A Tale of Two Collaboratives

Research into ME should be clear and obvious. This is not a new disease and the suffering and devastating effects of the disease on patients and their families has been chronicled for a generation.

Yet comparatively little biomedical research has been funded, no joined-up thinking has been applied to the research and the research landscape has remained bare - lacking agreed and correct diagnostic criteria, lacking adequate funding and lacking correct and rational information.

There must be a better way forward.

Despite this comparative paucity of relevant and adequate research elements several initiatives have been started in recent times - some based on accumulated years of experience from those researchers and clinicians who have doggedly remained with this disease and stayed with the patients; some created by those who have entered the field and brought with them new ideas and new technologies to benefit research and patient treatment; and some from new research spawned from chance findings.

This gives hope for new discoveries for this disease.

Even though, in the UK, the widely criticised and flawed PACE Trial [1] has wasted several years and scarce resource funding there is perhaps a new era of ME research finally beginning with the promise of a new way forward.

This is reflected in the theme of the 8th Invest in ME International ME Conference 2013 in London on 31st May - Mainstreaming ME Research - an acceptance that, despite the past, research into ME is now joining the mainstream research area deserving of more funding and of the interest of top biomedical research institutions. The IIMEC8 conference will highlight the major biomedical research initiatives into ME now taking place.

And it has been largely also patients who are forcing change and making things happen - making a difference.

The Let's Do It For ME campaign has forced biomedical research into ME - by amazingly positive efforts by people who are not interested in complaining all the time without offering anything - but instead put their thoughts and energy into imaginative ways of crowd funding biomedical research - often pushing themselves beyond their limits. IiME supporters have been showing the real side of ME patients - people wanting to get better and willing to be proactive in achieving this.

The promise of treatments developed from the exciting research at Haukeland University Hospital in Bergen has generated campaigns by three European ME Alliance members - Norway’s ME Association, Sweden's RME and Switzerland's Verein ME/CFS.

And the MEandYOU campaign in Norway has an ambitious target to raise 7 million Norwegian Kroner in 90 days.

Where establishment organisations have refused to perform proper research into ME in the past this is now challenged by increasingly more knowledgeable and determined patient population, thanks to conferences and organisations highlighting ME research and to the immediacy and effects of social media. It was patients who thoroughly debunked the hype of the PACE trial despite coordinated efforts by establishment forces to encourage acceptance of it as valid research.

Last year in 2012 the Invest in ME Biomedical Research into ME Colloquium 2 (a two-day Clinical Autoimmunity Working Group (CAWG) meeting organised by Invest in ME and the Alison Hunter Memorial Foundation of Australia, in London) brought old and new researchers to the same table for two days of discussions.

Initiatives came from this meeting and surely influenced the latest calls for research in the latest MRC highlight notice [2] from last year -

“There is now preliminary evidence supporting the view that inflammatory mechanisms in the brain and spinal cord may underlie the pathophysiology of some severe disease CFS/ME phenotypes. Biobanks are now becoming available and create a unique opportunity for interrogation. Immune dysregulation: There is evidence for a disturbance in innate and adaptive immunity in CFS/ME including alterations in cytokine profile, absolute and functional alterations in T cells and NK cells and occurrence of autoantibodies and allergic reactions that may explain some of the manifestations such as fatigue and flu-like symptoms. A number of infectious and environmental exposures have been associated as triggering these changes.

- UK Medical Research Council

This developing recognition of the real disease in ME needs to be backed up with an appropriate response.

The overwhelming need is for research - and essentially biomedical research into ME.

But how can we make more and quicker progress?

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In the UK two collaborative meetings for ME research are planned.

Soon the Science Media Centre and Professor Stephen Holgate and Dr Esther Crawley will host an afternoon event to publicise a "research collaborative" for CFS - UK CFS/ME Collaborative. We shall refer to this as the SMC collaborative. This event on 22nd April will be organised by the Science Media Centre in London.

One month later, in London, Invest in ME and the Alison Hunter Memorial Foundation will convene a Biomedical Research into ME Colloquium 3 (BRMEC3) - click here. Invited will be biomedical researchers from seven countries.

The SMC event apparently follows on from the MRC CFS/ME panel which was disbanded after three years, having held just a handful of meetings.

Invest in ME has been invited to attend - due to the research which the charity has proposed and funded - and, along with other invitees, the charity received an email from Dr Crawley and Professor Holgate containing information about the SMC event.

The chair of the SMC collaborative will be Professor Holgate - the deputy chair will be Dr Esther Crawley. Charities such as AfME, MEA, AYME and MER UK will have been involved in the planning with Professor Holgate and Dr Crawley.

The invitation to the SMC event sent by Dr Crawley to invitees states -

"In addition to joining forces for raising the profile of research and prioritising key areas for research, a UK CFS/ME Research Collaborative could look to jointly fund projects, capacity building (especially through involvement of those not currently engaged in the field and looking to support young scientists), encouraging targeted fund raising as well as galvanising some clear directions of travel in the field."

These seem like creditable objectives.

Yet on closer examination one finds that included in this SMC collaborative there will also be many of those who believe ME is a somatoform disorder. Included will be those behind the PACE Trial, the SMILE study etc.

So the question might be posed exactly what are the "..clear directions of travel in the field" for this SMC collaborative to which Dr Crawley refers?

Professor Holgate's reasoning behind this SMC collaborative is that -

"a similar collaborative, as well as an MRC Highlight Notice, has helped to increasing MRC, Industry and Charity investment into respiratory disease 4-fold over the last 5 years when it was recognised that more needed to be done in this field".

and

"Two key principles for the success of this (respiratory research) has been a willingness to join forces, support of ALL types of research and ensuring high quality as judged by robust peer review."

We have stated before that it will be interesting to know how this can be achieved.

The problem with transposing a model of research for respiratory disease onto the ME landscape is, of course, that respiratory disease is a universally accepted disease and is not questioned by an influential and controlling ideology that continues to describe and treat ME as a behavioural illness and refuses to accept that it is of organic origin.

For many years two opposing views of ME have been maintained - whether for genuine reasons or for political and financial expediency. This has pitted patients against establishment organisations who deny this disease as real or of organic origin.

To discard the politics and machinations that have gone on for a generation with regard to this disease is certainly something we can understand might be convenient - we have to move on from the past.

Yet the past cannot be completely ignored if one is truly intent on building a force for change and progress which includes people who still hold ME to be a behavioural illness. A great deal of re-invention of their positions by some leading figures would need to be made before one can really believe such a strategy would work.

The MRC CFS/ME panel achieved little when compared to the amount of time it was meant to be active. More importantly three more valuable years of opportunity were lost.

The problems and issues which the MRC panel really should have resolved have not been addressed - instead a void remains where these elements for a sensible and scientific strategy for research should have been agreed.

An example is the lack of agreement (or even discussion ?) regarding a standard diagnostic criteria set to define ME and differentiate from Chronic Fatigue.

Only the Canadian Consensus Criteria and International Criteria accurately describe the symptoms of ME and therefore should be the only ones used. Psychiatrists who purport to study ME use the Oxford Criteria which simply describes fatigue. An illness cannot be studied unless it is accurately defined.

After three years of existence of the MRC CFS/ME panel only a comparatively small amount of funding was awarded for research which either did not cover ME or was not related to establishment of causality. The current highlight notice from the MRC [2] is more promising, if the right type of researchers apply and get funding.

Another questionable area in this new MRC/SMC collaborative will be the requirement for anyone participating to agree to support and fund "ALL research into CFS/ME including fatigue".

The only way any organisation can be included in this SMC collaborative is to sign up to a charter created by Professor Holgate, Dr Crawley and presumably the four charities who have already been instrumental in creation of this charter and can then drive it. The letter from Dr Crawley includes the comment that the charter -

"will lay out the terms for membership that will strongly emphasise the need for ALL types of high quality research (into CFS) and a joined-up approach to deliver this", including fatigue.

The full contents of this charter - though known to some - will not be revealed until that April 22nd meeting.

We have written in the past that we feel it is impossible to marry the views of those who believe in the deconditioning/behavioural and wrong illness belief model of ME with those from the biomedical side. The failed PACE Trial has demonstrably proven that the behavioural view of ME cannot deliver and should not continue to command more funding.

This naturally leads to many questions about this MRC/SMC collaborative and its proposed method of working. The composition of the MRC/SMC collaborative includes polarised views of ME so is it really possible, or wise, to try to marry these widely differing views together? Why is a charter actually required that all must sign up to, as indicated by Dr Crawley?

Will the mandatory charter reject or remove those who disagree with the psychosocial side of the MRC/SMC collaborative? Who will peer-review applications for funding from biomedical researchers? What cohorts of patients will participate in research and what diagnostic criteria will be used? Will funding generated by this MRC/SMC collaborative be used to create a strategy of biomedical research? Why is fatigue necessary to be mentioned in the handouts?

These are questions which will hopefully be answered.

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Maybe there is another way - perhaps a better way forward for ME research.

We believe there is a clear case to be made for segregating the biomedical from the psychosocial here and now. This could then force a separation of fatigue research from ME research and possibly also settle on the correct taxonomy for this disease which currently remains, to us, as myalgic encephalomyelitis.

Why not agree on a strategy of biomedical research into ME with a biomedical research collaborative into ME being formed consisting of biomedical researchers, using resources and facilities across continents - hooked up to share research and data and crowd fund new research?

Such was the meaning behind the Biomedical Research into ME Colloquium 3 organised by Invest in ME and the Alison Hunter Memorial Foundation to be held in London on 30th May. This meeting follows on from the collaborative two-day Clinical Autoimmunity Working Group meeting organised by the two charities and held last year.

It aims to interest other biomedical researchers to the field of biomedical research into ME, assist those who are undertaking research or planning research into ME, and look for future collaborative projects and funding which could be generated by new ideas.

We believe future research into ME must be based on collaboration. But it would seem quite meaningless to base the strategy on those failed policies and directions of the past - which have served patients so poorly and caused such suffering [6].

If we are seriously to have a way forward for proper research into ME then we need not just funding, but correctly defined cohorts, standardisation on diagnostic criteria and a collaborative of researchers who will not blur science with politics.

Such is the meaning behind the OMI MERIT initiative [3] which is actively proposing and initiating just these ideas with an impressive array of research and technology being outlined.

The OMI MERIT initiative is the closest we have seen to the ideal of what a strategic approach to research and treatment should be.

The OMI MERIT initiative proposes a new way of collaborating, of sharing data, of using new technology to assist in diagnosis, treatment, research. It proposes to crowd fund research into ME and crowd source ideas and efforts and experiences. These are the same goals of IiME.

It is why Dr Andreas Kogelnik will be returning to the Invest in ME conference in May to spearhead the theme of the conference - Mainstreaming ME Research. It is why Linda Tannenbaum from OMI will be speaking at the IiME pre-conference dinner preceding the conference.

In fact there is the makings of a truly great collaborative - with OMI MERIT which has signatories from most biomedical projects currently taking place. Not forgetting the important work of the Enterovirus Research Foundation which concentrates on the role of enteroviruses in ME. To this we can add promising initiatives such as the proposed Norwich research facility in UK, and those in Norway and Sweden.

And this is the meaning behind the IiME/AHMF BRMEC Biomedical Research into ME Colloquium 3 in London in May.

International collaboration is a necessity for research into ME.

Research into ME needs a strategic approach - but it may be destined to fail completely by attempting to establish the way forward on foundations which include so much of what has been wrong in the past.

Surely the way forward ought to be -

• to establish homogeneous research cohorts

• to adopt and endorse the latest ICC or CCC criteria for ME - for research and for diagnosis

• to separate research into fatigue and chronic fatigue from ME

• to establish transparent peer reviewing by professionals with the relevant experience and background

This is the "clear direction of travel" which this charity believes we could take - not just to discard the incorrect and deleterious approach of the past but to discard that inadequate way of thinking which has consigned a generation of ME patients and their families to a neglected and dreadful existence.

If a collaborative is to be created of researchers and support organisations then perhaps the only charter which would be necessary is to agree to the above principles.

A clear break from the past needs to be made and a new way forward taken up - with international collaboration and transparent and appropriate research into ME. This would be a clear differentiation between objective and subjective research.

On 22 April the MRC and Science Media Centre will hold an event to publicise the launch of one collaborative which proposes to bring together ALL research, 'including fatigue', into one hat - a collaborative tent which only those organisations who sign up to a pre-arranged charter will be able to join.

On 30th May two small charities with a BIG Cause will convene a Colloquium which will be held in London bringing together all of the major biomedical research into ME initiatives in the world. The meeting is open to researchers who will contribute to biomedical research into ME and will be funded by the charities themselves.

We wish both ventures well - Invest in ME supports all good research initiatives which are truly meant to advance the cause of ME patients and their families and lead to correct information and treatment for the disease.

Indeed, we are certain that the IiME/AHMF Biomedical Research into ME Colloquium in London in May will create ideas and support research which will benefit those biomedical research initiatives that may, possibly, eventually emanate from the MRC/SMC collaborative and from those organisations included who are genuinely interested in biomedical research into ME.

The motives of IiME and AHMF are to make rapid progress in translational biomedical research into ME which will benefit ME patients and their families and provide hope that something is being done for them, that there truly is a promise of better times ahead and not just further delaying tactics to waste more years.

Maybe there will be credible and positive change ahead.

Charles Dickens' words would have described well the experiences of ME patients and their families of the past, and their aspirations for the future -