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

Abstract

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 × 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.

Key words::

• Dalfampridine
• Minimally important clinical difference
• Multiple sclerosis
• Timed 25-Foot Walk

Transparency

Declaration of funding

This study was funded by Acorda Therapeutics. The authors of this report are entirely responsible for its content.

Declaration of financial/other relationships

C.I.C. has disclosed that he has received grant funding to conduct research and honoraria as an advisory board member for Acorda Therapeutics. L.N.M. has disclosed that he is an employee of Acorda Therapeutics. D.M.S. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to thank the biostatistics group at Acorda Therapeutics, Inc. for their assistance with statistical analysis, and Dr Risa Torkin and Ms Laura Williamson at Acorda Therapeutics for their editorial assistance. No funding for their assistance was provided.