Authored by over 50 international specialists in this area, the study questions the NICE review process for this guideline and its use of scientific standards in considering the evidence. Researchers suggest that the consequence is a guideline that deviates from the scientific evidence and will result in patients being unable to access treatments that may help them.

Co-led by researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, the study highlights that implementing the recommendations from the 2021 review could result in patients missing out on helpful treatments which could potentially increase the risk of persistent ill health amongst those with CFS and ME.

The study was published in Journal of Neurology, Neurosurgery and Psychiatry.

ME, also called CFS, is a long-term condition with a wide range of symptoms of which the most common is extreme tiredness. Other symptoms include muscle pain, mental fogginess, and insomnia. CFS/ME is believed to affect about 250,000 people in this country.

The United Kingdom National Institute for Health and Care Excellence (NICE) provides evidence-based summaries that offer recommendations for the treatment of health conditions. In 2007 NICE produced the first guideline for CFS/ME which recommended two forms of rehabilitation to help those with CFS/ME: Graded Exercise Therapy (GET) and Cognitive Behavioural Therapy (CBT).

In 2021 NICE reviewed the scientific evidence, concluding the strength of evidence of benefit from both CBT and GET was low or very low, and also concluded that GET was unsafe. It recommended that GET should no longer be used to help those with CFS/ME and CBT should only be used to manage symptoms and distress, and not to aid recovery. Instead of CBT and GET, the new guideline recommended energy management (pacing) which provides advice on how to live with the illness, making best use of energy without making symptoms worse.

Through analysing the evidence cited by NICE and the recommendations in the guideline, this review identifies eight flaws in the process and outcome:

1. The 2021 guideline proposed a new definition of CFS/ME which required the presence of four symptoms. One of these was ‘post-exertional symptom exacerbation’ (post-exertional malaise), which had not been mandatory in previous Applying this new definition retrospectively, the NICE committee downgraded the large majority of trials of CBT and GET that had not specifically and explicitly required post-exertional symptom exacerbation to be present.
2. The NICE committee considered outcomes for each trial at a time furthest away from when participants were allocated to their groups and received their treatments. This meant that some treatment outcomes were simply ignored. In other trials, participants in the comparison (control) groups had received another therapy by this longest follow up, making it impossible to accurately assess differences between groups, which is methodologically imperative in the context of a clinical trial.
3. The assessment of harm from treatment in the NICE 2021 review prioritised evidence from qualitative studies and patient organised surveys. On this basis NICE concluded GET was unsafe. However, rigorously conducted systematic reviews, which included gold standard randomised controlled trials, found no evidence that GET caused harm.
4. In their assessment NICE downgraded all outcomes related to fatigue, considering it to be too subjective to measure. But how else than asking patients how they are can one assess whether a treatment has worked?
5. Normal NICE guideline development involves the synthesis of research evidence by experts but for this guideline there was remarkably little aggregation and meta-analysis, making it hard to conclude what treatments worked. The analysis fell short of international standards.
6. In the 2021 guideline NICE described GET as incorporating fixed increments of exercise that are pursued irrespective of how the patient feels. However, this does not reflect the therapy reported in the research. Clinical trials, and the previous NICE guideline are clear that activity in GET is determined collaboratively with the patient and only increased as the patient feels able. NICE banned a treatment that no one provides.
7. In NICE guidelines on other relevant health conditions such as chronic unexplained pain, GET and CBT are still recommended. Since such pain is common in CFS/ME, how can a clinician choose which guideline to follow?
8. Having downgraded the evidence for trials of CBT and GET, NICE recommended the use of “energy management,” in which patients are encouraged to stay within the energy limits imposed by their illness, also known as pacing. But there is little or no evidence to support such an approach. The only substantial trial of pacing for CFS/ME published to date showed that such an approach was no more effective than specialist medical care alone and less effective than either CBT or GET.

Co-author on the review, Paul Garner, Professor emeritus of evidence synthesis in Global Health, who has worked in evidence synthesis and guideline methodology at a global level for 25 years, stated: “Taking all these errors leads to one conclusion: that NICE has not followed international standards for guideline development, which has led to guidance that could harm rather than help patients. The implications of this are complicated. The flaws really do shake the credibility of this 2021 update of the NICE guideline for CFS/ME”.

 

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis (DOI 10.1136/jnnp-2022-330463) (White et al., 2023) was published in Journal of Neurology, Neurosurgery and Psychiatry. 

For further information about the paper, please contact Patrick O’Brien (Senior Media Officer)