Access to disease modifying drugs
- Access to disease modifying drugs throught the Department of Health Risk-sharing Scheme
- Access to fingolimod (Gilenya)
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 MS treatments.
NICE considered the clinical and cost-effectiveness of disease modifying therapies for MS - beta interferons and glatiramer acetate - in a technology appraisal (TA32) in 2002.
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 patient 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.
Access to the drugs was set up through the MS Risk-sharing Scheme in which the manufacturers agreed to provide the drugs on the basis that they would meet certain clinical outcomes.
The scheme is a long-term observational study and 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 a pivotal role within the Risk-sharing Scheme, working alongside the Department of Health to ensure the effective collection of the research data. We act as the administrator for the research, managing the research provider to ensure effective interaction with the clinical centres and collection of the data, managing the scientific advisory group, and the finances.
Two-year analysis
Data from the first two years of follow-up have been collected, analysed and interpreted by an independent group.
Its paper concludes that it is premature to reach any conclusion about the cost-effectiveness of the drugs used to treat relapsing remitting multiple sclerosis from this first interim analysis.
The paper was published in the British Medical Journal:
The Department and its partners in the scheme have produced a leaflet to update patients and their carers, healthcare professionals and other interested parties on the progress of the scheme.
Four-year analysis
This section provides more detailed information on the progress in undertaking the four-year analysis of the data and, in particular, emphasises the complex methodological issues that we are attempting to resolve as well as tackling some misunderstandings about the nature of the scheme.
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 is not entirely 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 modelling. 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 best way of allowing for this fundamental lack of comparability led to widely differing results about the performance of the drugs. We are addressing these concerns in the four-year analysis. 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.
We understand that some commentators and commissioners of services have been concerned that this 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 products should achieve a cost per quality adjusted life year (QALY) of £36,000 as evaluated on the model used for NICE's 2001 appraisal over 20 years. If the scheme's monitoring 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.
Benefits of the scheme
The Department recognises the concerns about the initial analysis, but remains committed to the scheme. The scheme has realised many benefits for people with MS, but principally it has secured consistent access for thousands of patients to these drug treatments across the UK. Additionally, it has led to substantial improvements in the provision of MS services, particularly the support available from extra specialist nurses. Some of this additional support has been provided under the auspices of the scheme by the pharmaceutical companies engaged in the scheme. However, it is the longer term findings which we believe will be of most benefit because this could genuinely inform and change the way in which MS is treated.
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 (include a link) (defined as two relapses in a year plus a supportive MRI) and is also available on the NHS.
A further treatment, fingolimod (Gilenya), has now received a licence for use in highly active MS. Gilenya is the first oral treatment to receive a licence and it will be appraised by NICE in the usual way. Subject to receiving a positive recommendation from NICE, Gilenya will become available on the NHS alongside the risk-sharing drugs and Tysabri. It should be noted that the risk-sharing scheme has not detracted from the availability of other licensed treatments.
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.
Four-year analysis
In response to the difficulties in analysing the two-year data, the scheme's Scientific Advisory Group has decided to adopt a new 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 additional work, the year-four analysis will be delayed, but the Scientific Advisory Group has concluded that this is justified by the additional scientific rigour that will result from the methodological improvements. Further details of the development of the scheme, of the problems with the 2-year analysis, and of the proposals for the four-year analysis are included in the presentation made at the Multiple Sclerosis Steering Group meeting held on 25 February 2011 (see below).
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.
The Steering Group met on 25 February 2011 and agreed the plans for the four-year analysis outlined by Professor Lilford.
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.