NICE | Dr. Malcolm Kendrick

A reader of this blog sent me this e-mail message that she had just received:

“This is a special Cholesterol e-News Bulletin asking for your help to draw your urgent attention to a recent decision by NICE that is of great concern to us.

There has been significant progress in the management and treatment of cardiovascular disease (CVD) over the past two decades, which has resulted in an overall decline in CVD deaths in the UK. Heart disease still remains one of the UK’s biggest killers. Over half of all UK adults have raised cholesterol increasing their risk of cardiovascular disease; leading to heart attacks and strokes. Not only does it have a devastating impact on patients and their families, but it also places significant burden on our health service and wider economy.

Innovative new medicines, such as PCSK9 inhibitors, are an exciting development in the treatment of cholesterol, with little known side effects and very good scientific evidence that they work to significantly reduce the levels of bad cholesterol in those at high risk of CVD.

NICE reviewed the first of these PCSK9 medicines and recommended that it should not be available for NHS patients.

HEART UK is concerned by NICE’s recent decision to turn down the use of the first of the PCSK9 medicines. This means patients will not have access to the best possible treatment options to help lower the levels of bad cholesterol, particularly those at high risk such as people with an inherited high cholesterol condition called Familial Hypercholesterolaemia.

NICE are conducting a second round of consultation, closing on Tuesday 8th December, before issuing final guidance. On behalf of the patients in England adversely affected by this decision, please join HEART UK’s efforts to reverse this decision and allow PCSK9 inhibitors to be more freely available for NHS patients.”

NICE = The National institute for Care and Health Excellence. Let us not dwell for too long upon that self-aggrandizing title. NICE was set up in the UK, initially to look at whether or not various healthcare interventions represented good value for money, or poor value for money.

For reasons beyond the understanding of man, they plucked a figure from the sky one day (well not a figure, a range) from £20 – £30K ($33 – $48K) per year. If the intervention cost more than £20 – £30K/year to provide one added year of full quality life, then they turned it down. [One year of full quality life = 1 QALY (quality adjusted life year)]. And breathe.

Of course, NICE make all sorts of exceptions (all cancer drugs get funded no matter how much they cost, or how useless they are – go figure) and the way NICE words out how much interventions actually cost/ per QALY is complete nonsense in many cases. Be that as it may, they do make an effort to say ‘How much!’ ‘You must be joking,’ Reject…bong!

If NICE do say, reject, bong! This basically means that the drug will not be prescribed to anyone in the UK. In addition, such is the influence of NICE that many other countries use their decisions as an important guide for what they will do with regard to funding. So if NICE turn a drug down, this is very bad news from the manufactures or said drugs.

Now, when it comes to the new cholesterol lowering agents (PSCK-9 inhibitors) the manufacturers have a problem. Which is that they cost around £4 – £8K ($6.4 – $12.8) per year, per patient. Now, at those sort of costs, you are going to have to have some seriously impressive benefits. At present, however, the manufacturers have no data on mortality, or morbidity. Which makes the current cost per QALY = infinity. Just slightly above the NICE thresholds.

For those who read my blog you will know that I wrote the following in ‘Changing the definition of Familial Hypercholesterolaemia.’

At present I would think that the response of NICE (to PCSK-9 inhibitors) would be ‘Are you out of your tiny little minds. Why the [[…] insert swear work of choice here], would we fund this?’ At least I would certainly hope this would be their response. Imagine if everyone on statins in the UK, around seven million, changed to PCSK9 inhibitors This would cost £56 billion pounds [$80Bn] a year. A tidy little sum. Half of the entire NHS budget.

As it turns out NICE did turn down the first PCSK9-inhbitor, no surprise there. And this is where HEART UK comes in….

Before going any further I should state that there are, currently, two PCSK9-Inhibtors launched/launching. They are Repatha ‘evolocumab’ made by Amgen. And Praluent ‘alirocumab’ to be co-marketed by Sanofi and Regeneron. They are, to all intents and purposes, identical drugs doing identical things. Remember the names Amgen and Sanofi. Amgen and Sanofi….

Now HEART UK states that it is a charity. ‘HEART UK – The Cholesterol Charity – campaigns to increase general public and policy makers’ awareness of raised cholesterol as a major public health concern. We campaign to keep action on cholesterol at the forefront of the health debate.’ ¹

Where do HEART UK get their funding from. Difficult to tell precisely. They claim to get money from public donation… how much? It’s a secret. What I do know is that they receive a very large amount of funding from companies that have cholesterol lowering products. So, for example Nestle, who make Shredded Wheat, pay HEART UK money, and HEART UK says stuff like

‘HEART UK dietician Linda Main said: “Shredded Wheat and Shredded Wheat Bitesize are low in saturated fat and can play an important role in a heart healthy diet and HEART UK is delighted that these products are supporting National Cholesterol Month and the Great Cholesterol Challenge.’²

Kerching!

Of course, when it comes to cholesterol lowering PCSK9-Inhibitors are the big daddies, with the big, big, budgets. So, you would expect that Amgen and Sanofi would be very, very, close to HEART UK. Well, if you expected that, you would be right. If you want to visit the HEART UK website, and look at the sponsors of their conference we have³:

Sanofi: Exclusive conference sponsor

Amgen: Sponsored symposia 1

Sanofi: Sponsored symposia 2

Amgen: Privileged sponsor…etc.

And now, to bring the two strands of this little tale together. NICE have just turned down the first PCSK9-inhbitor and so we have HEART UK reaching out to everyone that they know, or have contact with, to plead with them to sign a petition ‘On behalf of the patients in England adversely affected by this decision, please join HEART UK’s efforts to reverse this decision and allow PCSK9 inhibitors to be more freely available for NHS patients.’ Sob. But what about Tiny Tim?

Some people, were they to be truly cynical, would allege that HEART UK may not be trying to get NICE to reverse their decision on PCSK9 – inhibitors, for the great good of humankind. But because they are being paid large sums of money by the manufacturers of PCSK9-inhbitors. Shame on anyone for thinking such a thing. With Christmas coming this should be a time of peace and happiness. Such cynicism has no place in my thoughts. No sirree.

[And for my Christmas quiz the reader with the best answer to the following question will have it published on my blog. ‘What is a health charity, and should they be allowed to accept sponsorship from pharmaceutical companies?’]

1: http://heartuk.org.uk/policy-and-public-affairs

2: http://heartuk.org.uk/latest-news/article/press-release-shredded-wheat-to-support-heart-uks-national-cholesterol-mont

3: http://heartuk.org.uk/news-and-events/meetings-conferences/heart_uk_annual_conference/sponsors

“Don’t bother me with facts, son. I’ve already made up my mind,” Foghorn Leghorn

NICE stands for the National Institute for Health and Care Excellence. It is a little known fact that it started life as the National Institute for Cost Effectiveness, before rapidly transforming into the National Institute for Clinical Effectiveness, then the National Institute for Clinical Excellence. As you can see it changed again, and now it should be NIHCE, but we do so like our acronyms also to be words. A life of simple puns is the life for me.

I was involved with NICE early on; I set up their first website for them, before being rather rudely elbowed aside. Naively, at the time, I thought the underlying concept of NICE was sound. An attempt to try to work out which medical interventions both worked, and also provided good value for money. This would bring rational thinking to the complex and difficult world where limited resources have to be rationed in some way.

Clearly, I knew that the Government of the time had basically set NICE up to act as a barrier to attacks by the public and a restless media. As everyone knows, the minute you refuse treatment to a young child for, say, cancer, the front pages of the newspapers light up in outrage. By getting NICE to say no, the Government could cower behind NICE’s decisions in relatively safety.

For, as we all know, even if a treatment costs two million, and the chances of success are one in a hundred, most people simply adopt the ‘pay anything, do anything, to save this child.’ mode. The counter argument, that I could use that two million to save fifty lives elsewhere rarely gets an airing. ‘A child is dying….’ Is an argument that usually shuts everyone else up pretty quickly. You can look a tad heartless, very rapidly.

In reality, the cowering didn’t last too long, for as some of you will know, the UK Government is now happy to pay almost unlimited monies into the cancer drugs fund. NICE says it is too expensive… don’t worry, ‘Our caring kind and compassionate Government is willing to pay anything for cancer drugs.’

Of course this rather destroys the entire point of NICE whose decisions are simply bypassed, and also makes it clear that people with cancer are considered far more valuable than anyone else. ‘Dying of motor neurone disease, or heart failure, or kidney disease…. Sorry mate, no money. We have spent it all on cancer drugs.’ The NHS, for a system so terrified of discrimination, against anyone, on the grounds of anything, it seems strange to positively discriminate in favour of people with one form of disease vs. another. Oxford entrance exam, discuss.

Don’t worry, it has long been clear that vote winning irrationality will crush evidence and judgement at every turn.

Anyway, I am getting far away from the point of why I set out to write this blog. NICE, like most organisations started out with a fairly clear aim. To look at medical interventions, then decide which ones provided enough benefit, at reasonable cost, to be funded. But it has grown and grown, or perhaps I could say that its role has metastasised.

It now has become – primarily – a guideline generating monster. Every couple of weeks NICE will drop six hundred pages of ‘how condition x must now be treated,’ onto the medical profession. Dense and verbose and boring and very, so very very, long, and then what?

Are they rules, must they be followed? This all becomes very opaque. Last year NICE decided (super short summary) that everyone with a risk of a cardiovascular event greater than 10%, over the next ten years, should be put on a statin. There was much debate, and the BMA (British Medical Association) voted – unanimously – that these guidelines should not be followed.

Did this make any difference? No. Did it make any difference that the Local Medical Committees (that represent all GPs) at their annual conference voted unanimously against these guideline? No. What are NICE doing about the fact that, at least, two thirds of GPs are completely ignoring these guidelines. Nothing…yet. No debate, no discussion. Nothing. They know that, over time, their guidelines will solidify into something that becomes, effectively, mandatory.

‘Our great and magnificent guidelines have been written, they shalt be distributed to the populace who shalt fall upon them with gratitude. This is the word of NICE.’ The huge stone gate to the citadel, that encloses the enclave of the wise men of NICE, then swings shut, until the next holy set of guidelines will be brought out, to magnificent fanfare. ‘All hail the NICE guidelines.’

Can you discuss anything with them? No, you cannot. A number of people, including me, wrote an open letter to NICE criticising the guidelines. NICE deigned to read our letter, they reviewed their own decision making, and they decreed that they could find no errors in what they had done. They were good enough to inform us of this fact citing the eminence of their ‘experts’ whose greatness and wisdom passes all mortal understanding.

Then what could we do? Nothing. NICE, you see, are both the prosecution and the defence council, the Judges and the Supreme Court all wrapped in one. There is no higher authority. There is no executive, no Ombudsman. The only authority that can review a NICE guideline is… NICE.

Which means that, for example, when a study comes out showing that long term statin use increases the risk of Parkinson’s disease by 230% (Relative Risk increase)¹, NICE can feel free to totally ignore it. In fact, when confronted with this study they said it was ‘nonsense.’ An interesting response, I felt, before they had even seen it.

Ignoring NICE’s view that this study was nonsense, I did a little calculation based on this paper. It went something like this.

Parkinson’s disease affects about 1 in 250 people. It is not rare, but not that common. The NICE guidelines on statins mean that, at the very, very, least, 50% of people should take statins from the age of fifty, for the rest of their life [how many actually will is a moot point, but stay with me here].

If 50% of people take statins and the risk of Parkinson’s increases by 230% it follows that the 1/250 lifetime risk of developing Parkinson’s becomes an extra 2.3×1/250/2 = 0.0046.

IN short, the NICE guidelines will result in an extra 0.0046% of the population developing Parkinson’s. On the face of it, this may not seem like a massive problem. But the population of the UK is around sixty million, and if we multiply sixty million by 0.0046, we get 276,000. That is more than a quarter of a million people who will develop Parkinson’s disease who would not otherwise have done so.

Just from a purely economic basis, this would be hugely costly. Like all things in medicine, it is difficult to establish exactly how much it costs to look after a Parkinson’s patients, but in the UK it has been estimated as between £3,500 to £10,000 per year². (Up to $100K in the US, I have read).

Multiply these two figures by 275,000 and we get a range of: £962,500,000 – £2,750,000,000/year ($1.443 – $4.12Bn/year)

Now you can argue these figures, and I am sure that NICE would – were they ever to engage in this debate. They will say that Parkinson’s is less common than this (I have seen both higher and lower estimates), they will argue the exact costs, they will bore you into submission with NPVs and suchlike.

You can argue all you like on the minutia, but if this paper is right, and I see no reason to suspect it is not, the NICE guidelines will inevitably result in hundreds of thousands of extra people developing Parkinson’s disease, at a cost of billions to the NHS. Leaving aside the added suffering and Disability Added Life Years (DALYs) this will bring.

Now this represents a massive and very major issue. If NICE were to take this research seriously, they would have to reconvene and review the evidence, and work out the ‘new’ costs and harms to patients, and perhaps they would have to reverse their guidance.

However, I know that they will not do this. They will just ignore this paper, and the implications thereof. I knew this would happen even before they started off by calling it nonsense, as you will remember they did that before they even read it. Even if they do actually read it, they will dismiss it as just one study to set against (my most hated of phrases) the ‘weight of evidence in favour of statins.’

The simple truth is that there is too much at stake here for NICE, and the entire spider’s web of interconnected reputations, and status, and opinion leaders, and money, for NICE to ever reconsider their guidance on statins. Facts and evidence are puny weapons in this battle.

NICE?

Next week, dear reader, we shall examine the economic consequences of statins increasing the risk of type II diabetes by 46%. Get ready for some pretty gigantic figures. The zeros, they shall stretch as far as the eye can see.

1: Huang X et al: ‘Statins, Plasma cholesterol, and risk of Parkinson’s Disease. A Prospective study.’ J of Movement Disorders (epub ahead of print).

2: http://www.bgs.org.uk/index.php/topresources/publicationfind/goodpractice/376-parkinsonsdisease