Findings
Decentralized clinical trials (DCTs) improve trial accessibility, efficiency, and patient-centricity but require careful planning and stakeholder engagement.
Digitally-derived novel endpoints remain underutilized in clinical trials due to challenges in validation, regulatory acceptance, and stakeholder collaboration.
Updated recommendations emphasize meaningful measures, early regulatory engagement, and sharing lessons learned to advance endpoint development.
Resources like the question bank and process map help sponsors and investigators align measures with patient needs and regulatory expectations.
Addressing interoperability, privacy concerns, and diverse participant needs is critical for broad implementation of DHTs in trials.

Recommendations
Engage all stakeholders early, including patients, regulators, and technology providers, to address trial needs and risks effectively.
Develop endpoints that are meaningful to patients and clinically relevant by incorporating stakeholder input and aligning with regulatory expectations.
Use digitally-derived endpoints in early-phase trials to validate their fit-for-purpose status and optimize their positioning in pivotal trials.
Provide training and support for investigators, sites, and participants to enhance DCT implementation and reduce burdens.
Promote collaboration and data sharing to advance standardization and facilitate the adoption of novel endpoints.

Regulatory Considerations
Use the revised Regulatory Engagement Guide to clarify when and how to engage with FDA and EMA for digitally-derived endpoint validation.
Align trial designs with regulatory requirements for data reliability, privacy, and endpoint applicability.
Leverage evidentiary considerations to demonstrate endpoint reliability, meaningfulness, and clinical relevance.
Integrate feedback from regulators early to avoid delays in endpoint acceptance and ensure compliance with regional laws.
Address concerns related to data privacy, interoperability, and participant diversity to meet regulatory and ethical standards.