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
The adoption of BYOD in clinical trials has been accelerated by the COVID-19 pandemic and supportive regulatory guidance, which now recognize it as an acceptable means for remote data collection. Studies have shown high measure completion and equivalent data quality between provisioned devices and BYOD, supporting its use in diverse patient populations. Key challenges to BYOD implementation include ensuring data equivalence across a wide variety of personal devices, managing participant technical support, and addressing data privacy and security concerns. The choice between native apps and web-based solutions involves trade-offs in usability, data security, and operational complexity.

Recommendations
Sponsors should develop a clear BYOD strategy that considers the target patient population, the complexity of the required data collection, and the global regulatory landscape. A robust training and support plan is essential for both participants and site staff to ensure proper device use and troubleshooting. Sponsors should work with technology vendors to ensure their platforms are user-friendly, secure, and capable of handling data from a variety of devices. It is crucial to establish clear communication channels for participants to report technical issues and receive timely assistance.

Regulatory Considerations
Both the FDA and EMA have issued guidance that supports the use of BYOD in clinical trials, provided that data integrity, security, and privacy are maintained. Sponsors must be able to demonstrate the equivalence of data collected via BYOD with data from provisioned devices. All BYOD solutions must comply with relevant data protection regulations, such as GDPR and HIPAA. The regulatory submission should include a clear description of the BYOD strategy and a justification for its use in the trial.

Findings
Vendor selection should assess 13 categories, including General organizational operation and products, Quality Management Principles, Practices of product or service design, Device supply and provisioning, Account provisioning, Study specific materials, Live trial support, Trial closeout activities, Data handling/processing and data flow (GDPs), Device and Data (sensors + raw data) algorithm accessibility, Interoperability/Integration, Validation/Clinical Relevance/standard of documentation, and Cybersecurity. Key aspects to consider include having Validation and verification of the device and algorithm in place, ability to support multiple countries, an established quality management system. Vendors must assure maintained data integrity and quality, and provide evidence of Good Clinical Practice (GCP) compliance. Robust practices in Good manufacturing practice, Good product development practices (for hardware and software, including software lifecycle documentation), and Good scientific practices are required.

Recommendations
Sponsors should engage with vendors early in study design to tailor the technology capabilities and data requirements to patient needs and preferences. Vendors are typically responsible for device verification and analytical validation, but collaboration with sponsors and other stakeholders on clinical validation is beneficial to establish validation thresholds, specific needs of target clinical populations, and acceptability and usability of the technology. Sponsors should enable a feedback loop from patients back to vendors to improve technology for specific target populations. Sponsors or researchers should prioritize access to high-fidelity and sensor-level data to enable novel research and assessment of additional health aspects. Specific inquiries for vendors should cover: measurements offered (Accelerometry output for scratch detection, sleep measurement, environmental factors, and vitals), device material and safety testing (irritation/sensitization), usability/patient burden (e.g., disturbance during sleep), and applicability to Pediatrics, different ethnic groups, and different skin colors.

Regulatory Considerations
For software development, vendors should document and monitor the software lifecycle for quality, and demonstrate that algorithms have been tested with appropriate datasets. Assurances of GCP compliance are necessary. Vendors should demonstrate that their manufacturing practices ensure devices from different batches provide the same result measurements. Collaboration on clinical validation with sponsors and other stakeholders is a key component to generate the necessary evidence for the Validation/Clinical Relevance/standard of documentation requirement for regulatory purposes.

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
The CardiacSense PPG device can reliably detect heart rate in various situations, but noise suppression during activity remains a challenge.
The study did not directly address the device's ability to detect atrial fibrillation in ambulatory patients, indicating a gap in current research.
Further studies are needed to confirm the device's effectiveness in detecting AF during ambulatory conditions.

Recommendations
Improve noise suppression technology to enhance the device's accuracy during motion.
Conduct further studies to validate the device's ability to detect atrial fibrillation in ambulatory patients.
Continue research to address the limitations identified in the current study.

Regulatory Considerations
Adherence to FDA guidance for new medical device applications is crucial.
Ensure compliance with regulatory standards for digital health technologies.

Findings
The term "clinically validated" is frequently used in marketing but lacks a clear, standardized meaning, leading to confusion. The rapid development of BioMeTs has outpaced the creation of systematic, evidence-based evaluation frameworks, creating a knowledge gap. Existing validation standards from software, hardware, and clinical development are often applied in silos and are not fully sufficient for modern BioMeTs. Evaluating a BioMeT requires assessing the entire "data supply chain," from the sensor hardware (verification) and data processing algorithms (analytical validation) to its performance against a meaningful clinical concept (clinical validation).

Recommendations
The digital medicine field should adopt the V3 (Verification, Analytical Validation, Clinical Validation) framework as a foundational evaluation standard for all BioMeTs to ensure they are fit-for-purpose. Technology manufacturers, clinical trial sponsors, and researchers should transparently report their V3 processes and results to overcome "black box" approaches and build a common evidence base. Technology manufacturers are primarily responsible for verification , while the entity developing the algorithm (e.g., manufacturer or sponsor) is responsible for analytical validation. The sponsor or clinical team using the BioMeT for a specific purpose is responsible for clinical validation in that context of use.

Regulatory Considerations
The V3 framework is designed to inform and align with the current regulatory landscape, although the regulatory pathway for a specific BioMeT depends on its intended use and marketing claims, not just its underlying technology. The 21st Century Cures Act and the concept of Software as a Medical Device (SaMD) have created new regulatory paradigms that decouple software from specific hardware. BioMeTs used to support drug development may follow a tool qualification pathway, while those marketed as standalone medical devices are subject to device clearance or approval processes. Stakeholders should engage with regulatory agencies early to determine appropriate validation approaches.

Findings
Concerns about data accuracy, particularly variability in measurements across different age groups and devices.
Issues with data provenance, as raw data from wearables are often transformed and filtered before storage, making comprehensive analysis difficult.
Regulatory challenges due to lack of specific FDA guidance for clinical trials using wearables and mobile devices.

Recommendations
Improve data accuracy through standardized approaches and expert recommendations.
Enhance data provenance by developing methods to trace data lineage and ensure transparency in data processing.
Develop specific FDA guidance for the use of wearables and mobile devices in clinical trials.
Implement robust security measures to protect data integrity and privacy.
Follow the ePRO Consortium's recommendations for device suitability in clinical trials.

Regulatory Considerations
The need for FDA guidance specific to clinical trials using mHealth technologies.
Sponsors' responsibility to validate the reliability of mHealth technology in capturing and transmitting data.
Security vulnerabilities in devices, necessitating adherence to privacy standards and robust security protocols.

Findings
There is uncertainty regarding the regulatory acceptability of data collected from wearable devices.
There is a lack of specific regulatory guidance on implementing wearables in clinical trial protocols.
The need for evidence to demonstrate the appropriateness and clinical relevance of new endpoints derived from wearable data.

Recommendations
Identify essential properties of fit-for-purpose wearables and propose evidence needed to support their use.
Extend the FDA's definition of a PerfO to include unsupervised settings.
Ensure that any wearable device adheres to basic properties important to clinical trials, such as source data control, traceability, and security.
Provide evidence supporting the reliability, validity, and interpretability of data generated by wearable devices.

Regulatory Considerations
Market clearance/certification is not a requirement for device selection in clinical trials if evidentiary considerations are satisfied.
The need for a robust framework for adopting wearables in regulatory trials despite the lack of specific guidance.
The evidence needed to support a device and its endpoint depends on the ultimate use of the endpoint.

Findings
Significant changes to device design, basic principles of operation, or clinical protocols require prior FDA approval through an IDE supplement.
Developmental changes made in response to information gathered during a clinical investigation and minor protocol modifications may be implemented with a 5-day notice if they meet specified criteria.
Changes that do not affect the scientific soundness of the investigational plan, risk-benefit profile, or participant rights and safety can be reported in an IDE annual progress report.
Sponsors are responsible for conducting risk analyses and using credible information, such as design controls or peer-reviewed literature, to justify changes.
The FDA reserves the right to question the appropriateness of changes implemented without prior approval.

Recommendations
Conduct a risk analysis for any device or protocol change and ensure no new risks are introduced.
Use credible information, such as design control data, preclinical testing, or published literature, to assess the impact of proposed changes.
Submit IDE supplements for significant design or protocol changes that affect the validity of study data, participant safety, or investigational plan soundness.
Use the 5-day notice process for developmental changes that improve safety or effectiveness but do not represent significant design changes.
Report minor investigational plan changes, such as clarifying instructions or updating IRB information, in the IDE annual progress report.

Regulatory Considerations
IDE Supplements: Required for significant changes to device design, manufacturing processes, or protocols that may impact study data validity, risk-benefit analysis, or participant safety.
5-Day Notices: Applicable for developmental changes and protocol modifications that do not introduce new risks or affect study soundness.
Annual Progress Reports: Used for minor changes, including clarifications to instructions for use or informed consent materials, provided they do not affect participant safety or study data integrity.
FDA reserves the right to reclassify changes implemented under a 5-day notice or annual report if they determine the changes required prior approval.