ME/CFS PSP Question Verification Form

The purpose of this Question Verification Form is to enable Priority Setting Partnerships (PSPs) to describe clearly how they checked that their questions were unanswered, before starting the interim prioritisation stage of the process.

The JLA requires PSPs to be transparent and accountable in defining their own scope and evidence checking process. This will enable researchers and other stakeholders to understand how individual PSPs decided that their questions were unanswered, and any limitations of their evidence checking.

Name of the PSP

ME/CFS PSP

Please describe the scope of the PSP

The scope aims to be inclusive and transparent. ME/CFS is a long-term (chronic), fluctuating, neurological condition that causes symptoms affecting many body systems, more commonly the nervous and immune systems. ME/CFS affects an estimated 250,000 people in the UK, and around 17 million people worldwide.

The World Health Organization has classified ME as a neurological disease since 1969. The underlying mechanisms of the condition are not known however people with ME/CFS experience severe, persistent symptoms associated with post-exertional malaise (the body’s inability to recover after expending even small amounts of energy).

For the purposes of identifying research questions, we will assess existing research using well-accepted diagnostic criteria: the Institute of Medicine (IoM) 2015 or the 2003 Canadian Consensus Criteria (CCC), but not the Oxford or NICE criteria. Studies with other criteria will be considered only where post-exertional malaise (PEM) is considered a mandatory symptom. This is because patients, patients’ organisations, and ME/CFS biomedical researchers all regard it as a defining symptom of the disease.

Target audience includes:

people with ME/CFS diagnosed by a clinician;
people who have had ME/CFS;
all of UK;
ages 16 and older;
carers of younger children with ME/CFS.

The Steering Group trusts that people participating in the project have a clinical diagnosis of ME/CFS, or they are the supporter or a clinician for a person with ME/CFS. This does mean that someone can participate even if they do not have a clinically verified diagnosis. However, the number of people who might do so is not expected to impact the process, and it is preferable to keep any barriers for participation to a minimum.

The questions may be about:

causes, prevention, risk factors, diagnosis;
living with and disability associated with ME/CFS;
symptoms, relapses, treatment or management;
issues for carers;
services relevant to the condition and access to services.

The scope of the PSP excludes:

People without a diagnosis of ME/CFS (or CFS/ME or CFS or ME)
The symptom of Chronic Fatigue caused by other conditions is excluded.
Studies of ME/CFS using the Oxford Criteria, NICE 2007 criteria, Fukuda Criteria without mandatory PEM.

The scope may have implications for the amount of data that will be collected, and how this can be analysed.

Please provide a brief overview of your approach to checking whether the questions were unanswered

Evidence uncertainties were verified by the data analyst by reviewing published literature and drawing on the knowledge and experience of Steering Group members of research in this field.

Please list the type(s) of evidence you used to verify your questions as unanswered

Published systematic reviews (or higher) identified through literature search of sources and parameters listed below

Please list the sources that you searched in order to identify that evidence

The following sources were used:

The Cochrane Library
NICE Guideline evidence reviews
PubMed
Google Scholar

What search terms did you use?

The following search terms were included:

ME
CFS
ME/CFS
CFS/ME
myalgic encephalomyelitis
myalgic encephalopathy
chronic fatigue syndrome
SEID (systemic exertion intolerance disease)

+ ‘systematic review’.

Please describe the parameters of the search (eg time limits, excluded sources, country/language) and the rationale for any limitations

All reviews in English published since 2016 (in the last five years) that met the search criterion were included

Names of individuals who undertook the evidence checking

Kristina Staley

On what date was the question verification process completed?

23 September 2021

Report considered by Steering Group on 30 September 2021.

Any other relevant information

None of the summary questions were found to be answered by research.

The literature search included general reviews, as well as question specific papers. The questions specific references are provided in the JLA Data Spreadsheet, the general reviews are cited below.

General reviews

Kim DY, Lee JS, Park SY, Kim SJ, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020 Jan 6;18(1):7. doi: 10.1186/s12967-019-02196-9.To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.
Conclusion: There was no definitely effective intervention with coherence and reproducibility.\
Huth TK, Eaton-Fitch N, Staines D, Marshall-Gradisnik S. A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID). J Transl Med. 2020 May 13;18(1):198. doi: 10.1186/s12967-020-02356-2.
In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID.
Conclusion: The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.
Mengshoel AM, Helland IB, Meeus M, Castro-Marrero J, Pheby D, Bolle Strand E. Patients' experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome - a scoping mixed methods review. Int J Qual Stud Health Well-being. 2020 Dec;15(1):1764830. doi: 10.1080/17482631.
Conclusions: Methodological differences make comparisons across NPTs impossible, and from a patient perspective the relevance of the specific contents of NPTs are unclear. Future well-designed studies should focus on developing NPTs tailored to patients' concerns and evaluation tools reflecting what is essential for patients.
Cochrane M, Mitchell E, Hollingworth W, Crawley E, Trépel D. Cost-effectiveness of Interventions for Chronic Fatigue Syndrome or Myalgic Encephalomyelitis: A Systematic Review of Economic Evaluations. Appl Health Econ Health Policy. 2021 Jul;19(4):473-486. doi: 10.1007/s40258-021-00635-7.
Conclusions: We identified a limited patchwork of evidence on the cost-effectiveness of interventions for CFS/ME. Evidence supports CBT as a cost-effective treatment option for adults; however, cost-effectiveness may depend on the duration and frequency of sessions. Limited evidence supports the cost effectiveness of GET. Key weaknesses in the literature included small sample sizes and short duration of follow-up. Further research is needed on pharmacological interventions and therapies for children.
Muller, A.E., Tveito, K., Bakken, I.J. et al. Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched. J Transl Med 18, 484 (2020). https://doi.org/10.1186/s12967-020-02665-6
Conclusion: The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.

Version 1
Date 17.05.22