A wearable sensor that measures stride velocity has been validated as a primary endpoint for clinical trials involving ambulatory patients with Duchenne Muscular Dystrophy (DMD). This digital health technology (DHT) offers a more sensitive and objective measure of disease progression compared to traditional clinical assessments, potentially accelerating drug development and reducing the burden on patients.
Analytical and Clinical Validation
Analytical validation of the wearable sensor showed high accuracy in stride detection. In healthy participants, the device detected 98.7% of strides in a motion capture setting. Among DMD patients, the difference in 6-minute Walk Distance (6MWD) measured by physical therapists versus the wearable was minimal (0.75 ± 8.9 m, or 0.24%).
Clinical validation demonstrated strong convergent validity. SV95C, the stride velocity 95th centile, significantly correlated with 6MWD, NSAA (North Star Ambulatory Assessment), and 4SC (4-Stair Climb) at baseline and multiple time points (3, 6, 9, and 12 months), indicating a close relationship with established clinical outcomes.
Test-retest reliability was excellent, with an intraclass correlation coefficient (ICC) of 0.970 (95% CI: 0.947-0.983) for SV95C measurements taken one month apart. This reliability was comparable to or better than that reported for 6MWD (ICC 0.75-0.92) and NSAA (ICC 0.86-0.98).
Sensitivity to Change
Longitudinal data revealed that SV95C is more sensitive to disease progression than traditional measures. In DMD patients on a stable corticosteroid regimen, the median relative change from baseline in SV95C was -2.500% at 3 months (p = 0.0019), -3.094% at 6 months (p = 0.0009), -5.155% at 9 months (p = 0.0005), and -12.842% at 12 months (p = 0.0003). Significant changes in 6MWD and NSAA were only detected after 9 months.
These results suggest that SV95C can detect disease progression earlier than 6MWD and NSAA, potentially enabling shorter clinical trials with fewer participants. A change of at least -0.10 m/s in SV95C is considered beyond measurement error, while a change of -0.10 to -0.20 m/s is considered clinically meaningful.
Regulatory Qualification and Implications
The European Medicines Agency (EMA) has qualified SV95C as a primary endpoint for clinical trials in ambulatory DMD patients. This marks the first regulatory qualification of a digital outcome measure as a primary endpoint for any indication.
This qualification sets a precedent for the acceptance of data acquired with DHTs and digital endpoints for drug approval purposes. The US Food and Drug Administration (FDA) Drug Development Tool qualification procedure is ongoing.
Patient and Clinician Perspectives
Surveys of patients and caregivers indicated that limiting falls, self-transfer ability, and walking ability are highly important. Patients expressed a preference for using wearable devices in real-world settings over clinic-based assessments. Over 70% of respondents felt that a wearable device would make trial participation more attractive, and most were willing to wear it continuously throughout a trial.
Clinicians also acknowledged the value of measuring maximal ambulation speed to evaluate changes in walking abilities and the utility of wearable devices for detecting these changes.
Challenges and Future Directions
While wearable technologies offer numerous benefits, challenges remain regarding technical reliability, data privacy, and patient compliance. Proper design, testing, and quality control are essential to minimize technical failures. Patient and caregiver education is crucial for ensuring robust compliance.
Ongoing research aims to develop and validate disease-specific variables in other conditions, including facioscapulohumeral muscular dystrophy, spinal muscular atrophy, multiple sclerosis, and Angelman syndrome.
