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.

Adaptive and robust smartphone-based step detection in multiple sclerosis

Background: Many attempts to validate gait pipelines that process sensor data to detect gait events have focused on the detection of initial contacts only in supervised settings using a single sensor. Objective: To evaluate the performance of a gait pipeline in detecting initial/final contacts using a step detection algorithm adaptive to different test settings, smartphone wear locations, and gait impairment levels. Methods: In GaitLab (ISRCTN15993728), healthy controls (HC) and people with multiple sclerosis (PwMS; Expanded Disability Status Scale 0.0-6.5) performed supervised Two-Minute Walk Test [2MWT] (structured in-lab overground and treadmill 2MWT) during two on-site visits carrying six smartphones and unsupervised walking activities (structured and unstructured real-world walking) daily for 10-14 days using a single smartphone. Reference gait data were collected with a motion capture system or Gait Up sensors. The pipeline's performance in detecting initial/final contacts was evaluated through F1 scores and absolute temporal error with respect to reference measurement systems. Results: We studied 35 HC and 93 PwMS. Initial/final contacts were accurately detected across all smartphone wear locations. Median F1 scores for initial/final contacts on in-lab 2MWT were >=98.2%/96.5% in HC and >=98.5%/97.7% in PwMS. F1 scores remained high on structured (HC: 100% [0.3%]/100% [0.2%]; PwMS: 99.5% [1.9%]/99.4% [2.5%]) and unstructured real-world walking (HC: 97.8% [2.6%]/97.8% [2.8%]; PwMS: 94.4% [6.2%]/94.0% [6.5%]). Median temporal errors were <=0.08 s. Neither age, sex, disease severity, walking aid use, nor setting (outdoor/indoor) impacted pipeline performance (all p>0.05). Conclusion: This gait pipeline accurately and consistently detects initial and final contacts in PwMS across different smartphone locations and environments, highlighting its potential for real-world gait assessment.