Findings
Challenges in patient adherence and acceptability of digital endpoints.
Issues with algorithm validation and use in diverse populations.
Barriers due to proprietary software and lack of transparency.
Vast heterogeneity in digital endpoints and lack of standards.
Need for ongoing ethical support and consideration of environmental impact.

Recommendations
Foster multi-stakeholder cooperation and open-forum discussions.
Integrate patient needs into the design of digital health technologies.
Include implementation science expertise in research proposals.
Develop standards for selecting and reporting digital endpoints.
Provide ongoing ethical support throughout the research lifecycle.

Regulatory Considerations
Early engagement with regulators is crucial.
Understanding regulatory requirements for clinical trials versus clinical care.
Need for harmonised terminology and guidelines for digital endpoints.

Findings
Standard assessments lack sensitivity in early stages of neurodegenerative diseases.
Challenges with the validity and quality of RMT measurements.
Issues related to equity and inclusion in deploying digital tools.
Importance of considering feasibility, acceptance, usability, and ecological validity of digital endpoints.

Recommendations
Develop regulatory strategies early on.
Ensure equity and inclusion in deploying digital tools.
Address challenges related to the validity and usability of digital endpoints.
Promote public-private partnerships to address privacy and security concerns.
Involve patients and stakeholders in the design and implementation of digital tools.

Regulatory Considerations
Acceptance of digital endpoints by regulatory authorities is crucial.
Validation with current gold standards and clinically meaningful legacy endpoints.
Ensure data security and privacy.

Findings
Digital health technologies often produce noisier data with additional sources of variation compared to traditional clinical trial settings.
There is a significant challenge in maintaining participant engagement and adherence in digital trials.
The need for pilot studies to address data flow, integration, and integrity is crucial.

Recommendations
Enhance participant engagement through hybrid approaches combining digital and traditional methods.
Conduct pilot studies to test data flow and integration before full-scale trials.
Refine data management guidelines based on experiences from digital trials like AHS.
Include diverse expertise in trial leadership, such as software engineers and biostatisticians.
Plan for comprehensive data analysis, including handling missing data.

Regulatory Considerations
Ensure data security, privacy, and integrity throughout the trial.
Develop a comprehensive plan for data analysis and management.
Consider the composition of the Data & Safety Monitoring Board to include diverse expertise.

Findings
Advantages of MCTs: Investigators highlighted remote data capture, access to real-time data for monitoring, and improved data quality as major benefits. They also noted reduced participant burden due to fewer in-person visits and increased participant engagement through real-time data access.
Challenges of MCTs: Increased site burden due to additional time required for technology setup, troubleshooting, and managing high data volumes was a common theme. Participants faced challenges such as technology unfamiliarity, device management, and potential behavior changes from real-time data access.
Support Needs: Investigators emphasized the need for technical support, staff training, and increased budgetary resources to manage devices and train participants. They also highlighted the importance of clear communication about device selection and capabilities from sponsors.

Recommendations
Sponsors should supply comprehensive device training, including hands-on and supplemental materials, and establish systems for ongoing technical support throughout the trial.
Include funds for device management, staff training, and participant support to accommodate the additional demands of MCTs.
Prioritize user-friendly devices to minimize participant burden and improve adherence.
Collaborate with investigators and participants during trial planning to ensure technologies align with study objectives and participant needs.
Focus on in-person, hands-on training to ensure staff and participants are comfortable with the technologies.

Regulatory Considerations
Devices must meet data security and safety requirements to address Institutional Review Board (IRB) concerns.
Provide detailed information about device safety, storage, and capabilities to ensure compliance with regulatory standards.
Clearly communicate data access levels to participants, minimizing risks of data misinterpretation.

Findings
Adherence: Participants achieved an overall adherence rate of 90.18%, demonstrating the feasibility of home-based data collection over a 30-day period.
Participant Feedback: Most participants found the technology easy to use, though some reported difficulties with specific devices, such as sleeping with a wearable watch.
Device Selection: Precision, consistency, and participant preferences guided the selection of spirometry devices, with single-blow spirometry favored for ease of use.
Accuracy: Home spirometry measurements underestimated forced vital capacity (FVC) compared to historical in-clinic data, possibly due to device differences or disease progression.
Future Participation: Nine out of ten participants expressed interest in joining longer virtual studies using similar technologies.

Recommendations
Evaluate Adherence and Usability: Conduct feasibility studies to assess adherence rates and identify usability challenges before full-scale implementation.
Incorporate Participant Feedback: Use cross-over designs to gather participant preferences and feedback on device usability, data sharing, and frequency of data collection.
Validate Accuracy and Consistency: Ensure that DHTs provide precise, reliable measurements comparable to in-clinic standards and assess their performance in real-world settings.
Optimize Technology for Long-Term Use: Address issues such as wearability and participant burden to improve device acceptance and compliance.
Refine Training and Communication: Provide clear instructions and training to participants, setting expectations for using and troubleshooting the technologies.

Regulatory Considerations
Validate Home-Based Data Collection: Demonstrate that data collected remotely with DHTs are accurate, reliable, and clinically relevant for trial endpoints.
Pilot Studies for Regulatory Submissions: Use feasibility data to strengthen regulatory submissions, ensuring endpoints are validated for use in pivotal trials.
Address Technology Limitations: Acknowledge and mitigate potential discrepancies between home and clinic data, using feasibility study insights to refine protocols.

Findings
Feedback on training for both sites and patients is a critical focus, including its clarity, duration, and accessibility.
Common site challenges include managing logistics, technical troubleshooting, and adapting workflows to accommodate patient-facing technologies.
Patient Experience: The questionnaire captures patient compliance, usability issues, and burden, particularly in remote or decentralized trial setups.
Feedback is collected at three distinct points—early (training), mid-study (technical issues), and post-study (overall impressions)—to address evolving challenges.
Strong communication and timely support from sponsors and vendors are emphasized as critical to resolving issues and maintaining trial integrity.

Recommendations
Incorporate PTSFQ into Trial Protocols: Sponsors should integrate this feedback tool into study plans to systematically capture insights from sites.
Provide comprehensive, multi-format training tailored to diverse learning needs for both site staff and patients.
Establish clear, accessible points of contact for technical and logistical support, ensuring rapid resolution of issues.
Use patient feedback to minimize burden, improve device usability, and ensure compatibility with daily routines.
Regularly review feedback from all PTSFQ sections to identify trends, address issues early, and refine technology use in ongoing and future trials.

Regulatory Considerations
Not provided.

Findings
The PPG-based Wrist-monitor provides comparable measurements to traditional devices with less inconvenience.
Further research is needed to confirm accuracy in specific subpopulations.
Current ABPM devices may impact long-term adherence due to discomfort.

Recommendations
Conduct further studies on the device's accuracy in various subpopulations.
Consider the PPG-based device for continuous BP monitoring.
Use the device for hypertension diagnosis and treatment.
Explore the device's use in other inpatient settings.

Regulatory Considerations
The device is FDA cleared for BP measurements.
It is undergoing validation for other inpatient settings.

Findings
There is a lack of consensus on outcome measures and adherence definitions across studies using wearables in oncology.
There is significant heterogeneity in study designs and outcomes, making comparisons difficult.
Limited guidelines exist for designing or reporting trials using wearables in oncology.

Recommendations
Establish standardized definitions for wearable outcomes and adherence to improve study comparisons.
Encourage research using advanced wearable devices and active data use.
Conduct more randomized clinical trials to create consensus on implementing wearables in oncological practice.
Develop guidelines for designing and reporting trials using wearables.

Regulatory Considerations
The Clinical Transformation Initiative (CTTI) provides recommendations for the use of mobile technology in clinical trials, which could inform regulatory frameworks.

Findings
Researchers face challenges in scientific methodology, regulatory, legal, and operational aspects.
Many consumer-grade devices lack scientific evidence for their health claims.
There are significant challenges in data management, infrastructure, analysis, and security.
Lack of mobile technology data standards and transparency in data processing algorithms.
The need for a shared understanding of methodologies and terminology.

Recommendations
Develop industry-wide standards for data and terminology.
Foster dialogue between biopharmaceutical industry and device manufacturers for methodological development.
Ensure a patient-centric approach in clinical trials using wearable devices.
Conduct well-powered studies with clear medical problem statements.
Implement rigorous analytical and clinical validation processes.

Regulatory Considerations
Separate marketing approval paths for drugs and devices in the US.
Most wearable devices are classified as Class II devices requiring 510(k) clearance.
Compliance with HIPAA for data obtained via medical devices.
Need for device performance validation in specific populations relevant to device label claims.
Differences in US and EU regulations regarding data protection and consent requirements.

Findings
Traditional DMD endpoints focus on ambulation, excluding non-ambulatory patients and limiting trial inclusivity.
Accelerometer technology offers objective, real-world data collection, reducing the burden on patients and caregivers while enabling longitudinal assessment.
"Total arm movement" as a concept of interest captures meaningful functional activities across ambulatory and non-ambulatory populations.
Challenges include ensuring compliance with device use, minimizing variability from external factors (e.g., seasons, school schedules), and correlating data with meaningful treatment effects.
Continuous collaboration and data sharing among stakeholders, including regulators and technology manufacturers, is essential for endpoint development.

Recommendations
Define meaningful activities of daily living (ADLs) for DMD patients and correlate them with accelerometer-derived metrics, such as total arm movement.
Validate accelerometer data through natural history studies, cross-sectional analyses, and correlation with existing DMD-specific measures (e.g., DMD Upper Limb PROM).
Optimize measurement schedules to balance patient compliance with longitudinal data collection needs, focusing on real-world settings.
Collaborate with regulators to align endpoints with evidentiary requirements for clinical trials, ensuring their relevance and applicability.
Develop frameworks for continuous data sharing and standardization to streamline endpoint validation and regulatory acceptance.

Regulatory Considerations
Validate the endpoint to reflect meaningful treatment effects and ensure alignment with regulatory standards for phase III trials.
Address variability in data collection due to environmental or behavioral factors to enhance reliability and applicability.
Develop methodologies to correlate accelerometer-derived metrics with clinically meaningful outcomes and validated DMD measures.
Engage regulators early to obtain feedback and ensure endpoints meet the criteria for use in pivotal trials.
Explore the potential for composite endpoints combining accelerometer data with PROs to provide a comprehensive view of patient outcomes.