The ink has barely dried on the Iona Heath independent panel report into the demands from Rory Collins that two papers, which dared to reference another peer-reviewed paper that mentioned statins having side effects, be retracted. Heath’s panel very sensibly concluded that the papers should not be withdrawn and the panel admonished Collins for trying to buck the open and transparent BMJ system for handling such issues.
Collins complained about the articles by email to Fiona Godlee, editor of the BMJ, at the end of October 2013. He insisted on a private meeting, which was held in December 2013. Collins was asked by Godlee to express his concerns in a rapid response to the BMJ or an article – as is the normal process for open debate on matters of wide importance. Collins never did this. Instead he continued to try to use private channels to censor that which he did not want published.
The new stunt
On September 18th I received an email forwarded from a doctor specialising in heart disease.
Date: Thu, 18 Sep 2014 10:46:50 +0100
Subject: BCS Statins Survey<
IMPORTANT: STATIN SURVEY
The British Cardiovascular Society is keen to know of any potential adverse effect on cardiovascular disease prevention which may have resulted from recent media stories and articles such as those published in the BMJ (1,2) and in an open letter to NICE (3).
We would be grateful if members would complete this short survey. Your response will be anonymous and the link below is unique to you allowing you to complete the survey once only.
The survey closes on 30th September and results will be made available subsequently on the BCS Website and in the BCS newswire.
(1) Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013; DOI:10.1136/bmj.f6123.
(2) Malhotra A. Saturated fat is not the major issue. BMJ 2013; DOI:10.1136/bmj.f6340
PLEASE CLICK HERE TO COMPLETE THE SURVEY
The two papers referenced just happen to be the ones that Collins didn’t like. The ones that he wanted removed from the BMJ altogether. Having failed, a society that you have probably never heard of, The British Cardiovascular Society, is trying to stir up trouble to smear the authors of these papers and the letter to NICE.
The end in mind
This is not an open and genuine survey – honestly interested in evidence based medicine. This is a loaded and leading survey with a clear end in mind. The British Cardiovascular Society (BCS) are not interested in any positive outcomes from the publicity surrounding Collins vs. The BMJ. They are not interested in Mrs Jones, who decided to come off statins, having heard about the side effects, who now finds that she can walk again. They don’t care about Mr Smith whose libido may have come back – along with his mind, mood and memory. They are only interested in adverse effects and anecdotes about adverse effects.
As Dr Malcolm Kendrick explained here: “Now, why would they be doing this? I do not think it is that difficult to work it out. The BCS is trying to gather evidence that the articles by Abramson, Malhotra and the open letter to NICE have caused harm to patients. They will be asking their members if they know of people who have stopped taking statins, or who will not go on statins, because of what they have read in the BMJ and suchlike.
Once they have done this, they will then extrapolate the raw figures to the entire population of the UK, in order to claim that ‘Thousands have died.’ Abramson will be attacked, along with Malhotra and the BMJ. I will get a few attacks as well for drafting the letter to NICE. This is a very unsubtle variation of the ‘You’re killing my patients’ tactic which is regularly used to silence any who dares criticise currently medical opinion.”
Who are the British Cardiovascular Society?
The May 2013 annual report tells us that “The British Cardiovascular Society is dedicated to the promotion of cardiovascular health.” (Download from this page).
The web site thanks its main partner: “The British Cardiovascular Society (BCS) is grateful to the generous support of its Industry Partner, Bayer PLC.” I bet it is.
The office address is 9 Fitzroy Square, London, W1T 5HW. Remember this.
I emailed BCS on September 24 to ask:
On your web site you share that “The British Cardiovascular Society (BCS) is grateful to the generous support of its Industry Partner, Bayer PLC.”
Please can you help with the following:
– Do any other pharmaceutical companies provide funding, directly or indirectly to the BCS?
- How much does Bayer donate?
I have had no response.
A web of conflict
I started to look at the “Officers of the Society” for individual conflicts of interest and I started to recognise some names from previous conflicts of interest research. What emerged was a glimpse into a web of conflict involving a large number of self created organisations/charities, in the field of heart disease, with connections to and funding from pharmaceutical companies. I suspect that I have barely scratched the surface.
There are individual organisations, such as the BCS and/or Heart UK (the ultimate voice piece of the statin industry) and then a representative from each of them meet together as a body called the Joint British Societies. The president of BCS, Iain Simpson, is a member of the Joint British Societies (JBS). He declares no conflicts of interest at JBS. His thought process must go something like – I’m at JBS representing BCS and so I don’t have to declare the fact that BCS is funded by Bayer? No, that doesn’t work for me either.
The Joint British Societies
The representatives from other organisations, which form the JBS, are as follows. Where Declarations Of Interest (DOI) have been made, they derive from this document, which is dated March 2014. Where declarations have not been made, I have searched for them and referenced the source:
Prof John Deanfield Represents the British Heart Foundation and claims “No DOI”, despite the fact that the BHF is in bed with Flora margarine.
Dr Susan Connolly Declares “Travel grant and advisory board for Merck Sharp Dohm”.
Prof Patrick Doherty Represents BACPR – the British Association for Cardiovascular Prevention & Rehabilitation. Despite being supported by the BHF (Flora) and being “an affiliated group of the BCS” (Bayer), Doherty declared “no DOI.” The address for the BACPR is also 9 Fitzroy Square, London, W1T 5HW.
Prof Keith Fox Declares funding from: “British Heart Foundation; Medical Research Council; Wellcome Trust” and “Additional Grant Funding and honoraria: Sanofi Aventis, Lilly, Bayer/Janssen, Astra Zeneca, GSK.”
Prof Richard Hobbs Declares consultation and speaking engagements with BI, Bayer, BMS/Pfizer, Medtronic all in non-prevention of CVD areas.
Prof Aroon Hingorani Declares that he is on the advisory board for Roche.
Prof Steve Jackson Co-representing the British Hypertension Society, one of the British Cardiovascular Society affiliates. Jackson declared “no DOI.” Really? Daiichi-Sankyo, Boston Scientific and Omron Healthcare are friends of the society.
Dr Catriona Jennings Represents another of the British Cardiovascular Society affiliates: British Association for Nursing in Cardiovascular Care (BANCC). She is President of this society, which also has 9 Fitzroy Square as its address. She states “No DOI.” Pfizer and Astra Zeneca are declared here, however.
Prof John Potter Declares that he has served on the Advisory Boards of several Pharma companies including Merck Sharp Dohm and Bayer, from whom he has received honoraria.
Prof Naveed Sattar Has consulted for: Amgen, Sanofi, Astrazeneca, BMS, Roche, UCB and Boehringer Ingelheim. Speaker Bureau for Lilly, Merck Sharp Dohm.
Dr Fran Sivers Has worked with Unilever on HeartAge and has advised a Medical Charity called Dipex.
Prof David Spiegelhalter Claimed no DOI. Yet on his own web page he states “I have acted as a paid statistical consultant to a variety of organisations, including the Healthcare Commission, World Anti-Doping Agency, Novartis, and GlaxoSmithKline.”
Prof Gerard Stansby Claimed no DOI. This page clarifies “GS has received research funding and fees for speaking and chairing meetings from a number of pharmaceutical companies.”
Dr Paul Stevens Claimed “No DOI”. In CG182 here, Appendix D has the declarations of interest for this NICE development group. Stevens are listed as “Honoraria for lectures and attendance at international meetings for Ortho Biotech, Bayer, Amgen, Pfizer and Hoffman La Roche and a research grant from Roche UK for developing an expert system for the management of chronic kidney disease.”
Prof Peter Weissberg Represents the British Heart Foundation and claims “No DOI.” Not even Flora?
Dr David Wheeler Declared consultancy Fee/Honoraria from: Amgen, Janssen, Astellas, Baxter, Merck Sharp Dohm, Vifor Pharma, Otsuka, Fresenius, Shire Research grants: Genzyme, AstraZeneca.
Prof Bryan Williams Claimed “No DOI.” He’s Chair of Medicine at the Institute of Cardiovascular Sciences. Can you imagine that being free from pharma funding? Here’s a throw away comment on his bio page “He holds grant awards from the NIHR, MRC and the BHF as well as collaborative grants with industry.”
Dr Peter Winocour Served on clinical expert advisory boards supported by Novo Nordisk, BI, Sanofi Aventis, Merck Sharp Dohm, and received support to attend meetings from Novo Nordisk and BI.
Prof David Wood Declared honoraria for Advisory Boards (Merck, Sharp & Dohme) and invited lectures (including AstraZeneca) Unrestricted research grants to the European Society of Cardiology from several pharmaceutical companies (AstraZeneca, Bristol-Myers Squibb/ Emea Sarl, GlaxoSmithKline, F. Hoffman-La Roche, and Merck, Sharp & Dohme).
There are two more members, whom we will come to shortly.
The position of the JBS
The Joint British Societies – when declarations are fully made – reads like a pretty comprehensive representation of the statin making pharmaceutical industry. Sure enough, this is the Joint British Societies view on Lipid lowering therapy:
* Intensive statin therapy is recommended in all patients following MI, in the absence of a contraindication or intolerance, irrespective of initial cholesterol values.
* Statins should be prescribed with a ‘lower is better’ approach to achieve values of at least <2.5mmol/L for non-HDL-c (equivalent to <1.8mmol/L for LDL-c).
At the end of this article, the Competing interests are declared as follows: “There are no significant competing interests.”
Did you spot the address for correspondence for the Heart journal? Yes – Heart is the publication of the British Cardiovascular Society, 9 Fitzroy Square, London, W1T 5HW.
The Connection to the NICE statin guidelines.
My newsletter back in February 2014 shared that the Guideline Development Group (GDG) had serious conflicts of interests, which should have led to the exclusion of 8 out of 12 panel members from the group. NICE showed that it really couldn’t care less about this and went ahead with their ‘everyone should be on statins‘ advice.
Two of the members of the Joint British Societies were on the NICE statin GDG:
Alan Rees as a member of the JBS declared “Advisory Board and talks for: Aegerion, AstraZeneca, Merck Sharp Dohm, Sanofi-Aventis, Pfizer, BMS and Novo Nordisk.”
Dermot Neely declared that he was representing Heart UK and that he had “No DOI”. This whole DOI thing is getting beyond a joke. These are the partners of Heart UK – how are these not conflicts of interest? The declaration for the NICE GDG also included “In the past 12 months I have participated in one-off advisory boards for pharmaceutical companies developing lipids modifying therapy for specialist use in poorly treatment responsive and/or severe inherited lipids disorders, including Roche Pharma (dalcetrapib), Genzyme (mipomersen), and Aegerion (lomitapide).” Not relevant?
What started as research into the British Cardiovascular Society, for a leading and loaded survey, with a clear and underhand end in mind, ended up as a discovery of a web of organisations, charities and affiliates with pharmaceutical funding, shared addresses and what seems to be an extensive network of statin pushers.
I can think of two reasons:
1) It gives the appearance of a number of ‘respectable’ organisations/charities all believing in the same thing. In this case that “Intensive statin therapy” should be enforced with a “‘lower is better’ approach.”
2) It creates a ‘once removed’ structure, so that the pretty much universally conflicted members of the Joint British Societies group seem to think that it’s OK that they put their names to a “lower is better” policy as members of the JBS and then ‘forget’ that they are funded by the companies who will benefit from this exact policy.
Conflict is conflict. I often say that liver is the most nutritious food on the planet, because that’s what nutrient analysis shows. If I received any funding whatsoever from a liver association/organisation/producer – you should know about it. And it should not matter which meeting I am attending one day or the next – the liver conflict would prevail and should always be declared. Given my abhorrence towards conflicts of interest you won’t be surprised to know that I have received no such payments from any organisation and never will I sell my soul in this way. It’s just disgraceful that this position is not shared by people in positions of power and influence.
I got a call at 8.30am today (Sept 11th 2014) to ask if I’d go on Radio 5 live between 10-11am to talk about ‘the fat shaming’ story. What fat shaming story?!
The Daily Mail headline was “Telling someone they’re fat makes them eat MORE: People made to feel guilty about their size are six times as likely to become obese.” The Telegraph went with “Fat shaming ‘makes people eat more rather than less‘”. The Guardian got a teeny bit more accurate, but not much, with “‘Fat shaming’ does not help people lose weight, study finds.”
Here’s the link to the original study (Dr Jackson very kindly whizzed me over a copy this am).
The article & press release
Please note from the outset the title of the study and the objective set out by the researchers.
Title: “Perceived weight discrimination and changes in weight, waist circumference and weight status” (my emphasis).
Objective: “To examine associations between perceived weight discrimination and changes in weight, waist circumference and weight status” (my emphasis again).
The press release was undeserving of an academic study – the usual headline grabbing, sensationalist, misleading at best and disingenuous at worst, which we have sadly come to expect. “‘Fat shaming’ doesn’t encourage weight loss.”
The study was not an intervention. It was an observational study using the English Longitudinal Study of Ageing (ELSA) for data. As the ELSA is a study of people aged 50 years or older and as the initial sample of participants was drawn from responses to the Health Survey for England (HSE) in 1998, 1999, and 2001, this is not a study of the general adult population. This was a study of people with an average age of 66 at baseline.
2,944 people were studied over 4 years.They had BMI and waist circumference recorded in 2008-09 and 2012-13 and they were asked for their perceived weight discrimination in 2010-2011 in response to five (subjective) questions.
‘In your day-to-day life, how often have any of the following things happened to you:
1) you are treated with less respect or courtesy;
2) you receive poorer service than other people in restaurants and stores;
3) people act as if they think you are not clever;
4) you are threatened or harassed;
5) you receive poorer service or treatment than other people from doctors or hospitals.
On the basis of these questions, 5% of participants perceived that they had experienced weight discrimination. The study has just become a study of 150 people perceiving discrimination against a control group of 2,794. This is not a study of weight discrimination among 2,944 people.
The perception of weight discrimination ranged from 0.7% in the normal weight category to 35.9% of those classed morbidly obese. Men and women reported similar levels.
This is interesting. I see two shop assistants chatting rather than helping me and I just think that they’re rude. If I were morbidly obese, would I perceive that they were treating me differently because of my size?
Weight: Those who perceived weight discrimination started the study almost 22kg heavier than those who didn’t.
Those who reported weight discrimination gained, on average, wait for it, 0.95kg – not even 1 kilogram! During a four year study.
Those who didn’t report weight discrimination lost, on average, wait for it 0.71kg – that’s about how much dark chocolate I eat in a week. During a four year study.
Another interesting thing – which was completely swept under the carpet – check figure 1 in the paper. There were 6 categories that were studied: normal weight at baseline; overweight at baseline; obese (BMI 30 or higher); obese class I (BMI 30-34.9); obese class II (BMI 35-39.9); and obese class III (BMI 40 or higher). The only groups that gained during the study were the normal weight and overweight people who perceived weight discrimination. All the obese categories – whether they perceived discrimination or not – lost weight on average during the study and the normal/overweight people who did not perceive discrimination lost weight or experienced no change.
Table 1 tells us that there were 7 normal weight people who perceived weight discrimination and 15 overweight people who perceived weight discrimination. Today’s world-wide nonsense is thus based on the perceptions and negligible weight change for 22 people.
From the numbers in the paper, I calculate that the Daily Mail headline about “six times more likely to become obese” derives from the following… The paper reports that “Among participants who were not obese at baseline, perceived weight discrimination was associated with higher odds of becoming obese (25.2 vs. 4.4% OR=6.67).” There were only 22 participants who were not obese at baseline who perceived weight discrimination. To achieve 25.2%, 5.5/22 of these became obese (not sure how). There were 2,102 participants who were not obese at baseline who didn’t perceive weight discrimination. To achieve 4.4%, 92.5/2,102 became obese. So, 5.5 people became obese in one group and 92.5 in the other group. The significant thing that differs is the group size. A couple of people makes a big difference in the group with 22 people. Plus – two thirds of the small group were already overweight, compared with half the large group. It is far more likely that overweight people became obese than normal weight people – in a four year period – and thus the group of 22 had another factor stacked against them. Do you think 5 people justify the Daily Mail headline?
Waist circumference: Those who perceived weight discrimination started the study with an almost 20cm greater waist circumference than those who didn’t.
Those who reported weight discrimination gained, on average, wait for it, 0.72cm – not even a centimeter! During a four year study.
Those who didn’t report weight discrimination lost, on average, wait for it 0.4cm – I doubt you could measure my waist to a 0.4cm degree of accuracy from one day to the next. Again, during a four year study.
I mean – seriously journos – do you ever look beyond the press release?!
Association, not causation.
AND this is – as always – association not causation.
Dear Daily Mail, we have no evidence that anyone was told that they were fat, just that they perceived being treated differently.
Dear Daily Mail & Telegraph, we have no evidence that people ate more. We do have evidence that obese people lost weight whatever their perception of weight discrimination. Maybe they ate less? Maybe they ate more, but better? Who knows.
Dear The Guardian, obese people did lose weight, whether ‘fat shamed’ or not.
Nothing MADE 150 people do anything. There was an association between gaining less than a kilo and losing less than a kilo and the subjective answers to 5 questions in 22 normal weight/overweight people and not even this association in 128 others.
I have been told by many people of all ages, male and female, about the abuse experienced by obese people – particularly morbidly obese people. During the Radio 5 live discussion, “Zanita” made me gasp out loud when she shared comments that had been directed towards her. “Jenny” had been insulted by someone close to her. I’ve just been on BBC Radio Tees and Mike Parr shared comments made to him. Such behaviour is completely unacceptable, rude and ignorant.
Insulting people for any personal attribute – gender, age, diversity, size, attire, anything – is gross human behaviour and it says way more about the abuser by a margin that the abused. I think that people know if they need to lose weight. I know that they want to lose weight. I believe that our current eat less/do more advice sets them up to fail. I think that food is addictive and that obesity is a complex problem, which no insult or abuse is going to help.
BUT – a bag of sugar either way affecting 22 people in a study who perceived that they had been treated differently between two weigh-ins four years apart. Really?!
On September 2nd 2014 a story broke in the field of diet and nutrition, but it barely made it across the pond. The New York Times headline was “A call for a low carb diet that embraces fat.” The Huffington Post covered the story, but didn’t devote a whole article to it. Instead they combined the findings of this study with another to report “What can we really learn from that low-fat vs. low-carb study?”
The BBC ignored it. The Mail did an on-line only piece “Time to throw out the bread! A low-carb diet IS the most effective way to lose weight – and it cuts the risk of heart disease, too.” Great headline, but you wouldn’t have come across the article by chance. I had to do a very specific search on the mail site to see if they had covered it. Similarly the Guardian had an on-line story “Low-Carbohydrate Diet Protects Against Heart Disease Study Shows.”
This is the link to the original article “Effects of low-carbohydrate and low-fat diets.” Dr Michael Eades has very kindly dropped it in his box for you to be able to see the full article.
Start, as usual, with any conflicts of interest. The study was funded by the National Institutes of Health, which is very interesting in itself. It’s the first study I’ve seen funded by a public body to review the effect of low-carb diets, let alone as compared to low-fat diets – the latter typifying public health advice. There is a full conflict of interest form, covering all authors involved in the study here. It is unusually and refreshingly completely void of any conflicts whatsoever. Oh to find a drug or food item study so genuinely independent.
The study was simple in design and meticulous in execution. Many of the medical site reviews of the study detailed and/or complimented the care that had been taken to make the trial as controlled as possible.
The study involved 148 men and women without cardiovascular disease or diabetes. The men and women were aged 22 to 75 years and had a BMI of between 30 and 45, so that they had sufficient weight to lose over the study period. The participants were recruited from the general public through open adverts. This generated more response from females than males, resulting in 89% of the subjects being female. The study was undertaken in New Orleans, Louisiana. 51% of the participants were black, 45% were white and the remainder were Asian and Hispanic.
73 of the participants were randomly allocated to the low-fat diet and 75 were randomly allocated to the low-carb diet. Table 1 in the paper shows the baseline characteristics of the participants. This is where we can check that the randomisation ‘has worked’ and we are equally like to have similar numbers of females in each diet group, similar numbers of different ethnic origins, similar starting weights and so on. The low-fat group were a couple of years older than the low-carb group and they were 1.6kg heavier on average (i.e. more weight to lose), but, Table 1 overall is reassuring that the groups started off from a very similar baseline.
The study noted that there have been very few attempts to study low-carbohydrate diets and none had ticked two important criteria of 1) actually being a low-carb diet and 2) studying a diverse population. The Gary Foster (2003) study did compare an actual low-carb diet (Atkins) to a low-fat (government advice) diet, but this did not involve a diverse/carefully randomised population. This study, covered in the BBC Horizon programme about The Atkins Diet, concluded that Atkins was better for weight loss and cholesterol measures. The usual attempt to study a ‘low-carb’ diet has involved carb intake in the 100-200g range. That’s a high-carb diet to the low-carb world!
This was different. The low-carb diet group target was less than 40g of carbohydrate a day. The low-fat diet group target was less than 30% of daily energy intake from total fat and less than 7% from saturated fat – model government advice therefore. I emphasised the word target because the discussions on-line about the study didn’t pick up the actual intake reported in the paper.
Table 2 reported the actual intakes of carbohydrate and fat for the two groups:
The low-carb group were supposed to consume <40g carb per day. They did in fact consume, on average: 97g carbohydrate/day at 3 months; 93g/day at 6 months and 127g/day at 12 months. The low-carb group thus substantially missed their targets.
The low-fat group, in contrast, did hit their total fat targets (they recorded saturated fat intake of between 8-9% during the study). They were supposed to consume less than 30% of their daily intake from fat and they achieved this: 27.5% at 3 months; 27.9% at 6 months and 29.8% at 12 months.
The researchers reported that 5 people dropped out of the low-fat group and 5 people dropped out of the low-carb group after 3 months. By the end of the study (at 12 months), 13 people in total had dropped out of the low-fat group and 15 had dropped out of the low-carb group. That was an 18% drop out in the low-fat group and a 20% drop out in the low-carb group. That’s a reasonably low drop out rate for a diet study and a number dropped out due to life stressors and/or pregnancy – understandable with a largely female group 22 years old and above.
The results fell into two main areas: weight and what the researchers called “cardiovascular risk factors.” One of these I value (weight), the other I don’t (cardiovascular risk factors – apart from to wave at people who do value it).
Weight: To quote verbatim from the study: “Weight loss was greater in the low-carbohydrate group than in the low-fat group at 3, 6, and 12 months.”
The main results are worth capturing in a little table (this is an extract from Table 3 in the paper).
|Body weight (kg):
|- at 3 mths
|- at 6 mths
|- at 12 mths
|Lean mass (%):
|- at 3 mths
|- at 6 mths
|- at 12 mths
|Fat mass (%):
|- at 3 mths
|- at 6 mths
|- at 12 mths
This tells us many interesting things:
1) As the researchers reported, weight loss was greater in the low-carb group at 3, 6 and 12 months – at least double at all three checks. This was despite the fact that the low-fat group achieved their dietary target of <30% fat and the low-carb group did not achieve their target of <40g carb a day – not even close.
2) Lean mass increased more, at every checkpoint, with the low-carb group.
3) Fat mass decreased more, at every checkpoint, with the low-carb group.
4) Even with the low-carb group missing the 40g/day target quite substantially, this group continued to have good results for weight, lean mass and fat mass at 12 months. Notice the low-fat group displaying the classic 6 month turnaround – with regain following. This was clearly illustrated by Marion Franz’s 2007 review of 80 studies involving 26,455 people. The classic graph from this study can be seen here. By 12 months, the low-fat group had regained 50% of the weight loss at 3 months and started to decrease lean mass and increase fat mass.
5) Perhaps most interesting of all – this study disproves the calorie theory (not that any study has ever proven the calorie theory – every study proves it wrong). The low-fat group were consuming, on average, 2,034 calories at base line and the low-carb group were consuming 1,998 on average. At 3 months, these averages had dropped to 1,418 and 1,258. At 6 months, these averages were 1,481 and 1,324. At 12 months, these averages were 1,527 and 1,448.
I’ve calculated what the 3,500 calorie theory says each group should have lost and it works out as follows:
– The low-fat group should have been 7.3 kilograms (multiply by 2.2 for an approximate conversion to pounds) lower at 3 months; 13.9 kg lower at 6 months and 25.9 kg lower at 12 months. They were, in fact, 1.8 kg lower at 12 months.
– The low-carb group should have been 8.8 kilograms lower at 3 months; 16.8 kg lower at 6 months and 29.8 kg lower at 12 months. They were, in fact, 5.3 kg lower at 12 months.
Remember that the calorie theorists say that low-carb diets only work because people eat less. Both groups did eat fewer calories, but the calorie theory was as ridiculously inaccurate as it always is.
The saddest finding for me, working in the field of obesity, was how little both groups lost, on average, over the course of a year with heavily supported and well monitored conditions. There was no mention of real or processed food in the study, so continuance of processed food in both groups may have hindered weight loss. I would also have loved to see the results for a group that actually achieved the 40g/day carbohydrate intake target, as this could have been impressive. As I find, and so do many others in the world of real food/managed carb, results can be substantially better than 5 kilograms a year.
Cardiovascular risk factors: I will report these rather than discuss them because, as people who know me will know, I have no time whatsoever for the notion that cholesterol is a risk factor in anything. It requires one to assume that the body makes cholesterol to kill the host – quite possibly the most absurd assumption that one can hold. Notwithstanding this, as most of the medical world is obsessed with total cholesterol and the lipoproteins LDL and HDL (while thinking that these are bad and good cholesterol and not lipoproteins ha ha), here are the results from the cholesterol jury:
At 6 months (comparing the period in which the low-carb group were at least below 100g/day):
– The low-fat group had higher total cholesterol, the low-carb group had lower total cholesterol.
– The low-fat group had higher LDL, the low-carb group had lower LDL.
– The low-fat group had lower HDL at 3 months and no change at 6 months, the low-carb group had higher HDL at both checkpoints.
– The low-fat group had higher triglycerides at 3 months and virtually no change at 6 months, the low-carb group had lower triglycerides at both checkpoints.
The only good thing about all this is that people who believe the diet-heart hypothesis say that low carb (by definition higher fat) diets raise cholesterol, LDL, triglycerides etc and NONE of this was found to hold true.
Perhaps the biggest story of all, however, was that the UK largely ignored this. Let not the evidence get in the way of public health advice eh?!
I was on the circulation list for a recent email entitled “Breast cancer: 2 peaches/week 41% lower risk”.
The email opened by saying :
“Women who ate two servings of peaches per week had a 41% lower risk of breast cancer over the next 24 years according to a study from the Harvard School of Public Health in Boston, Massachusetts, USA.
“Women who ate one serving of blueberries per week had a 31% lower risk of breast cancer over the next 24 years.
“This study followed 75,929 women (part of The Nurses’ Health Study), 38- to 63-years-old at baseline, and followed them for up to 24 years.”
Here is the original paper. (Ref 1)
My first reply was
Association, not causation.
Relative risk, not absolute.
Nonsense, not science!
The more considered reply develops these further
Association, not causation
As Dr Malcolm Kendrick beautifully says “Association does not prove causation, but lack of association disproves causation”.
The way that science should work is that epidemiology/observational studies suggest association and then possible associations should be tested in a sufficiently powered, long enough, randomised controlled trial to see if there could be causation – changing the hypothesised thing alone. We have largely abandoned this step in science since, and including, the Seven Countries Study. We now see an overweight sedentary person and assume that being sedentary made them overweight. What about being overweight made them sedentary? What about a lousy high-carb-following-gov-advice diet made them both overweight and low in energy? What about a thyroid condition led to both?
If we observe association, we should look for a plausible mechanism to see if the intervention would be worth testing. If (to use another Dr Malcolm fab example) we push someone out of an airplane without a parachute we can do an n=1 to say that being pushed out of an airplane without a parachute causes death and jumping out of a plane with a parachute rarely causes death and so the parachute has a plausible mechanism in life extension.
What is the plausible mechanism with peaches and breast cancer?! I would not be surprised if women eat more peaches then men and substantially more women develop breast cancer – so where does that leave us? Is it antioxidants? Coffee and cocoa powder are massively higher in antioxidants than fruit so there could be a better intervention. Is it general nutrition? Fruit is pretty rubbish for nutrients compared to animal foods and dark green veg. I can’t even see a plausible mechanism.
Relative vs. Absolute risk
This study followed 75,929 women, 38- to 63-years-old at baseline, for up to 24 years. During this time there were 792 cases of post-menopausal breast cancer recorded. The study title did clarify that it was solely looking at post-menopausal cancer. The email I received didn’t clarify this.
That’s an incident rate during the 24 year study of 1.04%.
In any one year, the incident rate was 0.043%. Can you even get your head round such a tiny number?
So now we introduce the relative risk. The following table is extracted from Table 3 in the paper. It tells us the incidents among consumers of peaches/nectarines – don’t forget the nectarines.
The study used women who never eat peaches/nectarines as the base line. The baseline is given a risk ratio of 1.0. Relative to this group, those who had peaches up to a couple of times a month had exactly the same risk ratio – 1.0. Those who had peaches more than a couple of times a month but fewer than once a week had virtually the same risk ratio: 0.98. Those who had peaches between once and twice a week had a risk ratio of 0.87 BUT the confidence interval was 0.66-1.15, which includes the baseline number of 1.0 and thus we can’t be sure that we are not seeing the same result as at baseline and therefore we call this not significant.
The only significant result (where the confidence interval excludes 1.0) is the two or more peaches/nectarines a week:
||Up to 2/mth
||>2/mth to <1/wk
||1/wk to <2/wk
|Breast cancer cases
|Adjusted relative risk (RR)
1.0-0.59 = 0.41, which is where the 41% headline comes from.
The incidents and person years tell us the following:
We know from the overall numbers (792 incidents from 75,929 women in 24 years) that, in any one year, the incident rate was 0.043%.
This incident rate was 0.062% for never eat peaches and 0.038% for eat more than 2 peaches a week.
Are you any more able to get your head round those numbers?
No – me neither.
Now how does the 41% risk headline, with no explanation offered, look?!
Table 3 also tells us that they did not adjust for education, which is a well known marker for being better off…
If this study told us anything (apart from the fact that researchers continue to NOT understand association vs causation and relative vs absolute risk) it may have confirmed what we already know, which is that better off people enjoy better health.
Take UK regional life expectancy. The lowest for men and women occurs in Glasgow with life expectancy of 71.6 and 78 years respectively. The highest for men and women is found in Kensington and Chelsea – 85.1 for men and 89.8 for women.
Another interesting finding of the study was that there was not even an association with breast cancer and other fruits and vegetables. None. Zippo. Only peaches/nectarines and blueberries have magic breast cancer prevention plausible-mechanism-unknown properties. Peaches are posh fruits – P for posh. Passion fruit, Papaya, PawPaw, Pequi, Persimmon, Pewa, Pineapples, Pitahaya, Pitomba, Pomegranates, Pashminas (ho ho).
Q) Would you more likely find peaches in a fruit bowl in Kensington and Chelsea or in Glasgow?
Did the researchers not think – we’ve just reinforced better off = better health? And we should research health inequalities? No – the researchers want to carry on researching nonsense.
The abstract ends with these words: “These results are considered exploratory and need to be confirmed in further studies.” That’s academic speak for “we need funding, so please give us some money.” Bet the Blueberry Association has been in touch already.
Ref 1: Fung TT, Chiuve SE, Willett WC, Hankinson SE, Hu FB, and Holmes MD. Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women. Breast Cancer Res Treat, 2013 Apr; 138(3): 925-930.
This is a short blog about a new game, as I see it…
The headlines on 6th August 2014 were that millions more people should be taking aspirin daily for a minimum of 5 years, ideally 10, heck – make that for ever…
The original article is here. The BBC reported the story as “Daily aspirin ‘cuts bowel and stomach cancer deaths.'” Of course nothing cuts deaths – we are all going to die – but let not the facts get in the way of the story.
The article is interesting in that it’s the first that I’ve seen to detail explicitly how many people might be saved and how many might be killed by taking aspirin. Yes, killed. Check out figure 1 and the researchers have estimated how many men and women they claim will be saved by taking aspirin and how many deaths they forecast “due to stroke, GI bleeding or peptic ulcer caused by aspirin.”
On balance, they say more will be saved than killed and so an aspirin a day for loads of people will kill a few here and save more there. And here’s the big point. Aspirin is as cheap as chips, cheaper than chips no doubt, so why would you not want to put every over 50 year old on aspirin (the age will no doubt get lowered) if you can save more than you kill?
Conflicts of interest
The first thing I check in any article is declarations of interest. If someone tells me walnuts are going to save lives and they and/or the study were funded by the walnut foundation, I am inclined not to take much of what I read very seriously.
In this article the disclosure states: “JC [that’s the lead author – the one who was on the TV that day]: Member of the Bayer advisory board. JB: Consultancy for Bayer Pharma. Research funding from Bayer Pharma. A stockholder and medical director in QuantuMDx, a new medical devices company which will develop point of care pharmacogenetic testing. Aspirin sensitivity is one of company’s targets. JAJ: Consultant to Astra-Zeneca, Dr Falk Pharmaceuticals, Chief investigator of AspECT trial and ChoPIN trial. PMR: Has received honoraria for talks, advisory boards and clinical trial committees from several pharmaceutical companies with an interest in antiplatelet agents including Astra-Zeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, Biotronic, Johnson & Johnson and Servier, and is on the executive committee of the ARRIVE trial. Research funding from Boehringer Ingelheim. All remaining authors have declared no conflicts of interest.”
If all the companies with an interest in antiplatelet agents (things that aim to prevent blood clotting) – Astra-Zeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, Biotronic, Johnson & Johnson and Servier etc – were seen to be behind a paper saying “give millions of people antiplatelet agents”, we would probably see through this and wonder about the drug cost and not just the cost of those ‘killed’ by stroke and stomach bleeds weighed up against those ‘saved’ from cancer.
So here’s the plan:
1) Do a paper about the benefits of the cheap, generic, everyone-has-it-in-the-medicine-cabinet, friendly, aspirin.
2) Call for millions of people to be given cheap aspirin for years and years and a humongous medication opportunity has just been created.
3) As soon as possible after the aspirin prescribing occurs, show that the expensive, branded, drug company antiplatelet agents are so superior to aspirin that to keep people on the generic, cheap aspirin would be a crime. Particularly, I suspect, having highlighted the stomach bleed/ulcer problems – these branded drugs will no doubt be better at avoiding stomach problems. Then millions of people will be switched to the patented drugs and stay on them for decades.
4) Make riches beyond wild dreams.
Watch this space…
The CTSU is the Oxford Clinical Trial Service Unit. Where this ends and the CTT (Cholesterol Treatment Trialists) Collaboration begins or where CTT ends and where Sir Professor Rory Collins and Colin Baigent and co. begin or end, I know not. One gets the impression that the web between the parties is not intended to be clear.
This is the group that promotes statins. This is the group that holds data on statin side effects, which it won’t share with doctors and patients who would like to know about these statin side effects. Pause to digest that for a second. There is clinical trial information about what the most prescribed drugs in the US and UK could do to humans and researchers refuse to share it.
It was the lead member of this group, Sir Professor Rory Collins, who recently attacked the BMJ for publishing two articles that referenced the same peer review article finding about statin side effects. Not only did Collins attack the BMJ he went entirely outside the journal’s normal process and demanded that the two articles be retracted. The first was by John Abramson, Harriet Rosenberg, Nicholas Jewell and James M Wright; the second was by Dr Aseem Malhotra.
I covered Collins’ attempt at censorship in this post (after the Dr Maryanne Demasi Catalyst bit). In writing the post I found a declaration of interest involving over £115 million by CTSU member, Colin Baigent, repeatedly mentioning Collins/CTT/CTSU. This is in fact less than half the funding that the CTSU has received from commercial organisations. The MRC (Medical Research Council) and BHF (British Heart Foundation) funding, which they declare more readily, is in addition to the eye watering sums that they get from the hands that feed them.
The documents published as part of the panel review
The BMJ’s editor, Dr Fiona Godlee, called for an independent panel to be set up to investigate Collins’ demands. The full report of the panel is here, (published 1 August 2014). The outcome was that the panel found that neither the Abramson et al paper nor the Malhotra paper should be retracted.
The far more interesting outcome was the supplementary information that was published alongside the panel’s full report, in the BMJ spirit of openness and honesty. In particular, some “not for publication” letters written by Collins. If you make such serious demands, that a world regarded journal retract two papers, you don’t get to call the shots on what remains hidden. Hence much “Supporting Documentation” has been published by the panel called upon to investigate Collins’ demands.
Letter SP17, dated 31 March 2014, has an interesting “P.S.” (direct Collins’ quotations in blue and italics for ease of reading).
“P.S. Conflicts of interest: There have been a number of comments in the BMJ and elsewhere about potential conflicts of interest in this area, so it may be helpful to provide you with some background. CTSU’s coordination of the Cholesterol Treatment Trialists’ Collaboration (CTTC) has been funded by the Medical Research Council and British Heart Foundation, without any commercial funding.”
You can read the full P.S., for it is quite long. It ends as follows:
“As we are all aware, a range of potential conflicts of interest exist and it is important that there is transparency (as, for example, with the BMJ’s advertising and sponsorship revenue from vaccine manufacturers which it inadvertently omitted to report when commenting on the MMR vaccine and autism story). With respect to CTSU, we have had a policy for more than 20 years of not accepting honoraria, consultancy or other payments directly or indirectly from industry, except for research grants and reimbursement of travel and accommodation to take part in scientific meetings (see attached)… Please could you let me have details of all conflicts of interest that have been declared by the authors of the Abramson and Malhotra papers (including the size of all payments that they have received for any statin-related work)?”
The conflicts of interest for the Abramson article were openly declared at the end of the article (as is BMJ policy) (JDA is John D. Abramson and NJ is Nicholas Jewell):
Competing interests: JDA and NJ serve as experts for plaintiffs’ attorneys in litigation involving the drug industry (including a statin). JDA has received payment for lectures from several universities, medical schools, and non-profit organisations. He was formerly executive director of health management for Wells Fargo Health Solutions.
The conflicts of interest for the Malhotra article were openly declared at the end of the article (as is BMJ policy). There were none to declare.
Competing interests: None declared.
Letter SP18, dated 14 April 2014, reiterated demands for the conflicts of interest of Abramson and Malhotra to be declared. “Please would you let me have the details of all conflicts of interest for Abramson et al and Malhotra, including the amounts of any payments that they have received for any statin-related work? This is information that should quite properly be in the public domain. In a spirit of reciprocity, I have attached the details of all grants from industry to CTSU for our research covering the past 20 years and more…” You’ll find this item – SP21 - in the supplementary information. If you open one link in this whole blog, make sure it’s this one.
This is priceless. “In a spirit of reciprocity, I have attached the details of all grants from industry to CTSU for our research covering the past 20 years and more…” Just look at that list. It doesn’t even include funding from the MRC, Cancer Research-UK or the BHF. It’s difficult keeping track of all the millions but I got to £268 million give or take a few hundred thousand. Plus, as Hannah Sutter discovered here, (point 4 especially), the MRC seems to be an indirect delivery mechanism for further pharmaceutical funding.
Who is being open and honest here?
Abramson & Malhotra declared their interests openly in their original articles, the latter having nothing to declare.
On 31 March 2014, Collins demanded “details of all conflicts of interest for Abramson et al and Malhotra” when all he needed to do was read them at the end of the articles to which he so objected. In the same letter, Collins told the BMJ “CTSU’s coordination of the Cholesterol Treatment Trialists’ Collaboration (CTTC) has been funded by the Medical Research Council and British Heart Foundation, without any commercial funding” (my emphasis).
Just two weeks later, Collins sent the BMJ “all grants from industry to CTSU for our research covering the past 20 years and more…” “In a spirit of reciprocity...” The commercial funding came to c. £268 million.
Does that seem open and honest to you?
In the most recent statin article listing Collins as an author on pubmed, scan all the way down to “funding” and the funding declaration opens with info on the China part of the study. The bit relating to Collins/CTSU etc states “the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at Oxford University also receives core funding for it from the UK Medical Research Council, the British Heart Foundation, and Cancer Research UK.” What about the £268 million?
Does that seem open and honest to you?
I thought I’d see when Collins last wrote for the BMJ and what he declared when he did so. He wrote about confidential data of all things! Sadly not on open view, but I have seen a copy of the full paper. At the end of the article we see the following:
Competing interests: None declared.
What, not even the fact that you have commercial agreements in place prohibiting the sharing of data? i.e. keeping that data confidential?
Does that seem open and honest to you?
The real scandal
I have followed this saga with interest because it has been a saga – of arrogance, accusations and demands. We must not let the Eastenders style drama detract from what the real scandal is here. The real scandal is that a research body holds data, which could provide vital information for patients and doctors about the serious adverse effects for the most widely prescribed drugs in the Western world and the body will not release the data. This blog confirms this fact. See the email from Colin Baigent to Dr Maryanne Demasi (the Catalyst Programme presenter who has also been censored) on 24 Sep 2013 10:44:01: “It is important to recognise that data from participating trials are not owned by the Collaboration [CTT], but remain the property of the trial sponsors, so we are not able to provide unlimited access to the combined database.”
I interpret this as – we receive £268 million from trial sponsors and it is not in their interests for side effect data to be shared. And if some patient loving cardiologist, with no such conflicts of interest, dares to suggest that statins have side effects (when we hold that information and won’t tell him) we’ll bypass the BMJ process and demand retraction.
My contempt for Collins, Baigent, the CTSU and the CTT – wherever the web lies – knows no bounds.
This is extracted from: “The Obesity Epidemic: What caused it? How can we stop it?”
Marjorie R. Freedman, Janet King, and Eileen Kennedy wrote an article called “Popular Diets: A Scientific Review”, where 17 studies of weight loss with different macro nutrient (carbohydrate, fat and protein) composition, were reported with the concomitant results.[i] The authors stated that “no published studies are excluded”, so I have assumed that these are the only studies between 1956 and 2001. The three authors concluded “Caloric balance (calories in vs. calories out), rather than macro nutrient composition is the major determinant of weight loss.”
Yet I analysed all the data for these 17 studies and found no relationship between low calorie intake and high weight loss (0.009 correlation coefficient), but a significant relationship between low carbohydrate intake and high weight loss (0.79 correlation coefficient) (Tables below). How can the authors have concluded as they did, unless they set out to prove an already held point of view?
“Popular Diets: A Scientific Review”[i]
||Authors & publication
||# of people
||grams lost/ day
||Rickman, JAMA (1974)
||Benoit et al, Ann Intern Med (1965)
||Yudkin & Carey, Lancet (1960)
||Fletcher, Br J Nutr (1961)
||Lewis et al, Am J Clin Nutr (1977)
||Kasper et al, Am J Clin Nutr (1973)
||Evans, Nutr Metab (1974)
||Golay et al, Int J Obes relat Metab Disord (1996)
||Young, Am J Clin Nutr, (1971)
||Golay et al, Am J Clin Nutr (1996)
||Cedarquist, J Am Diet Assoc (1952)
||Worthington & Taylor, J Am Diet Assoc (1974)
||Rabast et al, Int J Obes relat Metab Disord (1979)
||Rabast et al, Nutr Metab (1978)
||Wing et al, Int J Obes relat Metab Disord (1995)
||Alford et al, J Am Diet Assoc (1990)
||Baron et al, Am J Public Health (1986)
* 21 studies were included in tables 5a and 5b in the paper. Three had no results for weight change, so could not be included (Kekwick 1957, Bortz 1968 and Krehl 1967).
* I excluded Larosa et al (1980), as the table said that the study was for 12 weeks when, in fact, the article and the original journal revealed that the subjects followed their normal diet for two weeks at the start and two weeks at the end of the 12 week period. We cannot determine what the weight loss per day was in relation to a measured carbohydrate and calorie intake period.
* The 17 remaining studies are above. There was a material error in the article. This has been corrected in the table above, as follows: Study 8 (Golay et al) – the weight loss in table 5a is given as -8.0 kilograms over 6 weeks, which was commuted to -111 grams per day in table 5a. This is wrong and -8.0 kilograms over 6 weeks equates to -190 grams per day. However, the table appears to be wrong in more way than one and the original journal (and the text in the article) state that the weight change for the group on 37.5 grams CHO was -8.9 kilograms +/- 0.6 kilograms. I have taken the mid point of -8.9 kilograms and this equates to -212 grams per day. This is the number in the table for this appendix and the number I have used for the correlation.
* A number of ranges were taken at mid point level, as follows:
– Study 7 (Evans) – the range of weight loss was given as -76 to -119 grams per day, so I took the mid point of -97.5 grams per day;
– Study 11 (Cedarquist) – the range of weight loss was given as -78 to -150 grams per day, so I took the mid point of -114 grams per day.
* Five of the studies were directly comparable isocaloric studies i.e. the studies had parallel groups on a different carbohydrate level and the same calories per day (these are studies 6, 8, 10, 12 and 14). In every such isocaloric study in the article, the weight loss was substantially higher in the low carbohydrate group than in the higher carbohydrate group. At the highest calorie intake (Kasper et al, study 6, 1707 calories per day), the group consuming 56 grams of carbohydrate per day lost 300 grams per day vs. the 156 grams of carbohydrate per day group, which only lost 50 grams per day. This supports Kekwick and Pawan’s findings that large numbers of calories can be consumed and weight still be lost with a low carbohydrate diet composition.
Correlation between (low) calories & (high) weight loss
||Benoit et al
||Yudkin & Carey
||Lewis et al
||Kasper et al
||Golay et al
||Golay et al
||Worthington & Taylor
||Rabast et al
||Rabast et al
||Wing et al
||Alford et al
||Baron et al
N = the number of pairs of scores (17)
∑xy = sum of the products of paired scores (-6,094,862)
∑x = sum of x scores (21,373)
∑y = sum of y scores (-4,854.5)
∑x2 = sum of x scores squared (28,593,253)
∑y2 = sum of y scores squared (1,865,057)
r = 0.009
Correlation between (low) carbs & (high) weight loss
||Benoit et al
||Yudkin & Carey
||Lewis et al
||Kasper et al
||Golay et al
||Golay et al
||Worthington & Taylor
||Rabast et al
||Rabast et al
||Wing et al
||Alford et al
||Baron et al
N = the number of pairs of scores (17)
∑xy = sum of the products of paired scores (-147,786)
∑x = sum of x scores (711.5)
∑y = sum of y scores (-4,854.5)
∑x2 = sum of x scores squared (40,158.25)
∑y2 = sum of y scores squared (1,865,057.25)
r = 0.79
I reiterate, how can the authors have concluded as they did, unless they set out to prove an already held point of view?
[i] Marjorie R. Freedman, Janet King, and Eileen Kennedy, “Popular Diets: A Scientific Review”, Obesity Research, (March 2001).
On Wednesday February 12th 2014 the UK National Institute for Health and Care Excellence (it used to be the National Institute for Clinical Excellence, hence NICE) published draft guidelines on statins. The guidelines have been published today on 18th July 2014. NICE recommends lowering the threshold for giving statins to healthy people with no symptoms of heart disease to anyone deemed to have a 10% risk of developing heart disease over the next 10 years.
All shall be statinated. Resistance is futile
This risk calculation is so heavily dependent on age, by the way, that EVERYONE has a date at which they should be statinated, as Dr Malcolm Kendrick explains here playing with the American risk factor toy, which came out in November 2013.
You can play with the QRISK2 UK toy here to your heart’s content. I’ve just worked out my “must be statinated age”. I’m a non-smoker, no diabetes, no history of heart disease, no atrial fibrillation, no kidney disease, no arthritis, (very) low BP and a BMI of 20-21. I have no idea what my cholesterol and HDL is and could not care less. So I entered what the NHS considers ideal for a cholesterol/HDL ratio of 4 (Honestly – where do they get this nonsense?!)
The result? If I were aged 64 today, my risk over the next 10 years would apparently be 8.2%. Aged 65 it would be 9%. Aged 66 it would be 9.8% and aged 67 is would be 10.7%. (Look how it’s just going up by almost 1% per year). So – somewhere between my 66th and 67th birthday (thankfully a long way away!) I should be on statins.
The key priorities for implementation say that everyone up to the age of 84 should be targeted. Don’t the powers-that-be read patient leaflets? Here’s the patient leaflet for Liptor, cautioning that Lipitor may not be suitable for anyone over the age of 70. That’s because there is much evidence for low cholesterol being especially bad in the elderly – if you fancy living longer that is.
So we all have a statin use-by date – super healthy as I am, mine is 66-67.
Statin conflicts of interest
It took me less than an hour following the NICE publication of the draft guidelines in February to uncover the conflicts of interest of the panel – 8 out of 12 people having clear connections to drug companies. I blogged about it for Health Insight UK here. The Sunday Express covered the conflicts here. And an extraordinary open letter from doctors and academics to NICE and the UK Secretary of State for Health, Jeremy Hunt, raised conflicts as one of many concerns about the then proposed (now finalised) statin guidelines.
I wrote to Jeremy Hunt on 17th February 2014 about the NICE conflicts. Someone replied on 28th February, on Hunt’s behalf, to say “NICE, as an independent body, has its own procedures in place for managing conflicts of interest.” The letter suggested that I raise my concerns with Sir Andrew Dillon – Chief Executive of NICE. So I did. I wrote to him on 5th March, chased on the 7th April and finally received a reply from a communications executive dated 23rd April.
Having set out the details of the conflicts of the Guidelines Development Group in my letter, the four questions I asked were as follows. I’ve summarised the answers I got back from NICE below each question:
Q1) Please can you confirm if you knew about the conflicts of interest on this Guideline Development Group?
Q2) Do you agree that the conflicts, in this case, negate the claim of NICE to be independent and unbiased?
Q3) What action will be taken to redress the bias and conflict in this group and the publication that it produced?
Q4) What steps will be taken to restore NICE to the body it claims to be: “evidence based guidance … created by independent and unbiased advisory committees.”
NICE’s position incredibly seems to be – people just need to declare conflicts and then we carry on knowing their conflicts.
Such arrogance no doubt inspired the academics and doctors to write that open letter, on 10th June, calling upon NICE to rethink their guidelines and to refrain from making these guidelines policy until all trial data (side/adverse effects especially) are shared. The latter are withheld by ‘researchers’ funded by the statin manufacturers under commercial arrangements made with the hand that feeds them.
NICE’s response to the open letter is detailed in the previous link. Probably best summed up by an unprofessional and bizarre mix of attack and defence, but overall dismissal.
And now for bariatric surgery guidelines and conflicts
As soon as I saw the headlines on 11th July 2014, announcing that Christmas had come early for the bariatric surgery industry, I suspected that conflicts would be discoverable (and I was not alone in this, receiving a call from a surgeon friend suspecting the same).
The NICE statement was published on line early that afternoon. Fewer than five minutes later, the conflicts were apparent. Follow the link through to details of the draft guidelines and you can see a link through to the “Guideline Development Group” and this reveals that four bariatric doctors and two bariatric surgery patients formed the substantive part of the group. One of the doctors is Head of Obesity and bariatric services at University College London Hospital.
The patients are not just patients – one particularly. Check out this article on Ken Clare who works for Gravitas (bariatric surgeons and clinicians) and runs a web site and forum, funded by Gravitas?, to help people who are considering surgery or have had surgery. Alexandra Blakemore was so pleased to have had surgery, she made a youtube video about it. I have stopped attending obesity conferences because the agendas have been infiltrated by the barbaric surgery industry and their spokespeople (paid and/or given free surgery?) to promote the procedure.
This is a disgrace. There is no way that NICE can continue to claim to be independent, let alone authoritative and evidence based. A guideline group should have NO conflicts whatsoever. A guideline group should be staffed with researchers and statisticians – ideally who know nothing about the drug/intervention in question. Then the data speaks entirely for itself and no prejudice (literally to pre-judge) can enter the debate.
The Nolan Principles of Public Life
I have been an Executive Director at the Welsh Development Agency (2002-2005) and a Non Executive Director at University Wales, Institute Cardiff (2006-2012) and the Wales NHS National Delivery Group (2009-2012). In all of these roles I was bound by The Nolan Principles of Public Life (selflessness,integrity, objectivity, accountability, openness, honesty and leadership). All public roles should carry the same obligation. In my public sector work, the way that conflict of interest worked was that – if you had any connection to any item on the agenda you declared this to the clerk/meeting secretary before, or at the start of, the meeting. When this item came up you left the room. You did not even stay in the room, as your position could inhibit free exchange of views. If your conflict was such that even being a member of the board would be inappropriate (i.e. you could gain in any way from your affiliation with the body), you would not be on the board. Full stop.
At the first meeting of the guideline development group, the conflicts were recorded and ‘addressed’ as follows: “The GDG members verbally declared their DOIs (as per the DOI register) and the Chair agreed there were no conflicts of interest therefore no action was required.”
You may need to read that twice. The group members declared their conflicts and the chair agreed there were no conflicts. This is the same NICE response to the statin conflicts. Yes we were aware of the conflicts, but we saw no problem in these conflicts.
NICE seems to think that one merely needs to declare a conflict and then it no longer need be deemed a conflict. To use a topical, if disturbing, analogy, this would be like Jimmy Savile declaring that he’s a paedophile and then being allowed to play with children because his conflict was known about.
The NICE approach to conflict is an utter disgrace and the Department of Health needs to intervene urgently to establish a medical advisory body that is genuinely independent and evidence-based. Not one that is staffing guideline development groups with conflicted majorities and then publishing the views of these drug/surgery representatives as policy for practitioners to be ordered to adhere to.
p.s. Thank you to The Independent on Sunday for giving me the opportunity to give my view on the bariatric surgery guidelines and conflicts…
On 10 June 2014 there were global headlines about a ‘condition’ called pre-diabetes. From the Mail telling us that “A third of adults have ‘borderline’ diabetes – but most don’t know: Rising tide of obesity means number who have ‘pre-diabetes‘ has trebled since 2006″ to the Huffington Post proclaiming “Most People In England Have Borderline Diabetes, New Study Reveals“. One third was never most people when I did proportions, but anyway.
Here is the summary of the study and findings from a journal web site and here is the original (full) article.
A quick review of the article should have made the media far more challenging, instead of just taking the press release headlines:
1) The study used data already gathered for Health Survey England (HSE), which started in 1991. The number of adults involved in the HSE, from whom blood samples were taken, was 7,455 in 2003; 6,347 in 2006 and 1,951 in 2009. I can’t find the numbers for 2011, but they are likely to be small if the trajectory continues. There are over 40 million adults in England. Using 2009 as a guide, projections on this concept of ‘pre-diabetes’ have been made based on 0.0048% of the population. I can’t get my head around such numbers.
2) People were diagnosed with pre-diabetes if they had glycated haemoglobin (an indicator of blood sugar levels) between 5.7% and 6.4%. This is the US guideline for ‘pre-diabetes’. The UK guideline is 6.0-6.4%. This would have over-predicted the idea of having a pre-condition.
3) The introduction to the full article in the BMJ is worth a read. The introduction notes that England set up a scheme to offer people aged between 40 and 74 a health check to try to pick up blood glucose concerns (and other things). Then it admits that “the scheme is controversial since randomised trial evidence does not show that health checks reduce morbidity or mortality.” i.e. these health checks made no difference to health or death. The article then notes the concern about “the extent to which medicine is extending the boundaries of illness through new definitions of disorders, with a consequent risk of treating more people than necessary.” I couldn’t have put it better myself. That should have been the headline.
The issues with the headlines on pre-diabetes aren’t, however, the main focus of this post. This post is about the fact that normal is being redefined as abnormal to the point that normal is no more. The whole concept of pre-diabetes is just one example and it’s by no means the first distortion in the diabetes world…
Aside from this created condition of pre-diabetes, the definition of diabetes itself has been manipulated. There’s a useful diagram here (scroll about half way down), which has a clear illustration of the game being played.
The curve in this graph is known as a “normal distribution”. This means that, when we plot the population, people are normally (typically) distributed as this curve indicates – most people are in the middle and fewer people at both ends. The peak of the hump indicates the average (mean and mode in this case if you like stats). The average fasting blood glucose level is 100 mg/dL (this is the US measurement – UK would be 5.6 mmol/L). Don’t worry about the mgs and the mmols – we’ll just call them US and UK measures from now on. So 100 (US)/5.6 (UK) is the true average of the population. There are very few people with a fasting blood glucose level of 50 (US) and about the same number of few people with a fasting blood level of 150 (US) – most people fall within the 60-140 range (US) (3.3-7.7 UK).
Then see what has happened. Diagnosis of diabetes used to occur at a fasting blood glucose level of 140 (US) 7.8 (UK). This is a number on that normal distribution curve and so is an entirely normal reading for a section of the population. Normal was redefined as high. But then it got worse. Back in 1997, high was re-re-defined as 126 (US) and another large segment of entirely normal people became abnormal.
The UK uses the same benchmark to diagnose diabetes. This states that diabetes is diagnosed at a fasting blood glucose level above 6.9 UK (126 US). If you look at what the UK thinks is normal, it is arguably worse than the US graph. The UK has defined normal fasting blood glucose levels as 4.0-5.9 (72-106 US). The true centre of the norm from the graph is 100. The range which captures most people is thus 80-120 – not 72-106.
Normal is not normal. The medical world has overruled the human population and decreed that normal is not normal. Normal is now high and people shall be treated accordingly. Now that we have pre-diabetes on top, joy of joys, we can start medicating people even sooner than our re-re-defined norm would otherwise let us drug them. (Or we can give them ‘base your meals on starchy foods’ dietary advice and speed up their pathway to type 2 diabetes.)
This doesn’t just happen in the world of diabetes. Cholesterol is perhaps the most successful and horrific redefining of normal that the medical world has ever got away with. Here is a graph of a normal distribution for cholesterol in the UK. The most common reading is 5.5-5.9. The normal distribution in this case is not as symmetrical as the diabetes curve. This one is what we call a “skewed distribution”. There are four groups below the most common group and eight groups above. This graph tells us that a cholesterol reading of 3.5-3.9 is normal, if uncommon and a cholesterol reading of 9.5-9.9 is also normal, if uncommon. Can you imagine the reaction of your doctor if your cholesterol reading were 9.5?! And yet it is absolutely normal that a section of the population will have this as their normal reading.
Just as happened with diabetes, normal is not allowed to remain normal. The medical profession has redefined cholesterol to be high at the absurdly low number of 5. You can see from the graph that only a small proportion of the population would have a cholesterol level below 5 in normal circumstances. Indeed, if you look at government data measuring people against this made-up target – the Health Survey for England for example (summary of key findings) - we have the crazy situation (page 22) where it is noted that 80% of men and women in many age groups have cholesterol levels above the government target of 5.0 mmol/L. That’s not because 80% of people have ‘high cholesterol’, but because normal has been redefined as high so people cannot be normal any more.
You know why this happens. Normal people have no value whatsoever to the pharmaceutical industry. But redefine ‘normal’ as high and suddenly healthy people can be medicated. This is how Lipitor was able to earn $125 billion for Pfizer during its patent. And who sets the targets?
In America, they are set by the National Cholesterol Education Programme (NCEP). The 2004 NCEP financial disclosure report reveals that ALL members of the 2004 guideline participants had received payments and/or grant funds from some, many or most of the following organisations: Abbott, Astra Zeneca, Bayer, BMS-Sanofi, Bristol-Myers Squibb, Esperion, Fournier, Glaxo SmithKline, Kos, Lipid Sciences, Merck, Novartis, Pfizer, Procter & Gamble, Reliant, Sankyo, Takeda, Tularik, Wyeth. (For full details of conflicts see point 3 on this post.)
In the UK they are set by the National Institute of Clinical Excellence (NICE). Here are their conflicts - 8 out of 12 of the NICE panel members have conflicts of interest with the statinators.
Blood pressure is the same. Here is a journal article with a couple of very interesting graphs – open up figure 1 and figure 2. Figure 1 is the higher number when you have your blood pressure reading (the 140 in 140/90 kind of thing). This shows that the normal blood pressure range for the general population is anywhere from 90 to 240 as the top number, with 130 being the most common reading (mode) and the average (mean) being around 140.
Figure 2 is the lower number (the 90 in the 140/90) and this ranges from 50 to 130. The most common is around 85 and the average is around 90. So the true average blood pressure (BP) in the normal population is approximately 140/90. You may be aware that 140/90 is the definition of high BP. Yet again, normal has become high and now everyone who is deemed high shall be medicated, when they are in fact normal.
Height and foot size
In the Western Journal of Medicine, (May 2002) Thomas Samaras and Harold Elrick posed the question “Height, body size and longevity – is smaller better for the human body?” The study took 100,000 males from 6 different ethnic populations – in the same city (California) to try to normalise other factors. The table had the following height orders (tallest first): African Americans; White Americans; Hispanics; Asian Indians; Chinese and Japanese (the first two groups were recorded as of equal average height – 70 inches).
The death rates for all causes and coronary heart disease (CHD) were presented in the study. A clear pattern was immediately obvious. I calculated the correlation coefficients as 0.85 for height and CHD and 0.9 for height and all causes of death (1 is a perfect relationship – scores of 0.85 and 0.9 are very strong relationships).
What if we concluded that height were a cause of CHD (and all causes of death) and that we should therefore redefine the average height to declare the actual average of 69.7 inches (for all American men) to be abnormal? What if we made up a new target 10% lower than the actual average and decreed that normal height should be 63 inches? We could then administer drugs to stop growth hormones from doing their job. I trust that this analogy disturbs you and yet…
The Chinese practice of foot binding – an artificial intervention in the normal development of the human body, to achieve an artificial ‘norm’ – was thankfully outlawed in the early twentieth century, but trying to reduce many other genuine human norms – from diabetes to BP – has now become common practice and big business.
Last week something quite extraordinary happened in the UK medical world. The National Institute of Health and Clinical Excellence (NICE) describes itself as follows: “We provide independent, authoritative and evidence-based guidance on the most effective ways to prevent, diagnose and treat disease and ill health, reducing inequalities and variation.”
Overnight on June 10th 2014, an open letter was sent to NICE and the Health Secretary, Jeremy Hunt, and a press release was issued by a group of doctors and academics. The letter essentially said to NICE – you are not independent and you are not evidence based and we call on you to withdraw the latest guidelines on statins until the drug company funded ‘researchers’ conducting trials and withholding vital data are forced to share that data.
This is the letter that was sent. This is the press release .
The points made by the doctors and academics
To summarise the six subheadings in the letter, the authors questioned:
1) Whether five million more healthy individuals should be medicated.
2) How could vastly conflicting information on side effects be explained (we’ll come back to this one).
3) How can it be right that the Cholesterol Treatment Trialists (CTT) Collaboration have commercial agreements with drug companies, which seem to exempt them from sharing what doesn’t suit their paymasters.
4) Why is NICE relying upon trials funded by drug companies when evidence shows (unsurprisingly) that these will find in favour of their drug. The open letter included the conclusion of the one major non-industry funded trial on statins (ALLHAT-LLP). This lone independent study found “No benefit was demonstrated in ALLHAT-LLT, the largest clinical event trial of pravastatin published to date.”
The open letter made two final damning points – the first reminding NICE that it is not considering all data because data is being withheld – and the collective view of GPs on this:
5) A recent meeting of the General Practitioners Committee (GPC), which represents GPs, passed a resolution requesting that NICE refrain from issuing its statin recommendations until there is complete disclosure of all clinical trial data.
The second, bringing into question the claimed independence of NICE:
6) We have serious concerns that 8 out of 12 people on the NICE statin guidelines committee have ties to the drug companies (I shared the conflicts here soon after the guidelines were issued). We have serious concerns about NICE’s reliance upon the CTT/Clinical Trials Service Unit (CTSU) drug company funded trials. e.g. the REVEAL study for which the CTSU received £96 million in funding from Merck Sharp & Dohme.
It is difficult to describe just how extraordinary this turn of events has been in the world of the statin/cholesterol debate. I highly recommend reading the letter and press release in full (there’s some classic Dr Malcolm Kendrick humour in the press release) if you’re interested in the world of health/drugs and doctors. This has been a seminal moment in the doctor/guidelines relationship.
There was some more humour in Dr Malcolm’s appearance on BBC breakfast when statin side effects were being discussed: “Statins will add 15 years to your life – they won’t make you live 15 years longer; they’ll just make you feel 15 years older!”
Statin side effects
You may be aware from this post that there is a debate going on about the true extent of statin side effects. This has become a much discussed issue after Professor Rory Collins demanded that the BMJ remove two articles, which referenced a peer reviewed paper that estimated the side effects of statins to be approximately 20%. Dr David Newman has rightly called this “An assault on science“. I’m in possession of a document showing that the true extent of the pharma funding for the CTSU is £250 MILLION. This is not just an assault on science, it’s an absolute disgrace that a Sir/Professor/Lord-high-executioner can make demands in this way from the worst position of conflict I have ever seen.
The open letter to NICE/Jeremy Hunt presents some inexplicable data. Under subheading 2 (conflicting levels of adverse events), the letter notes that the LIPID trial reported total adverse effects [side effects] as 3.2% for pravastatin and 2.7% for the placebo. The METEOR trial reported total adverse effects as 83.3% rosuvastatin and 80.4% for the placebo. There were six other trials listed (falling between 2.7% and 80.4% in side effect rates) and yet the placebo and statin adverse effects were almost identical every time. This raises two questions, which the open letter has invited NICE to explain:
i) How can there be a thirty fold difference in side effects from statins (80% over 2.7%)?
ii) How can the placebo be virtually the same as the statin in every trial – whether or not the statin results in 2.7% side effects or 80%?
I can’t explain this. Jerome Burne can’t either. Here’s my best guess – the data has been manipulated to ensure whatever side effects were reported in the statin victims, the placebo arm looks the same. I’m open to other suggestions.
This part of the letter alone also makes a mockery of Collins’ claim that you’ll see side effects in barely 1 in 100 cases. If we average the eight trials, side effects in the statin takers were 19.8%. Oh look – just like the 20% in the Zhang et al paper, referenced by Dr Aseem Malhotra and Dr John Abramson.
The NICE reply
The NICE response was almost as extraordinary as the open letter. The NICE response was posted on the same day that the letter was issued (10th June). I appreciate that they would have had advance notice before the open letter was issued, but they still don’t appear to have devoted much time to a considered response.
The NICE response opened by quoting its own Professor Mark Baker, Director of the Centre for Clinical Practice at NICE: “Cardiovascular disease maims and kills people through coronary heart disease, peripheral arterial disease and stroke. Together, these kill 1 in 3 of us. Our proposals are intended to prevent many lives being destroyed.”
I heard Mark Baker saying that exact comment on Sky news interviews and almost fell off the sofa. That’s emotive, scare-mongering worthy of a Hollywood trailer – not a public health body trying to be taken seriously.
Here are the facts on your chance of dying from heart disease. You would have needed to know 3,030 men (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. You would have needed to know 12,500 women (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. (Double these odds if you like, to capture the broader concept of cardiovascular disease rather than heart disease. I’d still need over 6,000 female friends under 65 to be attending one of their funerals from CVD).
We have to die of something. Arguably we all die of heart disease because death is confirmed when the heart stops beating. Cancer is just about the only other major thing that claims a place on death certificates. So yes, one in three of us have the likelihood that cardiovascular disease will be on our death certificate. The chance of that happening is so massively related to age that we should worry way more about birthdays than we do anything else.
The second astonishing approach taken by NICE was to present no defence whatsoever of the “8 out of 12 statin committee members prefer drug money” allegation. Paragraph four opens with “The independent committee of experts found…”. Paragraph five opens with “NICE guidance is developed by independent expert committees…”
Dear NICE – simply repeating that you’re independent does not make you so.
NICE has this to say: “They [independent expert committees] review all of the available evidence …” Yes – but what are you doing about the unavailable evidence? The evidence deliberately being withheld? If the CTT/CTSU have commercial arrangements, which ‘exempt’ them from sharing inconvenient data, why do you, NICE, not reject every study that they publish until they do fully disclose serious adverse effects and other information that they refuse to share.
The open letter recommends that the Cochrane group (the group set up to be genuinely free from big pharma) be allowed to scrutinize the CTT/CTSU data. It is just incomprehensible that NICE don’t seem bothered that they have 8 out of 12 fat cats dealing with biased pharma controlled data.
Mark Baker’s other ‘fall on the floor’ comment was along the lines of “because the price of statins has fallen [they’re off patent now], we can afford to give them to more people”. Smarties are fairly cheap – it doesn’t mean that we should hand them out to everyone. What happened to first do no harm? What happened to leaving healthy people alone? What happened to truly understanding the side effects of a drug before assuming them to be as safe (or as harmful) as Smarties?
This rationale for statins also illustrates the naivety (or even more sinister conflict) of NICE. There were similarly naive (or conflicted) comments on newspaper websites: “statins don’t cost as much now – so why not dish them out?” Apart from the harm, here’s why…
As the open letter explains in subheading 6, people like Dr Malcolm Kendrick and Dr Aseem Malhotra, who work with true independence in the statin world of reward, are aware of where statins are going next. When a drug as lucrative as statins ($125 BILLION for Lipitor alone) is approaching the end of its patent, you can bet that the replacement is being worked on in haste. And it is. And it will come in the form of PCSK9 inhibitors. And the chair of the NICE guidelines panel just so happens to be the lead UK investigator for the Pfizer RN-316 (anti-PCSK9 antibody) programme and the site investigator AMG-145 (anti-PCSK9 antibody) Osler lipids follow-on study. Oh and guidelines panel member Michael Khan just happens to be on the advisory board for Amgen for PCSK9 and he’s doing a clinical trial for Amgen on PCSK9. Oh and Emma McGowan is also doing a PCSK9 clinical trial. Oh and Dr Alan Rees (Mr Heart UK) is advising Sanofi AND Aegerion AND Amgen on PCSK9 and getting honorarium payments, speaker fees – no payment details shared. Mr Heart UK is also principal investigator on two PCSK9 trials. It’s all here – Appendix B - runs for 20 pages.
So – is the NICE panel naive to not realise the PCSK9 game being played or corrupt?
We are currently in that vital window for drug companies where they have a unique opportunity to expand a market in preparation for the next drug-of-riches-beyond-wild-dreams. This is what is happening right now. If only five million more adults (in the UK alone – more in US, Australia, NZ, Europe etc) could be put on these ‘cheap’, off-patent statins, when ‘son of statins’ (as Dr Malcolm calls PCSK9 inhibitors) are introduced, doctors will be deemed reckless if they do not move all their statin patients to the ‘new and improved’ medication. The ‘new and improved’ medication that will be able to return even more than statins Mark I having just expanded the client base. If you’re interested in learning more about PCSK9 inhibitors, you may enjoy this and this and this.
Where are we now
We end the week commencing 9th June 2014 with NICE badly wounded. They would not take a cheap swipe in their response at …”the American doctor, who co-signed the letter…” if they were not hurting.
I wrote to Health Secretary, Jeremy Hunt, on 17th February 2014 about the NICE conflicts of interest and he left it to NICE to reply. It will be interesting to see if the Health Secretary replies to this open letter, or if the NICE immediate response is all that we will get.
The February “extend the use of statin” guidelines from NICE have been out to consultation since then and final recommendations are due to be published next month. It will be interesting to see what final position NICE adopts. We may then have the unprecedented situation where GPs are openly rejecting guidelines issued by their advisory body.
The comments sections under media articles and even the BMJ rapid responses alongside Fiona Godlee’s editorial are littered with stories from individuals sharing their own statin experiences. The diabetes statin lawsuit continues in the US – women seem to be particularly badly affected – as the open letter to NICE detailed. The Collins “Assault on Science” has at least opened up awareness of statin side effects and angry people are sharing their unpleasant and disabling experiences.
Meanwhile the drug companies are really not bothered. Even if Collins is forced to declare the full extent of side effects and release raw data, so that people like me can have some fun with it, it will be too late. The only question now is – how many people will be on “son of statins” – the millions who are on statins now or five million more? It would be like you or me winning £109 million or £115 million on the lottery – would it really matter?