Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop Free

Ellen M Goudsmit, PhD

Retired

June 21, 2015

Information on ME and Post Viral Fatigue Syndrome might mislead

As someone who has studied myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) since the 1980s, I appreciate the work completed by The National Institutes of Health Pathways to Prevention Workshops on what is now known as ME/CFS. Unfortunately, some of the information in the two reviews is inaccurate, incomplete and misleading (1,2). For example, in the report on diagnostic methods, the reviewers included the London criteria for ME but gave details in the table based on a version written by a layperson, rather than the four individuals cited in their reference (3). Moreover, they did not consider the updated criteria for ME (4), although one of the authors had emailed the panel on two separate occasions during the consultation phase to alert them to their existence.

The second review (2) encourages further research on subgroups and outcomes other than fatigue and function but did not identify one of the few controlled studies which had employed such a design (5). For instance, in the Appendix, Table 1 lists the programme evaluated by Goudsmit and colleagues under ‘counseling and behavioural therapies’, and describes the treatment as ‘counseling’. It also states that patients were selected using the Oxford criteria, that the duration of follow-up was six months and that the outcomes were function and fatigue.

In fact, the trial evaluated a physician-led multi-component programme comprising medical care, information on the illness, diet and relaxation, as well as advice on activity management and some counselling (5). It was conducted in the naturalistic setting of an NHS hospital clinic, patients were diagnosed using criteria for post-viral fatigue syndrome as well as the Oxford criteria, and data were available for a number of symptoms including cognitive impairment, as well as other variables. Fatigue improved as noted in the review but the latter did not convey that 82% of the patients rated themselves as ‘better’, that 23% were well enough to be discharged at six months and that the improvements were maintained at 1 year. Given the missing details, the study’s rating as ‘poor’ is understandable.

The reviewers concluded that “more definitive studies comparing participants meeting different case definitions, including ME... are needed to fill research gaps”. It was therefore disappointing that they did not recognise the positive aspects of a study that used a different case definition and assessed a range of symptoms, not just fatigue.

1. Haney E, Smith MEB, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Diagnostic methods for myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162: 834-40. [PMID: 26075754] doi:10.7326/M15-0443

2. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:841-
50. [PMID: 26075755] doi:10.7326/M15-0114

3. Dowsett E, Goudsmit E, Macintyre A, Shepherd C. London Criteria for myalgic encephalomyelitis. In: Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Westcare. 1994. 96-98. Available from: http://www.actionforme.org.uk/Resources/Action%20for%20ME/Documents/get-informed/national%20task%20force.pdf

4. Goudsmit E, Shepherd C, Dancy CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33. Available from:
http://shop.bps.org.uk/publications/publications-by-subject/health/health-psychology-update-vol-18-no-1-2009.html

5. Goudsmit EM, Ho-Yen DO, Dancey CP. Learning to cope with chronic illness. Efficacy of a multi-component treatment for people with chronic fatigue syndrome. Patient Educ Couns. 2009;77:231–6. [PMID: 19576714 ] doi:10.1016/j.pec.2009.05.015

Ellen M Goudsmit PhD FBPsS

James Webster, MD, MS, MACP

Feinberg School of Medicine of Northwestern University

July 6, 2015

Comment

​As recommended by Haney et. al. (1) the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is best made using nine sets of "inadequately tested" clinical criteria. These are quite non-specific symptoms and there are no associated positive laboratory findings. Thus it is not surprising that most physicians have problems with the diagnosis much less with the difficult diffuse treatment approaches (2) for this entity.

​In a large, but admittedly convenience, sample of patients with the symptoms outlined (1) for ME/CFS the experience was that the overlap with the diagnosis of major depression and persistent (formerly dysphoric) depressive disorder (DSM V, 300.4) was huge. For these illnesses there are diagnostic criteria and proven effective therapies which were used to benefit a number of these latter patients. The differential diagnosis of ME/CFS and depressive disorders is difficult, but not impossible (3). The patients with the symptoms of depression and ME/CFS do indeed have real illnesses (4), but to ignore clear psychiatric possibilities and aspects, including the potential for a therapeutic trial, does them a great disservice.


1. Haney E, Smith MEB, McDonagh M, et al. Diagnostic methods for myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a national institutes of health pathways to prevention workshop. Ann Intern Med. 2015:162:834-840.


2. Smith MEB, Haney E, McDonagh M, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome. A systematic review for a national institutes of health pathways to prevention workshop. Ann Intern Med. 2015;162:841-850.

3. Hawk C, Jason LA, Torres-Harding S. Int J Behav Med. 2006;13:244-51

4. Komaroff AL. Myalgic encephalomyelitis/chronic fatigue syndrome: A real illness. Ann Intern Med. 2015;162:871-872.

M.E. Beth Smith, DO, MCR, Marian McDonagh, PharmD

Oregon Health & Science University

February 23, 2016

Author's Response

In Response: We thank Dr. Goudsmit for her comments. She indicated that we had not identified her study but in fact it was identified and reviewed. Eligible outcomes were reported. We considered studies that recruited participants who fulfilled one of the case definitions for CFS, ME, or ME/CFS. Although her study may have considered additional criteria, it met our inclusion based on use of the Oxford criteria. Our review considered interventions in the categories of medications, complementary and alternative treatments, counseling and behavioral therapies, and exercise. Her study was considered in the category of counseling and behavioral therapies. The types of interventions in this category were broad and varied. We elected to categorize these as cognitive behavioral therapy (CBT), counseling including learning coping and self-sufficiency strategies, pragmatic rehabilitation, and supportive listening. The intervention in her study was multifactorial and included elements of CBT, education, and medical care. The lack of formalized CBT did not allow us to compare it to other interventions in that category, and the psycho-educative approach seemed more aligned with other studies in the counseling category.

When calling for additional outcomes in future research, we are referring to outcomes universal to the patient population such as post-exertional malaise and harms of interventions rather than individual symptoms such as pain, anxiety, depression. Standardized criteria are used to evaluate each study’s risk of bias or quality as outlined in the appendix. The design of Dr. Goudsmit’s study (pre-post) placed it at high risk of bias, which was reflected in its quality rating.

EM Goudsmit PHD FBPsS

Formerly Visiting Research fellow UEL, UK.

February 25, 2016

A matter of confusion and disappointment

I wish to thank Dr Smith and her colleagues for responding to my letter written in June 2015. Unfortunately, the delay seems to have confused the writers and consequently, they did not deal with the issues I raised.

My old eyes may be deceiving me but my copy of the response seems to suggest that I had complained that my study had not been included. From my original comment: " ... in the Appendix, Table 1 lists the programme evaluated by Goudsmit and colleagues under ‘counseling and behavioural therapies’, and describes the treatment as ‘counseling’. It also states that patients were selected using the Oxford criteria, that the duration of follow-up was six months and that the outcomes were function and fatigue."

What I focused on were the factual errors relating to the ME research criteria (London criteria of 1993 and 2009). The team reviewed the criteria published in the Westcare report, which, despite the references, were not authored by me or any other scientist she cited. NB If you click on the pdf for those criteria, you will not find any authors listed and it's a mystery why I was linked to what I and others consider was nonsense. The latest ME criteria (2009) which the team overlooked, are not.

Re quality. Pre-2000, many studies used alternative criteria for post-viral fatigue syndrome, and the trial I described was one of these. I would have given the study a brownie point for using sound criteria to select a more homogenous sample. And I would also have acknowledged the external validity because it was conducted in a hospital setting, as opposed to a well resourced research clinic.

As for the 'pre-post' comment, I'd note that all evaluations of interventions I'm aware of are 'pre-post', so I am mystified at the comment that "The design of Dr. Goudsmit’s study (pre-post) placed it at high risk of bias, which was reflected in its quality rating." The point missed is that a significant number in the Goudsmit et al trial were well enough to be discharged at six months (i.e. after one and a half hours clinic attendance). Isn't that what physicians want to know? Good outcomes in the real world?

I see many refer to ME/CFS but they do not know that the ME stands for. And how it differs from CFS. 'Malaise' is a vague lay term for something subjective and difficult to measure. It's why it has been criticised and is being dropped by specialists (in favour of PENE etc, as described in the article). The 2009 ME criteria provides an objective measure to assess criterion 1, which takes some of the guesswork out of diagnosis. I find it strange that none of the authors were interested.

Finally, to focus on fatigue and post-exertional malaise is a little like a cancer study which assesses the primary tumour and tiredness and ignores the secondaries and nausea. There's more to ME/CFS than fatigue and malaise. I am so disappointed, both with the original paper and the response. Good science depends on precision to detail. It's the least that we, and patients, deserve.