The National Institute for Clinical Excellence (NICE) is dragging its feet and Herceptin should be offered to the breast cancer patients who need it
- 'Fury over Cancer Drug Delays', BBC News (15 August, 2001)

This recommendation is outrageous. If upheld, NICE is burdening doctors with the task of telling up to 1,500 people a year that they cannot receive treatment, despite there being an effective therapy available
- Steve Winyard, head of public policy at the Royal National Institute for the Blind, in the Daily Telegraph (13 June, 2002)

NICE's decision was condemned as 'abhorrent and disgusting' by Lillian Turner, whose husband Keith, 69, was diagnosed with Alzheimer's
- Daily Mail (18 July, 2007)

NICE claim they are 'protecting us', but in my view what they are doing is evil
- James Whale, 'shock-jock' radio presenter who has kidney cancer, in Mature Times (10 October, 2008)

Campaigners [...] accuse NICE of condemning sufferers to an 'early death sentence'
- Daily Telegraph (28 November, 2008)

The National Institute for Health and Clinical Excellence (NICE) was established in England and Wales in 1999 as an independent body¹ to advise which medications and procedures should be made available free on the National Health Service (NHS²). The aim seemed simple: assess the merits and cost of various treatments, and decide which ones the NHS should buy using a limited budget. However, the organisation has made regular headlines with its decisions not to recommend various high-profile drugs, and NICE often seems to exist to save the government money by denying funding for expensive life-prolonging treatments. Is this the case, or is NICE really just a misunderstood organisation with an unpleasant task to perform?

Some Ancient History

The NHS was established in 1948 with the aim of providing healthcare free at the point of need. This principle is still in operation today, although charges are made to some patients for services such as prescriptions, dental treatment and eye tests.

In the years after the formation of the NHS, medical science moved on rapidly. The fledgling NHS did not have to deal with the expensive staples of modern medicine such as intensive care units, MRI scanners, organ transplants, kidney dialysis and advanced neonatal care. Furthermore, recent decades have seen a huge expansion in the number of drugs available. By the 1980s, doctors were left scratching their heads at the sheer volume of data available to inform their treatment choices. Was drug A better than drug B? Should they be prescribing the latest 'wonder drug', or would an older, cheaper agent be just as effective?

Some Less-ancient History

In 1986, the government tried to address the problem by introducing the 'Selected List Scheme'. This allowed doctors and pharmacists to see which treatments had been investigated and were considered to be obsolete or less effective than the alternatives. However, the rapid pace of development made it increasingly difficult to keep the list up to date, and doctors were again left with no real way of knowing which of the newest treatments they should be using. The upshot of all this was that bane of the tabloid newspapers: 'postcode prescribing'³. Because decisions were left to individual healthcare authorities, who could commission and carry out their own reports, a situation arose where a person living in one part of the country could receive a treatment not available to someone in another region, sometimes even a neighbouring district or county.

Some Relatively Recent History

In 1997, a government White Paper⁴ was published called The New NHS, in which the idea of an independent body to evaluate cost-effectiveness of medical treatments was first proposed. Further details were presented a year later in a government paper called A First Class Service - Quality in the New NHS, and NICE finally came into being on 1 April, 1999.

What Does NICE Actually Do?

When a new drug is developed, it must first be approved by regulatory authorities, who examine all the evidence to determine whether it is effective and safe⁵. In the European Union, the job of licensing new drugs falls to the European Medicines Agency (EMEA)⁶. When a new drug is licensed, it becomes available for prescription to patients. Unfortunately, pharmaceutical companies hold patents on any new drugs they produce, and the huge cost of developing drugs combined with a need to make profit means that new drugs are generally very expensive. It is the job of NICE to determine which drugs give the best combination of benefits for patients and value for the NHS.

Based on a list drawn up by the government's Department of Health, NICE investigates drugs and medical procedures to determine whether they are cost effective. This can be in the form of a 'technology appraisal' or a 'clinical guideline'. In a technology appraisal, one specific treatment (or group of very similar treatments) is investigated, while clinical guidelines cover the whole range of treatments available for a particular disease or condition.

First, NICE invites submissions from anyone with a vested interest in the treatments under investigation. This includes the company or companies that make any relevant products, patient groups and professional bodies such as the Royal College of Physicians. Based on the submissions from these 'stakeholders', and a very detailed review of the available evidence from clinical trials and economic studies⁷, NICE publishes a draft guideline. There is then at least one consultation period, during which the stakeholders get the chance to comment on the draft. Finally, a set of guidelines are published specifying whether the drug should be made available free on the NHS and, if so, to which groups of patients.

The key parameter that NICE looks at is the Quality-Adjusted Life-Year (QALY⁸). A measure of 1 QALY indicates that a patient experiences an extra year of life of a good quality⁹. Information on QALYs is generated in complex computer-based mathematical models, which are tailored to the drug and disease in question. Data from clinical trials is used to generate the model and, using parameters such as drug efficacy, the chance of side effects and improvements in quality of life, a cost-per-QALY is generated. NICE's decisions are usually based on the assumption that a treatment costing £30,000 or less per QALY gained is cost-effective¹⁰. This means that treatments that dramatically improve patients' lives, or extend their lifespans, are more likely to be cost effective than those that have only minor effects. Conversely, the more expensive a treatment, the less likely it is to be cost effective, even though it may be clinically effective when given to patients in a trial. Even when a drug is not cost effective overall, NICE will often specify certain groups of patients who can receive the drug, such as those with a particular sub-type of a disease, or with disease of a certain severity.

You Can't Please All of the People...

As noted above, NICE came into being in April, 1999. By October of that year, it was already clear that the new organisation was not going to have an easy time.

One of the first drugs to be evaluated by NICE was the anti-influenza drug zanamivir (Relenza®). NICE's decision not to approve the drug was met with heavy criticism from the drug's manufacturer, Glaxo Wellcome¹¹, with the company's chairman threatening to remove future research from Britain. In what was described by perennial NICE-bashers, the Daily Telegraph, as a 'U-turn', NICE issued updated guidance a year later¹². Based on new data, NICE recommended that the drug be used for elderly patients and those at high risk of death from influenza.

The drug companies weren't the only ones putting pressure on NICE, and in June 2000, NICE again revised an initial decision not to recommend a drug. This time it was the multiple sclerosis drug beta-interferon. Under pressure from patient groups, NICE revised its decision, despite the fact that a comprehensive independent review of clinical trial data for the drug has shown its effects to be 'modest'¹³.

Patient groups and charities again waded in when, in 2002, NICE issued preliminary findings on a drug to treat age-related macular degeneration (ARMD), a condition leading to blindness. Initially, NICE decided that use of verteporfin (Visudyne®) should be limited to patients who had already lost the sight in one eye. Perhaps predictably, the Daily Mail and Daily Telegraph immediately published stories under almost identical headlines: 'You must [lose sight/go blind] in one eye before NHS will treat you'. Eventually, the final assessment issued by NICE in 2003 declined to make any specific recommendations about verteporfin.

NICE also ran into trouble early when it emerged that its recommendations so far had actually failed to address the issue of postcode prescribing. Local healthcare trusts were still making independent decisions whether to fund particular treatments, regardless of any advice issued by NICE. The situation was finally resolved in 2002 with an edict that NHS trusts were legally obliged to provide funding for those treatments recommended by NICE.

One of the most high-profile cases involving NICE was that surrounding the breast cancer drug trastuzumab (Herceptin®). NICE was twice involved in controversy over trastuzumab; once relating to its use in advanced breast cancer, and then later relating to early breast cancer. Trastuzumab was initially licensed for use in Europe for patients with advanced breast cancer in 1999, leading to calls for it to be available free on the NHS. NICE's review process took longer than expected, however, and a recommendation for the drug was not issued until 2002. In 2006, the European licence for the drug was extended to patients with early breast cancer, and two weeks later NICE issued a 'fast-tracked' guidance recommending its use on the NHS. On this occasion, NICE were perhaps railroaded more than usual by a judgement in the Court of Appeal that Ann Marie Rogers, a patient with breast cancer, should be given the drug, despite the decision of her local NHS trust and an initial High Court ruling¹⁴.

The NHS kindly allows me to buy my own Aricept because I'm too young to have Alzheimer's for free, a situation I'm OK with in a want-to-kick-a-politician-in-the-teeth kind of way
- Sir Terry Pratchett, novelist, quoted in the Daily Telegraph

Another high-profile NICE entanglement was related to three drugs for the treatment of Alzheimer's disease: donepezil (Aricept®), galantamine¹⁵(Reminyl®) and rivastigmine (Exelon®). As the three drugs work in an identical way, NICE considered them as a group. The initial decision by NICE was to approve all three for the treatment of patients with Alzheimer's disease of mild or moderate severity. In 2006, as part of a planned review of the guidance, NICE re-evaluated the three drugs, taking the most recent data into account. The evaluation also included a fourth drug, memantine (Ebixa®), which works in a different way to the others. NICE's conclusion was that use of the original three drugs, while appropriate for patients with moderate Alzheimer's disease, could not be justified in patients with mild disease, while memantine should not be used outside of clinical trials. Predictable outrage met this decision, and the ramifications are still being felt. In response to the decision, Eisai and Pfizer - the manufacturers of Aricept - together with the Alzheimer's Society, took NICE to court. The court ruled strongly in favour of NICE, leading the Alzheimer's Society to withdraw from proceedings. Eisai/Pfizer were not to be put off, however, and went to the Court of Appeal. As in the Herceptin case, the second court found against NICE, ruling that the economic model used by NICE to appraise the drugs should be released for the drug companies - and any other interested parties - to study. At this point, The Sun weighed in with an article beginning 'Drug watchdogs face a massive climbdown' (2 May, 2008). The aforementioned climbdown has yet to occur, although NICE has been collating comments on the model from those who have reviewed it.

Abhorrent, Outrageous and Evil?

The main problem that NICE has is one over which they have no control, and one that is invariably forgotten by those wishing to pursue an anti-NICE agenda. It is simply that the NHS has a finite amount of money that must be distributed as equitably as possible among all the potential patients in England and Wales. In an ideal world, every patient would receive precisely what they need, regardless of cost or availability. In the real world, this is not possible.

When the NICE guidance on drugs for Alzheimer's disease was published, some newspaper articles chose to focus on the fact that treatment cost 'only' £2.50 per day. What few of them seemed interested in was what else the NHS could do with £2.50 per day. Is the best use of that money to provide an elderly person with Alzheimer's disease with, perhaps, an extra year or two before their memory deteriorates completely? Clearly this would be of enormous benefit to the patient and their family. But would it be better to put that money towards paying for an incubator for a premature baby? Or treating a child with leukaemia? Or a mother with breast cancer? Or someone with a non-life-threatening but extremely painful condition? Or helping someone to stop smoking, or lose weight, thereby potentially freeing up thousands of pounds in future NHS spending on tobacco- or obesity-related disease? Who is supposed to make these decisions? The patient? Their family? Their doctor? Or does it make more sense that these decisions are taken centrally, based on the best scientific evidence available? The answers that come out of NICE, when they add up their cognitive function scales or their mortality curves, their quality of life scales and their QALYs, may seem a little calculating, but are they really evil?

In the organisation's own words, 'The decisions NICE makes are amongst the most difficult in public life'. It is only to be expected that patients and their families will protest and appeal when expensive new drugs are withheld for cost reasons. However, withholding those drugs almost certainly means that, somewhere else in the NHS, other patients are receiving the treatment they need. For better or worse, someone has to decide where the money goes. NICE is not perfect. It has been criticised for working too closely with the pharmaceutical industry, and for the phenomenon of 'NICE blight', a situation where drugs that have been licensed but not yet reviewed by NICE are not being prescribed. In particular, the slowness with which a number of cancer drugs have been reviewed has been highlighted. NICE has instituted a 'fast-track' procedure for important new drugs, but this of course means that the appraisal process is less thorough. NICE's focus on new treatments at the expense of older treatments has also been criticised. In addition, NICE's focus on QALYs means that it perhaps lacks some flexibility. For example, NICE does not take into account the benefits of treatment on a patient's family or carers, something that Eisai/Pfizer stressed in the Aricept case. Whatever its flaws, though, NICE is doing an almost-impossible job with far more successes than failures, even if this is not reflected in the media. It is certainly not the monstrosity that certain braying voices would have us believe.