Supplementary Material for: Real World Postural Transitions as Biomarkers of Functional Impairment in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that impairs daily functioning and results in premature death. Current clinical assessments are widely used for characterizing functional impairment but have limitations due to their subjective and effort-based nature and because they only capture a snapshot of symptoms at a single point in time. Digital health technologies, such as wearable devices, allow continuous collection of movement and physiological data during daily life and could provide objective measures of the impact of DMD symptoms on daily functioning. For example, measurement of the 95th centile of stride velocity has recently gained endorsement by European regulators as an endpoint for evaluating functional changes in DMD, but the use of wearables for this purpose is just beginning. In this study, we present preliminary investigations of candidate digital biomarkers of functional impairment using real-world data, and further explore the relationships between these parameters and established clinical assessments. We found nine candidate biomarkers for detecting DMD-related functional impairment, all exhibiting large to very large effect sizes in our sample of 14 boys with DMD and matched controls (9 DMD, 5 control, age 4-12 years). Each candidate biomarker was moderately or strongly associated with clinical measures of function in DMD. Six of the biomarkers are novel and/or understudied in DMD including objective measures of gait acceleration and variability; postural control immediately before and after a postural transition; and the smoothness of postural transitions. Notably, postural transition measures were more sensitive to DMD-related impairment than gait, activity, and cardiac measures. These results suggest that the quality of postural transitions could serve as a sensitive and objective measure of functional impairment in DMD and point toward the need for further exploration of these measures in DMD.

杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）是一种进行性神经肌肉疾病，会损害日常功能并导致过早死亡。当前的临床评估被广泛用于描述功能障碍，但由于其主观性、依赖努力程度的本质，以及仅能捕捉单一时间点症状的快照，因此存在局限性。数字健康技术（如可穿戴设备）能够在日常生活中持续收集运动和生理数据，并可为DMD症状对日常功能的影响提供客观测量指标。例如，步速第95百分位数的测量最近已获得欧洲监管机构的认可，作为评估DMD功能变化的终点指标，但使用可穿戴设备实现这一目的的研究才刚刚起步。本研究利用真实世界数据，对功能障碍的候选数字生物标志物（digital biomarkers）进行了初步调查，并进一步探索了这些参数与已确立的临床评估之间的关系。我们发现了9个用于检测DMD相关功能障碍的候选生物标志物，在14名DMD男孩和匹配对照（9名DMD患者，5名对照，年龄4-12岁）的样本中，所有标志物均表现出大到极大的效应量。每个候选生物标志物都与DMD的临床功能测量指标存在中度或强相关性。其中6个生物标志物在DMD研究中是新颖的和/或研究不足的，包括步态加速度和变异性的客观测量指标、姿势转换前后即刻的姿势控制，以及姿势转换的平滑度。值得注意的是，姿势转换测量指标对DMD相关障碍的敏感性高于步态、活动和心脏测量指标。这些结果表明，姿势转换的质量可作为DMD功能障碍的敏感且客观的测量指标，并提示需要在DMD研究中进一步探索这些指标。