Last week something quite extraordinary happened in the UK medical world. The National Institute of Health and Clinical Excellence (NICE) describes itself as follows: “We provide independent, authoritative and evidence-based guidance on the most effective ways to prevent, diagnose and treat disease and ill health, reducing inequalities and variation.”
Overnight on June 10th 2014, an open letter was sent to NICE and the Health Secretary, Jeremy Hunt, and a press release was issued by a group of doctors and academics. The letter essentially said to NICE – you are not independent and you are not evidence based and we call on you to withdraw the latest guidelines on statins until the drug company funded ‘researchers’ conducting trials and withholding vital data are forced to share that data.
The points made by the doctors and academics
To summarise the six subheadings in the letter, the authors questioned:
1) Whether five million more healthy individuals should be medicated.
2) How could vastly conflicting information on side effects be explained (we’ll come back to this one).
3) How can it be right that the Cholesterol Treatment Trialists (CTT) Collaboration have commercial agreements with drug companies, which seem to exempt them from sharing what doesn’t suit their paymasters.
4) Why is NICE relying upon trials funded by drug companies when evidence shows (unsurprisingly) that these will find in favour of their drug. The open letter included the conclusion of the one major non-industry funded trial on statins (ALLHAT-LLP). This lone independent study found “No benefit was demonstrated in ALLHAT-LLT, the largest clinical event trial of pravastatin published to date.”
The open letter made two final damning points – the first reminding NICE that it is not considering all data because data is being withheld – and the collective view of GPs on this:
5) A recent meeting of the General Practitioners Committee (GPC), which represents GPs, passed a resolution requesting that NICE refrain from issuing its statin recommendations until there is complete disclosure of all clinical trial data.
The second, bringing into question the claimed independence of NICE:
6) We have serious concerns that 8 out of 12 people on the NICE statin guidelines committee have ties to the drug companies (I shared the conflicts here soon after the guidelines were issued). We have serious concerns about NICE’s reliance upon the CTT/Clinical Trials Service Unit (CTSU) drug company funded trials. e.g. the REVEAL study for which the CTSU received £96 million in funding from Merck Sharp & Dohme.
It is difficult to describe just how extraordinary this turn of events has been in the world of the statin/cholesterol debate. I highly recommend reading the letter and press release in full (there’s some classic Dr Malcolm Kendrick humour in the press release) if you’re interested in the world of health/drugs and doctors. This has been a seminal moment in the doctor/guidelines relationship.
There was some more humour in Dr Malcolm’s appearance on BBC breakfast when statin side effects were being discussed: “Statins will add 15 years to your life – they won’t make you live 15 years longer; they’ll just make you feel 15 years older!”
Statin side effects
You may be aware from this post that there is a debate going on about the true extent of statin side effects. This has become a much discussed issue after Professor Rory Collins demanded that the BMJ remove two articles, which referenced a peer reviewed paper that estimated the side effects of statins to be approximately 20%. Dr David Newman has rightly called this “An assault on science“. I’m in possession of a document showing that the true extent of the pharma funding for the CTSU is £250 MILLION. This is not just an assault on science, it’s an absolute disgrace that a Sir/Professor/Lord-high-executioner can make demands in this way from the worst position of conflict I have ever seen.
The open letter to NICE/Jeremy Hunt presents some inexplicable data. Under subheading 2 (conflicting levels of adverse events), the letter notes that the LIPID trial reported total adverse effects [side effects] as 3.2% for pravastatin and 2.7% for the placebo. The METEOR trial reported total adverse effects as 83.3% rosuvastatin and 80.4% for the placebo. There were six other trials listed (falling between 2.7% and 80.4% in side effect rates) and yet the placebo and statin adverse effects were almost identical every time. This raises two questions, which the open letter has invited NICE to explain:
i) How can there be a thirty fold difference in side effects from statins (80% over 2.7%)?
ii) How can the placebo be virtually the same as the statin in every trial – whether or not the statin results in 2.7% side effects or 80%?
I can’t explain this. Jerome Burne can’t either. Here’s my best guess – the data has been manipulated to ensure whatever side effects were reported in the statin victims, the placebo arm looks the same. I’m open to other suggestions.
This part of the letter alone also makes a mockery of Collins’ claim that you’ll see side effects in barely 1 in 100 cases. If we average the eight trials, side effects in the statin takers were 19.8%. Oh look – just like the 20% in the Zhang et al paper, referenced by Dr Aseem Malhotra and Dr John Abramson.
The NICE reply
The NICE response was almost as extraordinary as the open letter. The NICE response was posted on the same day that the letter was issued (10th June). I appreciate that they would have had advance notice before the open letter was issued, but they still don’t appear to have devoted much time to a considered response.
The NICE response opened by quoting its own Professor Mark Baker, Director of the Centre for Clinical Practice at NICE: “Cardiovascular disease maims and kills people through coronary heart disease, peripheral arterial disease and stroke. Together, these kill 1 in 3 of us. Our proposals are intended to prevent many lives being destroyed.”
I heard Mark Baker saying that exact comment on Sky news interviews and almost fell off the sofa. That’s emotive, scare-mongering worthy of a Hollywood trailer – not a public health body trying to be taken seriously.
Here are the facts on your chance of dying from heart disease. You would have needed to know 3,030 men (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. You would have needed to know 12,500 women (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. (Double these odds if you like, to capture the broader concept of cardiovascular disease rather than heart disease. I’d still need over 6,000 female friends under 65 to be attending one of their funerals from CVD).
We have to die of something. Arguably we all die of heart disease because death is confirmed when the heart stops beating. Cancer is just about the only other major thing that claims a place on death certificates. So yes, one in three of us have the likelihood that cardiovascular disease will be on our death certificate. The chance of that happening is so massively related to age that we should worry way more about birthdays than we do anything else.
The second astonishing approach taken by NICE was to present no defence whatsoever of the “8 out of 12 statin committee members prefer drug money” allegation. Paragraph four opens with “The independent committee of experts found…”. Paragraph five opens with “NICE guidance is developed by independent expert committees…”
Dear NICE – simply repeating that you’re independent does not make you so.
NICE has this to say: “They [independent expert committees] review all of the available evidence …” Yes – but what are you doing about the unavailable evidence? The evidence deliberately being withheld? If the CTT/CTSU have commercial arrangements, which ‘exempt’ them from sharing inconvenient data, why do you, NICE, not reject every study that they publish until they do fully disclose serious adverse effects and other information that they refuse to share.
The open letter recommends that the Cochrane group (the group set up to be genuinely free from big pharma) be allowed to scrutinize the CTT/CTSU data. It is just incomprehensible that NICE don’t seem bothered that they have 8 out of 12 fat cats dealing with biased pharma controlled data.
Mark Baker’s other ‘fall on the floor’ comment was along the lines of “because the price of statins has fallen [they’re off patent now], we can afford to give them to more people”. Smarties are fairly cheap – it doesn’t mean that we should hand them out to everyone. What happened to first do no harm? What happened to leaving healthy people alone? What happened to truly understanding the side effects of a drug before assuming them to be as safe (or as harmful) as Smarties?
This rationale for statins also illustrates the naivety (or even more sinister conflict) of NICE. There were similarly naive (or conflicted) comments on newspaper websites: “statins don’t cost as much now – so why not dish them out?” Apart from the harm, here’s why…
As the open letter explains in subheading 6, people like Dr Malcolm Kendrick and Dr Aseem Malhotra, who work with true independence in the statin world of reward, are aware of where statins are going next. When a drug as lucrative as statins ($125 BILLION for Lipitor alone) is approaching the end of its patent, you can bet that the replacement is being worked on in haste. And it is. And it will come in the form of PCSK9 inhibitors. And the chair of the NICE guidelines panel just so happens to be the lead UK investigator for the Pfizer RN-316 (anti-PCSK9 antibody) programme and the site investigator AMG-145 (anti-PCSK9 antibody) Osler lipids follow-on study. Oh and guidelines panel member Michael Khan just happens to be on the advisory board for Amgen for PCSK9 and he’s doing a clinical trial for Amgen on PCSK9. Oh and Emma McGowan is also doing a PCSK9 clinical trial. Oh and Dr Alan Rees (Mr Heart UK) is advising Sanofi AND Aegerion AND Amgen on PCSK9 and getting honorarium payments, speaker fees – no payment details shared. Mr Heart UK is also principal investigator on two PCSK9 trials. It’s all here – Appendix B – runs for 20 pages.
So – is the NICE panel naive to not realise the PCSK9 game being played or corrupt?
We are currently in that vital window for drug companies where they have a unique opportunity to expand a market in preparation for the next drug-of-riches-beyond-wild-dreams. This is what is happening right now. If only five million more adults (in the UK alone – more in US, Australia, NZ, Europe etc) could be put on these ‘cheap’, off-patent statins, when ‘son of statins’ (as Dr Malcolm calls PCSK9 inhibitors) are introduced, doctors will be deemed reckless if they do not move all their statin patients to the ‘new and improved’ medication. The ‘new and improved’ medication that will be able to return even more than statins Mark I having just expanded the client base. If you’re interested in learning more about PCSK9 inhibitors, you may enjoy this and this and this.
Where are we now
We end the week commencing 9th June 2014 with NICE badly wounded. They would not take a cheap swipe in their response at …”the American doctor, who co-signed the letter…” if they were not hurting.
I wrote to Health Secretary, Jeremy Hunt, on 17th February 2014 about the NICE conflicts of interest and he left it to NICE to reply. It will be interesting to see if the Health Secretary replies to this open letter, or if the NICE immediate response is all that we will get.
The February “extend the use of statin” guidelines from NICE have been out to consultation since then and final recommendations are due to be published next month. It will be interesting to see what final position NICE adopts. We may then have the unprecedented situation where GPs are openly rejecting guidelines issued by their advisory body.
The comments sections under media articles and even the BMJ rapid responses alongside Fiona Godlee’s editorial are littered with stories from individuals sharing their own statin experiences. The diabetes statin lawsuit continues in the US – women seem to be particularly badly affected – as the open letter to NICE detailed. The Collins “Assault on Science” has at least opened up awareness of statin side effects and angry people are sharing their unpleasant and disabling experiences.
Meanwhile the drug companies are really not bothered. Even if Collins is forced to declare the full extent of side effects and release raw data, so that people like me can have some fun with it, it will be too late. The only question now is – how many people will be on “son of statins” – the millions who are on statins now or five million more? It would be like you or me winning £109 million or £115 million on the lottery – would it really matter?