The Young ME Sufferers Trust www.tymestrust.org March 2003 ====== Detailed response to the Medical Research Council’s CFS/ME Draft Research Strategy ====== Introduction The Young ME Sufferer’s Trust is the longest running UK national support organisation for children and young people with ME, their families, and the professionals involved in their care and education. As such, we worked on the CMO’s Independent Working Group, specialising in the children’s section (Chapter 5). Although the MRC’s Draft Research Strategy represents a serious attempt to square a very difficult circle, we have reservations about statements in the Strategy Document, which we list below along with other statements that we particularly welcome. We shall be pleased to be consulted as part of the MRC’s declared intention of involving ME charities in research projects. We have a number of Partner Groups around the UK and a large database, which may be helpful in planning research into children. Response detail 1We welcome the MRC’s statement that it ‘fully endorses the conclusions of the Report of the CMO’s Independent Working Group, namely that CFS/ME is a real, serious and debilitating condition, and that research into all aspects of CFS/ME is needed’. However, we would appreciate clarification as to how the Research Group interprets the word ‘real’, given the statements at para 95 that there is ‘good evidence that muscle strength, endurance and recovery are normal and in para 102 that the general opinion […] is that there is no physiological basis to the weakness and/or fatigue’. We find these conflicting statements puzzling, and likewise the lack of reference to research such as that showing abnormal mitochondrial function. 2We appreciate that the MRC wishes to ‘reduce suffering’ amongst patients. However, the recommendation for more extensive research into interventions, rather than into causation and identifying subgroups, is, we feel, putting the cart before the horse. Without more understanding of subgroups and of causation, there may be an active risk of increasing the suffering of those who consistently report exacerbation of their illness due to CBT and GET. 3The recommendation for a classification of severity in para 141 without reference to the stages through which the illness typically passes is of major concern. Severity assessment can only represent a snapshot in time. Patients in the early stages can be extremely fragile. In our experience, the condition can deteriorate alarmingly if incorrectly treated at this stage. A ‘mild’ case can soon become ‘severe’, thus nullifying the original classification. If a child has ‘mild case of CFS’ written on their medical records, this could result in less support being offered and in disbelief when the child becomes worse. Disbelief in the child is already widespread. 4We welcome the recommendation in para 157 that ‘any research into rehabilitation must establish why some people experience a deterioration whilst others find the process beneficial’. Para 160 further states: ‘It will be important to understand why some people with CFS/ME experience a deterioration when participating in an exercise approach to treatment’. We do feel, however, that this type of research into the severely affected could carry a high risk of exacerbation. 5We are pleased to see in paras 9 & 142 the recommendation that outcomes reported in studies of interventions should not just be based on subjective measures. The recommendation to find objective measures to identify a ‘clinically important improvement’ is of major import, especially as ‘the difficulties in defining objective outcome measures means that such studies may have positive results even with ineffective interventions’ - para 145. However, the corollary of this - the development of objective measures to identify a clinically important deterioration - is also needed. We welcome the recommendation that patients’ reasons for dropping out from studies should be included in assessments of the effectiveness - or otherwise - of interventions. 6We welcome the recommendation for epidemiological studies to assess prevalence and incidence, despite the complications and expense of such studies. However, given the MRC’s suggestion in para 70 for this to be carried out at Primary Care level, would it not be possible for GPs initially to take part in a Census, whereby they report how many patients with diagnosed CFS/ME they have on their books on a given date? Whilst this takes no account of case definition, as a statistical exercise it would give an initial indication of the scale of the problem and enable more effective NHS services planning. 7We are pleased that the MRC states in para 38 that ‘the umbrella term CFS/ME may no longer be appropriate’ once the condition is better understood. However, without studies of causation we fail to see how this can be achieved. Studies of causation are a priority amongst those with the illness. 8We note the statement in para 86 that ‘there is reasonably strong evidence that retroviruses and enteroviruses are not causally related to CFS/ME’. Given the host of similarities between polio myelitis and ME, it concerns us that the extensive research of decades is dismissed in one sentence with no recommendation for further exploration. Widespread immunising diseases such as polio myelitis and related conditions do produce a population in whom most people carry antibodies at various levels. The fact that not all have succumbed to serious effects does not negate the causation, any more than, for example, it does with the Epstein Barr virus, to which almost everyone carries antibodies. We note that polio myelitis was notoriously difficult to diagnose and, just as in CFS/ME, ‘it is entirely possible that an original, precipitating factor may no longer be detectable in a person with CFS/ME, or was present at a subclinical level’ - para 48. 9In para 43 reference is made to research into children, which is discouraged. We accept the difficulties in such studies, but feel that research into cognitive difficulties may be a less invasive form of research into children. Since the MRC states in para 131 that ‘knowledge of the relevant cognitive factors could contribute to the diagnosis of CFS/ME’, this could be a promising avenue in children. 10We welcome the recommendation in para 46 that ‘selection bias should be considered at the earliest stages of any study’. 11The fatigue definitions of the illness now known as CFS/ME did not arrive until the 1980s. There is a substantial body of knowledge about ME from before that time. We find that the MRC’s statement in para 6 that ‘a strategy is proposed which reflects the current state of knowledge in CFS/ME’ is not entirely correct. It is unfortunate that the Research Advisory Group does not seem to have utilised the earlier work. Its function as stated in para 82 did not include ‘a detailed review of the current level of scientific knowledge’ so it would have been helpful if it had contained members who had that knowledge already. 12We are concerned at para 161: ‘At present, there is no empirical evidence of efficacy for ‘pacing’, which should come from randomised controlled trials.’ The dictionary definition of empirical when related to medical treatment states: ‘based on practical experience rather than scientific proof’. There is a vast body of practical experience amongst those with CFS/ME which we note has been excluded from the MRC Research Strategy document and it therefore appears that this experience has been discounted under the MRC’s definition of empirical. 13Paras 164-166 give an extensive description of CBT and GET, recommending more extensive studies of these therapies. We do not feel that this totally squares with the MRC’s conclusions, which recommend concentrating on ‘new’ approaches to management. However, we understand that several members of the MRC Research Advisory Group have an interest in these therapies and have published papers on them, which surprised us as the MRC had stated its intention of appointing people to the Research Group with no prior CFS/ME experience. In para 208 we note that new approaches to management are relegated to small trials. In conclusion We agree wholeheartedly with the MRC that there is a need for good quality research. However, paras 50 & 211 recommend publication in ‘high quality, peer reviewed journals’. We would draw the MRC’s attention to the fact that the peer review process has been extensively criticised of late, both from within and from without the medical press. It has been alleged that certain journals use reviewers with a particular bias. To overcome this it may indeed be necessary to use ‘additional alternative mechanisms of dissemination, preferably involving an independent peer-review mechanism’ as referred to in para 211. We would endorse this suggestion by the MRC. ====== Copyright (c) 2003 The Young ME Sufferers Trust