Neuroimmune Alliance Responds to the Pace Trial

The responsible physician Per Julin for a newly opened ME/CFS clinic at the Danderyd hospital in the area of Stockholm of Sweden comments the PACE trial. His letter has been published in a blog operated by a different person. He has made comparisons to outcomes of treatments of MS patients.

http://www.dagensmedicin.se/Pages/Blogs/BlogPostView.aspx?id=104123

Here is a translation of a part of the letter of Per Julin:

"I interpret the findings of the PACE-trial in a different way than the authors. The interpretation that CBT and GET are efficient (nearly curative) treatments of ME/CFS is not correct. The effect on the SF-36 physical function is moderate (to say the least) after a whole year of training (in a small but well done study of MS patients one could see the same effect within 6 weeks with a different form of treatment [1].

In the PACE-tial the final are results after one year of training in terms of the SF-36 physical function still below the mean for MS patients who had their disease in average during 11 years [2].

Our interpretation is that the study neither APT (adaptive pacing theraphy), GET or CBT can cure ME - the positive effect is very small in terms of duration - they actually react worse to the training than MS patients can do. Earlier studies have also shown more negative data for CBT and GET for ME/CFS [3]."

Introduction

The main three PACE Trial protagonists are mental health professionals. Comprising of two psychiatrists (Professors Peter White and Michael Sharpe) and a behavioural therapist (Professor Trudie Chalder who works with Professor Simon Wessely), the PACE trial has less to do with the neurological disease M.E and more to do about politics. Why does a disease that the Department of Health accepts as Neurological need overseeing by mental health professionals? And why do the press keep repeating that the disease known as M.E/CFS can be cured by exercise and talking therapies; who are these people who claim success using these treatments?

The answer comes down to that age old argument about patient representation and cohorts? Study the right patients and you get the right answers. Open a trial to literally any patient with mental health problems and fatigue, close it to anyone severely affected and bedbound and you get the wrong selection criteria and a flawed study.

Please observe here that when referring to M.E/CFS, I am not referring to the variety of patients PACE included in its study, i.e. “I’ve overdone it a bit, been feeling one degree under” chronic-fatigue. I am referring to the Neurological Disease Myalgic Encephalomyelitis, about the full-blown syndrome, a distinct entity under ICD-10 which is NOT stress, burning the candle at both ends, anaemia, obesity or lack of exercise.

I am also not referring to any form of mental illness, which incorporates its own dissimilar trials and tribulations concerning the exploitation of patients.

The early PACE documents came with an attachment circulated amongst the Wessely School that said “watch out for lobbyists”. When thousands of people with M.E/ CFS are up in arms, forming a Resistance against the classification of a psychiatric/hypochondriacal diagnosis, we are not discriminating against people with mental illness or refusing to accept the label, it’s because WE ARE NOT MENTALLY ILL. The misdiagnosis and subsequent treatment aimed at the mentally ill does not help us. Banging down our doors and carting us off to mental wards where we die does not help us.

The disease Myalgic Encephalomyelitis (M.E) has been catalogued by the World Health Organisation (WHO) as a neurological disease since 1969.  It is presently listed under the International Classification of Diseases (ICD), chapter 6, under Disorders of Brain at ICD-10 G 93.3.  During the 1992 modification of the ICD coding, it was permitted that the term “Chronic Fatigue Syndrome” (CFS) would be a name by which the disease M.E may be classified as. The actual term “CFS” is classified only to ME at ICD-10 G93.3, hence the confusing terminology “ME/CFS” has arisen.

This report is a worldwide testimony of patient’s unease and distress over the recently published Medical Research Council’s PACE Trial report and the deliberate intention of the trial coordinators, Professor Peter White and Professor Michael Sharpe to treat M.E/CFS as a Somatic Disorder.

PACE was created and overseen by a prominent and high ranking group of British psychiatrists, Professors Michael Sharpe, Peter White and Trudie Chadler (often referred to as the “Wessely School”( Hansard; Lords, 9th December 1998:1013). These psychiatrists do not recognize nor acknowledge the World Health Organisation classification of M.E/CFS as a neurological disease but stress that it is a functional somatic syndrome (i.e. a psychosocial disorder).

Evidence in the PACE manuals indicate that the although the literature does not specifically state that M.E or CFS is a somatform disorder, the language used implies that they believe that M.E/CFS patients refer to physical symptoms that are not the product of biomedical disease but are purely the outcome of abnormal illness beliefs and that these entrenched beliefs are the cause of said disability. These psychiatrists would like to see the classification of M.E/CFS replaced by a mental health classification and are working scrupulously to achieve their endeavour.

In the years following the early recruitment for the PACE trial, more evidence of neuro-immune pathology in M.E/CFS patients has materialized, particularly the 2009 Science Paper’s XMRV findings, therefore in order to ensure the PACE trial fairly represented the M.E spectrum, one would have thought that recruitment would include patients with these specific clinical signs and symptoms but we couldn’t be more wrong.

Evidence that the PACE Trial Coordinators consider ME/CFS to be a somatoform disorder

 

As pointed out by Professor Malcolm Hooper in his submission for DSM-5 (Hooper, M and Williams, M,1999: Submission re: DSM-V and ME/CFS, for submission by The 25% ME Group: available at http://www.25megroup.org/News/DSM-V%20submission.doc), Professor Michael Sharpe is a member of the DSM–V Somatic Symptom Disorder Work Group and also a member of Conceptual Issues in Somatoform and Similar Disorders Project (CISSD, not to be confused with CSSD) that was launched by Richard Sykes to stimulate dialogue about the taxonomy of functional somatic syndromes, which the CISSD Group asserted included irritable bowel syndrome, Chronic Fatigue Syndrome and fibromyalgia.  (Richard Sykes was formerly Director of the ME charity Westcare, now merged with the charity Action for ME, whose brother Sir Hugh Sykes is a non-executive Director of Action for Employment known as A4e, the largest European provider of Welfare to Work programmes that implements a social policy introduced in the UK in 1997 which focuses on specific groups of people claiming benefits, including those on disability benefits). According to Sharpe and Sykes, the CISSD Group’s aim was to make the criteria for Somatoform Disorder either “more inclusive” or to add a “lower threshold category” (Kurt Kroenke, Michael Sharpe, Richard Sykes. Review Article: Revising the Classification of Somatoform Disorders.  Psychosomatics 2007:48:277-285). 

Of particular concern is the fact that a diagnosis of somatisation may depend on a “total symptom count”, which “may bypass the methodological difficulties in arbitrating symptom aetiology”, because there are over 50 recorded symptoms in ME/CFS (The Disease of a Thousand Names. David S Bell. Pollard Publications, New York, 1991). At the Royal Society of Medicine meeting on 28th April 2008 on CFS, Professor Peter White advised that once a CFS patient has more than four symptoms, it was likely that s/he had a psychiatric disorder. Such a belief cannot be objectively verified and is not in accordance with the British Medical Association’s advice on complex medical disorders. The Foreword to The British Medical Association Complete Family Health Guide is clear: “The Guide is based on advice from a panel of medical consultants chosen by the BMA, and their experience provides an unrivalled assurance of quality and reliability”. Under hyperthyroidism, the BMA consultants list 10 symptoms; under Cushing’s syndrome, 11 symptoms are listed; under asthma, 11 symptoms are listed; under chronic kidney failure, 8 symptoms are listed; under AIDS, 13 symptoms are listed.  (Hooper, M and Williams, M,1999: Submission re: DSM-V and ME/CFS, for submission by The 25% ME Group: available at http://www.25megroup.org/News/DSM-V%20submission.doc)

 

Peter White himself has tried on many occasions to over ride the ICD10 classification.

Therefore how one can take this maverick trial seriously is beyond comprehension.

Professor Michael Sharpe

Professor Michael Sharpe is the Director of the Psychological Medicine Research Group at the University of Edinburgh and studies the nature, cause and management of symptoms in medical patients. His work includes the study of symptoms in patients with cancer and with neurological disease as well as symptoms which are regarded as "medically unexplained". Our methods are principally those of clinical epidemiology and include case control studies and clinical trials. The research group is based in the University Division of Psychiatry with research teams located within the Divisions of Oncology, Clinical Neurosciences and Primary Care.

Professor Sharpe asserts that M.E/CFS patients are not ill because of any pathological disease; he has been quoted on record as maintaining that ME is “a pseudo-disease diagnosis” (Occup Med 1997:47:4:217-227); his personal belief about M.E/CFS “has long been that the issues surrounding (it) are the same as those surrounding acceptance and management of (patients) who suffer conditions that are not dignified by the presence of what we call disease” (J Psychosom Res 2002:52:6:437-438). Sharpe also upholds that sufferers of M.E/CFS choose the “advantages” of the “sick role” and therefore should not qualify for welfare benefits and has famously stated that ME/CFS patients are “the undeserving sick of our society and our health service” because they “refuse to be placed into and accept the stigma of mental illness” (Michael Sharpe;  “ME.  What do we know – real physical illness or all in the mind?” lecture given in October 1999 hosted by the University of Strathclyde).

 

In 2002, Michael Sharpe published a paper titled “Functional Symptoms and Syndromes: Recent Developments” (published in “Trends in Health and Disability” by the insurance company (UNUMProvident: http://www.unumprovident.co.uk/NR/rdonlyres/E03B0BCF-EAA0-45B6-95E2-54BEC5C600F8/0/CMOReport2002.pdf) in which he stated that functional somatic syndromes have been referred to as “’hysteria’, ‘abnormal illness behaviour’, ‘somatisation’, ‘somatoform disorders’….Recently, the terms MUS and ‘functional symptoms’ have become popular amongst researchers”. In his table of “Common medically defined functional syndromes” Professor Sharpe included the taxonomically separate disorders Chronic Fatigue Syndrome, fibromyalgia (classified in ICD-10 at M79), irritable bowel syndrome and multiple chemical sensitivity and proposed that “these conditions be considered together as a ‘general functional somatic syndrome”.

 

PACE Co-ordinators beliefs of M.E as a “classical psychosomatic disorder”:

 “Anorexia Nervosa (AN) and chronic fatigue syndrome (CFS) are classical psychosomatic disorders where response to social threat is expressed somatically” (advertisement for a psychology graduate to work with ME/CFS patients placed by the Institute of Psychiatry; the closing date for applications was 13th July 2007 and the job reference was 07/R68.  The post-holder was to work under the direction of Professor Trudie Chalder, a behavioural therapist who, together with Michael Sharpe and Peter White, is one of the Principal Investigators of the MRC PACE Trial).

 

Consequently, it is also the conviction of the PACE psychiatrists that “cognitive distortions” (ie. uncharacteristic illness beliefs) are wholly accountable for the prolonging of primary M.E/CFS symptoms. I quote:

 

“The clinical problem we address is the assessment and management of the patients with a belief that s/he has an illness such as CFS, CFIDS (chronic fatigue immune dysfunction syndrome, a term used in the US) or ME….The majority of patients seen in specialist clinics typically believe that their symptoms are the result of an organic disease process…Many doctors believe the converse” (Sharpe M, Chalder T, Wessely S et al.  General Hospital Psychiatry 1997:19:3:185-199).

 

The MRC PACE Trial Identifier states: “CBT will be based on the illness model of fear avoidance.  There are three essential elements: (a) assessment of illness beliefs and coping strategies, (b) structuring of daily rest, sleep and activity, with a graduated return to normal activity, (c) challenging of unhelpful beliefs about symptoms and activity”  (Section 3.2). 

 

“the symptoms and disability are perpetuated predominantly by unhelpful illness beliefs (fears) and coping behaviours (avoidance)” (MRC PACE Trial CBT Manual for Therapists, page 18).

 

How the Government can state that they recognise the World Health Organisation ICD10 classification of M.E then allow the PACE trial to outright dismiss the WHO classification is a breach of human rights, the PACE coordinators declare:

“Medical authorities are not certain that CFS is exactly the same illness as ME, but until scientific evidence shows that they are different they have decided to treat CFS and ME as if they are one illness” (http://pacetrial.org/PCL%20version%2009.pdf) and instructs doctors involved with the Trial that: “if a participant calls their illness ME don’t attempt to challenge this, ME or CFS is an appropriate term to use”  (MRC PACE Trial; SSMC manual for participating doctors, page 13).

Professor Peter White

With his colleague working abhorrently on the DSM-5 classification in the United States it is easy to overlook Professor Peter White’s intent on classifying M.E/CFS as a mental health disorder, in full support of his colleague.

On 28th April 2008, as part of his presentation at the Royal Society of Medicine’s conference on Chronic Fatigue Syndrome, Professor Peter White said: “I’m going to try to define what Chronic Fatigue Syndrome is.  By doing so, I’m going to review the ICD-10 criteria for the illness and see if they’re helpful.  The answer will be, they are not helpful…Does the ICD-10 help us? Unfortunately not; there are at least five ways of classifying CFS using the ICD-10 criteria. What are they? We start off well: myalgic encephalomyelitis is in the neurology chapter of ICD-10…and helpfully, “chronic fatigue syndrome, postviral”.  So it starts off well.  What if the viral illness is not a clear trigger for the illness?  Well, you’ve got alternatives: in the Mental Health Chapter, you’ve got Neurasthenia…”.

White also reiterated this point again on 20th October 2009 at a presentation in Bergen, talking AGAINST the World Health Classification of M.E. Who are these Psychiatrists to challenge a World Health Directive?

“So it starts off well. You get a virally triggered chronic fatigue syndrome - that’s your diagnosis. Or is it? What if it’s not postviral? What if the viral illness is not a clear trigger for the illness? Well, you’ve got alternatives: in the Mental Health Chapter, you’ve got Neurasthenia, which of course was talked about back in the last, and previous to last century.”

“But actually, if you are more neutral - you don’t know whether it’s physical or mental, you want to use a more neutral term - well you have got something you can use in ICD-10, in the “R Chapter” - Chronic fatigue, unspecified which helpfully includes [R53.82] Chronic fatigue syndrome NOS. You could actually use that if you don’t want to jump off the fence as to whether this is physical or mental in the dualistic mood.”

Professor White has continually stated, and the Government believe it, that “psychogenic / psychosocial fatigue” (ICD10-F.48.0) and “Chronic Fatigue Syndrome” (ICD-10 G93.3) are one and the same.

He has conversed the various somatoform classifications within the ICD-10 on previous occasions, stating:

 “The trouble with these diagnoses is, you somehow have to guess that psychological factors have an important role to play in their aetiology”. He concluded one presentation by stating:

 “ICD-10 is not helpful and I would not suggest, as clinicians, you use ICD-10 criteria.  They really need sorting out, and they will be in due course, God willing" (“What is Chronic Fatigue Syndrome and what is ME?”; webcast:  (http://rsm.mediaondemand.net/player.aspx?EventID=1291).

Was that not a clear attempt to direct medical professionals to take no notice of the ICD-10 classification of M.E/CFS as a neurological disease and reclassify?

The specific accuracy of diagnosing M.E/CFS is of critical importance. A patient with a complex multi-organic  neuro-immune disease like ME/CFS calls for exceptionally different treatment and care from a patient with a vaguely defined diagnosis of chronic “tiredness” – something the PACE manuals do not take into account.

It is beyond any reasonable doubt that Sharpe and White have incorporated a diverse range of unexplained fatigued states under the umbrella of the disease M.E/CFS (for example somatisation disorders, bipolar disorder, states of depression, deconditioning). They deliberately ignore specific key markers of M.E/CFS such as post-exertional malaise and hold in contempt any published literature by world class researchers as well as described symptoms by the patients themselves. Instead, Sharpe and White choose to remain blinkered and concentrate on ‘fatigue’ and patients so called “cognitive distortions”. (Moss-Morris, 1997: Cognitive Factors in the Maintenance

of Chronic Fatigue Syndromehttps://researchspace.auckland.ac.nz/bitstream/handle/2292/3225/01front.pdf?sequence=3)

It is safe to say that the MRC PACE Trial was designed specifically around this model of M.E/CFS, on the conjecture that all M.E/CFS patients are deconditioned and that the fatigue patients experience is down to this sliding level of activity and motivation levels – not due to mitochondrial dysfunction or myopathy. The very specified form of exhaustion experienced from cellular depletion and mitochondrial dysfunction is not on par to the everyday tiredness experienced by normal individuals yet White and Sharpe associate it as tiredness due to laziness, not disease.

The PACE trial coordinators have stated overtly that M.E/CFS can be cured by using cognitive behavioural therapy and/or graded exercise therapy. Professor Michael Sharpe has stated “There is evidence that psychiatric treatment can be curative” (British Medical Bulletin 1991:47:4:989-1005) and Professor Peter White has asserted “recovery from CFS is possible following CBT….Significant improvement following CBT is probable and a full recovery is possible” (Psychotherapy Psychosom 2007:76(3):171-176).

From reading the above it is astonishing that Professor Peter White was allowed to become the PACE Trial Chief Investigator – surely his beliefs about M.E stand as a conflict of interest and go against any medical ethics laws that stand under the European Convention of Human Rights.

Professor Trudie Chadler

 The venomous views of Professor Trudie Chadler are another reason why the cohorts for the PACE trial were deemed to be flawed from the beginning.

As pointed out again by Professor Hooper in Magical Medicine, “there is compelling evidence linking ME/CFS with exposure to environmental toxins, specifically to organophosphates and chemical warfare agents, demonstrating that patients with ME/CFS have reproducible alterations in gene regulation, especially those genes associated with immune, neuronal and mitochondrial function (N Kausnik, ST Holgate and JR Kerr et al. J Clin Pathol 2005:58:826‐832). “

However, Trudie Chalder supposes that CBT is able to repeal these acquired alterations in gene regulation (Presentation to the Group of Scientific Research into ME at the House of Commons [the Gibson Inquiry] 7th June 2006).

Chalder also states that CBT can restore people with “CFS/ME” to full time employment (Occupational Aspects of the Management of Chronic Fatigue Syndrome: a National Guideline; NHS Plus, October 2006: DH Publications 2006/273539).

Professor Chalder believes that patients and perhaps also their doctors can be difficult to “brain‐wash” with CBT, so she appears to have put in place a rather disturbing strategy to overcome such difficulties – bitterly reminiscent of Esther Crawley and the SMILE trial. 

In “Biopsychosocial Medicine” edited by Peter White, Trudie Chalder made an outwardly distressing contribution: “Rather than start with the physicians, which might be quite a difficult task, we could make a start with youngsters in schools. My experience is that they are much easier to educate. The only barrier is the parents. Once we have the child on our side we are in a very good position” (http://www.meactionuk.org.uk/PROOF_POSITIVE.htm).

 “A Cognitive Model of CFS/M.E” as used in the PACE Manuals

“The model as a whole attempts to explain how early life experiences lead to the formation of assumptions that combined with certain lifestyle stressors, many precipitate CFS in predisposed individuals”

The model then attempts to explain how cognitive, behavioural, biological and social factors interact in a vicious circle to perpetuate or maintain the illness.

According to this model the interpretation of symptoms was not any manifestation of physical illness. This model was based around 100 patients. We know that almost 50% of the trial participants also had significant mental disorders such as depression, OCD or anxiety. Yet we know that the frequency of these disorders is not higher in true ME patients. Therefore the trial comprised of an exceptionally curious group of depressed patients that were able to exert themselves without any side effects. Therefore to include people with mental illness in the trial and ignore the immunological, neurological and endocrine factors in M.E despite hundreds of published articles citing these abnormalities in patients and reclassifying M.E/CFS according to their own flawed model is something that needs to be addressed in a Court of Law.

Yet the MRC claimed in a letter to Professor Malcolm Hooper on 23rd February 2011 that “the peer reviewers and the MRC Board were satisfied that the PACE trial was adequately justified based on the extant literature when the funding decision was taken” and that “the MRC does not believe that the beliefs regarding the aetiology of CFS/ME materially affect the ability of members of the Data Monitoring and Ethics Committee to act independently, since data provided to the DMEC were blinded as to treatment allocation.”

Sharpe and White assert that there is no biomedical reason for the symptoms M.E/CFS patients’ experience. Described on Pages 9-16 of the PACE Trial CBT Manual for Participants, Sharpe and White claim that there is no pathology causing the troubling symptoms and even more worrying, they do not differentiate between physiology and pathophysiology – merely stating that the physical changes in the body result from deconditioning and therefore are reversible by CBT and GET.

This contradicts the multitude of published evidence showing states of chronic low grade immune activation in M.E/CFS patients and evidence of frequent latent active infections with various entoviruses and herpesviruses. Professors De Meirleir and Englebienne have done extensive research into M.E/CFS and a common finding is the dysfunction of the 2-5A.RNase L pathway - causing cell death (apoptosis) and inflammation, processes observed in M.E/CFS. New treatment approaches may involve immunomodulators such as bile salt or retinoic acid derivatives.

 

As stated in “Chronic Fatigue Syndrome: A Biological Approach by Paula M. Carnes (http://www.name-us.org/ResearchPages/ResearchArticlesAbstracts/ImmuneArticles/EnglebeinneDeMeirleirSummaryCarnes.pdf)”What are the most likely causes of CFS? The simple answer is CFS is an acquired immune dysregulation with persistent ongoing infections. But what causes this?

 

Approximately 72% of CFS patients came down with an infection initially. No one has found a single precipitating virus but that does not mean there is not one. It does seem that EBV and HHV-6 are reactivated with CFS rather than the cause, as most people on earth have had these viruses in childhood.

 

Therefore I deem it sheer madness to tell patients to ignore their symptoms when their bodies are fighting chronic infection.

 

Peter White and the Warped London Criteria

 

In 2006 it appeared that White was finding it a challenge to recruit patients to the trial. In a letter dated 14th July 2006 to the West Midlands MREC, White asked for permission to advertise the PACE Trial to GP’s.

The wording of the advertisement to GPs is curious: “If you have a patient with definite or probable CFS/ME, whose main complaint is fatigue (or a synonym), please consider referring them to one of the PACE Trial centres”. Just how scientifically rigorous the inclusion of patients with “fatigue (or a synonym)” might be is a matter for speculation. (Hooper 2010)

Such lax criteria has resulted in a patient who had shingles being included on the PACE trial. Since the Oxford Criteria allows any person who is chronically “fatigued”, patients with post‐herpetic tiredness are acknowledged to have been included in the PACE Trial, even though herpes zoster is not the same disorder as ME/CFS. Such a haphazard use of selection criteria indicates that the results of the PACE Trial are futile. (Hooper 2010).

25% of the study participants had been ill less than 16months at baseline – which questions whether or not these patients had been screened accurately for genuine M.E – the early stages of the illness are the hardest to diagnose.

This is highlighted by the fact that at the end of the trial after 52 weeks only 63% were reporting post exertional malaise in the control group - the definitive symptom for ME. At baseline this was 87%, yet in the GET group only 82% has post exertional malaise at baseline.


But overall 52 and 53% in the CBT and GET groups reported feeling the same or slightly worse and 6% and 7% reported feeling much worse. So 60% of people were not helped or were made worse.

There are no exact figures for comparing the London ME group that excludes depression for physical functioning, but from the graph you can see that the control (SMC) is almost identical to CBT and GET. Therefore I have said that the difference is less than 5%, which it clearly is from the graph. Obviously the authors do not want this fact published in actual numerical value.

Peter White moves the goalposts and changes the criteria to suit himself!

A discussion on the Phoenix Rising forums (pointed out that the PACE trial compared and contrasted the subsets using “the London criteria for ME (criteria requiring post exertional malaise…”). The initial objective of the trial was to use the Ramsay definition of M.E. As stated by Professor Malcolm Hooper on page 417 of “Magical Medicine” these were date-stamped by the MREC as received on 21st March 2003. (http://www.meactionuk.org.uk/magical-medicine.htm).

The use of the Ramsay definition of M.E sounds all well and good but disparagingly, Professor White revised the definition and he used instead what looks as if to be his own warped version of the “London Criteria” for the Ramsay definition. If one looks at page 417 of Magical Medicine, obligatory symptoms under the Ramsay definition are: fluctuation of symptoms from day to day or within the day; headaches; giddiness; muscle pain; muscle cramps; muscle twitching; muscle tenderness; muscle weakness; pins and needles; frequency of passing water; blurred vision; double vision; increased sensitivity of hearing; increased sensitivity to noise; feeling generally awful, and muscle weakness after exercise.

On the contrary, Professor White’s revision of the “London Criteria” explicitly states on page 188 of the Full Protocol that neurological disturbances “are not necessary to make the diagnosis” and they continue to state that “the usual precipitation by ‘physical or mental exercise’ should be recorded but is “not necessary to meet criteria”.

According to Professor White’s adaptation of the “London Criteria”, there is no requirement for impairment of short-term memory and loss of concentration, nor is there any necessity for primary depression or anxiety disorder to be existing (note: if depression or anxiety disorder are present, the Full Protocol states “This means if any depressive or anxiety disorder is present, the London criteria are not met”).

This highlights the perturbing fact that the trial participants reported a 47% prevalence of mood and anxiety disorder at baseline.  The Lancet article states that of the 641 participants, 329 (ie. 51.3%) met Professor White’s version of the “London Criteria”; the underlying meaning being that almost everyone who did not have anxiety or depression met the “London Criteria” used in the PACE Trial, but Professor White’s version of the “London Criteria” in the Full Protocol do not require exacerbation of symptoms by physical or mental exercise.

In other words, of the 53% who did NOT have anxiety or depression at baseline, 96.8% met Professor White’s “London Criteria”, but this revised criteria did not require the prime attribute of ME to be present.

This leads one to ask exactly what disease was being studied here under the band of ME/CFS, because the obvious characteristic highlighting Ramsay-defined ME and somatisation disorder has been purposely blurred by Peter White, manipulating the criteria to fulfil his flawed theories of M.E, again bringing the question of ethics into the fore.

Taking into consideration that although the Ramsay definition for M.E does exist (Postgrad Med J 1990:66:526-530), the “London Criteria” in reality does not and that the citation referred to in the Lancet is to the 2004 Westcare Report, which purely stated that the London Criteria was “proposed” criteria only; it has never been published, has no acknowledged authors; they have never been published and furthermore, as stated by Angela Kennedy on Phoenix Rising there is no methods paper which distinctively describes the criteria as a “case definition”; they have never been approved nor have they even been finally defined (there are various versions); they have never been validated and they are not on PubMed thus are not available for scrutiny so they cannot be accessed for comparison.

This basically means that Professor White was fundamentally able to invent his own version of the “London Criteria”.

Now, back to the issue of the exclusion of genuine M.E patients from the PACE trial. Should the trial have used the Canadian Criteria for M.E, the following symptoms would have been included in the cohorts, as pointed out by Angela Kennedy:

1. POST-EXERTIONAL MALAISE AND FATIGUE: There is a loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional fatigue, malaise and/or pain, and a tendency for other symptoms to worsen. A pathologically slow recovery period (it takes more than 24 hours to recover). Symptoms exacerbated by stress of any kind. Patient must have a marked degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level. [Editor’s note: The M.E. Society prefers to use “delayed recovery of muscle function,” weakness, and faintness rather than “fatigue.” Further, we disagree that the muscle dysfunction and post-exertional sickness is “unexplained.”

2. SLEEP DISORDER: Unrefreshing sleep or poor sleep quality; rhythm disturbance.

3. PAIN: Arthralgia and/or myalgia without clinical evidence of inflammatory responses of joint swelling or redness. Pain can be experienced in the muscles, joints, or neck and is sometimes migratory in nature. Often, there are significant headaches of new type, pattern, or severity. [Editor’s note: neuropathic pain is a common symptom and should be added here as well.]

4. NEUROLOGICAL/COGNITIVE MANIFESTATIONS: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, difficulty with information processing, categorizing, and word retrieval, intermittent dyslexia, perceptual/sensory disturbances, disorientation, and ataxia. There may be overload phenomena: informational, cognitive, and sensory overload -- e.g., photophobia and hypersensitivity to noise -- and/or emotional overload which may lead to relapses and/or anxiety.

5. . AT LEAST ONE SYMPTOM OUT OF TWO OF THE FOLLOWING CATEGORIES:

(a) AUTONOMIC MANIFESTATIONS: Orthostatic Intolerance: e.g., neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension, vertigo, light-headedness, extreme pallor, intestinal or bladder disturbances with or without irritable bowel syndrome (IBS) or bladder dysfunction, palpitations with or without cardiac arrhythmia, vasomotor instability, and respiratory irregularities. [Editor’s note: low plasma and/or erythrocyte volume should be added as another explanation for orthostatic intolerance in this disease. More cardiac symptoms should be listed such as left-side chest aches and resting tachycardias, which, in addition to low blood volume, have also been documented in the research. The full text of the case definition does suggest 24-hour Holter monitoring, and when tachycardias with T-wave inversions or flattenings are present that they not be labeled as nonspecific since they aid in the diagnosis of ME/CFS. The frequent tachycardias seen in ME/CFS have been shown by Dr. Paul Cheney to be a compensatory mechanism that serves to increase cardiac output in the presence of low stroke volume due to diastolic dysfunction in the heart. Orthostatic problems may also be related to diastolic dysfunction as recently shown by Dr. Paul Cheney. See our Cardiac Insufficiency Hypothesis page.]

(b) NEUROENDOCRINE MANIFESTATIONS: loss of thermostatic stability, heat/cold intolerance, anorexia or abnormal appetite, marked weight change, hypoglycemia, loss of adaptability and tolerance for stress, worsening of symptoms with stress and slow recovery, and emotional lability.

(c ) IMMUNE MANIFESTATIONS: tender lymph nodes, sore throat, flu-like symptoms, general malaise, development of new allergies or changes in status of old ones, and hypersensitivity to medications and/or chemicals.

 

Now the issue here is what symptoms are the majority of UK M.E sufferers presenting to their G.P’s with prior to diagnosis, whether that diagnosis ends up being M.E, PVFS or CFS.

Perhaps I am wrong, but 99% of sufferers I have encountered have a myriad of symptoms, primarily neurological ones.

Now, more than 2300 people referred to one of six Chronic Fatigue clinics by their GP’s were considered unsuitable for the PACE trial because apparently they did not have “Chronic Fatigue Syndrome”. Now 2300 people is an awfully high number of misdiagnoses – where did all these patients go? Perhaps they were like me, suffering with so many subsets of the Canadian Criteria such as POTS that the clinics discharged them in an uneasy flurry, after all we don’t actually want real M.E patients to be studied now do we? These clinics work as hard as they can to faze these ‘real’ patients out, leaving the ones behind to actually fit the Oxford/Reeves criteria.

Despite furious criticism from Action for M.E, Invest in M.E and the M.E Association as well as critiques in the US press, the PACE trial publication will probably mean that NICE will strengthen their Guideline to reflect the trial recommendations of cognitive behaviour therapy and graded exercise therapy, despite evidence to the contrary and against the best interests of the patient.

Instead of investing in Biomedical Research and patient organisations lobbying for such, the Medical Research Council are still leaning towards the psychiatric lobby, with interest expressed at the latest APPG meeting not in biomedical research but in Esther Crawley’s Lightening Process study in children, another thorn in the side of M.E patients.

Therefore, the PACE trial has cemented  the fact that M.E clinics will never provide benchmark medical care with a appropriate and knowledgeable consultant who treats  using therapies that have proven to be helpful such as B12 therapy,  antivirals and anti-biotic therapy, supplementation a and immune modulators and instead patients will be subjected to more harmful psychological interventions.

 

Media Links:-

http://www.nhs.uk/news/2011/02February/Pages/therapies-moderately-improve-CFS.aspx

http://news.sky.com/skynews/Article/201102115935405?ref=nf

http://www.latimes.com/news/nationworld/nation/wire/sns-bc-eu-med--chronicfatiguetreatments,0,3203489.story

http://www.independent.co.uk/life-style/health-and-families/health-news/got-me-just-get-out-and-exercise-say-scientists-2218377.html

http://www.bbc.co.uk/news/health-12493009

http://www.cnn.com/2011/HEALTH/02/17/chronic.fatigue/

http://www.guardian.co.uk/society/2011/feb/18/study-exercise-therapy-me-treatment?INTCMP=SRCH

http://health.usnews.com/health-news/family-health/brain-and-behavior/articles/2011/02/18/study-says-2-therapies-help-fight-chronic-fatigue-syndrome

http://www.nytimes.com/2011/02/18/health/research/18fatigue.html