What is a conflict of interest anyway?

Whilst away on my holidays I have been watching the battle between the BMJ and Professor Sir Rory Collins. A couple of years ago I watched the battle between Professor Sir Rory Collins and the Cochrane Collaboration. A month ago I was taking part in the battle between various professors and cardiologists and Professor Sir Rory Collins.

He, as you probably know, thinks statins are wonder drugs that should be prescribed to almost everyone. Actually, that is not entirely true. He doesn’t believe they should be prescribed to almost everyone. He believes that they should be prescribed to everyone.

He thinks statins have no adverse effects at all. In fact, they actually make people feel better when they take them. He viciously attacks anyone who might dare to suggest otherwise, and has accused them of killing people by frightening them off taking these uniquely lifesaving medications. This has been the basis of his attacks over the last couple of years.

Now, he might really believe all this to be true. In fact, I think he probably does. Of course, he might not believe it to be true, but he is just saying it anyway. One of the great frustrations of life is that you can never know what another person is really thinking. You can guess all you like, but it is only ever a guess.

The problem that we have here is that Professor Sir Rory Collins runs a unit called the Clinical Trials Service Unit at Oxford. This unit has received nearly £300m ($500m) in funding from pharmaceutical companies over the years. Without this funding, his unit would be very much smaller. It probably would not exist at all.

Now, you could say that this makes Professor Sir Rory Collins utterly dependent on pharmaceutical company funding, and therefore you should not believe a single word that he has to say about anything to do with statins, and other such drugs. He is completely corrupted.

You could counter argue that this is a ridiculous stance to take. His is a highly motivated and ethical researcher who works with the industry, purely in order to develop effective medicines that will help humanity. After all he is both a Sir and a Professor.

You could say that his Knighthood and professorship are completely irrelevant, and simply ask the following question. Why does he say he has no conflicts of interest to declare. Why does he state that he receives no money from industry. Why has he never admitted to the association between himself, the CTSU, of which he is a director, and £300m in drug company funding? Why does he never disclose these financial interests? Why not, indeed?

His argument, I believe, is the following. If the pharmaceutical industry pay the CTSU, who then pay him, he is not actually being paid any money directly by the pharmaceutical industry. So he has no conflicts of interest to declare. Discuss. [Shouldn’t take long].

Whether or not you think his is conflicted (and I do), this discussion leads into a rather more complicated area. What is the purpose of declaring that you have a conflict of interest in the first place? What does it matter if you are paid money by someone else who has a vested interest in making sure that certain things are said, and done.

Now, you may think the answer is simple. If Professor Sir Rory Collins states he has a conflict of interest e.g. the unit he runs is paid £300m by the industry, we can then….. We can then…..We can then what?

Believe nothing that he says about statins. Believe everything that he says. Believe most of what he says. Believe a bit of what he says. The problem is that there are only two rational positions here.

  • Believe everything
  • Believe nothing

How can you believe most, or a bit, of what Professor Sir Rory Collins says? Which bits could you ignore, which bits could you pay attention to? How could you possibly know? The answer is that you cannot.

Which then leads onto the next question. Why do medical journals, and suchlike, demand that researchers, lecturers and authors declare their conflicts of interest? What does this achieve? If having a conflict means that the author/researcher is biased, then surely the article cannot be published – as the journal is accepting a biased piece of work. Believe me, properly done, bias is impossible to spot. It’s like hearing the dog that didn’t bark.

On the other hand, if conflicts of interests mean nothing. In that you can have financial conflicts of interest, but this makes no difference to anything you say or do – why bother demanding that the conflicts of interests are declared.

In short, I cannot see what declaring a conflict of interest achieves.

Man on the Street 1: ‘Oh, I see Professor Sir Rory Collins unit has received £300m in funding from the pharmaceutical industry. Most interesting. However, this clearly makes no difference to anything he has to say on the matter.’

Man on the Street 2: ‘Oh, I see that Professor Sir Rory Collins unit has received £300m in funding from the pharmaceutical industry. Clearly he is corrupt and biased and I shall pay no attention to any he has to say.’

Man on the Street 3: …. ‘I shall believe 82% of what he has to say.’

Man on the Street 4: …..’I shall believe 23% of what he has to say.’

Which of the men on the street has the right idea? There is no way to tell, without becoming a mind reader. At present, when it comes to conflicts of interest, we just have a gigantic fudge. So long as people declare their conflicts they are then free, it seems, to do anything they like. Carry out research, write papers, sit on guideline committees, advise the Government and NICE. Declaring the interest…what? Makes the possibility of bias disappear?

But what should really happen. My view is relatively simple. I have said it before, and will say it again. If you get paid money by the pharmaceutical industry then, fine. I have no problem with that. Good for you. Buy that luxury ski chalet in the Alps if you want. Indoor swimming pools are lovely things to have. Have both – you will certainly be able to afford it.

However, once you have taken the money, directly or indirectly, you should not be allowed to sit on guidelines committees e.g NICE. Nor should you be allowed to educate your fellow doctors on best forms of drug treatment, or act as a Government advisor on healthcare matters – or suchlike. Because you are, even if you don’t think you are – and get very angry with anyone who suggests that you might be – biased.

This nettle needs to be grasped, and it needs to be grasped soon. I am not a great believer in absolutist positions, as they tend to block the compromises that are necessary for things to work in life. However, when it comes to conflicts of interest I think that the only possible position to take is absolutist. If you are paid money by the pharmaceutical industry, you cannot be appointed to a position that allows you to influence how drugs are used. End of.

Immovable Object

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 18th 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.

Another backlash begins

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

10th 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

Calling All Physicians: The Salt ‘Debate’ Must Stop

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

You are killing patients

(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

Catalyst crushed?

“A lie gets halfway around the world before the truth has a chance to get its pants on.”
Winston Churchill

ABC takes down Catalyst heart disease episodes after review criticism

Controversial TV program on cholesterol-lowering statins found to have breached editorial standards1

And that, as the Guardian reported, seems to be pretty much that. Here is some of the accompanying text.

‘Two episodes of the TV science program Catalyst will be removed from the ABC’s website after an internal review found the program had breached editorial standards on impartiality.

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.’

If this was all you had heard about the matter you would assume that ABC had done a very shoddy job, with sloppy and potentially dangerous reporting. Well, this is all very interesting. However, if you were to criticise sloppy reporting you could start with the Guardian report itself.

To begin with there were two programs, covering different issues, one of which had nothing to do with statins at all. However, the Guardian headline suggests there were two episodes ‘on statins and heart disease’. Not true. The first episode discussed whether or not saturated fat consumption caused heart disease. This episode was called ‘dietary villains’. It had nothing whatsoever to do with statins. The internal review found that this episode contained no errors. (Yet still it is being taken down?)

The second mistake the Guardian made is to accept Norman Swan’s statement that Indigenous Australians are especially likely to ‘suffer from high cholesterol’. Well this is complete rubbish. In one of the very few studies to report cholesterol levels in this population, published in the BMJ, the average cholesterol levels were very low (around 4.4.mmo/l)2. Lower than in any Western country.

Really, dear Guardian reporter, you ought to check your facts before writing such stuff – as should Norman Swan. But hey, checking facts is very time consuming, I think you will find. Moving on, I should also point out that you cannot ‘suffer’ from high cholesterol as there is no level of cholesterol that causes any symptoms. Mind you, if it were possible to ‘suffer’ from high cholesterol then the Swiss, with an average cholesterol level of 6.4mmol/l, would be suffering mightily. [Instead of having an extremely low rate of heart disease.]

Blimey, a few short paragraphs, and this article is already full of cock-ups. Of course, if you decide to go through anything with a fine toothcomb you will be able to pick up all sorts of errors. Writing scientific stuff is not easy. There is always a choice between absolute factual accuracy and providing the broader picture.

There is another choice between which facts to include, and which to exclude. Because of these inevitable tensions, and difficulties, if you want to attack any study, article, TV program, you will always find some traction. Sure as eggs is eggs, any program criticising statins was bound to be attacked mercilessly. Dr Uffe Ravnskov, a long time statin critic, had his book burned live, on air, in a Finnish TV studio. Part of a highly scientific debate, no doubt.

As a disclosure of interest, I did help the programme’s producer, and presenter, Dr Maryanne Demasi with questions and background information whilst she was putting the Catalyst programs together. I tried to give her as much factual information as possible. The day after the programmes came out, I wrote her this e-mail on 31st October 2013:

Maryanne,

Just seen part II. Brilliant, well done…….. I feel a sense of pride being able, in a small way, to help you put this together.

I now hope that you are viciously attacked, because that means you have won. (And it also means that thincs has won). Be ready – I suspect the attacks have already started.

She wrote back on the 4th of November:

Malcolm

OMG!! I am getting attacked in the media. They’re out for blood!!

Where do I hide??!!

Since then, the attacks have been relentless, from many directions. Page after page of criticism from the National (Australian) Heart Foundation (NHF). Withering attacks by the likes of Norman Swan – who seems to have set himself up at the ultimate arbiter of science in Australia. Somehow or other. Despite the fact that he believes people ‘suffer’ from high cholesterol, and has no idea about risk factors for heart disease in Indigenous Australians.

These attacks were battered backwards and forwards until my brain began to overheat. I provided supportive information to counter the criticism. As did several others. Point after point was refuted. It became quite exhausting.

Eventually, it seems ABC effectively caved in and removed the programmes. Why, I am not sure. The judgements on the programmes were almost entirely supportive – with a single exception, which I shall get to. Here, for example, was the commentary on the first programme on the link between saturated fat and heart disease.

Accuracy and impartiality

Episode 1 – ‘Dietary Villains’

The role of dietary saturated fats in heart disease has been controversial since the theory was first postulated at the beginning of the twentieth century. Notwithstanding the lack of definitive proof, mainstream medical organisations such as the National Heart Foundation (NHF) believe there is enough good quality evidence to recommend a diet low in saturated and trans fats…

In our view, the program could have done a better job of teasing out the mainstream perspective to leave audiences better informed.

However, in our assessment this did not amount to a breach of the impartiality standard in the first episode because judgements about impartiality require a number of factors to be weighed. While there were problems with structure and tone:

1. The factual information in the program was accurately presented and the reporter has demonstrated that she diligently sought and considered a variety of views on the subject. No material inaccuracy has been demonstrated by any complainant.

2. The principal perspectives were presented.

3. Neither position was endorsed by the program.

4. Neither perspective was misrepresented.

5. The nature of the program necessitated that the unorthodox theory was given more time and explanation. The Code does not require that they receive equal time, nor that every facet of every argument is presented.

As an important aside, I find it fascinating that the committee accepted that there is no ‘definitive proof’ that saturated fats cause heart disease. Check.

Yet, in a complete rupture of logic, the report stated that the ‘National Heart Foundation believe there is enough good quality evidence to recommend a diet low in saturated and trans-fats.’

Well, if there is enough good quality evidence, there must be, by definition, definitive proof. Either one statement is correct, or the other. They cannot both be, as they are mutually contradictory. This I am afraid is the level of thinking that goes on here. As expected, there is no criticism of the National (Australian) Heart Foundation for recommending a diet for which where is no ‘definitive proof.’ ‘It’s okay, they believe there is enough good quality evidence, and they are good chaps. So that is good enough for me.’

This is the usual kowtowing to the experts. If the roles had been reversed, Catalyst would have been crucified for promoting dietary advice based on nothing at all. Yet, the NHF are completely let off the hook with this pathetic statement.

‘Notwithstanding the lack of definitive proof, mainstream medical organisations such as the National Heart Foundation (NHF) believe there is enough good quality evidence to recommend a diet low in saturated and trans fats.’

Hang your heads guys. What is sauce for the goose should also be sauce for the gander.

And what of other ‘complaints.’ Here is another judgement, from this very, very, long document:

Did the program incorrectly state that it had sought comment from Merck Sharp & Dohme?

Complaint

Catalyst reported that it sought comment from MSD. MSD says that no contact was made.

Assessment

Catalyst has provided emails demonstrating that it approached MSD for responses to a number of detailed questions. MSD replied that it would not comment on the specific questions and stated only that:

‘MSD is committed to ethical research and abides by the principals of good clinical practices. All clinical trials and their protocols undergo review by hospital ethics committees.’

We are satisfied that Catalyst contacted MSD for comment and they declined to provide specific responses to allegations.

Conclusion – No breach of section 2.1.

Basically, MSD lied. They complained that no-one had sought any comment from them. It turned out this was nonsense, they were simply telling porkies. Any criticism of the company? No.

Here is another of the complaints:

Undue favouring of the perspective that saturated fats do not cause heart disease by raising cholesterol – part I – Code of Practice sections 2.2 and 4.5

Complaint

The hypothesis that eating saturated fats can increase cholesterol levels which in turn can cause heart attacks is widely accepted by the medical community and is the basis for most official dietary advice. Some medical researchers and physicians believe the hypothesis is flawed – Catalyst presented and examined their criticisms.

Complaints, including from the National Heart Foundation, allege the analysis lacked balance and omitted critical evidence…..

Assessment

We are satisfied on the basis of our review that the program’s scepticism towards the diet-heart hypothesis was not unjustified and its presentation of an alternative approach did not amount to an undue favouring of that approach.

Conclusion – No breach of section 4.5, no breach of 2.1

Are you getting some sense of what happened here? In point after point, it turns out that the Catalyst programmes had not, in any way, got anything wrong. Nothing, zip, nada. If you are so inclined, you can read the whole report3. To save you the trouble I have pulled out all the complaints, and added in the conclusions in as concise appendix as I can manage. [There is also a short appendix to make it clear what the Codes of Practice mean].

COMPLAINTS

[There were a total of twelve separate complaints, looking at seventeen possible breaches of editorial standards]

1: Ancel Keys’ population studies were misrepresented – Part I – Code of Practice section 2.2

Conclusion – No breach of section 2.2

2: Mediterranean Diet & The Lyon Diet Heart study – Part I – Code of Practice section 2.2 (Did the program accurately describe the Lyon Diet Heart study?)

Conclusion – No breach of 2.2

3: Misrepresentation of the composition of margarine in Australia – Part I – Code of Practice sections 2.1 & 2.2

Conclusion – No breach of section 2.2

4: Inaccurate description of the structure of polyunsaturated and saturated fats – Part I – Code of Practice section 2.1

Conclusion – No breach of section 2.1

5: Misrepresentation of the National Heart Foundation & Dr Grenfell – Part I – Code of Practice section 2.2

Conclusion – No breach of section 2.2.

6: Undue favouring of the perspective that saturated fats do not cause heart disease by raising cholesterol – part I – Code of Practice sections 2.2 and 4.5

Conclusion – No breach of section 4.5, no breach of 2.1

7: Misrepresentation of the 4S trial data – Part II – Code of Practice section 2.2

Conclusion – No breach of section 2.1 or 2.2

8: Merck Sharp & Dohme (MSD) – Part II – Code of Practice section 2.1 (Did the program incorrectly state that it had sought comment from Merck Sharp & Dohme?)

Conclusion – No breach of section 2.1.

9: Unfair characterisation of Australia’s medicines industry – Part II – Code of Practice sections 2.1 & 4.5

Conclusion – No breach of section 2.1 or 4.5.

  1. Failure to provide material context by not disclosing the commercial interests of some of the experts featured – Parts I & II – Code of Practice section 2.2

Conclusion – No breach of section 2.2.

  1. Failure to provide material context in relation to use of statins and undue favouring of view that statins do more harm than good – Part II – Code of Practice 2.2, 4.5 and 7.6

Did the program unduly favour an anti-statin viewpoint in its presentation of the evidence for the benefits and harms of statins?

Conclusion – Breach 4.5; No breach 2.2; No breach 7.6 (4.5 Do not unduly favour one perspective over another.)

  1. The program falsely claimed that the National Heart Foundation had ‘signed off’ on Catalyst’s evidence (PM 31/10/13) – Code of Practice sections 2.2 & 4.4

Conclusion – corrective action required, no breach 4.4

Twelve complaints about seventeen possible breaches of conduct, one upheld (I don’t think I have ever written anything that accurate in my life). There was another part of the report where the judgment is so weird that I cannot understand it. I defy anyone else to understand it either. You can read the whole report if you wish, and see what you think.

It seems to be saying that stratifying risk in primary prevention of heart disease is something that is contentious, but a lot of doctors believe in it, so it should have been mentioned. Something with no evidence to support it, that happens to be believed in by a number of doctors, should be presented as what….the truth? That bit is bonkers. It seems they thought they should say something, but descended into gibberish.

When you get down to it, the judgement is that there was a single breach. Represented thus:

‘The program’s treatment of use of statins in secondary prevention focused solely on mortality benefits in a way that reinforced the view that statins were overprescribed and their benefits exaggerated. The principal relevant perspective that statins have wider benefits for this group was not properly presented. This perspective was necessary to a fair understanding of the pros and cons of statin use in this group.’

Turning this into English. What the committee believe they found was the second Catalyst program ‘Cholesterol drug war’ did not mention that statins have benefits on non-fatal outcomes e.g. non-fatal heart attack, and non-fatal stroke. By failing to mention this point it was judged that the program gave a misleading perspective on the overall benefits of statins (in secondary prevention).

And that, ladies and gentlemen, is that. Perhaps not quite the crushing indictment you thought. Now, you must remember that this committee was starting from scratch, knowing bugger all about the area of statins and heart disease. Given this, they didn’t do too badly. But on the point about non-fatal strokes and non-fatal heart attacks they failed to spot the Elephant in the room. An Elephant that I need to describe to you.

Pharmaceutical companies hide data

The elephant in the room is that, when it comes to data on statins (and most other drugs), we are completely reliant on pharmaceutical companies to provide it. Increasing attempts have been made to get them to release all the data they have, but this has proven virtually impossible. Recently, we have seen a battle over the Roche drug Tamiflu:

‘The British Medical Journal (BMJ) has alleged that pharmaceutical giant Roche is deliberately hiding clinical trial data about the efficacy of oseltamivir (Tamiflu) in patients with influenza. The journal says global stockpiling and routine use of the drug are not supported by solid evidence and alleges that Roche concealed neurological and psychiatric adverse events associated with the neuraminidase inhibitor drug.

In an open letter from Fiona Godlee, MD, editor-in-chief of BMJ, to Professor John Bell, FRS, HonFREng, PMedSci, Regius Professor of Medicine at Oxford University in the United Kingdom and a Roche board member, published online October 29, Dr. Godlee reminds Bell of concerns that were initially voiced in 2009 about the reliability of Tamiflu research.

At that time, BMJ published an updated Cochrane review of neuraminidase inhibitors in healthy adults. That study “took the view that, since eight of the 10 [randomized controlled trials] on which effectiveness claims were based, were never published, and because the only two that had been published were funded by Roche and authored by Roche employees and Roche-paid external experts, the evidence could not be relied upon,” Dr. Godlee writes.’ [From medline, needs registration to view]

To quote the Cochrane collaboration on this matter:

“Patients around the world are being harmed because clinical decisions on their health care are skewed by the absence of clinical trials data,” said Mark Wilson, CEO of The Cochrane Collaboration, in announcing this new partnership. “For 20 years The Cochrane Collaboration has been working to give clinicians, researchers and patients the best possible evidence-based information to help them make informed decisions, and it is a scandal that we still do not have access to all trials data so that we can be confident in our conclusions…”4

Many people find it difficult to believe that companies just hide the data. But they did, and do, and shall do into the future, I would imagine. The 4S study, the single most positive study on statins ever done, by a long way, is more than slightly worrying in this respect. To quote from a blog by Dr Walter Ferneyhough, discussing the 4S study:

‘Did I mention the study bias. Well, it was funded by Merck (the pharmaceutical responsible for simvastatin (a.k.a. Zocor)), was monitored by the Scandinavian subsidiaries of Merck, and the data analysis was performed by Merck. A financial disclosure (conflicts of interest) of the researchers were not given, which is odd, since most studies provide this information.’5

If you believe that there is no possibility that the industry might present biased data, or fail to provide data that is not positive about their products, then you can sleep soundly in your bed…..you poor deluded fool. The reality is that negative studies are not published. Even when a study is positive the ‘raw’ data are held by the pharmaceutical companies. They release what they like, and keep secret what they like. Perfectly legal, so I am reliably informed.

When it comes to statins, this is highly significant when it comes to the issue of Serious Adverse Event (SEA) data. To explain this in a bit more detail, because the terminology here is confusing.

Drugs can cause adverse effects e.g. flushing, pain, headaches. These are known as drug related adverse effects. They are commonly called side effects, but this is inaccurate. A side effect can be positive, or negative.

On the other hand there are Serious Adverse Events (SAEs). SAEs include deaths. They also include nasty things such as a non-fatal MI, or a non-fatal stroke. Things that could be prevented by a statin. So that is good news for statins. However, an SAE could also be an episode of Rhabdomyolysis, or liver damage requiring hospitalisation, or Transient Global Amnesia, or tendon rupture. These could be caused by the statin, and would therefore be bad news for statins.

As you can see, after mortality, SAEs are the next best measure of how beneficial, or harmful, a product might be. Whilst pharmaceutical companies are delighted for us to have the data on positive SAEs, they are completely silent on the data on negative SAEs. Here is what the Cochrane collaboration first had to say on the matter, after they tried to get hold of the data from the statin trials:

Are SAEs reported in the major lipid-lowering trials?

SAE data were sought in the major placebo-controlled trials published up to September, 2001 using statins (5 trials)3-7 or fibrates (5 trials).8-12 Remarkably, only one study, the AFCAPS trial,3 reported total % SAEs in the treatment and placebo groups. In this study, lovastatin was compared with placebo in patients without cardiovascular disease (primary prevention). Similar total % SAEs were reported for the lovastatin, 34.2%, and placebo groups, 34.1% (RR = 1.0 [0.94-1.07]). What this indicates is that the 1.4% absolute risk reduction in total MI or CV death (see Table Letter #27) has been negated by an absolute risk increase in other SAEs. No information is provided as to what these other SAEs might be. The only other trial that reported anything approximating SAEs was the coronary drug project (CDP), a secondary prevention trial. This trial reported the percentage of patients ever hospitalized at 5 years: 55.1% for clofibrate and 52.4% for placebo (RR = 1.05 [0.99-1.12]).

Later on, they had this to say:

‘How can CHD (Coronary Heart Disease) SAEs decrease, but not total SAEs?

All CHD events are SAEs and are counted in both categories. Therefore a reduction in major CHD SAEs should be reflected in a reduction in total SAEs. The fact that it is not suggests that other SAEs are increased by statins negating the reduction in CHD SAEs in this population. A limitation of our analysis is that we could not get total SAE data from all the included RCTs. However, we are confident that the data from the 6 missing RCTs would not change the results, because they represent only 41.2% of the total population and include ALLHAT-LLT10, where one would not expect a reduction in total SAEs; in that trial there was no effect on mortality or cardiovascular SAEs.6

Yes, these reports from the Cochrane collaboration are getting a bit old now. But so are the placebo controlled statin trials, the ones that are used to support all the guidelines on the use of statins. So, when you get down to it, the fact is this. Serious adverse events are simply not reported from the major statins trials, the data are not released.

Which means that the data that are reported are completely skewed. Yes, statins (in secondary prevention) can reduce non-fatal MI and non-fatal strokes. But they increase other unpleasant things by approximately the same amount.

Now, let me take you back to the judgement on the Catalyst program.

‘The program’s treatment of use of statins in secondary prevention focused solely on mortality benefits in a way that reinforced the view that statins were overprescribed and their benefits exaggerated. The principal relevant perspective that statins have wider benefits for this group was not properly presented. This perspective was necessary to a fair understanding of the pros and cons of statin use in this group.’

The committee that sat in judgement of the Catalyst programme was, in my opinion, very fair in the vast majority of what they said. But on this issue they got it terribly wrong. I cannot really blame them, for they probably cannot believe that critical trial data on SEAs are simply withheld. It cannot even be seen by independent researchers.

Because you probably do not believe that this can possibly be true either, I am about to do something that I possibly should not. I have taken advice from a number of people on this, and the views are contradictory. I am about to reveal e-mails that I was sent, and I have not sought permission to do so. Frankly, I know that if I did I would never get permission from all the parties involved [as you will understand once you have read them]. However, I think they are of such enormous importance that people should know they exist, in order to make their own minds up.

The e-mails come from the following discussion. Whilst making the Catalyst programme, Maryanne Demasi contacted Professor Colin Baigent from the Cholesterol Treatment Triallists Collaboration (CTT). The CTT are Oxford based group that hold all the data from the statin trails (Exactly how much, and in how much detail, I have no idea). They are hugely influential, and their meta-analyses form the basis for guidelines on the use of statins around the world. In the UK, the latest NICE guidance will be based entirely on them.

I have known for some time that the CTT will not release the data that they hold, to anyone. But when I speak to journalists they don’t really believe me, much eye-rolling occurs. So, please read on, and find out the truth for yourself. [The only editing I have done to this e-mail trail is to remove all contact details, apart from the address of the CTSU which can be easily found]. You can amuse yourself by spotting the point where the lawyers get involved in drafting the e-mails.

 

To: Enquiries at CTT
From: Maryanne
Sent: 22 September 2013 05:05
Subject: URGENT COMMENT NEEDED PLEASE: ABC TV AUSTRALIA

Hi, I am a medical reporter for ABC TV AUSTRALIA and I am doing a report on statins in primary and secondary prevention.

I have interviewed Harvard Dr John Abramson about the over use of statins within the population and also the lack of transparency of data when it comes to clinical trials.

In the interview he mentions the CTT collaborators being one group who have access to individual data but will not share their data with the public or other researchers even though they’ve been asked.

Prof Rita Redberg from University of California San Francisco supports these statements.

I would like a comment from CTT collaboration regarding Dr Abramson’s and Prof Redberg’s statements please?

Why has the CTT Collaborations refused to release all the data requested of them?

Kind Regards
Maryanne Demasi
Producer
ABC TV AUSTRALIA

 

To: Maryanne Demasi
From: Colin Baigent – CTT
Date: Mon, 23 Sep 2013 21:37:01 +0000
Subject: FW: URGENT COMMENT NEEDED PLEASE: ABC TV AUSTRALIA

Dear Maryanne

Drs Abramson and Redberg are incorrect in stating that the Cholesterol Treatment Trialists’ (CTT) Collaboration has not shared data on the effects of statin therapy in healthy people. Comprehensive analyses of the effects of statins in people at low risk of heart disease or stroke were published (and widely publicised) in the Lancet in 2012, and directly addressed questions about the balance of benefits and risks of statins in such people. The work showed clearly that statins are of net benefit even among those with no previous history of cardiovascular disease.

I would be pleased to discuss this issue with you over the telephone if this would be helpful. I can be reached on +44…

Colin Baigent
Professor Colin Baigent
MRC Scientist & Hon Consultant in Public Health

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU)
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford OX3 7LF

 

To: Rita Redberg and John Abramson
From: Maryann
On Sep 23, 2013, at 2:51 PM

Hi Rita and John,

Both of you mentioned in the interviews that the CTT collaborators don’t give full access to their data to public but the deny this. Please see below and respond as soon as possible please?

Many thanks

 

To: Maryanne Demasi
From: John Abramson
24/09/2013

To: Maryanne, Jim Wright

Maryanne,I have forwarded this to Jim Wright, who is the Co managing director of the Therapeutics Initiative in British Columbia. He has direct experience re ctt data sharing. I do not want to speak for him, but I believe he will be interested in the email below from Dr. Baigent.

Best wishes,
John

 

To: Maryanne Demasi
From: Rita Redber
24/09/2013

Publishing data that they have analyzed is NOT at all the same as giving full access to the public, or to other researchers. In whatever they publish, they maintain control and access to their data, the analyses etc. I am referring to the fact that CTT will not make their data available to any colleagues and other researchers who wish to study risks and benefits of statins. THe CTT data is not accessible publicly.

Rita

 

To: Colin Baigent
From: Maryanne Demasi
24 September 2013 00:50

Hi Colin, thanks for your time. 

I wasn’t referring to the published data, its the unpublished data. Dr Redberg has been specific:

“Publishing data that they have analyzed is NOT at all the same as giving full access to the public, or to other researchers. In whatever they publish, they maintain control and access to their data, the analyses etc. I am referring to the fact that CTT will not make their data available to any colleagues and other researchers who wish to study risks and benefits of statins. THe CTT data is not accessible publicly.”

Comment?

Cheers
 Maryanne

 

To: Maryanne
From: Colin Baigent
Tue, 24 Sep 2013 10:44:01

Dear Maryanne

This is again incorrect. The trials participating in the Collaboration contributed their data to the combined database on the understanding that the data would be held securely and that analyses would be  discussed and agreed by the collaborators before they are conducted. We meet annually, and discuss proposals for new analyses at those meetings. We welcome suggestions for new analyses from scientists who are not formally part of the Collaboration. If, after discussion, such proposals are felt to be scientifically worthwhile (and are feasible) they are conducted by the Secretariat, and the work is shared with collaborators (which then includes those who proposed the analyses).  It is important to recognise that data from participating trials are not owned by the Collaboration, but remain the property of the trial sponsors, so we are not able to provide unlimited access to the combined database. We do, however, provide a mechanism through which the data can be utilised for public benefit.

I hope this is helpful.

Colin Baigent

 

To: Colin Baigent
From: Maryanne Demasi
24 September 2013 13:26

Hi Colin,

Thanks for your moments. I just want to be clear about how i interpret your email.

The data from the clinical trials is “owned” by the trial sponsors – the statin manufacturers.

Hence, the CTT researchers can’t give full disclosure of the data to the public because the trial owners won’t allow them to? Correct?

Maryanne

 

To: Maryanne Demasi
From: Colin Baigent
Date: Tue, 24 Sep 2013 12:30:22

Dear Maryanne

No, this is again incorrect. I think it may be more efficient if you were to call me so that I can explain the process to you. If you wish to speak then I can be reached at the direct line below.

Colin Baigent

 

To: Rita Redberg, Jim Wright, John Abramson
From: Maryanne
Date: Tue, 24 Sep 2013 22:32:28

Hi Dr Redberg, Dr Abramson and Dr Wright

I wrote to the CTT collaborators (Colin Baignet) a second time specifying that its is the “unpublished” data that they are withholding.  His email is below.  Is it possible that I am asking the wrong CTT collaborators?

Am I missing something?

Regards

Maryanne

 

To: Colin Baigent
From: Maryanne Demasi
Tue, 24 Sep 2013 22:09:39

Unfortunately, I don’t have access to a work phone as its late here in Oz.  Also, our lawyers will want to see all these emails to ensure there hasn’t been a misunderstanding or misrepresentation of your position.  I will have to further clarify further with Prof Redberg, Dr John Abramson and Dr Jim Wright from the Therapeutics Initiative in Canada who all claim that the CTT collaborators do not give full disclosure of their data to the public and other researchers.  They have gone on record with this so the matter must be clarified.

Can you explain why they would say something like this?

Maryanne

 

To: Maryanne Demasi
From: Colin Baigent
Tue, 24 Sep 2013 17:02:23

Dear Maryanne

The CTT secretariat has agreement with the principal investigators of the trials and, in those instances where trial data were provided directly by the drug manufacturers,  with the companies themselves, that individual trial data will not be released to third parties.  Such an agreement was necessary in order that analyses of the totality of the available trial data could be conducted by the CTT Collaboration: without such an agreement the trial data could not have been brought together for systematic analysis. Such analysis has allowed the CTT Collaboration to conduct and report all of the analyses on efficacy and safety that have been sought directly or indirectly by others (eg by Dr Redberg in her papers on the efficacy and safety of statins in primary prevention, and in questions raised by the Cochrane Collaboration). Hence, the CTT Collaboration has made available findings that would not otherwise have emerged.

I would be very happy to ring you at whatever time is convenient for you in order to help you to understand our approach, and then address in writing any residual concerns. It would be a shame if we were not able to speak as this would be the most effective way of explaining things.

Please let me know where and some times when I can reach you, and I will endeavour to telephone.

Colin Baigent

 

To: Colin Baigent
From: Maryanne Demasi
24 Sep 2013, at 22:41

Hi Colin,

I am happy to talk to you.  Ive just arrived at work but understand if its too late in London to call you?!

I have to be honest.  I’m not sure why you keep saying my interpretation of the situation is incorrect because the way I read your last email, it tells me that “individual trial data will not be released to third parties”. (that is a direct quote from the email).

I completely understand the reasons why the CTT can not release this information but the purpose of this correspondence was to confirm that the comments of Prof Redberg, Dr Abramson and Dr Wright were factually correct – that they were not making false statements.

They explained that this is the problem with the data from clinical trials – that drug companies “own” the information and will only release what they want rather than having full disclosure of all the data to the public.

Regards

Maryanne Demasi

 

PHONE CALL WITH COLIN BAIGENT NOTES

I had a follow up conversation with Colin.  He stressed that while the CTT made an agreement with the drug companies not to give full disclosure of the individual data to third parties, the CTT had a very important role in providing doctors with the best information available.  He hoped that my report did not undermine the workings of the CTT.

 

To: Maryanne Demasi
From: Jim Wright
26/09/2013

To: Maryanne Demasi

The truth is that Colin agreed for me to send a student to do that analysis in 2007.  When the student Michelle Wong arrived there he would not let her have access to the data and do the analysis.  We would have done the analysis differently and had a better idea of whether the benefits outweighed the harms in low risk people.  I am not convinced by their 2012 analysis, which is based on little or no harm.

Kind regards,

Jim Wright
Editor-in-Chief
Therapeutics Letter

 


Postscript

So now you know that no-one can see the data. Now you also know that the criticism of the Catalyst programme was unfounded. Balance on the ‘non-mortality’ data on statins is impossible as the data on SEAs are hidden. Yes, know the things that statins can prevent e.g. non-fatal heart attacks, but we do not know the equal and opposite things they cause.

The reality is that, if you all did present the data on non-fatal CV events prevented with statins, you would be presenting catastrophically flawed data. Biased, and unbalanced. Yet, Catalyst is told that this is what they should have done.

I know that nothing anyone says will make any difference to ABC now. They just want the attacks to go away. However, I hope that a few thousand more people are now aware of the truth of this matter.

References (may require site registration or membership to access)

1: http://www.theguardian.com/media/2014/may/12/abc-takes-down-catalyst-heart-disease-episodes-after-review-criticism

2: http://bmjopen.bmj.com/content/3/1/e002308.long

3: http://about.abc.net.au/wp-content/uploads/2014/05/Catalyst-Heart-of-the-Matter-ACA-Investigation-Report.pdf

4: http://www.cochrane.org/features/cochrane-signs-alltrials-initiative-campaign-registration-and-reporting-all-clinical-trials

5: http://www.drfernyhough.ca/Cardiovascular%20disease/files/tag-cardiovascular.html

6: http://www.ti.ubc.ca/newsletter/serious-adverse-event-analysis-lipid-lowering-therapy-revisited

 

 

 

Salt is good for you

One of the most pervasive and stupid things that we are currently told to do is to reduce salt intake. This advice has never been based on controlled clinical studies, ever. Yet, as with the cholesterol myth, the dogma that we should all reduce salt intake has become impervious to facts. I find that the ‘salt hypothesis’ is rather like a monster from a 1950s B movie. Every time you attack it with evidence it simply shrugs it off and grows even stronger.

Very recently, a study was done in Australia looking at salt intake. Actually it looked at sodium intake, not salt intake. I find this interesting, as no-one that I know eats sodium. In fact, it would be interesting to see someone try. To quote from Wikipedia

‘Sodium is generally less reactive than potassium and more reactive than lithium. Like all the alkali metals, it reacts exothermically with water, to the point that sufficiently large pieces melt to a sphere and may explode; this reaction produces caustic sodium hydroxide and flammable hydrogen gas.’

Consuming two grams sodium would likely cause you to explode, splattering sodium hydroxide over the walls. Along with various organs and other body parts.

So why do people talk about sodium consumption? I have never really worked this one out. But it does make things rather confusing. The latest guidelines suggest we should consume less than 2300mg of sodium a day, even as low as 1500mg. Go on, try it. Any idea how much salt (NaCl) that would be? Any idea how much salt you consume every day? No, thought not.

Yes, we have been given guidelines that are totally meaningless, and impossible to follow. In fact 2300mg of sodium is roughly 6000mg of salt (NaCl). So why are we not advise to eat six grams of salt a day? I have no idea. Perhaps someone can tell me. What is this sodium nonsense? [Not that anyone has any idea what six grams of salt even looks like poured out of a salt shaker – I know, I have tried this several times.]

Of course, when I started looking into this area, I went at it sideways. If we eat salt we are eating both sodium, and chloride. You cannot have one without the other. So I became interested in the chloride issue, not the sodium. We are always warned about sodium, but no-one ever mentions chloride levels. Is there any evidence that high chloride consumption is bad for us?

This is an area mostly defined by silence, and zero research. But I have found a few papers looking at chloride levels in the blood and, guess what? They have all found that a low chloride level is associated with a higher mortality. Here is one such, entitled ‘Serum chloride is an independent predictor of mortality in hypertensive patients.’

‘Low, not high Serum Chloride- (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl- and risk.’  (view here)

There you go. Having a low chloride level makes it more likely you will die early. Yet, having a high level of sodium consumption makes is supposed to kill you? And you cannot eat sodium without eating chloride at the same time. Go figure. You mean you can’t?

Anyway, to return to the, not yet published Australian study, here is what they found.

‘In a multivariate-adjusted model, those who consumed less than 3000 mg of sodium per day had a 25% increased risk of all-cause mortality and cardiovascular events compared with those who consumed between 4000 mg and 5990 mg/day (reference group).’ [1]

The guidelines tell us to eat less than 2300mg of salt. At this level, if we use the Australian data, overall mortality will be increased by 25%. Excellent advice then. And this is not just one contradictory study. Several other trials have clearly demonstrated that reducing salt intake significantly increases mortality in high risk patients. Particularly those with heart failure, where it would be expected that salt reduction would have the greatest benefit. Yet the trials showed the exact opposite.

As explained in the Journal Stroke. The section I have quoted below is taken from a reply to an article entitled “Reducing Sodium Intake to Prevent Stroke: Time for Action, Not Hesitation” In this article Appel, the author, argues strongly that we must, absolutely must, reduce sodium intake. In reply, three cardiologists make the following points:

‘In regards to patient-oriented outcomes, Appel dismisses randomized trials in patients with heart failure as irrelevant because of the unconventional treatment approach of the investigators. Yet these trials—showing increases in hospitalizations and mortality with low-sodium intake versus normal-sodium intake—tested identical diets in intervention and comparison arms with the only difference being the level of ingested sodium (making these trials more relevant than DASH-Sodium and other trials Appel cites). Also, Appel fails to cite 3 relevant heart failure trials, all consistently show harm with reduced sodium intake.’ [2]

In short, Appel, along with most ‘experts’ in this area had dismissed evidence he did not like.

The simple fact is this. If you strip out all the data on salt consumption there is considerably more, and considerably more powerful data, suggesting a strong link between low salt consumption and increased mortality than the other way around.

In reality, you can eat just about as much salt as you can stand – without harm. (Unless you have damaged kidneys and/or very high blood pressure)

How can I possibly state this? Well, a very wise Swedish professor pointed something out to me a few years ago. If a patient is very ill in hospital and cannot eat, or drink, they will have a drip put up to replace fluids. This very often contains 0.9% NaCl. Or nine grams of salt per litre. Quite often the patient will have two litres of this replacement fluid a day – which is (as you may have figured) 18 grams of salt.

So, we quite happy to give critically ill patients 18 grams of salt per day to help them get better – which has no discernable effect on their blood pressure, or anything else. Yet we tell people that they cannot eat more than six grams a day. Ho, ho. You earthlings are so funny.

References (may require site registration or membership to access)
[1] http://www.medscape.com/viewarticle/824749?src=emailthis
[2] http://webappmk.doctors.org.uk/Session/1405533-8qblkO84E9hsUXe6OUa4-aoqmidt/MIME/INBOX/125637-02-B/Stroke-2014-DiNicolantonio-STROKEAHA.114.005067.pdf to be published soon

The dog that did not bark

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)

 

 

$9Bn – open a bottle of Bollinger please

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.’

Conflict of Interest at the CTT?

What is a conflict of interest? One definition is thus: ‘A conflict of interest is a set of circumstances that creates a risk that professional judgement or actions regarding a primary interest will be unduly influenced by a secondary interest.’

Or, in my simple world. ‘Someone pays you money. You then say or do things that you would not have said or done, if they hadn’t.’ The secondary interest doesn’t have to be directly monetary. It could be a promise of a promotion, or an invitation to be chairman of an important committee, or a chance to meet someone famous, or watch a world cup final, or suchlike.

However, for the sake of keeping things simple, we are talking about money here. We are talking about pharmaceutical companies paying money to medical ‘experts’, who may then say or do things that they would not otherwise have said or done.

The first problem is, thus. How do you know they would not have said or done it anyway? If the dairy industry paid me a million pounds to say ‘Dairy foods do not cause heart disease.’ This would be a bonus. Because it is what I believe, it is what I say already, and you really don’t need to pay me a million pounds to say it. [Although I am open to offers].

However, if I was paid a million pounds and I then said ‘dairy foods to do not cause heart disease’, and you discovered that the dairy industry had paid me a million pounds, what would you think? I know exactly what you would think. ‘I trusted him, now it turns out he is just lining his wallet, the same as everyone else.’ Some would state this more vehemently than others. However, any reputation that I have would never be the same again. There would always be that loss of trust. That doubt.

The people we admire and trust the most do not take backhanders. Pity.

For many years, pharmaceutical companies paid doctors ‘honoraria’, which is just a posh word for money. The doctors happily stuffed said honoraria into their bank balances, and no-one seemed much bothered. You did not need to declare any financial interests, and the only limitation on how much you got paid was your perceived value to the companies.

Your value was measured in a few different ways:

1. Ability to influence other doctors – your status as an ‘opinion leader’
2. Your quality as a speaker at meetings and/or ability to set up and run clinical trials
3. Your influence within the healthcare system i.e. do you advise Governments on treatment, do you sit on committees that advice NICE, or the Food and Drugs Administration (FDA)
4. Your position on Guideline committees. Can you play a key role in writing the guidelines that other doctors have to follow e.g. drug x a must be used first line in all patients with condition y.

These things are, of course, all linked. As an expert you start on rung one and two, and then move onto three and four. Your progress up this ladder requires very close links with the industry. You cannot influence other doctors if you haven’t done research, and it is very difficult to do research without industry funding. If not impossible.

At a certain point in the process, you become exceedingly important to the industry. In fact there are companies who support the pharmaceutical industry whose entire raison d’etre is to manage Key Opinion Leaders (KOLs).

According to Dan Mintze, senior director, heartbeat experts, “The management of KOLs needs to be broader than identifying, segmenting, influence mapping and working with clinicians in order for products to gain clinical approval. Rather a comprehensive KOL solution which includes the identification and appropriate engagement of KOLs who impact market access decisions e.g. KOLs who serve as Government or payer advisory board members (see figure 3) should be adopted.” Such pharma-KOL engagement will lead to the development of value messages that can help pharma to access the market faster, gain quicker product adoption, and increase bottom line performance.’ [my words in bold]  Original PDF here

The more you increase bottom line performance, the more you are worth, and the more you get paid. Strangely, some left-wing commies a.k.a ‘people’ began to object to this cosy relationship. A bit too much potential for the situation whereby… a primary interest will be unduly influenced by a secondary interest.

Luckily this problem was instantly solved, amid scenes of wild rejoicing, by ensuring that doctors who did major studies, or wrote articles and suchlike, must disclose their conflicts of interest. Once this had been done there was nothing to worry about, ever again. [joke]
Although, what we are supposed to do with a disclosure of interest has never really been explained. As a Swedish doctor wrote to me:

‘While we are at this: I have often wanted to ask the purpose of revealing possible/probable conflicts of interest. Just what are we supposed to do with that editorial caveat? Does it mean the data might be suspect? If the editors want us to know it is suspect then why do they publish it?

If it means we should interpret the data with caution, can someone tell me how one is to be cautious. Does it mean one believes none of it or does one believe some of it? If the latter then which part do we believe and/or which do we not believe. Just how are we supposed to judge these things, after having been warned to beware?

Indeed, what are we supposed to do? The other problem is that, whilst doctors are meant to declare their conflicts, quite often they do not. Here is an addendum taken from the Journal of the American Medical Association.

It was in response to an article which was written by a number of authors, who did not see to need report any of their conflicts. Some eagle eyed readers wrote in to complain, and the journal responded thus [I put in bold those companies who would have benefitted financially from the original paper]:

Unreported Financial Disclosures in: ‘Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis.’

….the following disclosures should have been reported: “Dr Mora reports receipt of travel accommodations/meeting expenses from Pfizer; Dr Durrington reports provision of consulting services to Hoffman-La Roche, delivering lectures or serving on the speakers bureau for Pfizer, and receipt of royalties from Hodder Arnold Health Press; Dr Hitman reports receipt of lecture fees and travel expenses from Pfizer, provision of consulting services on advisory panels to GlaxoSmithKline, Merck Sharp & Dohme, Eli Lilly, and Novo Nordisk, receipt of a grant from Eli Lilly, and delivering lectures or serving on the speakers bureau for GlaxoSmithKline, Takeda, and Merck Sharp & Dohme; Dr Welch reports receipt of a grant, consulting fees, travel support, payment for writing or manuscript review, and provision of writing assistance, medicines, equipment, or administrative support from Pfizer, and provision of consultancy services to Edwards, MAP, and NuPathe; Dr Demicco reports having stock/stock options with Pfizer; Dr Clearfield reports provision of consulting services on advisory committees to Merck Sharp & Dohme and AstraZeneca; Dr Tonkin reports provision of consulting services to Pfizer, delivering lectures or serving on the speakers bureau for Novartis and Roche, and having stock/stock options with CSL and Sonic Health Care; and Dr Ridker reports board membership with Merck Sharp & Dohme and receipt of a grant or pending grant to his institution from Amgen. (original JAMA correction here.)

As you can see, Paul Ridker had board membership with Merck Sharp and Dohme, and simply forgot the mention it. The authors’ collective punishment? Well, you have just seen it. Essentially, there is no punishment. A bit of momentary embarrassment, soon forgotten. [Although not by everybody, guys].

However, the steady pressure for doctors to provide disclosures of interest has had one major impact. It has made it a bloody site more difficult to know where the conflicts of interest might actually lie.

For it has been decreed….I don’t know who decreed, or agreed it, that if you are paid money directly by a pharmaceutical company, or say a PR company working for the industry, you have a financial conflict of interest that you must/should declare.

However, if you work for an organisation such as the Cleveland Clinic, or the Clinical Trials Research Unit (CTSU) in Oxford things are different. The clinic is paid money by the industry, and then the clinic pays you. This means that you are not conflicted in any way. You need not declare anything. Why?

I don’t know who stated that this is acceptable. As with most things in this area we are in a shadow world full of ghostly apparitions that elude your grasp. ‘They said it was fine.’ And who, exactly, are they. There is no oversight committee here, no investigations carried out, no rulebook, no punishment. Just a very woolly gentlemen’s agreement amongst the great and the good of medical research.

However, because it has been agreed, in some mysterious way, that ‘second hand’ payments are fine, it means that those working at the Cleveland Clinic, the CTSU, and suchlike, feel able to state that they have no financial conflicts – at all. Even if the organisation they work for earns hundreds of millions, or billions, in industry funding.

If those working at the CTSU do, somehow, find themselves working directly with the industry, they now give any money they might have eared to charity. To quote their rules on the matter:

Guidelines for CTSU staff with respect to honoraria and any
other payments offered and share ownership

——-

d: If an honorarium is declined, the intended CTSU recipient can still mention that a
corresponding amount might be donated to a specific charity.

A corresponding amount to a specific charity. What charity?

‘I guess if I had any advice for reporters, I would say, ask your local university if they’ve set up any associated [non-profit organizations]; many universities have an associated charity or foundation through which they solicit donations from corporate sponsors to support medical research. Find out about who those corporate sponsors are. Unfortunately, many universities set up these associated charities and foundations in such a way that they don’t have to disclose much publicly – ask about that, you know, try to push.’  (original article here)

Push away, but I don’t expect you will get very far.

Anyway, we are now supposed to believe that highly qualified and very influential KOLs, who work at the CTSU in Oxford, carry out work on behalf pharmaceutical companies for no payment, whatsoever. This is just charity work. Helping impoverished pharmaceutical companies is the same, really, as helping starving orphans in Africa.

Strangely, it appears that the CTSU doesn’t mind in the least that their staff are spending large chunks of their professional life helping pharmaceutical companies – out of the goodness of their hearts. The CTSU gets nothing; the pharmaceutical companies get nothing, other than a warm glow in their hearts. Meanwhile a ‘specific charity’ is doing rather well. Whatever that specific charity may be?

Of course the CTSU itself does rather well from the industry. Just for carrying out one of their many studies, REVERSE, they received £96million ($155million) from Merck Sharp and Dohme.

Yet, despite the huge sums of industry money sloshing about in the CTSU there are absolutely no conflicts of interest going on here. We are told this by none other than the CTSU itself. No-one is paid money directly by the industry in any way. So that is fine.
As Robbie Burns said: ‘O, wad some Power the giftie gie us to see oursels as others see us. It wad frae monie a blunder free us.’

As a sort of footnote to this blog, you may be interested to know that the Cholesterol Treatment Triallists Collaboration (CTT) in Oxford is probably the most influential organisation in directing the management of CV disease around the world.
The ACC/AHA guidelines launched last year in the US are based on the latest CTT meta-analysis; as are the latest NICE guidelines in the UK. The Cochrane Collaboration, which is also highly influential world-wide, changed their guidance on the use of statins in primary prevention, based on the CTT meta-analysis.

In short, if you want to identify a group of KOLs who can truly increase ‘bottom line performance’, you will not find any organisation more powerful than this. Best of all, CTT have absolutely no conflicts of interest with the pharmaceutical industry either. If you want to contact the CTT about any of this, you can e-mail them at: CTT@ctsu.ox.ac.uk

Another point of view

As someone who considers myself to be a scientist, I thought I should present another view to you on statins. This piece (a transcript of a talk) can be seen on Medscacpe1.

Please read on, and see what you think of his arguments:

I am Dr. Frank Veith, Professor of Surgery at New York University Medical Center and the Cleveland Clinic. Today I am going to talk about what I call the “statin witch hunt” and why, despite it, we should give more patients statin drugs.

The question of whether to give statins to more healthy patients is one of considerable interest to the public and considerable debate in both the medical community and the lay press. In November, the American College of Cardiology (ACC) and the American Heart Association (AHA) released their long-awaited new guidelines on the treatment of blood cholesterol to reduce the risk for adult atherosclerosis. T

This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. The guideline was greeted with many objections in both the medical community and the lay press. Most notable was a November 14 New York Times op-ed by 2 respected experts, Drs. John Abramson and Rita Redberg, titled “Don’t Give More Patients Statins.”

Other New York Times articles about Drs. Paul Ridker and Nancy Cook, and another by Gina Kolata, expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. All three of these New York Times articles were part of what I call the “statin witch hunt” which has generated much confusion among the public.

The op-ed by Drs. Abramson and Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate the expansion of statin usage to more patients because such expansion “will benefit the pharmaceutical industry more than anyone else.” They state that the guideline’s authors were not “free of conflict of interest.” In addition, they claim that “18% or more” of statin recipients “experience side effects” and that the increase in statin administration will largely be in “healthy people” who do not benefit and who would be better served by an improved diet and lifestyle.

Although the latter is true for everyone, Drs. Abramson and Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis — most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.

 They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of side effects equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are only healthy until they get sick. Many individuals over the age of 40 take a daily aspirin.

Statins are far more effective than aspirin in preventing the heart attacks and strokes that often occur unexpectedly in previously “healthy people.” Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects, if it would lower their risk for such vascular catastrophes and premature death.

In contrast to what is implied in the Abramson-Redberg article, these drugs are an easy way for people to live longer and better, and statins cannot be replaced with a healthy lifestyle and diet — although combining the latter with statins is a good thing.

Lastly, with respect to the comments about the pharmaceutical industry benefiting from statin prescriptions, and the guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many excellent and well-controlled statin trials. Moreover, most statins are now generic, so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.

The statin witch hunt is a bad thing, and more patients should be on statin medication. I am Dr. Frank Veith, and that is my opinion.

1: http://www.medscape.com/viewarticle/822145?nlid=51963_1985&src=wnl_edit_medn_card&spon=2

(You will need to subscribe to Medscape to see the talk, and transcript. It is fairly straightforward to gain access. The site is www.medscape.com It is one of the biggest medical websites.)

I though you should know if Frank Veith has any conflicts of interest. He works at the Cleveland Clinic, so he probably doesn’t, as most of the medical experts who work there state that they give all of their income from working with the pharmaceutical industry to charity. Steven Nissen, a man of whom you may have heard me speak on a regular basis, is the chairman of Cardiovascular medicine at the Cleveland Clinic.

Here, for example, is Steven Nissens conflict of interest statement

Dr Steven Nissen
Medical Director
Cleveland Clinic Cardiovascular Coordinating Center

Dr. Nissen has received grant/research support from AstraZeneca Pharmaceuticals, Atherogenics; Eli Lilly and Co., Lipid Sciences, Pfizer Labs, Sankyo Pharma, sanofi-aventis, and Takeda Pharmaceuticals North America with all reimbursement directed to the Cleveland Clinic Cardiovascular Coordinating Center; and has been a consultant for Abbott Laboratories, AstraZeneca Pharmaceuticals, Atherogenics, Bayer Corp., Eli Lilly and Co., Forbes Medi-tech, GlaxoSmithKline Pharmaceuticals, Haptogard, Hoffman-LaRoche, Isis Pharmaceuticals, Kemia, KOS Pharmaceuticals, Kowa Optimed, Lipid Sciences, Merck/Schering Plough, Novartis Pharmaceuticals Corp., Novo-Nordisk, Pfizer Labs, Protevia, Roche Pharmaceuticals, Sankyo Pharma, sanofi-aventis, Takeda Pharmaceuticals North America, Vasogenix, Vascular Biogenics, Viron Therapeutics, and Wyeth Pharmaceuticals, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen; and has served on the speakers’ bureaus of AstraZeneca Pharmaceuticals and Pfizer Labs, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen.

Cleveland Clinic physicians and scientists may collaborate with the pharmaceutical or medical device industries to help develop medical breakthroughs or provide medical education about recent trends. The collaborations are reviewed as part of the Cleveland Clinic’s procedures. The Cleveland Clinic publicly discloses payments to its physicians and scientists for speaking and consulting of $5,000 or more per year, and any equity, royalties, and fiduciary relationships in companies with which they collaborate. The Cleveland Clinic requires its doctors to approve the public disclosures of their scientific collaborations with industry. As of 3/21/2014 the review process regarding Dr. Veith’s disclosure had not been completed. Patients should feel free to contact their doctor about any of the relationships and how the relationships are overseen by the Cleveland Clinic. To learn more about the Cleveland Clinic’s policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.

Although now dead, the Cholesterolosaurus will march on

A meta-analysis including 530,525 people, partly funded by the British Heart Foundation, and published in the Annals of Internal Medicine has just come to this conclusion:

Conclusion: Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats1.

Or to put it another way, there is no evidence that saturated fat consumption has anything, whatsoever, to do with causing heart disease, or strokes. Once again I get to say ‘I told you so.’ Ah, the four most satisfying words in the English language. That is, when arranged in that particular order.

So, eat butter, drink milk, and throw away the horrible sugar-loaded low fat yoghurt. Go to France and enjoy the highest saturated fat diet in Europe and you, too, can enjoy the French rate of heart disease. Yes, of course, the lowest in Europe.

But now what happens? You see, the entire edifice of the cholesterol hypothesis is held together by two links in a chain. Link one is that saturated fat consumption raises cholesterol levels. Link two is that raised cholesterol levels then cause heart disease.

Various ‘experts’ have simplified this to the very simple equation:

A (saturated fat in the diet) > B (high cholesterol levels) > C (heart disease)

This is the cholesterol hypothesis, or the lipid hypothesis, and it has driven medical thinking for the last sixty years.

I have had it painstakingly explained to me, by very clever people, exactly how saturated fat raises cholesterol levels. Indeed, you will find ‘evidence’ for this almost universally accepted fact in literally thousands of clinical studies. Here is what Wikipedia has to say on the matter

There are strong, consistent, and graded relationships between saturated fat intake, blood cholesterol levels, and the mass occurrence of cardiovascular disease. The relationships are accepted as causal2.’

Okay, let us accept that eating saturated fat does raise cholesterol levels. However, if consumption of saturated fat does not increase the rate of heart disease then….. Then raised cholesterol levels can have nothing whatsoever to do with causing heart disease. Just keep chasing the implications of that statement around in your head for a while.

So what happens now? We now have a cholesterol/lipid hypothesis that just had its head blown off. Yet, it still continues to wander about, unaware that it is actually dead.

As everyone knows you can chop the head off a chicken and it can wander about for years. I was also informed, when I was an open-mouthed child, that you could shoot a dinosaur through the head and it would continue to blunder about for some time, the rest of its body blissfully unaware that it was actually dead.

Well, the cholesterol hypothesis has just been shot dead, but I suspect it will continue to rampage about, stomping on puny humans for many years, before it finally keels over and admits that it is dead.

But I say, farewell Cholsterolosaurus. You are now a deceased hypothesis. Gone to meet your maker. You just don’t know it yet. Because the people that believe in you do not understand logic.

1: http://annals.org/article.aspx?articleid=1846638
2: http://en.wikipedia.org/wiki/Saturated_fat

A ghost in the machine

I suppose most people missed this story about life expectancy in the UK. If you didn’t pick it up, this article comes from the Doctors net website. A site for doctors registered to practice medicine in the UK.

Life expectancy fall alarm 14/02/2014

The life expectancy of England’s elderly population has fallen for the first time, it was reported last night. Women at the age of 75 can expect to live a little less longer than they would have at the beginning of the decade, according to new figures.

The figures for 2012 are still provisional and represent a reduction of two and half months in life expectancy for women at the age of 75.There was no change in life expectancy for men, who could expect to live 11.3 years.

The Department of Health calculations, obtained by the Health Service Journal, show that life expectancy for women at that age fell from 13.2 years to 13 years. The figures may reflect the growing problems of caring for an elderly population – or simply growing numbers of elderly people.

John Newton, of Public Health England, told the journal: “Life expectancy reflects what has happened in people’s lives, and these people were born in wartime, when there were profound changes in diet. We have seen an unprecedented increase in life expectancy and it’s possible that is coming to an end.

“But we do also expect fluctuation. As we have an older population, the proportion of deaths that will fluctuate due to flu and cold weather is greater.

So it seems that life expectancy in the UK is falling amongst elderly women, and it is staying stationary for elderly men. Which is rather the opposite of what was supposed to happen, and reverses many years of increasing life expectancy.

Why is this happening? Ten years ago the UK Government embarked upon the most expensive, and extensive, initiative ever undertaken in preventative medicine. The Quality Outcome Framework (QoF). This was launched with a great fanfare.

QoF is a system whereby GPs have to screen the entire population for conditions such as diabetes, high blood pressure, chronic kidney disease, high cholesterol, etc. etc.

Once any early stage diseases had been picked up, treatment is instigated. Then there is regular monitoring to ensure that targets for blood pressure lowering, blood sugar control, and suchlike were met. This system has cost billions upon billions of pounds.

It was supposed to stop people dying prematurely from diseases, or conditions that could be properly ‘treated’ and ‘controlled.’ Because the elderly are, by the nature of being elderly, far more likely to have various early stage diseases, and are therefore at highest risk, this is the population that has been most tightly monitored and ‘treated’.

I work, part-time, in Intermediate Care. A unit where elderly people who have had an accident, broken a hip, or suffered other acute illnesses are cared for. Our job is to get them as fit as possible to return home. There are nurses, physiotherapists, occupations therapists, and me, sorting out underlying medical conditions such as anaemia. Some patients arrive from the community, others from hospital.

I did a small audit last year, and found that the average number of drugs that our patients are taking when they arrive in the unit is ten point three. That is, ten point three different drugs. Some of which are taken three or four times a day. So, a total of twenty or thirty tablets a day, in many cases.

This is the very definition of polypharmacy. And how much harm could polypharmacy do? Well here is a study from Israel, looking a study where people in nursing homes had drugs discontinued [They stopped as many drugs as was considered ethical]. Here is the abstract of the paper.

The war against polypharmacy: a new cost-effective geriatric-palliative approach for improving drug therapy in disabled elderly people.

Background:

The extent of medical and financial problems of polypharmacy in the elderly is disturbing, particularly in nursing homes and nursing departments.

Objectives:

To improve drug therapy and minimize drug intake in nursing departments.

Methods:

We introduced a geriatric-palliative approach and methodology to combat the problem of polypharmacy. The study group comprised 119 disabled patients in six geriatric nursing departments; the control group included 71 patients of comparable age, gender and co-morbidities in the same wards. After 12 months, we assessed whether any change in medications affected the death rate, referrals to acute care facility, and costs.

Results:

A total of 332 different drugs were discontinued in 119 patients (average of 2.8 drugs per patient) and was not associated with significant adverse effects. The overall rate of drug discontinuation failure was 18% of all patients and 10% of all drugs. The 1 year mortality rate was 45% in the control group but only 21% in the study group (P < 0.001, chi-square test). The patients’ annual referral rate to acute care facilities was 30% in the control group but only 11.8% in the study group (P < 0.002). The intervention was associated with a substantial decrease in the cost of drugs.

Conclusions:

Application of the geriatric-palliative methodology in the disabled elderly enables simultaneous discontinuation of several medications and yields a number of benefits: reduction in mortality rates and referrals to acute care facilities, lower costs, and improved quality of living.

The first thing to say here is that, if there ever was a ‘war’ against polypharmacy, then polypharmacy won a long time ago…at least in the UK.

For those who find scientific papers somewhat opaque, the key point from this paper is the following

The one year mortality in those who did not have their medications reduced was 45%

The one year mortality in those who did have their medications reduced was 21%

This is a fifty three per cent absolute reduction in overall mortality risk in a year. Which is a better figure than I have seen for any drug intervention, ever, anywhere. So it would seem that the best possible drug treatment discovered…. is to stop taking drugs. As an added bonus you save lots of money, and make the patient feel much better, all at the same time.

Just one paper? No, of course not. There are a number of different studies demonstrating that discontinuing medication in the elderly is a good thing to do. A review paper in the Journal of the American Medical Association (JAMA) came to the following conclusions:

‘The finding that simultaneous discontinuation of many drugs is not associated with significant risks and apparently improves quality of life should encourage physicians to consider testing this in larger RCTs (randomised controlled studies) across a variety of medical cultural settings. Polypharmacy may have different faces in different countries or clinics but there is no doubt that the problem is global. This approach has international relevance; it combines our best existing evidence with patient-focused care while actively avoiding extrapolation from inappropriate populations where no evidence exists for treatment in elderly patients.’

In fact, I cannot find any evidence that polypharmacy, however you define it, does anything but harm. In the face of such evidence what did the UK authorities decide to do? Why, they set about create a system designed to drive the biggest explosion of polypharmacy ever seen. What else would you expect them to do?

So why has the mortality gone up in the elderly population in the UK? Well, I know where I would put my money. On the very system designed to stop them dying in the first place.

The pharmaceutical industry now controls NHS policy – hoorah.

I noticed the other day that the pharmaceutical industry have managed to achieve something they could surely once only have dreamed of. Creating policy documents. Here is the offending headline from the Guardian newspaper:

NHS hires drugmaker-funded lobbyist

As the secondary headlines say:

‘Conflict of interest concerns as Specialised Healthcare Alliance (SHCA), funded by pharmaceutical companies, advises NHS England.’

A lobbying organisation with links to some of the world’s biggest pharmaceutical companies and medical equipment firms has been asked by NHS bosses to write a report that could influence health policy, it has been reported.’

It seems lobbying is now ‘so five minutes ago.’ Who needs a lobbyist when this organisation, the Specialised Healthcare Alliance (SHCA), which is entirely bought and paid for by the pharmaceutical industry, has been commissioned to write a report on funding specialised services for the NHS.  Services worth £13,000,000,000.00p (£13Bn/$20Bn) per year.

The article does point out, though, that we are misguided to think that this could be in any way an issue. For John Murray, the director of the SHCA, a lobbyist, and author of the report, has made it clear that:

.…..there was no link between his lobbying business and the SHCA other than providing secretariat services and said the SHCA “never takes a position on particular products or treatments in any of its activities”.

John (Pinocchio) Murray’s nose is now in the Guinness Book of Records for being the longest nose ever recorded on a human being, at seven point three miles. He is a lobbyist, paid for by pharmaceutical companies, and his organisation never takes a position on particular products…..hahahahahahahahahaha. Well then, sack him immediately for being useless…. sack him for failing to do what he is handsomely paid to do.

The final part of this newspaper report, which I savoured, is the following:

‘James Palmer, clinical director of specialised services at NHS England, said he was aware of Murray’s role as a lobbyist but “there are no opportunities for lobbying in the process of forming clinical policy”.’

This, of course, is true. There are no opportunities for lobbying in this particular process of forming clinical policy. Once a lobbyist starts to write clinical policy, they have moved well past the annoying requirement to lobby anyone. For the lobbyist has now managed to become the very person that they should be paid to lobby.

Instead of trying to influence someone who may not listen to him, he can just talk to himself…. Imagine that this short section of imagined dialogue is like Smeagol talking to Gollum in Lord of the Rings (Smeagol and Gollum are, or course the same person):

John Murray: ‘We must put the following phrase into the report, my precious. A “clear commitment” to “disinvest in interventions that have lower impact for patients” in favour of “new services or innovations”.

John Murray: “But why would you like me to put this in the report, wont this harm the hobbits? Hobbits have been kind to me…yes they have.”

John Murray: ‘I needs it in the report you fool. I represent precious pharmaceutical companies that are bringing new products onto the market. We needs to ensure that there will plenty of money to pay for them. So they must stop paying for stupid old fashioned treatments…yes, they must, foolish Hobbits.’

John Murray: ‘But won’t the kind Hobbits be worried this will just look like lobbying.’

John Murray: ‘Don’t be so stupid. How can the nasty Hobbits accuse me of lobbying? I am their friend, and I am trying to help them…yes I am.. Yes John Murray likes the friendly Hobbits. John Murray want to help the Hobbits, yes he does.’

John Murray: ‘You are so clever Smeagol, our master will be pleased.’…….

Duchess: ‘You’re thinking about something, my dear, and that makes you forget to talk. I can’t tell you just now what the moral of that is, but I shall remember it in a bit.’

“Perhaps it hasn’t one,” Alice ventured to remark.

“Tut, tut, child!” said the Duchess. “Everything’s got a moral, if only you can find it.”

A sorry little patient tale

Working as a GP in England becomes increasingly difficult as the drive to put more and more people on statins gathers pace. Virtually every day I see a patient taking statins who is suffering a clear adverse effect.

I know that this is a very biased sample, because patients in the area know that I am ‘the doctor who writes stuff about statins.’ So there is a degree of self-selection going on here. People who think they may be having adverse effects choose to see me.

However, there is another degree of self-selection going on here. When I see that a patient is on statins, I tend to be on high alert for any mention of statin related adverse effects. Whilst most other doctors happily dismiss such things as: tiredness, memory loss, joint pains, muscle pains depression, irritability, impotence, stomach pains, skin rashes and the like as ‘nothing to do with statins.’ I tend to think the statin may be the cause.

I then usually say. Stop the statin for a couple of months and see what happens to your, tiredness, memory loss, joint pains etc etc. Very often these symptoms go away. Then what? Then the practice statin prescribing statistics start to look quite bad. The senior partner (who is pretty sympathetic to my cause), has had words. The practice is losing money. I have had to ‘exempt’ more and more patients from the cardiovascular disease indicators.

The prescribing lead from the local Clinical Commissioning Group has also had words. It is clear that my non-prescribing of statins is very much frowned upon. Although nothing concrete has yet happened, the pressure to conform cranks up. At times I wonder why I bother. Should I just focus my anti-statin efforts at a more global level? Writing articles, lecturing, speaking to journalists, writing books, and the like. .What difference can I make with a few patients in the practice?

Yesterday, however, I saw a lady who had been admitted to hospital with severe abdominal pains. So severe that she had scans, tests, and was very nearly taken down to surgery for an exploratory operation. Did she have galls stones, appendicitis, cancer? Nothing could be found.

She was discharged with strong painkillers, and follow-up appointments were arranged. She came to see me between Christmas and the New Year to get more painkillers to tide her over. I suggested that the statin may be causing her stomach pain, and that she should stop them, which she did.

Guess what. Of course, the stomach pains have gone. She also reported that she’d had three episodes of Transient Global Amnesia whilst taking statins. This is where your memory goes, you wonder about as if in a fugue, and can remember nothing of what went on. She had not reported these episodes to anyone, but since being made aware that stains can cause them, she now knows what happened.

Since stopping the statins she also reports that her energy levels are back to normal, and that she feels human again. Her life, her quality of life, has returned.

After thanking me for helping her, she then asked. ‘What do you think I should do, doctor. Should I go back on them again, the other doctors say that I should, but I don’t want to.

Please sign

I just got this as an e-mail this morning.

Friends,

I’ve just heard that companies like Coca-Cola, Nestle and others will be able to claim their products are ‘healthier’ thanks to a new EU regulation on using fructose. But consuming high levels of fructose is a leading cause of obesity around the world.

This decision was made by the EU Food Standards Agency in Parma, Italy. We need to push back on food industry lobbying by demanding the EU Food Standards Agency thinks again.

Can you sign this petition demanding the EU Food Standards Agency thinks again?

http://action.sumofus.org/a/eu-fructose/

So, now, it will be claimed that Coca-Cola is a health food. You really couldn’t make this stuff up, could you? Or if you did you would be accusing of stretching credibility far beyond breaking point.

Anyway, if you feel you can, I would hope that you can sign this petition. It takes about thirty seconds.

For those of you who sometimes feel that big business is now running the world, whilst Governments jerk up and down on their strings. ‘All citizens must now drink Coke for a healthy and fulfilling life…’

“In a way, the world−view of the Party imposed itself most successfully on people incapable of understanding it. They could be made to accept the most flagrant violations of reality, because they never fully grasped the enormity of what was demanded of them, and were not sufficiently interested in public events to notice what was happening. By lack of understanding they remained sane. They simply swallowed everything, and what they swallowed did them no harm, because it left no residue behind, just as a grain of corn will pass undigested through the body of a bird.”  1984

Please protect the community

The primary functions of government are to maintain order, settle conflicts, and protect the community. So I am told.

Generally I am a small state man. In fact I refer to myself, when I don’t think anyone important is listening, as an anarchist. I believe that humans should be allowed as much freedom as is possible, without being allowed to seriously harm others. Rules and regulations and bureaucracy are not really my thing. So I am achingly reluctant to demand that the State gets involved in creating yet another agency, or add to its powers in any way.

But sometimes the State must intervene to carry out one of its three primary functions. Namely, to ‘protect the community.’

Where Governments around the world have to step in, right now, is to gain proper control of the creation of medical guidelines. Something that they have spectacularly failed to do, up to now.

As you may be aware, a row is rumbling under the surface about European guidelines on the use of beta-blockers in surgical operations, guidelines that were based on corrupt research. Doctors following these guidelines have probably killed 800,000 people. Give or take.

Some people have written into this blog stating that the numbers cannot be that high, and that the calculations are probably wrong. They were not my calculations, I hasten to add. My view on this is that many many thousands have certainly died unnecessarily. It doesn’t really matter if it was one hundred thousand, five hundred thousand, or eight hundred thousand.

How many would be acceptable?

The answer is, of course, none. But when guidelines go wrong the potential for killing hundreds, thousands, or even millions, is always there. If, for example, your guidelines state that fifty per cent of the population must take a drug for a condition, and these guidelines are wrong, you can kill millions,.

Recently, I did the back of a fag packet calculation on the number of people who were killed by the advice that patients must be managed with six weeks of strict bed rest after a heart attack. Here is some advice from that era: ‘The patient is to be guarded by day and night nursing and helped in every way to avoid voluntary movement, or effort.’ Thomas Lewis.

According to my figures, and I am not going into them here, strict bed rest for six weeks after a heart attack killed fifteen million people worldwide. Yes, fifteen million. More than died in the fighting in the first and second world wars added together.

This, I hope, gives you some idea of the potential death toll when medical guidance goes wrong. Given this, you would hope that the process that leads to the creation of guidelines would be checked, and double checked, then triple checked, then monitored.

You would also hope that the evidence underpinning the guidelines was free from bias, and corruption. Furthermore, that all data – positive or negative – would be freely available, with no possibility of hiding anything away. You would also hope that those creating the guidelines had no possible conflicts of interest.

The fact is that NONE of these things are true. We have a system that is almost perfectly free from scrutiny of any sort. Many, if not most, guidelines are based on trials that are designed, set up and run by the pharmaceutical companies. They own and control the data, and are under no obligation to let anyone else see it, if they don’t want to. Negative data are regularly buried, never to see the light of day.

A few brave souls e.g. Ben Goldacre, Fiona Godlee (editor of the BMJ), and Peter Gotzsche have been demanding that all clinical trial data are made available for scrutiny, but almost nothing has happened. Currently Roche are refusing to release data on their flu drug Tamiflu. Various studies remain unpublished, no data released. The UK Govt. seems powerless to act. Or maybe it just doesn’t want to, with so much money at stake.

Last year AbbVie and InterMune, two drug companies, took legal action against the European Medicines Agency to stop them releasing any data from clinical studies, and to ensure that no trials data could made available, anywhere, to anyone, ever again. I like to think I helped to kick this monstrous and terrible legal action into touch. But, companies still do everything in their power to ensure that data will not, ever, be released.

Then we have the enormous problem that that ‘experts’ chosen to write guidelines work hand in glove with the pharmaceutical industry. The US guidelines on cholesterol lowering written in 2004 were put together by nine people. Here is a conflict of interest statement. I have put this up before, but I think it bears almost endless repetition:

ATP III Update 2004:  Financial Disclosure

Dr. Cleeman: (Chairman) has no financial relationships to disclose.

Dr. Grundy: has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.

Dr. Bairey Merz: has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.

Dr. Brewer: has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.

Dr. Clark: has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.

Dr. Hunninghake: has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.

Dr. Pasternak: has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.

Dr. Smith: has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.

Dr. Stone: has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm

Those companies that I have marked in bold sell (or at the time sold) statins and/or other cholesterol lowering medications. A mere eight members (the chairman was employed by the NIH who was not allowed close ties with industry), and we have almost seventy direct financial conflicts of interest with companies who made, and sold, cholesterol lowering agents.

How we can possibly allow doctors with enormous financial conflicts of interest to create guidelines that will be followed around that world, and will affect hundreds of millions (in this case billions) of people….How can this possibly be allowed.

We currently have a system of guideline creation that relies on three things being true, if they are to be sare – all three things:

1: That the clinical trial data are not corrupt, or biased

2: That negative data are made available when requested

3: That the medical experts tasked with creating the guidelines are completely unaffected by their financial conflicts of interest

The fact is that none of these critical requirements are followed….even remotely.

How many other guidelines out there are wrong, damagingly wrong, and horrifyingly wrong? How many millions of people are being put at risk by a system that is wide open to corruption, and bias? I have not the slightest idea, but I suspect many….

The public are most certainly not being protected. We have put the foxes in charge of the chicken coop, with entirely predictable results. Time for the farmer to pull out the shotgun and start blasting away. Time for the state to start doing what it is there to do. Namely, ‘protect the public.’

Guidelines kill 800,000

A few days ago a friend sent me this headline by e-mail.

‘Guideline Based on Discredited Research May Have Caused 800,000 Deaths In Europe Over The Last 5 Years.’

I would replace the word ‘May’ with these two words ‘almost certainly.’ You would think, would you not, that if any other event in the world, at any time, had killed eight hundred thousand people, this would be front page headlines around the world for weeks, probably months, maybe even years.

Governments would spring into action, those guilty dragged into court. Thousands would protest in the streets, petitions would be signed, laws passed.

The reality is, I am willing to bet, that you have never even heard of this gigantic scandal. It will not have appeared in any national television programme, or newspaper. The blogosphere is also, almost totally silent.

Eight hundred thousand people. Please let that figure sink in for a few moments. If you dropped a major thermonuclear device on Manchester (UK) and killed every single living person, this would be roughly equivalent. If you laid the corpses end to end, the line of dead people would stretch from John O Groats to Land’s End (the entire length of the UK). Walking briskly each day, it would take you two months to pass them.

Think on that.

To an extent the actual guidelines themselves are not the most important thing here. They are now in the process of being changed (although they have not yet been changed). Nobody can be brought back to life, those who could have died – are dead. The issue here is that the processes leading to the creation of guidelines, that have almost certainly killed 800,000 people, are still in place, with no prospect of any change.

Those who have read this blog may be aware of my distaste for medical guidelines, and my concerns about their impact. I wrote an earlier blog called ‘Who shall guard the guardians.’ This outlined some of the problems, but even I was overwhelmed by the sheer scale of deaths involved when guidelines go wrong. I could have worked it out, but never did.

Guidelines are based on evidence, and evidence is based on clinical trials. And major clinical trials are, almost without exception, paid for, run, and controlled by the pharmaceutical industry. The great and good of medicine, the ‘Key Opinion Leaders’ KOLs, who put together the guidelines will almost all have very close connections with the industry. In some cases they will have been paid millions by pharmaceutical companies.

Whether they think so, or not, these opinion leaders are biased. Biased in favour of pharmaceutical products that are promoted through biased research, and launched on an unsuspecting world. And there is no-one out there to check what these KOLs and guideline committees are doing. If, to pluck a name from the air, the European Society of Cardiology (ESC) decides to create a guideline committee, how do they do it?

They choose a chairman, who will be on one of their committees. A well regarded, sound chap, with expertise in the area. He, very rarely she, will then decide on which of his friends and colleagues would be most suitable to be committee members.

They will have a few meetings, gather the evidence together, decide on what best practice should be, and produce their guidelines. No other organisation checks on them, or their decision making, or their conflicts of interest. Or, indeed, the evidence itself.

Yet, when the guidelines come out, many countries will slavishly follow them. They will form the basis for instructions to their medical services. Doctors who fail to follow the guidelines can be censured, or lose their jobs. They virtually carry the force of law.

Something this powerful and important and critical to medical care is dealt with in an almost completely cavalier fashion. Which is, frankly, inexcusable.

I suppose you are wondering what these guidelines were? Well, they were on the use of beta-blockers to protect the heart during surgery. To see more on this story go to the Forbes website

I cannot send you to the article published in the European Heart Journal, because one hour after going up on their website, it was pulled. Here is the comment from the authors of this paper, Graham Cole and Darrel Francis, on the decision of the Editor to disappear the article.

‘Our article is a narrative of events with a timeline figure and a context figure. We had not considered it to contain scientific statements, but we admit that it does multiply together three published numbers.

It is not an analysis of individual trials considering design, molecule, dose and regimen. We published last year the formal meta-analysis under stringent peer review in Heart and addressed the questions, including dosing, in that paper and associated correspondence.

The first of our two EHJ articles merely says that our community, which races to take credit when research-led therapy improves survival, must be equally attentive to the possibility of harm.  The leverage of leadership means the magnitude of either may be far from trivial.

Where our article relayed numbers, we made clear that alternative values were possible. The focus for readers was on how serious the consequences can be when clinical research goes wrong.

We thank Prof Lüscher for highlighting the scientifically important point that the pivotal trial, DECREASE I, has not been retracted by NEJM because the investigative committee did not recommend this. Unfortunately the committee could not have done so, because DECREASE I was outside its brief, displayed on the first text page of the first committee report. Can readers suggest why DECREASE I, from the same trial family, was exempted from inquiry?

We admire Prof Lüscher’s diligence in sending for peer review what we thought was merely multiplication. We await the review of the pair of articles. The first narrated one instance of a pervasive problem. The second suggests what each of us can do to reduce recurrences.

We respect the process Prof Lüscher has set in motion. We ask readers to join with us, and the journal, in maximizing the reliability of clinical science for the benefit of patients.’

Well, I am really glad that this article is being sent for peer review, because – as we know – peer review is a jolly good thing. To quote Richard Horton, Editor of the Lancet:

‘The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability — not the validity — of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.’

Let me just repeat that last bit. Peer-review is:

….biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.

Frankly, I wouldn’t hold my breath waiting for peer-review on this matter.

I suppose you may also be wondering how the problem with these guidelines came to light. Well, it turns out that the chairman of the guidelines committee was Prof Don Poldermans. A man who has now been booted out of his job at Erasmus Hospital in the Netherlands for making up his research. The very research that was used to create these guidelines.

Don Polderman’s also had financial conflicts of interest with Merck, Pfizer, Novartis and Medtronic. To name but four. (One conflict of interest statement can been seen here).

Anyway, here is a summary of what has happened:

      • Don Poldermans had financial conflicts of interest with several pharmaceutical companies
      • Con Poldermans carried out corrupt research, supporting the use of pharmaceutical products
      • Don Poldermans was the chairman of an ESC committee that recommended widespread use of drugs to protect the heart during surgery
      • Widespread use of drugs to protect the heart during surgery has killed 800,000 people over 5 years in Europe (alone)
      • The paper outlining the scale of deaths has been pulled by the ESC

I hope the hell there are no more Don Poldermans out there…..but you would have to be a brave man to think so. Personally, I believe there is an endemic problem with bias and corruption in medical research, and we should be very afraid indeed.