National Public Health Service for Wales / Guidelines and care pathways for chronic fatigue syndrome: a rapid review of the evidence.

Guidelines and care pathways for chronic fatigue syndrome: a rapid review of the evidence
Author:Dr Mary Webb, Public Health Practitioner
Date:16/11/2018 / Version:1
Status:Approved
Intended Audience:Welsh Assembly Government
Purpose and Summary of Document:Following a request from the Welsh Assembly Government this documentreports a rapid review of the evidence used to produce guidelines and care pathways for the diagnosis and treatment of chronic fatigue syndrome. An estimate of the prevalence of chronic fatigue syndrome (CFS) in Wales was also made.
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© 2009 National Public Health Service for Wales

Material contained in this document may be reproduced without prior permission provided it is done so accurately and is not used in a misleading context.

Acknowledgement to the National Public Health Service for Wales to bestated.

Key Messages

  • The true prevalence of CFS in the United Kingdom (UK) is unknown, but has been estimated to be between 0.2% and 0.4%.
  • Using the mid range population prevalence of 0.3% producedprevalence rates for CFS in Wales of 8,898 in 2006, 9,339 in 2011 and 9,558 in 2016.
  • There are several published guidelines, both in the UK and internationally.
  • The guidelines produced, in 2007, by the National Institute for Health and Clinical Excellence (NICE) have received intense criticism and a judicial review was mounted, which was over turned in the High Court. Other published international guidelines have also been the subject of controversy.
  • The diagnosis of CFS is a clinical one. No discriminating diagnostic tests are currently available, for adults or for children and young people.
  • A range of tests should be performed to exclude alternative and common diagnoses, such as endocrine diseases or mood disorders.
  • Most guidelines recommend making a diagnosis of CFS when symptoms (usually fatigue and myalgia) have persisted for 6 months; NICE recommended making the diagnosis after 4 months in adults or 3 months in children. The evidence base for the NICE recommendation has been questioned by other guideline producers.
  • Specialist referral is necessary, but more robust evidence is required to substantiate the time periods for specialist referral.
  • The treatments most studied are cognitive behavioural therapy (CBT), graded exercise therapy (GET) and pacing. The NICE guidelines recommended CBT and GET. Evidence was lacking for other forms of conventional medical treatments and for complementary and alternative therapies
  • There was Level 1- evidence that CBT is effective in reducing the symptoms of fatigue at post-treatment compared with usual care.
  • The evidence base for CBT in adults at follow-up is limited to a small group of studies with inconsistent findings. There was a lack of evidence on the comparative effectiveness of CBT alone, or in combination with other treatments. Expert opinion acknowledges that CBT and GET may not be suitable for all CFS patients.
  • There was some evidence to supportthe fact that positive effects of CBT in adolescents with CFS are sustained. Higher fatigue severity of the mother predicts lower treatment outcome in adolescent patients.
  • There was preliminary evidence to suggest that CFS patients have some degree of cerebral atrophy and that CBT is able to correct this.
  • The evidence for GET was inconsistent and the guidelines differ on their recommendations for pacing or GET, as an effective treatment..
  • The search revealed limited published economic evidence on the cost-effectiveness and clinical effectiveness of CBT and GET versus other therapies. The guideline recommendations for CBT and GET are based on only 1 study performed in Norway.
  • The Map of Medicine and NICE care pathways are available to guide diagnosis and treatment of CFS.
  • There was a lack of evidence to support the best model of care for CFS, but in Scotland, where considerable research has been performed, a tiered model of care based on the long term conditions model has been proposed.
  • The analysis of the published guidelines has highlighted what consensus and difference exists, it alsoshows that there is a relatively small evidence base on which to base clinical guidance for CFS.
  • More research is necessary in the field of CFS, especially on the implications of different forms of care organisation and effective forms of treatment.
  • The resultsof two RCTs,due in 2009/2010should help to clarify the effectiveness of CBT, GET, pacing and self help treatment.

1.Introduction

Chronic fatigue syndrome (CFS) is a debilitating condition characterised by unexplained fatigue that lasts for at least 6 months, accompanied by symptomsincluding headaches, muscle painand cognitive difficulties such as poor memory and concentration. The terms CFS and myalgicencephalomyelitis/encephalopathy(ME) are very often used interchangeably, although there is dispute about whether the two conditions are identical entities; the term CFS is used in the present review.

The exact pathogenesis of CFS is unknown and currently with the lack of diagnostic laboratory investigations for CFS it is defined by specific diagnostic criteria. The two most widely used definitions of CFS are the International Centre for Disease Control (CDC) 1994 definition [1] and the Oxford definition. [2] In addition, there are also Canadian and Australian definitions.[3][4] All definitions include the requirement for severe, disabling fatigue to have been present for at least six months. There is considerable debate about defining CFS and full consensus has not been obtained.

Several guidelines for the diagnosis and management of CFS have been produced in the UK[5][6][7]and internationally3[8]and the guidelines have also been used to develop care pathways to aid the treatment of CFS-ME patients. [9]5 Some of the guidelines have been the subject of intense criticism, both from healthcare professionals and patient groups and it has been acknowledged by the guideline developers that the evidence base for the guideline recommendations is poor The NICE guideline was the subject of a judicial review that was ultimately rejected in the high court.[10]The basis for the legal case was the lack of evidence for the recommendation for cognitive behavioural therapy (CBT) and graded exercise therapy(GET) and the constitution of the guideline development group.

The National Public Health Service was asked by the Welsh Assembly Government to look at the available evidence based guidelines and care pathways and the quality of the evidence supporting them.An assessment of the extent of the problem in Waleswas also made by determining the CFS prevalence figures for Wales.

2.Aims

  • Rapid review of the evidence used to develop existing guidelines and care pathways for CFS and appraisal of newly published evidence, not included in the guidelines.
  • Estimate of prevalence of CFS patients in Wales.

3.Methods

3.1Identifying existing and ongoing research

3.1i Literature searching

Systematic searching: In 2007 the Library and Knowledge Management Service had performed a scoping search on the diagnosis and treatment of CFS, as per the protocol contained in The evidence checklist[11]to identify published evidence and refine the final search strategy and for the present review this was updated by the author. The search terms were kept broad to maximise retrieval of references (chronic fatigue syndrome, CFS, myalgic encephalomyelitis, myalgic encephalomyelopathy, ME, cognitive behavioural therapy; graded exercise therapy; pacing; diagnosis; treatment; epidemiology)were usedto search Medline, Embase, Cochrane Database of Systematic Reviews, ACP Journal Club EBM reviews; Database of Abstracts of Reviews of Effects; Cochrane Central Register of Controlled Trials; BritishNursing Index and the Health Management Information Consortiumdatabases.

The type of literature on CFS necessitated the use of a pragmatic approach to searching for evidence in order to achieve production of the review, within the short timescales for delivery. It is clear that there had to be a balance between timeliness and rigour and high quality evidence and systematic reviews, meta-analyses, randomised controlled trials (RCTs), health technology assessments and clinical guidelines were identified first. It should be emphasised that the review is not a systematic review of primary studies.

High level searching: It is well known that the classical databases for medical literature, such as Medline, do not adequately index all relevant literature. The reviewer used previously described validated methods [12]that involved the use of meta-search engines and other databases, such as INTUTE, ME Research UK, and Google, for high level searching to quickly identify relevant evidence. [a]

For critical appraisal, the tables recommended for use in the National Institute for Health and Clinical Excellence guideline development methods manual were modified to accept the type of studies identified for CFS. The quality of the evidence was graded using the NICE hierarchy of evidence and the quality checklists. Evidence was rejected if graded as poor quality, apart from where it was of Level 1 type (see Appendix 1 for explanation of evidence grading system) and was highly relevant to the question. The level of evidence is given after each reference in the reference section of the paper.Due to practical limitations a single reviewer performed the final selection, critical appraisal and data extraction.

Inclusion Criteria

Search period January 2000 - May 2009

Papers in English, German, French or Spanish

Papers relating to guidelines and care pathways for CFS.

Randomised controlled trials

Systematic reviews

Meta-analyses

Guidelines

Care pathways

Observational studies (where higher quality evidence was not available)

  1. Results

The scoping searches revealed several key documents relevant to the topic and in particular the recently published health care needs assessment (HCNA) in Scotland[13]and the Belgium Health Care Knowledge Centre (KCE) report[14]which were extensively used to inform the present document. Primary evidence was also used, where relevant to the questions.

4.1Prevalence

The true prevalence of CFS is unknown and estimates vary considerably depending on the definition used and the population studied.In particular there is a lack of epidemiological data for the UK, but evidence from other countries suggests a population prevalence of at least 0.2–0.4% (between 107,458 and 214,915 people in England and Wales) with approximately 25% patients severely affected (between 26,865 and 53,729 people in England and Wales). 6

The National Institute for Clinical Excellence (NICE) guidance on CFS is based on an estimated prevalence of 0.2-0.4%.5 Such prevalence indicates that a general practice with a population of 10,000 patients is likely to have up to 40 patients with CFS, half of whom will need input from specialist CFS services Prevalence estimates also differ according to the period of evaluation and whether point prevalence, 4 year prevalence or lifetime prevalence is reported.[15] Women are at higher risk of developing CFS/ME than men with a relative risk of 1.3–1.7. [16]

Although CFS/ME can affect any age group, including children, it commonly presents in people in their twenties, thirties or fortiesand therefore at a time of life when occupational issues are likely to be important.7 Prevalence estimates for adolescents (> 10 years) range from between 0.0027% and 0.0338%. Such estimates indicate that a general practice with a population of 10,000 adolescent patients is likely to have between 1 and 34 adolescent patients with CFS. For younger patients (5-15 years) prevalence estimates are 0.1% in the community, indicating that 10 patients would have CFS diagnosis in a population of 10,000 children.14Similar prevalence rates have been found in people of different socio-economic status and in all ethnic groups. 5

A report to WAG published in 2004[17], suggested that there could be as many as 11,600 sufferers of ME and CFS in Wales and that 25% of those could be severely affected (i.e. housebound or bedbound). A study in 2003 from Action for ME calculated the total cost to the community per patient of £14,746.[18] Based on this estimate the cost of the illness to Waleswas £171 million in medical costs, benefits payments and lost earnings.

TheHCNA performed by the Scottish Public Health Network 13 emphasised the problems with obtaining accurate epidemiological data on CFS prevalence. The authors used the estimated prevalence of 0.2% – 0.4%, used in the NICE guidance to calculate the prevalence and projected numbers of people with CFS-ME. Results for Wales were calculated using a similar methodology and are shown in the Table 1.

Table 1 Estimated and projectionnumber of people in Waleswith CFS-ME for 2006, 2011, 2016.

2006 / 2011 / 2016
Population / Prevalence / Population / Prevalence / Population / Prevalence
Lower estimate
0.2% / Mid Estimate
0.3% / Higher Estimate
0.4% / Lower estimate
0.2% / Mid Estimate
0.3% / Higher Estimate
0.4% / Lower estimate
0.2% / Mid Estimate
0.3% / Higher Estimate
0.4%
2,966,000 [b] / 5,932 / 8,898 / 11,864 / 3,038,000 / 6,076 / 9,114 / 12,152 / 3,113,000 / 6,226 / 9,339 / 12,452

No data for the UK was found to base an estimate of under diagnosis. Data from the US Centers for Disease Control (CDC) indicatedthat 1 in 5 US citizens with CFS-ME will have been formally diagnosed.[19] Using this estimate Table 2 shows the number of people in Waleswho will have received a diagnosis for CFS-ME.

Table 2 Estimated and projection number of people in Waleswith diagnosed CFS-ME for 2006, 2011, 2016. (Mid estimate 0.3%)

2006 / 2011 / 2016
Estimated number / Diagnosed number / Estimated number / Diagnosed number / Estimated number / Diagnosed number
8898 / 1780 / 9,114 / 1,823 / 9339 / 1868

The Welsh Association of ME and CFS Support undertook a mapping exercise in 2007 [20] with the 22 local health boards in Wales and Health Commission Wales. The results indicated that approximately 176 CFS patients are treated in secondary care each year in Wales, 80 at the two NorthWales CFS clinics and 96 patients at the BronllysHospital;the patients seen atBronllys are however, a mixture of chronic pain and CFS patients.

The Health Information Analysis Team from the NPHSwill provide up to date hospital activity data for CFS.

4.2Guidelines

As mentioned previously there were a number of published guidelines for the care of patients with CFS-ME. The British56and Australian8 guidelines have received considerable criticism from both within the health professions and from the public. These criticisms included claims of bias in the recommendations toward a psychiatricoutcome and failure to understand the limitations of patients to performexercise programs and the recommendation for CBT and GET. The Canadian guidelines differ in their development as they were developedby a committee following input from invited world leaders inthe research and clinical management of CFS patients. 3 An overview of the international guideline perspective was performed by the New Zealand Guidelines Group (NZGG) that also provided a comparison of approaches to CFS across Australia, Canada, the US and the RCPCH UK.[21] The authors concluded that all four sets of guidelines are open to methodological and interpretationcriticisms. Subsequently in order to address the lack of definitive good quality evidence to guide CFS treatment and management, several systematic reviews and evidence based reports have been performed, both in the UK and internationally and the resulting new evidence has been used to inform and compare guidelines. 1314[22][23][24] For the present evidence review,the data presented in these documents was supplemented with literature published subsequently and any papers found by the searches directly relevant to the management of CFS inWales.

4.2iDiagnosis

Currently there are no physical signs or diagnostic laboratory tests that identify CFS specifically, but investigations have an important role in ruling out alternative conditions. To exclude alternative diagnoses a battery of tests is recommended in the guidelines (see e.g.references59).The diagnostic criteria used in the published guidelines are shown in Table 3 and it can be seen that the only criterion present in all the guidelines is the presence for between 4-6 months of fatigue, with sleep disturbance and myalgia present in 6/8 guidelines. NICE recommended making a diagnosis of CFS when symptoms have persisted for 4 months. This recommendation was made by consensus of the NICE guideline development group, because of lack of consistent definitive evidence. The evidence base for this recommendation has been questioned by the authors of the Belgian review14who suggested that this may lead to over diagnosis by notawaiting the occurrence of spontaneous natural regression (e.g. post-viral aesthesia). The NICE guidelines also recommendeda shorter duration of symptoms (3 months) todiagnose CFS in children and adolescents, arguing that 6 months of symptoms is toolong for young persons.The evidence to support this argument is not available and is contentious in the knowledge that the syndrome in adolescents often resolvesspontaneously and a premature diagnosis can lead to a learned illness state. 14

4.2iiCare management andtreatment options

There was international agreement that management of care and/or treatment should beindividualised and the aim shouldbe to provide symptomatic treatment and supportive care to increase the person’s quality oflife, without making their condition worse. Many interventions have been tried for the treatment, management and rehabilitation of patients with CFS from prolonged rest to drug therapies and dietary supplements. The treatments most reported in published outcome studies are CBT, GET, building up activity, return to work and relapse prevention. The NICE guideline recommended only two forms of treatment, CBT and GET and the fact that no other treatments were recommended is one of the major causes of criticism of the guidelines. The guideline was also criticised because of restriction of the level of evidence used for the NICE guideline and bias of the guideline development group towards a psychosocial model.

The judicial review mounted against the NICE guideline examined the decision making processes that were claimed to be basedon a foundation of insufficient evidence of clear benefit being available to recommend the widespread use of CBT and GET. In particular the way in which the Yorkreview24, used to inform the guideline had failed to demonstrate the sort of robust consistent evidence that should be used to make a guideline recommendation.