Multiple sclerosis modelling

MS is a demyelinating disease of the central nervous system (CNS).1 It is the most frequent cause of neurological disability in young adults. MS causes damage to the myelin nerve fibre in the brain and spinal cord through the development of hardened sclerotic plaques, which in turn interrupt the transmission of nerve impulses. MS is characterised by a variety of debilitating symptoms including pain, fatigue, muscle spasticity and spasm, ataxia and tremor, bladder disturbance and micturition problems, sleep disturbance, balance and postural problems, optic neuritis, paraesthesiae, diplopia and vertigo. The Kurtzke Expanded Disability Status Scale (EDSS) is commonly used to measure the disease progression in terms of impairment and disability.2 There is no cure for MS, hence a central aspect of managing MS focuses on improving the quality of life of patients experienced on a day-to-day basis through managing those symptoms which represent the most significant burden on the physical, social and emotional wellbeing of patients, their families and their carers.

Until the 1990s there was no disease modifying therapy in MS. Management of the disease consisted of symptom control, physiotherapy, psychiatric and social support, and disability aids. At present the only known disease-modifying therapies available for Relapsing/Remitting MS (RRMS) and Secondary-Progressive MS (SPMS) are beta-interferon and glatiramer-acetate, which reduce both the number of relapses experienced and the rate at which patients progress through the disease. It has been conservatively estimated that around 63,000 people in England and Wales have MS.3 Four products are licensed as disease-modifying therapies in the UK. These are:

  • Interferon beta-1a (Avonex)
  • Interferon beta-1b (Betaseron)
  • 20mg Glatiramer-acetate (Copaxone)
  • 22/44mcg Interferon Beta-1a (Rebif)

Modelling the cost-effectiveness of beta interferon and glatiramer acetate in the management of MS in England and Wales

There have been many attempts to estimate the cost-effectiveness of disease-modifying therapies for MS. Existing analyses have produced cost-effectiveness estimates ranging from greater than £1 million per QALY gained to cost saving.4-8 Significant flaws in the modelling of the natural history of MS, efficacy, discontinuation of therapy, mortality and the analysis of uncertainty, mean that none of these estimates can be considered robust.9 The Cost Effectiveness of Multiple Sclerosis Therapies Study Group was commissioned by the National Institute for Clinical Excellence (NICE) to undertake this economic assessment in consultation with all stakeholders to its appraisals process, using the best available evidence.

The objective of this study was to evaluate the cost-effectiveness of three beta-interferon products and glatiramer-acetate. The effect of each drug was assessed against a comparator of conventional management. We constructed a model to simulate the natural history of MS, modelling individual EDSS states from 0 through 10 in RRMS, and from 2 through 10 in SPMS. Disease course, cost and utilities with and without treatment are assessed over a 20-year horizon.

The base case cost per quality adjusted life year gained by using any of the four treatments
ranged from £42,000 to £98,000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost-effectiveness better than £20,000 at 20 years is below 20%. The key determinants of cost-effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. To view the full report and the BMJ article, use the links above.

Expected value of perfect information associated with disease-modifying therapies for MS

In 2001, ScHARR was commissioned by the National Coordinating Centre for Health Technology Assessment (NCCHTA) to develop methods for undertaking Expected Value of Perfect Information Analysis (EVPI) for computationally expensive health economic models. We used the ScHARR MS model as a case study for this methodological work. The EVI approach uses a decision analytic framework in order to prioritise further research through identifying those areas in which additional data collection, and hence the reduction of uncertainty, would be of most value. Value of information analysis describes the opportunity cost of uncertainty regarding a commissioning decision in terms of the probability that a sub-optimal intervention is selected and the associated economic disbenefit. Further data collection is valuable if it reduces the likelihood of making the wrong decision.

Gaussian Process metamodels were constructed to estimate the Expected Value of Perfect Information using the 2-level algorithm. Assuming independent treatment efficacy, the population EVPI for all parameters within the MS model was approximately £86 million. The analysis suggests that further research is indicated on the long-term effectiveness of the disease-modifying therapies, the proportion of patients who drop off therapy, and the relationship between the EDSS, costs of care and health-related quality of life. The full study report can be accessed using the links above.

Modelling the cost-effectiveness of beta interferon and glatiramer acetate in the management of MS in the US

The model developed on behalf of NICE is currently being used to assess the cost-effectiveness of disease-modifying therapies in the management of MS in the US. This work has been commissioned by the Agency for HealthCare Research and Quality on behalf of the Centers for MEDICARE and MEDICAID. An updated systematic review of treatment effectiveness has been undertaken. The revised model will incorporate US-specific evidence relating to the costs of treating the disease, as well as Canadian data on the relationship between the EDSS and health status. A study report and publication of this work will be forthcoming.

References:

  1. Compston A, Ebers G, Lassmann H, McDonald I,Matthews B,Wekerle H. Natural history of multiple sclerosis. McAlpine's multiple sclerosis. Edinburgh: Churchill Livingstone, 1998:191­221.
  2. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale, Neurology 1983; 33:1444-1452.
  3. Richards RG, Sampson FC, Beard SM, Tappenden P. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess 2002; 6(10):i­73.
  4. Parkin D,McNamee P, Jacoby A, Miller P, Thomas S, Bates D. A cost­utility analysis of interferon beta for multiple sclerosis. Health Technol Assess 1998; 2(4):i­58.
  5. Brown MG, Murray TJ, Sketris IS, Fisk JD, LeBlanc JC, Schwartz CE, et al. Cost­effectiveness of interferon beta­1b in slowing multiple sclerosis disability progression. First estimates. Int J Technol Assess Health Care 2000;16:751­67.
  6. Forbes RB, Lees A, Waugh N, Swingler RJ. Population based cost utility study of interferon beta­1b in secondary progressive multiple sclerosis. BMJ 1999; 319:1529­33.
  7. Kendrick M, Johnson KI. Long term treatment of multiple sclerosis with interferon beta may be cost­effective. Pharmacoeconomics 2001; 18:45­53.
  8. Prosser L. The cost-­effectiveness of treatments for multiple sclerosis. Cambridge, MA: Harvard University, 2000.
  9. National Institute for Clinical Excellence. Minutes of the technology appraisals committee meeting 13 Dec, 2000. www.nice.org.uk/article.asp?a=16091 (accessed 6 May 2001).

Other ScHARR Publications (links above):

  • Tappenden P, Chilcott J, O'Hagan A, McCabe C et al. Cost effectiveness of beta interferons and glatiramer acetate in the management of multiple sclerosis: Final Report to the National Institute for Clinical Excellence. 2001.
  • Chilcott J, McCabe C, Tappenden P, O'Hagan A et al. Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. BMJ 2003 326(7388):522-528
  • Tappenden P, Chilcott JB, Eggington S, et al. Methods for expected value of information analysis in complex health economic models: developments on the health economics of interferon-β and glatiramer acetate for multiple sclerosis. Health Technology Assessment, 2004, 8(27).