Many thanks for your swift response to my previous email regarding the MEGA study and for passing our concerns on to those who are preparing the bid for funding…
It is heartening to hear from your email that the inclusion of very severe patients is under discussion by the MEGA team. I notice, however, that you mention ‘financial limitations’ in this context. The reaction of other patients with whom I have shared this issue echoes my own: that severely affected patients should be the priority. People with ME/CFS in general are offered little in the way of treatment but most of the severely affected are abandoned entirely by doctors. They are left to lie in darkened rooms, often unable even to sit up in bed or converse with their loved ones, and without any prospect of medical intervention. I’m sure you know all this. Though I cannot claim to have taken a scientific sample of opinion, the overwhelming impression I get from patients is that if there are financial constraints regarding MEGA then these should apply to the overall number of samples taken rather than be focussed on the severely affected, who are the ones most in need of help. I am reminded of Prof Ron Davis’ observation that data from severely affected patients is the most important ‘because their biology would show the greatest differences compared with healthy controls’. It seems incongruous to be envisaging such an enormous study yet even at this stage, while the grant submission is still being prepared, to be talking about insufficient money for full inclusion in the study of those most in need of help.
A further issue regarding patient selection occurred to me while reading through the ‘questions and answers’ update on the MEGA petition website:
The update says: “The only way to do this is to recruit patients through NHS clinics throughout England.”
As I described in my previous email, taking patients from the clinics alone would produce a sample of patients biased towards the less severely affected. Since that earlier email, I have had chance to listen to Prof Davey Smith’s talk at the CMRC conference and it seems evident that using only the clinics to recruit patients would result in precisely the kind of selection bias he warns against. I’m pleased that plans are now being made to also include the severely affected. However, patients on social media are concerned that we might end up with a sample consisting mainly of mildly affected patients from the clinics along with a small token sample of the severely affected to keep the patient community happy. This will not win patient support. What we need is a fully representative spectrum of patients from mild to severe through moderate. This will require the inclusion of patients from outside the clinics not only to ensure the representation of severe patients but also of those moderately affected, for these would also be underrepresented in a sample which came entirely from the clinics (as I argued in my previous email).
The Q&A update also says with regards to patients from the clinics: “The clinicians will be asked to identify patients they judge from NICE criteria to have CFS/ME” and “Patients will have been examined and a full history taken.”
Speaking to a senior clinician from one of the clinics has confirmed my impression (mentioned in my previous email) that most of the clinics actually consider the NICE criteria to be too broad for use and rely instead on Fukuda and/or their own clinical experience. So a cohort from the clinics will not be a homogenous sample but will have been diagnosed according to the individual expertise of the clinicians involved. As for patients being examined and a full history taken, this seems unlikely to be the norm. Clinicians at triage will usually be nurses or OTs rather than doctors so there is unlikely to have been a full medical examination or a full medical history taken. The emphasis will have been on the symptoms the clinician considers to be typical of ME/CFS. As in some cases these clinicians have little previous experience of the condition and come from a mental health background, this may not necessarily coincide with what experienced doctors – or indeed patients – consider to be ME.
I think the point I am trying to make here is this: The impression is given that one of the main motivations for using the clinics is the belief that a lot of the work of data collection with regard to these patients has already been done. In actual fact, this is unlikely – and certainly not to the uniform standard that reliable research would require. In contrast, the approx. 500 samples in the National Biobank have been rigorously catalogued. Hopefully they will be used as part of the study.
I cannot speak for the whole patient community, of course, but I like to think that the majority of patients would very much support the study if the various issues I’ve described in my two emails (and possibly one two more which may not have occurred to me!) are addressed. If we can reach that stage, I think people with ME would be happy to do whatever they can to help, especially if we can be persuaded there is a genuine desire for a truly representative sample of patients. I mentioned previously that Prof Newton and (especially perhaps) Victoria Strassheim who assisted her in her severely affected project, would be ideal people to ask about reaching patients through social media and the national support groups. Further to which, I feel that local groups like ours could be a source of additional patients – perhaps we could even organise local ‘clinics’ in hired rooms or homes etc to take samples if this would be appropriate. If we can establish trust and work together, we can really make this project into the success we all want to see…
But one last thing… I have tried to stick to issues rather than personalities yet I feel I have to make a final point which unavoidably involves both.
As you well know, precision is vital for any study. But there are one or two people in the MEGA team, and you can probably guess who I mean, who seem to have some very strange ideas about acceptable science. I understand you know all about the damaging misinformation which has been produced by the now largely discredited PACE trial but I should also like to draw your attention to a study on ‘Chronic Fatigue Syndrome at Age 16 Years’.
As the name implies, this study was designed to assess the prevalence of the condition in children at age 16. The authors declared: ‘it is important that the uncertainties regarding the population prevalence of pediatric CFS are resolved.’
However, the children in this study were selected on the basis of no established criteria, but rather:
- a parental questionnaire asking if the child had been “feeling tired or felt she/he had no energy” and whether this had affected their education and activities, and
- the child’s score of 19 or over on the Chalder Fatigue Questionnaire.
It is worth contrasting this makeshift means of ‘diagnosis’ with Fukuda, which requires four out of eight additional named symptoms in addition to fatigue, and even the NICE criteria (which, as mentioned previously, most clinicians seem to discard as being too broad to actually use) which requires one additional named symptom in addition to post-exertional malaise.
Furthermore, there was no attempt in the ‘age 16’ study to exclude other conditions which might have produced fatigue in these children (with the exception of depression which was again assessed on the strength of only a simple questionnaire enquiry about the children’s feelings). There was no doctor or medical testing involved and no attempt to assess the nature of the fatigue. All that appears to have been identified, therefore, though by no means precisely, were the number of children with ‘generic fatigue’.
In spite of this, Prof Crawley (who was lead author of the study) described these children in the media as having ‘CFS also known as ME’, effectively equating ME with generic fatigue. Yet these are two very different things.
And this was billed as a study helping to ‘resolve uncertainties about prevalence’!
I mention this to help you understand at least some of the reason why patients are so unhappy about Prof Crawley’s involvement with patient selection for MEGA. She has received millions in research funding in recent years yet she produces research like ‘age 16’ which, far from ‘resolving uncertainties’, is so imprecise that it only leads to further misinformation. Patients want quality biomedical research (yes please!) but we do not want another study as poor as PACE which might take us another five years to expose and would soak up all available funding for years to come.
I do not want to make this about personalities but I am anxious for you and your colleagues to be aware of the rational basis of patient concerns, especially with regard to patient selection, for the idea of simply taking all the patients from the clinics seems to us to be little more accurate in terms of patient sample than the makeshift criteria used for ‘age 16’ – and it is hard to avoid the suspicion that both ideas have come from the same source.
I personally am not asking for any personnel to be removed from the MEGA team (as long as there is adequate oversight from patients) but I can fully understand why other patients may be doing so.
P.S. You can read more about the ‘Age 16’ study in this previous post.