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
Sites must establish effective data privacy and security plans, especially considering regional and global regulations like GDPR.
Risk mitigation is critical, including plans to address unanticipated issues and potential patient disengagement due to technology challenges.
Budgeting and contracting often involve additional considerations, such as storage, training, and technical support requirements for connected devices.
Sites require adequate training to ensure staff and patients are prepared to use connected devices efficiently.
Companion applications or services often play an essential role in device functionality and data transmission.

Recommendations
Develop a clear plan for data pathways, including storage, security, and regulatory compliance.
Establish detailed risk mitigation and management strategies to handle unexpected challenges.
Ensure comprehensive training programs for site staff and patients to enhance device usability.
Incorporate device storage and resource allocation into budgeting and contracting processes.
Facilitate effective communication with sponsors and vendors to resolve operational and technical issues promptly.

Regulatory Considerations
Ensure connected devices comply with CFR 21, Part 11, and other relevant data collection and transmission regulations.
Understand and adhere to local and regional data privacy laws, such as GDPR, when managing patient data.
Verify that appropriate licenses and regulatory approvals are in place for device data transmission and storage.
Assess and address shipping and handling regulations for devices, ensuring safe and compliant transportation.

Findings
The field lacks a centralized, standardized database of validated digital health technologies, making it difficult for researchers and clinicians to select appropriate tools.
Non-wearable sensors and software applications are the most common types of DHTs, with 83% of ambient technologies categorized as software or applications.
Most DHTs focus on mild cognitive impairment (MCI) and early Alzheimer’s disease, with fewer technologies validated for moderate or severe dementia stages.
Uneven Distribution of Dementia Subtypes – The review identified a gap in DHT validation for frontotemporal dementia (FTD) and Lewy Body dementia, with Alzheimer’s disease being the predominant focus.

Recommendations
Expand and maintain an open-access database of validated DHTs to improve accessibility and standardization.
Increase research on digital measures applicable to moderate and severe stages of dementia, as well as non-Alzheimer’s dementias.
Promote integration of wearable, ambient, and cognitive assessment tools to generate comprehensive digital phenotypes of patients.
Follow clear guidelines for analytical and clinical validation of DHTs to improve regulatory acceptance and research applicability.
Conduct more usability and feasibility assessments, especially for populations with cognitive decline, to ensure DHTs are accessible and effective in real-world settings.

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
High rates of missing data in DHTs compared to traditional measures due to technical and software difficulties.
Practical issues such as unfamiliarity with platforms, connectivity difficulties, and lack of data visibility.
Specific technical issues like blocking of websites by firewalls and failed software updates leading to data loss.

Recommendations
Ensure appropriate workforce training for those involved in DHT deployment.
Conduct pilot evaluations in study sites to identify potential issues early.
Improve data visibility at both site and central coordinating team levels.
Implement robust feasibility testing before full-scale deployment.
Co-design DHTs with study staff and patients to enhance usability.

Regulatory Considerations
The FDA requires adequate training, education, and experience for those responsible for data capture using mobile technologies.
Ensure data integrity through oversight responsibilities as recommended by the Clinical Trials Transformation Initiative.

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
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
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
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
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.

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.