Barry, Kelley, Tan, Finlay
Abstract
In 2021, the National Institute for Health and Care Excellence produced an evidence-based guideline on the diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling long-term condition of unknown cause.
The guideline provides clear support for people living with ME/CFS, their families and carers, and for clinicians.
A recent opinion piece published in the journal suggested that there were anomalies in the processing and interpretation of the evidence when developing the guideline and proposed eight areas where these anomalies were thought to have occurred.
We outline how these opinions are based on a misreading or misunderstanding of the guideline process or the guideline, which provides a balanced and reasoned approach to the diagnosis and management of this challenging condition.
(In this issue of the ME Global Chronicle we only include the first but maybe most important one. The link to the entire article is at the bottom – the editors)
Defining ME/CFS
There have been over 25 published case definitions for ME/CFS.5 There is no single diagnostic test to establish a diagnosis. It is instead a diagnosis based on the exclusion of other disorders, and the recognition of a cluster of characteristic symptoms, many of which are individually also seen in other conditions.
Some criteria are based on an explicit definition of these symptoms and their duration and so may exclude people with ME/CFS who are not ‘typical’ in their presentation. Other criteria are less specific and may define not only people with ME/CFS, but also people with other fatigue-related conditions. The lack of a ‘gold-standard’ diagnostic test means it is impossible to assess the validity of the diagnostic criteria in terms of accuracy and precision.
The guideline committee examined the criteria currently in use to assess which might be most appropriate for suspecting and establishing a diagnosis of ME/CFS. The development of the criteria was appraised using Appraisal of Guidelines for Research & Evaluation II Instrument (AGREE II) to establish whether they demonstrated an unbiased, clearly reported, evidence-based and consensus-driven process using the expertise of patients, clinicians and researchers. All criteria were found to have serious or very serious limitations. Most criteria included post-exertional malaise (PEM), severe and prolonged fatigue unexplained by activity, cognitive difficulties and unrefreshing sleep, although there were differences in the way these symptoms were defined and whether they were compulsory for diagnosis.
The committee considered the balance between overdiagnosis and underdiagnosis. While the Institute of Medicine (IoM) criteria are potentially more encompassing than the International Consensus Criteria, reducing the probability of missing a diagnosis, the IoM criteria are narrower than others such as the Fukuda criteria, reducing the risk of overdiagnosis. The decision of the committee to use a slightly modified version of the IoM criteria derived from assessment of the quality, benefits and harms, and usability of the criteria. It does not represent a new set of diagnostic criteria.
NICE evaluated scientific evidence for ME/CFS as it is currently defined, based on the IoM criteria. This is the definition that the US Center for Disease Control uses when providing information to healthcare providers. Other reviews on ME/CFS, such as the recent one by IQWiG (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) in Germany, have used a similar approach.10
The committee’s criteria for diagnosing ME/CFS are more restrictive than in the previous NICE guideline,since patients are required to have all the following: debilitating fatigue, PEM, unrefreshing sleep and cognitive difficulties. Symptoms such as fatigue and sleep problems are generic to many conditions and the current NICE guideline therefore contains a definition and explanation of these terms. The fact that these individual symptoms are not specific to ME/CFS does not invalidate their mandatory inclusion in the diagnostic criteria. Fever, for example, is a mandatory feature in the American Heart Association diagnostic criteria for Kawasaki disease,12 but those criteria are not invalidated just because fever also occurs in tonsillitis.
PEM is a required component of the Revised Canadian Consensus Criteria, the International Consensus Criteria and the IoM diagnostic criteria. Wider definitions, such as the Oxford criteria or the London criteria, both used in the PACE trial, do not mandate the inclusion of PEM and therefore risk including people with fatigue from other causes.
In one study of over 6000 participants, 85% of those identified by the Oxford criteria as having CFS were healthy subjects with mild fatigue who had been inappropriately labelled. The committee agreed that papers that had used diagnostic criteria that did not include PEM would be downgraded due to ‘indirectness’ in the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) assessment. This does not mean that papers were ignored or excluded, but that the uncertainty as to whether some trials accurately represent the population with ME/CFS was taken into account when assessing the evidence.
In summary, the diagnostic criteria chosen by the committee were based on those of the IoM, the most recent and widely accepted criteria. It adds another set of consensus criteria to the literature but is not new. The guideline committee recommended further research to define clear diagnostic criteria to differentiate ME/CFS from other causes of chronic fatigue.
Source: BMJ Journals/Neuropsychiatry, open access
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