Findings
Existing guidelines lack pragmatic application and systematic approach for device selection.
Device choice is dependent on measurement objectives, user population, and available resources.
Current frameworks do not systematically consider verification, validation, feasibility, and protocol design.
Rapid obsolescence of digital devices due to technological advancements.
Need to incorporate social/psychological factors into device selection.

Recommendations
Develop a practical guide with a systematic approach for selecting wearable devices.
Use five core criteria: continuous monitoring capability, device suitability and availability, technical performance, feasibility of use, and cost evaluation.
Prioritize feasibility of use to ensure user needs are incorporated into the selection process.
Adapt guide criteria to accommodate novel innovations.
Foster clarity and transparency in decision-making among researchers, HCPs, and device users.

Regulatory Considerations
Follow FDA guidance for digital health technology usage in clinical investigations.
Consider CTTI recommendations for improving clinical trial quality and efficiency.
Use ePRO Consortium's factors for device suitability in regulatory trials.
Apply international guidelines for specific measurements when available.

Findings
The V3+ Use Specification must contain a detailed description of the user groups, use environments, and the sDHT user interface. The user groups include end-users (individuals from whom data is captured) as well as carepartners, clinicians, researchers, and administrators. Characteristics of users (e.g., demographics, literacy, physical/cognitive capabilities, disease characteristics) and use environments (e.g., temperature, network availability, clutter) must be considered for risk management .

Recommendations
Developers must follow these four steps to create the Use Specification:
Identify all user groups: Create a list of users, including sub-categories (e.g., different types of researchers), and describe the characteristics of each group (e.g., health literacy, physical capabilities) to create detailed descriptions of representative users.
Identify all likely use environments: Create a list of typical environments (e.g., Home, Hospitals) and describe their characteristics (e.g., temperature, noise, network availability), also considering "edge cases" (e.g., extreme weather).
Describe the sDHT user interface: Detail all aspects of the hardware and software (visual, auditory, tactile cues), accessories (e.g., packaging, chargers), and all written materials and training (e.g., instructions for use, helpdesk troubleshooting).
Keep it up to date: The Use Specification is a living document that requires ongoing updates and maintenance throughout the sDHT development and usability validation process.

Regulatory Considerations
The development of the Use Specification is presented as the foundational step for the usability validation component of the V3+ framework. This document directly informs the subsequent Use-Related Risk Analysis.

Findings
Misclassification of wakefulness during sleep periods and issues with tracking outside main sleep bouts.
Bias in performance evaluation studies due to limited representation of diverse populations.
Hidden complexities in consumer-grade devices related to data access, fees, privacy, and security.

Recommendations
Carefully interpret study results based on wearable sleep-tracking technology data.
Address biases in study populations by including diverse cohorts.
Ensure proper preprocessing of data from consumer-grade devices.
Avoid inserting personally identifiable information in device settings.
Evaluate issues related to specific populations like minors.

Regulatory Considerations
Complexity of privacy laws across different countries.
Need for strategies to protect personal information in device settings.
Consideration of specific population issues, such as minors, in regulatory frameworks.

Findings
There is a need for comprehensive validation and verification processes for DHTs.
Ensuring data security and privacy is a significant concern.
Usability issues for diverse populations need to be addressed.
There is a lack of clarity on whether certain DHTs meet the definition of a device under the FD&C Act.
The guidance does not establish legally enforceable responsibilities.

Recommendations
Ensure DHTs are fit-for-purpose for clinical investigations.
Implement robust data security measures to protect participant information.
Conduct usability evaluations to ensure DHTs can be used by intended populations.
Engage with FDA early to discuss the use of DHTs in clinical investigations.
Develop a risk management plan to address potential issues with DHT use.

Regulatory Considerations
Verification and validation should be addressed regardless of device classification.
Sponsors should ensure compliance with data protection and privacy regulations.
FDA evaluates DHT data based on endpoints, medical products, and patient populations. Sponsors can engage with FDA’s Q-Submission Program for feedback on DHT usage in clinical trials.
Sponsors should understand the legal implications of using DHTs in clinical investigations.
The guidance provides recommendations but does not establish legally enforceable responsibilities.

Findings
Novel digitally-derived endpoints can provide more reliable data, increase trial efficiency, and enhance patient centricity.
Selecting appropriate outcome measures that are meaningful to patients and clinicians is critical to success.
Developing these endpoints requires a resource-intensive, systematic approach to meet stakeholder needs.
Demonstrating validity and utility of novel endpoints poses unique challenges, especially for new measures without established validation standards.
Sharing lessons learned and promoting transparency can advance the field by enabling collaboration and establishing standards.

Recommendations
Focus on measures that are meaningful to patients and clinically relevant by incorporating both patient and clinician perspectives.
Select technology after identifying the appropriate outcome to ensure alignment between the technology and trial objectives.
Engage with regulators early and often to ensure endpoint acceptance and alignment with regulatory requirements.
Include digitally-derived endpoints in early-phase trials and observational studies to validate their fit-for-purpose status.
Encourage knowledge sharing and collaboration among stakeholders to establish shared standards and accelerate adoption.

Regulatory Considerations
Engage with FDA, EMA, or other regulatory bodies during early stages of endpoint development to gather critical input.
Use established regulatory frameworks, such as Investigational New Drug (IND) or Investigational Device Exemption (IDE), for guidance on endpoint use in pivotal trials.
Validate technologies to meet performance characteristics, ensuring outputs correspond to clinical concepts of interest.
Include digitally-derived endpoints in exploratory studies to build evidence for their regulatory approval.
Reference resources such as the FDA and EMA guides for navigating endpoint-related regulatory interactions.

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
DHT selection should be guided by the trial's scientific goals, unmet needs, and potential to reduce participant burden.
Verification ensures the DHT accurately measures physical parameters, while validation confirms it reliably captures the desired clinical outcomes.
Conducting feasibility studies is essential to identify potential usability or compliance issues before full trial implementation.
Clear communication, training, and support plans for participants and sites are critical to the success of DHT-enabled trials.
Operational challenges, including DHT malfunctions, must be anticipated with robust management and mitigation plans.

Recommendations
Define Measurement Goals: Identify the scientific and patient-centered needs driving the decision to use DHTs.
Specification-Driven Selection: Tailor DHT selection based on technical performance, trial needs, and participant preferences, collaborating with manufacturers for transparency.
Verify and Validate Technologies: Conduct both verification and validation processes in controlled and real-world settings, focusing on the target population.
Pilot Feasibility Studies: Test the DHT in small-scale studies to assess usability, compliance, and real-world functionality.
Operational Planning: Develop detailed standard operating procedures (SOPs) for managing DHTs, addressing potential malfunctions, and supporting participants.

Regulatory Considerations
Regulatory status should not solely determine DHT selection; instead, focus on its fit-for-purpose performance in the trial context.
Maintain transparency with manufacturers to document DHT performance characteristics and limitations for regulatory submissions.
Validate endpoints and DHT data to meet evidentiary standards required by regulatory agencies.
Ensure clear roles and responsibilities for managing DHTs to align with regulatory compliance requirements.
Address interoperability, data privacy, and security concerns to adhere to ethical and legal standards in clinical trials.

Findings
The lack of standardization in vendor onboarding processes increases operational inefficiencies for sponsors and vendors.
Essential topics such as data security, quality management systems (QMS), and validation studies are under-addressed in ad hoc vendor assessments.
Cybersecurity and patient data privacy, especially compliance with GDPR, HIPAA, and global regulations, require enhanced focus during vendor evaluations.
Tailoring vendor assessments to specific trial requirements and patient populations is critical for effective implementation of digital health tools.
Greater collaboration between sponsors and vendors can improve operational alignment and mitigate risks during trials.

Recommendations
Utilize the 13 vendor assessment categories as a baseline for customizing questionnaires to meet specific project needs.
Establish standardized templates for evaluating data privacy, regulatory compliance, and patient-facing user experience.
Prioritize cybersecurity measures, including penetration testing, access management, and encryption standards, as a core assessment criterion.
Implement continuous feedback loops during vendor selection and onboarding to refine assessment processes and address emerging risks.
Encourage industry collaboration to evolve and expand the open-source framework based on practical implementation experiences.

Regulatory Considerations
Ensure all vendors adhere to relevant global standards, including 21 CFR Part 11, GDPR, and HIPAA, for data security and compliance.
Verify the regulatory status of medical devices and algorithms used in digital health solutions, including certifications such as ISO 13485 and IEC 62304.
Require documentation of informed consent processes and adherence to regional data protection regulations for patient data handling.
Align vendor capabilities with regulatory guidelines for clinical trial endpoints, emphasizing validation studies and clinical relevance.
Maintain transparent and audit-ready documentation for inspections and compliance verifications.

Findings
Key considerations include accuracy, precision, sampling frequency, resolution, and data processing. Metadata and communication protocols must ensure reliable and secure data collection.
Sponsors must assess data access, security, and compliance with regulations like 21 CFR Part 11. Clarity on manufacturer and sponsor responsibilities is essential for maintaining data integrity.
Safety risks should be minimized, especially for vulnerable populations. Specifications should ensure that devices pose minimal risks when used solely for data capture.
Human Factors: Acceptability, tolerability, and usability directly impact participant recruitment and adherence. Feasibility studies can help evaluate these factors in target populations.
Operational Considerations: Firmware updates, failure rates, battery life, and customer support must be planned for to avoid disruptions in data collection and participant experience.
Non-Performance Specifications: Cost and customer service must be accounted for, ensuring smooth implementation and user support.

Recommendations
Tailor DHT selection to trial needs, focusing on measurement accuracy, precision, and reliability.
Engage sponsors, technology manufacturers, and patient groups to align specifications with practical and clinical requirements.
Ensure compliance with regulatory standards and implement robust processes for secure data transfer and storage.
Test DHTs for usability, tolerability, and operational reliability in representative populations before full-scale implementation.
Develop clear protocols for managing firmware updates, device malfunctions, and participant support to ensure trial continuity.

Regulatory Considerations
Ensure all data management processes comply with regulatory requirements like 21 CFR Part 11 and align with FDA guidance.
Validate DHTs within the target population to confirm their reliability and relevance for the specific trial context.
Clearly communicate how data will be used and shared to maintain ethical standards and informed consent compliance.
Minimize participant risks by selecting devices with proven safety profiles and addressing potential vulnerabilities during feasibility testing.

Findings
Patient-centeredness is a key criterion, with higher importance assigned to endpoints identified by patients as meaningful.
The tool includes predefined weighting criteria to ensure that endpoints addressing unmet needs are prioritized.
A structured rating scale facilitates the comparison of novel endpoints across different therapeutic areas.
Digital measurement technologies, such as wearables and ePROs, are increasingly considered viable novel endpoints.
The tool provides a standardized approach to endpoint selection but requires user input to tailor scores to specific trial needs.

Recommendations
Clinical researchers should use the tool to systematically evaluate novel endpoints before incorporating them into study designs.
Weighting criteria should be adapted based on the specific therapeutic area and patient population to reflect real-world priorities.
Endpoint selection should incorporate regulatory and scientific considerations to ensure alignment with study objectives.
Digital health technologies should be leveraged where appropriate to support novel endpoint validation and implementation.
Stakeholder engagement, including patient advocacy groups, should be integrated into the endpoint selection process.

Regulatory Considerations
Novel endpoints should align with FDA and regulatory body expectations for evidence generation and validation.
The tool does not replace regulatory guidance but can serve as a structured framework for early-phase endpoint assessment.
Sponsors should document endpoint selection rationale in submissions to regulatory agencies.
Digital health endpoints should comply with data integrity and privacy regulations, including HIPAA and GDPR.
Ongoing validation and post-market evidence generation may be required for novel digital endpoints used in pivotal trials.

Findings
The selection of DHTs must align with the specific goals of the trial, focusing on unmet patient or scientific needs.
A specification-driven approach, rather than solely relying on a technology's regulatory status, ensures alignment with trial requirements.
Verification and validation are distinct processes; both are critical to confirm the reliability and clinical relevance of DHTs.
Pre-trial feasibility studies help identify potential issues, such as wear-time compliance or usability concerns, before full implementation.
DHTs can alter participant interactions and trial workflows, necessitating clear communication, training, and management plans.

Recommendations
Define Measurement Goals Before Selection: Ensure that the decision to use a DHT is based on unmet needs or the promise of reducing trial burdens.
Adopt a Specification-Driven Selection Process: Tailor DHT selection to technical performance, participant needs, and study-specific requirements.
Verify and Validate Technologies Thoroughly: Collaborate with manufacturers to ensure DHTs are tested in both controlled and real-world settings and validated for the target population.
Conduct Feasibility Studies: Test DHTs for tolerability, usability, and compliance within the specific trial context to identify and address issues early.
Prepare for Operational Challenges: Develop a robust management plan with standard operating procedures (SOPs) to address potential failures and ensure smooth implementation.

Regulatory Considerations
The regulatory status of a DHT should not solely drive its selection; instead, focus on its ability to meet trial specifications.
Ensure transparent collaboration with manufacturers to document DHT performance characteristics and limitations.
Validate endpoints and DHT data to align with evidentiary standards for regulatory submissions.
Use feasibility studies and SOPs to ensure that DHTs comply with regulatory and operational requirements during trials.