Factors affecting the measurement variability of SV95C in ambulant patients with Duchenne muscular dystrophy

Stride Velocity at the 95th Centile (SV95C) is a novel clinical outcome measure that is captured during normal daily living using wearable technology and represents the maximum ambulatory ability of a patient. SV95C is qualified by the European Medicines agency (EMA) for use as a secondary endpoint in pivotal studies in DMD, and is an important real-world functional endpoint complementary to the traditional in-clinic assessments such as the North Star Ambulatory Assessment scale and the Six Meter Walk Test. The Context of Use of SV95C as defined by EMA states that SV95C should be measured for at least 50h during normal daily living to yield an outcome variability that would render SV95C suitable for regulatory decision-making. Considering the increasing use of SV95C in drug development for DMD, it is critical to understand the most common drivers of endpoint variability. Using data from ActiLiège-NEXT, a prospective natural history study in ambulant patients with DMD designed to longitudinally characterise functional disease progression using multiple outcome measures, we evaluated the impact of the time of day, the day of the week as well as seasonal changes on the measurement variability of SV95C in ambulant patients with DMD. Specifically, SV95C will be computed for morning only (8am-12pm) and afternoon recording periods (2pm-6pm) and compared. A similar sensitivity analysis will be done for SV95C computed on weekdays (Monday-Friday) and weekend (Saturday-Sunday). The seasonal impact on the compliance and SV95C will be conducted on longitudinal data and adjusted by the geographical location of the patients, restricting to countries where the maximal temperature difference over the year exceeds 15° and maximal temperature does not exceed 30°C. This data provides important context to the factors that impact the measurement variability of SV95C and will be useful to inform clinical trial design in DMD, when using SV95C as an outcome measure of efficacy.