Leveling the Field
by Malcolm Wheatley
October 2007
As the U.K. experience has shown, proving the safety, efficacy and value of medications can be a murky affair.
In May 2006, a group of women in Shropshire, England, staged a sit-in protest at the offices of Shropshire County Primary Care Trust, the health care body responsible for providing hospital and primary medical care in the local area. The sit-in, which ended after three days and nights, raised complex issues of patient care and captured widespread attention.
The protest revolved around the drug Herceptin (trastuzumab), proven to be effective in the fight against early-stage breast cancer. Despite being widely available—and free—in many locations elsewhere within the National Health Service (NHS), the Shropshire Primary Care Trust had elected not to make the drug available, pending a review of its cost-effectiveness by the U.K.’s National Institute for Health and Clinical Excellence (NICE), the public body charged by the British government with producing guidance on health technologies and clinical practice in England and Wales.
Supplanting Physician Choices?
Prior to the establishment of NICE, it was up to individual Primary Care Trusts to make their own decisions—with some, such as Shropshire, deciding not to prescribe Herceptin, even though health secretary Patricia Hewitt had previously issued a statement that Primary Care Trusts should not refuse treatment on the basis of cost. As a result, patients living in Shropshire had to fund Herceptin treatment themselves, even if their doctor recommended it. The cost for treatment is £20,000 pounds per year—around US$40,000—an amount far beyond many people’s means in a country where a 50-year provision of free health care had left many people feeling that private health care insurance, taken out individually or through an employer, was an unnecessary expense.
By chance, one of the issues that brought the Shropshire sit-in to national prominence in the U.K. media was the proximity of the hospital in question—the Royal Shrewsbury Hospital—to the Welsh border. Primary Care Trusts in Wales, it turned out, had taken a different view, with the result that Welsh patients receiving treatment at the Royal Shrewsbury Hospital could receive Herceptin free of charge—even as Shropshire patients, receiving treatment at the same clinic at the same time, had to pay.
“It’s just a postcode lottery,” complained the husband of one of the women involved in the sit-in, to the BBC. To many Britons schooled on universal access to free drug provisions, the prospect of random choices about where to live affecting one’s right to treatment—in some cases a life or death decision—seemed plain wrong. In one case, patients located just two miles away over the Welsh border were entitled to the free treatment that was denied people living in Shropshire.
As the controversy mounted, hospital officials, NICE, politicians and NHS officials scrambled to explain how what they were doing was in the public’s best interest. NICE committed itself to fast-tracking the drug through its approval processes and pointed out that it couldn’t approve the cost-effectiveness of any drug or treatment for a purpose for which it hadn’t yet been formally licensed, as was the case with Herceptin at the time.
And to questions regarding why Shropshire was refusing treatment when other Primary Care Trusts weren’t, Julie Grant, chief executive of Shropshire’s health authority, pointed to a recent Court of Appeal case, where judges had ruled that although a breast cancer patient from Swindon should have the drug, its cost was indeed a legitimate consideration for Primary Care Trusts deciding whether or not to make particular treatments available. “Yes, there is that statement from Patricia Hewitt, but from [the Swindon] case, it’s clear that it is legitimate for Primary Care Trusts to consider cost-effectiveness,” she told the BBC.
Value Proposition
After the Shropshire incident, the actions of NICE and Primary Care Trusts were in the media spotlight, and under public and media scrutiny. Even as the fast-track approval of Herceptin was granted just weeks later, NICE’s deliberations on another drug—Tarceva (erlotinib), a once-daily oral treatment for lung cancer that was licensed for use in the U.K. in September 2005—were underway, prompting an eventual refusal. Yet apparent inequalities once again seemed manifest in NICE’s decision—flaws all too clear to Tarceva’s manufacturer, Roche, which announced in early March 2007 its intention to appeal the decision.
NICE had jurisdiction in England and Wales, for example, and not Scotland, where another, comparable body, the Scottish Medicines Consortium (SMC), held sway. But while NICE had not approved Tarceva, the drug was accepted as clinically and cost effective by the SMC in June 2006 and was prescribed freely since then. “The decision by NICE not to approve Tarceva is disappointing, especially considering the fact that Scottish patients have had access to Tarceva since June 2006,” says Nick Thatcher, professor of medical Oncology, at the Manchester, U.K.’s Christie Hospital, a well-known cancer treatment center. “Other European countries have had access to this treatment for over a year and it is very frustrating that English patients are once again losing precious time waiting for Tarceva to be made available to them. It is critical that NICE work with Roche to find a way to make this important treatment available to all eligible patients as soon as possible,” he says.
It’s easy to see the disagreements over Tarceva, Herceptin and others as a purely British phenomenon, limited to the areas where NICE holds sway. But beyond the typical measures of a drug’s safety and efficacy, many national health systems around the world require, or will require, proof of cost-effectiveness. Ireland, for example, is contemplating a health technology appraisal system for oncology therapies.
As the U.K. experience has shown, NICE guidance has indisputable power in determining which treatments the NHS ultimately includes in the formulary. “Ten years ago, every general practitioner or prescriber within the NHS would be what we call an independent prescriber,” says Gareth Thomas, managing director for sales and marketing information specialist Cegedim, located in Chertsey, U.K. But recent market research data complied by Cegedim highlights a significant shift in behavior, Thomas says. “According to our most recent figures, there has been an extraordinary shift towards on-formulary prescribing, with only minor differences between therapy areas.” Thomas adds that within 12 months of a change in policy, on-formulary prescribing in line with a Primary Care Trust’s directives has risen to between 70 and 85 percent. “And this will only continue to grow,” he concludes.
What’s more, guidelines from Primary Care Trusts and others—such as NICE—have resulted in an enormous rise in the dispensing of generic equivalents, rather than branded drugs, Thomas says. “Some 70 to 80 percent of British prescriptions are now for generic drugs, which is a figure much higher than in the United States or elsewhere in Europe.” This is borne out by Cambridgeshire Primary Care Trust who now sets prescribers’ individual targets for the use of generic statins, stipulating that all initial prescriptions for statins are generic drugs, not branded. “Only if there are side effects, or clinical considerations, will a branded statin be prescribed,” Thomas adds.
Relative Merits
Campaigners, both inside and outside the medical profession, are taking up arms against what they see as accountants making prescribing decisions that ought to be left to doctors acting in the interests of their patients—and not their budgets. Owen Paterson MP, the Member of Parliament for North Shropshire, first became involved in the issue when the 10-year-old daughter of Susan Morgan, one of the sit-in Herceptin campaigners, wrote to him. The child wrote the letter because her mother needed to raise £47,000 (around US$92,500) because they lived in Shropshire, whereas if they lived two miles away in Wales, they would get the treatment paid for out of national taxation. It was a letter that, when made public, resulted in an anonymous businessman offering to fund the treatment.
“If you have a National Health Service funded by comprehensive national taxation, as we do in the U.K., then there has to be comprehensive national availability of treatments,” Paterson says. “In a national system, you can’t have two people living two miles apart, yet having different levels of entitlement. Nationally, British taxpayers are funding the National Health Service’s purchase of drugs, but individual taxpayers are only receiving those drugs if they live at particular addresses.”
Herceptin and Tarceva could be the tip of a large iceberg, says Julia Black, a recovered cancer patient who helped stage the Shropshire sit-in protest, and who has since become a vocal campaigner for a the provision of a nationwide “level playing field” when it comes to prescription entitlement. Nexavar (sorafenib) and Sutent (sunitinib malate), she points out, are two drugs widely used in 50 countries around the world in the treatment of renal cancer, but which are not yet in the NICE-approved formulary. And more than that, as NICE itself affirms, neither drug was even on the list to be considered as of March 2007. “A Primary Care Trust may prescribe them if it wants to—but if it doesn’t, or doesn’t think that it can afford it, then people are simply told that they have terminal cancer and will die,” Black says.
But even as some campaigners tackle the issue from the perspective of equality of treatment and natural justice, others are looking more closely at how NICE reaches its decisions regarding cost-effectiveness—and pondering the broader implications for the pharmaceutical industry itself. Dr. Jesme Fox, for example, medical director of the Liverpool, U.K.-headquartered campaign group the Roy Castle Lung Cancer Foundation, argues that in looking at a drug’s relative merits and cost-effectiveness, NICE is overlooking the absolutes.
“Tarceva offers hope to advanced lung cancer patients, for whom there has historically been few therapy options. It is taken in tablet form and has relatively low toxicity. In England, NICE has reached a different conclusion than the SMC in Scotland,” Fox says. “What NICE is really saying in not approving Tarceva, is that despite it giving benefits, the benefits aren’t enough for our national health system to fund it. We think this is a terrible message to send out.” Longer term, she adds, those messages could signal to the pharmaceutical industry that the U.K. isn’t a place to conduct drug trials because the drug might not even get prescribed in the NHS.
Development or Deterrent
With NICE’s lengthy appeal process exhausted, the Alzheimer’s Society is spearheading a legal challenge to overturn the NICE recommendations with respect to prescribing the following drugs: Ebixa (memantine), manufactured by Lundbeck Pharmaceuticals Aricept (donepezil HCI), manufactured by Eisai; Reminyl (galantamine hydrobromide), manufactured by Shire Pharmaceuticals and Exelon, manufactured by Novartis. “NICE argues that they’re looking at the cost-effectiveness of a treatment, but we believe that they have failed to accurately reflect the benefits of treatment for people with dementia and their families,” says Andrew Chidgey, the head of policy and campaigns for the Alzheimer’s Society, in London, U.K.
In particular, Chidgey says, the Alzheimer’s Society is concerned that NICE has failed to take into account important benefits of the drugs—particularly benefits to caregivers. The Society is also challenging the costing NICE has used for long-term care places and the discriminatory impact the recommendations have against atypical groups of people with dementia. “The very fact that a number of pharmaceutical companies have gone to the trouble of seeking a judicial review of NICE’s decision, which is a very expensive process, suggests very strongly that this particular case has the potential to have a significant impact on the development of treatments in future,” he says. In other words, if NICE isn’t going to approve a treatment, why gamble millions on developing it?
It’s a downbeat assessment, but one partially countered by Dr. Gordon McVie, a former chief executive of the London, U.K.-based Cancer Research Campaign, and now a senior consultant at the European Institute of Oncology, based in Milan, Italy. The U.K. has the lowest per capita spend on drugs in the Western Europe, he notes—a position it has held for more than 10 years. So although the U.K. certainly is a major market, it’s not the only game in town, McVie says.
McVie, who also worked for many years in the health care sector in the Netherlands, says there are noticeable contrasts between the U.K.’s NICE-led approach and the stance taken in other countries. “France and Italy are much more sensitive to patient care issues, and adjust their cost-effectiveness decisions accordingly,” McVie says.
Nor is the sort of campaigning going on in the U.K. with respect to drug formularies typical of elsewhere in Europe, McVie says. “There a lot less patient advocacy in Italy and Germany, for example, probably because patients don’t have problems getting the drugs in the first place.”
Concerns of Methodology
But at least in the short term, radical changes are unlikely. NICE in its present form was set up in 2004—well into the present Labor government’s term of office—and politicians are unlikely to pull the plug, or even repurpose its mission, any time soon. Nor, thanks to rocky finances, are the Primary Care Trusts likely to change their stance any time soon, either—although figures released by the NHS in early June 2007 show a reduction in the number of Trusts operating at a deficit: 22 percent, down from 33 percent a year ago. The logic is clear: it’s only by watching the pennies so carefully that deficits have been either avoided or reduced.
“NICE exists and it’s here to stay,” says Richard Ley, spokesperson for the Association of the British Pharmaceutical Industry, in London, U.K. “It’s part of the environment in which we work, and we have to deal with it accordingly.” Acceptance, however, shouldn’t imply unstinting approval. “It certainly doesn’t mean that we think that NICE is a perfect body doing its job in a perfect way,” Ley stresses. “NICE was the first body of its type in any advanced country of the world, its only been established for a few years and frankly, has a lot to learn about doing its job in a better way.”
In particular, he points out, the association takes issue with the mechanisms through which the cost-effectiveness of a treatment is established. “Frankly, we don’t think that NICE’s methodology for determining cost-effectiveness goes far enough to determine the true value of a medicine,” he says. “For example, is a treatment reducing a patient’s dependency on caregivers? Is it keeping them out of hospital? Is enough notice taken of a patient’s concerns over the way a treatment is administered, or its side effects? These are all things that NICE inadequately takes into account today.”
Flawed or not, there seems little doubt that Primary Care Trusts and other dispensing authorities within the NHS do take account of NICE’s attitude to a drug’s cost-effectiveness—even though, as Ley says, they are technically under no obligation to do so. But are the flaws significant enough to adversely affect the process of drug development—acting as a disincentive to R&D spend?
“We’re not packing our bags, but it is a worry,” Ley says. Therapeutic advances are often a series of small steps, he points out, and a disincentive to take one seemingly minor step can have [ripple] effects. “It’s perfectly possible that a setback in one step can have an adverse impact on a treatment some way down the course,” he adds.
Results-Based Reimbursement
And NICE, it seems, may at last be responding to some of the criticisms that have been leveled at it. Sir Michael Rawlins, Ph. D, chairman of NICE, for example, is casting NICE in a more responsive light. “We say ‘no’ to a drug a lot less than 10 percent of the time,” he says. “More typically, what we do is say ‘yes,’ but not right across the full range of indications, only those where we feel it is most cost-effective and delivers good value for money—a ‘moderate’ condition of an illness, for example, and not a mild one.”
Rawlins stresses that NICE is looking at value and that the actual price is almost irrelevant. “Herceptin, for instance, offers very good value for money, as it’s extremely cost-effective in preventing recurrence,” he says. “So we don’t mind rewarding the manufacturer for developing the treatment. What we don’t want to do is reward innovation that delivers only modest value for money compared to existing treatments.”
A role model for the future may come on the heels of an announcement in June 2007 that NICE is adopting a new “payment by results” approach to Velcade (bortezomib) for the treatment of patients with multiple myeloma who respond well to treatment with the drug. Following an evaluation of a refund scheme put forward by the drug’s developers and marketers—a consortium of Millennium Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Ortho Biotech Products and Janssen-Cilag — NICE proposed that all suitable patients should be offered treatment. The scheme stipulates that patients showing a full or partial response to the drug should be kept on it, with the treatment funded by the NHS. NICE proposes that patients showing a minimal or lack of response should be taken off the drug, and the drug costs refunded by the drug’s manufacturer.
At press time, the scheme had not received formal approval; the final decision on whether to put the refund plan into practice rests with the manufacturer and the Department of Health. “If the drug’s manufacturer accepts the proposals that we are consulting on today, it will mean that when the drug works well the National Health Service pays [for it], but when it doesn’t the manufacturer should bear the cost,” says Andrew Dillon, NICE’s chief executive, in a public statement. “All patients suitable for treatment will get the chance to see if the drug works well for them.”
But this will not happen immediately. Noting that the proposal stemmed from an appeal by the drug’s manufacturer, NICE stated that it expected to issue final guidance to the NHS in October 2007, unless further appeals were lodged. And until it issues that final guidance, funding for the use of bortezomib for treating multiple myeloma will continue to be determined at a local level, based on a local assessment of available evidence. More than a year after the Shropshire sit-in first brought the issue to national prominence in the U.K., it seems, the postcode lottery remains.
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