The OMEGA Petition – Email to Professor Holgate

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,

Simon Ounsley

Chris Ounsley

Lyn Gillam

John Peters

Sean Wilson

P J Barnes

Tina Rodwell

Catherine Hale – lead author of ‘Close to Collapse’ Action for ME social welfare report.

Carol L Binks

Henry Anderson

Andy Hugh

Dr Simin Ghatineh

Mary Cardwell

Anthony Bradstock

Fiona Symington

Andy Devereux-Cooke

Anita Lim

Annabel Schleutker

James Foulger

Geoff Allen

Steve Downing

Rita Gacon

Zoe Williams

Claire Louise Barber

Paul Watton

Katie Wicks

Amy Bakewell

Jan O’Malley

Trish Davis

Naomi Whittingham

Michelle Yuill

Nicky Baker

Imogen Mitchell

Keith Bradbury

Manuel Goldstein

Mary Lance

Anita Dawson

Tim Hood

Teresa Greenwood

Sarah Lawry

Gabi Lewis

Mags Net

Gary Rogers Brennan

Joan Mcparland

Katie Ash

Jayne Wilson

Darron Stone

Caroline Bader

Susan Bakewell

Sally Burch

Chris Perry

Di Kirk

Ragnhild von Harling Lien

Susan Atkins

Janet Graham

Dr Speedy

Arnold Byrne

Jane Wysner

Anne Liconti

Jackie Rounsley

Kate Behrend

Elizabeth Corran

Barbara Robinson (Suffolk and Norfolk ME   and CFS Service Design Working Group)

Jane McFadden

Janet Smart

Cuspschen

Lynn Ball

Jan Laverick

Margaret Laverick

Jackie Scoones

Jane Giak

Aine Hefferon

David Hefferon

Julia Browell

Sukhita

Sheila Dindar

John Murphy

Andrew Taylor

Jackie Adam

Kathy Berry

Graham McPhee

Phil Murray

Norma Ledua

Jacqueline Wilson

Mike Harley

Sally Lambert

Aran

Steve Hawkins

Amanda G Williams

Greg G Williams

Denise Longman MSc

Frances Johnston

P Jones

Andrew Burgess

M Ghatineh

Margaret Smith

Susanna Degaardt

Claire ‘Cooper’ Brown

Jenny Wilson

Hil Patten

Jan Masleid

Janine Bailey

Rachel Thomas

Christine Fenton

Talulah Miers

Clare Stiles

Jane Hurst

Ciara Kennedy

Simone Eyssens

Susannah A

Leonie Potgieter

Claudia Heath

Katie Lloyd

Margaret Lloyd

Melvin Lloyd

Dr Andy Lloyd

Natasha Jackson

Karen Castro

Jen

Kitty Lobert

Robin Australia

Mary O’Dwyer Barker

Jessica Kuijper

Flora Cumming

Kerrie Ryan

Elaine Stammers

Paul Gray

Rachel Miles

Penny Hassack

Eilidh Hewitt

C White

Andy McLellan PhD

Shannan

Kristin Stempf de Vargas

Annette Barclay

Karen Dodsworth

Hilde Larsen

Helen Humphries

Louise Wilkie

Carolyn Westwood

Robert Saunders

Christopher Lance

Amble Skuse

LS – severely affected

Vineta Daniele

Dalvir Singh Jakku

Clare Inigo-Jones

Nasim Marie Jafry

A Biggs

Kerryn Groves

Steve Morgan

Genevieve Gillard

Clare Bray

Claire Brown

Noreen Murphy

Peter James

Caged Bird

Lizzie Corran

Ciara Kennedy

Michael Evison

Wendie Evison

Dave Brown

Iszak Brown

Lee Krikham

Sean Kirby

Anna-Karin Ulpe

hbotandme

Caroline Newbury

Germaine Hypher

Samantha Jenkin

Jenny Horner (Tips for ME)

Rosa Davies

Sarah Hill

Emma Goodson

Anthony Murphy

Gareth Flynn

Danielle Lee

Elmorchard2

Nigel Brough

Kathryn Wilusz

Amy Scroggie

Michael Brennan

Tom Dinnen

Carole Carrick

Paul Gadsden

Nicola cartlich walker

Tracy Holland

Alison Head

Amber Blair

Richard Gillam

Shonagh Hill

Dominique Doran

Roger J Griffin

Leela Play

Tori Dinnen

Jennifer Bloomer PhD

Alison Orr

Nick Farrar

Heather Webster

Barbara Kell

Rob Wijbenga

Miss Julie Jobson

John Gabor

K Wimhurst

Sonya Green

Sara-Joy Brown

Vikki Louise

Valerie Barnes

Nicola

Liz Willow

Joan Byrne

Pat Williams

Sarah Bellany

Lydia Neilson – National ME/FM Action Network

Tanya Marlow

Jessica Sanders

Rosemary Platts

Thomas Roucoux

Wendy Boutilier

Marina Wray

Sue Roberts