Findings
A unified digital measurement lexicon is critical for clear communication across stakeholders during development and evaluation processes.
Stakeholder and patient engagement is essential for identifying meaningful aspects of health (MAH) and defining context-specific concepts of interest (COI).
Establishing proof of concept via observational studies or exploratory trial phases de-risks investment and demonstrates feasibility.
Evaluation frameworks such as V3 ensure that digital measures meet analytical and clinical validation requirements, even in the absence of established comparators.
The lack of robust comparators in underserved conditions creates both challenges and opportunities for the development of novel digital measures.

Recommendations
Engage Early and Continuously: Involve patients, caregivers, clinicians, and other stakeholders early to identify MAH and COI that align with patient needs and trial objectives.
Adopt V3 Framework: Follow the V3 process for verification, analytical validation, and clinical validation to ensure measures are fit for purpose.
Design Iterative Proof of Concept Studies: Use small-scale studies or exploratory trial phases to validate the technical and clinical feasibility of digital measures.
Seek Early Regulatory Engagement: Initiate discussions with regulatory agencies (e.g., FDA or EMA) early in the evaluation process to refine applications and address potential challenges.
Collaborate Across Stakeholders: Foster multi-stakeholder collaboration to pool expertise and resources, especially for challenging therapeutic areas or underserved populations.

Regulatory Considerations
Use tools like FDA’s Drug Development Tool Qualification Program or EMA’s Innovation Task Force to refine evidence requirements and address legal or technical challenges.
Understand COI and COU: Tailor digital measures to specific contexts of use and intended applications, which determine whether measures are classified as biomarkers or COAs.
Demonstrate that digital measures are valid and reliable through rigorous analytical and clinical validation studies.
Use longitudinal clinical studies to gather evidence supporting the use of digital measures for regulatory decision-making.
Work within consortia to align standards and generate shared evidence, particularly for challenging use cases or rare conditions.