The multiple sclerosis risk sharing scheme

Four linked articles discuss the UK multiple sclerosis risk sharing scheme.1 2 3 4 The scheme was set up in 2002 to allow patients access to certain disease modifying drugs (interferons and glatiramer) after the National Institute for Health and Clinical Excellence (NICE) recommended that these drugs should not be used.

No one could say that patients with multiple sclerosis have an easy time. We offer no cure. We cannot tell patients what causes the disease. We are poor at estimating prognosis. And when in the 1990s orthodox medicine did deliver treatments (three interferon beta preparations and copolymer-1), not only were they so expensive as to be virtually unavailable in most of the United Kingdom, but the profession could not—and still cannot—agree on their true efficacy. Now Raftery and McCabe and colleagues argue that either they should be withdrawn from the NHS altogether or have their price reduced to zero.3 4

The disease modifying treatments are essentially prophylactic, and like all drugs whose aim is to prevent events (relapses) that are unpredictable and relatively uncommon (the average relapse rate in multiple sclerosis is around one a year), their efficacy is difficult to assess even in large scale trials and impossible in the real world of clinical practice. If a treated patient is relapse-free for, say, two years, is that because of the efficacy of the drug or the natural course of the disease? No one knows.

To make things even more difficult, the calculations assessing whether disease modifying treatments might be affordable in the NHS were predicated on the putative effects of preventing the accumulation of disability in multiple sclerosis, not on relapse rates. To many this seemed hazardous—firstly, because only a proportion of patients (who are unidentifiable) become progressively disabled; and secondly, because the relation between relapses and disability is more complex and more indirect than many imagined.5 Reducing the frequency of relapses does not necessarily reduce the progression of disability. Indeed, studies with powerful monoclonal antibodies show that progression can continue unabated even when relapses are abolished completely.6

In 2002, NICE judged the cost effectiveness equation unfavourable and ruled against provision on the NHS. But the Department of Health brokered a deal with the drug companies in the same year—the risk sharing scheme—whereby disease modifying treatments would be available within the NHS under the conditions of a large study. Treated patients would be regularly assessed and disability measured and recorded. If the drugs were more effective than the NICE predictions, and so achieved cost effectiveness, then all would be well. If not, there would need to be a financial reckoning—payback from the drug industry to the Department of Health or reduced drug costs—to achieve “affordability” post hoc.

The first substantial assessment of the accumulation of disability within the 5000 patients who were recruited and treated has now been performed.7 It found that patients taking disease modifying treatments have acquired more disability than an untreated historical control group. Cost effectiveness and Health Technology Assessment experts now call for the “deal” to be honoured and the risk sharing scheme discontinued—presumably meaning reversion to the original negative NICE judgment and so “their withdrawal from NHS practice”—or alternatively for the drug to be provided free by the drug companies.

These may not be canny suggestions, or realistic. The reaction by patients, patient groups, charities, and the medical profession would be unbearable for any government. The UK already has the lowest prescribing rate of disease modifying treatments of any of the developed nations. Nonetheless, would they be right in principle?

One surprise is that the critical articles are notably free of that healthy scepticism and caution that are normally the health economists’ stock in trade.3 4 After all, this is just one study, unblinded, unrandomised, with an historical control group, using a measure of disability that Raftery and McCabe and colleagues say (rightly) is “not fit for purpose.” Would a positive recommendation for any new treatment be based on such evidence? If these authors really do accept the results at face value, then on safety grounds should they not be stridently alerting the world to the danger that disease modifying treatments accelerate progressive disability in multiple sclerosis? (It is not, after all, impossible to imagine a mechanism for this—immune activation and inflammation are important for tissue repair,8 so reducing them might impair repair.) No one really seems fearful that this result might actually be true. But Raftery and McCabe and colleagues might at least call for a more intensive comparison of these data with any of the large drug company sponsored trials of interferon or copolymer-1 that have studied disability and been published since the scheme started.

What of the benefits of the risk sharing scheme? It has spawned an extremely successful infrastructure of specialist multiple sclerosis care in the UK, including some 250 multiple sclerosis nurses. All contribute to patient care immeasurably beyond the administration of disease modifying treatments, and for all people with multiple sclerosis, not just the small treated minority. Specialist care in other complex neurological diseases has looked enviously at this multiple sclerosis revolution, and followed whenever possible. If the scheme—expensive and flawed, as Professor Ebers points out—turns out to have been no more than a clever wooden horse, then the army of multiple sclerosis healthcare specialists it delivered may make it more than worthwhile. Also, the drugs prescribed will have prevented thousands of relapses, which the health economists might acknowledge. And as Professor Compston stresses, it leaves a platform for introducing new treatments and executing clinical research that is second to none in the world. Meanwhile, a treatment rate in the UK of around 10-15% of patients, compared with 55-70% in the United States and 40-50% in France and Germany, suggests that we may not have strayed excessively from a sound evidence base.

As for the financial reckoning, the expiry of patents beckons, and substantially cheaper interferon beta preparations are already available and being used (such as Extavia). To add a political point to this lively mix of medicine and economics, the workings of the market may ultimately achieve what central planners have not.