Findings
Fragmented and inconsistent measurement approaches currently hinder the generation of decision-grade evidence for pediatric rare diseases. Small and geographically dispersed patient populations make traditional site-based clinical assessments operationally difficult and burdensome for families. Digital health technologies can capture subtle functional changes and “functional fingerprints” in home settings that are often missed during infrequent clinic visits. Standardized core digital measures across conditions allow for the aggregation of data and the creation of a shared evidence base for rare disorders. Meaningful aspects of health identified by patients and caregivers include motor function, communication, sleep quality, and autonomic stability.

Recommendations
Sponsors should adopt the core set of digital clinical measures to reduce trial timelines, lower development costs, and decrease participant burden. Researchers should prioritize passive and objective data collection to minimize the need for manual tracking by caregivers. Clinical trial designs should transition toward decentralized or hybrid models to improve access for children and families regardless of their location. Stakeholders should use the project’s conceptual model to identify and customize digital measures that align with the specific health priorities of their target population. Developers should focus on human-centered design to ensure digital tools are usable and sustainable for pediatric patients and their support networks.

Regulatory Considerations
The FDA and EMA provide specific pathways and interaction opportunities to accelerate the acceptance of digital endpoints in rare disease trials. Digital measures must be validated as “decision-grade” endpoints to meet the evidentiary requirements for regulatory submission and marketing approval. Alignment with industry standards for data elements and interoperability is necessary to ensure data integrity across multi-site studies. Early engagement with regulatory bodies through meetings and formal submissions is critical for confirming the suitability of new digital biomarkers. Compliance with data privacy and ethical standards is paramount when collecting continuous, real-world data from vulnerable pediatric populations.