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The European Union's (EU) orphan drugs programme is marking its fifth anniversary, but a report sponsored by the European Commission (EC) says that for patients with rare diseases, access to treatments still varies from country to country.

Orphan drug prices in Britain are among the lowest in Europe, however, the report says that pricing is highly arbitrary in all markets because purchasers are unable to assess the medical benefits of these treatments. By definition, there are usually no clinical alternatives to an orphan drug, and data are limited because of small patient numbers.

However, accessibility does not depend on price alone, the report concludes. For patients trying to get treatment, what makes the difference is the nature of each country's healthcare and reimbursement system.

Complex networks
In the UK, the system for purchasing specialist services is complex and fragmented. Understanding how the system works, and identifying key decision-makers, requires a lot of ground work. A centralised approach applies to 34 very rare conditions covered by the Department of Health's National Specialist Commissioning Advisory Group (NSCAG - see box 1, at end of article).

Specialist services required by larger populations are commissioned on a regional basis, and each region has developed its own system. There is an additional tier, with some services being commissioned by local PCTs, usually acting through a consortium arrangement. Systems differ yet again in Scotland, Wales and Northern Ireland.

The NSCAG approach is seen as working very well. The NSCAG system does a favour for patients, says Dr Frances Macdonald, general manager of Actelion Pharmaceuticals UK. You are marketing the product to people who are very much specialists and you feel they have a good understanding. I think NSCAG gives the NHS a way of handling these expensive drugs.

However, she can also see how the situation might be more difficult for products that treat rare diseases falling outside NSCAG's remit.

Funding issues
One problem for NHS purchasers is that the costs of some drugs for rare diseases are covered by national specialised commissioning arrangements, while others are not.

It may be that we need a better arrangement for funding of these types of drugs, rather than putting the onus on PCTs to find the money, says Peter Sharott, pharmaceutical adviser to the London Regional Public Health Group.

This view is supported by Michael Sobanja, chief officer of the NHS Alliance: One thing the government can do to make it easier is provide a national contingency fund for orphan drugs. Sometimes a PCT might only get one case in any year and it's difficult to make financial provision for what suddenly comes up as a big sum.

However, Sobanja concedes that more centralised funding is not a very realistic prospect. He notes that while it can cause individual problems, overall, orphan drugs are not a common preoccupation for PCTs.

It is the high cost of orphan drugs related to their limited evidence base that is the main issue, Sharott adds. The two go together because PCTs have to balance the cost against the evidence and think about the cost commitment in terms of their overall priorities.

For rare diseases, there may be only a handful of specialist centres, so purchasers do not have a large body of clinical opinion to draw on, either.

You do get variation in the way some of these drugs are adopted, Sharott says. This needs to be seen in the climate of weighing up the evidence in the proper way and then putting it within the overall priorities. It is not an easy thing to do.

NICE and orphan drugs
In the future, the task of evaluating the evidence may fall to the National Institute for Clinical Excellence (NICE). At present, the Institute acknowledges, uptake of orphan drugs varies across the country and there is no national policy as to whether, and how, such treatments should be provided through the NHS.

With a few exceptions, NICE has not so far issued guidance on rare diseases or orphan drugs. Yet, at the request of the Department of Health, the institute has found itself in the midst of an exercise designed to determine whether it could appraise the clinical merits and cost-effectiveness of ultra-orphan drugs appropriately on a routine basis, using its established methodology.

NICE is defining ultra-orphan drugs as products for conditions with a prevalence of less than 1 in 50,000 or, put another way, conditions where there are less than 1,000 patients in the UK. The institute is trying to assess the situation systematically, with involvement from stakeholders.

It held a conference on drugs for rare diseases at the Royal College of Physicians in London, in October 2004, which brought together approximately 150 clinicians, managers and other people from the industry to discuss ethical issues and different approaches to the evaluation of orphan drugs.

A feasibility study is another key aspect of the project. With cooperation from the manufacturer, Genzyme, two treatments for Gaucher's disease are undergoing a mock appraisal at NICE. Evidence is being assessed in the usual way and members of NICE's three appraisal committees will meet to determine whether they could make a recommendation based on this data, if required to do so.

The committee will not actually reach a verdict on the drugs and the exercise should not have an impact on any future appraisals, should these eventually take place.

We think that it is our duty to collaborate on research projects like this that are trying to look at scientific issues raised by society, says Dr Erik Tambuyzer, Genzyme's senior vice president of corporate affairs for Europe. He believes that his company can provide valuable expertise in the disease area, accumulated from around the world, and over a period of many years.

NICE has also consulted the public. Its Citizen's Council, which advises NICE from the lay person's point of view, considered the ethical issues around the funding for orphan drugs at a meeting in November 2004. The council published its conclusions in a report in January this year (report available through: www.nice.org.uk).

NICE's final recommendations, drawing together all strands of the project, are due to go to the Department of Health in Spring this year. Following that, ministers will decide whether to refer orphan drugs to NICE for appraisal in the future.

On a grander scale
In the NHS, purchasers are ambivalent about NICE's potential role in this area, yet it is always helpful to have objective guidance from the institute, Sobanja, at the NHS Alliance, points out.

The only problem with NICE looking at orphan drugs is that you don't have the same assembly of evidence. He suggests that review at a European level might be more useful because a larger, international, pool of expertise could be drawn upon.

Guidance from NICE would be a step forward but it won't necessarily resolve the funding issue, Sharott adds, noting however, that what could be good about it might be to centralise the decision-making process in terms of clinical effectiveness of a drug.

The Scottish Medicines Consortium and the All Wales Medicines Strategy Group have been issuing guidance on a few orphan drugs, and the two organisations have sometimes come to conflicting conclusions about the same medicine. NHS decision-makers would prefer to see a unified approach between these agencies and NICE.

What the industry can do
If the NHS is looking to the centre for guidance and funding, what will it look for from the manufacturers? Companies should start talking to PCTs when an orphan drug is nearing the completion of phase III trials, Sobanja advises, as commissioners need to know likely patient numbers and costs.

Aside from pharmaceutical advisers and specialist clinicians, I don't think a lot of people in the health service are very aware of orphan drugs, he says. Planning revolves around the NHS budget cycle and in advance of launch, purchasers want to know the actual cost - rather than a speculative figure, says Sharott. They also want to know when a licence will be granted, but informing purchasers is not enough in itself.

That gives an impression that it's a matter of pushing the right buttons in the health service to release the money; and it clearly isn't as simple as that, he adds. It's about accessibility and affordability, and it's a difficult balance to achieve. I think the answer is a partnership between the industry and health providers.

But what purchasers really want is lower prices. The key challenge is justifying the higher price of orphan drugs, which have the same development costs as any medicine but a much smaller market, says Actelion's Dr Macdonald.

About NSCAG

Aims:

• Improve access to uncommon services
• Sustain high levels of expertise by preventing proliferation of too many centres
• Smooth out risk for commissioners
• Assure cash flow to support rare and expensive treatments
• Provide a focus for discussion about service development

Criteria for NSCAG designation

To qualify for centralised commissioning, a super-specialist service must:

• Be an established clinical service
• Relate to a clearly defined group of patients
• Be provided in a small number of centres which between them can meet the national caseload
• Have justifiable costs when set against alternative uses of NHS funds
• Have a national caseload that does not exceed 1,000 and would normally be about 400
• Have sufficient financial impact, when cases arise, that PCTs are unable to respond in-year from contingency funds.

For more information go to: www.advisorybodies.doh.gov.uk/NSCAG/

The Author
Colleen Shannon is a freelance healthcare journalist