Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive–behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.
We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which ‘downgraded’ the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.
We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.
- CHRONIC FATIGUE SYNDROME
- RANDOMISED TRIALS
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Contributors PW drafted the manuscript. All authors have contributed equally and have commented on iterative drafts and agreed the final version.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests PW was a coauthor of trials of both graded exercise therapy and cognitive behaviour therapy, including the PACE trial, is a trustee of the Voluntary Hospital of St Bartholomew’s Charity, was a previous member of Independent Medical Experts Group, which advises the UK MoD on its Armed Forces Compensation Scheme, and receives personal consultancy fees from Swiss Re reinsurance company. BA was a centre leader in the PACE trial. AJC reports grants from NIHR (Physio 4 FMD) and CSO (Long Covid Cognitive phenotyping). AJC is a paid associate editor of JNNP and unpaid president elect of the Functional Neurological Disorders Society (FNDS), he gives expert testimony in court on a range of neuropsychiatric topics on a 50% claimant 50%: defender basis. He is the author of a self-help book based on CBT principles for treatment of FND (no royalties taken). DJC declares grants from Pfizer and Aptinyx; consulting fees from AbbVie, Allergan Sales, Heron Therapeutics, Eli Lilly and Company, Aptinyx, H. Lundbeck A/S, Neumentum, Pfizer, Regeneron Pharmaceuticals, Samumed, Swing Therapeutics, Tonix Pharmaceuticals, Virios Therapeutics. Fees from Fasken Martineau DuMoulin, Kellogg, Hansen, Todd, Figel & Frederick, PLLC, Marks & Clerk Law, Nix Patterson, Pfizer, Zuber Lawler & Del Duca. JC reports consulting fees from Bial, and honoraria from Janssen, Bial and Brittania. BAD reports NIH R13 infrastructure grant for 2022 Functional Neurological Disorders Society meeting in Boston. TC was co-investigator of several trials of behavioural interventions for CFS/ME, including the PACE trial, has received royalties for several books and book chapters on CFS/ME and received payments for workshops on CBT for CFS/ME. BAD is on the board of directors of the FNDS and receives royalties from Oxford University Press for 'Psychogenic Nonepileptic Seizures: Towards the Integration of Care'. She does paid consultancy for Bioserenity (EEG interpretations) and Best Doctors (clinical consultations). She received support to attend the American Epilepsy Society Board of Directors meeting in 2021. She chairs the data safety monitoring board of the DSMB NIH-ESETT trial 2015–2019, and received travel expenses to attend the American Epilepsy Society Board of Directors FNDS meeting and Epilepsy Foundation of New England PAB. MJE reports royalties from Oxford University Press for the book 'The Oxford Specialist Handbook of Movement Disorders', consulting fees from UCB (personal) and Merz Pharma (to his institution), honoraria from the International Parkinson’s Disease and Movement Disorder Society, medicolegal fees for personal injury and clinical negligence cases, support to attend meetings from the FNDS, leadership roles in International Parkinson’s Disease and Movement Disorder Society and Dystonia UK, and is a medical board member of FND Action and FND Hope, and board member of the FNDS. JE was the President of the Faculty of Sport and Exercise Medicine at the time of the Royal College of Physicians’ review of this guideline and submitted comments on behalf of the Faculty. He is Medical Director of a company which occasionally manages patients with CFS/ME. AJE has received grant support from the NIH and the Michael J Fox Foundation, personal compensation as a consultant/scientific advisory board member for Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Bexion, Kyowa Kirin, Sunovion, Supernus (formerly, USWorldMeds), Avion Pharmaceuticals, and Herantis Pharma, and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. He received an honorarium from Avion. He cofounded REGAIN Therapeutics (a biotech start-up developing nonaggregating peptide analogues as replacement therapies for neurodegenerative diseases) and is co-owner of a patent that covers synthetic soluble nonaggregating peptide analogues as replacement treatments in proteinopathies. PF declares consulting fees from FADL Forlag, Munksgaard, Ny Nordisk Forlag and Arnold Busk, an honorarium from Lundbeck Pharma,and medicolegal fees from Retslægerådet. SF was a co-founding member of the GRADE working group and a member of the GRADE guidance group. She has been engaged in debates related to the evidence regarding CFS/ME for many years from a biopsychosocial perspective. PGlasziou declares an NHMRC Investigator Award: 'Neglected Problems in Health Care' supporting his salary; grants from the National Heart Foundation, Commonwealth Department of Health and WHO for work unconnected to this paper, and is a board member (unpaid) for Therapeutic Guidelines. IH has an NRS Fellowship from CSO, has been paid for medicolegal consultations, receives travel expenses for attending medical conferences and one honorarium from Bristol NHS Neurology Department, and is on the board of Fowler’s syndrome UK Charity. WH was a member of the 2007 NICE Guideline Development Group, and is Chief Medical Officer of LV=, an insurance company. PH was part of the steering committee of the German clinical practice guideline on functional somatic symptoms. MH reports fees for medicolegal expert court reports (none concern CFS/ME). HK reports grants from ZonMw, Stichting NKCV, MS Research, and Dutch Cancer Society, was coauthor of trials of cognitive behaviour therapy, reports royalties for a published treatment manual for CBT for fatigue in CFS/ME, and an honorarium for a lecture from Intercept Pharma Deutschland. A Lehn is an unpaid director of the FNDS. AL reports grants for investigator initiated research grants from Gilead Sciences, AbbVie and Sequiris. AM has been on a trial steering committee for a trial of graded exercise therapy, was formerly the Chair of the British Association for CFS and ME (BACME) and Principal Medical Adviser for Action for ME. IM has been paid honoraria by The@WorkPartnership for lectures on the occupational health management approach to managing long-term conditions (including CFS/ME) in the workplace, is the Academic Dean of the Faculty of Occupational Medicine and commented on the NICE guidelines on the management of CFS/ME on behalf of the Faculty. MM received an honorarium for a lecture in 2020 for ViiV, received financial support to attend the EACS 2021 conference (virtual) and ViiV EACS 2019 conference, and was a centre co-lead for the PACE trial. IN reports research grants received from NIHR and MRC to conduct clinical trials on complex interventions, not specific to CFS/ME, has served on several Data Safety Committee as an independent member for trials on complex interventions, one of which related to CFS/ME, and is Co-Chair of Wellcome Trust/Indian Alliance DBT Team Science Grant and Clinical and Public Health Research Centers Grants Committee. DLP reports grants from the National Institutes of Health and Sidney R. Baer Jr. Foundation for work unrelated to this paper, has received honoraria for continuing medical education lectures at Harvard Medical School and the American Academy of Neurology, royalties from Springer Nature for a textbook on Functional Movement Disorder, is a member of the Board of Directors of the FNDS, senior (paid) editor of Brain and Behavior and is an Editorial Board Member of Epilepsy & Behavior. WP reports occasional paid lectures pertaining to FND (most payments donated to charity), has received fees for expert testimony in court on a range of neurological topics including FND, is a board member of FND Hope and FND Action, and is on the board of directors of the BNPA. MR reports a grant from Elsevier, royalties from Oxford University Press, honoraria from UCB Pharma, LivaNova, Eisai, and Angellini and sits on a data safety monitoring board for IqVia Medtech. WR reports grants from the German Research Foundation, royalties from books and fees for German legal opinions. AS was a member of the 2007 NICE Guideline Development Group for CFS/ME (CG53)]. TS reports being a member of the Board of Directors and Membership and Liaisons Committee of the FNDS and being a member of the Functional Movement Disorders Study Group (Movement Disorders Society). MS was a co-principal investigator for the PACE trial and has led a trial of CBT for CFS/ME. He is current President of the European Association of Psychosomatic Medicine Current (unpaid) and was the previous President of the Academy of Consultation Liaison Psychiatry (unpaid). BS is a Council Member of the Association of British Neurologists and Medical Expert Committee member of FND Hope UK. JS reports grants from Scottish Government and NIHR; royalties from UptoDate, the Donald Baxter Lecture Award, Montreal, titled 'Multiple Sclerosis at the limits', personal fees from expert witness work, Secretary FNDS, Medical Advisor FND Hope, Medical Advisor FND Action, running a self-help website for patients with FND. DTW reports consulting fees for expert opinions on patients in a prolonged disorder of consciousness, fees for occasional medicolegal and personal injury cases, member of NIHR grant Programme Supervisory Committee of a trial of vocational rehabilitation after head injury, Deputy Secretary to British Society of Physical and Rehabilitation Medicine (unpaid) and is employed at a nursing home where he sees 2-3 patients with functional disorders. SCW reports honoraria from two talks on psychological impacts of COVID to Swiss Re during the pandemic, but neither covered CFS nor Long Covid. He is on the Board of the ESRC and am also a member of the Judicial Appointments Commission for which he receives renumeration. None are relevant to this paper. SCW is also on the Board of the South London and Maudsley Foundation NHS Trust for which he receives no renumeration. SCW reports receiving grants to research CFS and has published over 150 papers on this subject, including being an author on several RCTs relevant to this submission, but none within the last 36 months. VW is Head of the Collaborative on Fatigue Following Infection (COFFI) (unpaid). AZ reports fees for expert witness medicolegal reports, but not in cases specifically focused on CFS/ME. No other authors declared any relevant competing interests.
Provenance and peer review Not commissioned; externally peer reviewed.
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