Building the ideal ME/CFS research institute

Dear all,

I'm keen to sound out opinion on what the ideal ME/CFS research institute would look like.

Much of the forum discussion is (rightly) about what the medical community should be focusing on in terms of ME/CFS biomedical research, but this thread is about the 'how' - not on a technical level, but at the level of institutional architecture (mandate, staffing, governance, incentives, funding and organisational design).

In my line of work (strategy consulting) we sometimes encourage clients to sketch out what their toughest competitor would hypothetically look like - literally asking them to draw out on one page an operating model with all the key functions and capabilities of a world-beating organization in their field, and how they fit together. This helps identify where the gaps are in their own operations and how to address them. I want to do a similar thought experiment here but re-purposed to sketch out the key attributes of the ideal ME/CFS research institute. This can draw as much on lessons we've learned over the years about what doesn't work as what does.

To get the ball rolling, my initial thoughts include:

• Funding: The ideal institution would perhaps be funded by, and housed within, a single philanthropic foundation. This is potentially better than government agencies like NIH because many foundations are essentially the private 'toy set' of a single wealthy donor or family: provided those benefactors are on board, there can be huge flexibility, unity and speed of approach which is impossible amidst the bureaucracy, hierarchy and wrangling of a tax-payer funded institution.
• Funding should be long-term, condition-free and represent a step change in anything we've seen before; e.g. an open-ended drawdown facility of $2bn-$3bn.
  
• Examples that come to mind are (1) the Seattle-based $49 billion Bill & Melinda Gates Foundation, where there may be an opportunity to introduce ME/CFS and Long Covid as an R&D focus if and when the foundation splits its programme portfolio between the Co-Chairs' offices (i.e. between Bill Gates and Melinda French Gates).
• (2) The UK-based Gatsby Foundation and related Sainsbury family trusts. These trusts operate with a good degree of autonomy, many have a scientific research focus, and as a former Science & Technology Minister in the Blair government, Lord David Sainsbury may perhaps take an interest in an under-researched area such as ME/CFS.
• The UK-based Wellcome Trust also comes to mind, mainly because it's huge, but as they funded the Science Media Centre to the tune of several hundred thousand pounds for many years, I question their judgement.
• Organisation: There should be several semi-autonomous research teams that are given the space to pursue their own research agenda/focus area without funding pressure or arbitrary deadlines, but these individual teams should all be co-located and supported by a central strategy-setting team that ensures (i) knowledge is shared in real-time between teams; and (ii) there is shared access to a large pool of common resources (e.g. access to pre-screened patients willing to participate in tests and trials). This 'portfolio' approach is akin to a venture capital fund placing multiple bets on different types of start-up business model on the basis that one or two ideas out of ten will succeed & it's hard to tell ahead of time which.
• Incentives should be set in a way that creates no penalty (financial or career-wise) for failure, e.g. as and when teams hit a dead end, they merge with another and are guaranteed continued backing.
• All research findings should be made publicly available without undue delay and in formats (e.g. clean and complete data sets) that can easily be used as a foundation for further research globally.
• A global advisory board should regularly monitor ME/CFS research developments around the world and establish direct lines of communication & data-sharing between the institute and any other high potential research initiatives on-going in other countries.
• Location: US rather than UK/Europe.

Once we've pooled more ideas, I would like to develop a concept note that captures what a best-in-class ME/CFS research institute could/should look like. My aim would then be to pull together a coalition to engage with the top global foundations that have a mandate to fund Health R&D in order to campaign for investment to make it happen.

This will of course need a great deal of other work, including a prioritization exercise to establish which organisations are most likely to be receptive. My health may fail or I might not have the bandwidth. But it's an area in which I've worked successfully before; you have to start somewhere; and to be honest it's the only way I can think of to be useful in the cause of ME/CFS research as I have no medical training or aptitude.

Thanks in advance to anyone who has time to engage with this. And if you know of a similar exercise that's been conducted before, please put me out of my misery by sharing it! No need to reinvent the wheel.

 

We definitely need a zillionaire, and a detailed organisational blueprint might whet their appetite, although it’s equally likely that anyone with a few billion to spend on curing ME would have their own whims regarding location, publication policies, academic engagement and so on.

But the most important things to build into the funding and governance structure would be institutionalised patience and some kind of defence against mission creep. ME could remain mysterious for years while the DARPA-esque research teams you envisage would constantly be distracted by exciting adjacent findings, perhaps with enormous potential to cure other illnesses. Could a research director with a conscience nix those projects? And why would the zillionaire benefactor want them to?

If the institute is going to solve ME, it needs a governing board which adheres to the original terms of reference with legalistic fervour. Perhaps the best way to secure that is for the zillionaire to be beyond the point where they can change their mind - so, ideally, the institute is funded by a legacy endowment.

 

Is there any hope, particularly with Long Covid, of getting an actual zillionaire on board? For example I don't see why whoever controls the Gates research money wouldn't be interested at this point. This is clearly affecting millions of people worldwide and there is an increasingly well-known massive knowledge and research gap.

 

See the Arc Institute https://www.s4me.info/threads/arc-institute-launches—includes-stanford-berkeley.23853/#post-415653

with deep funding from https://en.m.wikipedia.org/wiki/Patrick_Collison

 

Radical transparency and accountability. The usual secretive ways of medicine are terrible for us, they allow the worst behavior and failure to be hidden by bureaucratic inertia.

The main issue with chronic illness is always the complete imbalance of stakes. We have all the stakes, our entire lives are in play, while the people who do the work generally couldn't care less what happens to us, unless we happen to have allies involved, or it's work the patient community funds. They're playing with Monopoly money, it makes zero difference what happens to us, what the outcomes are. There is generally no urgency, not even any interest, and even less incentives.

For sure that's the future of medicine, but medicine isn't ready for this yet. They have a working model in AIDS, and it's only ever been used once and it seems almost like it's considered a very bad thing that will never happen again. As long as patients have no influence in what medicine does to us, they will keep failing, they can't even tell the difference between complete failure and the kind of success that deserves awards.

 

Patient and carer involvement at every decision making stage at least, and preferably within work teams on every project. Substantive monetary compensation for those representatives, and adaptation of the research workflow to the limitations of those representatives. Yes, this will mean research will take longer, but the chances of it being meaningful and valuable research will be increased.

 

An interesting proposal. At base - " to sell to a US based philanthropist or foundation, the proposition that sustained research into ME/CFS is a worthy application of the resources they have to hand".

A couple of recent S4ME threads that have relevance: https://www.s4me.info/threads/article-how-philanthropy-can-nurture-your-research.31537/ and https://www.s4me.info/threads/the-p...-into-clinical-registries-and-research.31591/

My first concern would be the definitional challenge - what is it that this new Institute is being charged with achieving ? At this point there is no clear direction for a "science of ME/CFS" to follow and having that direction is going to be essential to actually create a bureaucratized structure whose whole purpose is to unravel a problem that in concise scientific language is profoundly difficult to articulate. Doing a James Lind style wish list https://www.s4me.info/threads/resea...rity-setting-exercise-2022-tyson-et-al.29743/ is unlikely to impress the hard nosed project assessors of a major foundation, these are people who are going to be concerned with optics and bang for bucks, they'll want clear statements of what is the science, what is the possible reward, and who benefits - the latter a rating scale with 3rd World sick children at 10.

My inclination is that while working this up as a project is valuable, it would make sense to at least wait until DecodeME has reported, and perhaps also the NIH Intramural Study before trying to sell it because both these studies have the possibility of narrowing the definitional challenge by providing a clearer picture of where in the whole of human physiology that the condition(s) that we currently call ME/CFS is, at least in some part, located and thereby be able to what specialisms are needed to ensure the institutional structure provides for progress.

The alternative is to accept some broad headline which may turn out to lack the specificity needed to ensure that ME/CFS is not lost in translation. There's currently frequent reference to ME/CFS being a 'post viral condition' - an Institute of Post Viral Studies has a good ring to it and is very current so could be a good sell, this might be fine if indeed ME/CFS has a definitive post viral association, however if ME/CFS is strongly correlated but only weakly causatively associated with viral infections then ME/CFS could end up in a poorly funded annex of the otherwise bright and shiny IoPVS.

A key thing will be selling the project 'high' - better nothing at all than another Whittemore .

 

My question would be, in a different sense, 'where are the patients?

Research into disease mechanism and treatment has to be based on physicians acquiring a deep understanding of the natural history of the illness - in other words what it is like day in, day out, year in, year out, for people to experience it. Setting up research into ME without the centre being active caring for patients, and for the sort of programme envisaged at least 1000 patients with ME doesn't make much sense. Moreover, I don't think those patients should be involved in any financial conflicts of interest around the research. They should be able to take it or leave it. They certainly shouldn't be recruited via the internet just for interventional studies (epidemiology and genetics are a bit different).

In the old days this sort of facility was provided by university centres in both Europe and the USA and maybe Veterans Administration centres with patients receiving free care. Most major progress in clinical research has come out of that sort of model I suspect. Philanthropic institutes are fine for blue sky basic science but that is not much good if nobody knows what the letters PEM mean.

 

Yes one of the things i find most frustrating is because so many researchers (even outside the BPS crowd) dont seem to understand what ME/CFS even is, as an experience. It leads to a great deal of wasted money i think.

Classic example is people doing research on animals, thinking they have induce ME/CFS in mice by making them exhuasted - believing thats what ME/CFS is.

Its infuriating.

 

In the minds of many researchers and clinicians, CFS is a state of unusually strong or persistent fatigue. And some of them then oppose research into the illness on the grounds that this definition is too vague. They aren't wrong, but the nonsense is not the illness per se but their own inaccurate mental model of it.

A problem is that even the people who obsessively learn everything about ME/CFS don't really know what it is either, just that it's not that kind of fatigue state the others are imagining. For all we know even with mandatory PEM case definitions it could still be several different problems.

 

There's huge enthusiasm for 'remote/digital medicine' e.g Preparing the healthcare workforce to deliver the digital future , where all the clever stuff happens well away from actual patients. It seems unlikely that any 'bright and shiny' world leading Institute is going to want to embrace the grubbiness of actually dealing directly with bodies, so perhaps the epidemiology and genetics of ME/CFS would be the sexy option for a sell to philanthropy ?

 

precisely

indeed. This is one of the issues, because its human nature for people to think that whichever 'version' of, or whichever interpretation/experience of them we have, then that is what PEM 'is'. I dont know what the answer to any of it is tbh. I'm glad better minds than mine are working on it!

 

Just to follow on with the remote/digital theme: "wearables and multi-omics microsampling"

https://www.s4me.info/threads/multi...nges-in-health-2023-xiaotao-shen-et-al.31609/

 

Thank you to everyone who has posted - especially the longer posts which really get to the heart of the challenge and which I suspect reflect years of prior reflection on a subject I'm relatively new to.

I'll be quiet on this thread for a couple of weeks but plan to take some time away from the day job in February to think this through more thoroughly and build on the ideas shared above.

Thanks again.

 

Of course but my point was 'where are the patients being involved in this institute?'.

I am not suggesting that patients pay to be involved. I had hoped to make that clear by saying that they should not be affected by financial conflict of interest. Their being looked after at the institute should cost them nothing extra - as is the case for NHS or I guess for Veterans Admin.

The question in the thread title says nothing about this being a commercial enterprise. That to me is the death knell right at the start.

I am simply suggesting the model that I was able to make use of. A university centre, funded by charities with revenues from legacies and contributions, associated with a universal health insurance system. In that environment people like Tiny Maini, Pat Woo and myself managed to shift RA from a disease with no very useful treatments to one with remission-inducing therapies. The same model has been the basis for most major breakthroughs in cancer therapy in the UK at least. Why not use a model that works?

It may well be that the financial agreements between charitable funders and government health services have to be very different now, with all the bureaucracy. Funders may find it odd that they have to pay to treat patients as well as run labs, but in cancer this has already been done. McMillan has funded a major cancer clinical service centre at UCL. They paid towards building an outpatient block as I understand it. Diabetes charities have got involved in clinical service alongside research.

If at least some of the staff at this institute have not seen hundreds of people with ME in a clinical setting I see the plan as doomed. Nobody would suggest that for cancer or diabetes, would they?

 

An obstacle appears to be:

For a doctor to justify seeing patients with ME/CFS, some useful treatment or diagnostic procedure needs to exist that can be used.

But there is no proven treatment or generally useful diagnostic procedure. That's probably why there are so few specialized clinics.

And with very few of these clinics, no competence on the clinical side can be developed, and it becomes harder to recruit patients into clinical trials.

But maybe there needs to be a change in thinking and we need to open more clinics that don't primarily exist to treat, but just to observe, collect data, and recruit patients into clinical trials. The diagnostics and treatments will hopefully come later when there is more understanding.

 

But why? When I started out in rheumatology to study rheumatoid arthritis RA patients were routinely seen every three months for years and years and we had no really useful treatments. Diagnosis was made on history and physical examination. Blood test told us about complications and things but didn't really alter the diagnosis.

Admittedly a lot of unproven treatments were used at a time when we thought we knew they helped, but by the 1980s we had moved on to trying to ensure that things were subjected to proper trials.

I agree that there has been resistance to providing a regular ME service, but I am not sure this is based on logic. It is based on prejudice. That may be just as hard to change, but it is not that there is no justification for a service. Moreover, at least UK NICE has indicated that such a service should exist, at least in principle.