Revisiting NICE Expert Testimony on trials in ME/CFS: Professor Jonathan Edwards

The following expert testimony was provided to the NICE ME/CFS Guidelines Committee by Professor Jonathan Edwards. It regards the difficulties of conducting trials in ME/CFS and the implications of not accounting for these.

The difficulties of conducting intervention trials for the treatment of myalgic encephalomyelitis / chronic fatigue syndrome

Summary testimony

Therapeutic trials for ME/CFS are particularly at risk from expectation bias because of the subjective core features and fluctuating nature of the illness. Therapist-delivered treatments, with lack of blinding, and particularly those involving cognitive intervention, are even more at risk because of role-playing and deliberate influence on attitudes to health status. Trials of drug treatments have tended to navigate difficulties adequately but have yielded negative (or equivocal) results. Trials of therapist-delivered treatments to date have not met basic requirements for minimising bias and are therefore unsuitable as an evidence base for treatment recommendations. Inasmuch as they are interpretable, they suggest that although attitudes to health status maybe influenced this does not lead to significant improvement in objectively measures of disability. There are also specific ethical concerns with trials of treatments that aim to persuade patients of an unproven theoretical model for their illness and for which there is prima facie evidence of significant harm (for exercise therapy). The failure to meet basic requirements indicates a problem with quality control through peer review in this area, as illustrated with problems with Cochrane reviews (see bibliography: Vink and Vink-Niese, 2018; Vink and Vink-Niese, 2019). Trials to date have failed to make use of methods that can significantly mitigate difficulties with bias from subjective outcomes, but it may be that for unblindable treatments new forms of trial methodology will be needed if useful assessment is to be achieved. In my view, the uninterpretability of evidence from trials that fail to overcome basic difficulties, combined with ethical concerns, means that it is inappropriate to recommend either cognitive behavioural therapy or exercise therapies for ME/CFS.


I have been asked to act as an expert witness for the NICE ME/CFS guidelines committee in relation to difficulties of conducting intervention trials for treatment of ME/CFS. The following comments lay out my views on what I see as relevant issues. I have taken an interest in ME/CFS over the last five years, having been asked to advise on research quality by charities and funding bodies. My prior professional expertise was in translational rheumatology/immunology. I managed patients with illnesses involving fatigue, including ME/CFS, but had no special interest in the illness at the time. My research focused on mechanisms and treatment of autoimmune disease, including the introduction of rituximab for non-haematological diseases. I was involved in both basic laboratory science and clinical trials, from pilot studies through to large proof of concept trials. Since retirement I have acted as expert witness in major patent cases involving interpretation of clinical trials.

When asked to review research into ME/CFS my general impression was that, apart from some useful epidemiology studies and some well-designed mechanistic and clinical studies with negative results, research quality was disappointingly low. In terms of intervention trials there also appears to bea mismatch in standards of evidence applied to pharmacological and non-pharmacological treatments.

For clinical trials of pharmacological agents directed at the illness itself, rather than intercurrent symptoms, there is a consensus that in the absence of positive studies with either adequate blinding or objective endpoints we have no reliable evidence of efficacy. I assume that no recommendations are likely to be made regarding pharmacological treatments for ME/CFS per se. I will refer to drug studies only to illustrate the difficulties that beset trials for ME/CFS in general and the extent to which they can be, and have been, navigated.

The situation for therapist-delivered treatments is more difficult. Despite a similar absence of positive studies with either adequate blinding or objective endpoints there is a lack of consensus on use of these treatments. Both cognitive behavioural therapy (CBT) and graded exercise therapy (GET) were recommended previously and I agree that the justification for their inclusion needs reviewing. Trials of these treatments highlight the difficulties posed by clinical trial design for ME/CFS and this needs to be addressed.

Complete testimony

(PDF embedded and directly viewable in supported browsers – scroll down to download otherwise)

More NICE ME/CFS Guideline 2021 Content

NICE 2021: A Triumph of Science over Discrimination

Doctors with M.E. stands ready to work with partners and organisations to bring medical education up-to-date and assist in developing the right services for ME/CFS patients. “The new guideline represents a positive and total paradigm change, uniting around the science, official disease classification and medico-legal compliance implications.” “This translation of scientific knowledge into clinical practice…

girl leaning her head on her hand while closing her eyes

Public Letter to RCPCH: DwME Associate and Neurodisability Paediatrician Dr. Ben Marsh calls for explanation

A call for the Royal College of Paediatrics and Child Health to explain undermining of scientific review Doctors with M.E. Associate, Neurodisability Paediatrician and representative on the JLA Priority Setting Partnership Steering Group, Dr. Ben Marsh, has publicly written to the President of The Royal College of Paediatrics and Child Health (RCPCH). He requested an explanation for the College’s…

The NICE debacle – will NICE survive?

The current NICE debacle and extraordinary deviation from normal procedure and published protocol is further evidence of institutionalised discrimination by large sections of the UK medical establishment.  That one professional and patient group should be treated in a manner at odds with clear and growing scientific knowledge would be unacceptable in any other disease.  Yet…

Doctors with M.E. Honorary Fellow and founding father of the Human Genome Project comments on the NICE pause – “it is time for the UK to join the rest of the scientific community”

Doctors with M.E. Honorary Fellow Professor Ron Davis has issued a powerful statement condemning the failure of the UK National Institute of Clinical and Care Excellence to maintain its independence. He describes how it has instead accommodated vested interests, which perpetuate low standards and contra-scientific medical belief systems. “It is a travesty that NICE is…

Global scientific communities and clinicians urge NICE to Publish ME/CFS Guideline now

Doctors with M.E. Board, Fellows & Associates are co-signatories to a public letter written by Dr. David Tuller of the Center of Global Public Health at the University of California, Berkeley. The letter writes to urge NICE to publish the new ME/CFS guideline. It is signed by scientists, clinicians, academics and other experts from the…

BBC Radio 4: Doctors with M.E. feature on flagship Woman’s Hour

ME, Long Covid and the NICE Guideline 2021 Delay Doctors with M.E. Director, Dr. Nina Muirhead, and Doctors with M.E Honorary Fellow and Action for ME Medical Advisor, Dr. David Strain, discuss ME/CFS, Long Covid, the NICE guideline delay and the need for more education and resources in an interview on BBC Radio 4 Woman’s…

Mayo Clinic: ME/CFS Essentials of Diagnosis and Management Consensus Statement

This comprehensive article, co-authored by Doctors With M.E. Honorary Fellows, Dr. Lucinda Bateman and Professor Anthony Komaroff, summarises best clinical practice recommendations for generalist and specialist health care providers treating adults affected by ME/CFS. The article covers epidemiology, prognosis, etiology and pathophysiology, diagnostic approach with new diagnostic criteria, and management of ME/CFS. The clinicians behind…

bridge over river in city

Public Letter to DHSC, MHRA, HoC, NICE: Call for a ‘Medical Regulatory Agency’

A call for change in the face of long-standing regulatory failure The following public communication from our Governance Board regards the opportunity for a new “Medical Regulatory Agency”, ready for the post-brexit and the machine learning digital eras.  The letter also contains background pertaining to long-standing regulatory failure, unlawful medical norms, contra-scientific medical belief systems and…

Rapid Response and Expert Comment: NICE Guideline Delay and Accommodation of Unlawfulness

We are very disappointed to hear of the ‘pause’ in publication of the NICE ME/CFS Guideline, already delayed in April. Following the hard work of the Guideline Development Group, we received news of the further delay of guideline publication with both dismay and profound concern for practitioners, their organisations and patients. Continued delay or deviation…

Honorary Fellow on the new NICE Guideline for ME/CFS: Ten Questions Answered

Your questions regarding the new NICE Guideline announcement this week have been broken down and addressed by Doctors with M.E. Honorary Fellow, Professor Brian Hughes: 1. What’s going on? 2. How is the new guideline different to the old one? 3. Why is the new guideline being welcomed? 4. Why was the old guideline problematic?…