This email has been sent to Professor Holgate of MEGA. Many thanks to all those who signed. (Whoops! missed a few… Total signatures now updated to 221)
((Please note that we are not the organisers of the OMEGA petition.))
Dear Professor Holgate – We comprise a number of M.E. patients and carers, 218 in all. Please see our signatures at the end of this email..
We are writing because we notice your suggestion in your letter to Professor Jonathan Edwards that OMEGA (the petition opposing the MEGA study) has attracted so many signatures due to the support of Invest In ME. We are writing to assure you that we patients and carers are able to look at the evidence and make up our own minds on such issues.
Here are some of the grave concerns that we have about the MEGA study as it has been proposed. It seems likely that you have heard many of them before but in view of your professed perplexity about the OMEGA petition, we want to make sure you are aware of the issues. For the same reason, we are copying this to the other members of the MEGA team and to those you copied in to your letter to Professor Edwards. We are also sending a copy to Professor Edwards himself, and the email will be posted online at the Spoonseeker blog.
Our concerns about MEGA include the following:
Patients from the NHS CFS/ME clinics (apparently the intended source for MEGA) will not yield a representative sample of people with M.E. The reasons for this include:
- Most severely affected patients cannot access the clinics and so will not be included in the study.
- There will be an inevitable selection bias towards the mildly affected because
- the clinics will tend to select such patients as those most likely to respond to the behavioural therapies on offer, and
- the more severely affected patients will be more likely to reject such therapies – and hence the clinics – as inappropriate.
- Other more severely affected patients will no longer be on the clinic’s system
- either because they have not responded well to the therapies, dropped out, and not been followed up (as feedback suggests is often the case) or
- they are among the long term sick who are no longer on the system because treatment is time-restricted
There has been a suggestion, following representations from patients, that some severely affected patients will be included in the study, yet couched in language which suggests that this will be a token gesture only. Most patients believe that the severely affected should in fact be the priority, not least because they are likely to yield the most important data.
In contrast, a cohort with a mildly affected bias (as is likely to emerge from the clinics) is more likely to include patients who really have other forms of fatigue, not least because some of those responsible for diagnosis in the clinics fail to recognise the difference. (More of this in a moment…) These mildly affected patients will be much less likely to have the cardinal symptom of post-exertional malaise, the importance of which was stressed by Professor Chris Ponting in the discussion which followed his recent blog on the MEGA site.
As Professor Jonathan Edwards put it in his email to you: “My experience with specialist colleagues who diagnose CFS/ME is that diagnosis is often heavily coloured by (varying) irrational personal views about the nature of the illness. Moreover, clinics are unlikely to reflect the true demographics without systematic bias that might involve both genetics and comorbidities”.
To summarise, the NHS clinics will not provide a representative, consistently diagnosed and documented sample of patients. We strongly believe that another source would need to be found. An expansion of the existing UK ME/CFS Biobank would seem to be the most obvious choice.
There is, however, another vital concern. As Professor Edwards says, “various comments suggest that (Esther Crawley) is heavily involved in cohort selection”. Unfortunately we have no confidence in any study involving Professor Crawley and certainly not one in which she is involved in this all-important role. It should go without saying that a study of people with M.E. should involve a cohort of people who have M.E., not some other condition. In spite of having received considerable funding for numerous prestigious studies, Professor Crawley seems unable to distinguish between M.E. and generic fatigue.
This was made abundantly clear by the recent extraordinary spate of publicity about Professor Crawley’s upcoming FITNET trial, a study presented in the media as an overwhelming success even though it was still only recruiting patients. In numerous interviews, Professor Crawley repeatedly cited a prevalence figure of 1 in 50 for CFS/ME in children. This figure came from her ‘CFS at Age 16 Study’ which was based on questionnaires filled in by children and their parents, with no medical examination or any attempt to exclude other fatigue conditions. Neither was there any requirement for the cardinal symptom of post-exertional malaise. Prof Crawley effectively selected children with generic fatigue yet called it CFS/ME and presented the (grossly inflated) results as definitive figures, repeated time and again in the media.
As for her FITNET trial itself, Professor Crawley’s protocol says she is using the NICE diagnostic guidelines. These are intended for clinical rather than research purposes and many of the clinics don’t use them because they are too broad, picking up patients who have other fatigue conditions. On closer inspection, however, the FITNET criteria are actually a subtly altered version of NICE which is even broader, requiring only ongoing fatigue as the core symptom rather than the post-exertional malaise stated by NICE. (See page 11 of the fitnet-protocol) So once again Professor Crawley is recruiting a group of patients with generic fatigue yet calling it CFS/ME.
It is clear that M.E. is an inherently complex issue to study, yet progress has been made so much harder over the years by the diverse series of criteria used to describe it, often seemingly utilised at random by researchers. Yet here is Professor Crawley further confusing the picture by selecting new definitions willy nilly for no obvious reason.
Not only does Professor Crawley fail to distinguish between M.E. and generic fatigue, she continues to defend the now discredited PACE trial and similar behavioural studies. She continually refers to the Dutch FITNET trial having a 63% success rate even though its long term follow up showed no difference between the FITNET and control arms of the study; three of its four post hoc definitions of recovery (as noted by Tom Kindlon) were virtually the same as the entry criteria; and even PACE authors White and Chalder criticised the ‘liberal criteria’ used.
Even more astounding is her continued defence of the PACE trial itself, which she recently described (on BBC Radio Bristol) as ‘a great, great trial’, claiming ‘they did it as well as anybody could have done’ and dismissing the recent reanalysis of data (released by order of a hotly disputed Freedom of Information tribunal) as of no significance.
What the reanalysis actually showed was that according to the recovery definition in the trial’s original protocol, there was no statistically significant benefit from the GET & CBT therapies studied. In contrast, the amended definition (as published in the study) had shown benefits approx. four times higher. The authors changed the definition after the trial was underway, so producing more impressive results.
This was a classic instance of ‘moving the goalposts’, yet Professor Crawley’s judgement seems to have been that one size of goal is as good as another.
This was only one of an extraordinary number of irregularities in PACE, including:
- Thresholds were set such that participants could be disabled enough to enter the trial, get worse, yet still be classed as ‘recovered’ at the end
- The trial relied entirely on subjective outcomes. The objective outcomes described in the protocol showed no significant improvement and were dismissed as ‘irrelevant’ even though they had been selected by the authors.
- A newsletter released to some participants mid-trial contained glowing testimonials of the GET and CBT therapies tested
- The authors failed to disclose conflicts of interest, including links to disability insurance companies, to trial participants.
These and other irregularities were brought to light by individual patients, some labouring from their sick beds, and are fully described in journalist David Tuller’s detailed critique of the trial.
On top of all this, the Oxford diagnostic criteria used in the trial have since been ‘retired’ by the US medical authorities as it was acknowledged that they were too broad and included patients with other fatigue conditions. The Agency for Healthcare Research and Quality (AHRQ) has accordingly withdrawn its recommendation of GET and CBT due to insufficient evidence.
In this country however, the NICE guidance recommending GET and CBT remains unchanged and Professor Crawley, the PACE authors, and their close associates insist on pretending there is nothing wrong with PACE and nothing has changed. Perhaps most alarming is Professor Crawley’s intention to proceed with the Magenta Trial, effectively a PACE trial for children, in spite of the debunking of PACE and the evidence from patients of severe and sometimes permanent deterioration as a result of GET.
You say you find OMEGA perplexing. Well we find the state of denial about the debunking of PACE and Professor Crawley’s insistence that there is still ‘good evidence’ for CBT and GET equally – if not more – perplexing. At what stage, we wonder, do things start to change? When do the facts become more important than researchers’ aspirations?
I hope we have helped to explain why we are so concerned about MEGA: in particular patient selection and Prof Crawley’s involvement in that.
New developments such as genomics and supercomputing are opening up exciting new opportunities for the study of M.E. in all its complexity. We patients and carers dearly wish to see such studies proceed and are immensely grateful for the interest of the many eminent researchers who have shown an interest in studying our condition. We are told that our complaining will ‘scare them away’ and that is the last thing we wish to do. But surely it is vital that suitable groundwork is established upon which to build this research and accurate patient selection is clearly a crucial component of this. There already seem to be moves in hand to combine MEGA with similar studies worldwide, so providing an even larger selection of data. That makes it even more important that we get things right at this early stage lest we end up with misleading data not only in our own study but in further studies worldwide. It should be expected that new researchers to our field and parents & carers alike would be able to trust the ME ‘experts’ to deal with such fundamentals but sadly this is not the case. For this reason, we cannot remain silent. We feel that for MEGA to go ahead on the basis currently envisaged would be a waste of funding, a waste of the time and abilities of the researchers who have kindly offered their services, and a source of further confusion rather than enlightenment in the struggle to understand and treat this devastating condition.
(PS: Since we wrote the above, David Tuller has produced an invaluable article on the FITNET Trial – well worth a read.)
With Kind Regards,
P J Barnes
Catherine Hale – lead author of ‘Close to Collapse’ Action for ME social welfare report.
Carol L Binks
Dr Simin Ghatineh
Claire Louise Barber
Gary Rogers Brennan
Ragnhild von Harling Lien
Barbara Robinson (Suffolk and Norfolk ME and CFS Service Design Working Group)
Amanda G Williams
Greg G Williams
Denise Longman MSc
Claire ‘Cooper’ Brown
Dr Andy Lloyd
Mary O’Dwyer Barker
Andy McLellan PhD
Kristin Stempf de Vargas
LS – severely affected
Dalvir Singh Jakku
Nasim Marie Jafry
Jenny Horner (Tips for ME)
Nicola cartlich walker
Roger J Griffin
Jennifer Bloomer PhD
Miss Julie Jobson
Lydia Neilson – National ME/FM Action Network