“One of the most damaging things to happen to the treatment of RRMS is NICE stating that the injectable therapies (interferon-beta and glatiramer acetate) were not cost-effective. This created the perception amongst neurologists that these drugs did not work, despite a wealth of evidence to the contrary. This is a common problem with NICE when it says ‘NO’ to new drugs. It’s not NICE’s role to assess efficacy of drugs this is done by the EMA and MHRA. All NICE do is state that the drug is too expensive given the established benefits to be prescribed under the NHS. It is therefore reassuring that after 13 years we have the results of the NHS’s Risk Sharing Scheme (RSS) that finally show that these drugs do what they say they do on the tin and they are cost effective. The comparator used in this study was the Canadian British Columbian database that is a bit of an outlier in its own right; compared to other registries MSers in this database do much better than expected. This means that despite a relatively benign comparator IFNbeta & GA do okay. I suspect when compared against other natural history cohorts they would do even better. I really hope these results change prescribing behavior and finally slay therapeutic nihilism that is so prevalent in the UK. A large number of neurologists have always been of the opinion IFNbeta and GA don’t work and that it is a waste NHS resources to be prescribing them.”
“Since the launch of the RSS things have moved on with the licensing of more effective DMTs and oral DMTs. In addition, or therapeutic target has moved on from simply reducing the frequency of clinical attacks with a modest effect on disability progression, to treating-2-target of NEDA (no evident disease activity). Some of us are beginning to move beyond NEDA to try and prevent end-organ damage to maintain brain health. Some of us are even daring to ask about what a MS cure looks like.”
Background: In 2002 the National Institute for Clinical Excellence (NICE) concluded that interferon beta and glatiramer acetate would be cost effective as disease-modifying therapies (DMTs) for multiple sclerosis only if the short-term disability benefits reported in clinical trials were maintained. The UK Multiple Sclerosis Risk Sharing Scheme (RSS) was established to assess whether disability progression was consistent with a cost-effectiveness target of £36,000 per quality-adjusted life-year projected over 20 years.
Findings: 5610 MSers starting a DMT were enrolled in the UK RSS between Jan 14, 2002, and July 13, 2005 (72 sites), of whom 4137 were included in our clinical cohort. We included 898 BCMS MSers in the control cohort who met the RSS inclusion criteria and had at least one EDSS score after baseline. RSS MSers had a mean follow-up of 5·1 years (SD 1·4). Both models showed slower EDSS progression than predicted for untreated controls (Markov model, 75·8% [95% CI 71·4–80·2]; multilevel model, 60·0% [56·6–63·4]). Utility ratios were consistent with cost-effectiveness (Markov model, 58·5% [95% CI 54·2–62·8]; multilevel model, 57·1% [53·0–61·2]).
Interpretation: Findings from this large observational study of treatment with interferon beta or glatiramer acetate provide evidence that their effects on disability in MSers with relapsing-remitting multiple sclerosis are maintained and cost effective over 6 years. Similar modelling approaches could be applied to other chronic diseases for which long-term controlled trials are not feasible.
Funding: Health Departments of England, Wales, Scotland, and Northern Ireland, Biogen Idec, Merck Serono, Bayer Schering Pharmaceuticals, Teva Pharmaceuticals Industries, UK National Institute of Health Research’s Health Technology Assessment Programme.
Background to the Risk-sharing Scheme (RSS): The Risk-sharing Scheme was that NICE (National Institute for Health and Care Excellence) had considered the clinical and cost-effectiveness of the disease modifying therapies for MS – beta interferon and glatiramer acetate – in a technology appraisal (TA32). 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 a twenty year time horizon. However, NICE invited the UK Health Departments to enter into a discussion with the license 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 and the Risk-sharing Scheme was enshrined within Health Service Circular 2002/004. Prior to entering the Scheme the manufacturers reduced the prices of the drugs to ensure they were cost effective using the NICE model.
Previous data analysis
Data from the first two years of follow-up were 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 two year data showed a number of issues with the methodology being used. Firstly, the natural history database used to compare disease progression on treatment with expected disease progression off treatment as part of the NICE review did not allow improvement and yet circa 40% of patients treated with drug therapy in the RSS cohort showed improvements. Secondly, the statistical assumptions underlying the model were uncertain.
Benefits of the Scheme: The Department of Health and the Health Departments across the UK remain committed to the Scheme. It has realised many benefits for all 100,000 people with MS, including infrastructure development of services, consistent access for thousands of patients to drug treatments, and the development of the specialist centres across the UK. The support has been provided under the auspices of the Scheme by the pharmaceutical companies engaged in the Scheme (Bayer, Biogen Idec, Merck Serono and Teva). 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. This new information may allow the manufacturers to put up their costs.