Establishing the Minimal Clinically Important Difference (MCID) for Smartphone-Derived Gait Measures in Multiple Sclerosis

Background: Digital health technologies allow for frequent, remote gait monitoring in people with multiple sclerosis (MS). However, to differentiate daily variability from actual disease progression in longitudinal data, established minimal clinically important differences (MCID) are required. Currently, there is limited literature defining these thresholds for digital gait metrics. Objective: To establish MCIDs for digital gait measures reflecting progression in MS. Methods: Digital gait measures were captured via daily, remote, smartphone-based Two-Minute Walk Tests in CONSONANCE (NCT03523858), a phase 3b study of ocrelizumab in progressive MS. Using an anchor-based approach, median changes from baseline at Week 96 on digital gait measures were computed for patients showing clinically meaningful worsening on either Timed 25-Foot Walk, Ambulation Score, Expanded Disability Status Scale, or 12-item Multiple Sclerosis Walking Scale. These changes were subsequently triangulated to derive the MCID estimates. Results: 243 patients with progressive MS (female: n=125 (51%); mean [SD] age: 49.3 [9.3]; mean [SD] EDSS: 4.8 [1.4]) had digital gait data available at baseline and Week 96. Median changes were generally consistent across anchors. Triangulated MCIDs are: Step Velocity = -0.16 m/s, Step Velocity Scaled to Walking Time = -0.18 m/s, Step Duration = 0.06 s, Step Length = -0.07 m, Total Number of Steps = -28, and Total Distance Walked = -24 m. Conclusion: These MCIDs provide a framework for interpreting meaningful gait changes and integrating digital measures into MS outcome evaluation. Beyond facilitating novel clinical trial endpoints to evaluate treatment efficacy, they enable objective, real-world monitoring to advance personalized patient care.