Key objectives of the initiative include:
Developing a step-by-step framework (PE Digital Roadmap) for implementing meaningful patient engagement in digital health
Clarifying the role of patients in designing and developing digital health solutions
Addressing challenges in digital health stakeholder alignment through the Stakeholder Expectations Matrix
Promoting transparency in patient involvement processes for digital health solutions

Findings
Digital endpoints must not only support regulatory approval but also provide evidence that meets payer expectations for reimbursement and value-based care. The lack of early engagement with payers and health technology assessment (HTA) agencies is a key barrier to the adoption of digital clinical measures. Digital measures can enhance value-based care models by capturing patient-centered outcomes, reducing healthcare costs, and improving early disease detection. The scalability and generalizability of digital endpoints remain challenges, particularly for diverse populations and real-world healthcare settings. Technical and systematic barriers—such as data heterogeneity, stakeholder knowledge gaps, and inconsistent regulatory-payer alignment—are slowing the adoption of digital endpoint data for reimbursement decisions.

Recommendations
Pharma and medical product developers should engage early with payers and regulators to ensure digital endpoints align with reimbursement expectations. Payers and HTA bodies should establish clear evidence thresholds for digital endpoint validation, ensuring consistency in market access decisions. Digital endpoints should be validated against health-related quality of life (HRQoL) measures and patient-reported outcomes (PROs) to demonstrate clinical relevance. Real-world evidence (RWE) should be incorporated into clinical trials alongside digital endpoints to strengthen reimbursement applications. Stakeholders should prioritize scalable, patient-centered digital measures that capture disease progression over time and across different care settings.

Regulatory Considerations
Integrated Evidence Plans (IEPs) should be developed early to align digital endpoint evidence with regulatory and payer requirements. Digital endpoints should be assessed through multi-stakeholder collaboration, ensuring validation across pharmaceutical, regulatory, and reimbursement frameworks. Payers and regulators should work together to create aligned pathways for digital measure acceptance, reducing delays in market access. Data security, privacy, and interoperability must be addressed to support regulatory approval and patient trust in digital health solutions. The industry should leverage international regulatory-payer collaboration models, such as the HTA-EMA partnership and the FDA Payor Communication Task Force, to accelerate global digital endpoint adoption.

Findings
Product development firms are hesitant to increase DHT use despite regulatory support.
Conventional hardware-based technologies are preferred over newer digital tools.
Operational barriers contribute to the low adoption of DHTs in product development trials.

Recommendations
Reduce operational barriers to facilitate DHT adoption.
Provide additional regulatory clarity to encourage DHT use.
Encourage the incorporation of more DHTs and patient-centric endpoints in clinical trials.

Regulatory Considerations
The FDA's guidance on DHT use is evolving and not yet fully formalized.
There is a need for harmonization between US and non-US regulatory agencies.
The impact of recent regulatory support may take years to be fully realized.

Findings
The review includes 275 studies, with neurology, musculoskeletal disorders, and cardiology as the most common therapeutic areas.
The studies focused on sensor performance (48%), algorithm development (86%), operational feasibility (46%), and software development (9%).
Gaps in reporting included insufficient details on software used (27%), comparator measures (17%), and participant demographics (e.g., age and gender were missing in 9% and 15% of studies, respectively).
Sixty-seven percent of the studies used wearable sensors, while others incorporated smartphones, tablets, cameras, and implantable devices.
The lack of methodological and reporting standards across studies hinders reproducibility and broader applicability.

Recommendations
Develop methodological and reporting standards to improve consistency across feasibility studies.
Include comprehensive participant demographic data, including sociodemographics and health indicators, to ensure inclusivity and generalizability.
Conduct small feasibility studies to validate sensors, optimize algorithms, and identify operational challenges before launching full-scale trials. Use the database created from this review to inform trial design and technology selection, ensuring alignment with specific research goals.
Encourage collaboration among investigators, sponsors, and regulators to standardize methods and share insights to avoid redundant studies.

Regulatory Considerations
Align sensor verification and algorithm validation processes with regulatory requirements for reliable clinical endpoints.
Ensure secure and ethical data transfer, storage, and sharing practices for compliance with privacy regulations.
Address barriers to participation for underrepresented populations by assessing and reporting equity-related data during feasibility studies.

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
Advantages of MCTs: Investigators highlighted streamlined study operations, remote data capture, and higher-quality, real-time data collection as key benefits. MCTs were also noted for their potential to reduce participant burden by enabling remote participation.
Challenges of MCTs: Investigators reported increased operational challenges, such as device setup, maintenance, and troubleshooting. They also noted time burdens for staff and uncertainties regarding data quality, including potential biases and technical malfunctions.
Support Needs: Investigators emphasized the need for technical support, comprehensive training for staff and participants, and adequate budgetary planning to address additional costs associated with MCTs.
Participant Considerations: While MCTs offer convenience and engagement opportunities for participants, challenges include the intrusiveness of data capture, technology adoption barriers, and potential negative impacts of real-time data access on participant behavior.
Recommendations: Investigators stressed the importance of collaborative relationships between sponsors and sites, user-friendly technology selection, and participant-centric trial designs.

Recommendations
Improve Training and Support: Sponsors should provide hands-on training for staff and participants, including troubleshooting support and device-specific materials.
Plan Budgets Appropriately: Include funds for device procurement, staff time, and technology management in trial budgets.
Enhance Technical Support: Sponsors should establish centralized technical support systems to address technology-related issues during trials.
Select Participant-Friendly Technologies: Prioritize devices that are intuitive, minimally intrusive, and suitable for the target population's needs.
Engage Stakeholders Early: Collaborate with investigators, participants, and sponsors during trial planning to align expectations and address potential challenges.

Regulatory Considerations
Data Security: Ensure data collected by mobile technologies comply with privacy and security regulations, and communicate these measures to IRBs.
Device Validation: Validate devices for the intended trial context to ensure reliability and minimize technical risks.
Participant Communication: Clearly inform participants about how their data will be used and provide transparency regarding data access.

Findings
Sufficient resources must be allocated, including infrastructure costs, training, and site reimbursement, to ensure smooth PT deployment.
PTs must be intuitive, validated, and able to withstand technical or environmental challenges to avoid burdening patients and sites.
PTs must comply with data privacy laws (e.g., GDPR, HIPAA) and regulatory standards (e.g., 21 CFR Part 11), and address import restrictions and age limitations.
Scaling PTs requires plans for device maintenance, multilingual support, and consistent availability across geographies and populations.
Sites need adequate training, realistic responsibilities, and clear workflows to avoid overburdening site staff and ensure patient compliance.

Recommendations
Involve key stakeholders (e.g., clinical technologies, regulatory affairs, site relations) early in the planning process to address potential challenges.
Identify risks related to usability, compliance, and data integrity, and establish mitigation strategies before implementation.
Provide tailored training materials for patients and site staff, ensuring clarity and accessibility in multiple formats and languages.
Develop Clear Vendor Contracts: Clearly outline responsibilities for maintenance, data management, and support in vendor contracts to avoid operational ambiguities.
Create Scalability Plans: Address challenges like multilingual support, long-term device maintenance, and cross-region deployment during the initial planning stages.

Regulatory Considerations
Ensure PTs comply with GDPR, HIPAA, and other relevant data protection regulations, particularly in global trials.
Verify if PTs qualify as medical devices and adhere to corresponding regulatory frameworks.
Assess and plan for country-specific import restrictions and data privacy laws to avoid delays.
Validate PTs according to Good Clinical Practice (GCP) guidelines, ensuring reliable data generation and compliance with regulatory standards.
Account for age-related legal restrictions, ensuring PTs are suitable for all intended patient populations.

Findings
Patient technologies were used across 55 countries, with mobile applications (53%) and wearable devices (33%) being the most common technologies.
Common data issues included data transmission failures, duplicate or missing data, and integration challenges with other datasets.
Factors like technical literacy, device usability, and preferences for paper-based alternatives affected adoption rates, particularly in elderly populations.
Varying broadband connectivity, importation hurdles, and compliance with regulations like GDPR posed significant challenges.
Most sponsors (54%) were willing to reuse technologies, citing improved retention, compliance, and remote monitoring capabilities as key benefits.

Recommendations
Consider patient demographics, such as age and technical literacy, when selecting and implementing technologies.
Offer multi-format training for sites, patients, and monitors, and provide robust support systems to address technical and compliance issues.
Risk Mitigation: Anticipate potential issues like data loss, non-compliance, and technical failures by incorporating backup processes into protocols.
Conduct feasibility assessments for site infrastructure and regulatory compliance in target regions to minimize delays.
Regularly gather experiential feedback from patients to refine technologies and improve future trial designs.

Regulatory Considerations
Seek advice from regulators to ensure patient technologies align with clinical trial protocols and data submission requirements.
Ensure Compliance with GDPR and Local Regulations: Address privacy concerns and adapt technologies to meet country-specific requirements.
Prepare Documentation for Importation: Account for additional time and costs related to import licenses and customs requirements.
Plan for the impact of technical updates on clinical data reliability and regulatory submissions.

Findings
Lack of security and confidence in digital health technologies hampers adoption.
Absence of suitable guidance for selecting BioMeTs based on clinical requirements.
BioMeTs (DHTs) and algorithms are often created without expert guidance and transparency.
No standardized evaluation resources for testing, verifying, and validating BioMeTs.
Inconsistencies in algorithm application across different cohorts.

Recommendations
Develop a standardized BioMeT and algorithm evaluation framework.
Create professionally tailored standardized guidelines for BioMeT use.
Implement a framework with unique identifiers for BioMeTs and algorithms.
Establish mechanisms for dynamic updates of hardware or software.
Use systematic reviews and Delphi processes to inform framework development.

Regulatory Considerations
Assign unique identifier numbers to BioMeTs and algorithms.
Provide mechanisms for dynamic hardware or software updates.
Ensure robust deployment through standardized evaluation protocols.

Findings
1. Challenges related to patient privacy and lack of sufficient validation for digital endpoints.
2. Lack of transparency in endpoint calculations and operational challenges.
3. Added complexities due to software version changes and regulatory unknowns.

Recommendations
1. Increase patient-centricity and reduce patient burden through digital health technologies.
2. Foster collaboration among pharmaceutical companies, regulators, academia, and technology companies.
3. Embrace innovation and ensure senior leadership support for digital health initiatives.
4. Utilize real-time data access to enrich clinical trial data sets.
5. Implement outpatient sampling to augment decision-making processes.

Regulatory Considerations
1. Request feedback from regulatory agencies as part of the development plan for outpatient sampling.
2. Consider the FDA's guidance on bioanalytical method validation for dried blood sampling.
3. Note examples of regulatory acceptance of digital biomarkers as primary or secondary endpoints.

Findings
The COVID-19 pandemic has highlighted the need for decentralized clinical trials (DCTs) due to the closure of traditional trial sites.
There is a lack of a national electronic medical system, which poses a challenge for digital risk minimization.
The current regulatory framework is not fully equipped to handle the rapid advancements in digital health technologies.

Recommendations
Increase the adoption and integration of decentralized clinical trials (DCTs) to ensure continuity of research during disruptions.
Develop a national electronic medical system to support digital health initiatives and improve data integration.
Enhance collaboration between regulatory bodies and technology developers to create flexible and adaptive regulatory frameworks.
Encourage the use of real-world data and digital endpoints in clinical trials to improve efficiency and relevance.
Promote patient engagement and input in the development and implementation of digital health technologies.

Regulatory Considerations
The need for standardization and integration of digital health technologies across different platforms and systems.
The importance of developing regulatory guidelines that can adapt to the rapid pace of technological advancements.
The necessity for collaboration between regulatory bodies and standards development organizations to ensure effective oversight of digital health technologies.