful change thresholds (MCTs).
• Analysis of methodologies used in digital endpoint (DE) development and qualification.
• Examination of regulatory documentation and submission reviews for DE qualification.

Main Results:

• Meaningful change must be determined for each DE and population, reflecting patient-perceived importance.
• Existing methodologies for MCT determination are being applied in DE development.
• Successful DE development requires ensuring DEs capture patient-relevant concepts and align with strategic goals.

Conclusions:

• Establishing robust MCTs is essential for validating DEs as reliable drug development tools.
• Insights from regulatory reviews can strengthen the development and validation of DEs.
• This work aims to guide researchers new to determining MCTs for DEs.