Patient-centered Development of a Composite Digital Endpoint of Mobility and Pain for Knee Osteoarthritis

Knee osteoarthritis (OA) is a predominant cause of chronic pain and walking impairments in middle-aged and older adults. The heterogeneity of OA, the discordance between structural changes and symptomatic presentations, and the reliance on outcome measures that inadequately capture clinically meaningful improvements have collectively hindered the development of effective therapies to manage OA-related pain and disability. Given that the patient experience with knee OA is primarily characterized by concurrent pain and walking limitations, this project aims to develop a novel composite digital endpoint tailored to integrate synchronous digital measures of pain and gait patterns in daily life. This endpoint has the potential to be more clinically meaningful, responsive, and ecologically valid than currently available measures. The project will employ a patient-centered approach within the Verification, Analytical Validation, Usability Validation, and Clinical Validation (V3+) framework. During the UG3 phase, the project will focus on technology selection and development, analytical validation (n = 60), and initial usability validation. The UH3 phase will involve clinical validation using data from an existing large-scale cohort study (the Multicenter Osteoarthritis Study, MOST; n ~ 2000) and a new placebo-controlled randomized clinical trial (n = 140) of intra-articular corticosteroid therapy in individuals with knee OA. Patient experts and stakeholders will be involved from the outset to refine the concept of interest and context of use, ensuring that the measures incorporated into the endpoint are meaningful and relevant to the patient experience. The overarching goal is to achieve regulatory approval of the digital endpoint. The project team comprises specialists in biomechanics, OA clinical trials, epidemiology, pain measurement and neurobiology, advanced statistics, machine learning, and patient engagement methodologies. Support is provided by key stakeholders, including prominent OA advocacy and research organizations, digital health entities, leading scientists, and industry sponsors. A validated composite digital endpoint integrating pain and gait in daily life, which reflects patient priorities, could facilitate shorter, more efficient clinical trials, reduce costs and participant burden, and enable decentralized study designs to advance novel therapeutic strategies for knee OA.