Findings
Regulatory Acceptance is Complex: Gaining regulatory acceptance for endpoints derived from Digital Health Technologies (DHTs) is a lengthy, multifaceted, and costly process that requires a global strategy and early health authority consultation.
“Fit-for-Purpose” is Key: A DHT’s clearance or approval as a medical device does not automatically ensure it is fit-for-purpose in a clinical trial; its intended use must align with the specific context of use (COU) in the study.
Meaningfulness is a Hurdle: Demonstrating the clinical meaningfulness of novel digital endpoints, especially for abstract concepts like cognitive decline in Alzheimer’s Disease, remains a significant challenge for regulatory acceptance.
International Harmonization is Lacking: Differences in regulatory requirements for DHT validation between major health authorities can delay or prevent the successful implementation of digital measures in global clinical trials.
Technology Changes Pose Risks: Software and hardware updates to DHTs during a clinical trial can have significant implications, potentially invalidating study results if not managed through a predetermined change-control plan.

Recommendations
Engage Health Authorities Early and Often: Sponsors should conduct multiple consultations with major health authorities (e.g., FDA, EMA) early in the development process to align on the Concept of Interest (COI), COU, and the validation roadmap.
Develop a Comprehensive Regulatory Strategy: A global regulatory strategy should be an integral part of the overall development plan, tailored to the program’s objectives and endpoint hierarchy.
Establish “Fit-for-Purpose” Criteria: Before selecting a DHT, sponsors should establish the minimum technical and performance specifications required for the specific COU to guide the selection of a fit-for-purpose device.
Create a Conceptual Framework: For novel endpoints, sponsors should develop a conceptual framework that visualizes how the DHT-derived measure relates to meaningful health concepts and patient experiences.
Plan for Change and Missing Data: Sponsors should establish predetermined change-control plans with manufacturers to manage DHT updates and create risk management plans to minimize and handle missing data from remote acquisition.

Regulatory Considerations
Distinct Pathways in US vs. EU: The US FDA uses a risk-based approach for DHTs that are medical devices, while in Europe, CE marking for the intended COU is generally expected by the EMA.
Qualification is an Option, Not a Requirement: Both the FDA and EMA offer voluntary qualification programs for Drug Development Tools (DDTs), which can validate a DHT for a specific COU across multiple drug programs, though the process is resource-intensive.
Scientific Advice for Individual Programs: For DHTs used within a single drug development program, engaging with health authorities through scientific advice meetings is a more targeted and confidential pathway for gaining feedback and agreement.
Data Privacy and Security are Paramount: Sponsors must ensure that the collection, transfer, and storage of personal data via DHTs comply with all applicable regulations, such as GDPR in the EU, including cybersecurity and data transfer measures.