Peter Walter Barry, Kate Kelley, Toni Tan, Ilora Finlay
This publication is especially important because it is NICE’s own response to all the “accusations ” made in Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis, the publication by 51 European psychiatrists and psychosomatics to undermine the 2021 NICE guideline.
Therefore, we publish here parts of those passages from it that relate to those assumptions.
Since NICE’s response it has been remarkably quiet. Although we assume that the authors of the criticisms of the guideline will not give up their areas of power without further fight.
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.
The committee’s criteria for diagnosing ME/CFS are more restrictive than in the previous NICE guideline,11 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.
Endpoints to assess efficacy
All NICE guidelines follow the process for evidence synthesis set out in ‘Developing NICE guidelines: the manual’.1 This process defines what outcomes and endpoints will be used when determining clinical and cost effectiveness. These are defined before evidence is examined. Any inference that the committee looked at the evidence review and picked the outcomes which best matched their pre-conceptions is simply incorrect.
Data on treatment harm
Treatment harm and side effects are routinely considered in evaluations of interventions, and qualitative evidence, appropriately analysed, is important for assessing patient impact in NICE guidelines.
Twenty-five qualitative studies were included in the review of non-pharmacological interventions. These were analysed using robust and accepted methodologies. In studies relating to GET or other exercise interventions, participants reported that following the exercise programme was ‘hard work’ and in some, this led to worsening of symptoms after each session. For others, trying to persist with the exercise programme led to a worsening of their symptoms in the longer term. Debilitating exacerbation of symptoms was a reason for discontinuation. In one study, up to 74% of patients have reported experiencing harms after GET.
Fatigue as an outcome
Blinded trials that used fatigue as an outcome were not downgraded for this risk of bias. ‘Downgrading’ in critical appraisal indicates the quality of the evidence, it does not mean exclusion of the evidence. Fatigue was one of ‘the outcomes that matter most’ in the evidence review.
Many of the intervention studies for ME/CFS rely on unblinded subjective outcomes. Where reported, objective outcomes data such as activity levels, employment levels, disability payments or fitness data showed no or minimal improvement in these trials.
Evidence synthesis methodologies
NICE guidelines follow the process for evidence synthesis set out in ‘Developing NICE guidelines: the manual’1 and accepted methodologies, such as GRADE.34 GRADE methodology is not used to exclude or reject evidence, but to assess the quality and certainty of the evidence.
In accordance with GRADE methodology,35 trials were downgraded due to indirectness, for example, where trials included patients with different diagnostic criteria; due to imprecision, where a CI crossed the minimally important difference; or due to risk of bias, such as where therapist encouragement might reasonably lead to response bias rather than therapeutic effect.
Graded exercise therapy
Aside from the different definitions of the term ‘graded exercise therapy’, the content and application of such programmes also differ… For instance, the GET Therapists manual from the PACE Trial instructs practitioners to ‘negotiate meaningful goals’ and then, as its next step, to increase the duration of exercise by a fixed increment, such as ‘add 20% duration, up to 30 min’.36 If people have exacerbation of their symptoms, they are encouraged to maintain the same exercise level that led to their deterioration and told that ‘hurt does not equal harm’.
Some stakeholders stated that GET, as defined in the guideline, is not what is delivered in practice. Others report that GET, as defined in the guideline, is still used and that has caused significant harm.
Cross-referencing NICE guidance
NICE recommends different therapies for different conditions, even though many share common symptoms such as pain or breathlessness… Pain is commonly experienced in many conditions, including in people with ME/CFS who comprise less than 1% of the total population with chronic pain.
People with ME/CFS differ from people with chronic primary pain who are the main focus of the Chronic Pain Guideline, making other guidance more appropriate for these individuals. Although exercise has been shown to improve chronic pain, exercise in individuals with ME/CFS can exacerbate both fatigue-related and pain-related PEM.
Evidence about energy management
There is a lack of evidence supporting energy management in people with ME/CFS, and no evidence that it is a ‘cure’. But there is also no signal of harm or deterioration with energy management programmes, unlike with GET.
One principle of energy management is an attempt to avoid PEM, and so there is no drive to increase activity by setting graded goals and no suggestion that worsening symptoms are a natural response to increased activity, as there is in GET.
Conclusion
Development followed a transparent process that conformed to recognised standards for guideline development, including extensive consultation with stakeholders prior to publication.
All evidence needs interpretation: evidence alone cannot determine the content of a recommendation. Criticisms of the guideline discussed in this paper are misplaced. The guideline has been welcomed and widely accepted by patient groups and clinicians leading services for people with ME/CFS in the UK.
We hope that the guideline will lead to better care and the development of more effective therapies for people with ME/CFS.
Source: BMJ Journals
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