Construct validity of the timed 25-foot walk and robustness of clinical benchmarks in multiple sclerosis: exploratory analyses of TEAMS study.

Background: The Timed 25-Foot Walk (T25-FW) is a widely used performance measure of ambulatory disability in multiple sclerosis (MS). Fewer studies have examined its construct validity relative to patient-reported outcomes or assessed robustness of previously proposed benchmarks in large cohorts. Objective: To examine the construct validity of T25-FW using patient-reported health outcomes and to evaluate robustness of previously proposed clinical benchmarks. Methods: Baseline data from 759 participants with MS enrolled in Tele-Exercise and Multiple Sclerosis (TEAMS) trial were analyzed. Associations between T25-FW performance and Short Form-36 physical functioning and emotional well-being subscales were evaluated using Spearman correlations. Previously proposed clinical benchmarks (<6 s, 6-7.99 s, ≥8 s) were evaluated in relation to patient-reported outcomes. Additional exploratory analyses included median-based anchors, segmented regression, and ROC methods. Results: T25-FW performance showed a strong association with SF-36 physical functioning (ρ = -0.71), which remained significant after adjustment for demographic factors (ρ = -0.39). In contrast, correlations with SF-36 emotional well-being were negligible. Stratification by established T25-FW clinical benchmarks demonstrated a clear gradient in physical functioning, with highest scores among participants completing the test in <6 s and lowest among those requiring ≥8 s or unable to perform test. Candidate cut points derived from multiple analytical approaches clustered around similar walking-time ranges and demonstrated consistent associations with physical functioning. Conclusions: The T25-FW demonstrates strong construct validity with patient-reported physical functioning and clear divergent validity from emotional well-being. Findings support robustness of proposed T25-FW benchmark categories and reinforce the utility of T25-FW as measure of ambulatory disability in MS.Clinical trial registration: ClinicalTrials.gov Identifier: NCT03117881.