title: Convergence yet Continued Complexity: A Systematic Review and Critique of Health Economic Models of Relapsing-Remitting Multiple Sclerosis in the United Kingdom.
abstract: OBJECTIVE
  Several disease-modifying therapies have marketing authorizations for the treatment of relapsing-remitting multiple sclerosis (RRMS). Given their appraisal by the National Institute for Health and Care Excellence, the objective was to systematically identify and critically evaluate the structures and assumptions used in health economic models of disease-modifying therapies for RRMS in the United Kingdom.
  
  
  METHODS
  Embase, MEDLINE, The Cochrane Library, and the National Institute for Health and Care Excellence Web site were searched systematically on March 3, 2014, to identify articles relating to health economic models in RRMS with a UK perspective. Data sources, techniques, and assumptions of the included models were extracted, compared, and critically evaluated.
  
  
  RESULTS
  Of 386 results, 26 full texts were evaluated, leading to the inclusion of 18 articles (relating to 12 models). Early models varied considerably in method and structure, but convergence over time toward a Markov model with states based on disability score, a 1-year cycle length, and a lifetime time horizon was apparent. Recent models also allowed for disability improvement within the natural history of the condition. Considerable variety remains, with increasing numbers of comparators, the need for treatment sequencing, and different assumptions around efficacy waning and treatment withdrawal.
  
  
  CONCLUSIONS
  Despite convergence over time to a similar Markov structure, there are still significant discrepancies between health economic models of RRMS in the United Kingdom. Differing methods, assumptions, and data sources render the comparison of model implementation and results problematic. The commonly used Markov structure leads to problems such as incapability to deal with heterogeneous populations and multiplying complexity with the addition of treatment sequences; these would best be solved by using alternative models such as discrete event simulations.
authors.affiliation: Novartis Pharmaceuticals UK Ltd., Frimley, UK.
authors.forename: Felicity
authors.initials: F
authors.lastname: Allen
authors.affiliation: Costello Medical Consulting Ltd., Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Montgomery
authors.affiliation: Costello Medical Consulting Ltd., Cambridge, UK.
authors.forename: Maciej
authors.initials: M
authors.lastname: Maruszczak
authors.affiliation: Costello Medical Consulting Ltd., Cambridge, UK.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Kusel
authors.affiliation: Novartis Pharmaceuticals UK Ltd., Frimley, UK. Electronic address: nicholas.adlard@novartis.com.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Adlard
mesh_terms: D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D004185:Disability Evaluation; D016527:Drug Costs; D005102:Health Expenditures; D006302:Health Services Research; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D008390:Markov Chains; D018803:Models, Economic; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics* / Q000503:physiopathology; D011237:Predictive Value of Tests; D020127:Recovery of Function; D015203:Reproducibility of Results; D013222:State Medicine / Q000191:economics*; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D007155:Immunologic Factors
keywords: cost-effectiveness; health economics; multiple sclerosis; systematic review