Input to UKCRC Research Working Group Meeting 14 October 2022
An Overview of Requirements
The next meeting of the research UK Clinical Research Collaboration (UKCRC) research working group is
scheduled for 14th October 2022 - the second time Invest in ME Research
has been invited to attend one of these meetings.
See Background to this below.
Professor Simon Carding, from the Quadram Institute in Norwich Research Park,
was also eventually invited to this working group and has input
meeting the following list of requirements
that are seen as necessary to build the
capability and capacity for real progress to be made for ME.
Invest in ME Research endorses all of these points.
Indeed, we have made many of these same points continuously over the years as well as facilitating some of them to become reality - and these points have also been discussed by the European ME Research Group (EMERG) in discussions over the last years.
Research Strategy and Building Capability and Capacity
Objective outcome measures need to (must) be deployed in research studies and clinical trials
Historically, too much emphasis has been placed on subjective questionnaires the outcomes of which
are of limited use for comparison across studies.
For our upcoming clinical trial  , we will be using objective measures of activity and cognition to assess outcomes as well as quantitative blood-based biomarkers.
The European ME Research Group (EMERG) worked with the NIH to form a working group for outcome measures following the #BRMEC10 Colloquium held in 2021.
This work is ongoing.
As Professor Carding writes above the RESTORE_ME clinical trial will use objective measures and collaboration has been set up with other departments and disciplines in Norwich Research Park to effect and analyse these measures.
A good basis is therefore becoming available for future research.
Stratification of clinical subtypes and uniform acceptance and adoption of single diagnostic criteria
This is essential for comparing findings across different studies.
Use of standardised criteria is long overdue in research into ME.
Any research into ME that receives public funding ought to have as a pre-requisite that standard and consistent criteria have been used for stratification  .
For the RESTORE_ME clinical trial the research criteria being used are the ICC criteria.
Inclusion of marginalised groups of patients, particularly those that have severe ME/CFS and are house/bed bound
Extreme phenotypes can often provide unique insights into disease aetiology.
The charity has often stated that severely affected patients should not be excluded from research into ME where practical.
Despite limited resources this has been evident from early on in the first research project funded by Invest in ME Research the research team were involving severely affected, sometimes even travelling for a day to reach patients who would not otherwise have been included.
Some comments from the IIMEC8 international conference in 2013 .
Consideration of environmental factors in disease progression
Consideration of whether environmental factors play a role in disease progression needs to be made. To this end patients from different geographical and socioeconomic groups need to be included in studies – as diverse and as broad a group of participants as possible is needed.
More thought needs to be given to control groups (beyond age/gender) and ensuring
that they are appropriate for the type of study being undertaken.
Healthy individuals from the same household as the patient would aid in controlling for local environmental factors in studies looking at immune, diet, microbiome aspects.
Funding to Reflect Multi-organ/system nature of ME
ME/CFS is a multi-organ/system disorder and research studies to date rarely reflect that,
focusing instead on one system in isolation.
Multi-disciplinary groups of researchers are needed therefore, which requires more funding than can be provided by conventional UKRI-response mode grants. Multi-partner/PI centre/programme grants are more effective in delivering impact and establishing/supporting multiple research groups working in collaboration and not competition.
This was one of the reasons for forming the European ME Research Group (EMERG) where experienced research teams can collaborate across disciplines as well as across sites and more funding could be attained due to the increased capacity offered.
Advocate(s) for ME research in UK funding agencies
There is an urgent need for a strong advocate(s) for ME research in UK funding agencies.
The MRC has made a faltering attempt at this but it has failed to achieve the required degree of commitment, advocacy and momentum to make a sustained impact.
In fact the MRC record over the decades has been extremely poor, bordering on the inept. Despite communicating several times to Sir John Savill - CEO of the MRC  .  . - and being assured that this was in hand nothing tangible has been done.
There have been no worthwhile champions for ME in the agencies dispensing public funding in the UK. One can look back as far as 2003 and 2011  . to see words, but no actions.
This is another reason for recommending further development of the Centre of Excellence for ME in Norwich Research Park that the charity has been proposing and facilitating since 2010.
Imagine what could have been achieved if the MRC had invested in our proposal instead of spending years of ineffective sideshows and funding of the wrong type of research?  .
An International View
Any ME/CFS research strategy needs to be outward looking and include international researchers particularly in the rest of Europe and North America – establishing links not only with researchers but funders which have, by comparison to the UK, made more significant contributions to funding ME/CFS research (e.g., USA-NIH, Netherlands)
Invest in ME Research has had this view since our 2nd International ME Conference in 2007. Since 2011 the charity has been organising annual international research Colloquiums bringing international researchers together  and has been working with European partners in the European ME Alliance (EMEA) and initiating the European ME Research Group (EMERG) and Clinicians Group (EMECC), with joint research projects being developed  .
We have been talking to our Dutch colleagues over the past years and seeing them develop their research agenda and this could easily be harmonised as we have links already established  .
We have suggested already to the UKCRC working group that the research agenda created in the Netherlands should be considered  as there is no need for reinvention and a possibility could be created to create synergy between the projects and share funding costs with a European collaborative venture.
We also suggest that the model already established and underway in the Netherlands should be considered.
International Research Community
An international annual ME/CFS research conference would be an effective means of bringing together ME/CFS researchers to promote collaborative research.
The Invest in ME Research charity has been arranging annual international conferences and international research meetings for researchers since 2006, regularly bringing researchers from twenty countries (including USA and Australia) to London.
This is true and only the pandemic and lock downs have paused this and forced us to use online meetings.
Our international ME research Colloquiums and public conferences have brought together researchers and clinicians and allowed patients to interact  .
We return to in-person meetings in 2023.
We have already created a family of international researchers and this group has been growing in number.
Proactively Foster Increased Research Capacity
Doctoral training programmes involving different institutions that share responsibility for individual PhD projects would be a cost-effective means of initiating and promoting collaborative multidisciplinary research programmes.
We have already tried to create such an environment, albeit with limited resources. PhDs funded by the charity have worked with other institutes in Norway and Sweden and with the EMERG research group we have supported the development of cross-site projects. 
With our partners in EMEA we have offered to co-fund joint studentships that will bring institutes in multiple countries together.
The charity has also funded and involved medical students in the research.
From page 5 of our Journal of IiMER 2015 - describing two IiMER funded medical students (Navena and Bharat) -  .
"The charity has for a long while stated the importance of international collaboration and we are pleased that Professor Maureen Hanson enabled Navena to spend over three months at Cornell University in Itacha USA to learn about their gut microbiota research.
Meanwhile Bharat is currently working intensely with Professor Angela Vincent in her laboratory at Oxford University. This is the essence of the IiME approach to research.
Finding the cause, working in collaboration, using opportunities for international collaboration, bringing new expertise into studying ME and facilitating the education of healthcare staff. "
Centre of Excellence for ME
Identifying a small number of centres for ME/CFS research that already have established specialisms in biomedical/fundamental research that can establish and develop collaborations and joint projects with other research groups across the UK that might otherwise lack the required critical mass/expertise to undertake research projects in a hub and spoke type model should be seriously considered.
One such centre in Norwich Research Park has been established  with researchers at the institute performing projects related to ME, working with other disciplines, collaborating with university, clinical trials unit, university hospital and a local ME clinic that has a couple of thousand people with ME - and collaborations with European researchers.
The research team at Quadram is already doing this and has the experience and capability to expand this.
We already see the overlap between disciplines and research teams in Norwich Research Park and this has enhanced the research being performed - in the clinical trial, in development of objective outcome measures, in raising awareness of ME.
So the model is proven - it just needs more investment to augment what Invest in ME Research has been able to fund so far. 
The charity continues to facilitate collaboration with other European hubs.
Without long-term investment and reliable sources of significant levels of funding attracting new
young investigators to ME/CFS research is unlikely to be successful.
Targeted young/new investigator grant schemes for ME/CFS research would be a good place to start.
We suggested to the UKCRC working group that a statement should be issued to the health minister that funding for research should be established and made available up front - already before any plan is established.
If capacity is required to be increased in the research community and if interest and awareness is required to be gained then funding is a pre-requisite.
Otherwise, the end result will just be more documentation that will be left on the shelf.
None of the above will be possible without required funding.
It was a flawed decision in the statement from the Secretary of State for Health that no new funding would be available. Existing methods of applying for funding for research into ME have obviously been failures and attracted little interest or any long lasting changes for people with ME.
This has to change.
Consideration ought to be made to the IiMER proposal to demand funding for the steps outlined above to be performed.
Regarding targeting young/early career investigators - Invest in ME Research had already started this process with our Thinking the Future Young/ECR workshops that were attached to our research Colloquium events  .
We collaborated with the NIH to create three workshops in 2018 and 2019, and only paused due to the pandemic situation.
Making a Rapid Start to Change
We have already suggested that we need to make use of what exists already rather than building an extensive list of funding requirements that will likely not be funded  .
What is already present, supported and functioning should be considered for further investment rather than reinvention or using up more time to delay progress.
Using the points above then a start can be made already to augment foundations in place.
Nothing will happen without adequate funding.
So, we restate that the working group should provide a push-back to the Department of Health and demand adequate public funding already to be allocated for research into ME  br>
The first invitation to Invest in ME Research to participate in the UK Clinical Research Collaboration (UKCRC)
Working Group meetings was to a meeting held on 1st September 2022, after other meetings
had already taken place and decisions already made.
Our submission to that 1st September meeting can be seen here  .
We commented in our submission document
that what has been achieved and developed and is present already
ought to be considered for investment (such as the centre in Norwich Research Park)
rather than reinvent the same.
We suggested looking at what our colleagues in the Netherlands had already set in motion with a research agenda that had been funded and was underway, and was covering much of what needs to be started.
At least we can see that this point has been included as an item for the next meeting.
We also stated that the UKCRC needed to push back and request funding up front for research - otherwise the only output from this exercise will be more documentation.
Meeting 14 October
For this meeting we were supplied four documents two days before the meeting. These four documents were:-
- The agenda
- Proposed Actions for a Delivery Plan
- A revised (final) Terms of Reference document
- A list of volunteers for each of the subgroups
- Minutes from the meeting of 1st September 2022 (The IiMER submission to the previous meeting is here - )
The input made by IiMER included again suggesting that any plan ought to support, emphasise and fund centre(s) of excellence - such as established in Norwich Research Park.
We asked if Professor Carding's input to the meeting had been distributed to all beforehand
(see above, or as pdf here).
It had not.
We stated that we did not understand why this input, which had been submitted a week before the meeting, in line with the requirements of the working group, had not been distributed and that it was of little use being left on some shelf.
We already have experienced the situation where our submission to the working group for the first meeting to which we were invited on 1st September had similarly not been distributed before that meeting.
Previously we had stated that we believed that building a strategy of research via the centre(s) for ME would likely also lead to greater capacity and capability and raised awareness and better education.
We again stated that this group should push back to the health ministry to demand funding up front for research.
We stated our belief that the description of research required ought to retain the term 'biomedical' - i.e. biomedical research.
We do not believe this would compromise the type of research for which funding is required.
We stated that we believed that people with ME are likely quite happy and familiar with the term 'biomedical research'.
We mentioned the amount of funding given by MRC in the period 2004 - 2017 - had amounted to only about £6.7 million. Such a paltry amount
when compared to the disease burden.
We stated that previous methods of funding including highlighting ME had failed.
We again stated that we believed that the minutes of all meetings should be made available to people with ME and their families (i.e. the public).
There is no reason to avoid giving these minutes out in full as already no references made regarding individuals.
This point was made in our earlier submission to the Terms of Reference document in the first meeting to which we were invited .
- Sajid Javid – 2022 Statement on ME/CFS
- Input to 1st September UKCRC Working Group meeting
- Input to UKCRC ME Research Working Group - Our View on a Different Approach
- RESTORE_ME Clinical Trial
- MRC Letter to MRC CEO
- MRC Letter to MRC CEO
- MRC Funding of Research into ME/CFS
- The Wrong Stuff
- 10 international colloquiums - collaboration
- European Research Collaboration
- Dutch research agenda
- Colloquiums and conferences
- PhDs in Europe
- Journal of IiMER 2015 Page 5
- UK Centre of Excellence for ME
- Thinking the Future - Young/Early Career Investigators Workshops
- Input to UKCRC ME Research Working Group - Our View on a Different Approach
- Our proposal in the UK parliamentary debate 2019 to provide funding for research into ME year for five years