title: Timed walk as primary outcome measure of treatment response in clinical trials for HTLV-1-associated myelopathy: a feasibility study.
abstract: BACKGROUND
  To advance the treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), randomised controlled therapeutic studies with appropriate and sensitive outcomes are reuired. One candidate outcome is the 10-metre walk test (10MWT), a patient-centred, simple and functional measure. To calculate sample size based on 10MWT as the primary outcome, variability within and between subjects must be known.
  
  
  METHODS
  Data on 10MWT from 76 patients with HAM/TSP were prospectively collected from four specialist centres in Brazil, Japan, USA and UK. Data, collected at two time points, 6 months apart, were log transformed and subjected to analysis of covariance.
  
  
  RESULTS
  Baseline mean (standard deviation = SD), median 10MWT were 23.5 (18.9), 16.3 s/10 m and at 6 months 24.9 (23.9), 16.4 s/10 m. The mean (SD) % increase in walk time was 5.74 % (28.2 %). After logarithmic transformation, the linear correlation between baseline and 24 weeks 10MWT wasr= 0.938. Using these data, it was determined that a randomised controlled trial with 30 participants per group would have 90 % power to detect a 19 % decrease or a 23 % increase in 10MWT.
  
  
  CONCLUSIONS
  The intra-patient variability of 10MWT is relatively small in HAM/TSP over 6 months. 10MWT is a feasible outcome measure for a clinical trial in HAM/TSP. To our knowledge, this is the first ever recommendation for the sample size required for trials in HAM/TSP patients.
authors.affiliation: Department of Biology, Centre for Immunology and Infection, Hull York Medical School, University of York, York, UK.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Martin
authors.affiliation: National Centre for Child Health and Development, National Medical Centre for Children and Mothers, Research Institute, Tokyo, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Inoue
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA.
authors.forename: Irene C M
authors.initials: IC
authors.lastname: Cortese
authors.affiliation: Advanced Laboratory of Public Health, Gonçalo Moniz Center, Fundação Oswaldo Cruz, Salvador, Bahia Brazil ; Bahian School of Medicine and Public Health (EBMSP), Salvador, Bahia Brazil.
authors.forename: Ramon
authors.initials: R
authors.lastname: de Almeida Kruschewsky
authors.affiliation: Department of Medicine, Section of Virology, Imperial College London, London, UK.
authors.forename: Adine
authors.initials: A
authors.lastname: Adonis
authors.affiliation: Advanced Laboratory of Public Health, Gonçalo Moniz Center, Fundação Oswaldo Cruz, Salvador, Bahia Brazil ; Bahian School of Medicine and Public Health (EBMSP), Salvador, Bahia Brazil.
authors.forename: Maria Fernanda Rios
authors.initials: MF
authors.lastname: Grassi
authors.affiliation: Advanced Laboratory of Public Health, Gonçalo Moniz Center, Fundação Oswaldo Cruz, Salvador, Bahia Brazil ; Bahian School of Medicine and Public Health (EBMSP), Salvador, Bahia Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
authors.affiliation: Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Department of Medicine, Section of Virology, Imperial College London, London, UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: Department of Health Sciences, University of York, York, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
keywords: 10-metre walk test; Clinical trial; HAM/TSP; HTLV; Myelopathy; Rare disease; Sample size