The Pharmaceutical Journal Vol 267 No 7173 p672
10 November 2001

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NICE and MS: the saga will continue

NICE (National Institute for Clinical Excellence) published the final consultation document of its appraisal on beta-interferon and glatiramer acetate for multiple sclerosis (MS) on 2 November. Clare Bellingham finds out what the document says and how people are responding to it

NICE (National Institute for Clinical Excellence) is not a popular organisation in the world of MS. The long-awaited NICE appraisal of beta-interferon and glatiramer acetate moved a step forward this week with the publication of the final appraisal determination (FAD) document on NICE's website (www.nice.org.uk). The FAD states that neither drug is recommended for the treatment of MS on the National Health Service in England and Wales. Patient organisations and the industry appear united in their disappointment with the document's content.

What does NICE say?

The aim of the appraisal was to consider whether or not beta-interferon and glatiramer acetate, drugs that aim to reduce the frequency and severity of relapses, and to slow disease progression, should be available on the NHS. It is important to note that the FAD document is not guidance to the NHS but is part of the consultation document before the final guidance is released. Interested parties now have the opportunity to appeal against the appraisal before 14 November and appeals will be heard at a meeting on 26 November. A successful appeal could change the appraisal's recommendations. However, if no appeals are submitted, a situation that seems unlikely, or if none is successful, the final guidance is unlikely to differ greatly from the FAD.

The main conclusions of the FAD are:

• On the balance of their clinical and cost effectiveness, neither beta-interferon nor glatiramer acetate is recommended for treatment of MS
• Patients currently receiving treatment with either drug can continue therapy until it is considered appropriate to stop
• The Department of Health and National Assembly for Wales might consider strategies for securing the drugs in a manner that could be considered to be cost-effective

Beta-interferon works by reducing the inflammatory process in MS, although its precise mechanism of action remains unknown. Three beta-interferon products are available: Avonex, Rebif and Betaferon. NICE says that clinical trials show that beta-interferon reduces relapse frequency and severity in patients with relapsing remitting MS by about 30 per cent, on average, equivalent to avoiding one relapse every 2.5 years. Although disability progression is delayed by beta-interferon, NICE says that the effects on disability in the long term, after treatment has stopped, cannot be reliably predicted.

Glatiramer acetate (Copaxone) reduces inflammation around nerves. It also reduces relapse frequency in patients with relapsing remitting MS by about 30 per cent on average NICE says, again adding that the effects on long-term disability cannot be accurately predicted.

It is the cost-effectiveness part of NICE's appraisal which is causing the most concern. Cost-effectiveness was initially measured in terms of costs per quality adjusted life year (QALY) but problems with this model meant that a new analysis — cost per QALY gained (CQG) — was used instead. Assessments were based on extrapolating trial data to effects over five, 10 and 20 years. NICE did not consider cost-effectiveness beyond 20 years because it says that errors in extrapolating data beyond 20 years were likely to be great. The approximate CQG figures found were: at five years, between £248,000 and £810,000; at 10 years, between £120,000 and £339,000; and at 20 years, between £35,000 and £104,000.

NICE says that extrapolation of data becomes less certain as time increases. Therefore, confidence at 10 years is greater than that at 20 years. On this basis, NICE decided that it "could not form its conclusion on the cost-effectiveness of any of these products solely on a time horizon of 20 years and that, therefore, on the balance of costs and benefits, beta-interferon and glatiramer acetate are not cost effective".

Effect on patients

At least patients currently taking either drug can continue to do so. NICE says that because of potential loss of well being resulting from unanticipated changes in treatment, patients already taking either drug should continue to so until a time when consultants and patients consider it is appropriate to stop. NICE suggests that trusts and health authorities should collect data on the drugs' efficacy in these patients.

But for patients who do not fall into this category, NICE's appraisal is bad news. However, there is a ray of hope. Last week, the Department of Health announced that it was in discussions with manufacturers of beta-interferon and glatiramer acetate about possible schemes to fund the drugs (see PJ, 3 November, p633). One such scheme involves patients trying a course of treatment. If it works, manufacturers would be paid for it but, if it does not, payments would be reduced on a sliding scale.

NICE says that it is pleased that these discussions have begun. It comments: "Unless further evidence emerges which reveals a significant improvement in their clinical effectiveness, the cost-effectiveness of these medicines can only be improved if there is a significant reduction in the total cost of their acquisition by the NHS in England and Wales."

The MS Trust reacted to the FAD with disappointment and frustration. Christine Jones, the trust's chief executive, said: "The process clearly demonstrates that those involved have little understanding of MS. It is a complex and long-term condition and so focussing on a limited time frame for assessing the clinical or cost-effectiveness of beta-interferon or glatiramer acetate is neither realistic nor appropriate." The MS Society is even stronger in its criticism saying that NICE has "turned its back on people with MS". Ken Walker, the society's acting chief executive, said: "NICE has ignored the compelling evidence of people whose lives have been changed by the only drugs which can reduce the symptoms and slow the progression of the disease. It has used measures of cost-effectiveness which do not work for a fluctuating life-long illness." The society has said that it will be submitting an appeal.

The pharmaceutical industry is not happy with NICE's conclusion either. The Association of the British Pharmaceutical Industry (ABPI) described it as a "final bad judgement at the end of a long and costly appraisal process". The ABPI says that NICE's recommendation adds weight to concerns held by the industry that it is putting costs before benefits to patients. It adds that the appraisal demonstrates the need for a review of the institute.

Among the manufacturers of beta-interferon, Biogen says that it believes that NICE's conclusions are wrong. It points to a number of flaws with NICE's economic model. The company intends to appeal against the FAD. Schering Healthcare is also planning to appeal. Dr Peter Longthorne, the company's medical director, said: "The clinical evidence provided to NICE simply does not support this assessment. Nor do we believe that cost-effectiveness arguments support this decision because MS costs the economy approximately £1.2bn per year of which only a small proportion falls directly on the NHS."

So NICE is to be hit by more appeals. Patients and the industry will have to wait a little longer to hear NICE's final verdict on MS treatments.