title: Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease.
abstract: OBJECTIVE
  Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed.
  
  
  METHODS
  The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness).
  
  
  RESULTS
  Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28).
  
  
  CONCLUSIONS
  Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.
authors.affiliation: C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Piscosquito
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Reilly
authors.affiliation: Department of Neurology, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schenone
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Fabrizi
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Cavallaro
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Manganelli
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.|Clinical Centre NEMO SUD, Fondazione Aurora Onlus, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Vita
authors.affiliation: Neurology Clinic, Neuroimaging Research Unit, National Research Council, Magna Graecia University, Catanzaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Quattrone
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopaedics - Università Cattolica del Sacro Cuore, Rome, Don Carlo Gnocchi Foundation, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Padua
authors.affiliation: Department of Neurosciences, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gemignani
authors.affiliation: Department of Pharmacological Sciences, University School of Pharmacy, Milan, Italy.|Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Visioli
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Laurà
authors.affiliation: C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Calabrese
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
authors.forename: R A C
authors.initials: RA
authors.lastname: Hughes
authors.affiliation: Department of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Radice
authors.affiliation: C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Solari
authors.affiliation: C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005080:Exercise Test / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000592:standards
keywords: Charcot−Marie−Tooth disease; clinical trials; evaluative outcome measures; hereditary motor sensory neuropathy; responsiveness