title: Sample sizes for lesion magnetisation transfer ratio outcomes in remyelination trials for multiple sclerosis.
abstract: BACKGROUND
  Enhancing remyelination in MS might improve function and protect axons from future damage. Lesion magnetisation transfer ratio (MTR) is sensitive to myelin content, and may be a useful measure for trials evaluating potential remyelinating agents.
  
  
  OBJECTIVE
  Estimating sample sizes required for a parallel group, placebo-controlled trial in MS using change in mean MTR of all T2lesions as a primary outcome measure.
  
  
  METHODS
  The primary sample size calculation was derived from data from a natural history study of relapsing remitting MS (n=18). The MTR values observed in demyelinated and remyelinated lesions in an ex vivo study were used to estimate the effect of remyelination on lesion MTR. The ex vivo data were also used to independently calculate sample sizes in order to inform the robustness of the in vivo estimates.
  
  
  RESULTS
  Calculations suggest that 30% remyelination of T2 lesions could be detected with 80% power in 38 (95% confidence interval 12-96) patients per arm based on the in vivo data, and in 66 per arm based on the ex vivo data.
  
  
  CONCLUSIONS
  The sample sizes derived are in a range that makes MTR a feasible outcome measure for proof-of-concept trials of putative therapies achieving remyelination in MS lesions.
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK; Medical Statistics Department, London School of Hygiene & Tropical Medicine (LSHTM), Keppel Street, London WC1E 7HT, UK. Electronic address: daniel.altmann@lshtm.ac.uk.
authors: D R
authors: DR
authors: Altmann
authors: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Electronic address: tombutton@cantab.net.
authors: T
authors: T
authors: Button
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK; Blizard Institute, Centre for Neuroscience & Trauma, Barts and The London School of Medicine & Dentistry, London, UK. Electronic address: schmierer@qmul.ac.uk.
authors: K
authors: K
authors: Schmierer
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK. Electronic address: k.hunter@ucl.ac.uk.
authors: K
authors: K
authors: Hunter
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK. Electronic address: d.tozer@ucl.ac.uk.
authors: D J
authors: DJ
authors: Tozer
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK. Electronic address: c.wheeler-kingshott@ucl.ac.uk.
authors: C A
authors: CA
authors: Wheeler-Kingshott
authors: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Electronic address: ajc1020@medschl.cam.ac.uk.
authors: A
authors: A
authors: Coles
authors: Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK. Electronic address: david.h.miller@ucl.ac.uk.
authors: D H
authors: DH
authors: Miller
keywords: Magnetic resonance imaging; Magnetisation transfer ratio; Multiple sclerosis; Remyelination; Research design; Sample size