NICE and the CDF: Are they still up to scratch?

pharmafile | October 4, 2016 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  CDF, Cancer Drugs Fund, NICE 

Originally published in the October issue of Pharmafocus, Matt Fellows explores medical and pharmaceutical opinion of the divisive institute to determine whether it is the fit-for-purpose appraisal system the industry needs.

If a manufacturer wants a drug to be made available to patients in England on the NHS, it has to go through NICE. As the arbiter of patient availability for all drugs on nationalised healthcare in England, the National Institute of Health and Care Excellence (NICE) carries a duty which few would consider enviable. It is NICE’s job to assess the cost-effectiveness of any drug in order to issue a recommendation for its use on the UK’s National Health Service (NHS) in England. It’s a tough (and some would argue impossible) job, weighing up the benefits of a potentially life-altering drug against a strict and ever-shrinking budget. It’s a heavily problematic area, and that’s even before you get to issues surrounding cancer treatments.

An “unethical political fix?”

Within NICE’s remit lies the Cancer Drugs Fund. Set up in 2008 by NICE on the orders of then-prime minister David Cameron in 2008, the fund’s aim was to enable dying patients to gain access to last-chance life-extending treatments that would otherwise be unavailable due to delays or outright rejection when it came to approval proceedings.

While this sounds like an admirable goal, it’s efficacy thus far is up for debate; both the institute and the fund have become a target of ire for just about everyone at some point in their lifespan, from the big drugmakers to industry analysts to the patients ultimately affected, and its ability to adequately assess crucial treatments and make them accessible has come under increasing scrutiny over the past years.

Particular criticism has been levied against the CDF from the medical community, with some doctors claiming the fund is nothing more than “an unethical political fix”, a disingenuous PR move designed to end the government’s embarrassment every time the tabloids cried that cancer patients were being denied “life-saving” treatment. Professor Richard Sullivan, director of the Institute of Cancer Policy in London, explains that, beyond the obviously self-preservatory nature of the move, it inherently places more value on treating certain patients over others: “The Cancer Drugs Fund was a cheap political fix. Worse, it is unethical. You cannot give priority to cancer over all other serious illnesses, including coronary ailments and dementia. These types of patients are just as deserving of expensive medicines as are cancer patients.”

And this is the area where the failures of NICE’s appraisal system become most starkly evident; the discrepancy in the CDF’s divisive approach towards the value of treatment has propagated a horde of indignant views like those of Mangesh Thorat, a cancer surgeon at Queen Mary’s Hospital London who states: “Saying that cancer cases deserve exemptions from cost controls – while other diseases are not permitted these exemptions – is basic discrimination. You are saying that one type of disease is more important than any other type.” It exhibits a basic failing to adequately distinguish cancer treatments – those which seek to mitigate the effects of an incurable, and often heavily empathic disease – from all other treatments.

Roche is one of many companies who have voiced their disapproval of the system on this basis. The firm’s neoadjuvant treatment of HER2 positive early breast cancer Perjeta (pertuzumab) has been provisionally turned down by NICE. At the time, NICE CEO Sir Andrew Dillon said: “In order to be able to recommend pertuzumab… the committee needed to have more evidence of its long-term clinical benefits, particularly its impact on overall survival.”

“Broken at both ends”

In response, Roche UK’s general manager and managing director Richard Erwin criticised NICE’s methodology as well as highlighted Roche’s commitment to provide cost savings on the drug: “NICE’s assessment criteria, which rely on survival data, make it unable to adequately appraise medicines in the neoadjuvant setting where survival data can take many years to mature. We have been waiting more than two years for a final decision on Perjeta… where again NICE’s methodology is unable to find combination treatments cost-effective, even when they significantly extend overall survival for late-stage disease.”

“These decisions highlight that the appraisal system is broken at both ends. We have offered more than £110 million in savings over the next four years on Perjeta and Kadcyla (trastuzumab emtansine) but NICE’s assessment criteria needs to be reformed to be able to accept these flexible pricing and assessment arrangements.”

Pharmafocus spoke to Deborah Lancaster, Roche’s head of market access, to further explore this fundamental failing:

“It’s been 15 years and NICE haven’t changed their methodology or the ISA threshold since then, and now we have products like Perjeta rewriting the science books and they are more high-cost; the world has moved on,” she explains. “It’s virtually impossible for us to hit that threshold without giving discounts that would put us at risk of selling below cost of goods, which of course is illegal. We know that you’re not going to cure these people, all you’re going to do is extend their life, and that isn’t given the same sort of value.”

As a result of this, some have argued that its already thinly-stretched resources would have been better spent elsewhere. In 2014, the Cancer Drugs Fund spent £280m on medicines, £80 million over its original £200 million budget, health economist Professor Karl Claxton of York University explains. “That money did some good but it would have done a lot more if it had been spent elsewhere in the National Health Service.”

Quality adjusted years of life is a metric used by health professionals to determine the efficacy of treatment. According to Claxton, 21,645 quality adjusted years of life would have been added to patients’ lives if that £280m had been used by the NHS on all illnesses rather than just a single area. Instead, fewer than 5,600 quality adjusted years of life were seen; “An appalling, unfair use of NHS resources,” Claxton laments.

The CDF continued to outgrow its budget year on year and faced withering austerity cuts, but it was never intended as a permanent measure. However, disorientated by budget cuts and the government’s general low-priority complacency over the issue, the original, perhaps well-meaning blueprint was never truly consummated; as Lancaster asserts: “It was meant to be bridge until we got value-based pricing or some other solution that was going to fix the issue, and that bridge hasn’t been finished at the other end.”

This has led, Claxton believes, to the fund causing more harm than good. Writing in New Scientist, he noted: “The Cancer Drugs Fund has enabled manufacturers to sell their drugs to the NHS at prices beyond those it can normally afford. The fund was originally proposed as a temporary measure until a price negotiation mechanism with manufacturers was in place. This has not happened. As a consequence, the problem that NHS patients face in accessing new cancer drugs continues to be their high prices. The fund has done nothing to address this issue. Indeed it has made it worse, because its existence means there is less incentive for manufacturers to agree to affordable prices.”

Eisai has also pitched in on the debate, stating its thyroid cancer drug Lenvima (lenvatinib) has been “stuck in limbo” under the institute’s appraisal process. Granted an accelerated assessment and approved by the European Commission in May 2015, the drug has been available in many European companies for some time. But after numerous rejections, and despite providing concrete evidence for the product’s efficacy, Eisai’s drug has been left out of the CDF’s evaluation list and will not see review until June 2018, meaning patients in England are forced to wait an “unspecified period” in order to access it.

On the decision, Gary Hendler, CEO of Eisai EMEA and president of the firm’s Global Oncology Business Unit, commented: This situation would indicate that England is turning the clock back and fast becoming the sick child of Europe in terms of access to innovative cancer drugs.” Frustrations with the UK appraisal process has even led to the Japanese firm threatening to pull its investments from the region.

A difficult position

But not everyone is queueing up to criticise NICE. Andrew Roberts, head of market access at Napp Pharmaceuticals told us in the latest issue of Pharmafile: “I think it’s very easy to criticise NICE. They have an extremely difficult job in that they have to take decisions about medicines based on cost-effectiveness. Therefore, the process is limited in itself because it is often driven by the data that is available.

“One of the things the industry has to get better at doing is, when it launches, it brings products to market with data that makes the job of evaluation easier,” he continued. “If you were able to give NICE, and other bodies like the SMC, better health and economic data at launch, maybe NICE wouldn’t be in such a difficult position. It’s a very difficult ethical debate when you get into cancer medicines. You have to try and put a price on extending life.”

Lancaster also feels it is important to resist the urge to let the controversy surrounding the fund eclipse its successes, noting: “It’s enabled over 80,000 patients to get access to medicines they wouldn’t have otherwise had, and all those extra years of survival add up and it’s had a huge impact. The UK moved from being 11^th in Europe for the use of innovation to 7^th in terms of cancer medicines for that period. So it was very, very effective.”

“Not sustainable”

Despite these successes, the fund has always attracted criticism for its decision-making and, on top of this, has become vastly overspent over its brief history. The original plan was to have the fund run until March 2014 with a budget of £650 million – an interim solution while government, regulators and industry devised a long-term pricing mechanism for cancer and end of life treatments. But the fund was extended until March 2016 and accrued a total lifetime budget of £1.27 billion – already almost twice the original intended cost.

An investigation by independent public spending watchdog the National Audit Office (NAO) examined the “rationale for the fund and how it relates to mainstream NHS processes” based on information identified during an NAO report on cancer outcomes and services published in early 2015.

Dr Richard Torbett, executive director of commercial at the Association of the British Pharmaceutical Industry (ABPI), said of the report’s findings: “Whilst the Cancer Drugs Fund improved patient access to cancer medicines that are not routinely available on the NHS, the report makes clear that the use of new cancer drugs in the UK still remains below the average in other comparable countries. We remain adamant that this needs to change.

“We want to see many more patients benefitting from new and innovative medicines, including cancer medicines, and we have long voiced the view that the Cancer Drugs Fund is not sustainable in its current form, as the NAO report highlights. What is needed is a wholesale reform of NICE, which, along with NHS England, needs to develop a longer-term sustainable solution to the evaluation and commissioning of cancer medicines.”

A fresh start?

Torbett may have got his wish, but perhaps not in the form he wanted. In July this year, much-delayed reforms have placed the decision-making process over access to cancer drugs back into the hands of NICE; the CDF becomes a managed access fund that covers the cost of promising new drugs for a set period while the NHS gathers real-world evidence on the their use. NICE then decides whether or not to recommend them for routine commission. This means that NICE is the sole referee on whether a cancer treatment is cost-effective in providing value to patients, in addition to all other therapies. This decision has not gone down well among industry associations, pharma companies, patient groups or charities. The ABPI described the new proposals as “largely unchanged”, saying they could in fact hurt patient access.

“This carries the very real risk of significantly setting back patient access to cancer medicines, now and for the foreseeable future,” said the ABPI’s value and access director Dr Paul Catchpole. “If cancer medicines go through more or less exactly the same NICE appraisal process that was in place five years ago – which necessitated the setting up of the CDF in the first place – we will largely get the same answers as before; the majority of medicines will be turned down. Turning the clock back five years just doesn’t make sense; substantial change is needed to the way that NICE appraisers cancer medicines to prevent this.

“We also need less draconian financial controls,” he continued. “It is unreasonable for companies to be expected to underwrite 100% of the financial risk in managing the CDF budget, something which is outside of their individual control. Without substantial changes, the ABPI estimates that under the proposals two-thirds of existing CDF medicines are likely to no longer be available to NHS patients by the end of the year. This is in addition to patients who are already waiting for access to around ten new cancer medicines which have been launched since the Fund was closed to new applications in May 2015.”

Eisai’s Hendler believes “the decision to implement the new CDF pretty much as it was proposed in the consultation will put cancer treatment back to where England was prior to the creation of the Fund which is a tragedy for patients. Time is not a luxury that these patients have.”

Lancaster shares these concerns: “The worry is with the initial high volume of things that NICE have now got to review because they’re going to be doing every cancer drug, not just the latest ones. I’m not sure if, without a major expansion, they’re going to be able to do that in a timely fashion.”

The revamped system works on the basis of awarding drugs a ‘yes’, ‘no’ or ‘maybe’ status to determine whether drugs are effective enough to be funded on the NHS, with those under the ‘maybe’ moniker showing promise, but requiring further evaluation and efficacy data within two years to be given a final verdict – an issue which Lancaster worries cannot be applied to all treatments indiscriminately:

“Only the medicines that get a ‘maybe’ from NICE will go into the CDF, and we don’t think there are going to be many medicines that get a ‘maybe’,” she notes. “Say you had a neoadjuvant treatment and pathological complete response is used as the endpoint. The ISA range could be anything from 2-99; you’re not going to be able to answer that question in a two-year data assessment, it would take a decade to get proper overall survival data. So it’s hard to see, particularly with the type of medicine we’ve got, what sort of questions you could answer in two years that would enable NICE to say yes or no. For some drugs [a two-year timeline] may well work, but I think for anything where you’re going to be looking at overall survival in cancer,  the majority, especially in the early setting, aren’t going to be able to answer questions in two years.”

So perhaps the biggest problem with these reforms is that, because NICE has not actually reevaluated its own assessment criteria, they haven’t actually brought any true reform to the system at all:

“Because NICE hasn’t changed, in effect we’re taking things that didn’t get through NICE in the first place and putting them back through without changing the system,” explains Lancaster. “We’re tipping it back into the same bucket that didn’t let it go through in the first place. The UK is the only country which works to a very, very strict ISA threshold and doesn’t take other things into account.”

A two-way street

It is clear the system doesn’t work for everyone, and that is a problem. But the solution is far from simple.

“I think there’s going to be some pressure needed from all parties,” Lancaster says. “It’s really urgent; things are coming off the Cancer Drugs Fund and being turned down by NICE now, and we know that that’s going to happen to more medicines as we move forward, and these are all affecting patients who are going to be going back to 2010 in terms of treatment options, and that’s really, really not fair.”

“I think we need to make sure that NICE have got the ability to positively assess innovative high-tech medicines and recognise the value in end of life,” she continues. “Innovative ways of pricing, innovative ways of looking at the way we can make things cost-effective, but NICE needs to be more flexible as well as the industry. It’s a two-way street.”

And ultimately it may all come back to the government in determining whether the system can achieve what they perhaps first envisioned: “It has come from government; it’s not up to NICE to say “we’re going to change,” Lancaster concludes. “There needs to be some pressure and they need to be given guidance.”

Matt Fellows