title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Connecticut School of Pharmacy, Storrs, CT 06102-5037, USA. ccolema@harthosp.org
authors.forename: Craig I
authors.initials: CI
authors.lastname: Coleman
authors.forename: Diana M
authors.initials: DM
authors.lastname: Sobieraj
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Marinucci
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009103:Multiple Sclerosis / Q000145:classification* / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D010919:Placebos; D026902:Potassium Channel Blockers / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012107:Research Design; D012189:Retrospective Studies; D013997:Time Factors; D016138:Walking / Q000502:physiology*; D055815:Young Adult
chemical_list: D010919:Placebos; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine