Findings
SV95C provides a reliable and sensitive measure of maximal ambulation, addressing limitations of traditional assessments like the 6MWT.
Real-world data collection via wearable devices enhances accuracy and reflects true ambulatory capabilities.
Longitudinal studies confirmed SV95C's ability to detect disease progression and response to corticosteroid treatments.
Correlations with existing clinical outcome assessments (6MWT, NSAA, and 4SC) validate SV95C’s construct validity.
Patients and caregivers support the use of wearable devices in clinical trials, emphasizing reduced burden and improved trial attractiveness.

Recommendations
Use SV95C as a primary endpoint in DMD clinical trials to monitor maximal stride velocity in real-world conditions.
Incorporate SV95C alongside traditional endpoints to ensure comprehensive assessment of therapeutic efficacy.
Establish training protocols for patients and caregivers to optimize compliance with device usage.
Expand normative data for SV95C in younger and more diverse patient populations.
Conduct further research on meaningful change thresholds (MCTs) to refine clinical relevance.

Regulatory Considerations
Ensure SV95C is included as a primary endpoint with supporting secondary endpoints (e.g., muscle strength assessments) for consistency.
Validate wearable devices used for SV95C measurement to meet regulatory standards for accuracy and reliability.
Address variability and standardize protocols for data collection to ensure regulatory compliance.
Collect additional longitudinal data to strengthen the predictive value of SV95C for regulatory submissions.
Incorporate privacy and data security measures to comply with data protection regulations, including anonymization and encryption.

Findings
Digitally-derived endpoints must align with trial goals, reflect the concept of interest (COI), and demonstrate clinical relevance.
Validation involves both verification of the digital tool's performance and ensuring the endpoint measures what it claims to measure.
Early-phase trials should assess usability, tolerability, and data privacy to ensure tools are operationally feasible for the intended population.
Regulatory alignment on endpoints, including their ability to demonstrate meaningful change, is critical before pivotal trials.
Statistical analysis plans must account for the unique aspects of digital endpoints, such as data quality and missing data considerations.

Recommendations
Define target populations and meaningful aspects of health (MAH) early in development to guide endpoint selection.
Conduct gap assessments of existing endpoints and propose clinically meaningful differences for patient outcomes.
Validate digital tools through verification (e.g., accuracy, reliability) and usability studies specific to the intended population.
Engage with regulators to align endpoints with evidentiary requirements for pivotal trials and label claims.
Prepare statistical plans and supporting evidence to justify the inclusion of digitally-derived endpoints in pivotal trials.

Regulatory Considerations
Verification and validation of DHTs should meet FDA and EMA standards, ensuring endpoints are fit-for-purpose and clinically relevant.
Align endpoints with regulatory requirements, demonstrating meaningful change that reflects treatment benefit.
Compile evidence of clinical validation, including how endpoints detect meaningful changes during treatment.
Address privacy, scalability, and operational feasibility to meet regulatory expectations for pivotal trials.
Consult regulatory guidance documents, such as FDA’s draft guidance on DHTs for remote data acquisition and EMA's methodologies for drug development.

Findings
Patient-Reported Outcome (PRO) instruments are a type of Clinical Outcome Assessment that provides valid scientific evidence for regulatory and healthcare decision-making regarding medical devices. The FDA encourages the integration of patient perspectives throughout the Total Product Lifecycle (TPLC). PRO instruments can be used to measure the effects of a medical intervention, including the impact on patient well-being and Health-Related Quality of Life (HRQOL). The validity evidence needed to support a PRO instrument's use is determined by its specific Context of Use (COU) and role (e.g., primary, secondary endpoint) in the clinical study protocol. To be "fit-for-purpose," a PRO instrument must measure a Concept of Interest (COI) that is meaningful to patients and whose measurement is supported by evidence that is consistent with the intended use population.

Recommendations
Sponsors should establish and clearly define the Concept of Interest (COI) the PRO instrument is intended to capture. It is recommended that sponsors clearly identify the role of the PRO (e.g., primary, secondary, effectiveness, safety) in the clinical study protocol and statistical analysis plan. The development or modification of PRO instruments should measure concepts important to patients to reduce unnecessary patient burden and ensure the outcomes are relevant to a patient's daily lived experience. Cognitive interviews should be conducted to ensure the instrument's instructions and items are understandable to the intended use population, including patients with limited English language proficiency. Sponsors are encouraged to leverage existing PRO instruments (by using them as-is, modifying, or adapting) as a least burdensome approach to take advantage of existing validity evidence. Alternative approaches, such as using Real-World Data (RWD) platforms or conducting parallel development work during clinical studies, are encouraged to efficiently generate validity evidence.

Regulatory Considerations
The FDA encourages sponsors to engage with the Agency regarding the relevance and suitability of a proposed PRO instrument early in the development process, prior to the Investigational Device Exemption (IDE) submission or pivotal study. The Q-Submission program is the recommended pathway for sponsors to obtain feedback from the FDA regarding cognitive interview approaches and the modification or adaptation of existing instruments. The Agency uses the fit-for-purpose concept as a flexible approach to determine the validity evidence needed for a PRO instrument's specified use for a regulatory purpose. The use of PRO instruments that have been qualified under the Medical Device Development Tools (MDDT) program is encouraged. Sponsors should prospectively specify the intent to generate validity evidence in the clinical study protocol and statistical analysis plan, even if the evidence will only support future studies.

Findings
SV95C is a promising secondary endpoint for evaluating drug efficacy in ambulant DMD patients aged 5 and above.
The wearable device provides continuous, objective measurements, overcoming the limitations of episodic tests like the 6MWT, which are influenced by patient motivation and clinic settings.
The system demonstrates strong correlation with existing endpoints (e.g., 6MWT, NSAA), but further longitudinal data are needed to establish it as a primary endpoint.
Variability in SV95C decreases significantly with longer recording durations, with 180 hours recommended as optimal.
Combining SV95C with other gait variables could enhance sensitivity to change and predictive capacity for disease progression.

Findings
SV95C is a promising secondary endpoint for evaluating drug efficacy in ambulant DMD patients aged 5 and above.
The wearable device provides continuous, objective measurements, overcoming the limitations of episodic tests like the 6MWT, which are influenced by patient motivation and clinic settings.
The system demonstrates strong correlation with existing endpoints (e.g., 6MWT, NSAA), but further longitudinal data are needed to establish it as a primary endpoint.
Variability in SV95C decreases significantly with longer recording durations, with 180 hours recommended as optimal.
Combining SV95C with other gait variables could enhance sensitivity to change and predictive capacity for disease progression.

Regulatory Considerations
SV95C requires validation in conjunction with traditional endpoints (e.g., 6MWT, NSAA) to support regulatory submissions.
Device and software updates must be accompanied by bridging data to ensure consistent measurement properties.
Patient data privacy and security must comply with regulatory standards, including encryption of recorded data and limited researcher access to identifiers.
Future applications of SV95C as a primary endpoint will require expanded normative datasets and stronger correlation with clinically meaningful outcomes.
Incorporate SV95C in early-phase exploratory trials to build a robust case for its clinical relevance in pivotal studies.