title: Effectiveness and cost-effectiveness of interferon beta and glatiramer acetate in the UK Multiple Sclerosis Risk Sharing Scheme at 6 years: a clinical cohort study with natural history comparator.
abstract: BACKGROUND
  In 2002, the UK's National Institute for Clinical Excellence (NICE) concluded that interferon beta and glatiramer acetate would be cost effective as disease-modifying therapies (DMTs) for multiple sclerosis only if the short-term disability benefits reported in clinical trials were maintained. The UK Multiple Sclerosis Risk Sharing Scheme (RSS) was established to assess whether disability progression was consistent with a cost-effectiveness target of £36 000 per quality-adjusted life-year projected over 20 years. We aimed to evaluate the long-term effectiveness and cost-effectiveness of these DMTs by comparing a cohort of patients with relapsing-remitting multiple sclerosis enrolled in the UK RSS with a natural history cohort from British Columbia, Canada.
  
  
  METHODS
  In our clinical cohort we included patients starting a DMT who were enrolled in the UK RSS who had relapsing multiple sclerosis at baseline and had at least one further clinical assessment. In our control cohort we included patients in the British Columbia multiple sclerosis database (BCMS; data collection 1980-96) who met the same eligibility criteria as for the RSS cohort. We compared disability progression at 6 years for RSS patients with untreated progression modelled from BCMS patients using continuous Markov and multilevel models. The primary outcomes were the progression ratio (treated vs untreated) measured both in Expanded Disability Status Scale (EDSS) score and utility. A ratio of less than 100% for EDSS implied slower than expected progression on treatment compared with off treatment; a utility ratio of 62% or less implied that the DMTs were cost effective.
  
  
  RESULTS
  5610 patients starting a DMT were enrolled in the UK RSS between Jan 14, 2002, and July 13, 2005 (72 sites), of whom 4137 were included in our clinical cohort. We included 898 BCMS patients in the control cohort who met the RSS inclusion criteria and had at least one EDSS score after baseline. RSS patients had a mean follow-up of 5·1 years (SD 1·4). Both models showed slower EDSS progression than predicted for untreated controls (Markov model, 75·8% [95% CI 71·4-80·2]; multilevel model, 60·0% [56·6-63·4]). Utility ratios were consistent with cost-effectiveness (Markov model, 58·5% [95% CI 54·2-62·8]; multilevel model, 57·1% [53·0-61·2]).
  
  
  CONCLUSIONS
  Findings from this large observational study of treatment with interferon beta or glatiramer acetate provide evidence that their effects on disability in patients with relapsing-remitting multiple sclerosis are maintained and cost effective over 6 years. Similar modelling approaches could be applied to other chronic diseases for which long-term controlled trials are not feasible.
  
  
  BACKGROUND
  Health Departments of England, Wales, Scotland, and Northern Ireland, Biogen Idec, Merck Serono, Bayer Schering Pharmaceuticals, Teva Pharmaceuticals Industries, UK National Institute of Health Research's Health Technology Assessment Programme.
authors.affiliation: Department of Clinical Neurology, Oxford University Hospitals Trust, Oxford, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
authors.affiliation: Department of Neurology, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Duddy
authors.affiliation: Department of Biostatistics, PAREXEL International, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bregenzer
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Lawton
authors.affiliation: Department of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The Townsville Hospital, Townsville, QLD, Australia.
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
authors.affiliation: Department of Biostatistics, PAREXEL International, Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Piske
authors.affiliation: Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Robertson
authors.affiliation: Department of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
authors.affiliation: Department of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: Department of Health, Leeds, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Dobson
mesh_terms: D000328:Adult; D001955:British Columbia; D003362:Cost-Benefit Analysis; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000191:economics / Q000627:therapeutic use*; D016899:Interferon-beta / Q000191:economics / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000191:economics; D010455:Peptides / Q000191:economics / Q000627:therapeutic use*; D012306:Risk; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta