The Department of Health Risk-sharing Scheme
The Multiple Sclerosis Risk-sharing Scheme was set up in 2002 to ensure that people with MS could access the original four first line disease modifying MS drugs on the NHS. The Scheme covers both the legal framework for routine NHS prescribing and the collection of data from a clinical cohort to assess cost efficacy over a 10 year period within routine clinical usage.
The backdrop to the Scheme is that NICE had considered the clinical and cost-effectiveness of the disease modifying therapies for MS - beta interferons and glatiramer acetate - in a technology appraisal (TA32) in 2002. At that time NICE concluded that it was not appropriate to recommend use of the treatments on the NHS because there was insufficient evidence to show their cost effectiveness over the expected lifetime of a person with MS. However, NICE invited the UK Health Departments to enter into a discussion with the licence holders of the four products to see whether there was a possible basis on which they could be cost-effectively used in the NHS.
Subsequently, the four UK health administrations reached agreement with the manufacturers of the MS drugs to make the treatments available on the NHS. Prior to entering the Scheme the manufacturers reduced the prices of the drugs to ensure they were cost effective using the NICE model.
The research element of the Scheme collects data from more than 5,000 patients to measure effectiveness of the treatments. The cohort was recruited by April 2005. Comprehensive details of the MS Risk-sharing Scheme, including how patients access treatments, are outlined in the Health Service Circular 2002/004.
The MS Trust has an administrative role within the Risk-sharing Scheme. In this role we manage the research provider to ensure effective interaction with the clinical centres and collection of the data. In addition the MS Trust administers the Scientific Advisory Group, and the finances for the Scheme.
Data from the first two years of follow-up have been collected, analysed and interpreted by an independent group who concluded that it was premature to reach any conclusion about the cost-effectiveness of the drugs used to treat relapsing remitting multiple sclerosis from the first interim analysis.
- The paper was published in the British Medical Journal:
- Multiple sclerosis Risk-sharing Scheme: two year results of clinical cohort study with historical comparator (BMJ 2009; 339:b4677)
Following the publication the Department and its partners in the scheme produced a leaflet to update patients and their carers, healthcare professionals and other interested parties on the progress of the scheme.
Subsequent analysis (Year 4 and onward)
This section provides more detailed information on the progress in undertaking the four-year and subsequent analysis of the data.
Initial analysis problems
Analysis of the two-year data, using the model developed for NICE's 2001 appraisal, failed to provide any conclusive results. On reflection, this was not surprising because the Scheme is a long-term observational study and it could not be expected to provide conclusive results within the first two years - the Scheme is designed to collect individual patient data for 10 years.
The main difficulties encountered in conducting the two-year analysis concerned, firstly, the natural history database used to compare disease progression on treatment with expected disease progression off treatment and, secondly, the statistical assumptions underlying the model. The original natural history comparator did not recognise that some patients show improvement from one year to the next, whereas this is common in patients in the Risk-sharing Scheme. The uncertainties over the model led to widely differing results about the performance of the drugs. Given these uncertainties, the scheme's Scientific Advisory Group advised the Department that it would be unwise to enter into discussions about price adjustments as a result of the first analysis, and the Scientific Advisory Group are now working to address these concerns for the subsequent analysis.
Some commentators and commissioners of services have been concerned that the lack of definitive findings supports the view that the NHS is being burdened with the funding of treatments where there is insufficient evidence of clinical effectiveness. However, a requirement for entering the scheme was that all the products should achieve a cost per quality adjusted life year (QALY) of £36,000 as evaluated in the model used for NICE's 2001 appraisal over 20 years. If the additional modeling undertaken within the Scheme demonstrates that the products continue over the longer term to show the same clinical benefits as those found in the original randomised controlled trials, then we can be confident that they represent a cost effective use of NHS resources. If, longer term, benefits fall short of those expected, the prices will be reduced.
In response to the difficulties in analysing the two-year data, the Scheme's Scientific Advisory Group has decided to adopt a different a natural history comparator - the British Columbia MS Dataset - in which patients' disease can get better or worse from year to year, as with the Risk-sharing Scheme. Statistical analysis will therefore be much more straightforward, and less subject to uncertainty, than for the 2-year analysis. In addition, two alternative methods will be used to analyse the data - a 'continuous Markov' model and an alternative approach using a 'repeated measures' model. This is highlighted in the presentation by Professor Richard Lilford, chair of the Scientific Advisory Group (see below).
As a consequence of this extensive work, the year-four analysis is delayed, but the Scientific Advisory Group has concluded that this is justified by the additional scientific rigour that will result from the methodological improvements.
Benefits of the scheme
The Department recognises the limitations of the initial analysis, but remains committed to the Scheme. The Scheme has realised many benefits for people with MS, including infrastructure development of services, consistent access for thousands of patients to these drug treatments across the UK and the development of 75 specialist centres across the UK. Some of the additional support has been provided under the auspices of the Scheme by the pharmaceutical companies engaged in the Scheme. In addition the longer term findings of the Risk-sharing Scheme have the potential to genuinely inform and change the way in which MS is treated.
Scheme Steering Group
The Scheme operates under the oversight of a Steering Group representing all the parties to the Scheme (the four UK health departments, the four companies whose products are made available through the Scheme, the Association of British Neurologists, the UK MS Specialist Nurses Association, the Royal College of Nurses, and the MS Trust). The Steering Group is advised on scientific issues by a Scientific Advisory Group.
Other licensed MS treatments
In addition to the four treatments covered by the scheme, NICE has produced positive appraisal guidance on natalizumab (Tysabri) for the treatment of highly active MS (defined as two relapses in a year plus a supportive MRI) and natalizumab is also available on the NHS.
A further treatment, fingolimod (Gilenya), has now also received a licence and been assessed by NICE for use in the UK in highly active relapsing remitting MS. Fingolimod, the first oral treatment, is recommended as an option for the treatment of highly active relapsingremitting multiple sclerosis in adults, only if:
- they have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon, and
- the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme.
There is one other licensed treatment, Extavia, which is chemically the same as Betaferon but is not one of the scheme drugs. Extavia has a different delivery package and support structures.
How to get the disease modifying drugs
The disease modifying drugs are only prescribed by neurologists in prescribing centres.
- Map of prescribing centres in the UK
- Disease modifying drug therapy - MS Trust book with more information on these drugs and the current prescription criteria
Drugs covered by the Risk-sharing Scheme
- Avonex (interferon beta-1a)
- Betaferon (interferon beta-1b)
- Copaxone (glatiramer acetate)
- Rebif (interferon beta-1a)
Drugs not covered by the Risk-sharing Scheme
Tysabri has a separate positive NICE guidance for use in highly active relapsing remitting MS, or where conventional treatment has failed.