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Wearable inertial sensors can be used to monitor mobility in real-world settings over extended periods. Although these technologies are widely used in human movement research, they have not yet been qualified by drug regulatory agencies for their use in regulatory drug trials. This is because the first generation of these sensors was unreliable when used on slow-walking subjects. However, intense research in this area is now offering a new generation of algorithms to quantify Digital Mobility Outcomes so accurate they may be considered as biomarkers in regulatory drug trials. This perspective paper summarises the work in the Mobilise-D consortium around the regulatory qualification of the use of wearable sensors to quantify real-world mobility performance in patients affected by Parkinson's Disease. The paper describes the qualification strategy and both the technical and clinical validation plans, which have recently received highly supportive qualification advice from the European Medicines Agency. The scope is to provide detailed guidance for the preparation of similar qualification submissions to broaden the use of real-world mobility assessment in regulatory drug trials.

Introduction: Concern about falling is a prevalent worry among community-dwelling older adults and may contribute to a decline in physical and mental health. This study aimed to examine the association between mobility performance and concern about falling. Methods: Older adults aged 65 years and older, with Mini-Mental State Examination score ≥24, and ambulatory (with or without the assistive device) were included. Concern about falling was evaluated with Falls Efficacy Scale-International (FES-I) scores. Participants with high concern about falling were identified using the cutoff of FES-I ≥23. Participants' motor capacity was assessed in standardized walking tests under single- and dual-task conditions. Participants' mobility performance was measured based on a 48-h trunk accelerometry signal from a wearable pendant sensor. Results: No significant differences were observed at participant characteristics across groups with different levels of concern about falling (low: N = 64, age = 76.3 ± 7.2 years, female = 46%; high: N = 59, age = 79.3 ± 9.1 years, female = 47%), after propensity matching with BMI, age, depression, and cognition. With adjustment of motor capacity (stride velocity and stride length under single- and dual-task walking conditions), participants with high concern about falling had significantly poorer mobility performance than those with low concern about falling, including lower walking quantity (walking bouts, steps and time per day, and walking bout average, walking bout variability, and longest walking bout, p ≤ 0.013), and poorer daily-life gait (stride velocity and gait variability, p ≤ 0.023), and poorer walking quality (frontal gait symmetry, and trunk acceleration and velocity intensity, p ≤ 0.041). The selected mobility performance metrics (daily steps and frontal gait symmetry) could significantly contribute to identifying older adults with high concern about falling (p ≤ 0.042), having better model performance (p = 0.036) than only walking quantity (daily steps) with adjustment of confounding effects from the motor capacity (stride length under dual-task walking condition). Conclusion: There is an association between mobility performance and concern about falling in older adults. Mobility performance metrics can serve as predictors to identify older adults with high concern about falling, potentially providing digital biomarkers for clinicians to remotely track older adults' change of concern about falling via applications of remote patient monitoring. [ABSTRACT FROM AUTHOR]