On the edge of darkness

Bill Foxen describes it as like watching a fast camera shutter opening and closing in his head. Without warning, the muscles at the back of the eyes would begin to twitch and his lenses start flickering rapidly. When the attack came, there was nothing he could do to stop the maddening sight of the world flashing on and off, except close his eyes. Effectively, he was blind.

"I spent a weekend in Budapest with my wife and I had to spend the whole time lying on the bed with my eyes shut," he says.

Worse, with equal suddenness, he would lose all power over his arms and legs. One attack saw him paralysed in a neurological ward for six weeks, with a further three months recuperation.

Such is the fearful power and unpredictability of multiple sclerosis in its "relapsing, remitting" form. An MS sufferer can be fit and well, leading a normal work and family life, and wake up one morning blind or paralysed or both.

Attacks also bring incontinence, depression, exhaustion, sexual dysfunction, difficulty in thinking clearly, mood changes and much, much pain. During an attack, the muscles of the vocal chords fail to work properly, and sufferers slur their words like drunks.

This was the dark world Foxen inhabited, the world he unwittingly entered at 17 when an optician giving him a routine sight test noticed a flickering in his eye. Where, throughout his student days, he put occasional epsiodes of numbness in his legs down to a trapped nerve. Where at the age of 27, a qualified architect, he was told he had the disease, and eight years later gave up lying to his boss, admitted he had MS, and quit to prepare for eventual life in a wheelchair.

Now 44, he has left that world behind, thanks to a remarkable drug called beta interferon. It's a drug which, he believes, has been responsible for transforming his life: his relapses have gone from two or three a year to none, he plays badminton, he looks after his children while his wife is at work, he's an active volunteer at the citizen's advice bureau, and he's using his architectural knowledge to advise a disabled access group.

Beta interferon isn't a cure for MS, which affects 85,000 people in Britain, but it is the best hope sufferers have of leading normal lives, of staving off permanent disability and dependence, albeit for a limited time. In North America and continental Europe, where the drug has been widely prescribed for years, the health authorities certainly think so.

But not the health authorities in Britain. Beta interferon is expensive, costing about £10,000 a year per patient. The MS Society, the leading MS charity, estimates that about 10,000 sufferers would be candidates for treatment. The arithmetic isn't difficult: a cost to the health service of £100m a year, every year, until a better drug comes along. And the government's national institute for clinical excellence (Nice), which is mulling over whether the NHS should or shouldn't pay for it, doesn't seem to think it's worth the money.

Nice has yet to make its final decision, due in August. But last month a leak of the agency's provisional opinion revealed that the assessors were against it.

Shortly after the leak, Nice's chairman, Professor Sir Michael Rawlins, said beta interferon was failing their value for money test: "Other than for those patients who are already receiving these medicines, they should not be made available in the NHS at the present time. This is because, on the basis of a very careful consideration of the evidence, their modest clinical benefit appears to be outweighed by their very high cost."

Outraged, the MS Society, standing for a powerful constituency, given that an estimated quarter of a million sufferers, carers and relatives have their lives affected by the disease in some way, accused Nice of failing to listen to testimony from the few British MS sufferers who have been given access to the drug so far, and from the many more who believe they should be given it. On the NHS today, access to beta interferon varies wildly according to where you happen to live, a classic example of postcode prescribing.

"The proposal as it stands is brutal and indefensible," the society says. "The idea that those who have been lucky enough to receive the drug will continue to enjoy its benefits while others go on suffering sets the postcode lottery in stone. It makes a complete mockery of the government's commitment to equality of access to health care."

David Harrison, a society spokesman, told the Guardian: "Our principal concern is that this is a drug which quite clearly works. It may not work 100%, but what drug does? It's the only one available."

Multiple sclerosis turns the sufferer's body against itself. In the biochemical equivalent of a friendly fire incident, when troops open fire on their own side by mistake, the body's defence mechanism, its immune system, turns on one of the most critical areas it is supposed to defend: the axons - channels which radiate out from nerve cells, carrying signals. Specifically, the immune system attacks myelin, a fatty substance which sheathes the axons like plastic round a copper wire. The axons experience a kind of short circuit: eventually, the damaged myelin is replaced by scar-like tissue. The brain andnervous system begin to break down.

Back in the 1980s, scientists discovered that a substance called gamma interferon, which normally works to rally the immune system against viral invaders, appeared to be implicated in MS: its presence in sufferers shot up before and during attacks. They turned to a cousin substance, beta interferon, which inhibits the action of gamma interferon. The results were promising and in 1993 the US food and drug administration approved the use of artificially synthesised beta interferon as a treatment for relapsing, remitting MS.

In North America and continental Europe, 12-16% of MS patients are prescribed the drug. In the UK, the figure is 3%. The beta interferon debacle is another reminder of how far the NHS has fallen below its peers in terms of funding, and it is likely that Nice is simply obliged to apply a tougher set of cost-effectiveness criteria than its counterparts across the Atlantic and over the Channel.

Yet are the necessarily ugly calculations of the health economists, replete with miserable sums trying to put a financial value on the alleviation of pain, dependency and disability, being applied fairly and sensibly by Nice? Beta interferon advocates - patient groups, drugs companies and doctors - say they are not.

They say Nice is basing its rejection of beta interferon - modest clinical benefits outweighed by cost - on a crude measure based on the immediate, observable effects on MS patients' health during two-year clinical trials of the drug in the 1990s. Yet in other countries, the health authorities have assumed the drug would be taken for much longer. Not only would it improve quality of life over as much as a decade, it would in all probability stave off the onset of permanent disability.

The accusation is that Nice is behaving like a short-sighted car fleet manager who refuses to replace spare parts in problem cars, as long as the cars are running - until the cars suffer a catastrophic breakdown and it is too late. But MS sufferers are human beings, not cars.

Dr Jonathan O'Riordan, director of the MS research unit at Ninewells Hospital in Dundee, says that the immediate, observable effects of beta interferon in clinical trials were clear. Patients' attacks happened one third less often, and were half as severe. This is the "moderate" effect which Nice considers too expensive at £10,000 a year for people who are not, strictly speaking, disabled.

But there is another, hidden effect of beta interferon. Studying MS patients, doctors take MRI scans of their brain. They have discovered that the attacks experienced by relapsing remitting sufferers show only a fraction - one tenth - of the civil war raging in the brain between the immune system and nerve cells.

And regardless of what a patient experiences, after three years the MRI scans show that those who have not taken beta interferon have a 25 % increase in the area of nerve damage. Those who have taken the drug show no increase in nerve damage at all - a dramatic, rather than a "moderate" effect.

"The Americans and the Europeans and a lot of people in the UK think the dramatic effect seen in the MRI scans is very significant, and does mean patients will probably be better off in the long term," says O'Riordan.

"That's why everybody in America and Europe gets it. But some people in the UK are just looking at the clinical effects on the attacks you see, as opposed to the attacks you don't."

Despite last month's leak, Nice is sticking to its insistence that details of its interferon study remain secret until a final decision has been made. The agency must now be regretting its decision to bow to the demands of the drugs companies for its reviews to be confidential, since it has gagged itself while everyone else involved in the consultation - including the drugs companies - is free to speak out.

Last week one of the manufacturers of beta interferon, the US biotech firm Biogen, trumpeted research it had commissioned from a "health outcomes" analyst, Dr Malcolm Kendrick, which suggested that if beta interferon was taken over a number of years it would be far more cost effective than previous studies suggested. If lower social costs were taken into account - if it was assumed that beta interferon beneficiaries would be able to work, pay taxes and remain free of dependency on carers for longer - the drug paid for itself.

There is a tension between the MS Society and firms such as Biogen; the society believes the drugs companies are charging too much for beta interferon in this country. The price is the same in each country - 10,000 - but in the US it's 10,000 dollars, in the UK 10,000 pounds. Still, Harrison backs the conclusions of the Biogen study.

"If it were proved that by getting at MS fairly early in the day people were able to remain in work, go on living a reasonably normal existence for a longer time than expected to and make a contribution to the economy through taxes, it would overturn the Nice conclusions," he says. "You can't just look at one enormous end of the bar chart with nothing to balance it."

Anne-Toni Rodgers of Nice would not comment on the agency's deliberations, saying only that "economic modelling is quite a challenging thing to do and does depend on the validity of the assumptions". She did point out that, in its short history, Nice has already changed its mind from provisional to final decision.

Until next month, then, MS sufferers are in limbo, and the struggle for what beta interferon is available on the NHS goes on. Scotland is not subject to Nice - another agency is about to do a cost-benefit study of beta interferon there - but O'Riordan's problem nicely illustrates the discrepancies of prescribing across the UK.

In Tayside region, where he is based, the health authority will pay for the drug to be prescribed to exactly seven patients, out of hundreds eligible. In Grampian and Fife, there is no set limit to numbers; in Glasgow and Edinburgh, no one gets beta interferon on the NHS.

"We're left with many patients who would benefit who aren't getting it," says O'Riordan. "My own opinion is that it's beneficial. If I had multiple sclerosis, I'd prefer to be on it."

Thanks to guardian.co.uk who have provided this article. View the original here.