Exclusive: Four members of NICE’s guideline committee on ME/CFS stand downBMJ 2021; 374 doi: https://doi.org/10.1136/bmj.n1937 (Published 03 August 2021) Cite this as: BMJ 2021;374:n1937
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The article by Torjesen on the NICE guideline development committee for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) does not provide information on why the evidence on rehabilitative interventions was rated as low quality. 
Reviews by Ahmed et al. , Wormgoor et al. , Vink et al. , Tack et al. , and Wilshere et al.  have highlighted methodological weaknesses in trials of rehabilitative interventions for ME/CFS such as graded exercise therapy (GET) and cognitive-behavioral therapy (CBT). Professor Emeritus Jonathan Edwards explained these limitations in his expert testimony to the NICE guideline committee. 
In brief, trials of GET and CBT relied on subjective outcomes while neither patients nor therapists could be blinded to treatment allocation. As both interventions encourage patients to interpret their symptoms more optimistically (resulting from deconditioning, disrupted sleep, and anxiety rather than a hidden pathology), there is a high risk of response bias. On objective outcomes such as actigraphy, employment data, and fitness tests no significant improvements were seen.  In many trials of GET and CBT, patients in the control group received no active intervention but were put on a waiting list. Nonetheless, at long-term follow-up, patients in the control group performed equally well as those who received GET or CBT. [8–10] This suggests that the recommendations in the 2007 NICE guideline were mostly based on expert opinion rather than sound scientific evidence.
It should be clarified that NICE is far from the only healthcare institution that downgraded the quality of evidence for GET or CBT. The Health Council of both Belgium  and the Netherlands  recently came to similar conclusions. In the US, the website of the Centers for Disease Control and Prevention (CDC) no longer recommends GET or CBT for patients with ME/CFS. Cochrane is currently updating its review on GET for ME/CFS after an internal review clarified that the evidence has multiple limitations. 
1. Torjesen I. Exclusive: Four members of NICE’s guideline committee on ME/CFS stand down. BMJ. 2021;374:n1937.
2. Ahmed SA, Mewes JC, Vrijhoef H. Assessment of the scientific rigour of randomized controlled trials on the effectiveness of cognitive behavioural therapy and graded exercise therapy for patients with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review. J Health Psychol. 2020;25:240–55.
3. Wormgoor MEA, Rodenburg SC. The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis. J Transl Med. 2021;19:1.
4. Vink M, Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. 2019;6. doi:10.1177/2055102919840614.
5. Tack M, Tuller DM, Struthers C. Bias caused by reliance on patient-reported outcome measures in non-blinded randomized trials: an in-depth look at exercise therapy for chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior. 2020;8:181–92.
6. Wilshire CE, Kindlon T, Courtney R, Matthees A, Tuller D, Geraghty K, et al. Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol. 2018;6:6.
7. Edwards J. The difficulties of conducting intervention trials for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome. 2019. https://www.nice.org.uk/guidance/gid-ng10091/documents/supporting-docume....
8. Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. The Lancet Psychiatry. 2015;2:1067–74.
9. Clark LV, McCrone P, Pesola F, Vergara-Williamson M, White PD. Guided graded exercise self-help for chronic fatigue syndrome: Long term follow up and cost-effectiveness following the GETSET trial. Journal of Psychosomatic Research. 2021;146:110484.
10. Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 2010;340:c1777.
11. Hoge Gezondheidsraad. Advies van de Hoge Gezondheidsraad nr. 9508. Myalgische Encefalomyelitis/Chronisch vermoeidheidssyndroom. 2020.
12. Gezondheidsraad. ME/CVS. Den Haag: Gezondheidsraad, 2018; publicatienr. 2018/07 https://www.gezondheidsraad.nl/documenten/adviezen/2018/03/19/me-cvs.
13. Cochrane. Publication of Cochrane Review: ‘Exercise therapy for chronic fatigue syndrome.’ https://www.cochrane.org/news/publication-cochrane-review-exercise-thera....
Competing interests: No competing interests
NICE published its draft updated guideline on ME/CFS on 10 Nov 2020. There are comments in this article re the quality of the evidence. If anyone is concerned re NICE's evidence review e.g. the determination that "The majority of the evidence was of low and very low quality"* then they have had had ample opportunity to challenge that [*page 317 -https://www.nice.org.uk/guidance/GID-NG10091/documents/evidence-review-7] .
Nor is there anything for researchers who e.g. wish to evaluate exercise, or psychological interventions, to fear from this review. Typically the studies determined to be of "low and very low quality" were unblinded and used subjective outcome criteria (questionnaires). Fluge and Mella e.g., who evaluated Rituximab in ME/CFS, used actigraphy/actimetry, an objective outcome indicator. In fact the PACE study was intended to include actigraphy/actimetry; however, these objective outcome criteria were dropped. Had objective outcome criteria been included in PACE then the quality of the evidence would not have been considered "low /very low quality". Of course objective outcome criteria are likely to have shown that exercise [GET] and psychological interventions [CBT] weren't effective.
To summarise, there is nothing in the NICE review for those wishing to carry out research into exercise, or psychological interventions, to fear - just those wishing to carry out "low and very low quality" studies using subjective outcome criteria (questionnaires) rather than objective outcome criteria (actigraphy/actimetry). From a Doctor's perspective there is a need for objective evaluation of interventions - the NICE review is therefore a step in the right direction.
Competing interests: Member of my family has disabling fatigue.