Is the UK’s drug evaluation system in need of an overhaul?

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n 15 March, a debate in UK parliament took place over making cystic fibrosis drug Orkambi available on the NHS.

The session came on the back of a public petition – which garnered some 115,000 signatures – for the UK to follow the likes of the US, Ireland, France and Germany and give the green light for the new treatment.

It highlighted once more the emotive context around rare disease drugs – sometimes known as niche-busters – such as Orkambi. On Twitter, the #Orkambinow campaign, supported by the Cystic Fibrosis Trust, continues to gain momentum. Last June, Orkambi protests, made up of hundreds of people suffering from the genetic disorder and their supporters, took place outside Downing Street.

Yet Vertex, the pharmaceutical company behind the drug, and the NHS remain locked in a stalemate over Orkambi’s price. Following the guidance of the National Institute for Health and Care Excellence (NICE), the medical board responsible for introducing new drugs in the UK, the NHS remains unwilling to countenance the current price tag, which stands at £104,000 per patient for every year of treatment.

As a result, NICE finds itself in the crosshairs over the way it appraises new medicines and treatments, with one MP denouncing it as “an analogue process for a digital age”.

Is there any weight behind such claims? Is the UK’s drug evaluation system in desperate need of reformation? Or is it a case of new drugs being simply too expensive to justify payment from an NHS already in the midst of a budget crisis?

To get to the root of these questions, it’s worth taking a closer a look at NICE’s traditional means of evaluation, which recommends drugs based on cost-effectiveness. This tends to be measured as cost per additional year of quality-adjusted life (known as QALY), using a threshold of somewhere between £20,000 to £30,000 QALY.

In short, drug companies are required to not only prove that their products are effective and safe, but that they offer real value for money. The NICE evaluation system is very much based upon technical decision-making, as opposed to that of the political or social kind.

“Over time, NICE has built a very strong reputation for developing transparent and robust guidance on the use of new technologies,” explains Dr Piotr Ozieranski, a lecturer from the Department of Social and Policy Sciences at the University of Bath.

“Of course, some of these decisions will be contested because of the very nature of evidence that is being evaluated, so this is unavoidable. This is especially the case with drugs for rare conditions, which – given the small patient populations concerned – have very high unit prices and therefore often do not meet the NICE threshold of cost-effectiveness.”

The alternative, says Ozieranski, would be to give policymakers or bureaucrats a greater hand in the decision-making process, in turn making it considerably more subjective and less science-based.

“This would probably shift the balance between the role of science versus political considerations in these decisions,” he explains.

“For example, politicians are generally much more susceptible to various forms of non-scientific considerations. Would we have more trust in decisions on these extremely complex allocative issues if politicians were put in charge of taking them?”

Let us return to the drug in question. Having been given the green light by the US Food and Drug Administration (FDA) in 2015, Orkambi is the first approved medicine to treat the underlying cause of cystic fibrosis (CF). It is specifically intended for patients aged 12 and over who have two copies of the F508del mutation, which accounts for approximately 45% of cases of CF.

Data from phase III studies show that the therapy can improve lung function by as much as 2.6%-4% in some patients. A recent spate of first-person editorials in the media, along the lines of “Orkambi has changed my life”, can be seen as a testament to this.

But while NICE was able to conclude in 2016 that the treatment is clinically effective, it is refusing to budge on its position – much to the frustration of Vertex.

“The challenge we face is the NICE approval process was developed 20 years ago before transformational medicines like Orkambi for small patient numbers existed,” says a company spokesperson.

“Traditional health technology assessments [HTAs] are designed to compare treatment in large populations in well studied indications. Methodology often can’t cope with the enormous value of innovative rare disease medicines that are often the first ever treatment in a small poorly understood patient population.”

For Vertex – which is planning to submit 18 applications to the NHS for new and existing treatments over the next seven years – there is a concern that “medical innovation is outpacing the systems used by the NHSto make new medicines available to those who need them”.

“In the last six years, Vertex has received EU approvals for two new medicines with the potential to treat nearly half of all CF patients in the UK,” the spokesperson continues. “But only 5% of patients in England can currently access our medicines routinely through the NHS.”

It is not the first time NICE and the NHS have been accused of denying UK patients access to life-saving medicines. In a 2016 interview with the Financial Times, AstraZeneca CEO Pascal Soriot spoke of a “disconnect” between NICE and other regulators after the body insisted his company’s lung cancer drug Tagrisso undergo phase III trials, despite have already been granted fast approval by the FDA and European Medicines Agency (EMA).

Nonetheless, a compromise was finally achieved in that particular case with the NHS reaching a final pricing agreement with AstraZeneca. Tagrisso was made available on the NHS in October 2016.

Can we expect any such reconciliation in the case of Orkambi? According to the Vertex spokesperson, the last meeting between both parties – on 25 April, at the time of writing – was “constructive”, but “there is still some way to go to reach an agreement”.

When asked for comment, a spokesperson for the Association of the British Pharmaceutical Industry said: “Where required, conversations between NHS England and companies to agree access to new medicines are entirely appropriate.

“We hope in this case that an agreement can be made so that those patients who stand to benefit from this innovative new treatment can receive it as quickly as possible.”

As for NICE, the body will continue to face the gauntlet of appropriately valuing treatments that satisfy the budgetary constraints of the NHS on one hand, and the pharma companies on the other. It’s an invidious position to be in, says Ozieranski.

“NICE is being asked whether the NHS should pay a lot of money for drugs about which we often know very little,” he says. “This is an extremely difficult question to answer and it is difficult to find a reasonable alternative.

“But then there is the role of the pharmaceutical industry and drug pricing. Drug companies produce many life-saving drugs and bear considerable investment risks especially in rare conditions where patient populations are low.

“So, for the drug industry – and equally some clinicians or patients – the prices reflect the true value of the medicines for patients and healthcare systems. This perspective may not be shared, however, by health economists or NHS managers, who are also involved in this process, as they need to consider other areas of the healthcare system as well.”

But for patients and their families, debate around balancing the books and investment risk are given short shrift. To hear one #Orkambinow campaigner tell it: “Sometimes the parents are as well informed as the healthcare professionals, and even have more of an idea of what is needed and what the results are or can be”.