The following is a copy in full of an article by MERGE and the 25% ME Group published at the website of ME Research Group UK (MERGE). A short version originally appeared in the August 2004 issue of the magazine InterAction.
"Severely ill are severely overlooked; just ignored and invisible." Chief Medical Officer (CMO) report 2002, Section 2.3.1
Ignored and invisible! When the authors of the Chief Medical Officer's report of 2002 coined that phrase they were referring to the exclusion of the most severely ill people with ME from community and social care provision. However, the same description also holds true for mainstream scientific research.
A cursory glance at the existing scientific literature on ME (largely held in electronic databases — mainly MEDLINE — and specialist resources like the downloadable database of some 3000 abstracts at the MERGE website) reveals the virtual absence of information on the most severely affected people.
The Table below gives the number of articles (loosely defined) published for some randomly-chosen illnesses, and it shows two things. First, that ME is a Cinderella illness compared with other comparable chronic conditions
in terms of volume of research publications; and second, that research on the severely ill is a rarity in most illnesses, including ME.
Table. Number of MEDLINE entries to May 2004 for a range of illnesses including ME/CFS.
The percentage of these relating to severe illness (variously defined) is also shown. These crude ballpark figures illustrate well enough the paucity of research into ME/CFS, and on severely ill people in particular.
Total no. of articles -- Estimated no. of "clinical trials" -- Estimated trials on the severely ill
221,828 -- 10,236 -- 0.27%
78,589 -- 4,351 -- 0.38%
29,032 -- 1,426 -- 0.32%
Low back pain
9,649 -- 969 -- 0.57%
Irritable bowel syndrome
2,978 -- 519 -- 0.47%
2,841 -- 146 -- 0.49%*
*In practice, very few of these studies deal specifically with the most severely ill people with ME/CFS (i.e., the housebound, bedbound or immobile).
The point is that severely affected people with ME are doubly disadvantaged: not only is this illness under-researched compared with other chronic conditions, but the most severely ill group of patients is under-represented in what little research is done. In fact, very few studies exist, and all define "severe illness" in different ways, complicating interpretation of the findings. And specific laboratory-based or experimental studies on severe sufferers are as rare as hens' teeth.
The findings so far...
For the record, the studies in question that present some kind of patient data (albeit with varying definitions of "severe" illness) include:
a) Effect of specialist hospital programmes
— The CFS team at Oldchurch Hospital in Essex surveyed the 72 most severely affected CFS patients admitted 1990–98. They found that 46% had actually been discharged with an alternative diagnosis to CFS,
that patients with a symptom duration greater than five years appeared to improve, and that the level of severity did not preclude improvement (Cox & Findlay, 2000). In a subsequent quasi-experimental study, this team found that their occupational therapy intervention significantly improved perception of health and "length of time tired" in patients compared with waiting list control patients (Cox, 2002).
The Oldchurch team have continued to audit the outcomes of their work, and the most recent of these (December 2003) examines 24 severely affected patients following an inpatient stay. While two-thirds saw their severity rating improve by one or two grades, on a scale of one to five, a third saw no change in their level of severity. However, 50% reported a positive shift in mood and 87% described an increase in their quality of life post-admission. Using a patient feedback questionnaire, 39% rated their satisfaction with the CFS service as 10/10, with just 4% giving a score of less than five.
Two similar, smaller outcome studies (Chalder et al, 1996; Essame et al, 1998) also reported appropriate multidisciplinary inpatient rehabilitation to be beneficial, at least in terms of "functional ability", to the majority of severely affected patients. (Five out of six patients "functionally improved" in the Chalder study and 17 out of the 19 followed up in the Essame study).
b) An experimental study of cardiac output
— Researchers examining 38 patients found that participants with "severe" CFS had significantly lower cardiac output than the controls and less ill patients (Peckerman et al, 2003). Post-exertional fatigue and flu-like symptoms of infection clearly differentiated the patients with severe CFS from those with a less severe presentation, and were predictive of lower cardiac output. These results, say the researchers, "provide a preliminary indication of reduced circulation in patients with severe CFS".
c) Investigating longer-term outcomes
— One study has evaluated the natural history of CFS in a severely ill group of 24 patients at three points in time (Hill et al, 1999). Over the four years of the study, thirteen patients remained severely ill, nine improved but still fulfilled the 1994 case definition for CFS, and one recovered. Illness duration, mode of onset, psychiatric status/depressed mood at intake, or chemical sensitivity did not appear to predict illness outcome. Not surprisingly, mood improved for those patients whose illness lessened. The researchers concluded that the prognosis for full recovery was extremely poor for the most severely ill subset of CFS patients.
Another outcome study of severely affected children (Rangel et al, 2000) followed up 25 children using child-parent interviews. After nearly four years, two-thirds of the children had recovered, and none had developed any other medical conditions, allowing tentative conclusions that severe illness can cause severe handicap but that most children recover.
In addition, one report has detailed outcomes for two wheelchair-bound CFS patients treated by a "pragmatic intervention" consisting of more than 50 face-to-face or telephone contacts with a therapist over approximately two years. By the end of the intervention, both patients were reported to be free of their wheelchairs and leading "relatively independent existences" (Powell et al, 1999). And two reports have also been published giving results from the Case History Research On Myalgic Encephalomyelitis (CHROME) database (Gibbons et al, 1996 & 1998).
Why is there so little research?
The CMO report defined the severely affected as those "patients whose physical disability is most severe, leading to serious restrictions in mobility and functioning. In many, these restrictions are accompanied by other markers of severity, such as cognitive impairment or prolonged course" (Section 3.4.3). Clearly, anyone who is severely affected would struggle to attend hospital-based investigations, which often require multiple visits.
However, even if they could attend, they might well be excluded for other reasons, such as the presence of "co-morbid" illnesses which often accompany severe ME and its consequences (e.g., long term immobility with accompanying deconditioning, susceptibility to infection, etc.), or their inability to fulfill the requirements of a trial (e.g., perform graded exercise or stop current medications). Sensible though these restrictions might seem to healthy young researchers, they are little comfort to severely ill people who wish to see scientific progress within their own lifetime! Of course, it is feasible to conduct a "pragmatic" study in which a "treatment" is given to a large group of diverse patients in their own homes, and one of these — the FINE trial — has just begun.
The FINE Trial — thanks a £million?
Heralded as offering a "promising new treatment" for people with severe ME, the FINE (Fatigue Intervention by Nurses Evaluation) Trial is presently recruiting staff and will report its conclusions in 2008 or even later. Costing £1,147,000, the trial is funded by the UK's Medical Research Council with a grant to Dr Alison Wearden, a psychologist based in the Department of Psychology, University of Manchester, and colleagues in Liverpool (Department of Psychiatry) and Manchester (Department of Psychiatry). In the preliminary supporting documentation, the FINE Trial is a described as a "randomised controlled trial of nurse-led, self-help treatment for patients in primary care... Referred patients will be randomly allocated to one of three treatment groups: (a) nurse-led self-help, (b) supportive listening or (c) GP treatment as usual." Patients will be visited in their own homes, and before "treatment" commences qualitative interviews will be conducted to explore"patient views on illness causation, beliefs about chronic fatigue, expectations of intervention, and previous experience of treatment and doctor-patient relationships". At the same time, the patients' GPs will be asked about their experiences of and attitudes towards patients with ME. After 20 weeks of "treatment", patients will be assessed for a variety of outcomes, and again after one year.
What is the "promising new treatment" on offer to the severely-ill patients? Called "nurse-led self-help" or "pragmatic rehabilitation", the approach "is designed to increase activity and challenge dysfunctional illness beliefs"
(Powell et al, 1999), and includes elements of the cognitive behavioural and graded exercise therapy championed by those psychiatrists and psychologists who promote the "biopsychosocial" model of ME. The basis of this model is that "once an illness has started, its expression is affected by beliefs, coping styles, and behaviours, while consequential physiological and psychological effects act in some ways to maintain and/or modify the disease process" (CMO Report 2002). Pragmatic rehabilitation, we are told, will help patients to understand their symptoms and, jointly with the nurse, agree a programme of rehabilitation. In support of its usefulness for the most severely ill patients, a single report in the scientific literature (Powell et al, 1999) describes two wheelchair-bound patients who had dramatic improvements in health following the pragmatic rehabilitation regimen now being rolled out to larger groups of patients as a full-scale MRC-funded trial. (Two other seemingly relevant reports in the scientific literature are, in fact, small pilot studies that refer to inpatient treatments within psychiatric wards, vis, Chalder et al 1996 and Essame et al 1998.)
This treatment is not new and hardly promising on the basis of two case reports. But will some people benefit and report improvement of a sort? Well, probably — given that the quality of life of us all (well or unwell) can be improved by changing some of our beliefs and coping behaviour, and increasing our activity levels. But as the authors of the new Canadian definition of CFS/ME make clear, the question is whether such treatments (generally recognised not to be a cure for patients' physical illnesses or suitable for everyone with ME) add anything to what is available in the general medical setting, and hence whether the taxpayer-spend of £1,147,000 (including £411,000 in NHS costs, very useful for oiling the wheels of academic departments) is value for money. And furthermore, there are considerable doubts about whether the trial will address the central problem of ME.
For instance, will each severely-ill person on the FINE trial be given a comprehensive medical assessment to identify somatic (physical) symptoms and signs? Autonomic disturbances, seizures, frank muscle weakness, neuroendocrine disturbances (like sweating episodes), recurrent flu-like symptoms — will they be recorded over the 70 weeks? Symptoms like musculoskeletal pain, neurocognitive problems and sleep dysfunction — will they be comprehensively assessed? Will patients receive treatment for any of these? Or will these signs and symptoms of ME be ignored while the patients' beliefs are explored by nurses steeped in the biopsychosocial culture of their paymasters?
Because the full protocol for this trial has not been made publicly available, despite being publicly funded, it is impossible to know...
But one thing we do know. The FINE trial is recorded under the "Mental Health in Primary Care" programme in the National Research Register 2004. And there's the rub. Given the expanding core of evidence for a biological pathology for this illness, it is widely felt by patients, support groups and their political representatives that scarce research funding would be better targeted at appropriate biomedical investigation and treatment of the physical basis of ME.
A scandalous situation overall
As regards biomedical research overall, there is a serious mismatch between published studies and the extent of the human problem.
While we know very little about the incidence and prevalence of ME generally, the proportion of patients with severe illness has been variously estimated at 25% (hence, the "25% ME Group for Severe Sufferers"), one third who experience "a severe and debilitating downhill course" (Dr Melvin Ramsay), and 34% as reported by Action for ME's Members Survey of November 2000. This evidence, conjoined with findings from the CMO's report that "a minority... remain permanently, severely disabled and dependent on others", illustrates the scale of the problem that still needs to be addressed.
To put it bluntly, if 30% of ME patients in the UK are severely affected at any one time, this means that between 36,000 and 72,000 people are severely ill. For such numbers to be so under-investigated by scientists, albeit for practical reasons, is surely scandalous
— yet this is the situation. The CMO's Report concludes that "Current provision of services falls well below what is needed for the vast majority of severely and very severely affected patients" (Section 184.108.40.206).
Stabbing in the dark
It's sobering to consider that in 2004 we still understand very little about the origin and outcome of severe illness in ME. Yes, we know that severe illness (and the other medical conditions that accompany it) complicates matters. We know that the prospects for recovery tend to be worse for those most severely affected, whether adults or children, and that specific viral triggers, duration of illness and socioeconomic status have all been associated with the severity of the clinical picture. Most importantly, we know that the cumulative impact of severe illness over many years, where there is no sense of improvement, is profound.
Yet, even these rather unsurprising findings are based on a relatively small number of investigations, and as such cannot be called definitive. The truth is that, after some stabbing in the dark, the complexity, severity and longevity of the illness are still only dimly perceived. The most meaningful information often comes from the dedicated efforts of specialist groups that have collected data on their severely ill members or clients (see the box below).
Sources of community-based information on severely affected ME patients
25% ME Group for Severe Sufferers — Severely affected analysis report, March 2004
• Community care provision either non-existent or inadequate
• Most patients unable to attend GP, yet minority get GP home visit
• Unhelpful psychological strategies, e.g., cognitive behavioural therapy (93% unhelpful) and psychotherapy (90% unhelpful)
• Worsening of condition with graded exercise therapy (tried by 39% of members, and 82% made worse by it)
• More than half waited longer than two years for formal diagnosis
Action for ME Report — Severely Neglected: ME in the UK, March 2001
• 41% reported having been bedbound now or in the past
• More than half reported to have felt suicidal because of their illness (especially those with severe pain and late diagnosis)
• 80% suffered severe pain as a result of their illness
• 15% had more than one close family member who had also had ME
Case History Research on Myalgic Encephalomyelitis (CHROME)
• Database providing ongoing monitoring and progress of adults and children severely affected by ME via regular questionnaires
Soft data and hard experience
Clearly, community-based surveys can be very useful for describing the experiences of people with severe ME, and might be important for hypothesis generation; i.e., they may uncover areas of concern (such as the lack of community care provision), and highlight areas where new research is needed (such as the urgent need for pain relief). In short, they can provide a systematic record of individual suffering, and point to ways to alleviate it.
However, there is a very real problem about the meaning of survey data generally to medical/scientific professionals outside of ME patient circles. Strange as it may seem, surveys come low (grade III or lower) in the hierarchy of research designs, since they are not valuable for determining causation, or the "specific effect" of treatment.
In addition, charities' "in-house" patient surveys have many limitations. First, most of the data has usually not been collected using validated, standardised outcome questionnaires that can be used for comparison with other studies or illnesses. Then there is the problem of poor response rates that range from 66% down to 31% in recent ME group surveys, raising the whole question of the meaning of non-responses, a statistical minefield (fortunately) beyond the scope of this article.
But the greatest flaw in the eyes of suspicious outsiders is the "Christine Keeler" effect — "they would say that, wouldn't they".
Since the survey data emanates from a so-called self-selecting group of people with self-reported symptoms, a question mark hangs over the veracity of the data, especially if — as some psychosocial professionals maintain — claiming to be severely ill can help maintain a sickness role and acquire state benefits.
A good example of the difficulties of getting such information published came in 2002 when the 25% ME Group and MERGE tried to publish a small table of data as a letter in the Journal of the American Medical Association. To say there was a lack of interest is an understatement: in the end, the data was presented in MERGE's report Unhelpful Counsel, and so was seen by — at most — a few hundred people instead of the 200,000+ members of the American Medical Association, the sort of audience the most severely affected patients, and the data, deserved. These problems with survey data are not specific to ME, by the way, but this illness — with its peculiar combination of public scepticism and professional uncertainty or outright distain — is probably more at risk than most.
Preparing to climb the mountain
Given that surveys are things that patient charities are well-positioned to undertake, there are in fact some simple things that groups representing the severely ill can do to facilitate the acquisition of valid information. One is to include with their custom-designed questionnaires at least one recognised validated outcome measure, such as the Medical Outcomes Study SF36, a short, easily-completed measure of quality of life that allows direct comparison with other illnesses and other types of ME patients. Again, groups could be willing to supply data for analysis by independent organisations though, of course, the ideal situation is for a university department or other professional group to be involved from the outset.
However, a most useful advance would be a national epidemiological investigation of the true prevalence and impact of severe ME.
Indeed, as the CMO report made clear, the organisation of primary care services in the UK offers a unique opportunity to undertake prevalence studies on the national scale needed to generate the requisite data.
To end where we began, the same report stated in 2002 that "care of people who are severely affected is an urgent challenge". Scientific investigation of the severely affected — their clinical status, experience of illness and treatment — is also a challenge that should be swiftly met.
Ignored and invisible, maybe — but it doesn’t have to be like that. Energy, vision and funding can transform any situation.
• A Report of the CFS/ME Working Group. Report to the Chief Medical Officer of an Independent Working Group. February 2002.
• 25% ME Group, 4 Douglas Court, Beach Road, Barassie, Troon, Ayrshire, A10 6SQ. http://www.25megroup.org/
• Carruthers BM et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. JCFS 2003; 11(1); 7-116.
• Case History Research on Myalgic Encephalomyelitis (CHROME). 3 Britannia Road, London SW6 2HJ. http://dspace.dial.pipex.com/comcare/chrome/
• Chalder et al. Inpatient treatment of CFS. Behav Cognit Psych 1996; 24: 351-365.
• Cox DL & Findley LJ. Severe and Very Severe Patients with Chronic Fatigue Syndrome: Perceived Outcome Following an In Patient Programme. JCFS 2000; 7(3): 33-47.
• Cox DL. Chronic Fatigue Syndrome: An Evaluation of an Occupational Therapy Inpatient Intervention. British Journal Of Occupational Therapy 2002; 65(10).
• Essame CS et al. Pilot study of a multidisciplinary inpatient rehabilitation of severely incapacitated patients with CFS. JCFS 1998; 4(2): 51-60.
• Gibbons R et al. Features of chronicity in ME/CFS: a case series in the UK. JCFS 1996; 2: 111-12.
• Gibbons R et al. Severe ME/CFS of Juvenile Onset. JCFS 1998; 4(4): 67-80.
• Hill NF et al. Natural history of severe chronic fatigue syndrome. Arch Phys Med Rehabilitation 1999; 80(9): 1090-4.
• Peckerman A et al. Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome. Am J Med Sci 2003; 326(2): 55-60.
• Powell et al. The treatment of wheelchair-bound chronic fatigue syndrome patients: two case studies of a pragmatic rehabilitation approach. Behavioural and Cognitive Psychotherapy 1999; 27: 249-60.
• Rangel L et al. The course of severe CFS in childhood. JRSM 2000; 93: 129-134.
Note: link to 25% ME Group can be found in my sidebar at ME AND OPHELIA.