MEA opposes plan to put review of NICE ME/CFS Guideline on hold | 23 October 2013

October 23, 2013

Proposal by NICE to move the guideline on ME/CFS to the static list

Submission from The ME Association

The ME Association is strongly opposed to the proposal to place the current (2007) NICE guideline on ME/CFS into the newly created static list.

We do so for the following four reasons:

1. Along with most other ME/CFS charities, and people with ME/CFS, we have been unable to endorse the current NICE guideline. We believe the ME/CFS guideline can only become fit for purpose following fundamental changes to the sections covering clinical assessment, investigation, diagnosis and management.

2. Important evidence from published sources, and from people with ME/CFS, has been either ignored or missed by NICE.

3. New and emerging evidence relating to clinical assessment, diagnosis and management of ME/CFS needs to be included in a comprehensive review.

4. Whilst accepting that there is a good case for placing conditions that already have a settled diagnosis and successful forms of treatment into a static list, ME/CFS is a condition that is still in a state of flux involving uncertainty and debate over diagnosis, cause and management.

Based on the content of the Quick Reference Guide that was produced by NICE for health professionals we highlight some key areas of concern relating to the above four points.

The list is not complete – it simply summarises a sufficient number of examples, along with references to relevant sources of published evidence, to justify a review.

Introduction (Page 3)

The guideline fails to adequately demonstrate that ME/CFS covers a wide range of clinical presentations/phenotypes and disease pathways.

Consequently, it is inappropriate for NICE to recommend that two specific forms of treatment (ie CBT/cognitive behavior therapy and/or GET/graded exercise therapy) are going to be safe and effective for everyone who comes under the ME/CFS umbrella.

We will cover this key point in more detail later in the submission.

Symptoms (Page 7, Box 1)

Having produced a new and inappropriate clinical definition for the diagnosis of ME/CFS in the guideline, and one that extends the heterogeneity even further, the symptom list has serious omissions, especially in relation to characteristic symptoms associated with autonomic dysfunction – eg orthostatic intolerance and/or hypotension and postural orthostatic tachycardia syndrome (POTS).

Evidence: Hoad A et al:

SUBJECTS: Fifty-nine patients with CFS/ME (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic assessment in the cardiovascular laboratory with continuous heart rate and beat-to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria). Haemodynamic responses to standing over 2 min were measured. POTS was defined as symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of >30 beats per minute or to a heart rate of >120 beats per minute on standing.
Maximum heart rate on standing was significantly higher in the CFS/ME group compared with controls (106 +/- 20 vs. 98 +/- 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9% (5) in the control population (P = 0.006). This difference was predominantly related to the increased proportion of those in the CFS/ME group whose heart rate increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue was associated with increase in heart rate (P = 0.04; r(2) = 0.1).
POTS is a frequent finding in patients with CFS/ME. We suggest that clinical evaluation of patients with CFS/ME should include response to standing. Studies are needed to determine the optimum intervention strategy to manage POTS in those with CFS/ME.

At the same time, the diagnostic list of symptoms produced by NICE includes symptoms such as palpitations that can occur in ME/CFS but are not characteristic of the condition. And the fact that palpitations have to occur in the absence of identified cardiac pathology would appear to exclude those caused by autonomic dysfunction or POTS.

When Professor Peter Littlejohns came to talk to the All Party Parliamentary Group on ME in February 2007, the Minutes record that he stated:

“…although NICE considered definitions, NICE was not in a position to define conditions”.

Yet what is widely perceived to be a new clinical definition of ME/CFS, that has been produced by NICE, appears in the guideline.

Differential diagnosis (Page 7, Box 2)

There is a significant problem with the misdiagnosis of ME/CFS – even where patients are being referred to specialist centres:

Evidence: Newton JL et al:

Of the 40% of patients subsequently found not to have CFS the most common diagnosis was fatigue associated with a chronic disease (47% of all alternative diagnoses); 20% had primary sleep disorders, 15% psychological/psychiatric illnesses and 4% a cardiovascular disorder. Thirteen per cent remained unexplained (5.2% of the total referrals). This study found a significant increase in the proportion of patients referred to National Health Service (NHS) CFS services diagnosed with CFS. A large proportion of patients presenting with fatigue are not eligible for referral to the Department of Health specialist fatigue services, which represents an unmet need in terms of symptom management in current NHS services.

This section therefore needs to include examples of conditions that are being misdiagnosed as ME/CFS in both adults and children – eg coeliac disease, primary biliary cirrhosis, joint hypermobility syndrome, systemic lupus erythematosus – and not just consist of a list of six very obvious ‘red flag’ symptoms and signs that are strongly suggestive of other possible explanation.

Investigations (Page 8, Box 3)

Following on from the previous point, the provision of information on the differential diagnosis of ME/CFS in this section needs to also provide examples of investigations that do not need to form part of the essential list of investigations but should be seriously considered, where appropriate, in the clinical assessment of someone with ME/CFS.

For example:

Vitamin D levels in people with moderate to severe ME/CFS who are mainly or totally housebound and are obviously at risk of developing vitamin D deficiency due to lack of exposure to sunlight.

Evidence: Berkovitz S et al:

Patients with chronic fatigue syndrome (CFS) may be at risk of osteoporosis due to their relative lack of physical activity and excessive time spent indoors, leading to reduced vitamin D synthesis. We hypothesized that serum 25-OH vitamin D levels are lower in CFS patients than in the general British population.
We performed a retrospective survey of serum 25-OH vitamin D levels in 221 CFS patients. We compared this to a group of patients attending the hospital for other chronic conditions and to a large British longitudinal survey of 45-year old women, using a variety of appropriate statistical approaches.
25-OH vitamin D levels are moderately to severely suboptimal in CFS patients, with a mean of 44.4 nmol/L (optimal levels >75 nmol/L). These levels are lower and the difference is statistically significant (p<0.0004) than those of the general British population from a recent national survey, but similar to those in patients with other chronic conditions.

Vitamin D deficiency often goes unrecognised and can cause bone or muscle pain and muscle weakness. It can co-exist with ME/CFS. Levels < 25ng/ml may be associated with symptoms.Short synacthen test where there are symptoms, signs or laboratory test results which indicate that there is significant hypocortisolaemia

Tilt table testing where there are symptoms and signs suggesting significant autonomic dysfunction or POTS.

Evidence: Lewis I et al:

Research aimed at characterising ME/CFS patients with and without POTS found that those with POTS were younger, less fatigued, less depressed, and had reduced daytime somnolence. They also had greater orthostatic intolerance and autonomic dysfunction. Those with POTS may require further investigation and consideration for therapy to control heart rate.

At the same time the guideline is in effect banning one investigation that could be of wider benefit:

Do not do: ……tests for serum ferritin in adults, unless other tests suggest iron deficiency (page 8)

This recommendation is over-restrictive and misleading because serum ferritin can be the first laboratory marker to change when iron deficiency/depletion is present.

Evidence: Guidelines for the Management of Iron Deficiency Anaemia: British Gastroenterology Society :

Iron deficiency/depletion without anaemia (as proven by a low serum ferritin – hypoferritinaemia) is three times as common as iron deficiency anaemia and may cause fatigue, cognitive dysfunction and restless legs – all of which occur in ME/CFS. Iron deficiency can also be a ‘red flag’ warning sign for conditions that are misdiagnosed as ME/CFS – coeliac disease for example.

Symptom management (page 11)

In addition to omitting any reference to orthostatic intolerance and/or hypotension, there is no information on the clinical assessment, self-help management and possible pharmacological management of orthostatic intolerance and hypotension, or POTS.

Education and employment (page 12)

ME/CFS is recognised to be a disability under section A6 of the 2010 Equality Act. This should be included in this section because the Act legislates for important adjustments in working hours and duties that could be used to help keep someone with ME/CFS in employment or at school/college/university.


A6.  A disability can arise from a wide range of impairments which can be impairments with fluctuating or recurring effects such as rheumatoid arthritis, myalgic encephalitis (ME)/chronic fatigue syndrome (CFS), fibromyalgia, depression and epilepsy

Strategies that should not be used for CFS/ME (Page 13)

We would accept that there is no indication at present to positively recommend the use of antiviral and immunomodulatory drugs. However, the recommendation to in effect ban the prescribing of antiviral drugs needs to be balanced with an acknowledgement that there is new and emerging evidence to indicate that antiviral medication using valganciclovir (Watt T et al) and B cell depletion using Rituximab (Fluge O et al) could be an effective form of treatment in at least a sub-group of people with ME/CFS – possibly those with evidence of reactivation of human herpes virus infection (ie valganciclovir) or where there is an autoimmune component (Rituximab).

Treatment approaches (Page 14)

The implication here is that any form of vitamin supplementation should not be prescribed or recommended.

As already noted, people with moderate to severe ME/CFS are at increased risk of developing vitamin D deficiency. Consequently, they should be treated with a vitamin D supplement when appropriate. For those at increased risk, consideration should be given towards the use of a prophylactic vitamin D supplement.

CBT, GET and Pacing (Page 18 onwards)

Our principle reason for opposing this proposal and requesting a fundamental review of the guideline relates to the recommendation that CBT and GET should be automatically offered to everyone with mild or moderate ME/CFS.

This is coupled with the continuing failure of NICE to take note of highly consistent patient evidence, dating back to evidence that was published in the 2002 Chief Medical Officer’s report on ME/CFS, regarding the efficacy and safety of these two behavioural treatments.

The largest ever survey of patient evidence relating to all aspects of the management of ME/CFS was carried out by The ME Association and published in 2010 (ME Association). The report provided important evidence regarding concerns over the efficacy of CBT and the safety of GET.

For CBT (997 responses)
Greatly improved: 2.8%
Improved: 23.1%
No change: 54.6%
Slightly worse: 11.6%
Much worse: 7.9%

For GET (906 responses)
Greatly improved: 3.4%
Improved: 18.7%
No change: 21.4%
Slightly worse: 23.4%
Much worse: 33.1%

For Pacing (2137 responses)
Greatly improved: 11.6%
Improved: 59.6%
No change: 24.1%
Slightly worse: 3.5%
Much worse: 1.2%

The MEA is currently in the final stages of preparing a further report covering the use of CBT, GET and Pacing – but this time in much greater depth. The report will be based on the answers to questions on the above three treatments that were provided through 3142 responses given by 1429 respondents during 2012.

Overall, the patient evidence contained in this new MEA report is very similar to the evidence contained in the 2010 report. The two MEA surveys show a total of 6599 responses about the effect of treatments on symptoms, and a total of 6838 responses about appropriateness of courses, effectiveness of self management and helpfulness of consultations and general satisfaction.

However, to date NICE has failed to consider any of this patient evidence and both MEA reports support the findings from patient surveys referred to in the Chief Medical Officer’s Working Group report into ME/CFS.

We are therefore looking at a consistent picture from patients with regard to all three approaches to management going back over at least a decade and the picture has not improved.

As a result of growing concern amongst people with ME/CFS about the efficacy and safety of CBT and GET, we will be making a number of radical recommendations regarding the future use of CBT and GET in ME/CFS in this report.

This is clearly important new evidence that cannot be ignored by NICE.

The PACE trial and the March 2011 surveillance review

Finally, in relation to CBT and GET and Pacing, we assume that the guideline surveillance review that took place in March 2011, and which followed publication of the PACE trial in February 2011, simply ‘rubber stamped’ the 2007 NICE guideline recommendations on the basis that the PACE trial had supported the recommendations relating to CBT and GET.

However, there has been widespread and valid criticism about the way in which the PACE trial was carried out, as well as the way in which the results were presented and reported (Shepherd CB).

In addition, it should be noted that the cost effectiveness paper (McCrone P et al) reported that take up of state sickness benefits had increased during the PACE trial for all four treatments (ie CBT, GET, Pacing and Standard Medical Care). The MEA report will also contain similar information on benefit status.


ME/CFS is a condition that is still in a state of flux involving uncertainty and debate over diagnosis, cause and management.

We have provided examples of existing or emerging evidence that fully justify a review of the NICE guideline on ME/CFS.

In addition, we do not believe that there is any justification for NICE to continue to recommend that everyone with mild or moderate ME/CFS requires CBT and/or GET.

The NICE guideline should therefore be thoroughly reviewed and there is no justification in the current circumstances to place it in a static list.

The MEA would be very willing to provide additional information, clarification or references.

We will send a copy of our new report on CBT, GET and Pacing on completion. We are aiming to complete this work by the end of 2013.

When Professor Littlejohns came to the APPG in February 2007 he stated:

“All NICE guidelines were produced on the basis of best available evidence and on a process based on transparency, active consultation and review”. 

=He added that:

“Guidance however robust is not set in stone; medical advances can happen very quickly and NICE aims to make guidance as up to date as possible.  Any organization affected by a guideline should be part of the development of that guideline”.

We do not believe that NICE has been listening to people with ME/CFS – the vast majority of whom do not endorse this current guideline – and we do not believe that patient support organisations are being allowed to play a meaningful role in the on-going development of this guideline.

So we hope and expect that NICE will listen to the people with ME/CFS and their representatives on this occasion.

Dr Charles Shepherd
Hon Medical Adviser
ME Association
7 Apollo Office Court
Radclive Road
Bucks MK18 4DF


22 October 2013


All Party Parliamentary Group on ME Minutes for meeting dated 22 February 2007:

Berkovtiz S et al. Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a retrospective study. International Journal for Vitamin and Nutrition Research, 2009, 79, 250-254.

Fluge O et al. Benefit from B-lymphocyte depletion using the anti-CD20 antibody Rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One, 2012, 6, e26358.

Guidelines for the Management of Iron Deficiency Anaemia British Society for Gastroenterology, May 2005.

Hoad A et al. Postural orthostatic tachycardia syndrome is an under- recognized condition in chronic fatigue syndrome. Quarterly Journal of Medicine, 2008, 101, 961-965.

Lewis I et al. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. Journal of Internal Medicine, 2012.

ME Association. Managing my M.E. What people with ME/CFS and their carers want from the UK’s health and social services (2010):

McCrone P et al. Adaptive pacing, cognitive behavior therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: A cost effectiveness analysis. PLoS One, 2012, 7, e40808.

Newton JL et al. The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same. Journal of the Royal College of Physicians of Edinburgh, 2010, 40, 304 – 307.

Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent Working Group. January 2002.

Shepherd CB. Problems with the PACE trial. Psychological Medicine, 2013, 43, 1790 – 1791.

Watt T et al. Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titres. Journal of Medical Virology, 2012, 84, 1967 – 1974.

6 thoughts on “MEA opposes plan to put review of NICE ME/CFS Guideline on hold | 23 October 2013”

  1. Well done on this.

    I hope you will make use of the following peer-reviewed paper in your upcoming report, or at least reference it. It lists various surveys and also discusses various issues regarding the safety or othewise of CBT and GET in ME/CFS:
    Kindlon T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Bulletin of the IACFS/ME. 2011;19(2):59-111

  2. A good start.

    A little concerned–as someone to whom POTS is not usually a severe problem–that this approach might lead to an over-emphasis on this one symptom.

    Would also like to see more recognition of the fact that, in other documents, NICE draws attention to the fact that the legal standing of their guidance has not been tested [The ME guidance legal fiasco was about what went into the guidance: not what the standing of that guidance was.], and that it is, in any case, not intended to substitute for the expertise of the physician in consultation with his patient. Any rewritten guidance should therefore begin with a statement of these caveats so that the physician knows that responsibility lies ultimately with him, not NICE.

    And, MEA needs to be a bit more careful with proof reading important letters like this. I would not expect to see bloomers like “iron efficiency anaemia”, and, “allowed to playing”, in official communications.

    Otherwise, good to see MEA keeping up the pressure, but do be aware that, by playing their game, you are endorsing a guidance system that masquerades as a de facto law without the authority to do so. Effort might more profitably be expended in knocking NICE off its unmerited pedestal, and letting the profession know that even NICE admits that individual doctors know best.

  3. My goodness, what an impressive document. Thank you, Dr Shepherd, for the enormous amount of time and effort you must have expended on its preparation.
    Sad to see some nit-picking.

  4. The model of ME/CFS on which CBT and GET is based is that of the Wessely group: That is that ME/CFS is an emotional overraction to minor physical symptoms following a viral infection, a set of ‘false beliefs’ that the individual has an illness with a physiological basis. On this model, the person needs help to change the false beliefs, and to be encouraged, or coerced, into physical exertion beyond what the patient believes might be harmful.
    NICE are being a bit paradoxical in purporting to accept that this is a genuine physical illness, but then recommending treatments which are based on a psychiatric model.
    The fact that there is convincing evidence that this is a physical illness which is defined by the fact that physical exertion exacerbates the symptoms makes a recommendation for physical exertion as a ‘safe and effective’ treatment nonsensical.
    However in supporting the title ‘Chronic Fatigue Syndrome’ it has been said that this label is useful because it allows the patient to believe that the doctor is stating that he/she has a physical illness when the doctor is actually meaning something else. Is NICE doing this as well?
    We need to look into the power relations behind this. Who has decided that the Guidelines do not need to be reviewed? Was that decision taken at a meeting? If so, who was at that meeting? Whose view prevailed? On what basis? Did the meeting actually have the power to make that decision, or was the decision made elsewhere and the meeting simply used as window dressing for power relations which were kept behind the scenes?
    It is very evident that the claim to give credence to evidence from patient advocacy organisations is not being honoured in practice. It also is evident that medical research on the physical nature of ME/CFS is being ignored. Presenting these will therefore be futile until we understand the power relations that are permitting this to go on. As I am currently working on a Ph.D. on the conflicting paradigms concerning ME/CFS and how it is that the psychiatric paradigm gains its dominance, I will welcome any help/information/advice on these questions that you may have, and I hope ultimately to be able to illuminate these issues for the ME/CFS community.

    1. Well put Nancy. I do hope that the MEA and other campaign groups, are encouraged to think outside the box, like this. Trying to change a broken system from within, is all but impossible. Effort needs to be addressed to the foundations that hold it in place, and the assumptions of authority that keep it there. Both the power relations behind the policies, and the undeserved mantle of quasi-legal status, need to be explored and exposed by campaigning organisations.

      Come out of the trees and see the wood!

  5. NICE guideline 53 is the first set of guidelines to be moved to a static list. Dr Shepherd’s excellent article quite rightly opposes this action, giving fuller details of the relevant evidence NICE identified when they last reviewed the guideline in 2011, which NICE has now chosen to ignore. The questions I would like to ask:

    1. Why does NICE not envisage any relevant evidence being provided in the next 3 – 5 years from the UK ME/CFS Research Collaborative formed in April this year?

    The only other reason for moving the guideline to the static list is because no quality standard is to be produced on the topic.

    2. Do we assume that the “static” list is government “speak” admitting the guideline is not “Fit for purpose”?

    Dr Shepherd mentions the short synacthen test as an investigation that should be carried out when there are indications of hypocortisolaemia. However, as readers may know from past correspondence in the ME Essential magazine, the short synacthen test is not infallible, and if symptoms persist a more sensitive test such as the glucagon stimulation test should be performed. The Pituitary Foundation has several endocrine experts on their Medical Committee and confirm this,-diagnosis-and-tests/tests/ .

    Well done MEA for giving us a voice; we must continue fighting to stop our needs being overlooked.

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