BACKGROUND

  This submission is limited to just one aspect of the workings of NICE, namely its production of a Guideline for the management of myalgic encephalomyeltitis/chronic fatigue syndrome (ME/CFS). There is no curative treatment for the disorder.

  There is significant concern because the draft Guideline that is currently out for consultation is seriously flawed and is potentially life-threatening to patients, especially the severely affected, yet on 22 February 2007 Professor Peter Littlejohns (Clinical Director at NICE) indicated to the All Party Parliamentary Group on ME that, despite the enormous number of representations NICE had received about its draft—said to be the highest ever on any NICE project—it was unlikely there would be a second consultation process. He stated that even if the final Guideline were to be rejected by all the UK ME/CFS charities, the Guideline would still be published.

  The management regime favoured by NICE is cognitive behavioural therapy and graded exercise therapy (CBT/GET), which is a psychiatric intervention based on a behavioural modification programme. It is tirelessly promoted throughout Departments of State by a group of (mostly) psychiatrists who do not accept the WHO classification of ME/CFS as a organic neurological disorder (a classification that has existed since 1969); instead, they advise Government bodies that "ME" is nothing but a "belief" which does not exist except in the minds of patients who think they suffer from it, and that "CFS" is a "biopsychosocial" (behavioural) disorder. They have designed a management regime whose aim is to change what these psychiatrists believe is patients' "aberrant" thinking about the illness in order to convince patients that they do not have a physical illness.

  It is vital that NICE is compelled to pay due heed to the biomedical evidence on ME/CFS it has received, because in oral evidence on 10 July 2006 to the Gibson Inquiry on ME/CFS held at the House of Commons, Professor Anthony Pinching (lead adviser to the Department of Health on "CFS/ME" and Principal Medical Adviser to the charity Action for ME) was emphatic that once published, the NICE Guideline would be imposed nationally in 2007.

  This submission attempts to demonstrate that NICE and its advisers are failing in their duty to produce a Guideline that is evidence-based and that medical science has been usurped by politics, which in turn have been usurped by vested interests.

EXECUTIVE SUMMARY

  In the production of its "CFS/ME" draft Guideline, NICE has demonstrably failed to conform to the AGREE Instrument to which it is party and to whose criteria it is obliged to conform in the production of its Guidelines. Specific examples are provided under the Committee's Terms of Reference.

THE HEALTH SELECT COMMITTEE'S TERMS OF REFERENCE

1.   First Term of Reference: Why NICE's decisions are increasingly being challenged

  1.1  NICE's decisions are increasingly being challenged because it can be shown that they are driven by Government policy, not by the evidence that has been submitted to NICE; it is thus a case of NICE creating "policy-based evidence" instead of evidence-based policy, no matter that the "policy-based evidence" is damaging to patients.

  1.2  In the production of its Guidelines, NICE is obliged to conform to the criteria set out in the AGREE Instrument (Appraisal of Guidelines Research and Evaluation). The AGREE collaboration started in 1998 and originates from an international collaboration designed to enhance effective healthcare policy by the dissemination of high quality clinical guidelines.

  1.3  The following examples of failure to conform to the AGREE Instrument are cogent reasons why NICE's decisions are being challenged by the ME community.

  1.4  All Guideline Development Group members must declare any conflicts of interest: in the "CFS/ME" draft Guideline, no mention was made of the proven vested financial interests of certain Group members, notably the fact that one member is Chief Executive of a medical insurance company in whose interests it is to keep ME/CFS categorised as a "mental" disorder so that claimants are excluded from benefit.

  1.5  Patients about whom a Guideline is intended must be specifically described: in the case of ME/CFS, failure in this regard underpins the resultant confusion: "CFS/ME" is not the same as ME/CFS: the former includes anyone with medically unexplained "fatigue" lasting for as little as one month and specifically includes those with psychiatric disorders, whereas the latter is a formally classified neurological disorder, one symptom of which is post-exertional fatigue and malaise, together with multi-system dysfunction—see below.

  1.6  Patients' views and experience should be sought and used; these should have equal status with other evidence such as random controlled trials: the Government's own guiding principle for the NHS is that it must be patient-led (see "The Expert Patient: A New Approach to Chronic Disease Management for the 21st Century"; Department of Health; September 2001; see also "The Expert Patient" by John Illman published in March 2000 by the Association of the British Pharmaceutical Industry, which notes that the Department of Health is inviting patients to join the information revolution and that patients who do not develop these skills could become the underclass in the health system). In the case of ME/CFS, NICE has completely disregarded this approach. This is the most significant area of concern. Patients with ME/CFS are in general far better informed about the disorder that most physicians and policy-makers.

  1.6.1  Overwhelming evidence has been submitted to NICE that CBT/GET is not only of no lasting benefit, but may result in a permanent worsening of the condition for a substantial number of patients. This is because it has been conclusively demonstrated that exercising muscle in ME/CFS patients is a prime contender for free radical generation. An article called `A Final Farewell to the Psychiatric Fallacy?' refers to the work of the Vascular Research Unit at Dundee (see www.meactionuk.org.uk/A_FINAL_FAREWELL_TO_THE_2_PSYCHIATRIC_FALLACY.htm and points out that in ME/CFS, raised levels of isoprostanes (abnormal prostaglandin metabolites which are highly noxious by-products of abnormal cell membrane metabolism) have been demonstrated and that these raised levels of isoprostanes precisely correlate with patients' symptoms. Such raised levels of isoprostanes have never been documented in any other known disorder.

  1.6.2  There are many other documented biomedical abnormalities that NICE has deliberately ignored and denied. These include abnormalities of the central nervous system (there is evidence of a chronic inflammatory process, with oedema or demyelination in 78% of patients tested; neuro-imaging has revealed inflammatory lesions in the brain of approximately 80% of those tested, as well as evidence of a significant and irreversible reduction in grey matter volume); abnormalities of the autonomic and peripheral nervous systems; cardiovascular dysfunction (with evidence of endothelial dysfunction, haemodynamic instability, aberrations of cardiovascular reactivity, and a left ventricle ejection fraction as low as 30%); respiratory system dysfunction (there is evidence of significant reduction in many lung function parameters including a significant decrease in vital capacity); there is a disrupted immune system, with evidence of an unusual and inappropriate immune response, including increased apoptosis (programmed cell death). There are documented virological abnormalities which include evidence of persistent enterovirus RNA in ME/CFS patients, as well as abnormalities in the 2-5 synthetase/RNase L antiviral pathway, with novel evidence of a 37 kDa binding protein not reported in healthy subjects or in other diseases; there is evidence of the presence of HHV-6, HHV-8, EBV, CMV, Mycoplasma species, Chlamydia species and Coxsackie virus in the spinal fluid of some ME/CFS patients. There is indisputable evidence of muscle pathology, including laboratory evidence of delayed muscle recovery from fatiguing exercise and evidence of damage to muscle tissue; there is evidence of impaired oxygen delivery to muscle, with recovery rates for oxygen saturation being 60% lower than in normal controls; there is evidence that creatine (a sensitive marker of muscle inflammation) is excreted in significant amounts in the urine of ME/CFS patients. There are documented neuroendocrine abnormalities, including evidence of HPA axis dysfunction, evidence of a profound loss of growth hormone and even when the patient is euthyroid on basic screening, there may be thyroid antibodies and evidence of failure to convert T4 (thyroxine) to T3 (tri-iodothyronine). There is evidence of defects in gene expression profiling, with an expression profile grouped according to immune, neuronal, mitochondrial and other functions, the neuronal component being associated with CNS hypomyelination. There are documented abnormalities in HLA antigen expression. There are documented disturbances in oxidative stress levels, with mounting evidence that oxidative stress and lipid peroxidation contribute to the disease process in ME/CFS: circulating in the bloodstream are free radicals which if not neutralised can cause damage to the cells of the body (a process called oxidative stress): there is evidence that incremental exercise challenge (as in graded exercise regimes) induces a prolonged and accentuated oxidative stress. There is evidence of gastro-intestinal dysfunction, with objective changes including delays in gastric emptying and abnormalities of gut motility; there is evidence of swallowing difficulties and nocturnal diarrhoea; there is evidence going back to 1977 of hepatomegaly, with fatty infiltrates: on administration of the copper response test, there is evidence of post-viral liver impairment; there is evidence of infiltration of splenic sinuses by atypical lymphoid cells, with reduction in white pulp, suggesting a chronic inflammatory process. There are abnormalities in the reproductive system, with clinical evidence that some female patients have an autoimmune oophoritis; there is evidence of endometriosis; there is evidence of polycystic ovary syndrome; in men with ME/CFS, prostatitis is not uncommon. There is visual dysfunction, including latency in accommodation, reduced range of accommodation and decreased range of duction (ME patients being down to 60% of the full range of eye mobility).

  1.6.3  The above list is by no means comprehensive but merely gives an overview of documented abnormalities seen in ME/CFS that can be accessed in the international medical literature, as well as in the abstracts and reports of Clinical and Research Conferences.

  1.6.4  It is beyond reason that so many documented abnormalities in people with ME/CFS should be disregarded by NICE, especially as there is no credible evidence—as distinct from opinion and assertion by a small group of psychiatrists and their adherents who act as Government advisers—of abnormal illness behaviour in patients with authentic ME/CFS.

  1.6.5  It is clear from the draft Guideline that not only the voice of the patients has been ignored, but so also have the views of those healthcare professionals who understand this complex illness and who have spent a professional lifetime dealing with it—a state of affairs that is indicative of a dictatorship, not a democracy.

  1.7  The benefits, side effects and risks of the recommendations must be considered: NICE acknowledges in its draft Guideline that it is aware of patients being damaged by Graded Exercise Therapy (GET) but then ignores this in its recommendations, stating on page 257 of the draft Guideline that the severely affected should receive the same management regime as that of any person with "CFS/ME"—in other words, NICE is recommending a "one size fits all" policy, even though NICE has been made aware that numerous surveys of over 3,000 patients carried out by patients' charities, support groups and independent researchers universally concluded that graded exercise makes many patients worse. Notably, exercise regimes have converted patients who were moderately affected into those who are severely and chronically affected, with some patients requiring tube-feeding.

  1.7.1  There is incontrovertible evidence that ME/CFS patients' ability to work is impaired and this can be shown by a serial exercise stress test: patients do not recover in 24 or even 48 hours after exercise. These changes in serial testing point to a significant and confirmable physical abnormality. The test/re-test is 100% objective and can prove that ME/CFS is neither malingering nor faking. In ME/CFS, the measurement declined by about 25%, far more than in other significant diseases such as chronic obstructive pulmonary disease and even heart failure. For NICE to recommend a national policy of forced exercise—and to compel such patients to undergo these exercise regimes on pain of having their benefits withdrawn if they do not comply—amounts to persecution of very sick people that is totally unjustified and unacceptable. Whilst NICE is at pains to emphasise that these regimes are for those who want to recover (which is not only patronising but implies a degree of choice, since NICE emphasises that the cornerstone of any management regime is "patient choice"), the end result is that benefits are contingent upon compliance.

  1.8  Cost implications of the recommendations must be considered: given that there is indisputable evidence that CBT/GET is of proven limited and short-lasting benefit and is not curative, there is no factual basis for NICE to recommend such regimes, especially as the cost of providing and delivering such inappropriate interventions throughout the country would be logistically impracticable and financially indefensible. Equally, less expensive programmes that deliver advice about "pacing" and/or counselling are unnecessary: most patients with ME/CFS do not lie in bed all day unless they are too sick to do otherwise, and they use common sense in the daily management of the disorder. They do not need professional therapists to instruct them how to manage their physical limitations—experience has taught them what they can and cannot do. Given that NICE is prohibiting life-prolonging drugs for other diseases on the basis of cost, the money that NICE is channelling into costly but ineffective and potentially harmful psychotherapy for ME/CFS patients would be far better spent on appropriate investigations such as immunological assays and neuro-imaging that address the pathology and so might in time offer hope of curative treatment.

  1.9  The recommendations must be supported by evidence: in a House of Lords decision in 1997, Lord Browne-Wilkinson said that medical evidence must be "capable of withstanding logical analysis" and if it is not, then "a judge is entitled to hold that the body of opinion is not reasonable or responsible". In the case of its recommendations for the management of ME/CFS, the evidence on which NICE relies is exceedingly weak and is based on a small number of research trials that had a number of serious shortcomings (for example, there were a limited number of outcome measures and no objective measure of activity levels against which the results could be measured; in one such trial, activity levels were decreased). A detailed Report by Professor Malcolm Hooper and Horace Reid which comprehensively exposed the flawed methodology of the York Systematic Review on the claimed efficacy of behavioural modification regimes in "CFS/ME" upon which NICE relies—to the exclusion of other credible evidence—was sent to NICE in January 2006 ("Inadequacy of the York (2005) Systematic Review of the CFS/ME Medical Evidence Base"); Nancy Turnbull, Chief Executive and Project Lead, National Collaborating Centre for Primary Care, acknowledged its receipt and gave written assurance that the Report would be considered by the NICE Guideline Development Group, yet the draft Guideline largely ignored the important evidence contained in this Report, including evidence of high withdrawal rates and patients' dissatisfaction. The Report showed unequivocally that the York Review was biased in favour of current Government policy and that it knowingly excluded the evidence that CBT/GET has little benefit in ME/CFS.

  1.10  The Guideline Development Group must include relevant specialists: in the case of its "CFS/ME" draft Guideline, NICE did not include representatives from the relevant medical and scientific disciplines.

2.   Second Term of Reference: Whether public confidence in NICE is waning

  2.1  Extensive biomedical information about ME/CFS was supplied to the Guideline Development Group but was ignored in favour of the pre-determined "biopsychosocial" model, so it is not surprising that public confidence in NICE is non-existent. There has been much media coverage about the lack of public confidence in NICE's recommendations, not only in ME/CFS but also in areas such as Altzheimer's Disease, breast cancer and osteoporosis. `Pulse', a medical magazine, reports this week that NICE has drastically revised its proposals for patients with osteoporosis and has effectively done a U-turn after coming under what was described as `a barrage of criticism' from clinical groups over its original plans to limit treatment for people with osteoporosis. In the case of ME/CFS, patients, as well as clinicians and medical scientists who support them, are aware of the extent of significant evidence that NICE has deliberately disregarded for political reasons, so inevitably there is no confidence in NICE.

  2.2  There is a widely-held belief that NICE is simply a mouthpiece for the Department of Health, whose advisers on ME/CFS are known to have vested financial interests in maintaining the status of ME/CFS as a "psychosocial" (ie. mental) disorder. These advisers are psychiatrists who also work for the medical insurance industry which, as long it can get away with claiming that ME/CFS is deemed by its own "experts" and "Government advisers" to be a "mental" disorder, can deny payment of rightful benefit under its terms of exclusion. A recent inquiry by a Committee of Parliamentarians (the Gibson Inquiry) found that this was such a serious matter that the Committee called for an investigation by the Standards body.

  2.3  There is also evidence that the pharmaceutical industry controls both medical institutions and medical education in the UK and that its aim is to create "life-style disorders" (ie. "psychosocial disorders") for which doctors are urged—even bribed—to prescribe unnecessary mind-altering drugs for the life of the hapless patient. Many think that this is where ME/CFS currently finds itself. In 2001 a leading Cambridge academic presented evidence that multi-national corporations are taking the place of elected governments and argued that the surrender of Government to big business is the greatest threat facing democracy. The alleviation of suffering used to be paramount in medicine but has now been replaced by the dictates of corporate interests whose life-blood is profit ("Politics Isn't Working: The End of Politics". Noreena Hertz; Channel 4 documentary; 13 May 2001). This disease-mongering for profit was established by the Health Select Committee itself in 2004 when it carried out an investigation into the influence of the pharmaceutical industry and looked specifically at the industry's influence on NICE. Members of the Health Select Committee are on record as being "horrified" by the evidence they heard (see www.meactionuk.org.uk/HoC_Select_Ctte_Inquiry_into_Pharma.htm ).

3.   Third Term of Reference: NICE's evaluation process and whether any particular groups are disadvantaged by the process

  3.1  There were many problems for patients with ME/CFS in this respect. The consultation process itself was badly thought-out and insufficient time was allowed for sick people to participate. The documents that were sent out were enormous and were too heavy for many people with ME/CFS to be able to hold or use. The York Review was 488 pages and was so large that when sent out by NICE's preferred option (ie. by email) caused computers to crash, so a printed version had to be sent by Royal Mail. This apart, many people with ME/CFS do not have—or are too sick to use—a computer. The following Questionnaire contained misleading instructions (which meant that replies were likely to have been skewed in favour of NICE's pre-determined recommendations); it was incomplete and it was very badly worded. The draft Guideline itself was also huge (269 pages), with the same difficulties for those with ME/CFS. The short version was 48 pages, but if people relied upon that version, they were likely to have been misled. In particular, many of NICE's self-protecting caveats and reservations set out in the full version have been omitted from the short version.

  3.2  Due to NICE's insistence that all replies concerning the consultation process must be by email, an unknown number of patients with ME/CFS were prevented from participating in the consultation process (which is in breach of the AGREE Instrument). There were confusing instructions on NICE's website about the format of the responses that NICE would accept: because so many patients were unable to use NICE's online pro-forma, NICE was contacted and written confirmation was sent by NICE clearly stating that as long as responses were typed, they would be accepted. NICE did also confirm that if people were unable to type, and submitted hand-written responses, these would be transcribed by sub-contracted temporary staff, but any handwritten responses must be sent in well before the deadline. People struggled to send in a response, believing it would be accepted and heeded. However, just a day or so before the deadline, NICE changed its mind and said it would only accept on-line responses. It took a personal letter from Dr Ian Gibson MP to the Chairman of NICE, Professor Sir Michael Rawlins, before this impasse was sorted out and a written promise was given by Sir Michael that all responses—in whatever format—would be considered with equal weight. Few people have any confidence that this will occur.

4.   Fourth Term of Reference: the speed of publishing guidance

  4.1  It is over five years since the Report of a Working Group to the Chief Medical Officer on "CFS/ME", at the launch of which (on 11 January 2002) the Chief Medical Officer stated NICE would be asked to draw up guidance for the treatment of the condition; the Medical Research Council's "CFS/ME" Research Advisory Group's Report was issued on 1 May 2003; neither of these so-called milestones resulted in any improvement in access to appropriate investigations or in the provision of necessary care and support for those with ME/CFS (as distinct from those with psychiatric "chronic fatigue"). It was not until 23 February 2004 that the Health Minister (Lord Warner) announced that clinical guidelines for the diagnosis and management of "CFS/ME" would be developed by NICE. Three years later, there is still no Guideline.

  4.2  In the US, ME/CFS is regarded as a Priority One category. In November 2006, the US Centres for Disease Control initiated an awareness campaign, at the launch of which Dr Nancy Klimas, Professor of Medicine at the University of Miami and President of the International Association for (ME) Chronic Fatigue Syndrome stated: "There is evidence that the patients with this illness experience a level of disability that is equal to that of patients with late-stage AIDS, patients undergoing chemotherapy and patients with multiple sclerosis". That message continues to escape NICE, whose only recommendation is that patients with the disorder must be given psychotherapy to try to brain-wash them into abandoning their conviction that they are physically sick and that they must undergo compulsory "physical rehabilitation" regimes so that they can exercise back to fitness and return to gainful employment. This is a medical scandal in the UK of breathtaking proportions.

  We hope that the Health Select Committee on NICE will take on board the submission made by the 25% ME Group.

Simon Lawrence,

Chairman, 25% ME Group

March 2007