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Volume 55, Issue 3, March 2026

Invited response to viewpoint article ‘Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome/myalgic encephalomyelitis harming patients?’

Daniel Ewald   
doi: 10.31128/AJGP-09-25-7845   |    Download article
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Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) remains a poorly diagnosed yet debilitating condition. The Handbook of Non-Drug Interventions (HANDI) aims to make evidence-based non-drug interventions accessible and easier for clinicians to use where appropriate.

HANDI’s development and review processes are detailed on the website:1 best evidence is reviewed and summarised, and tips are provided for implementation by a multidisciplinary editorial committee with a wealth of clinical and epidemiology experience. HANDI is not a guideline as it does not compare the treatments in entries to other treatment options, nor make recommendations. Hence assessment using the AGREE II instrument is inappropriate. HANDI interventions are graded using the National Health and Medical Research Council (NHMRC) standards, or the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process for quality of evidence (not strength of recommendation).

Clinicians should note that some patient support groups have rejected the evidence of benefit from appropriately graded exercise, which has fractured the healthcare for CFS/ME, pre-dating the significant PACE trial 2008.2 Debate on methodological quality of the PACE trial is addressed in The Lancet.3 Several randomised controlled trials (RCTs) examining graded exercise for CFS/ME are provided in the supportive Cochrane review.4 While Cochrane reviewers (2019) do account for study limitations, there is still moderate-strength GRADE evidence, for some patients, for a benefit of graded exercise over passive control groups or usual care with fatigue as the primary outcome.

For CFS/ME, all the studies reviewed by the HANDI editorial committee (and Cochrane review) are RCTs or systematic reviews of RCTs. The evidence offered for harm from exercise is from surveys at high risk of bias. Clinicians should be aware that some patients with CFS/ME cannot tolerate graded activity, but some may have been poorly guided in correct exercise implementation, triggering exacerbation of symptoms. HANDI provides some detail about the importance of patient selection and correct implementation.

HANDI recognises the underlying pathophysiology of CFS/ME is not known, and there are few proven treatment options. Current evidence supports appropriately graded incremental physical activity to manage symptoms.

The 2023 NICE guideline retraction was highly controversial and not aligned with research evidence, resulting in members of its writing group resigning. Details of the aberrant interpretation of evidence are outlined elsewhere.5,6

Competing interests: Chair, Editorial Committee for RACGP Handbook of Non-Drug Interventions.
AI declaration: The author confirms that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript.
Provenance and peer review: Not commissioned, externally peer reviewed.
Funding: None.
Acknowledgements
For editing comments: Professor (Emeritus) Paul Glasziou, Institute for Evidence Based Healthcare, Bond University, Qld and Donna Southern, RACGP staff.
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References
  1. The Royal Australian College of General Practitioners (RACGP). About HANDI (Handbook of Non-Drug Interventions): What is the HANDI project? RACGP, [date unknown]. Available at www.racgp.org.au/clinical-resources/clinical-guidelines/handi/about-handi/about-handi [Accessed 17 December 2025]. Search PubMed
  2. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol 2007;7(1):6. doi: 10.1186/1471-2377-7-6. Search PubMed
  3. Sharpe M, Goldsmith K, Johnson AL, et al. Patient reaction to the PACE trial – Authors’ reply. The Lancet Psychiatry 2016;3(2):e8-e9. doi: 10.1016/S2215-0366(16)00018-3. Search PubMed
  4. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev 2024;12(12):CD003200. doi: 10.1002/14651858.cd003200.pub9. Search PubMed
  5. Torjesen I. Exclusive: Four members of NICE’s guideline committee on ME/CFS stand down. BMJ 2021;374:n1937. doi: 10.1136/bmj.n1937. Search PubMed
  6. White P, Abbey S, Angus B, et al. Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry 2023;94(12):1056–63. doi: 10.1136/jnnp-2022-330463. Search PubMed

Chronic fatigue syndromeClinical guidelinesGraded exerciseIncremental physical activityMyalgic encephalomyelitis

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