EXECUTIVE SUMMARY

  ME/CFS is a neurological illness, which affects an estimated quarter of a million patients in the UK; a quarter (ca.60,000) are severely affected and about a tenth are children. The cause or causes of this disease have not yet been fully established. NICE was requested to prepare guidelines on diagnosis and management of this condition following the publication of the Chief Medical Officer's Report on CFS/ME in 2002. The draft guideline (in two versions) was released for consultation in September 2006, but was unanimously and comprehensively rejected by eight major UK ME/CFS Charities and many others. The main reasons for this are that the principal recommended management approaches of Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET) have been shown to be ineffective and potentially harmful respectively. Extensive and compelling input from patients and experts supporting the physical/organic nature of the condition has been largely ignored in preparing these draft guidelines. Instead a biased so-called "biopyschosocial" model of the disease has been suggested, largely based on a flawed 2005 Systematic Review of RCTs. It has been shown that NICE in preparing these draft guidelines has failed to comply with numerous conditions laid out in the AGREE Instrument, although it is a party to this.

  1.  This memorandum is submitted as an individual.

  2.  I am an independent researcher and writer, with a particular interest in ME/CFS and related disorders. I have conducted a large-scale post-graduate multifactorial study into ME and a number of smaller studies; I was a Reference Group Member of the CMO's Working Group on CFS/ME and have contributed to the NICE draft guideline on CFS/ME as a member of the wider consultation group. I am also a carer of a person with ME for 27 years.

3.  INTRODUCTION

  In September 2006 the National Institute for Health & Clinical Excellence (NICE) published a draft guideline in two versions for consultation on "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children"—the full version consisting of 269 pages and the "NICE Guideline" of 48 pages. This draft guideline has been unanimously rejected by eight major UK ME/CFS Charities in a statement released on 19 December 2006. In addition many formal responses by stakeholders were supplied to NICE by the end of the official consultation period in November 2006—all those by patient group stakeholders expressing severe criticisms of these draft guidelines in many respects. NICE has now decided to postpone publication of the final guideline from April to August 2007 due to a huge number of responses and feedbacks. At a meeting of the APPG on ME on 22 February 2007 Professor Peter Littlejohns said that NICE was still considering these responses and feedback, but he indicated that there was unlikely to be a further consultation, adding that even if the final guidelines were rejected by all UK ME/CFS Charities, they would still be published. This situation is causing great concerns amongst the ME/CFS community, their official representatives and many caring professionals and clinicians.

  Problems in compiling these particular guidelines are due in part because of confusion over the definition of the target population. NICE in their draft guideline refer to "CFS/ME" patients which is not the same as the definition relating to "ME/CFS" patients—the former relates to patients suffering from a variety of fatiguing illnesses, the latter to patients who suffer from a neurological disease, classified by the WHO under G93.3 and described in detail in the Canadian Clinical Guidelines on ME/CFS, published in 2003 in the Journal of Chronic Fatigue Syndrome. Important in this context is the fact that in the UK there has been very significant influence by a certain group of psychiatrists, who in many published articles, books and documents have unjustifiably stressed the psychological nature of the condition and have recommended behavioural management/treatment approaches, ie Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET). These views are not supported by experiences of patients, who have consistently stressed the physiological/organic nature of the disease. Whilst there is some divergence of views on the appropriateness of these approaches amongst some UK ME/CFS Charities, it has been recognized that a joint approach in dealing with these issues now is vital because of potential long-term serious detrimental health effects for many patients. Therefore a memorandum endorsed by 10 UK ME/CFS Charities and regional support groups has been supplied to the Health Committee for their current inquiry into NICE, and a separate submission has been made by the 25% ME Group on behalf of those most severely affected. There may be other separate submissions by ME/CFS Charities or organisations for their inquiry into NICE.

4.  CONTENTS OF THIS MEMORANDUM

  The Contents of this memorandum relate to four terms of reference of the Committee's Press Notice No.11—Session 2006-07 issued on 2 February 2007:

(a)  Why NICE's decisions are increasingly being challenged.

(b)  Whether public confidence in the Institute is waning, and if so why.

(c)  NICE's evaluation process, and whether any particular groups are disadvantaged by the process.

(d)  The speed of publishing guidance.

5.  SPECIFIC COMMENTS RELATING TO TERMS OF REFERENCE

 (a)   Why NICE's decisions are increasingly being challenged

  NICE has been heavily criticized for decisions made on drug treatments and drug availability; one recent example being that of drug availability for cases of early onset of Alzheimer's Disease, another that of the availability of the drug Herceptin for Breast Cancer cases. The case for ME/CFS patients is different: Here drug treatment is largely ineffective and can be detrimental (eg due to frequent severe sensitivity to drugs and chemicals and potential serious adverse reactions to many). For this group of patients behavioural approaches in the form of CBT and GET have been recommended as first-line management approaches. However, both are fraught with problems: CBT has been shown to be largely ineffective in numerous patient surveys, and GET has been reported to be potentially harmful for a significant number of patients, particularly those who are severely affected. NICE was advised of these concerns and although detailing the results of two patient surveys in the "full draft" on p58, has largely ignored these findings in its overall recommendation. In preparing the draft guideline NICE has relied heavily on a "Systematic Review of the CFS/ME Medical Evidence Base" carried out in 2005 by the Centre for Reviews and Dissemination at the University of York; but this review focused almost entirely on RCTs applying CBT and/or GET; it was severely flawed in many respects—a detailed critique was sent to NICE in January 2006 see section (iii) Key Item 8 below and was acknowledged. Whilst minor adjustments were made to the updated version of this "2005 York Review" when it was published in the Journal of the Royal Society of Medicine in November 2006 (ie adverse events and patient drop out of RCTs were mentioned), many other legitimate and justified criticisms were ignored.

  NICE's decisions with regard to recommendations made in the draft guideline on CFS/ME are challenged in part because in this instance the Institute has not complied with a number of conditions set out in the AGREE INSTRUMENT (Appraisal of Guidelines Research and Evaluation—The AGREE Collaboration, September 2001), to which it is party. The purpose of this Instrument is to provide a framework for assessing the quality of clinical practice guidelines; it was specifically designed for new guidelines (which applies to the Guideline) and is intended for Policy Makers and Guideline Developers (ie NICE and the Government in this instance). One key reference of this document is an article entitled "Development and Application of a generic methodology to assess the quality of clinical guidelines" published in the International Journal for Quality in Health Care, 1999;11:21-28, and one of its authors is Professor Peter Littlejohns (now Clinical and Public Health Director at NICE). This "Instrument" consists of 23 key items, organised in six domains, each designed to capture a separate dimension of the guideline quality.—It can be shown that a significant number of these key rules/clauses have not been adhered to by NICE in preparing the CFS/ME Draft Guideline. Below are five of these:

(i)  Key Item 3:  "There should be a clear description of the target population to be covered by the guideline". This has not happened in the draft guideline on CFS/ME issued by NICE in September 2006. The terminology "CFS/ME" does not describe a recognised specific and classified disease entity, but encompasses a range of fatigue illnesses, including psychological disorders like depression and anxiety; it is a term promoted by certain UK psychiatrists who maintain that it should be regarded as a "biopsychosocial" disease, which is amenable to behavioural modification techniques (ie CBT + GET). By contrast "ME", "CFS" as well as "PVFS" (Post Viral Fatigue Syndrome) are classified by the WHO as a neurological disease and "ME/CFS" as described in the 2003 Canadian Guidelines provides the best description of patients who suffer from this condition. This crucial issue is not addressed in the NICE draft guideline.

(ii)  Key Item 5:  "Information about patients" experiences and expectations of healthcare should inform the development of clinical guidelines, eg involve patients' representatives' etc. Although some patients and patient representatives were part of the GDG and testimonies of their experiences were recorded in the full draft report prepared by NICE, these details are not fully reflected in the key recommendations on the management and treatment of these patients. In various parts of this draft it is stated that GET is inappropriate for the severely affected and a better concept in these cases would be "activity management". However, on p257 of the full draft it clearly states that the severely affected should receive the same management regime as that of any person with "CFS/ME". More importantly, most of the caveats and restrictions indicated in the full NICE draft are omitted from their condensed 48-page version. GPs and healthcare professionals are unlikely to read a 269 page NICE guideline; they may not even have time to read a 48 page version and most probably will rely on a leaflet-type publication consisting of a few pages (similar to the NHS Plus leaflets on Occupational Aspects on the Management of CFS issued in October 2006, where none of these caveats and restrictions are mentioned). Summary details of four patient surveys on over 3,000 patients in total and originally submitted to the CMO's Working Group on CFS/ME in 2001, were provided to members of the GDG on at least two occasions—first in January 2006 and again during the summer of that year. The details of these surveys show very clearly that CBT was found to be largely ineffective and GET was the most harmful of a range of management techniques and treatments, which patients had tried. By contrast, an approach referred to as "Pacing", ie patients pacing activities according to their perceived energy levels, alternating with rest periods, was reported as most helpful by a large majority of patients, but other methods (including bed rest) as well as alternative treatments were also found to be more helpful than either CBT or GET. One survey reported counselling as being helpful to patients. These details were evidently considered by the GDG (results of two surveys were listed on p58 of the full draft), but given a very low weighting in their considerations. It is important to remember that neither CBT, GET, PACING nor COUNSELLING are curative approaches in treating these conditions.

(iii)  Key Item 8:  "Details of strategy used to search for evidence to be provided, including search terms used, sources consulted and dates of literature covered. Sources could include electronic data bases (eg Medline etc), databases of systematic reviews (eg Cochrane Library etc), hand searching journals, reviewing conference proceedings and other guidelines". NICE used the October 2005 Systematic Review carried out at the Centre for Reviews and Dissemination at the University of York. However, this review was shown to be severely flawed in many respects and a detailed critique entitled "Inadequacy of the York (2005) Systematic Review of the CFS/ME Medical Evidence Base" prepared by M Hooper and H Reid was sent to the GDG in January 2006; this was acknowledged by Nancy Turnbull, Chief Executive and Project Lead, National Collaborating Centre for Primary Care, in January 2006, but again most of many justified criticisms were ignored by NICE in their draft guideline. Instead a version of this flawed 2005 York Review was published by Chambers et al in the November 2006 issue of the Journal of the Royal Society of Medicine. As mentioned in the Introduction, some adverse events and patient drop out rates were mentioned in this published review, which also referred to some new papers.

(iv)  Key item 10:  "Description of methods used to formulate recommendations—formal consensus techniques (eg Delphi etc)".—The "Delphi" method was used for these draft guidelines, but the consultation method and process were highly unsatisfactory: Initially a copy of the 2005 York Systematic Review (which dealt almost exclusively with RCTs on CBT + GET approaches) was sent electronically to a number of volunteer parties, including patients and carers, to be studied in detail, in readiness for a questionnaire which would follow. This 488-page pdf document could not be accessed by many people and paper copies had to be supplied to many in the wider consultation group. These proved to be almost impossible to handle for many sick patients and the contents were virtually impossible to study properly by them, to enable assimilation of the relevant information. The questionnaires which followed (some electronic, some in printed format) were incomplete—they only covered a small proportion of all questions considered by the GDG, were poorly or misleadingly worded and the printed versions contained incorrect instructions relating to approx a third of all questions; they were sent to a relatively small number of people (399), completed by only 219 including 119 ME/CFS patients. Compared to an estimated number of 240,000 sufferers this translates to 0.05%. In the full draft NICE acknowledges on p203 that patients were "uncertain" about its recommendation on CBT, that they "disagreed" about GET and clearly preferred Pacing (p204). Therefore the feedback obtained by this method was largely unreliable and importantly, insignificant in magnitude.

(v)    Key Item 20:  "Recommendations may require additional resources in order to be applied, eg need for more specialised staff, new equipment ... These may have cost implications for health care budgets. There should be a discussion of the potential impact on resources in the guideline." This is an important failing in this draft guideline, because that issue has not been addressed. It has been pointed out to NICE representatives at 5 October 2006 "Implementation Planning Meeting" for this draft guideline that arrangements to administer CBT alone for approximately 180,000 mildly or moderately affected ME/CFS patients would cost in the region of £180 million (based on an estimated cost of approx £1,000 per person). There is already a shortage of suitably trained psychotherapists to administer this particular management technique for patients suffering from various mental disorders. To extend this regime to ME/CFS patients would be very costly to the NHS—and that for a regime, which is known to have no long-lasting benefits for patients. It would be far more appropriate to allocate such funding for comprehensive, biologically-based care that is available, for example, to MS patients, especially for the most severely affected ME/CFS patients within the framework of the so-called "FINE trials", which indicate the need for "Specialist Medical Care".

 (b)   Public Confidence in NICE is waning—why?

  A huge amount of information supporting the physical/organic nature of ME/CFS has been supplied to NICE during the development period and the consultation process. Much of this emanated from American or Canadian research. Virtually all of this was ignored by them in preference of a "biopsychosocial model" of the disease, as advocated by certain UK psychiatrists. This is an overtly biased decision taken by NICE, favouring government policy strategies instead of being based on medical and scientific evidence. At the APPG meeting on 22 February 2007 the two representatives from NICE were provided with a synopsis of research presented at the International Fort Lauderdale Conference on ME/CFS held in January 2007, entitled "Facts from Florida" by Margaret Williams, together with summarised details of some specific problems which have emerged from research shown and discussed by 250 clinicians and researchers from 28 different countries at this event. A short selection of these specific problems includes the following:

(i)  The cardiac index of ME/CFS patients is so severe that it lies between heart attack patients and those in shock.

(ii)  Brain imaging shows reduced cerebral blood flow (especially in areas involved in ANS functioning, sleep, concentration and pain).

(iii)  There is evidence of "arteriolar vasculopathy" (a blood vessel disease)—affecting all body organs.

(iv)  Various specific viruses are involved in this disease: HHV-6, EBV, Enteroviruses (ie echovirus, coxsackie virus and polioviruses). There is evidence of chronic inflammation.

(v)  In contrast to most other countries, the UK government is resistant to funding any biomedical research into ME/CFS and favours studies into behavioural modification regimes in these patients. Previous CBT/GET programmes were based on a false assumption that avoidance of activity, illness severity and increased attention to symptoms caused perpetuation of symptoms, but in reality are the result of the illness... These approaches do not work—ME/CFS patients do not have dysfunctional beliefs, but instead function at maximum activity levels, and exercise makes some worse. Any benefits are short-lived.

  The confidence of ME/CFS patients in the NICE process of preparing these draft guidelines and in their consultation is therefore non-existent.

 (c)   NICE's evaluation process

  Many shortcomings were identified in the consultation process for the CFS/ME draft guidelines. For more details see Key Item 10 under Section 5(a)(iv) above.

 (d)   Speed of publishing guidance

  NICE's process of producing this guideline has taken an extraordinarily long time—over five years since the publication of the CMO's report, which recommended that NICE prepare such a guideline. The entire process of developing the guideline was complex, laborious, cumbersome and protracted, but above all patients' views and those of knowledgeable clinical experts in the field were almost completely ignored. In the meantime a number of so-called "Specialist Centres" were established where ME/CFS patients are supposed to receive specialist care, but regrettably all that is on offer at these centres are CBT and/or GET approaches. Some patients are randomly allocated to a structured PACING regime within the framework of an ongoing part MRC-funded "PACE Trial". All this is highly unsatisfactory because none of these regimes are in any sense curative, CBT is largely ineffective and GET is often harmful. Whilst there may be few "official" complaints from patients about treatments provided at these centres sent to the main charities, it is known that many are very concerned about the options offered.

  At the APPG meeting on 22 February 2007 Professor Peter Littlejohns, one of the two representatives from NICE present at this meeting, acknowledged that the previously adopted "hierarchy of evidence" should be reconsidered, which presumably means that they may now give greater credence and weighting to patient evidence. He also confirmed that serious flaws in the 2005 York Systematic Review had been stressed in many responses which NICE received to the draft guideline. It is to be hoped that all these facts will finally convince NICE that a major re-write of this draft guideline is necessary, and so is further consultation with patient group representatives. It is astonishing that NICE should have adopted such an intransigent stance with regard to patient evidence, at a time when the government's own guiding principle for the NHS is that it must be patient-led, as outlined in the 2001 DoH booklet "The Expert Patient", which was endorsed by the CMO himself. A serious look at these crucial issues by the Health Select Committee would be most welcome.

  I would be prepared to give oral evidence to the Committee in support of the above complaints about NICE's preparations of their draft guideline on CFS/ME and the consultation process adopted in this instance, should this be required.

Doris M Jones

March 2007