Minimally important clinical difference of the Timed 25-Foot Walk Test: results from a randomized controlled trial in patients with multiple sclerosis

Background: Limited data define what constitutes a clinically significant change on the Timed 25-Foot Walk (T25FW) in multiple sclerosis (MS); however, most studies suggest a value of >= 20%. Analyses were undertaken to estimate the minimally important clinical difference (MICD) in walking speed as measured by the T25FW in patients with MS. Methods: Data from MS-F203, a randomized trial of dalfampridine extended release tablets, 10 mg twice daily (prolonged-release/sustained-release fampridine outside the US) in patients with MS, were used to calculate the MICD, as an absolute and percentage value, for the T25FW test. Both anchor- (using the Clinician Global Impression [CGI]) and distribution-based (2.77 X standard error of measurement or 0.50 standard deviation units) approaches were used. Using the anchor-based estimations, the proportion of patients in the dalfampridine and placebo groups achieving at least a MICD in MS-F203 was determined. Results: A correlation between change in T25FW speed during and CGI at the end of double-blind period was found (Spearman r = -0.39, p<0.0001). Irrespective of treatment group, participants categorized 'minimally improved' by the CGI had a mean improvement in T25FW speed of >= 0.36 feet/second or a 17.2% relative change from an average baseline walking speed of 2.1 feet/second (effect size = 0.49); values representing MICDs. MICD estimates of 0.35 and 0.37 feet/second were generated using distribution-based approaches. In MS-F203, a greater proportion of patients receiving dalfampridine achieved >= 0.36 feet/second (12/72 vs. 78/224, p = 0.007) and a 17.2% (11/72 vs. 87/224, p = 0.0005) improvement in T25FW speed compared to placebo. Limitations: MICD estimates from this analysis may not apply to patients with different disease characteristics from MS-F203. A different anchor may result in a different MICD estimation. Conclusion: Our MICD estimate for an improvement in T25FW is close to previous estimates of 20% change. Dalfampridine may improve walking speed in a considerable proportion of patients by a clinically relevant amount.