Tag Archives: nutrition

The latest Lancet paper on adverse effects – part two

52 Replies

Under-reporting or over-reporting?

I am going to start part two by looking at the evidence for statins causing ‘non-imagined’ adverse effects. Or, to put it another way, real effects. My own view on this is that the adverse effects of statins are significantly under-reported. Mainly because patients often don’t associate the drug with the problem. Such as muscle pain or weakness. This is especially true if it takes weeks or months for problems to develop. In some cases, even years.

Even if patients do report symptoms, doctors do not record many, if any, of the adverse effects. Which is true of all drugs, not just statins. The US does have an adverse drug reaction reporting system. But less than 1% of adverse reactions are captured by it 1:

As the article confirms: ‘Underreporting significantly delays the dissemination of critical information about such reactions.’ You don’t say.

In the UK, we have a yellow card system, specifically designed to make it a complete pain to report any problems. If you do fill in a yellow card, you find yourself bombarded with requests for masses of additional information. Past medical history, drug history, days and dates of starting the medication, exact adverse effect, lab tests etc. etc. This can all take many, many, unpaid, hours to gather. Which means that doctors rarely bother to use the system, and patients have never even heard of it.

The issues of adverse effect reporting has many other complexities. A few years ago, an interesting study caught my eye. It was not large, but telling. I have not seen the same research done, before or since. I may have missed it. It can be tricky to keep up with all the research done. Seventy-five patients were taking blood pressure lowering tablets – anti-hypertensives. They were asked the following questions:

  1. Did their quality of life improve on medication?
  2. Did it stay the same?
  3. Did it get worse?

Two other groups, the patient’s doctor, and the patient’s closest relative/partner were asked the same questions … about the person taking the tablets.

A little background. High blood pressure causes no symptoms. Because of this, hypertension is often referred to as the ‘silent killer’. Anti-hypertensives, on the other hand, are well known for causing a number of unpleasant effects. Therefore, you would probably expect that taking anti-hypertensives would have a negative effect on quality of life. Or, at best, it would remain about the same. Here is how the three groups answered.

Doctors:                      Quality of life improved:                                  100% agreed

Patients:                      Quality of life improved:                                  50% agreed

Patient’s relatives:      Quality of life improved:                                  0% agreed

Possibly most telling is that seventy-four out of seventy-five of the patient’s relatives reported that the quality of life worsened 2. What can we learn from this? Well, I might start by giving the doctors involved a good slap. I wouldn’t learn anything, but it might be a good lesson in humility for them. ‘Stop seeing what you want to see, and start seeing what is.’

The point here is that if there is a significant bias in the reporting of adverse effects, the bias is heavily weighted towards not reporting them. Not by patients, and certainly not by the doctors – remember that 1% figure. Which means that nothing is recorded for posterity. See no evil, hear no evil, speak no evil.

Another issue in play here, specifically, is that the authors of the Lancet paper do not appear to have heard of the placebo effect:

The placebo effect is a phenomenon where a person’s physical or mental health improves after receiving an inert, “dummy” treatment (like a sugar pill or saline injection). Triggered by the belief in, and expectation of, improvement, the brain induces real, measurable physiological changes—such as releasing endorphins or dopamine—that reduce symptoms like pain, fatigue, and anxiety.

One of the main reasons why we have such massive, complex, double-blind placebo-controlled trials is precisely because of the placebo effect. The drug could initially appear brilliant, but it may be achieving nothing; it may be that the ‘placebo effect’ is doing the heavy lifting.

Because of this significant ‘confounding factor’ clinical trials need to be ‘controlled’ by giving everyone a pill, or an injection. A percentage get the active drug, the rest get the dummy placebo. It is a major reason why clinical trials are so huge, complex, and costly.

However, the impact of taking an unknown ‘placebo’ is far less than being handed a real tablet by a doctor. Who will likely inform you, with great enthusiasm, that it is going to do you good 3. Especially if they add, as they do with statins. ‘And it will stop you dying from heart disease.’ Or words to that effect. [And if you dare stop taking it, you will die].

Strangely, it appears to have escaped the attention of the CTT in Oxford that there is such a thing as the placebo effect. For them, the only bias that exists with statins is that you read about nasty effects, then suffer from them. The Nocebo effect. Why did they not mention the placebo effect? Which does the exact opposite – far more powerfully. I leave it to you, dear reader, to decide on that matter.

Some evidence of causality

It is very difficult to know what the true rate of adverse effects with statins may be. So much heat, so very little light. I cannot possibly cover all adverse effects in this blog. Instead, I will focus primarily on muscle pain and damage. This is probably the most common problem, and the most easily explained and understood.

I want to make it exceedingly clear that, far from being an imagined problem, we have a well-established biochemical pathway that directly links from statins to muscle damage, pain and weakness. With all steps proven, multiple times, in multiple studies.

In its simplest form, the pathway goes like this. Statins block an enzyme known as HMG-CoA reductase. This inhibits an early step in the long and complex – thirty-six step process – that ends up with the synthesis of cholesterol. This mainly takes place in the liver, which synthesizes around five grams of cholesterol, per day. About twenty eggs worth.

However, if you block HMG-CoA reductase this is not the only pathway you inhibit. You are also blocking the production of many other highly important compounds at the same time. You can perhaps think of cholesterol synthesis as a tree that grows from the ‘root’ of a chemical compound called Acetyl CoA.

As the chemical reaction ‘tree trunk’ grows upwards it starts to branch out, leading to the creation of many other, vital, substances. Such as dolichols, Heme A, prenylated proteins, co-enzyme Q10 etc, etc. Don’t worry there won’t be a test at the end.

Forgetting the others, important though they are, I will focus on Co-enzyme Q10 here. Which is also known as ubiquinone. This co-enzyme is critical in the synthesis of Adenosine Triphosphate (ATP). This molecule is, in turn, the power source that drives everything in our bodies. When ATP is broken down to ADP, energy is created, and used. This is how we work. From ‘professor’ Wikipedia:

‘ATP (adenosine triphosphate) is the primary energy carrier and “molecular currency” of the cell, storing and transferring energy to power essential processes like muscle contraction, nerve impulses, chemical synthesis, and active transport.’

You could think of ATP as the fuel in our car, or the battery in an EV. ATP doesn’t’ last long, and is being constantly replenished within the mitochondria – the little energy factories that live inside our cells. But without ATP, everything stops, and you die.

So, you could say it is kind of important. And, yes, statins have a significant and detrimental effect on the production of coenzyme Q10 (CoQ10), and then on ATP production. If you want some ‘real’ boring science about what this does. Read this paper:

‘Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes 4.’

‘These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis (death) in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy (muscle damage and pain).’

Paper highlights – taken from the paper itself:

  • Statins can induce muscle weakness/myopathy.
  • In culture, simvastatin induced dose dependent atrophy of human myotubes.
  • Statin exposure decreased mitochondrial respiratory function and increased ROS (reactive oxygen species…ROS = ’bad’) production.
  • Activation of apoptosis (muscle cell death) also evident.
  • Findings suggest mitochondrial dysfunction underlies statin-induced myopathy.

It all sounds pretty damned unpleasant, does it not. The primary problem is that, without sufficient CoQ10 mitochondria cannot make enough ATP. This, in turn, ‘impairs ADP-stimulated respiration’ which leads to mitochondrial dysfunction then activation of apoptosis. Apoptosis means cell death.

In short. If the mitochondria can’t make enough ATP, the cell does not have enough ATP/energy to survive, and may commit suicide. Which is what ‘activation of apoptosis’ means.

You think the pharmaceutical companies didn’t notice this… this (imaginary) muscle cell destruction and death? Of course they did. They may be many things, most of which are far too rude to print here, but they are very good at science, and they certainly do notice stuff.

They knew very early on that statins block CoQ10 synthesis, and then ATP synthesis. Not entirely, but up to a fifty per-cent reduction. At one point it looked as if this could be such a significant problem that Merck took out two patents outlining how to neutralise it. The first was US4933165A:

Key Aspects of US4933165A

  • Assignee: Merck & Co., Inc.
  • Inventor: Michael S. Brown (Note: The patent is often associated with the work of Dr. Karl Folkers regarding CoQ10, though the listed assignee in the 1990 publication is Merck).
  • Purpose: The invention describes a method for reducing the side effects of HMG-CoA reductase inhibitors (statins) by combining them with Coenzyme Q10.
  • Mechanism: Statins work by blocking the HMG-CoA reductase pathway. This same pathway is used by the body to produce CoQ10. The patent addresses the depletion of CoQ10 caused by statins, which can lead to muscle pain (myopathy) and potential heart damage.
  • Scope: The patent covers the combination of CoQ10 with various statins, including lovastatin, simvastatin, and pravastatin.

They didn’t act on this patent. Perhaps it wasn’t seen as a great sales idea to stuff the antidote into the same packet as the statin. ‘These are perfectly safe, you say. So, what it this other tablet here for – precisely?’

One man who did take out a patent with regard to the muscle damage caused by statins was none other then Professor Sir Rory Collins himself, in 2009.

A leading Oxford medical researcher who says statins are safe is at loggerheads with a company that makes “misleading” claims about the drugs’ side effects to sell a diagnostic test he invented.

More than 6m people take statins — drugs which reduce cholesterol and save an estimated 7,000 lives a year — but there is a fierce debate about the benefits and side effects.

Sir Rory Collins, a professor of medicine and epidemiology at Oxford University, led a review into statins, published in The Lancet earlier this month, which found that not more than one in 50 people will suffer side effects.

Collins, who believes millions more Britons could benefit by taking statins, is also co-inventor of a test that indicates susceptibility to muscle pain from them.

In 2009, he and three co- inventors filed the patent for a genetic marker that identifies patients at increased risk of myopathy (muscular pain). The patent says the incidence of myopathy is around one in 10,000 patients per year on a standard statin dose*.

The test, branded as Statin–Smart, is sold online for $99 (£76) on a website that claims 29% of statin users will suffer muscle pain, weakness or cramps. The marketing material also claims that 58% of patients on statins stop taking them within a year, mostly because of muscle pain.

Oxford University said Collins had raised his concerns “several times” about “misleading” marketing claims made by Boston Heart Diagnostics, the American company granted the exclusive licence for Collins’s patent by the university5. [Lois Rogers was health editor for the Sunday Times].

*Muscle pain and myopathy are not quite the same thing. Myopathy is a serious adverse effect – assocatied with a significant rise in an enzyme called creatine kinase (CK). When muscles are damaged and/or, die they – usually – release enzymes, with CK being the main one. Myopathy can be the precursor to rhabdomyolysis (very widespread muscle death) which has an extremely high fatality rate. And yes, all statins can cause rhabdomyolysis – albeit rarely.

I think of it this way, as a spectrum.

Muscle pain                =          Moderate muscle damage/death ± moderate rise in CK

Myopathy                    =          Severe muscle damage (often, not always, a rise in CK)

Rhabdomyolysis          =         Catastrophic muscle damage, CK through the roof

Myopathy may be considered relatively rare 1:10,000 per year (according to Collins). But the diagnosis is not straightforward, and it is heavily reliant on the finding of raised CK levels. But…here is a small study looking at patients with severe myopathy, and no rise in CK. ‘Statin-associated myopathy with normal creatine kinase levels.’

‘Four patients with muscle symptoms that developed during statin therapy and reversed during placebo use… Muscle biopsies showed evidence of mitochondrial dysfunction…These findings reversed in the three patients who had repeated biopsy when they were not receiving statins. Creatine kinase levels were normal in all four patients despite the presence of significant myopathy 6.’

So, we have a condition that is considered rare … but which may not be as rare as you think it is. Because you are relying on a blood test that may, or may not, actually diagnose it. You may get a lot of false negative tests. [A test which says you do not have a condition, when you do]. And when does muscle pain transform into myopathy? It is arbitrary.

Enough of this, I think.

What do we now know? We know that statins block CoQ10 production, and this reduces the amount of ATP being manufactured by the mitochondria – by up to fifty per cent. This is a well-researched, and inarguable, scientific fact. It will be a particularly significant problem in cells that have a high energy requirement e.g. skeletal muscle, or heart muscle, or neurones.

In truth, the adverse effect issue mainly boils down to this. Do you have the reserves to overcome the mitochondrial damage that statin cause … or not. If you do have the reserves, you may not notice much, if anything. If you don’t, you could end up stuck in a chair, hardly, able to rise. Which I have seen happen to several patients. And my father-in-law. An early statin user.

One lady I was looking after in an elderly care unit was judged to be so physically and mentally incapacitated that she was going to be admitted to a nursing home with frailty and dementia. I stopped the statins, and she walked out of the unit two weeks later, bright as a button. The nurses were stunned. I got a letter from her GP a week later, condemning me for stopping her life saving medication. That was just one of many patients where I had very similar results. She was just the most dramatic.

Do I have other terrible tales about statins? Of course. I recall another lady with such severe abdominal pain that she ended up having a laparoscopy (sticking a camera into the abdominal cavity to have a look around). Nothing was found, a mystery. She stopped the statin, on my recommendation, and the pain went away. Completely and forever.

Yes, I am biased, yes these are ‘anecdotes’, easily dismissed – and, boy, they will be. But I have seen so very many. Far more cases of rhabdomyolysis, for example, than I should ever have seen in my career …statistically.  And so many more have written to me, telling me how they have suffered, and then been dismissed by their own doctors.

Here is one such. I could dredge up a thousand more, given a couple of days.

‘Thank you, Dr. Kendrick. I am one of the many unfortunates who suffered permanent muscle damage from a needless prescription of simvastatin from 2008 to 2012. No monitoring, but my CK reading of 20 x normal was discovered by chance and the alarm was raised. When referred to NHS specialists their attitude was very strange, complete denial and hostility. Now permanently disabled on the right side of my body.’ Georgina H (Reproduced with consent).

Before I finish this blog. I would like to return to my court case, and all the interesting documents that emerged, blinking into the light. Barney Calman was the Health Editor of the Mail on Sunday which ran the defamatory article against me. He put out a call for case histories from people who had stopped taking statins, then suffered a major event e.g. heart attack, or stroke, or suchlike. What he got was the following:

From: Barney Calman Sent: Tue, 26 Feb 2019 08:44:40 +0000From: “Barney Calman” To: “Fiona Fox” , “Rory Collins” , “Colin Baigent” , “samanin@bhf.org.uk” , “Sever, Peter S” , “Liam Smeeth” CC: “Greg Jones” Thread To: Fiona Fox Rory Collins Cc: Greg Jones Sensitivity: Normal Colin Baigent samanin@bhf.org.uk Sever, Peter S Liam Smeeth

‘Dear all, thank you again for all your input into this article so far. I wanted to readdress the issue of finding a case study. One of the key factors in your collective argument is that criticism of statins discourages use amongst high-risk patients, and this is a public health threat. Since putting calls out we have been inundated by stories of people who have stopped taking statins and felt far healthier.

We’ve had two quite dramatic stories of patients who have been taken off statins by their doctors because of developing serious liver problems, and then died. The families themselves both naturally question whether statins caused the problems. What we haven’t had is a single story which backs your thesis, and obviously I’m concerned.’

Yes, he was ‘inundated’ with stories of people who felt far better having stopped their statins. The only two case histories he had managed to get hold of, at this point, were two people who took statins which then (almost certainly) caused liver failure, then death. [Statins are known to cause liver failure leading to, in extreme cases, death].

One would hope, in an ideal world, that if an investigative journalist was running a story on the unrivalled benefits of taking statins, and the harm that would befall those who stopped taking them … then. Then, when he found himself literally, his word, ‘inundated’ with stories of people who felt far better after stopping statins, and two cases of people who were almost certainly killed by statins then … Then you may pause to wonder if you are grabbing the right end of the stick.

But no, he did not let this put him off in the slightest. He had his eyes on the prize.

Next, a few surprising facts about statins and the unpleasant effects they can cause. Before finally, my direct criticism of the Lancet paper. And the nonsense that it is.

1: https://www.ncbi.nlm.nih.gov/books/NBK599521/

Click to access jroyalcgprac00086-0041.pdf

2: jroyalcgprac00086-0041.pdf

3: Unraveling the mystery of placebo effect in research and practice: An update – PMC

4: https://www.sciencedirect.com/science/article/abs/pii/S0891584911011130

5:Statins expert in row over level of risk to patients – Lois Rogers

6: Statin-associated myopathy with normal creatine kinase levels – PubMed

The latest Lancet paper on statin adverse effects – Part One

49 Replies

‘A lie is halfway round the world, before the truth has a chance to get its boots on.’ A quote used most famously by Winston Churchill.

A few of you may have noticed a recent paper in the Lancet written by the Oxford Cholesterol Treatment Triallists Collaboration (CTT). Much to no-one’s great surprise it fully supported their long-held contention that statins have, virtually, no adverse effects [Often inaccurately called side-effects, as side-effects can be harmful or beneficial].

The central message of the paper is as follows. The reason why people report that they are suffering aches and pains, or other symptoms, is because they have heard about them, or read about them. In other words, they are imagining them. The so-called ‘nocebo’ effect.

The authors suggest that the main culprit for the disinformation causing this comes from the patient information leaflets themselves. Which can be found inside the tablet packaging, and are legally required to be there.

The authors have gone so far as to state that, based on the findings of their study: ‘ .there is a pressing need for regulatory authorities to require revision of statin labels and for other official sources of health information to be updated.’ My imagined scene.

Patient:                                    ‘I’m sure I am getting muscle pains since starting on statins.’

Professor X:                            ‘No, you are not. You are imagining it. For the recent paper at the CTT has proved that all but four adverse effects are entirely imaginary. Please read this incomprehensible paper, full of clever statistics that you are, sadly, too imbecilic to comprehend and, by the way, ignore the leaflet.’

Patient:                                    ‘Oh, OK, sorry. I will keep taking them.’

Professor X:                            ‘Yes, quite. I hate to say it, but you are stupid and easily led. Like most people – other than me, of course.

You can perhaps understand my joy at this article, and the worldwide headlines it created. I knew it would be jargon filled, full of complex statistics, and written in such a way as to make it virtually impossible to understand. Here is how the BBC reported its findings:

‘Cholesterol-lowering drugs called statins, used by millions, are far safer than previously thought, a major review has found.

Leaflets in packs should be changed to reflect this and avoid scaring people off using the life-saving pills, say the authors.

Statins do not cause the majority of the possible side effects listed, including memory loss, depression, sleep disturbance, weight gain and impotence, says the team funded by the British Heart Foundation. Meanwhile, they can slash a person’s risk of heart attacks and strokes.’

‘Slash a person’s risk of heart attacks and strokes’ – well that’s a scientific statement if ever I saw one.

All the other mainstream media outlets reported this study in very much the same way. Which I would define as, unquestioning acceptance. A long line of nodding dogs. There has been no real investigation into their claims, and certainly no criticism of any sort. What ended up in the media was, effectively, a summary of the press release.

‘Statins do not cause the majority of the conditions that have been listed in their package leaflets, including memory loss, depression, sleep disturbance, and erectile and sexual dysfunction, according to the most comprehensive review of possible side effects. The study was led by researchers at Oxford Population Health and published in The Lancet.’ Beep, message ends. 1

This is all most people will ever hear, or remember. However, I believe that a far more in-depth critique of this paper is needed.

What I hope to explain, in three blog posts, is that this may be one of the most highly manipulated and misleading studies I have ever come across, and I have seen some belters in my time. The assumptions they made are … contentious, to say the least. And they have not a scrap of evidence to support their conclusions.

So, as briefly as possible, I hope to highlight:

  • The massive conflicts of interest at the CTT. Which is why they are the last organisation on earth who should have done this research. They set out trying to prove a point – and, surprise, surprise, they did.
  • The games played to allow the researchers to come to their conclusions. Potentially, very dangerous games indeed.
  • Why the data they used itself is enormously, and I would argue, fatally biased.

The first two blogs provide background and context. The final blog applies a microscope to the data, insofar as this is possible [As they won’t let anyone else see the data they used].

The massive conflicts of interest at the Cholesterol Treatment Triallists (CTT) Collaboration?

This paper emerged from The Cholesterol Treatment Triallist Collaboration (CTT). A group based at Oxford University in the UK. It was not written by Oxford Population Health, as stated in their press release. It is true that the CTT group sits within Oxford Population Health (OPH) … sort of. This is the explanation that will be used if they are questioned about it. ‘Don’t be so picky.’

However, I believe there is an important reason why the press release chose to highlight Oxford Population Health, not the CTT, and I think you will understand that reason after reading this blog. In truth, pretty much everything about his paper is misleading, even stating who did it.

This may seem a very minor issue to highlight, but details matter, and they can be very damning. I would allege that this press release represents a clear tactic to distract attention away from the organisation who actually did the study. This matters, because most people will not look beyond the press release and will therefore not link the study to the CTT. This has certain benefits, for reasons that should become clear.

You think I am being oversensitive and unreasonable? Then why did the press release fail to mentionthis study was done by the CTT?  Did they not want to take the credit for it? Or were they trying to hide something.

Just in case you are wondering. Here is the title of the paper, with its affiliation, copied directly.

‘Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials.’

Cholesterol Treatment Trialists’ (CTT) Collaboration 2

The important point I want to make is that the CTT has long and, some would say, inglorious history in this area. Over the years they have attacked anyone who has dared suggest that statins carry a significant burden of potentially damage effects. Including in the British Medical Journal (BMJ). As far back as 2013 there was a major bust-up over two papers published in the BMJ which suggested that statins had more adverse effects than were reported in clinical trials.3

Professor Collins demanded that the BMJ remove, and then apologize for, the articles published. Such was the kerfuffle he created that an independent review panel was formed to decide if the articles should be taken down. The panel found Professor Sir Rory Collins’ criticisms were not valid.

An independent review panel has rejected a demand by a prominent researcher that The BMJ retract two controversial articles. The report largely exonerates the journal’s editors from any wrongdoing.

As previously reported Rory Collins, a prominent researcher and head of the Cholesterol Treatment Trialists’ (CTT) Collaboration, had demanded that The BMJ retract two articles that were highly critical of statins.2 

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

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

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

The panel also had this to say.

“The panel did have one final comment. It became very clear to the panel that the fact that the trial data upon which this controversy is based are held by the investigators and not available for independent assessment by others may contribute to some of the uncertainty about risks and benefits. Different investigators may come to different conclusions with the same data … The panel strongly believes that the current debates on the appropriate use of statins would be elevated and usefully informed by making available the individual patient-level data that underpin the relevant studies”

Yes, you read that right. The CTT hold all the data on the major statin trials done by various pharmaceutical companies. And they will not allow anyone else to see it. Science, where art though.

But how could Collins have known, in 2013, that the articles were misleading? Here is a quote from the man himself in 2015, made to the Sunday Express newspaper:

Head researcher Prof Collins admitted he had not seen the full data on side effects. In an email to this paper he stated that his team had assessed the effects of statins on heart disease and cancer but not other side effects such as muscle pain.

Klim McPherson, professor of public health at Oxford University, said: “We know these drugs have side effects but we do not know if these have been assessed properly by the drug companies who carried out the trials.’4  

So, by his own admission, in 2013, Collins did not have any data on the adverse effects of statins. Yet he attacked the BMJ on this very same issue. In fact, the CTT’s position on statins has been consistent for many decades now. Basically, they are fantastically beneficial drugs, and have almost no adverse effects. Various members of the CTT have stated this repeatedly. Extraordinarily, they even managed to make these claims, before they had the data to support it.

Sometime between 2015, and now, the CTT must have got hold of the missing data. Although the paper does not explain how, or from who, or exactly what these data were. It is … obscure. I think I know, but I am not sure.

At this point, a question to you, gentle reader. Do you believe that anyone working for the CTT – where Collins and Baigent are the leading members – could be considered unbiased. When it comes to the issue of statin adverse effects?

I would argue that even if there were no financial considerations at play, we are staring straight at massive intellectual bias. Collins, Baigent and the rest of those working for the CTT, have staked much of their status, and their reputations, on this matter. A touch of cognitive bias might be in play?

‘Cognitive biases in medical research are systematic errors in thinking that skew study design, data interpretation, and clinical decision-making, often leading to faulty evidence. Key forms include confirmation bias (seeking supporting evidence), anchoring (relying too heavily on early information), and publication bias (ignoring negative results).’

I believe that all three forms of Cognitive Bias are on full display here.

And, of course, there are financial issues to be considered here. Very significant ones indeed. The Cholesterol Treatment Triallists Collaboration was set up within Oxford University. It receives no direct funding from the pharmaceutical industry, something they are very keen to emphasise – repeatedly.

However, the CTT was established by Collins, and Baigent et al. alongside the already existing Clinical Trials Research Unit (CTSU) in Oxford. It is made up of exactly the same people.

Indeed, if you try to contact the CTT, you are actually referred to the CTSU site. Here is the e-mail address for the CTT. Email (Specific Research/Database): ctt@ctsu.ox.ac.uk. Yes, the CTT ‘at’ the CTSU.

I asked Google AI about contacting CTT, and this is what it brought up:

Any claim that these organisations can act independently of each other, in some strange way, is one hundred per cent pure … Don’t get it on your shoes.

Why is this an issue? Because the CTSU receives very large sums of money from the pharmaceutical industry to run clinical trials. Many of these involve cholesterol lowering agents, including simvastatin – as used in their initial HPS study. How much money are we talking about here?

The next section has been taken from a piece by Zoe Harcombe on the same Lancet article. She agreed to let me use it – because she has written about this many times, and I didn’t want to look it all up again, or tread on her toes.

Her section starts with the declaration that the CTSU had, by 2014, received ‘grants’ of £268 million for commercially funded research. How much have they earned since …who knows? No more declarations have been forthcoming……

[From Zoe Harcombe] The May 2014 declaration of funding (c. £268 million at that time, as above) was titled “Grants to Oxford University for any Clinical Trial Service Unit (CTSU) trials or other commercially-funded research over the past 20 years…”

‘My best guess as to how the CTT can try to claim no grant funding, given the self-declared grant funding, is that semantics have been relied upon between Oxford University, the CTSU and the CTT Collaboration. I’m open to any other explanations that may be on offer. I searched the latest CTT paper (the Lancet paper) for “Clinical Trial Service Unit” or “CTSU” and it appeared once – at the corresponding address “Correspondence to: Clinical Trial Service Unit…”

Whatever the semantics, the latest CTT paper focused on five statins. The manufacturers of the five statins chosen are Pfizer (atorvastatin), Novartis (fluvastatin), Bristol Myers Squibb (pravastatin), AstraZeneca (rosuvastatin), and Merck (simvastatin). The author declarations of interest took up over a page in the paper. Pfizer appeared 5 times, Novartis appeared 11 times, Bristol Myers Squibb appeared 3 times, AstraZeneca appeared 11 times, and Merck appeared 7 times.

Oxford University has strategic research alliances with several pharmaceutical companies including Pfizer, Bristol Myers Squibb and AstraZeneca. It has research partnerships with Novartis and Merck (Ref 21).

– “Pfizer has a longstanding research relationship with the University of Oxford” (Ref 22).

– “The Oxford-Bristol Myers Squibb alliance was established in 2015 … Oxford’s alliance with Bristol Myers Squibb continues to grow year on year, the total of Oxford-Bristol Myers Squibb Fellows is now 34 and many other collaborative projects are currently running” (Ref 23).

– “AstraZeneca (AZ) and Oxford have a long history of collaboration” (Ref 24).

While Novo Nordisk was not one of the companies helped by this paper, I noticed that “The alliance between Novo Nordisk and Oxford … has seen Novo Nordisk establish a presence onsite at the University of Oxford, with the Novo Nordisk Oxford Research Centre (NNRCO) employing up to 100 researchers between 2017 and 2021” (Ref 25).

Wow – 100 researchers – and how many people have been employed as a result of the few hundred million given to Oxford University for the CTSU or other commercially funded research?

There can be little doubt that relationships between Oxford University and pharmaceutical companies are of great mutual benefit. There can also be little doubt that it is inconceivable that any research would emanate from Oxford University that is critical of any drug made by any alliance companies. On the contrary, the higher the number of positive papers that can be published, the stronger the mutual alliance. [End Zoe Harcombe]

Yes, hundreds of millions in commercial funding. And that was twelve years ago. This figure will have grown considerably. In addition, hundreds of researchers have also been paid for by various pharmaceutical companies. Total cost? One hundred researchers at an employment cost of, at least, fifty thousand is five million, per year – minimum.

To claim, as they do, that the CTSU/CTT has no financial conflicts of interest is …what is the correct word here? Let me think.

At this point I will declare my own conflict of interest here – which has clear relevance to the discussion. Six years ago, I sued The Mail on Sunday for an article they published, way back in March 3rd 2019. I was accused, along with Zoe Harcombe and Aseem Malhotra, of being responsible for thousands of unnecessary deaths.

This was because we had ‘claimed’ that statins have more adverse effects than are widely reported. Also, that they were significantly less beneficial. With positive effects boosted by various forms of statistical manipulation.

The Mail on Sunday article stated that our talks, and blogs and publications had led to hundreds of thousands of people stopping their statins, leading to many thousands of excess heart attacks and strokes as a result. As one third of heart attacks are fatal, the implication, though not directly stated, is that many, excess deaths occurred. Hundreds, thousands?

Having, effectively, been accused of mass murder, I sued, along with Zoe Harcombe. And, yes, we won. [Which is why you cannot see the article anymore]. The libel case took over five years from start to finish. There was no evidence to support the central accusation of increased heart attacks and strokes. This accusation was based on a modelling study which had no outcome data on morbidity, or mortality. None.

Behind the scenes, Rory Collins and Colin Baigent were very active. They advised Barney Calman, the health editor on what to say. They even edited the paper. Here is one statement that Collins provided to Calman, which was in the article itself:

‘Professor Sir Rory Collins, the British scientist behind pivotal research into statins, says the potential consequences far outweigh that of the infamous MMR vaccine scandal, in which disgraced paediatrician Andrew Wakefield fabricated evidence to support his idea that the jab triggered autism in infants, leading to a decline in vaccination uptake and the resurgence of measles.’

Yes, Collins and Baigent, and various other Professors from the British Heart Foundation, were advising Calman on the best lines of attack. Collins and Baigent even congratulated him warmly after the article was published.

Below are just three of the hundreds of e-mails sent between the various players [All e-mails are on file. I am considering releasing the whole lot – as they are no longer confidential]. The first one here is from Barney Calman, health editor of the Mail on Sunday, to Rory Collins and Colin Baigent, among others, thanking them for ‘all their input’ into the article. [It includes Professor Nilesh Samani, medical director of the British Heart Foundation at the time].

Also named in the e-mail trail is Professor Liam Smeeth who was the lead author of the modelling study mentioned above. He has written widely on the fact that statins have no adverse effects. There is also Professor Peter Sever on the e-mail trail. And he is …stop right here Kendrick, libel goes both ways. A bit more info on Liam Smeeth…

‘Professor Liam Smeeth and Professor Sir Rory Collins are both prominent British academic experts in epidemiology and cardiovascular health who have closely intersected through high-profile, collaborative research on statins.’ From Google AI.

E-mail: From: Barney Calman To: Fiona Fox; Colin Baigent; Rory Collins; Professor Nilesh Samani; Sever, Peter S; Liam Smeeth Subject: [EXTERNAL] MOS/Statins Dear all, please find below our piece.

Thank you again for everything you’ve done to help so far. If you each separately send me back any amendments you have in tracked changes or some other trackable way, that’d be great. All comments welcome. BC by BARNEY CALMAN Health Editor

That was one e-mail proving that members of the CTT were commenting on, and even editing, the article.

After it was published, Rory Collins wrote this e-mail to Barney Calman:

E-mail From: Rory Collins Sent: Sun, 3 Mar 2019 18:07:05 To: Barney Calman Cc: Colin Baigent Subject: RE: all changes made Sensitivity: Normal External Sender:

Dear Barney: What a pleasure to see such a hard-hitting evidence-based article on fake news related to statins … and the page 2 article with Matt Hancock’s very direct comments was an unexpected bonus. Best wishes. Rory

Fake news …indeed. Twelve minutes later, Colin Baigent wrote this:

E-mail From Colin Baigent: Subject: Re: all changes made Sensitivity: Normal External Sender

Dear Barney: I’d like to echo Rory’s praise for your article. Thanks very much for taking the trouble to understand the issues, and also for your willingness to address last minute concerns, as I think the final product was admirable. Best, Colin

‘An admirable article’ … Although, as it turns out, it was also a libellous article. And you guys helped him to write it. Good job.

I knew where, and from whom, Calman was getting his information right from the start. Before the article had been published. To me, it was glaringly obvious that it had the CTT’s fingerprints all over it. Shortly before the article was published, Calman wrote to me, asking for my comments on the article (which he did not include in the e-mail), giving me twenty-four hours to respond to the various points he was making.

I then sent this e-mail on 28th February 2019 to others who share my views on statins:

On Thu, Feb 28, 2019 at 12:05 PM, malcolmken@doctors.org.uk [thincs] wrote: 

Dear all, 

The Mail on Sunday have contacted me about an article they plan to run, attacking me, and us. It is the usual Rory Collins attack. 

I have been given until tomorrow to reply. Does anyone have any good, concise ammunition? 

Regards 

Malcolm

Yes, these guys work tirelessly behind the scenes to destroy the reputation of anyone who dares to question statins. This time their activities, normally unseen, were exposed in documents that were required to be released to the court before the libel case was heard.

I think that is enough information about the conflicts of interest at play here. You may still feel that the CTT is fully independent, and their objectivity remains beyond question. If so, then I do not suppose that anything I write, nor any other evidence, could convince you otherwise.

Summary

  • The CTT, members of whom wrote the Lancet paper, have been aggressively attacking anyone who suggests that statins carry a significant burden of adverse effects for many years. Even when, by their own admission, they did not actually have the data on adverse effects.
  • The CTT, who also have all the data from the statin trials, will not share it with any other researchers. Claiming commercial sensitivity/confidentiality.
  • The CTT is intimately related to the CTSU, is part of the CTSU, and the CTSU has gained hundreds of millions of pounds in funds for running clinical trials on behalf of the pharmaceutical industry.
  • My own conflict of interest is that individuals within the CTT have attacked me directly, and indirectly, many times over the years. Their behind-the-scenes activities were laid bare in court disclosure documents.

I think it is important for everyone to understand this background before moving on. And I feel the need to repeat that this was not a study led by Oxford Population Health. It was a study by the Cholesterol Treatment Triallists collaboration. A group with a very long history in this area, which they may not have wished to publicise. I believe the CTT are far too conflicted to have carried out unbiased research on statins.

1: https://www.ox.ac.uk/news/2026-02-06-statins-do-not-cause-majority-side-effects-listed-package-leaflets

2: Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials – The Lancet

3: https://www.bbc.co.uk/news/health-28602155

4: Rory Collins wants to see safety checks made for statins | UK | News | Express.co.uk

Disruptive science – part one

76 Replies

I read an article in Nature magazine a couple of years ago which has nagged at me ever since. It highlighted the sobering fact there has been a collapse in disruptive science.

‘Disruptive’ science has declined — and no one knows why

04 January 2023

The proportion of publications that send a field in a new direction has plummeted over the past half-century.

I recently watched the film Oppenheimer where scientists argued about new ideas. Debating, pushing forward their thinking in exciting new ways. Niels Bohr, Heisenberg, Einstein, Van Neumann, Oppenheimer himself. They seemed like true intellectual giants whose names still echo through history.

In the same era Isaac Asimov was developing new ideas in his novels – the three laws of robotics. Foundation and Empire. Then there was Philip K Dick, Harlan Ellison, Ursula K Le Guin. Where are these giants now? Where is the new thinking? Why has it all got so … dull?

As a child I watched the Apollo moon landings, but when was the last time I woke up to the news that something earth shattering had just taken place in a scientific field? Some form of major disruption. Everything we thought we knew just got turned upside down. New directions …

Although it could seem a little on the trivial side, for me it was with graphene. Two scientists in Manchester were, essentially, larking about in the lab, trying to find out how thin a layer of graphite they could create by wrapping Sellotape round pencil lead. Turns out, you could get a monolayer of graphite. Allowing me to misquote Asimov who reckoned that the most exciting phrase in science is. ‘Well, I never expected that.’

I fully believe that graphene will change the world in many different ways, mainly for the better. A completely unexpected breakthrough in material science. I love this type of thing.

Medical science

Unfortunately, in my world of cardiovascular disease, you could go back fifty years and find almost exactly the same ideas remain in use, about virtually everything. It is hard to think of anything remotely disruptive, or even remotely novel. Cholesterol causes heart disease, check. Diabetics should eat a high carbohydrate diet, check…

Looking specifically at raised blood pressure. What causes it? In ninety-five per cent of people we have no idea. We didn’t know then, and we don’t know now. We still call it “essential hypertension” as we always did, which means – in plain English – a raised blood pressure of no known cause. The proposed management then, and now is … Lower it. Sorted. And we call this progress? Ahem (I say). No disruption here …check.

In this blog I want to look at one, specific area. The use of salt/sodium restriction to lower blood pressure and reduce the risk of dying early? An idea that has been around since before the second world war. Bonkers then, bonkers now. Unchanged …check.

Once some proper scientists managed to fully establish the neurohormonal system that controls blood pressure. Including the renin, angiotensin, aldosterone system (RAAS), it should have become clear to anyone with a functioning brain that restricting salt intake could very well do far more harm than good. An area that is both complicated and fascinating. But this new knowledge had no effect. Nothing was disrupted.

What about the evidence on salt intake. Below, I give you a graph of overall mortality [all cause death] vs. sodium intake 1.

I do love a graph, but I know a lot of people don’t. So, I shall attempt to explain it in a little more detail.

The bars that rise, and fall, from left to right, represent the percentage of people consuming different amounts of sodium. With most people it falls around the two-to-four-gram mark, or thereabouts. [Which is approximately the same as four to eight grams of table salt, sodium chloride. Most of our sodium intake comes from ‘salt’ but not all].

The solid line, heading down from left to right, shows the risk of death associated with different levels of sodium intake. The shaded area, around the line, represents the spread of ‘probability’. Or, to put it another way, the likelihood that the risk of death at various levels represents a statistically significant finding – at increasing levels of sodium intake. Got that? There will be an exam at the end of this blog.

In essence, though, this graph is very simple to understand. Namely, the more salt you eat, the longer you will live. And, or course, vice-versa. Which is the exact opposite of everything you are constantly told.

I shall repeat this to emphasize the point:

If you eat more salt, you will live longer.

And this benefit continues right up to twenty grams of salt a day. I don’t think they could find anyone who consumed more than that. Although me, swimming in a choppy sea on a sunny day, might manage.

I know what you may be thinking. I have cherry picked one study to make a point. Well yes, this is just one study. However, it is the biggest and longest ever done. It represents one small part of the National Health and Nutrition Examination Survey (NHANES).

And, although it is only a small part, it represents very nearly ‘one-million-person years’ of observation. Of course, like all nutritional studies it has its weaknesses, but you will find nothing bigger, longer, or better than this. And if you want to find one that contradicts it – feel free – and good luck.

But if you would like some more data. Here is the Scottish Heart Health Study. In this case the researchers looked at twenty-seven factors associated – in one direction or another – with cardiovascular disease [although they only mentioned 26?].

They also incorporated overall mortality (risk of dying of anything), and I reproduce their graph, for men, below. The graph for woman was pretty much identical. This was the first time I noticed that increased sodium intake may be beneficial, not harmful 2.

Again, a little more explanation is probably required to make sense of this chart. The numbers at the bottom 0 – 4 represent the Hazard Ratio (HR). A hazard ratio of one means the risk of a ‘factor’ is neither raised nor lowered. It is average. Two means risk is doubled, three means risk is trebled etc.

At the top of this chart lies ‘Previous myocardial infarction’ [Previous heart attack]. No surprise to find that having had a heart attack is a pretty good indication of serious problems and a potentially much-shortened lifespan.

There is another thing I need to explain here. You will notice that ‘Previous myocardial infarction’ is ranked +01 – the 01 = the most important factor. The plus sign in front of 01 means that risk of death is increased. If you go down to number five ‘Urine Potassium’, you will see – 05 (minus 05). The minus sign means risk is reduced…ergo, the hazard ratio is reduced. [I shall cover potassium at some point in the future].

If you keep going down the list, you arrive at sodium, at number eleven. As you can see, greater sodium excretion, which is directly related to greater sodium intake, is protective. Sitting at -11. And these researchers actually did a measurement – urinary sodium. Rather than asking people how much salt they consumed each day, because who has any idea about that?

As a further aside if you keep going down you will see the letters NS and NL.

NS = not statistically significant (probably not important one way or the other)

NL = non-linear (there is no consistent association at different levels – risk goes up and down randomly. Definitely not important)

Amongst the NS and NL ‘risk factors’ we find the following:

  • High Density Lipoprotein (HDL) a.k.a. ‘good’ cholesterol
  • Triglycerides (now considered a form of ‘bad’ cholesterol)
  • Total Cholesterol a.k.a. ‘bad’ cholesterol
  • Body mass index
  • Weight
  • Energy intake
  • Alcohol
  • Blood glucose

None of these things were found to have any effect on the risk of death. Sorry, possibly a bit too much disruptive evidence in one graph for easy digestion. In truth, I could talk about this graph all night, and still have time for more. But I do want to loop back to the start.

‘Disruptive’ science has declined — and no one knows why.’

Both of the studies here could have been, should have been, extremely disruptive. However, they have had no discernible impact whatsoever. Nothing has changed. Here, for example, is what the British Heart Foundation continues to say about sodium:

‘Some food labels call salt, sodium instead. Salt and sodium are measured differently. Adults should have less than 2.5 grams of sodium per day.’ [Approx 5 grams of ‘salt’]

Here is what the CDC has to say, as of today:

‘The CDC recommends that adults and teens consume less than 2,300 mg of sodium per day, which is about one teaspoon of salt.’

[There are many different salts. The one we generally call ‘salt’, table salt, is sodium chloride. NaCl. This is the form of salt from which we obtain most of our sodium. Sodium makes up, very close to, one half of the weight of ‘salt’. So, five grams of salt is around two and a half grams of sodium. No-one eats sodium alone, and it is certainly not recommended. There would be a rather large explosion].

Reading the CDC recommendation did cause my irony meter to reach its maximum recorded level, then break. How so? Because the NHANES graph that I showed earlier comes from research that is funded by, and run by, the Centres for Disease Control and Prevention (the CDC).

Yes, their very own study utterly contradicts their very own advice. Despite this, the CDC continue to harangue us to consume less sodium. Which is not merely health neutral, it is actively damaging. Why don’t they advise people to start smoking while they’re at it?

‘Our studies tell us cigarette smoking damages health. We advise cigarette smoking for all adults. At least ten a day should be tickety boo.’

Sound crazy? Yup.

Now, I know that it is bloody difficult to change an idea. And this has always been the case. To quote Leo Tolstoy from many moons ago:

‘The most difficult subjects can be explained to the most slow-witted man if he has not formed any idea of them already. But the simplest thing cannot be made clear to the most intelligent man if he is firmly persuaded that he knows already, without a shadow of doubt, what is laid before him.’

But science, if it is to be about anything, is the acceptance of new ideas. Disruptive evidence should not be attacked and silenced. Or, in this case, simply ignored. It should be welcomed with open arms. It is the very ground upon which science rests. To quote AI Google on Richard Feynman.,

‘Richard Feynman’s quote, “Science is the belief in the ignorance of experts,” means that genuine science is a process of constant questioning and scepticism, not a blind acceptance of authority. It emphasizes that knowledge is provisional and that experts, while valuable, are limited by their current understanding and should be questioned rather than treated as unquestionable authorities.’

Yes, every ‘scientist’ nods sagely when you say things like this. They then rush off to slam the doors in their minds and carry on regardless.

Were things this bad in the past? I don’t believe so. My sense is that disruptive science has been declining the last fifty years or so …. ‘And no-one knows why?’ But is it true that no-one knows why. Or is that almost everyone does know why, but no-one wants to say it out loud. Or even admit it to themselves. For myself, I believe the answer is, as is usually the case, staring us in the face.

It is money. Or to be more accurate, disruptive science is dying a death due to the enormous effect that financial considerations now have on research. Directly, or in the case of salt, indirectly.

I use the word indirectly because, as you have probably recognised, the impact of money cannot be straightforward with salt. The salt industry, if there is such a thing, can hardly be pushing for a reduction in salt consumption, and who else could get rich from this? So, why do we continue to be bombarded with anti-salt messages. And how can this possibly relate to money?

Next, let me take you on a long and winding golden paved road.

1: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-17582-8

2: ‘Comparison of the prediction by 27 different factors of coronary heart disease and death in men and women of the Scottish heart health study:cohort study.’ BMJ 1997;315:722

A little more on the trial

120 Replies

When the background information leading up to the libel trial was released to us, there was one trail of e-mails that struck me as very damning. It emerged that Barney Calman was very keen to find case histories where people had stopped taking statins and then suffered a catastrophic event, such as a heart attack or stroke, or dying. This ‘stopping statins and dying’ concept was pretty much central to the articles.

Barney Calman asked a Samantha Brick (no idea who she is) to find case histories. Real life stories are always considered to be very powerful by the mainstream media. Which they are. Barney also told her she could offer people money to people who came forward with tales to tell.

Unfortunately for him, the only two case histories she got hold of were people who had started taking statins, and then died. [I believe the information has been sufficiently anonymised so that no-one can work out who these two people were. Although they are already in the public domain, in the court documents bundle, so I am revealing nothing here that is not already open for scrutiny].

The first case concerns a young woman who was put on a statin. Then died from liver failure. Liver failure is a known, although relatively rare, serious adverse effect of statins1.  The second case is less clear cut, but also seems to point directly to a statin ‘caused’ death. [I have tidied up the e-mails a bit to make them easier to read but I have not changed any of the words used].

From: SAMANTHA BRICK [mailto:samantha.brick@btinternet.com]

Sent: 25 February 2019 18:29

To: Barney Calman <barney.calman@mailonsunday.co.uk>

Subject: possible statins case studies – both died after stopping them*

External Sender~~

Hi Barney,

These 2 replied to my £500 alert. I can probably reduce them to £200 each if you use them both. They are quite similar though in terms of what happened. I’m not sure if this is what you’re after? 39, married mum of two who lives in North London. She lost her sister 16 months ago.

She says:

My sister was 39 when she was prescribed statins. She was a mum of 4 and worked as a manager of a dairy company. When she was diagnosed with high cholesterol, she was advised to change her diet and exercise. Her Dr also told her to take Fluvastatin. She was reassured that even with her busy lifestyle it would lower her high cholesterol.

She took the tablet as prescribed for six months. She began to vomit a lot and had pain in her chest. On more than one occasion she called an ambulance. Each time she was admitted to hospital she was told there was nothing wrong with her heart.

The vomiting episodes began to increase. She was eventually diagnosed with a fatty liver. She stopped taking the statins on the doctor’s advice (a month before she died) and went to see her brother who lives in Berlin. There she was admitted to hospital. By now she still struggled to keep food down and was fed via a tube She was in hospital for a fortnight when she suffered a stroke and died.

This was 16 months ago. The whole family were devastated because her demise came out of the blue. She’d never had problems with her liver beforehand.

————————————————————————————————————————-

Lady 30, is married mum of one who lives in London (waiting on a picture of her with her dad).

She says:

My Dad died two years ago after he had stopped taking statins. (just waiting to find out exactly which ones he was taking) He’d had a heart by-pass in 1998 and was prescribed simvastatin afterwards. He’d been taking others since. He’d been taking them for over 16 years without – seemingly – any problems.

During that time, he’d call ambulance because of pain in his chest. But he was discharged each time without issues. He was also diabetic and taking medication for that. Three years ago, he was diagnosed with liver problems. Straightaway he told to stop taking the statins. At the time he was also throwing up and struggling to keep food down.

Mum would try to feed him jelly or mashed potato but he couldn’t keep it down eventually he was admitted to hospital and was fed via a tube.

While he was in hospital the focus was on the issue with his liver (need to confirm what this was –she thinks that they had to drain fluid from it – will know overnight). While the investigations into the liver problems were carried out, Dad had a heart attack and died.

He’d been on the tablets for years – was it stopping them that caused this. Or were they behind everything that snowballed. I’m worried because my mum also takes statins for her health too – she is on avastatin (I assume atorvastatin). They were married for 50 years mum is still grieving.

Samantha Brick

My book: “HeadOver Heels in France” is out now

Twitter: @samanthabrick

Instagram: Sammy brick

Facebook: Sam Brick

*this e-mail should have read. Both died after taking them.

In the first case I think it is clear cut that this young woman died as a direct result of statin induced liver toxicity. The second case is a little more confused, but the history of throwing up and struggling to keep food down is identical to that of the young woman. Loss of appetite, nausea and vomiting are well recognised symptoms of liver failure. It is also known that it can take months, or years, for statins to cause liver failure. [The final ‘event’ in liver failure is often a cardiovascular event].

Unfortunately for him, the case histories Barney Calman received totally contradicted his argument. At this point you would think Barney may have taken stock. He had two case histories, and two deaths, both almost certainly caused by statins. And it gets worse.

It’s not as if he didn’t understand what he was reading. To use his own words. ‘We’ve had two quite dramatic stories of patients who have been taken off statins by their doctors because of developing serious liver problems, and then died.’ So, he can’t claim he didn’t see them Or, that he failed to understand what he was reading.

But the very next day, he took it away and redoubled his efforts.

From: Barney Calman

Sent: Tue, 26 Feb 2019 08:44:40 +0000From: “Barney Calman” To: “Fiona Fox” , “Rory Collins” , “Colin Baigent” , “samanin@bhf.org.uk” , “Sever, Peter S” ,

“Liam Smeeth” CC: “Greg Jones” Thread

To: Fiona Fox Rory Collins Colin Baigent samanin@bhf.org.uk Sever, Peter S Liam Smeeth

Cc: Greg Jones

Sensitivity: Normal

Dear all, thank you again for all your input into this article so far. I wanted to readdress the issue of finding a case study. One of the key factors in your collective argument is that criticism of statins discourages use amongst high-risk patients, and this is a public health threat.

Since putting calls out we have been inundated by stories of people who have stopped taking statins and felt far healthier (I put this comment in bold). We’ve had two quite dramatic stories of patients who have been taken off statins by their doctors because of developing serious liver problems, and then died. The families themselves both naturally question whether statins caused the problems. What we haven’t had is a single story which backs your thesis (I put this comment in bold) and obviously I’m concerned.

I think it makes us look rather weak to use a very historic story about Clinton [Bill Clinton stopped his statin then had a heart attack]. What I do not want this piece to be is simply another exercise in singing to the choir and I fear without a real-life example, we may be veering towards it all just seeming like scary theories and doctors saying ‘because I said so.’

What has struck me is that the reason Kendrick, Malhotra, Harcombe and their ilk have really struck a chord is because they are great, emotive communicators. What we’re offering is a chance for you all to be that too, and we are planning to devote an unprecedented amount of space to this.

Have any of you heard a real-life example of someone who has suffered a heart attack or stroke because they declined/quit statins because they thought they didn’t really work anyway, or similar? I really want us do everything we can to make this work. Please do ALL let me know asap today your thoughts about how to move forward. BC

_________________

Barney Calman

Health & Lifestyle Content Director

Mail on Sunday

As you can see, in addition to his two incompatible case histories, Barney was also ‘inundated’ with stories about people giving up statins then feeling far better. Concerns, he still had none.  He only had eyes on the prize.

And what of glorious professors, such as Professor Peter Sever, who had proven themselves so eager to assist Barney in putting together his libellous articles. Did he feel the slightest nagging doubt at this point. Nope, nothing of the sort. In fact, this is what Professor Peter Sever had to say

From: Sever, Peter S

Sent: Tue, 26 Feb 2019 09:20:05

To: Colin Baigent Barney Calman Fiona Fox Rory Collins samanin@bhf.org.uk Liam Smeeth

Cc: Greg Jones

Subject: Re:

Sensitivity: Normal

External Sender~~

I’m afraid I disagree [Professor Baigent had argued against using case histories, as they were not scientific].

We (my bold) are not trying to convince a scientific audience. This is a communication to the public and they are influenced by case reports and anecdotes whether we like it or not. This is precisely why our opponents* are so successful.

If we are to be successful in countering their claims I’m afraid we have to play by their rules. I’m all for scientific integrity as Colin and Rory opine but this doesn’t work when dealing with the public

Look how many scientific reports have countered the Wakefield claims with so little effect. May I remind you that we all use case reports to illustrate optimal treatment strategies when are teaching. Perhaps not a perfect analogy but not far off!

I support Barney’s point and think we should find a case report (or two!)

Barney what is the timeline?

Regards

Peter**

*note the use of the words our opponents. Yes, ‘our’ opponents. This e-mail was sent to Barney Calman, amongst others. So, whose side do you think Barney Calman is seen to be on? I also made the word ‘we’ bold in the text.  At one point during the hearing our barrister asked the question, ‘who is, or are, ‘we’ in this case? Yes, you can damn your defence without even realising you are doing so. It is difficult to claim you are writing a personal opinion piece when your collaborators are using terms such as ‘we’ and ‘our’. And they are including you. Whose opinion is it anyway?

**note how friendly they have all become

Of course I knew, or suspected, that discussions like this had been going on in the background. I did not know who all the collaborators were. However, Barney did let me know, on the 1st of March 2019 that a critical article was going to be published, naming me. I had less than 24 hours to respond. One part of my reply was – as follows.

‘Listen, we all know where this attack is coming from. The CTT* and Professor Rory Collins and Baigent et al. They attacked Aseem Malhotra and Professor Abramson, then the BMJ, for publishing articles by Aseem and Abramson suggesting statins caused adverse effects in around 20% of people. Collins attacks were severe, and the BMJ was require to hold an investigation, in which Collins attacks on these papers were judged to be unfounded.’

*The Cholesterol Treatment Triallists Collaboration in Oxford. Headed by Collins and Baigent, among others.

As it turns out, I was bang on the money. Which was not difficult. These two lash out at anyone, or anything, who dares criticize statins in any way. It was Collins who first came out with the ‘worse than Andrew Wakefield and the MMR scare’ meme. If he wasn’t the first, he sure uses it a lot. Be careful about the language you use, for it can come back to bite you on the backside.

Next time. Let me have a think. So much to choose from. And, oh, by the way. How are things going Rory and Colin? [I have been told that they read my blog – through gritted teeth].

1: https://www.ncbi.nlm.nih.gov/books/NBK548067/#:~:text=(Review%20of%20safety%20of%20statins,and%200.04%25%20with%20placebo).

The legal case – naming a few names

148 Replies

When the Mail on Sunday published their libelous articles about me on March 3rd, 2019, I was expecting it. I wasn’t expecting them to arrive on that precise date, or in that specific newspaper. But I had been waiting for something very unpleasant to appear, somewhere. Although I have to say that the level of malice was far greater than anticipated.

But it was entirely predictable what the main thrust of any article was going to be.

I, Dr Malcolm Kendrick, with or without other co-conspirators, would be accused of spreading misinformation about cholesterol and statins. This misinformation would have resulted in many thousands of people giving up their medication and suffering heart attacks and strokes as a result. With thousands dying.

The spectre of Andrew Wakefield and the MMR ‘scandal’ would be raised. With the words ‘far worse than’ to be found somewhere.

I make no claim to be Nostradamus 2.0. But I am capable of adding two and two to make four. I had also taken note of many other attacks around the world. Storing away the accusations made, and phrases used. So, I was well aware of what was heading my way. At least some of it. It was simply a matter of time.

Why do these attacks happen?

The hypothesis that a raised cholesterol level causes heart disease [atherosclerotic cardiovascular disease (ASCVD)] is possibly the single most powerful idea in medicine. If not the most powerful. It has long since reached the hallowed status of a ‘fact’. It is also entirely resistant to all contradictory evidence. To quote from the film Inception.

‘What is the most resilient parasite? Bacteria? A virus? An intestinal worm? An idea. Resilient… highly contagious. Once an idea has taken hold of the brain it’s almost impossible to eradicate. An idea that is fully formed – fully understood – that sticks; right in there somewhere.’

The pharmaceutical industry put their weight behind this idea very early on and shoved mightily. They recognised there were vast fortunes to be made in lowering the cholesterol levels of hundreds of millions of people, if not billions…for life. The perfect money-making machine, sorry medicine.

And lo, the search began for drugs capable of doing this. Starting with nicotinic acid, then clofibrate in 1958. The first drug capable of blocking cholesterol synthesis in the liver was Triparanol, introduced in 1959. It was rapidly withdrawn due to horrible adverse effects. Which could have acted as a warning – but didn’t.

However, it wasn’t until statins were first launched in the 1980s that the money really started to flood in. Statins became the most widely prescribed and profitable medications ever. With sales of nearly one trillion dollars. Today, there are several new cholesterol lowering drugs to keep the party going – and the money flowing.

And while there were nasty attacks on anyone who questioned the mighty ‘cholesterol hypothesis’ from early on, it wasn’t until the mid-1980s that they became truly vicious and seemingly coordinated. A strange coincidence… or perhaps not.

In parallel, a massive nutritional market grew. Low fat foods claiming to reduce cholesterol created a modern day trillion-dollar industry today. And if you dare to suggest the idea that low-fat foods do not protect against heart disease, you get much the same treatment. Which can be distilled into the following statements.

‘You are stupid and dangerous and understand nothing about science. You are also a conspiracy theorist, and your actions are killing thousands.’ Message ends.

Of course, you can never engage with anyone over the science itself. The attacks are lobbed over the castle walls, where your enemy sits safely, refusing to engage on the battlefield. ‘Just pour a little more boiling oil on their heads, if you would be so kind? Their criticism is becoming tiresome.’

Why do these attacks happen. Money, mainly.

Who got attacked first?

I think it was John Yudkin – but I know someone will almost certainly correct me on this.

In 1972 Yudkin wrote the book ‘Pure white and deadly’ where he outlined why sugar was a probable cause of heart disease, not fat(s). Even before this he had been subjected to the full boiling oil treatment. As outlined by the Telegraph newspaper in the UK:

‘The British Sugar Bureau put out a press release dismissing Yudkin’s claims as “emotional assertions” and the World Sugar Research Organisation described his book as “science fiction”. When Yudkin sued, it printed a mealy-mouthed retraction, concluding: “Professor Yudkin recognises that we do not agree with [his] views and accepts that we are entitled to express our disagreement.”

Yudkin was “uninvited” to international conferences. Others he organised were cancelled at the last minute, after pressure from sponsors, including, on one occasion, Coca-Cola. When he did contribute, papers he gave attacking sugar were omitted from publications. The British Nutrition Foundation, one of whose sponsors was Tate & Lyle, never invited anyone from Yudkin’s internationally acclaimed department to sit on its committees. Even Queen Elizabeth College reneged on a promise to allow the professor to use its research facilities when he retired in 1970 (to write Pure, White and Deadly). Only after a letter from Yudkin’s solicitor was he offered a small room in a separate building.

“Can you wonder that one sometimes becomes quite despondent about whether it is worthwhile trying to do scientific research in matters of health?” he wrote. “The results may be of great importance in helping people to avoid disease, but you then find they are being misled by propaganda designed to support commercial interests in a way you thought only existed in bad B films.”

And this “propaganda” didn’t just affect Yudkin. By the end of the Seventies, he had been so discredited that few scientists dared publish anything negative about sugar for fear of being similarly attacked. As a result, the low-fat industry, with its products laden with sugar, boomed.’1

Lesson number one. If you launch a really venomous attack on one scientist, it tends to deter all the others. Can’t think why.

Then we had Dr George Mann. At one time he was the associate director of the Framingham Study. Which remains the single most influential study on cardiovascular disease, ever. But…

But then he realised there was no relationship between dietary fat or ‘cholesteremia’ – as a high blood cholesterol was called at one time – and heart disease. He discovered this by using the conspiratorial activity called…research. He went to Africa to study the Masai. The men ate almost nothing but meat and drank blood and milk… yuk. As for heart disease, there was none.

Following these, and many other contradictory findings, he formed the Veritas society and edited the book ‘Coronary Heart Disease – the Dietary Sense and Nonsense.’ Of which I have one of the few remaining copies. It cost me fifty pounds…fifty pounds, can you believe it. The things I do for science.

At one point George Mann attempted to arrange a meeting of scientists who agreed that the diet-heart/cholesterol hypothesis was bunk. He ran into problems:

‘Many declined because they felt that participation would jeopardize their grants and perks or, sadder still, because they believe their academic positions would be threatened… when he tried to organize a conference he was told. ‘I believe you are right, and that the diet-heart hypothesis is wrong, but I cannot join you, for that would jeopardize my perks and funding.

As he went on to say: ‘Vast profits are made selling products with trumped up, dishonest health claims. Physicians are co-opted by the media and the “detail men” (salesmen) to prescribe worthless diets and dangerous drugs.’

In the book itself, Professor James McCormick stated:

‘Future generations will look back at this present preoccupation with cholesterol with the same mixture of horror and incredulity with which we now regard colonic irrigation, bleeding and purging.’

James McCormick was a GP and professor of community health at Trinity College Dublin. He was especially critical of health promotion and health screening.

As he once wrote. “Health promotion mixes the obvious and widely known with the questionable and unproven.”. Good man. He described himself, and a few colleagues, as ‘abominable no-men.’ A few brave souls who dared to question the inexorable drive to ever greater health promotion and screening.

Most people are unlikely to have heard of Mann, or McCormick, or the few other brave souls who did turn up to the conference – which was held forty years ago. But they are all heroes of mine. Shunned, de-funded and attacked – in no particular order. I know exactly how they feel.

I could give many more examples of those who have been obliterated. And I will, in later articles. But it is not just personal attacks that are used to underpin profitable ideas and keep science at bay. Scientists are paid directly to promote what are, in essence, corporate lies. I have written about this before:

‘Influential research that downplayed the role of sugar in heart disease in the 1960s was paid for by the sugar industry, according to a report released on Monday. With backing from a sugar lobby, scientists promoted dietary fat as the cause of coronary heart disease instead of sugar, according to a historical document review published in JAMA Internal Medicine.

Though the review is nearly 50 years old, it also showcases a decades-long battle by the sugar industry to counter the product’s negative health effects.

The findings come from documents recently found by a researcher at the University of San Francisco, which show that scientists at the Sugar Research Foundation (SRF), known today as the Sugar Association, paid scientists to do a 1967 literature review that overlooked the role of sugar in heart disease.’2

Just in case you think this sort of thing died out years ago, of course it did not. In the Sunday Times of April 23rd, 2017, this article appeared, entitled ‘Kellogg’s smothers health crisis in sugar – The cereals giant is funding studies that undermine official warnings on obesity.’ Just to choose a few paragraphs.

‘One of the food research organisations funded by Kellogg’s is the International Life Sciences Institute (ILSI). Last year if funded research in the Journal Annals of Internal Medicine that said the advice to cut sugar by Public Health England and other bodies such as the World Health Organisation could not be trusted.

The study, which claimed official guidance to cut sugar was based on “low quality evidence”, stated it had been funded by an ILSI technical committee. Only by searching elsewhere for a list of committee members did it become clear that this comprised 15 food firms, including Kellogg’s, Coca-Cola and Tate and Lyle.

In 2013 Kellogg’s funded British research that concluded “regular consumption of cereals might help children stay slimmer.” The study, published in the Journal Obesity Facts relied on evidence from 14 studies. Seven of those studies were funded by Kellogg’s and five were funded by the cereal company General Mills.’

Just one small area filled with corruption, corruption and yet more corruption. It is a swamp.

Those behind the attacks

When Barney Calman wrote his articles attacking me, Zoe Harcombe and Aseem Malhotra, I wasn’t really bothered about him. I knew he was simply the patsy who had been dressed up in armour, given a shiny new sword to hold, and kicked out of the castle gate to attack us on behalf of his masters.

‘You go get them, you brave seeker of the truth. Hack away. Sever a few limbs. We may enjoy a few more glasses of red wine before joining you. Can’t tell you exactly when my dear boy. But don’t worry, we have your back. Toodlepip.’

Unfortunately for Barney, to mix metaphors, he hadn’t the slightest idea that he had turned up at a gun fight with a knife. He clearly believed this was going to be a one-sided battle where his victims would put up little or no resistance. And if we did fight back, he had the great knights of the castle to back him up if needed. [Rule One, never trust the knights].

Maybe he really thought he had truth and justice on his side. I have no idea what he thought, and I don’t much care. Whatever his motivations, he set out to do as much damage to me/us as he possibly could. His aim was to destroy. He hacked and sliced about him with gay abandon. He clearly believed himself to be invincible, and untouchable.

Unfortunately for him, one good thing about going to court is that all the discussions leading up to the articles have to be revealed to the prosecution. This would expose all the background discussions.

As Barney stated in an e-mail of the 4th of Feb 2019 to a fellow Mail on Sunday employee:

‘Can you take a look at this – we’re planning a big takedown of statin deniers.’ This comes from the media and communications list.3

‘A big takedown’… It was rather more than that. Virtually every insult known to man was brought to bear. In case you think I am exaggerating about the sheer vitriolic nastiness of what he wrote, here are some sections from the judgement.

These outline what the Judge considered the articles said about us. A distillation of their intent, if you like. This is taken directly from the Judgement itself, words unedited:

‘….the direct effect of the publication of these knowingly false statements by the Claimant(s) was (a) to cause a very large number of people not to take prescribed statin medication; and (b) thereby to expose them to a serious risk of a heart attack or stroke causing illness, disability or death;

..and in consequence, each Claimant was rightly to be condemned as a pernicious liar, for whom there was a special place in hell, whose lies, deadly propaganda, insidious fake news, scare stories, and crackpot conspiracy theories, had recklessly caused a very large number of people, like Colin, for whom the proven benefits of taking statins were demonstrated by indisputable scientific evidence, to stop taking them risking needless deaths and causing harm on a scale that was worse than the infamous MMR vaccine scandal.’

‘…each Claimant had made false public statements, knowing that they were false.’

‘Put shortly, the Articles alleged that the Claimants had a venal* motive for their lies. This was one of the aspects that made them so deserving of contempt, and a “special place in hell”.4

Yes, according to the judge, Barney Calman stated that we lied, and that we knew were lying in order to make money – our ‘venal motive’. Our pernicious lies, deadly propaganda, fake news, scare stories and crackpot conspiracy theories caused needless deaths. For which we were fully deserving of contempt and a ‘special place in hell.’ That is the Judge’s summary of the article’s intent. And if you are going to suggest that is not what the articles actually said, you could find yourself in contempt of court.

Well, I don’t know about you. But where I come from that there’s ‘fighting talk.’

So, we fought, for five and a half years. Yes, obviously I wanted to clear my name, but I was also keenly interested in something else. Which was to reveal the ‘experts’ lurking in the background. Those who I believe represent the organ grinders to Barney Calman’s dancing monkey. To mix my metaphors once more.

Fortunately, the Judge ordered that all e-mails and WhatsApp messages, indeed everything, and everyone involved, would be made available to the public – should they ever wish to read such things. Nothing here is confidential. Which means I can publish all three thousand pages, give or take, should I so wish. Praise be.

And lo, the great knights from the castle hove into view. Of course, I already knew who they would be. They included the usual suspects from the University of Oxford. Professor Sir Rory Collins and Professor Colin Baigent were two of the leading lights, baying for our blood.

This is one message that Professor Sir Rory Collins sent to Barney Calman after the articles were published.3

Dear Barney

What a pleasure to see such a hard-hitting evidence-based article on fake news related to statins … and the page 2 article with Matt Hancock’s very direct comments was an unexpected bonus.

Best wishes.

Rory

But, but…but. There was nothing in the articles that could prove to be an ‘unexpected’ bonus for Rory. Because he played a considerable role in editing the articles. Below are a couple e-mails taken from the Court Disclosures. One page among several thousand.

[I intend to publish a great deal more, to make it entirely clear that there were a group of ‘experts’ working hard in the background to destroy us.]

Yes, the great knights were brought together to terminate us, or at least terminate our reputations. And to be fair to them, they did a damned good job. In addition, they all played a significant part in editing the articles. As the Judge commented on this issue:

‘Although they were not able to dictate what Mr Calman included in the Articles, they nevertheless had (and Mr Calman allowed them to have) a very significant (and in my judgment, undue) influence over the editorial process and the terms in which the Articles were ultimately published.’

Where was the money lurking behind this? Well, Professor Sir Rory Collins and Professor Colin Baigent run the Clinical Trial Service Unit in Oxford. Which is, essentially, a contract clinical trial research organization.

It now sits under the banner of Oxford Population Health… in some complicated way, no doubt designed to throw people off the scent. The funding from Industry can be seen here 5. Under the heading ‘Independence of Research.’Hollow laugh.

I added up the funding this unit has received over the last nineteen years (although the CTSU has been around longer than that). After checking a few times, the figure I arrived at was £311,549,300.00p [See Appendix]. This is just over three hundred million pounds (~$400m).

Yes, Professor Sir Rory Colin and Professor Colin Baigent of the University of Oxford run an organisation that has received hundreds of millions in sponsorship. The vast bulk of which comes from the pharmaceutical industry, and the vast bulk of that is used to study drugs designed to lower cholesterol.

This, of course, has not had the slightest influence on anything they say or do with regard to statins, other cholesterol lowering agents, or the cholesterol hypothesis. How could anyone possibly think such a thing of the great knights in their mighty Oxfordian Castle. These eminent figures. Sir this, Professor that, Professor the other. The great and the good.

Of course, they are all desperately insistent that industry funding does not, indeed cannot, have the slightest influence on their research, or what they way. After all, no-one working there receives a penny directly from industry. Emphasis on the word, directly.

‘Research at Oxford Population Health is funded in a number of ways. Much of the funding is peer-reviewed*, which involves other experts independently assessing the Department’s planned research. Such support is provided by a number of government institutions and charities, including the Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, British Heart Foundation, Cancer Research UK and Wellcome. In addition, funding is obtained from healthcare companies, particularly for large studies of the treatment and prevention of disease. The department’s research is conducted independently of the funding sources**.5

*How do you peer-review funding, exactly? What does this mean? It is simply gibberish made up to make all the commercial funding seem above board. This is not just pharmaceutical company money. It is ‘peer-reviewed’ pharmaceutical company money. Who did the peer-review. A bunch of hedge fund managers? Rory Collins’ bank manager?

**So, a pharmaceutical company provides forty million quid to study their drug in heart disease, and Oxford Population Health (OPH) then heads off to use their money to study another drug in cancer research? I don’t think so. And OPH have absolutely no discussions with the company about the study, at all? I have read some utter bollocks in my life. This sits very near the top.

Maybe I should hire someone to go down and find out where Professor Sir Rory Collins lives and how much his house is worth. And spy on him to see who he hangs out with and suchlike. It would only be fair, as this is what the Mail on Sunday did to me.

Here is an e-mail to Barney Calman from Mark Wood. Barney had asked Wood to find out details about me. Where I lived, how much my house was worth, where I got my income from. I include part of the -email here. [I blanked out my address, as I think that is getting a little close to home, so to speak].

—————————————————————————————————————————–

From: mark wood

Sent: Wed, 13 Feb 2019 18:55:43

To: barney.calman@mailonsunday.co.uk

Subject: statin deniers

Sensitivity: Normal

Hi Barney

Below are some details on your three statin deniers which I’ve been able to collate so far. Got home addresses for all three, and Company House records on any directorships they have or have previously held.

I appreciate the thrust of this is to try and discover how they are benefitting financially from their anti-statin stance…

Dr Malcolm Kendrick

DoB: 17/09/1958 (Age 60)

On his blog describes himself as ‘a GP living in Macclesfield, having graduated from Aberdeen medical school many moons ago.’

He lives in executive detached house at

Property Location:

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

Property Description:

Detached

Council Tax Band: G

Average Property Value:

£ 733,709

Socio – Demographic Code:

Business Class – Alpha Territory

Property Sale Date:

27/09/1996

Property Sale Price:

£ 217,000

Author of: The Great Cholesterol Con…etc. [There is more].

——————————————————————————————————————————-

No doubt what they really wanted a picture of me lolling about in my luxury apartment in St Tropez, quaffing champagne and laughing uproariously in the company of Andrew Wakefield, whilst lighting a cigar with a fifty-pound note. I wish.

My wife calculated that, given the hours I spent working in my study on research and writing, I have earned about £5/hour from book sales, and the occasional lecture. I think that may be overly optimistic.

Next. A roll call of previous attacks on the ‘statin deniers.’ Then, what should we do about the ever-increasing corruption of medical research? Pitchforks at the ready. Burning torches will be provided to all those who turn up.

1: http://www.telegraph.co.uk/lifestyle/wellbeing/diet/10634081/John-Yudkin-the-man-who-tried-to-warn-us-about-sugar.html

2: https://www.theguardian.com/society/2016/sep/12/sugar-industry-paid-research-heart-disease-jama-report

3: KINGS BENCH DIVISION IN THE HIGH COURT Claim Nos. QB-2020-000799 QB-2020-000801

4: Neutral Citation Number: [2024] EWHC 1523 (KB) Case No: QB-2020-000799 QB-2020-000801

5: https://www.ndph.ox.ac.uk/about/independence-of-research

APPENDIX ONE – FUNDING

Received by the Nuffield Department of Population Health, University of Oxford, since 2005

ACE trial of acarbose (2008-2017)

Bayer: £135K *

ASCEND trial of aspirin and fish oils (2004-2017)

Abbott/Solvay/Mylan: £2.1M plus drug supply Bayer: £1.8M plus drug supply

ASCEND PLUS (2021 – ongoing)

Novo Nordisk A/S: £39.4M

Assessing the potential for SenseCam to fight the current global health crises of increasing obesity and physical inactivity (2010-2013)

Microsoft: £69K

ATLAS trial of tamoxifen duration (1997-2018)

AstraZeneca: £1.0M plus drug supply

BEST-D pilot trial of vitamin D (2012-2014)

Tishcon: free drug supply only

Big Data Institute (2018-2021)

Novartis Pharma AG Switzerland: £272K

Can wearables improve the prediction of all-cause mortality, cardiovascular disease, and cancer in UK Biobank? (2022-25)

Swiss Reinsurance Company: £645K

China Kadoorie Biobank (2002-ongoing)

AstraZeneca: $300K

Bayer AG: £300K

GlaxoSmithKline: £3.6M

Merck: £200K

Novo Nordisk A/S: £341k

Development of digital biomarkers for dementia (2016-2022)

Eli Lilly and Company USA: £600K

Development of digital biomarkers for dementia (2016-2022)

Roche: £600K

Diabetic Peripheral Neuropathy Treatment with Dorsal Root Ganglion Stimulation a Randomised Controlled Trial (2018-2020)

St Jude Medical Europe Inc: £52K

Doctor Referral of Overweight People to Low Energy Treatments (2015-2020)

Cambridge Weight Plan Ltd: £35K

DYNAMIC CONSENT USCF (2015-17)

Oxford University Innovation Ltd: £28K

Economic burden of malignant neoplasms in the EU (2011-2012)

Pfizer: £36.5K

Elinogrel feasibility trial (2010-2011)

Novartis: £500K

EMPA-KIDNEY (2017-ongoing)

Boehringer Ingelheim: £106.3M

Establishing Fuwai-Oxford research centre (2010-ongoing)

Merck: £1.1M

Estimating acceptable non-inferiority margins for antibiotic stewardship interventions using discrete choice experiments (2021-2023)

Mars Petcare UK: £25k

EXSCEL trial of exenatide (2009-2017)

Amylin: £473K *

FOXFIRE trial of chemotherapy with or without radioembolisation for bowel cancer that has spread to the liver (2009-2017)

Sirtex: £228K *

Genomic Data Working Group (2020-2025)

Regeneron Pharmaceuticals Inc: £107K

Heart Protection Study follow-up studies (2003-2010)

Merck: £1.2M

GlaxoSmithKline: $400K

Liposcience: £50K

HPS2-THRIVE trial of niacin/laropiprant (2005-2015)

Merck: £53M plus drug supply

HPS3/TIMI55-REVEAL trial of anacetrapib (2010-2022)

Merck: £108M plus drug supply

HPS 4/TIMI 65 – ORION-4 (2017-ongoing)

Novartis Pharma AG Switzerland: £73.7M

HPS 5/ORION-17 (2020-ongoing)

Novartis Pharma AG Switzerland: £1M

Integration of medical imaging and genetic data using machine learning for identification of micro and macro vascular disease targets (2021 – ongoing)

Novo Nordisk A/S: £1.2M

Large-scale multi-omics assays in China Kadoorie Biobank (2020 – 2023)

Bayer AG: £1.58M

LENS trial in Non-proliferative retinopathy in Scotland (2016-2022)

Mylan: free drug supply only

MaatHRI Project (Ultromics) (2018-2022)

Ultromics Limited: £79K

Measuring sleep characteristics using machine learning in wearable datasets (2020-2023)

Novo Nordisk A/S: £135K

Mexico City Prospective Study (2021 – ongoing)

AstraZeneca UK Ltd: £1.81M

Regeneron Pharmaceuticals Inc: £1.78M

NAVIGATOR trial health economics analysis (2013-2014)

Novartis: £15K *

Next generation sequencing analysis – a clinical study (2011-2014)

Life Technologies: £125K *

Non-invasive rapid assessment of liver disease using magnetic resonance (2016-2019)

Perspectum Diagnostics: £273K *

Novo-Nordisk Postdoctoral Fellowship Programme (2021-2023)

Novo Nordisk A/S: £221.3K

Observational study of a multi-cancer early detection test (2021-2023)

Grail Bio UK Ltd: £101k

Oxford-Janssen Human Genomics Fellowship Programme (2020 – ongoing)

Janssen Biotech: 1.22M

Oxford Participation & Activities Questionnaire (Ox-PAQ) Phase 2 Study (2014-2017)

Actelion: £58K

OxPod (2021-27)

Podium Analytics: £75K

Pandemic Science Institute Investigator Allowance (2022-23)

AstraZeneca UK Ltd £5k

Pharmacogenomic analysis of the Heart Protection Study using a CAD polygenic risk score (2020 – 2025)

Regeneron Pharmaceuticals Inc: £143K

PROCARDIS genetic study (1998-2011)

AstraZeneca: £1.7M

SEARCH trial of simvastatin dose (1997-2010)

Merck: £22.7M plus drug supply

SHARP trial of simvasatin/ezetimibe (2002-2013)

Merck/Schering: £40M plus drug supply

SHARP3 (2022-23)

Boehringer Ingelheim: £1.8M

Small open reading frames in drug discovery: from genetics to mechanisms to new therapies (2022-24)

Novo Nordisk A/S: £49K

STICS trial of rosuvastatin (2011-2014)

AstraZeneca: $100K

TECOS Trial Evaluating Cardiovascular Outcomes with Sitagliptin (2008–2022)

Merck & Co Inc: £140k *

Therapies for Influenza (2019-23)

Oxon Epidemiology Limited: £77K

The Transthyretin (ATTR) Amyloidosis Questionnaire (ATTRAQ) (2020-2022)

Pfizer: £147K

Thrombotic Microangiopathy associated Pregnancy Acute Kidney Injury in the United Kingdom: Incidence, Outcomes and Risk Factors (2021 – 2022)

Alexion Pharmaceuticals Inc: £32K

UK-HARP-III pilot study of LCZ696 (2013–2018)

Novartis: £2.6M

Using data from wearable devices to identify novel targets for cardiometabolic disease (obesity, T2DM, NAFLD, & heart failure) (2021 – 2024)

Novo Nordisk A/S: 1.25M

Using Whole Genome Sequencing Datasets to Identify Novel Disease Genes and Mechanisms (2020 – 2022)

GlaxoSmithKline Research & Development £359K

3-C trial of transplant rejection (2009-2017)

Pfizer: £530K

Novartis: £350K

* Funds received by the department’s Health Economics Research Centre for trials led by other Oxford University departments or Institutions.