Jo Best's Superb letter to Richard Horton of The Lancet on his comments on PACE

by Jo Best on Tuesday, April 26, 2011:

richard.horton@lancet.com
Dear Mr Horton,

I am writing to urge you to accept the personal invitation you have been given to attend the annual international conference on biomedical ME research hosted by the charity Invest in ME next month, as your comments about patients with ME in your recent interview on Health Report were remarkable for the ignorance they implied of the depth and breadth of published and cutting edge scientific ME research, and I am sure you will agree that you have a professional obligation to redress that dearth of knowledge if you are going to discuss the subject so freely in the media.

I wonder whether your comments stem from some confusion you may have over the important differences between the disease myalgic encephalomyelitis (aka chronic fatigue syndrome) and chronic fatigue, which is symptom of many different illnesses and disorders. You said the investigators were comparing conventional treatments for chronic fatigue. Cognitive behaviour and graded exercise therapies are available to patients with other chronic conditions such as cancer and heart disease. They are adjunctive therapies, offered alongside drug treatment and/or surgery – they are not considered as treatments for disease.

Pacing should not be described as a treatment either – pacing is merely a strategy that people with ME/CFS have to use in order not to exacerbate symptoms, in the absence of cure or treatment for the disease. The cardinal symptom of ME is post-exertional malaise (PEM). This is what distinguishes ME from other illnesses and this is why ME patients and experts in ME – scientists and doctors – object to the way the results of the PACE trial have been over-stated and misrepresented, as they know that exercise and over-exertion is indisputably physically harmful to genuine ME patients, just as it would be to patients with untreated heart and lung disease and patients with active viral infection. Patients learn how to pace through trial and error, according to their individual symptom profile, illness severity and circumstances - it is not an exact science or something that most people can stick rigidly to – it is often said that life gets in the way of a good pacing regime. Contrary to popular belief, people with ME, including adolescents, tend to do too much, not too little, and suffer the physical consequences arising from PEM. One of the problems of judging how much a patient can do is that the “payback” of PEM often does not onset until up to 48 hours after the activity itself. Again, this is another area where PACE results were unreliable – there was no account or measurement taken, of PEM following CBT and GET.

PEM is measurable and could be used as a diagnostic marker for ME. There is a high rate of over-diagnosis and mis-diagnosis of ME/CFS because biomedical disease markers for ME are not used by the NHS. In a study at Dundee University of patients with ME/CFS diagnosis, 12% were found to have a potentially treatable psychiatric disorder that could account for their symptoms, 7% had fibromyalgia, 21% had muscle, connective tissue and endocrine disorders. A second study at Newcastle University showed that 44% of patients had other conditions such as sleep apnoea, or depression and anxiety, to account for their symptoms. None of those conditions would produce the PEM so characteristic of ME. This is one reason why therapies seem to be effective for some patients and not others – they do not all have the same condition but are given the umbrella diagnosis of ME/CFS.

You said that the PACE researchers were: “really stepping back and comparing two philosophies, not just two treatments, two philosophies of what chronic fatigue syndrome was”.

I hope you can now see how illogical that comment was. Medical research should be concerned with science, not philosophy. Its aim should be to establish cause, effective treatment and prevention of disease. The researchers were not assessing two treatment approaches, as APT is not the same as pacing, it is more akin to GET. If you are suggesting that the two philosophies are the physical v psychological debate, then a study that only assesses the supposed treatments that are based on the psychological model can only prove or disprove that model. In which case, PACE soundly refutes the psychological model of ME, as you must realise from analysis of the results and a critical appraisal of the study protocol. CFS is a different matter, as it was invented in the 1980s by the small group of psychiatrists to which Peter White and Michael Sharpe belong. CFS will include people with mental health related fatigue because they wrote the criteria. As you know, criteria for inclusion in PACE effectively ruled out patients with ME. You know that ME is classified by WHO as a neurological disease yet neurological signs were not necessary for the entry criteria. Research has also shown that adults and children with ME have persistent viral infection yet patients with signs of active infection were also excluded from the study.

You said: “Yeah, I mean adaptive pacing therapy essentially believes that chronic fatigue is an organic disease which is not reversible by changes in behaviour. Whereas cognitive behaviour therapy obviously believes that chronic fatigue is entirely reversible. And these two philosophies are kind of facing off against one another in the patient community and what these scientists were trying to do is to say, 'Well, let's see. Which one is right?'”

You are completely mistaken by assuming that people with ME do not adapt their behaviour to the illness – that is exactly what pacing (not APT) is. They are forced to adapt their normal pattern of daily living in order to avoid deterioration and in the hope of recovery. Those who are working typically relinquish all leisure and social activities, partly as they are simply not well enough to participate any longer and partly as they need to reserve all their physical and mental energy for work. Their limitations put a strain on family life and relationships. With the more severely affected, unable to continue working, there are elderly parents who have to care for their adult children with ME and there are children who have to care for their parents with ME. As there is no treatment on the NHS that “reverses” ME, as you put it, those who can afford to, spend several thousands of pounds on trying to find the root cause of their symptoms and trying various treatments, both on the NHS and in private practice. Some of these are informative and helpful at alleviating symptoms, sadly, others are scams claiming to be cures that prey on the desperation of patients and parents of patients to recover. The average person with ME is far removed from the image you are portraying here as feeble-minded people who do not believe they can recover and give in to the limitations of their illness. I can assure you that many ME patients could write the book on CBT themselves.

You said: “the .. ME, population our critics claim contains a substantial number of people who are bedridden. Given the fact that treatments are being offered which do regard chronic fatigue as reversible, then that somehow undermines the view that ME is a neurological condition. There is this feeling that ME, being an organic disease in the views of some patients, that means that any view that contradicts that and offers a treatment against that particular perspective must therefore by definition be unethical”.

By using the word “claim” are you suggesting that people are making up that a substantial number of ME patients are bedridden? Exact numbers of people with ME are unknown as the DoH has never seen fit to collate these statistics, and there is the aforementioned problem of over-diagnosis and misdiagnosis of ME/CFS. Estimates vary from 150,000 to 250,000. Twenty or so years ago, before the psychological model of ME had taken hold, estimates were that about 25% of ME patients recovered, about 25% had it so severely that they were immobile and unable to speak or swallow and about 50% had ME to a mild or moderate level all their lives, whereby they could continue with daily life with adjustments to allow for the limitations and effects of the disease, which may be similar to the pacing model and may also include strategies, medications or therapies to help alleviate some symptoms. It was known that ME could be relapsing, remitting and also variable. It is not unique among diseases in that regard. It is notable that in those days, recovery was not a result of any treatments, but the natural healing processes of the body itself, as generally occurs with any viral infection. WHO classification at ICD-10 G.93.3 is Post-Viral Fatigue Syndrome: Benign Myalgic Encephalomyelitis.

PACE excluded the severely and even many moderately affected, in that participants had to be able to attend clinic for appointments – some moderately affected patients are housebound if not bedbound. This is only significant in that this was not emphasised in the commentary and media hype following publication of the results – i.e. the results cannot be extrapolated the whole ME population, aside from the valid criticisms that, given the entry criteria and subsequent changes to the entry criteria, results cannot be reliably applied to any ME patients at all. It is also worth noting that some of those patients who are now severely affected and bedridden deteriorated to that level of severity following CBT and GET. This is why medical and scientific experts on ME, as well as the patient community itself, are so concerned about the implications of the overstated and misrepresented results of PACE – i.e. they are being used by NICE as evidence that its guideline for ME does not need to be reviewed, whereas other research evidence shows, as do the PACE results if correctly interpreted, that there is urgent need for review. An example of this is a study published in September showing that researchers at Dundee University found evidence of persistent viral infection in children with ME/CFS – the same as had been found previously in research involving adults. These findings accord with expert Dr. Nancy Klimas, greatly experienced in working with both HIV and ME/CFS patients, who emphasises in her training for doctors, the high degree of inflammatory response in ME/CFS patients, which would contraindicate the value of GET, and her own recently published study showed that CBT and GET are of no value for ME/CFS patients.

You say that ME is reversible by CBT and GET, yet you have no scientific evidence of this – PACE certainly does not support your belief.

Dr. A. Martin Lerner, an infectious disease specialist, says anything that raises the heart rate of someone with ME/CFS is dangerous, unless they are well on their way to recovery (at a 7 on his EPIS® chart.) He says this from his experience of patients in practice that shows that ME/CFS involves the heart. Dr. Lerner has published studies about abnormal heart function in people with ME/CFS, showing dysfunction even at normal daily levels of exertion, abnormal movement both at rest and under stress, and T-wave abnormalities distinct enough to provide a diagnosis. I believe research in this area was presented at last year's IiME conference in London, and that a test that would show the damage to the heart in ME patients that mainstream cardiologists could use, was being developed.

Expert Dr. Paul Cheney has pioneered clinical research in CFS (ME) over 25 years. He has lectured around the world and is an internationally recognized authority on the subject. Dr. Cheney says:

“The most important thing about exercise is not to have them do aerobic exercise. I believe that even progressive aerobic exercise, especially in phase one and possibly in other phases is counter-productive. If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA".

Contrary to your unsubstantiated belief that ME is reversible by CBT and GET, the damage done by CBT and GET can be irreversible. One such case (of many) is the late Lynn Gilderdale, who died in 2008 aged 31 by her own hand with the assistance of her devoted mother, after 17 years of illness, having contracted ME at the age of 14. I urge you to read the book written by her mother Kay and published by Ebury, called One Last Goodbye. You can buy it via Amazon or by calling 0845 155 0720 (free p&p) or you could ask your local library to order a copy.

I also urge you read the case of Sophia Mirza, who died aged 32 in 2005, which her mother Criona Wilson has made available at this website: www.sophiaandme.org

The coroner recorded Sophia's cause of death as renal failure due to CFS (ME). Post-mortem showed damage to the spinal cord and basal root ganglia. At Lynn's post-mortem, the pathologist discovered dorsal root ganglionitis – infected nerve roots – and nodules of Nageotte, which Kay explains are little tombs of dead cells, in her spinal cord that would have caused her terrible pain and sensory nerve damage. Both post-mortems provide unequivocal evidence of the true pathology of ME and show that the classification of this disease by WHO is correct.

You said, “This is why I think the criticisms about this study are a mirage. They obscure the fact that what the investigators did scrupulously was to look at chronic fatigue syndrome from an utterly impartial perspective.”

This statement is simply not supported by the evidence. The scientific evidence (over 4,000 papers) shows that ME is a serious and potentially fatal neurological disease of the central nervous system of infectious onset with multi-systemic effects, affecting the heart, brain and other organs. It is unreasonable to expect that an organic disease of this complexity and seriousness can be “reversed” as you describe, by therapies such as CBT and GET. Given that these therapies were not being compared to drug or surgical interventions, your claims that the investigators were “scrupulous” and that their perspective was “utterly impartial” is simply unfounded.

You said: “The issue here which I still fail to understand is that nobody is claiming that chronic fatigue syndrome is an invented illness. It's taken just as seriously as any other condition.”

This statement is incorrect on three counts. Firstly, there are those who claim that CFS is an illness that was invented in the 1980s by the small group of psychiatrists that includes Simon Wessely, Peter White and Michael Sharpe. This claim is based on the fact that they conflated CFS with the already well documented and well-defined disease myalgic encephalomyelitis. There was no need to rename and redefine an existing disease. The effects of this group of psychiatrists' involvement with ME have been catastrophic for ME patients in terms of both research and treatment.

Secondly, the protocol for the CBT used in PACE is based on the premise that the patients' ongoing symptoms are psychosomatic and that they have become stuck in a pattern of helplessness and dependency, hence the idea that symptoms can be reversed by the patient changing their illness beliefs. The idea behind GET is that patients have become deconditioned and have developed a fear of activity. There is plenty of evidence in the training materials for health professionals and information leaflets given to patients at ME clinics run on these lines, that these are the ideas behind CBT and GET. In this sense, patients are seen as inventing their symptoms.

Thirdly, ME is not taken seriously by NHS doctors and other health professionals who have been influenced by the Wessely group school of thought about ME. On the contrary, they are actively encouraged not to take it seriously. They are advised to “perform the minimum number of investigations” as sending the patient for lots of tests will validate their mistaken belief that they are ill. The basic battery of tests recommended by NICE are tests of exclusion for other conditions, not tests to positively diagnose ME, and many GPs do not even authorise those basic tests. You can see how, with this guidance, there is such a high degree of misdiagnosis, over-diagnosis and missing of treatable conditions, with often serious implications for the health of patients, as relatively easily-identified conditions go undiagnosed, such as thyroid disease, endocrine dysfunction, Ehlers Danlos and other syndromes, liver disease, postural orthostatic tachycardia syndrome, which one third of ME patients are estimated to have. Some of these conditions may be ME-related due to the multi-systemic nature of ME and ME patients often develop auto-immune diseases for example, and also rare cancers - and some are separate conditions. Many doctors tell their patients there is no such thing as ME. There have been cases of people collapsing in the street and paramedics refusing to take them to hospital when they are told the person has ME/CFS, and others where patients have made it to A&E only to be sent home with no investigation of the cause of their collapse when the doctor is told they have ME. So, you are wrong that the illness is taken seriously by any other than those few doctors who either know that ME is an organic disease and treat it accordingly with symptom management, or who have no knowledge of ME but take their patients seriously and are willing to learn by treating their patients as individuals in relation to their symptom profile and management plan.

You said: “Not this kind of orchestrated response trying to undermine the credibility of the study from patient groups, but also the credibility of the investigators, and that's what I think is one of the other alarming aspects of this. This isn't a purely scientific debate; this is going to the heart of the integrity of the scientists who conducted this study.”

This is an unsubstantiated and unfair comment. Let's look at the facts. We live in the modern world and the age of the internet and the FOI Act. Individual patients who previously had no access to study protocols and research papers at source, had restricted access to information in general, and were, in many cases, confined to their homes and beds by ME, now have this direct access, and are able to judge for themselves and to communicate directly with each other as never before. Patient groups have been unable for the past 25 years to reintroduce a common sense approach to ME in the NHS. The upshot has been 25 years of medical and social abuse and neglect, misappropriation of MRC funds to proponents of the biopsychosocial model of ME away from biomedical research that may result in proper treatment. You may know that patients, such as Sophia Mirza, have been forcibly removed from their homes for psychiatric assessment and the very treatments that you have such confidence in, which in fact have shown what they already knew – they did not have a psychiatric disorder but an organic disease. You may know that this includes children, such as Ean Proctor, under the care of Simon Wessely at the time and famously put in a swimming pool on the basis that he would be forced to move his limbs to avoid drowning, which he could not do as he was genuinely immobile and mute at the time, and had to be saved from drowning. In-patients have been denied food for days on end and not taken to the toilet, again on the basis that need will force them to get up and move for themselves. A recent case of such mistreatment was that of Theda Myint in Australia, as reported in WAToday last week. Without proper medical treatment for her organic disease, she is in serious danger of becoming yet another death from ME.

Objections to the PACE trial itself and the misrepresentation of its results cannot be described as orchestrated, simply because patients have had enough of this artificially constructed “debate” about the underlying causes of ME and of millions of pounds of public funds being wasted on researching and providing treatments that we now know from these years of direct experience are at best unhelpful at treating ME and at worst, harmful to a majority of ME patients.

“The accusations that are being made about them is that they have behaved unethically, breached international standards of ethics, and indeed in a few examples allegations have been made to professional authorities, the General Medical Council here in the UK, about the work of these scientists, on the basis of the flimsiest and most unfair allegations. And indeed the study cost 4-million pounds to undertake but the allegations and the freedom of information requests and the legal fees that have been wrapped up over the years because of these vexatious claims has added another 750,000 pounds of taxpayers' money to the conduct of this study.”

This is a cheap shot at critics of PACE. If patients meekly accept this wastage of public funds that could be used for biomedical research and remain submissive to treatments that they know to unhelpful and harmful, then they remain in a limbo of medical neglect and abuse, the prospect of a real cure or real treatments ever more distant as the years pass. If they speak up and object, making use of their democratic and legal right to freedom of information, they are subject to allegations of making vexatious complaints and of costing yet more money.

You said: “Indeed, and I think this is where one sees a real fracture in the patient community. One is seeing a very substantial number of patients very willing to engage in this study, desperate to get good evidence on which to base their future treatment. But one sees a fairly small, but highly organised, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients.”

Here, you are perpetuating the myth of discord within the patient community – a method of divide and rule that has been used as an excuse for not progressing biomedical research and treatment. Every single patient with ME wants to recover and is willing to try anything and go to any lengths to improve their health status. They prove this by spending thousands of pounds of their own money in the process, or as much as they can afford. You are missing the point that the reason patients object to CBT and GET is that studies of these therapies have been done before and that many patients have already undergone these therapies under the NHS and thereby know from experience that they do not work and can be harmful.

Your implication that patients who are critical of PACE are not themselves desperate to get good evidence on which to base their treatment is totally unfounded. There is already a wealth of such good evidence, which patients want NICE to take account of and which is being wilfully ignored in favour of the Wessely school psychiatrists' approach. The patient critics of PACE are fighting for their lives by campaigning to the best of their limited abilities for long-awaited funding for biomedical research that may lead to treatment (likely to be anti-virals or immune modulators) and for adoption of the Canadian Consensus Criteria for ME/CFS, which can be used for both diagnostic and research purposes.

You said: “Well, what we're doing right now is waiting for the formal response from the authors to this 43-page attack on their integrity and the study, and the request for a retraction. We plan to publish their response to that attack. We will invite the critics to submit versions of their criticisms for publication and we will try as best as we can to conduct a reasonable scientific debate about this paper. This will be a test, I think, of this particular section of the patient community to engage in a proper scientific discussion.”

Your language is emotive and hardly conducive to the reasonable scientific debate that you claim to seek to engage in. Patients have been subjected to 25 years of systematic institutionalised abuse and neglect as result of the “philosophy” of the PACE trial investigators, and yet you describe their valid criticisms of this trial as attacks and plan to subject them to a test against seasoned professionals. This is quite extraordinary. Would you put patients with cancer or AIDS or any of the other neurological diseases such MS, Parkinson's and Alzheimer's to such a test? I also note that you have already declined to publish letters of response to your publication of PACE, which does not accord with your stated intention to engage patients in debate.

The simple fact is that your journal has published a research paper of which there is widespread criticism among a global community of patients, patient representatives, scientists and doctors. The paper and the criticisms can be debated in the interests of progressing scientific knowledge and bearing in mind that any research should be for the benefit of patients, not the researchers.

I find the remarks you made in the interview with Dr. Swan for Health Report insulting to a patient community that was not represented at the interview with a fair right of reply and verging on slanderous, as your assertions and allegations were unfounded and mis-representative of a disease and those afflicted by it. You have thus contributed to the mis-information about ME that is routinely propagated via mainstream media and have unfairly and unprofessionally maligned a whole community of patients. You should now issue a public apology.

You have an opportunity for insight into the world of biomedical research by attending the Invest in ME conference next month and once again, I urge you to accept that invitation.

Your sincerely,

Jo Best
Patient Advocate