title: Comparison of the King's and MiToS staging systems for ALS.
abstract: To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31).
  
  
  
  Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation.
  
  
  
  For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King's stage 3 corresponded to MiToS stage 1 most frequently, with earlier King's stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21.
  
  
  
  The distribution of timings shows that the two systems are complementary, with King's staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS.
authors.affiliation: a Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience , King's College London , UK.
authors.forename: Ton
authors.initials: T
authors.lastname: Fang
authors.affiliation: a Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience , King's College London , UK.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al Khleifat
authors.affiliation: b Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience , King's College London , UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Stahl
authors.affiliation: c Department of Neurology, University of Lleida , Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lazo La Torre
authors.affiliation: b Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience , King's College London , UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Murphy
authors.affiliation: d The Walton Centre NHS Foundation Trust , Liverpool , England.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Young
authors.affiliation: e Department of Neuroscience , University of Sheffield , England , and.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.affiliation: f Department of Neurology , Brighton and Sussex Medical School , England.
authors.forename: P Nigel
authors.initials: PN
authors.lastname: Leigh
authors.affiliation: a Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience , King's College London , UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016019:Survival Analysis
keywords: Clinical stage; King’s stage; MiToS stage; clinical trials; prognosis