Convergence yet Continued Complexity: A Systematic Review and Critique of Health Economic Models of Relapsing-Remitting Multiple Sclerosis in the United Kingdom

Value Health. 2015 Sep;18(6):925-38. doi: 10.1016/j.jval.2015.05.006. Epub 2015 Jul 30.


Objectives: 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.

Keywords: cost-effectiveness; health economics; multiple sclerosis; systematic review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Computer Simulation
  • Cost-Benefit Analysis
  • Disability Evaluation
  • Drug Costs*
  • Health Expenditures
  • Health Services Research
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / economics*
  • Immunologic Factors / therapeutic use*
  • Markov Chains
  • Models, Economic
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / economics*
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Predictive Value of Tests
  • Recovery of Function
  • Reproducibility of Results
  • State Medicine / economics*
  • Time Factors
  • Treatment Outcome
  • United Kingdom


  • Immunologic Factors