Real-world walking speed as a digital biomarker and outcome measure for clinical trials-a systematic review, regulatory status and future directions.

Introduction: Walking speed is a key measure of health and mobility across a wide range of diseases. Traditional gait assessments in clinical settings may not accurately reflect real-world mobility patterns. Wearable sensors offer an ecologically valid alternative by capturing every movement in daily life, but there are few robust, validated reports. We aimed to identify evidence on real-world gait speed measurements that have received or are seeking regulatory approval from agencies such as the European Medicines Agency and the U.S. Food and Drug Administration. Method: We conducted a systematic review following a comprehensive search strategy using the Ovid platform, guided by pre-defined selection criteria and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We also manually searched the websites of key regulatory agencies and the ClinicalTrials.gov database. Results: Our search identified 503 records, of which 10 met the inclusion criteria. Most studies were part of large-scale initiatives, including the qualification of the Stride Velocity 95th Centile and the MOBILISE-D project. No device or outcome measure that assesses walking speed in real-world conditions has been fully validated by the FDA. We found four letters of intent on the FDA website related to this concept. One outcome, the 95th centile of stride velocity, has been approved by the EMA as a primary endpoint for assessing ambulant patients with Duchenne Muscular Dystrophy. Conclusion: Despite the potential of wearable devices to enhance drug development and clinical decision-making, real-world walking speed remains insufficiently validated across most conditions because data is missing. The widespread adoption of digital outcomes to assess ambulation will require extensive validation efforts, regulatory pathway adaptations, and improved standardization of devices, algorithms, and study methodologies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633578, PROSPERO CRD42025633578.