[Bring it on]

A few months ago I was part of a group that wrote a letter to the National Institute of Health and Care Excellence (NICE) criticising their proposed guidance on the use of statins in primary prevention. I drafted the letter and it was signed by such people as the President of the Royal College of Physicians, past president of the Royal College of Physicians etc. This was not, in short, a group of fringe lunatics.

It caused a bit of a stir, and generated a considerable amount of air time. After receiving the letter, NICE reviewed their guidance and decided that they had been perfectly correct to promote the use of statins in primary prevention in the UK after all. NICE, in effect, judged NICE, and found itself not guilty of anything. Well, that’s one of the benefits of being judge, jury and executioner all wrapped up together in one body.

This letter, and the dismissal of all its points, followed a nasty outbreak of hostilities in which Professor Abramson and Dr Malhotra had been attacked by Rory Collins for publishing separate, but related, papers in the BMJ. These papers suggested that adverse effects from statins were quite common. Professor Rory Collins demanded retraction of the articles and also attacked the editor of the BMJ very publically. Generating articles such as this one:

‘Professor Sir Rory Collins, from Oxford University, said he believes GPs and the public are being made unjustifiably suspicious of the drug, creating a situation that has echoes of the MMR vaccine controversy.

The academic, one of the country’s leading experts on the drug, is particularly unhappy with the British Medical Journal (BMJ), which has run well-publicised articles by two critics of statins that he argues are flawed and misleading.

“It is a serious disservice to British and international medicine,” he said, claiming that it was probably killing more people than had been harmed as a result of the paper on the MMR vaccine by Andrew Wakefield. “I would think the papers on statins are far worse in terms of the harm they have done.”’ ¹

Stung by this attack, the BMJ brought together an independent panel in response to Rory Collins criticism. The result, as reported by Forbes, was as follows:

“As previously reported, Rory Collins, a prominent researcher and head of the Cholesterol Treatment Trialists’ (CTT) Collaboration, had demanded that The BMJ retract two articles that were highly critical of statins. Although The BMJ issued a correction for both papers for inaccurately citing an earlier publication and therefore overstating the incidence of adverse effects of statins, this response did not satisfy Collins. He repeatedly demanded that the journal issue a full retraction of the articles, prompting The BMJ’s editor-in-chief, Fiona Godlee, to convene an outside panel of experts to review the problem.

The report of the independent statins review panel exonerates The BMJ from wrong doing and said the controversial articles should not be retracted:

“The panel were unanimous in their decision that the two papers do not meet any of the criteria for retraction. The error did not compromise the principal arguments being made in either of the papers. These arguments involve interpretations of available evidence and were deemed to be within the range of reasonable opinion among those who are debating the appropriate use of statins.”

In fact, the panel was critical of Collins for refusing to submit a published response to the articles:

“The panel noted with concern that despite the Editor’s repeated requests that Rory Collins should put his criticisms in writing as a rapid response, a letter to the editor or as a stand-alone article, all his submissions were clearly marked ‘Not for Publication’. The panel considered this unlikely to promote open scientific dialogue in the tradition of the BMJ.””²

In short, Professor Sir Rory Collins was told that he was utterly wrong to demand retraction of the papers, and that by refusing to take part in an open discussion was trying to strangle scientific debate.

That, if you like sets the scene. A scene whereby anyone who dares to criticise statins, even a prestigious journal such as the BMJ itself, is subjected to vitriolic attacks and a demand for silence. Rory Collins tried to keep all correspondence with Fiona Godlee secret, which kind of backfired on him. Hoorah. Type ‘Rory Collins and Fiona Godlee e-mails’ into Google, and you can see for yourself.

Of course, things have not stopped here. The ‘statinators’ although briefly thwarted in their initial attack on Abramson, Malhotra and the BMJ – and less directly me – have switched track. The British Cardiovascular Society (which you will not have heard of), have decided to run a survey of their members. They are trying to gather information about the damaging impact of the articles, and the letter to NICE:

Here is an e-mail which was sent to all members:

“The British Cardiovascular Society is keen to know of any potential adverse effect on cardiovascular disease prevention which may have resulted from recent media stories and articles such as those published in the BMJ (1,2) and in an open letter to NICE (3). 
We would be grateful if members would complete this short survey. Your response will be anonymous and the link below is unique to you allowing you to complete the survey once only. 
The survey closes on 30th September and results will be made available subsequently on the BCS Website and in the BCS newswire.”

References
(1) Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013; DOI:10.1136/bmj.f6123.
(2) Malhotra A. Saturated fat is not the major issue. BMJ 2013; DOI:10.1136/bmj.f6340
(3) http://www.nice.org.uk/News/Press-and-Media/nice-responds-to-criticisms-of-its-draft-guidance-on-statins
PLEASE CLICK HERE TO COMPLETE THE SURVEY 

Now, why would they be doing this? I do not think it is that difficult to work it out. The BCS is trying to gather evidence that the articles by Abramson, Malhotra and the open letter to NICE have caused harm to patients. They will be asking their members if they know of people who have stopped taking statins, or who will not go on statins, because of what they have read in the BMJ and suchlike.

Once they have done this, they will then extrapolate the raw figures to the entire population of the UK, in order to claim that ‘Thousands have died.’ Abramson will be attacked, along with Malhotra and the BMJ. I will get a few attacks as well for drafting the letter to NICE. This is a very unsubtle variation of the ‘You’re killing my patients’ tactic which is regularly used to silence any who dares criticise currently medical opinion.

At this point you may be wondering what the British Cardiovascular Society (BCS) may be, and could it possibly have any conflicts of interest with the pharmaceutical industry? Well, of course it does. The BCS is heavily reliant on the industry for its very existence. I would say totally reliant, but such bodies do not reveal detailed financial information.

However, you can start looking at what they charge for sponsorship at their conference, and begin to multiply. For example, if you want an exhibition stand at said conference, here is what you pay for an Option 1 stand³.

Option 1 – £33,500 + VAT
To include:

• Stand – 8mx8m (64msq) island site
• Full Page Colour advert in Heart Journal
• Table (10 guests) at BCS Annual Dinner (Tuesday 3 June)
• 4 x Conference Badges (company name only so transferable)
• 20 x Stand/Exhibition Badges
• 50 word entry in the Conference Programme and on the website
• Opportunity to purchase additional adverts in Heart Journal

with up to a 50% discount of card rate

The BCS helpfully explains the benefits of exhibiting:

Why Exhibit?

The BCS Annual Conference is the most highly attended and respected cardiovascular event in the UK. The Exhibition is a crucial component to the success of BCS event, enabling cardiologists, physicians, scientists, physiologists and nurses to keep up to date with innovative and developing technologies, pharmacology, diagnostic equipment, educational materials and more.

Access over 2,300 cardiovascular healthcare professionals face to face – including top cardiologists, physicians, scientists, physiologists and nurses

Promote and demonstrate products and services directly to key cardiovascular healthcare professionals and gain first-hand feedback

Associate your brand/company with the Society for Cardiovascular Care – the British Cardiovascular Society

Introduce new products/services and test the market

Opportunity to network with industry peers

Of course there are other sponsorship opportunities, such as Advertising in the BCS Conference Programme, which will set you back another £10K:

Advertising in BCS Conference Programme

A copy of the Conference Programme is given to each delegate upon arrival to the event. This is the perfect opportunity to reinforce your presence and support of the BCS Annual Conference 2014.

Inside Front Cover: £2,000 + vat (exclusive)

Inside Back Cover: £2,000 + vat (exclusive)

Outside Back Cover: £2,000 + vat (exclusive)

Double Page: £2,000 + vat

Single Page: £1,200 + vat

There are limited opportunities available

I could go on, but I think you get the general drift. The BCS are funded and supported by the pharmaceutical industry. An industry that is not, currently, that bothered about statins – as the patents have run out. But it is an industry that remains extremely interested in the whole idea of lowering cholesterol. Which remains THE multi-multi-billion dollar market.

Any attack on statins threatens the foundations of this market, one that has been painstakingly constructed over the last thirty years. Keeping the cholesterol lowering idea alive, vibrant, and expanding, will make it far simpler to sell the next generation of cholesterol lowering agents that are currently lurking in the wings, engines purring.

To cut a long story short, the forthcoming attack by the BCS can be considered, to all intents and purposes, an attack by the pharmaceutical industry on anyone who dares to suggest that drugs lowering cholesterol may not be such a brilliant idea. So when you see the headlines in the newspapers damning and rubbishing Aseem Malhotra, John Abramson, and me (and a few others), you now know exactly where this attack originated, and why. Knowledge is, as they say, power.

References:

1: http://www.theguardian.com/society/2014/mar/21/-sp-doctors-fears-over-statins-may-cost-lives-says-top-medical-researcher

2: http://www.forbes.com/sites/larryhusten/2014/08/02/no-retraction-for-you-review-panel-exonerates-medical-journal-in-statin-kerfuffle/

3: http://www.bcs.com/pages/exhibition_09.asp?PageID=497&NavCatID=86

“And if all others accepted the lie which the Party imposed – if all records told the same tale – then the lie passed into history and became truth. “Who controls the past,” ran the Party slogan, “controls the future: who controls the present controls the past.” And yet the past, though of its nature alterable, never had been altered. Whatever was true now was true from everlasting to everlasting. It was quite simple. All that was needed was an unending series of victories over your own memory. “Reality control,” they called it: in Newspeak, “doublethink.” 1984

In my first book, the Great Cholesterol Con, I included a passage about Ancel Keys by Henry Blackburn, a colleague and admirer of Keys. It points out that Ancel Keys was humiliated by George Pickering at a meeting of the WHO in Geneva 1954 discussing the new ‘epidemic’ of heart disease. The quote from Henry Blackburn finishes thus:

‘My theory is that Keys was so stung by this event that he left the Geneva meeting intent on gathering the definitive evidence to establish or refute the Diet-Heart theory. Out of this single, moving, personal experience – so my theory goes – came the challenge, the motivation, the implantation of the Seven Countries Study.’

As I wrote in the book. ‘So there you have it. As a result, Ancel Keys stormed off, put together a huge research budget, hired a staff of thousands, did his study and was the able – in objective ‘scientific speak,’ of course – to say ‘I told you so, I told you so. Nyah, nyah, nyah.’ Not, as I pointed out, the best possible motivation for a research project.

Of course you are going to have to take my word on the exact events described. For, shortly after my book was published, this passage was removed from the University website it was on, never to be seen again. Cause and effect, who can say? But it does raise an important issue. If there is no record of a thing happening – did it happen? If you control the historical record, what is truth?

In the age of the Internet you might think it is more difficult to hide the historical record, but in some ways it is easier. If something only exists on a server somewhere, all you need do is delete it and it is gone – forever. Unless you ensure that you archive it yourself – something I did not do with the Henry Blackburn quote.

At this point you may wonder where this is all going. Well, for some years, I have used statistics from the European Heart Survey which looks at data from nearly a million people. The latest version is here http://www.bhf.org.uk/publications/view-publication.aspx?ps=1002098. This is very impressive bit of research, and is full of good stuff. For a few years I have included statistics from this study to produce tables such as the one below (See table).

The table makes it very clear that saturated fat intake has absolutely nothing to do with the rate of CHD deaths in any country in Europe. In fact, in general, the association is completely inverse i.e. the more saturated fat you eat, the lower the rate of coronary heart disease (CHD). Twenty times as low in France, as Georgia, despite the French eating three times as much saturated fat. This, of course, completely contradicts everything you have ever read about the impact of saturate fat on heart disease.

Jerome Burne, a friend and colleague, and medical journalist, wanted to use a couple of my tables for his blog. So I sent them over. He pointed out that my data was from the 2008 survey. In the latest 2012 survey – it take some time for the data to be published – the figures on saturated fat intake have simply gone. They are no longer published at all.

I hurriedly went back to the search the 2008 data to make sure that this had not been wiped from the record. They have not, although it is rather more difficult to find. I have now stored these data on my computer, and archived them. For I suspect that these data on saturated fat intake will gradually disappear from the historical record.

Of course, I am going to write to the researchers in charge of the European Heart Statistics and ask them why, of all the data, the data on saturated fat no longer features. Why have they done this? I strongly suspect I know the answer, and I suspect that you do to.

I am going to write although I already know the type of answer I will get. It will be some complete fudge, not answering the question but saying something along the lines of ‘Our panel of International Experts constantly review the data that we include and make decisions based on priorities that are determined by many different factors. For various reasons not all data are included, but we are always working to ensure that everything is done to provide the most useful and up to date information. Unfortunately, it is not possible to enter a discussion on specific issues.’ Beep, message ends.

It has long amused me the European Heart Statistics – if you look through them carefully – contradict almost everything we have ever been told about the causes of heart disease. Of course they are now somewhat less contradictory, because they have removed the data on saturated fat.

“Day by day and almost minute by minute the past was brought up to date. In this way every prediction made by the Party could be shown by documentary evidence to have been correct; nor was any item of news, or any expression of opinion, which conflicted with the needs of the moment, ever allowed to remain on record. All history was a palimpsest, scraped clean and reinscribed exactly as often as was necessary.” 1984

Someone I have come to know recently is Dr David Newman, Director of Clinical Research in Mount Sinai University, New York. He has been a great thorn in the flesh of the ‘statinators’ recently. He runs a website called http://www.thennt.com/ I recommend that everyone goes and has a look at it.

He is very concerned about providing information to the public that they can understand about various medical interventions. His work is excellent, he is clear, passionate and (nearly) 100% correct about everything.

He gave a talk called ‘The truth that lasts’ and you can catch it on you tube here. https://www.youtube.com/watch?v=UCk_vTkS6bU

For those of you, who have not had a heart attack or stroke, and are on statins, or are bullied into going onto statins, I suggest that you watch this. It is seventeen minutes long, and will be the most valuable seventeen minutes you have spent in your life.

Best wishes.

I love reading about the history of science. In part, because I think you can learn so much about the process of thinking itself. Especially when it goes wrong. More especially when you are looking at the process of immunisation.

Immunisation is something that Karl Popper was particularly interested in. Popper was a scientific philosopher who is a bit of a hero of mine (when I can actually understand what he is saying). Amongst many other things, he was interested in the techniques used by scientists to protect favoured scientific hypotheses, which he called ‘immunisations’.

An immunisation is essentially a way of explaining why a fact, which appears to contradict a favoured hypothesis, does not actually contradict it at all. For example, when it was found that the orbit of the planet mercury could not be explained by classical Newtonian physics, a mathematician called Le Verrier postulated that there must be another, smaller, planet inside the orbit of Mercury that was affecting Mercury’s orbit. The planet Vulcan.

Vulcan was invisible – primarily because it did not exist. But for many years the invisible and non-existent planet served its purpose. It protected classical Newtonian physics from a potential contradiction, or refutation. Or, to be more blunt, of being simply wrong. In this case, scientists were quite happy to believe in invisible non-existent things, if the alternative was to cast aside a hallowed hypothesis.

Of course, this is just one of thousands of examples whereby unwelcome facts have been simply swatted aside, or immunised against. It is not just the Catholic Church that refuses to look through telescopes.

Vulcan, although just one example, does provide a good case study of a widely used form of immunisation tactic, the ‘ad-hoc’ hypothesis. An ad-hoc hypothesis is a secondary hypothesis that is bolted on to the side of the main hypothesis in order to defend it, or protect it. A more recent example of this can be seen in the Global warming debate.

It has been noted that global temperatures have not increased by much, if at all, in the last 15 years. This, however, is not viewed as a contradiction to the hypothesis of man-made global warming. Why not? Because it is argued that the oceans are taking in the excess heat, and trapping it. This process has held back the degree of global warming that had been predicted by the experts.

I am not going to debate whether or not this is true. I am just using it as a more recent example of an ‘ad-hoc’ hypothesis which came into existence to protect the central hypothesis. I would further add that ad-hoc hypothesis are not always wrong. They can very often be right. Le Verrier, prior to inventing the planet Vulcan, had predicted the presence of the plant Neptune due to irregularities in the orbit of Uranus.

However, if you read his works, you will know that Popper was not a fan of ad-hoc hypotheses. He felt that a good hypothesis should be fully predictive of future ‘events’ without the need for additional explanations, adaptations, or suchlike.

He did not state how many ad-hoc hypotheses it took before you had to admit defeat. One, ten, a hundred, a thousand? No-one can give you a clear cut figure, but the more of them there are, the less likely it is your central hypothesis was correct in the first place. The phenomenon of adaptation/immunisation had been recognised many years before Popper.

‘A nice adaptation of conditions will make almost any hypothesis agree with the phenomenon. This will please the imagination, but does not advance our knowledge.’ J Black 1803

I have recently been pondering the ad-hoc hypothesis once more in relation to heart disease. For I suspect that never in the history of science has a central hypothesis had so many ad-hoc hypotheses bolted on to it. Indeed, we have now reached the point where ad-hoc hypotheses have had ad-hoc hypotheses bolted onto them, to protect the ad-hoc hypotheses themselves from being refuted.

Just to look at one example. There are a number of drugs that have been developed to raise High Density Lipoproteins (HDL), the supposed ‘good’ cholesterol. A few of them also lower LDL ‘bad’ cholesterol at the same time. Billions have been spend on this class of drugs known as ‘trapibs’ . The first of these was Torcetrapib.

At this point I should probably remind you that the ‘good’ cholesterol hypothesis was only created as an ad-hoc hypothesis to explain why some/many people with high total cholesterol levels do not suffer from heart disease. ‘It’s because they have a high HDL level.’

The logic here was obvious, if horribly facile. Raise the HDL and reduce the risk of heart disease. Anyway, ignore the chasms of logic, along came the ‘trapibs’, which were going to take over from statins:

‘Hailed as a potential blockbuster that could take Lipitor’s place, torcetrapib was a cholesteryl-ester transfer protein inhibitor (CEP-T inhibitor) designed to increase good cholesterol and lower bad cholesterol. Development of the drug began in 1990 with clinical trials starting nine years later. But it wasn’t until 2006 that Pfizer got close to submitting the drug to the FDA. The company touted torcetrapib as the answer to its near-term pipeline woes, predicting the potential blockbuster could make up for billions of dollars in lost Lipitor sales when that drug went off patent in 2011.’

Well, torcetrapib certain raised HDL by about 50%, and lowered LDL by about 10%. So, what could possibly go wrong?

‘What went wrong: In late 2006, the walls came crashing down around the company. Pfizer announced in December that it was halting development of it’s prized Phase III asset. The decision came after an independent Data Safety Monitoring Board recommended terminating the study because of an imbalance of mortality and cardiovascular events. Results from a 15,000-person trial showed that patients taking torcetrapib with Lipitor experienced excess deaths than those taking Lipitor alone. Not long after torcetrapib demise, Pfizer announced that it was cutting 10,000 jobs. The company spent $800 million developing the drug.’ http://www.fiercepharma.com/special-reports/pharmas-biggest-flops/torcetrapib-pharmas-biggest-flops

What went wrong was the Torcetrapib increased cardiovascular deaths about around 50% (relative increase in risk). Several other ‘trapibs’ have since come, failed, and slunk from the playing field, taking many billions down the drain with them. Yes, I know, you have never heard of them. At the risk of sounding rather big-headed, I predicted their total and abject failure long before the results of the clinical trials came out.

Now, there are those of us i.e. me who would suggest that this blows a hole in the entire good, bad, cholesterol hypothesis. But no. Why not? Because it was found that torcetrapib raised the blood pressure, and lowered potassium levels. This, it seems, was enough to explain the massive rise in CV mortality. Well, quite reasonable, you might say. Yes, but the rise in BP was minute, and the drop in potassium was equally minute. This could explain, perhaps, a 5% rise (at most) in CV mortality. Which should have been overwhelmed by the massive rise in HDL, and drop in LDL.

But no-one was going to look too closely into the figures themselves. An ad-hoc hypothesis had been found. The ‘experts’, rather than questioning the central good/bad cholesterol hypothesis simply bolted on the ‘BP rise, potassium falls’ ad-hoc immunisation device and moved on.

So, here we have an ad-hoc hypothesis, bolted onto an ad-hoc hypothesis, bolted onto the central hypothesis. We have another planet inside the invisible planet Vulcan, to explain why it is so difficult to find the planet Vulcan.

As you can see, the games played to protect the cholesterol hypothesis are, literally, endless. I am not sure when the games end? Perhaps they never do. Very clever people, given enough time and money can, it seems, twist reality round and round, inside out and upside down forever. I would call the process vulcanisation, but I think that has something to do with rubber.

I have not been blogging much recently. One of the reasons is that I have been involved with a group of doctors and professors who have been fighting against the latest guidelines on primary prevention of cardiovascular disease which were due to be announced in July. We have had, as I knew, precisely no effect.

Here is the latest NICE guidance that was announced, today 18^th July 2014. The committee having ignored any and all criticism:

Taking further steps to tackle the risk from heart attacks and strokes

NICE has today published its final updated guidance on the steps needed to prevent thousands of people from becoming ill and dying prematurely from heart attacks, strokes and peripheral arterial disease. NICE says doctors should consider many more people to be at risk of cardiovascular disease (CVD) which causes 1 in 3 deaths in the UK (180,000 each year).

NICE advises that the threshold for starting preventive treatment of these conditions should be halved from a 20% risk of developing CVD over 10 years to a 10% risk. Prevention includes stopping smoking, reducing alcohol consumption, taking exercise and eating a healthy diet. Once these factors have been addressed, the guidance says high intensity statin therapy should be offered.

People can be at risk from CVD because of factors they cannot change including their age, sex, ethnicity, and family history. The guidance recommends that risk factors which can be addressed should be managed.

Professor Mark Baker, Director of the Centre for Clinical Practice at NICE, says: “To make progress in the battle against heart disease and stroke, we must encourage exercise, improve our diets still further, stop smoking, and where appropriate offer statins to people at risk.

“Doctors have been giving statins to ‘well people’ since NICE first produced guidance on this in 2006. We are now recommending the threshold is reduced further. The overwhelming body of evidence supports their use, even in people at low risk of cardiovascular disease. The effectiveness of these medicines is now well proven and their cost has fallen.

“The weight of evidence clearly shows statins are safe and clinically and cost effective for use in people with a 10% risk of CVD over 10 years. “We’re not saying that everyone with a 10% or greater risk of CVD within 10 years needs to take a statin. The guideline recognises the importance of choice in preventing CVD and that this should be guided by information on the trade-off between benefits and risks.”

By recommending a systematic approach to identifying those at risk of CVD, the guideline will enable people to access treatments to address that risk by reducing their cholesterol levels. It will also provide further clarity for practitioners in primary and secondary care about how to manage patients both with and without pre-existing cardiovascular disease.

NICE recommends that people are assessed (using the QRISK2 calculator) for their risk of developing cardiovascular disease using measurements including whether or not they smoke, their cholesterol levels, blood pressure, and body mass index. The calculator then provides a percentage risk of developing CVD in the next 10 years. “This new guideline complements the NHS Health checks programme in helping to identify people at future risk of developing cardiovascular disease at a stage at which lifestyle modification can make a significant difference “says Guideline Development Group Chair Dr Anthony Wierzbicki. “It updates and simplifies treatment protocols for people with established CVD, with diabetes or kidney disease so that these people can derive maximum benefit from lipid-lowering therapies.”Liz Clark, a lay member of the Guideline Development Group, said:

“One of the key challenges is how to convince people who feel well that they need to make substantial lifestyle changes or that they benefit from lifelong drug treatment. This requires high quality information and communication on the benefits and risks of these therapies and this is reflected in the guideline.

“The guideline therefore places patients centrally in any decision making about their management and it emphasises the need to address all CVD risk factors in combination. “It highlights the need for doctors to encourage people to participate in reducing their CVD risk. For example, it recommends that doctors assess a person’s readiness and confidence to make changes to their diet, level of physical activity and smoking and alcohol consumption, as well as taking long-term medication. It also recommends that people are involved in developing a shared management plan.”

So, up to 17 million people in the UK will now be taking statins for the rest of their lives. Well, of course, we will never get anywhere near this number. After about a year 50% of people stop taking their statins – I wonder why. A lot of people will refuse to take them in the first place. But millions and millions will take these drugs for many years.

This is clearly, and absolutely, nuts. My major fear, as I tell anyone, is not that statins have a lot of adverse effects – which they do. You can always stop taking them and the adverse effects go away. If, that is, the effects are not permanent.

I have heard enough testimony from patients, and people who e-mail me, and reviewing FDA Medwatch (the system for picking up drug related adverse effects in America) to believe, one hundred per cent, that many people have been left permanently disabled from taking statins.

My personal belief is that the true burden of damage that will be caused by millions of people taking statins, forever, is very heavy. Every individual case of irreversible neuropathy, or muscle wasting, or degenerative neurological condition, or suchlike, is dismissed as anecdote by the great and the good – and the NICE. ‘Statins don’t do that.’ Is what I hear.

Well, part of me hopes that statins really don’t do that. But, frankly, I don’t believe it. I believe that mass statination of the entire adult population is an absolute medical disaster. I shall continue the fight.

Recently I was the author, and co-signee, of a letter sent to NICE (the National Institute for Care and Health Excellence) asking that their recommendations on primary prevention of cardiovascular disease should be withdrawn. Mainly the advice on the use of statins for those at low risk of a heart attack, or stroke. Those in the UK may have seen a bit a stir in the media.

Others who signed this letter included: Sir Richard Thompson, Chairman of the Royal College of Physicians, Dr. Clare Gerada, past president of the Royal College of General Practitioners and Dr. Kailash Chand – deputy chairman of the British Medical Association. [I have included this letter for you to read, if you wish]

So, we are not talking about a bunch of mavericks here – apart from me, of course. When people who are as much a part of the ‘establishment’ as this are willing to put their names to such a letter then you know that people are getting very concerned. Very concerned indeed.

NICE wrote back to me saying that their guidance was completely wonderful and that nothing should change [I paraphrase, but not by much]. This was pretty much as expected. However, in parallel with this letter, the organisation that represents all GPs in the UK (the General Practitioner’s Committee of the BMA) voted unanimously to reject the NICE guidelines. This happened in May.

Now, very recently, the Annual Representative Meeting (ARM) of the British Medical Association debated the NICE guidelines. The motion put to the meeting was,as follows:

‘This meeting believes that in any advisory committee of NICE, when guidance on any drug is issued it must be made clear that none of the members must have a financial interest in pharmaceutical companies which manufacture the drugs’.

Here is the speech made by Kailash Chand to the meeting:

‘Chairman, Representative Body (RB). This is a chosen motion for a purpose. Some of you will have been very concerned about the general direction of travel by NICE, others will have been concerned simply by the issue of conflict of interest.’

This motion calls for clarity in the role of the pharmaceutical companies and their relationship with those individuals who hold positions of considerable influence on the advisory committees of the NICE, which describes and defines what many consider to be best practice.

This motion is NOT seeking to discredit people who advise NICE or indeed to diminish the Institute itself, which has a vital role in interpreting complex modern clinical evidence.

In fact, it is precisely because we should value the Guidance provided by NICE, that it is absolutely essential for it to carry the TRUST and complete CONFIDENCE of the profession. Guidance which has the power to influence our everyday practice, and against which many of us are performance managed must be based on the highest principles of INTEGRITY and TRANSPARENCY.

It is possible that those involved in an advisory capacity to NICE believe that they are able to manage their conflicts of interest, but it is absolutely imperative that NICE should not only be free of even subliminal influence from the pharmaceutical industry, but perhaps even more importantly, be SEEN to be completely independent and not reliant on partial data disclosure of pharmaceutical industry trial data.

Today, we see a lack of confidence from the profession in NICE’s capacity to analyse data and provide reliable advice, when only selective trial information from drug trials is made available.

Recently, the conference of LMCs unanimously passed a motion calling upon NICE to defer a decision to recommend a reduction of the threshold for prescribing statins for primary prevention in the general population.

The BMJ, the Cochrane Institute and indeed this Conference last year called upon the pharmaceutical companies to release ALL data, as a means to increase transparency and to allow more independent verification of results. In fact NICE itself has joined this coalition to call for access to this data, yet continues to place itself in a position of advising with access to only limited information – the pharmaceutical industry have widely ignored these calls for transparent disclosure.

We know that pharma sponsored trials are twice as likely to produce positive results for a drug, and we also know that only half of trials are available in a published form for peer review. This excludes trials which may be stopped prematurely or have end points altered by the sponsors.

Earlier this year the Cochrane Review concluded that the early evidence which had shaped the advice from NICE before the Flu pandemic, had been flawed and had resulted in an exaggerated impression of the usefulness of these medications. The absence of transparency in the process by which data was released and then interpreted has been deeply regrettable. Some have called it a gross betrayal.

So, please support this motion. It is a call for NICE to review its methods where advisory boards may be populated by individuals with links to industry. NICE needs to recognise that those of us tasked to implement its guidance must have full confidence in the transparency and integrity of those individuals providing advice. NICE must be beyond reproach. It should not just be SEEN to be independent, it MUST be independent.

Otherwise its advice which most of us have to implement or adhere to, will continue to affect the lives of millions of patients.

I move.’

This motion was passed unanimously.

Once again, NICE is under fire. This time from the entire medical profession, and those who represent them. It seems that doctors are deeply concerned about the medical evidence. They feel it has been corrupted, and that those who sit on the guideline committees are, themselves, under the influence of the pharmaceutical industry.

Hoorah. Will anything change? I shall keep throwing rocks, or course. Now a few more powerful rock throwers are joining in. Perhaps the citadel will crumble.

Letter sent to NICE:

Professor David Haslam, Chairman
National Institute for Health and Care Excellence
10 Spring Gardens
London, SW1A 2BV

cc. The Right Honourable Jeremy Hunt, MP
Secretary of State for Health
Department of Health
Richmond House                                                                                                                                         79 Whitehall
London, SW1A 2NS

10^th June. 2014

Concerns about the latest NICE draft guidance on statins

Introduction:

We are concerned about your draft guidance on CV risk for discussion and debate. We would ask for a delay until our concerns are addressed. Whilst we agree with much of the guidance, our concerns focus on six key areas: medicalization of healthy individuals, true levels of adverse events, hidden data, industry bias, loss of professional confidence, and conflicts of interest

The draft guidance recommends offering statin treatment for the primary prevention of CVD to people who have a 10% or greater 10-year risk of developing CVD.

1. Medicalisation of five million healthy individuals.

Firstly, we believe that the benefits in a low risk population do not justify putting approximately five million more people on drugs that will then have to be taken lifelong.

The important questions for clinicians and for patients include: (1) does treatment of elevated cholesterol levels with statins in otherwise healthy persons decrease mortality or prevent other serious outcomes? (2) What are the adverse effects associated with statin treatment in healthy persons? (3) Do the potential benefits outweigh the potential risks? Recent papers have suggested that statin therapy should not be recommended for men with elevated cholesterol who are otherwise healthy.²

Furthermore, Atorvastatin 20mg is also recommended as the first-line treatment. This appears counter intuitive, as Atorvastatin has never been demonstrated to reduce mortality for primary prevention any clinical study. (3b)

2. Conflicting levels of adverse events

In emphasising the cost per Quality Adjusted Life Year (QALY), NICE is clearly making a major assumption that the key issue is mortality reduction, and that statins lead to very few adverse effects. We would question this very strongly.

The levels of adverse events reported in the statin trials contain worrying anomalies. For example, in the West of Scotland Coronary Prevention Study (WOSCOPS, the first primary prevention study done), the cumulative incidence of myalgia was 0.06% in the statin arm, and 0.06% in the placebo arm³.

However, the METEOR study found an incidence of myalgia of 12.7% in the Rosuvastatin arm, and 12.1% in the placebo arm⁴. Whilst it can be understood that a different formulation of statin could cause a different rate of myalgia, it is difficult to see how the placebo could, in one study, cause a rate of myalgia of 0.06%, and 12.1% in another. This is a two hundred fold difference in a trial lasting less than half as long.

Furthermore, the rate of adverse effects in the statin and placebo arms of all the trials has been almost identical. Exact comparison between trials is not possible, due to lack of complete data, and various measures of adverse effects are used, in different ways. However, here is a short selection of major statins studies.

AFCAPS/TEXCAPS: Total adverse effects losartan 13.6%: Placebo 13.8%

4S: Total adverse effect simvastatin 6%: Placebo 6%

CARDS: Total adverse effects atorvastatin 25%: Placebo 24%

HPS: Discontinuation rates simvastatin 4.5%: Placebo 5.1%

METEOR: Total adverse effects rosuvastatin 83.3%: Placebo 80.4%

LIPID: Total adverse effects 3.2% Pravastatin: Placebo 2.7%

JUPITER: Discontinuation rate of drug 25% Rosuvastatin 25% placebo. Serious Adverse events 15.% Rosuvastatin 15.5% placebo

WOSCOPS: Total adverse effects. Pravastatin 7.8%: Placebo 7.0%

Curiously, the adverse effect rate of the statin, it is always very similar to that of placebo. However, placebo adverse effect rates range from 2.7% to 80.4%, a thirty fold difference.

3. Hidden data

Without access to the raw data, it is difficult to understand how statin related adverse events, and placebo related adverse events can mirror each other so precisely, whilst the absolute rates can vary thirtyfold (almost three thousand per cent). These data most certainly require analysis by a third party with appropriate expertise.

A further serious concern is that the data driving NICE guidance on statins comes almost entirely from pharmaceutical company funded studies. Furthermore, these data are not available for review by independent researchers, only those who work for the Oxford Cholesterol Treatment Trialists Collaboration (CTT).

The CTT has commercial agreements with pharmaceutical companies which apparently means that they cannot release data to any other researchers who request to see it. Which, in turn, means that the latest reviews of the data by NICE and also by the Cochrane group are totally reliant on the CTT 2012¹ meta-analysis analysis of this concealed data?

4. Industry bias

The overdependence on industry data raises concerns about possible biases. Extensive evidence shows that industry funded trials systematically produce more favourable outcomes than non- industry sponsored ones.^5,6

Notably, only one major non-industry funded study on statins has been done. ALLHAT-LLP. The main findings were summarised: ‘Although pravastatin has been shown in multiple large clinical trials to reduce CHD morbidity and mortality, NO benefit was demonstrated in ALLHAT-LLT, the largest clinical event trial of pravastatin published to date.’ (6b)

True levels of adverse events

We are also concerned that the rate of adverse effects in post-marketing studies is, in most cases, far higher than that found in the pre-marketing studies. In part this is due to the fact that the clinical trial populations studied in premarketing trials are highly selected. Furthermore, industry sponsored trials include pre-randomisation run-in periods where those who fail to tolerate statins are excluded.RCT patientsmay therefore not represent the population that will actually take the drugs in the real world. RCTs may thus grossly underestimate adverse effects such as myopathy or cognitive impairment,⁷ and fail to detect drug interactions e.g. amlodipine and statins.

Important findings from some other non-industry sponsored studies

A double blind randomised controlled trial that compared 1016 low risk patients receiving simvastatin 20 mg or pravastatin 40 mg with placebo showed that both drugs had a significant adverse effect on energy/fatigue exercise score with 40% of women reporting reduced energy or fatigue with exertion.⁹ Reducing exercise capacity in a healthy group when physical inactivity is a major contributor to the development of cardiovascular disease is extremely counterproductive.

A large observational study involving 153,840 postmenopausal women aged between 50 and 80 years enrolled in the Women’s Health Initiative study found that statins were associated with a 48% increased risk of developing diabetes.⁸

Potential psychiatric symptoms including depression, memory loss, confusion, and aggressive reactions have also been associated with statin use.⁽¹⁰⁾

Erectile dysfunction, to take another significant adverse effect, is not mentioned in the statin trials. Yet, when it was specifically looked for, around 20% of men appeared to be affected.⁽¹¹⁾

5. Loss of professional confidence

We are also concerned that GPs feel that this guidance is a ‘step too far. It is instructive to note that a survey of 511GPs carried out by Pulse magazine revealed that ‘….almost six out of ten (57%) oppose the plan to lower the current 10-year risk threshold for primary prevention, while only 25% support it. Furthermore, 55% would not personally take a statin or recommend a family member does so based on a 10% 10-year risk score.’ ^(11b)

More recently the General Practitioners Committee (GPC), which negotiates on behalf of GPs in the UK passed the following resolution: ‘In light of the Cochrane review of the effectiveness of antiviral influenza treatments, the GPC will request that NICE refrain from recommending a reduction to the current treatment threshold for primary prevention of cardiovascular disease with statin therapy unless this is supported by evidence derived from complete public disclosure of all clinical trials’ data’ ^(11c)

Asking GPs to meet targets that they feel uncomfortable with risks a damaging split within the profession, and a loss of confidence among the public, who are likely to recognise increasingly that GPs are being asked to prescribe statins despite feeling it is inappropriate.

6. Conflicts of Interest (real and perceived)

We are also seriously concerned that 8 members of NICE’s panel of 12 experts for its latest guidance have direct financial ties to the pharmaceutical companies that manufacture statins. Furthermore, some members of the guideline panel are also involved in next generation, more expensive, cholesterol lowering drugs, which are not yet on the market. If cholesterol lowering becomes established in low risk people, the indications for these new cholesterol lowering drugs such as the ApoB Antisence drugs and PCSK9 inhibitors will probably expand as well. We feel that parties with industry conflicts should not be participants in generating recommendations regarding drug use that will influence medical care across the population.

We fear that the CTSU could be perceived as having a major conflict of interest in the area of cardiovascular disease prevention/lipid modification, which has an impact on the Unit’s perceived objectivity. We strongly urge that other researchers, for example, the Cochrane Stroke Group and Cochrane Heart Group, should be able to scrutinize and assess all the data that the CTT has utilised over the years to produce their extremely influential studies.

CTT is a part of the Clinical Trials Service Unit (CTSU) in Oxford, which has carried out many very large studies on statins, and other lipid modification agents with pharmaceutical company support, and has received hundreds of millions in funding over the years. To consider just one such study (REVEAL). REVEAL is being funded by Merck Sharp & Dohme, which developed anacetrapib. A grant of £96 million towards the cost of this multi-million dollar study has been provided to the University of Oxford.

We are concerned that financial conflicts of interest and major commercial bias may have corrupted the database on statins, resulting in an underestimate of the incidence of statin side-effects. Unless all of the data are made available it is impossible to establish a cost per QALY, as there may be DALYs [disability adjusted life years] not accurately accounted for.

We call for all of the data from the clinical trials to be made available to credible researchers, for example, the Cochrane Stroke and Heart Groups. We believe that there is a need for a more robust post-marketing analysis of suspected adverse effects from statins prescribed in a community setting.

To conclude we urge you to withdraw the current guidance on statins for people at low risk of cardiovascular disease until all the data are made available. The potential consequences of not doing so are worrying: harm to many patients over many years, and the loss of public and professional faith in NICE as an independent assessor. Public interests need always to be put before other interests, particularly Pharma.

Yours Sincerely

Sir Richard Thompson, President of the Royal College of Physicians

Professor Clare Gerada, Past Chair of the Royal College of General Practitioners and Chair of NHS Clinical Transformation Board

Professor David Haslam, General Practitioner and Chair of the National Obesity Forum

Dr J S Bamrah, Consultant Psychiatrist and Medical Director of Manchester Mental Health and Social Care Trust

Dr Malcolm Kendrick, General Practitioner and Member of the British Medical Association’s General Practitioners sub- Committee

Dr Aseem Malhotra, London Cardiologist.

Dr Simon Poole, General Practitioner

David Newman, Assistant Professor of Emergency Medicine and Director of Clinical Research, Mount Sinai School of Medicine, New York

Professor Simon Capewell, Professor of Clinical Epidemiology, University of Liverpool

 

References (may require site registration or membership to access)

1: Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C: ‘The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.’ Lancet. 2012 Aug 11;380(9841):581-90. May 17.

2: Redberg RF, Katz MH. Healthy Men Should Not Take Statins. JAMA. 2012;307(14):1491-1492. doi:10.1001/jama.2012.423.

3: http://www.nejm.org/doi/full/10.1056/NEJM199511163332001#t=articleDiscussion

(3b) http://www.health-heart.org/Pfizer’s49LipitorStudies.PDF

4: John R. Crouse, MD; Joel S. Raichlen, MD; Ward A. Riley, et al: ‘Effect of Rosuvastatin on Progression of Carotid Intima-Media Thickness in Low-Risk Individuals With Subclinical Atherosclerosis’: The METEOR Trial JAMA. 2007;297(12):1344-1353. doi:10.1001/jama.297.12.1344

5: Smith R. Conflicts of interest: how money clouds objectivity. J R Soc Med 2006;99:292-7.

6: Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. Jama 2003;289:454-65.

(6b) http://www.lipidsonline.org/commentaries/cme_pdf/commentary_039.pdf:

7: Mansi I, Mortensen E. The controversy of a wider statin utilization: why? Expert Opin Drug Saf 2013:12:327-37.

8: Culver AL, Ockene IS, Balasubramanian R, Olenzki BC, Sepavich DM, Wactawski-Wende
J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s
Health Initiative. Arch Intern Med 2012;172:144-52.

9: Tatley M, Savage R. Psychiatric adverse reactions with statins, fibrates and ezetimibe implications for the use of lipid-lowering agents. Drug Safety 2007;30:195-201.

10: Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial. Arch Intern Med. 2012;172(15):1180-1182. doi:10.1001/archinternmed.2012.2171.

11: Solomon H1, Samarasinghe YP, Feher MD, et al: ‘Erectile dysfunction and statin treatment in high cardiovascular risk patients.’ Int J Clin Pract. 2006 Feb;60(2):141-

(11b) http://www.pulsetoday.co.uk/clinical/therapy-areas/cardiovascular/majority-of-gps-reject-nice-proposals-to-extend-statins-to-millions-more/20005985.article#.Ux3eGPmKVcY

(11c) http://webappmk.doctors.org.uk/Session/2779737-8NrQN5n75yPDD0RVnLZy-aoqmids/MIME/INBOX/125049-02-B/News%2014%20-%2022%20April%202014.pdf

My last blog highlighted the bully boy tactics used to silence critics of mainstream medicine. Normally by threatening anyone who dares question the experts of ‘killing patients’, or words to that effect. It is a well-worn tactic which, surprisingly, seems to work every time.

‘If you dare to question breast cancer screening, women will die.’

‘If you question the use of statins, millions will die.’

‘If you….’ well you get the general gist.

There are of course slightly more subtle versions of this. However, when a medical ‘expert’ deigns to address mere mortals, we know what they mean when they say ‘The salt ‘debate’ must stop.’ What they are saying, albeit indirectly, is that if you don’t stop questioning what I say, millions will die. Maybe billions…..over the years, perhaps an entire Google.

On this note, several different people pointed me at a recent debate at the conference of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH) in Athens. Well, not a debate really, more of a tirade. Here is one part of the report

‘Any “controversy” over whether dietary salt is a cause of heart disease and stroke is the result of weak research methodology or commercial interference, Dr Norm Campbell (Libin Cardiovascular Institute of Alberta, Calgary) and Dr Graham MacGregor (Wolfson Institute of Preventive Medicine, London, UK) argued here….’¹

I shall translate their statement. If you do not believe that excess salt consumption is a cause of heart disease and stroke you are a flawed and misdirected scientist (weak research methodology), or you are corrupt (commercial interference). No other explanation is, of course, possible. You are either an idiot, or corrupt, and therefore – by definition – should be ignored. Or perhaps stoned to death for being an unbeliever.

Ah well, that put me in my place. Along with anyone else who dares to disagree with the mighty Norm Campbell and Graham MacGregor. Now Graham MacGregor makes great play of the fact that grubby commercial companies are pushing hard to get us to put more salt in his food. He, of course, has no commercial affiliations.

Hold on. Is he not on the board of the Blood Pressure Association? An organisation that receives funding from various different sources……

You may like to know that we have been very fortunate to have received substantial funding from a number of organisations who have helped the Association get off the ground. These Founder Members are listed below:²

• Astra-Zeneca UK Limited
• Bristol-Myers Squibb Pharmaceuticals Limited
• Merck Sharp & Dohme Limited
• The Community Fund
• Omron Healthcare UK Limited
• Pfizer Limited
• Servier Laboratories Ltd
• Solvay Healthcare Limited

Would some of these companies not be pharmaceutical companies? Would some of them make tablets to lower blood pressure? Well, gosh, let me think….

Astra-Zeneca, just to look at the first company on the list. They make:

• Candestartan
• Lisinopril
• Felodipine
• Metoprolol
• Atenolol

Well, that’s only five blood pressure lowering agents. Which means that Astra-Zeneca clearly have little interest in blood pressure lowering….not. If you were being a little cynical, you would think that an organisation almost entirely funded by pharmaceutical companies might be considered to have a dog in this fight? You might think that Graham MacGregor could, just possibly, have a little conflict of interest going on. No, surely not.

As for Norm Campbell.

‘Dr. Norm Campbell has given talks sponsored by Bayer, Sanofi Aventis, Biovail, Bristol Myers Squibb, Pfizer, Novartis and Merck Frosst and also has been on advisory boards for Novartis, Pfizer, Servier, Boehringer Ingelheim and Schering Plough.’ ³

As per usual. Seek the commercial conflicts, and ye shall find. You don’t get to be the sort of professor who gets to stand up, command the stage, and intone your words of wisdom at an international medical conference without a little background helping hand from a few pharmaceutical companies. Anyway, what were these two saying about commercial interference again? Difficult to think with the sound of all these cash registers ringing in my ears.

Of course, if confronted, these two will state that all the money they receive goes to charity, or that any funding makes no difference to what they say….or suchlike. As Robbie Burns once remarked. ‘Oh wad some power the giftie gie us, to see ourselves as others see us.’

‘You, are corrupt because you have accepted money from a commercial source; I, on the other hand, am not. Because I am a superior being incapable of being tainted by money.’

However, the main point here is the fact that we have more bully boy tactics going on. Two ‘grand fromages’ take the stage to beat the opposition into pulp.

‘When a member of the audience pointed to the PURE analysis showing that most of the world eats much higher levels of sodium than those recommended by most international organizations, MacGregor and Campbell leaped on this as an example of a study that had radically failed to measure salt in an appropriate fashion, even devising a new “formula” to estimate salt intake because even spot urine testing had been inadequate. “Please let [PURE principal investigator Dr] Salim Yusuf [McMaster University, Hamilton, ON] know that he should stop using spot urine analysis,” MacGregor said curtly.’

I do hope that everyone in the audience made their own minds up about what they were hearing. I suspect the reporter had their own view, by including the word ‘curtly’.

May I make, yet another, plea for medical experts to stop, cease and desist, attempting to bully into submission anyone who dares disagree with them. It is demeaning.

References (may require site registration or membership to access)

1: http://www.medscape.com/viewarticle/826970?src=emailthis

2: http://www.surgerydoor.co.uk/advice/living-with/living-with-high-blood-pressure/what-blood-pressure-association-do-for-you/

3:http://archive.cme.mcgill.ca/html/videos/2009.rural_en/20090923_JacquesGenest/homeblank.html

(Who me?)

Debate in science is essential. You would hope it were the very lifeblood of progress. One would also hope that researchers could disagree with each other in frank and open debate. But it has become increasingly obvious to me that if you criticise the experts in medical research you can expect a very rough ride indeed. You certainly risk being stomped into silence.

I have witnessed this quite a lot recently, and have found that the ‘stomping’ game is very simple. If a critic of an area of mainstream medicine seems to be gaining some traction with the public, they are very rapidly accused of ‘killing patients’ by various professors a.k.a. ‘experts.’

Sadly, it has become an article of faith that ‘experts’ cannot be argued with. For they have attained the status of demi-gods. Recently, I was reading an article about Daniel Kahneman, Nobel Prize winner in economics. He was discussing the irrationality of the financial system. He made many interesting points. For example:

‘The way scientists try to convince people is hopeless because they present evidence, figures, tables, arguments, and so on. But that’s not how to convince people. People aren’t convinced by arguments, they don’t believe conclusions because they believe in the arguments that they read in favour of them. They’re convinced because they read or hear the conclusions from people they trust. You trust someone and you believe what they say. That’s how ideas are communicated. The arguments come later.’

Slightly later on, he talks about his own belief in global warming:

‘Why do I believe global warming is happening? The answer isn’t that I have gone through all the arguments and analysed the evidence – because I haven’t. I believe the experts from the National Academy of Sciences. We all have to rely on experts.’

We all have to rely on experts? So says Daniel Kahneman. A man whom I generally greatly admire. In this case though, I could not disagree more violently. In one breath he states that people aren’t convinced by arguments; they’re convinced because they read or hear conclusions from people they trust. Then he says that we all have to rely on experts. But he does not link these two thoughts together to ask the obvious question. Just how, exactly, did the experts come to their conclusions?

By listening to people they trust? And who might they be? Other experts presumably. And how did they come to their conclusions….by listening to other experts. And how did they come to their conclusions. Hold on, it seems we are trapped in a loop of self-reinforcing logic. There is no escape.

In this area, I tend more to go along with Professor David Sackett:

‘According to the founder of Evidence Based Medicine experts are hindering the healthy advancement of science.

Writing in this week’s British Medical Journal (BMJ), Canadian-based researcher, David Sackett, said that he would “never again lecture, write, or referee anything to do with evidence based clinical practice”. Sackett is not doing this because he has ceased to believe in evidence based clinical practice but, as the BMJ comments, because he is worried about the power of experts in stifling new ideas and wants the retirement of experts to be made compulsory.

Sackett claims that the prestige of experts (including himself) gives their opinions far greater persuasive power than they deserve on scientific grounds alone.”Whether through deference, fear, or respect, others tend not to challenge them, and progress towards the truth is impaired in the presence of an expert,” he writes.

He also argues that expert bias against new ideas operates during the review of grant applications and manuscripts. “Reviewers face the unavoidable temptation to accept or reject new evidence and ideas, not on the basis of scientific merit, but on the extent to which they agree or disagree with the public positions taken by experts on these matters.” ¹

My rather cynical view is that experts can be compared to those men (usually men) who have grabbed hold of the microphone at the front of a mob during a protest march. With this simple act they have managed to gain status and authority. Shortly after they become spokesmen for the revolutionary movement, then leaders…then despots.

However, most newspapers, journalists, television producers never ask they question, how did an expert become an expert – what makes them so. Instead, they are completely in the thrall of the ‘expert, and greatly fear their power. Which means that when an eminent professor loads and fires the ‘you’re killing patients’ gun, all hell breaks loose and panic stalks the land. Journalists, newspaper editors, TV producers and suchlike quiver in fear. They instantly retract everything they have ever published on the matter, and promise never to do it again.

The example of Andrew Wakefield is familiar to all. He stands accused of causing the deaths of thousands of children. Fewer people have probably heard to Peter Gotzsche, who is a professor and head of the Nordic Cochrane Collaboration (yet, not an expert). He has long been a critic of a breast cancer screening. Which has not endeared him to many who work in that field. He is regularly accused of killing thousands of women.

He was forwarded a copy on e-mail by a colleague. It has been written to one of his greatest critics Lazlo Tabar by another ‘expert’. It contained this section – which I have reproduced in full from Professor Gotzsche’s book ‘Mammography screening, truth lies and controversy’

‘What is remarkable to me is that this man (i.e. Dr G) calls himself a scientist since he obviously and knowingly ignores the scientific method in order to further his own agenda, whatever that may be. I cannot believe he is so intellectually deficient that he cannot grasp the plethora of evidence that so strongly supports the benefits of screening. What then drives him so blindly in his crusade to convince us that all the world is flat? To become infamous as a contrarian, standing lonely on the curvature of the as he denies is spinning under his feet? Or is it something even more petty? An all-consuming hatred and jealousy of Lazlo Taber, whose impeccable trial facilitated by meticulous Swedish record keeping and a socialist society provides a setting unparalleled in the world for a scientific trial? What is tragic and make G’s ravings sinister is that I am sure his influence has resulted in women’s unnecessary deaths somewhere in the world. The Scandinavians are known for their fair-minded, progressive concern for women, as well as for their intellectual integrity. IN this regard, PG is certainly a Nordic contrarian.’ [G or PG in this case refers to Peter Gotzsche]

Well, that’s very pleasant. However the part that I wish to draw attention to is this short section…’I am sure his influence has resulted in women’s unnecessary deaths somewhere in the world.’ A difficult statement to either prove, or disprove – I would think. However, the weapon is familiar ‘You are killing patients.’

On pretty much the same lines, I reproduce two short sections from a letter written to Dr Uffe Ravnskov by Professor John Kastelein (A big noise in CV research). He is objecting to Ravnskov’s view that raised cholesterol does not cause heart disease:

‘If this was a joke, I could have laughed about your statements heartily, but they are in fact criminal and bordering on the insane….. I insist that you refrain from any advice to any patient anymore. You are lucky not to live in the Netherlands. I would have dragged you to court.’

Once again, a nice polite scientific debate. Accusing someone of being criminal bordering on the insane. More recently, you will have noted the successful attempt to crush the Australian Catalyst programmes. One of which criticised the diet heart/cholesterol hypothesis. The second program was critical of the ever increasing prescribing of statins. I mentioned it in my last blog

The controversial Catalyst program on statins and heart disease, The Heart of the Matter, was attacked by health experts even before it aired last year.

The presenter of ABC radio’s Health Report, Norman Swan, warned “people will die” as a result of the TV program’s messages about heart medications.

Swan, whose criticism of the program has been vindicated by the independent Audience and Consumer Affairs Unit report, had said the program made him “really angry” because it might affect Indigenous Australians, who are especially likely to suffer from high cholesterol.’

Once again the ‘you’re killing patients’ gun was prepped and fired to pretty devastating effect. Both programmes were pulled from the air with humble apologies all round. Even the first episode ‘dietary villains’ was pulled,which was found to contain no errors at all. Guilt by association I suppose.

A similar battle is being fought in the UK between the statin experts, and those who would criticize them. It has been going on for some time. In 2011 the Cochrane Collaboration published a report very critical of the benefit of statins in low risk/primary prevention patients.

Professor Sir Rory Collins, the most eminent statin expert took great affront, and started to pick the paper apart, claiming it was highly dangerous and damaging. At one point claiming it was far more dangerous than Andrew Wakefield’s Lancet paper.

I quote from 2011:

‘In public health terms it is potentially a far more serious misinterpretation than that of Wakefield and the MMR in the Lancet.’²

He doesn’t state that the Cochrane collaboration is killing patients directly, but by using the example of Wakefield, we know exactly what he means. ‘You are killing patients.’

Professor Collins has warmed to this theme more recently. As you may be aware he has been attacking the BMJ recently for publishing articles about statins which claim that they have significant side-effects. He vehemently protests that they have virtually none. I quote him again, this time from the Guardian:

“It is a serious disservice to British and international medicine,” Collins told the Guardian at the time, claiming that the alarm caused was probably killing more people than had been harmed as a result of the paper on the MMR vaccine by Andrew Wakefield. “I would think the papers on statins are far worse in terms of the harm they have done.”³

He has been recently followed on this theme by Professor Magdi Yacoub (A famous heart surgeon, now retired from this job). Who is pressing the ‘you’re killing patients’ button with great enthusiasm.

Hey guys, engage in scientific debate, or shut up. Accusing people of killing patients is a terrible and horrible insult, and should play no part in any discussions of this sort. It is the tactics of the playground bully. Yes, I mean you.

References (may require site registration or membership to access)

1:http://www.abc.net.au/science/news/health/HealthRepublish_124166.htm

2: http://webappmk.doctors.org.uk/Session/3366252-XXkGXnwQtec5BtkDi3av-aoqmidr/MIME/Trash/146856-02-B/collins%20statins%20exchange%20with%20cochrane.pdf

3: http://www.theguardian.com/society/2014/may/15/statins-bmj-statement-professor-collins-side-effects

Sorry that I have been a bit quiet recently. Just been finishing off my latest book ‘The dangerous book for grown-ups.‘ [Plug]. Anyway, I most amused to see the latest headline from a study that appeared in my inbox. I felt I had to comment.

‘Onglyza offers unparalleled confidence in a broad range of patients with Type 2 diabetes, delivering effective glycaemic control, without the worry of increased risk of CV events.’ This headline was from a site called MDLinx that pushes stuff at me – whether I want it to or not. Actually I did subscribe, as I am always interested in what the pharmaceutical industry is saying about itself.

Onglyza by the way is one a range of new drugs designed to lower blood sugar levels in diabetes. It works in a complicated fashion. However, the bottom line is that is increases insulin release – mainly after mealtimes. Onglyza also goes by the generic name saxagliptin.

Anyway, to return to the main point here. We have this wonderfully positive headline about a new trial on Onglyza, and what could be wrong with that, you may ask yourself? Well, once upon a time, it was assumed that if you lowered that blood sugar you would also reduce the risk of cardiovascular disease. Heart attacks and strokes mainly. This was because a raised blood sugar (or type II diabetes) is seen a very strong risk factor of cardiovascular disease.

Which means that you would kind of expect that if you lowered blood sugar using Onglyza, you might also see a reduction in heart attacks and strokes. instead we have a headline proudly announcing that doctors need not worry about Onglyza increasing cardiovascular risk. My but life does move on.

So what the bloody hell does it do then, exactly? Well, there is much concern that it might increase the risk of pancreatic cancer.  Anything more? Well, here from Wikipedia:

In February 2012, Bristol-Myers/Astra Zeneca distributed additional safety information on saxagliptin use in South Africa. The package insert is to be edited for South Africa. Contraindications will now include a history of sensitivity to saxagliptin (or another DPP4 inhibitor) as well as pancreatitis. Spontaneously-reported adverse events in South Africa have included anaphylaxis, angioedema and acute pancreatitis.

In a cardiovascular outcomes trial, saxagliptin treatment let to a small but statistically significant increase in the risk of being hospitalized for heart failure. http://en.wikipedia.org/wiki/Saxagliptin

Blimey, is there nothing this drug cannot do? Well, one thing it does not do, hooray, is that it does not actually increase the risk of cardiovascular disease. Just as well really, otherwise every effect that Onglyza has would seem to be completely negative. Heart failure, pancreatitis, possibly even pancreatic cancer.

We have reached an interesting point in drug development when the fact that a drug designed to prevent a disease (CV disease) is hailed for not causing an increase in that very disease. Has this really become the limit of our ambitions.

Having thought about this for a while I decided to create my new generic headline that pharmaceutical companies can feel free to use if they wish. Are there no limits to my generosity?

‘A groundbreaking study has found that (insert name of drug here) does not kill people from the disease it is supposed to be preventing. Internationally famous opinion leader (insert name of opinion leader here) says this is a landmark study and strongly recommends that (insert name of drug here) should become the drug of choice for (insert name of disease here)‘

 

 

Don’t worry it’s only $9Bn

Last week I noticed that Takeda, and Lilly had just been fined $9bn.

A US jury has fined Takeda and Eli Lilly $9 billion (£5.4 billion) for causing a man’s bladder cancer with their diabetes drug Actos (pioglitazone). The verdict came down hard on the companies after the case unearthed evidence that Japanese company Takeda had deleted emails, at least one of which raised concerns over Actos’ safety. ‘This serves as a wake-up call to those pharmaceutical companies that cut corners and hide or distort the facts rather than openly testing and educating about their drugs,’ Mark Lanier, who represented the plaintiffs, tells Chemistry World.

Takeda was unable to produce files for 46 clinical and sales employees, 38 of which were deleted after it ordered documents be preserved in 2002 ahead of legal action over Actos. ‘The breadth of Takeda leadership whose files have been lost, deleted or destroyed is, in and of itself, disturbing,’ wrote Judge Rebecca Doherty in a January ruling.  http://www.rsc.org/chemistryworld/2014/04/missing-emails-safety-risk-actos-takeda-eli-lilly-fine

I think that most industries would be somewhat shocked at a fine this big, and this truly was a whopper. However, it follows a pattern of massive fines. GSK was fined $3Bn in 2011 for suppressing clinical trial data on increased suicide risk in children, among many other activities, such as paying kickbacks to doctors. Pfizer was ordered to pay $2.3Bn in 2009 for a series of illegal activities, from mis-branding drugs, to bribery and corruption. AstraZeneca had to shell out $523 million in 2010 for illegally marketing Seroquel for use in children. Roche is accused of hiding data on Tamiflu, GSK is embroiled in corruption cases in China and elsewhere. Merck was hit with a $670 million fine over Medicare fraud in 2007. Eli Lilly shelled out $1.4Bn for illegal marketing in 2009…….etc.

These are vast fines, and the activities exposed are very disturbing indeed. Suppressing data on drugs causing cancer, or suicide, is very serious indeed. You would think these fines would be punitive, but clearly they are not. Or they wouldn’t keep happening. Perhaps the companies just see this as the price of doing business?

Say you have a drug that is making $5Bn a year in profit, and half of that profit comes from illegal marketing, or hiding data. It is not difficult to work out that after only five years, you have made an extra $12.5Bn in profit. I assume it takes at least five years for any case to come to court – probably far, far, longer. (Takeda, it seems, started suppressing data as far back as 1993)

I suppose the equation here is very simple, if dreadful. If you get fined a paltry £1Bn for hiding data, then you have made an extra $11.5Bn in profit from acting illegally. Even if you get fined $9Bn, you are still in the money. (Sales of pioglitzazone were very nearly £5Bn in 2010, so this is not an abstract discussion).

In short, if you do not possess a moral compass, and you are only interested in maximizing profit, it makes perfect sense to market your drugs illegally, pay bribes to doctors, suppress data on increased cancer risk – and all the rest of the corrupt and illegal activities that have been exposed in the courts. Why would you not? Any fine you have to pay is going to be smaller than the increased profit.

In my opinion the only real ‘why you would not‘ is if you, the CEO of Takeda, or Merck, or Pfizer can actually be sent to jail if it turns out that the company was acting illegally on thier watch. At present, the greater the profit, the greater the CEO bonus. Fines will usually arrive long after you have left the company, with a massive pay off, and a pat on the back for your great work in boosting shareholder value.

I think it would concentrate the mind if the CEO or Takeda, or Merck, or Pfizer knew that they would go to prison for a long time, if the company they run, or ran, is found guilty suppressing data. At present we are, effectively, rewarding corrupt behavior by pharmaceutical companies. Which is why there have been so many huge fines; and why I predict that there will be many more.

Currently, the situation is one of extreme moral hazard. A pharmaceutical company makes far more money acting illegally, than acting legally. If the activity is exposed, no-one goes to prison and no-one is personally bankrupted. All that is required is  to set aside enough money to pay the fine, if it ever arrives. ‘Don’t worry, dear shareholders, it’s only $9Bn.’ Phew, and I thought profits would be damaged.’