Doctors tell NICE you’re not independent & you’re not evidence based

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.

This is the letter that was sent. This is the press release .

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.

On conflict?

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.

On evidence?

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.

On smarties?

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?

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25 comments on “Doctors tell NICE you’re not independent & you’re not evidence based
  1. avatar Andy Liggins says:

    So did Professor David Haslam (GP) write to Professor David Haslam (NICE chairman) or have I misunderstood? Thank you

    • avatar Zoë Harcombe says:

      Hi Andy – you’ve got it – both Profs, both Davids, both Haslam’s – one is the chair of NICE and the other is a GP and chair of the National Obesity Forum :-)
      Best wishes – Zoe

  2. avatar Anna Watson says:

    That’s true, vaccine trials have no benign placebo (and no control group either) but that’s OK because some vaccines are ‘safe and pure’ and make excellent placebo! “My dear, all placebos are benign. We only use our most safe and pure vaccines” (such as Men C) Prof David Salisbury went in to tell me.
    And the last vaccine trial using a control group was in the seventies for BCG… Showing that the vaccinated group had slightly more risk of developing TB.
    I am still waiting for any good study that shows that the vaccinated are healthier than the vaccinated ….

  3. avatar Bryan Reed says:

    Congratulations, you deserve them. I wonder, though what the next move is going to be. Is there anybody who can be contacted, with a view to possibly suing NICE for fraudulently using false information, in a bid to feather their own nests, as is usually the case, these days.

  4. avatar Beatrice says:

    The ABC in Australia recently removed it’s Catalyst program two part series on Statins, it was deemed to be biased. The focus was on exposing statins for being useless, and having side effects (so many needed to treat to prevent one heart attack but no extension of life). Their own fault they used Jonny Bowden in the second episode, who sells his own ‘cholesterol’ pills while damning statins and is not qualified in anything as far as the critique indicated. Othewise the show was I thought, a real eye opener. Australia spends ONE BILLION dollars of taxpayer money subsidising statins. Everyone I know over 65 is on them, but they are not used as first line treatment as they are supposed to be. Cholesterol may not be the problem. This is how one woman I know takes her statins. Biscuits cake with cream and jam, wash down with statin and cup of tea with two sugars. Perhaps reducing the cakes might be just as beneficial. Perhaps walking for an hour a day may also just be as beneficial. Perhaps eating more greens would be also just as beneficial. Perhaps taxpayers would get more benefits from their donations if ‘first line’ interventions – lifestyle change -were actually carried out.

    • avatar Kim says:

      WOW biased or not why cannot it be available as information……………. that is shocking it’s up to the individual to decide if it is biased !!!

  5. avatar Nigel PJ says:

    Excellent post.
    I took statins. I developed aches and pains and was diagnosed with soft tissue rheumatism. I gave up statins and my symptoms largely disappeared.
    Now those three statements cannot be shown to be causally linked; however, when there is such a preponderance of similar reports it would be wise for them to be taken seriously.

    • avatar Michael B says:

      I love how such reports are dismissed as “anecdotal evidence” as if they are of no importance. Well, they ARE important if you are the anecdote!

      • avatar Frank weir says:

        Ive noticed my doctor is VERY dismissive if I ask if a symptom might be related to statin use…which i no longer take. Is it any wonder that health care organizations say side effects are limited? They just take drug company research and if doctors refuse to listen to their patients, there will be no reportage of side effects. Closed system.

        • avatar Zoë Harcombe says:

          Hi Frank – dismissive is the best that people tell me. Bullying, aggressive, and scare-mongering are the others. If these drugs have no side effects and only benefits (which defeats the law of equal and opposites anyway) then every doc who prescribes them should take them. Just to prove they’re fine. That would be an interesting test!
          Best wishes – Zoe

  6. avatar Mark Johnson says:

    I’ve just read the press release and whilst the whole statin fiasco is truly beyond belief, this summary by Dr David Newman, Assistant Professor of Emergency Medicine and Director of clinical research at Mount Sinai School of medicine, New York summed it up:

    “I am always embarrassed when I have to tell patients that our treatment guidelines were written by a panel filled with people who stood to gain financially from their decisions. The UK certainly appears to be no different to that of the United States. The truth is for most people a statin will give them diabetes as often as it will prevent a non fatal heart attack — and they won’t live any longer taking the pill. That’s not what patients are looking for.” (My emphasis)

    It’s truly shocking.

  7. avatar FrankG says:

    Another trick of which I’m sure you’re aware, is that many (most, all?) of the statin trials are pre-screened… after-all it would be unethical to include a patient in a trial knowing that they suffer the potential life-threatening side-effects.

    • avatar Zoë Harcombe says:

      Hi Frank – that one I had come across. Knowing what statins do, I would expect those most vulnerable to side effects would suffer them quite quickly and – as you say – it would be unethical for these people to continue and so they get dropped and the true side effect picture is totally distorted from that point on. This data is available and this is exactly the kind of data that has been requested and denied. It really is criminal that we have more information about harm that isn’t shared.
      Best wishes – Zoe

      • avatar Helge says:

        Hello. I wonder how the real outcome as regards “lives saved” in the statins trials would be without this screening process. I find it reasonable that the risk for people dying from statin use could be higher for those with the strongest adverse reactions than for the average. In that case I find it questionable if in reality there is any net benefit from statins, considering how small the alleged benefits are. Perhaps a realistic and honest study without the screening would show more deaths in the treatment group?

        • avatar Zoë Harcombe says:

          Hi Helge – watch this space – I’m aware of a paper being written looking at ‘benefit’ in a more relevant way :-)
          Best wishes – Zoe

        • avatar sten b says:

          Helge, very valid point. Here an extract from a paper about muscle weakness from statin use, to give magnitude and extent of this significant exclusion.
          “Why is statin-induced myopathy so uncommon in clinical trials?
          A reason may be that patients in clinical trials are carefully screened. To minimize toxicity, the clinical trials of statins excluded patients with renal insufficiency, hepatic insufficiency, a history of muscular complaints, and poorly controlled diabetes, as well as patients taking drugs with possible interactions. Large efficacy trials have excluded up to 30% of the participants in active prerandomization phases.13,14 (http://www.ccjm.org/content/78/6/393.full)

          30% exclusion is quite a lot! especially considering that the remaining elite patients still exhibited side effects in up to 20% !
          And if GPs were using the same exclusion critera, only perfectly healthy individuals would soon be statined, marking the end of this statin side effect crisis… But treating the remaining elite for what condition ? But do GP’s really know of the long exclusion list?
          It seems to me statins is a preventive medication that require perfectly healthy, and rather younger patients.
          A thought then goes to the heart bypass scandal in Redding, CA, US that also achieved extremely good statistics, low mortality figures. They operated mainly healthy patients merely to keep the operating theaters full most of the time.
          http://www.gjel.com/verdicts/tenet1.html

  8. avatar Jeff C says:

    A very comprehensive post, well done. The push back is truly a welcome sight, it does make one wonder if the medical establishment finally over stepped their bounds.

    You mentioned data manipulation suspicions to equalize side effects between statins and the placebo. Another thread worth pulling along these same lines is placebo fraud. Placebo content isn’t regulated and the placebo makeup often isn’t reported in studies. In vaccine trials, placebo fraud is rampant. Often the “placebo” will be a shot containing virtually everything except the antigen (as was done with the Gardasil HPV vaccine trials). Many vaccine adverse reactions are linked to the adjuvant, preservative, or other chemical ingredients rather than the antigen itself. Using the phony placebo cranks up adverse reactions within the control group thus making the actual vaccine look relatively safe by comparison. Another trick is that during the trial the vaccine is given in combination with other already approved vaccines. The given justification is that this is how a child will likely receive the vaccine when administered (a true statement given the number of vaccines in the schedule). However, this also tends to raise the “background noise” of control group as it now includes adverse reactions from the additional vaccines given simultaneously. Since the goal is to water down the adverse reactions caused by the vaccine on trial, it is extremely rare to find a vaccine tested singularly against a true inert placebo such as a saline injection. It just doesn’t happen.

    This is how the game is played with jabs; it wouldn’t surprise me to see variations on the same tricks used elsewhere.

    • avatar Zoë Harcombe says:

      Wow! Many thanks for that Jeff – another trick I didn’t know!

    • avatar Catherine says:

      That is seriously scary, Jeff. I would imagine that most of us would assume that a placebo is exactly what you suggest, saline solution, or a sugar pill, depending on what is on trial.

  9. avatar George Henderson says:

    PCSK9 is an inhibitor of Hepatitis C Virus cell entry. So everyone being prescribed this new drug will be regularly tested for HCV? Yeah, right.

  10. avatar robert says:

    http://qjmed.oxfordjournals.org/content/early/2012/01/18/qjmed.hcr265.full

    Graph #3: there is no ‘statin-kink’ whatsoever.

    If these drugs were so great as claimed, one would expect a massive impact, but it is a bloody straight line. These pills didn’t even make a small dent. Does not compute.

    “However, the death rate from CHD had already fallen by 90% by the time these publications appeared, and therefore before the widespread use of statins. The trend-line of decline of CHD deaths in the UK did not display any subsequent deflection (see figures) and there was no obvi-
    ous effect of statin therapy or other medical intervention.

    We tend to overestimate the benefits of medical intervention, and the reason for this is that not all patients benefit from that treatment.” (p. 512…)

  11. avatar Ash Simmonds says:

    “..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.”

    This just in: cure for heart disease – put less candles on the cake.

    • avatar sten b says:

      The cakes themselves may well be the serious problem considering that every blood sugar spike causes arterial injury in proportion to magnitude and duration; worsening when blood sugar control reduces, as today is common with age. (No cake for me, I am too old to chance it…)
      The yet unproven analogy for plaque formation is that every arterial injury causes a scab that normally heal and fall off like other visible scabs, provided healing is not disturbed with more injuries in between, causing at least our visible ones to just thicken and never heal…
      No wonder the Zoo gorillas got heart attacks when blood sugar inert leafs were changed to blood sugar spiking (modern) whole grains.
      Changing breakfast with a look towards egg and bacon or using a glucometer 1 hour after meal to be really sure is the safe bet compared to taking statins. Read Wheat Belly!

    • avatar HELENA WOJTCZAK says:

      “put less candles on the cake”

      You mean “fewer”.

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