Building the ideal ME/CFS research institute

J

Jacob Richter

Established Member (Voting Rights)
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.
 
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.
 
I don't think all the research teams and all the infrastructure need to be in one place. For one thing, trying to get all the great researchers and their teams that you want to be involved to move their lives to one particular place is likely to be difficult. OMF has teams in different places, and I think that works. Global communication and coordination is possible. Another reason is that parts of Europe and the US are typically expensive places to undertake research. I'm pretty sure that more research could be done for the same price in other places with no loss in quality.

I very much agree with Rvallee about the huge need to have people with ME/CFS at the heart of such an initiative and to have transparency. The 'nothing about me without me' idea. Even the best intentioned of researchers and institutions fall into the trap of being patronising, and not really hearing what patients are saying. Partly it's just the very uneven power situation. Particularly with ME/CFS though, I think, the prejudice that we aren't reliable reporters of our experience, that we are mentally unwell and flaky runs so deep. That would be my main criticism of OMF - it feels like something that is being done for us, with our only acceptable roles being to cheer the efforts on, and to donate money. My ideal research institute would empower people with ME/CFS, would be a model of how to treat people with ME/CFS, and patients in general.

To that end, I would embed Science for ME in the institution (!), and actually have people paid to run the forum and an extensive library, while still continuing to allow fearless commentary on all research from anyone interested. I would have the institute's research director put forward proposed research trials and programmes here, for people with ME/CFS and other interested people to comment on before final funding decisions are made. That level of transparency and patient involvement might be an attractive feature to some potential donors - trialling a new way of doing things.

I would have the institute provide a dedicated proportion of funds to research projects proposed and partnered by national charities. That way, the institute would help grow national capacity to identify what research is needed and to create awareness. That would be one way to minimise the risk of the institute being geographically blinkered. For example, a study in, for example, Uganda of Ebola survivors might deliver a crucial clue, but currently it would be so hard to make such a study happen. Having a study like that funded by an international institute in partnership with a fledgling national patient support group could give local ME/CFS sufferers so much hope and have a big impact on how medical professionals view ME/CFS.

I propose that idea of having some funding to partner with national charities because I have seen problems in the way international aid works. International charities think they have to do everything themselves and come into places where they don't have local knowledge or infrastructure. Their efforts can undermine and drain resources from local governments and local charities, reducing local capacity. With ME/CFS, there are some reasonable existing funders of research including national charities. A new institute doesn't have to crush those initiatives or act in competition with them, which often have their dedicated donors and supporters, and knowledge of which researchers are good and which aren't; it can instead bolster them. A potential international capacity might be attractive to some potential major donors of funding.

I see the primary aim of the institute as improving the quality of international ME/CFS research, regards of whether it itself was funding it.

To that end, I think one important initial focus would be research on suitable outcomes and trial design guidelines. Another important focus would be replicating promising research.

Thanks for the thread @Jacob Richter. I get tired of hearing myself complaining about what is wrong with ME/CFS research and administration, and would much rather help create something great.
 
Last edited:
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.
 
Jonathan Edwards said:
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.
Click to expand...
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.
 
Last edited:
Jonathan Edwards said:
My question would be, in a different sense, 'where are the patients?
Click to expand...
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 ?
 
strategist said:
but the nonsense is not the illness per se but their own inaccurate mental model of it.
Click to expand...
precisely

strategist said:
For all we know even with mandatory PEM case definitions it could still be several different problems.
Click to expand...
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!
 
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.
 
Jonathan Edwards said:
My question would be, in a different sense, 'where are the patients?
Click to expand...
Well, we are fairly sure that they are pretty much everywhere. Indeed, if it turned out that they aren't in a place that is inhabited by people, then that alone would probably be worthy of a study.

The problem isn't where the patients are, it's where the expertise is. And, at the moment, that is in a pitifully few number of locations. Which means that we are getting pitifully few really smart and informed people treating ME/CFS (or Long Covid) patients day in and day out.

So, I'd argue, there's a better approach than setting up one shiny new bricks and mortar institute with a waiting list thousands of patients long. Those patients would be either very fortunate to have lots of money to get there, or have mortgaged their house and are teetering on bankruptcy because they can't work, or they have used all their social capital fundraising on the internet. They may in fact present a very skewed and narrow sample of ME/CFS patients. Those patients may not react very well to getting to the shiny new institute after two years on the waiting list and being told, umm, well, we don't actually have any treatment that we can in good conscience prescribe for you. But we can put you in a study! umm, you might get a placebo, and the study is a year long during which time you can't undergo any other treatment. Many of those patients might come once or twice, decide that they aren't going to get cured anytime soon, and leave the institute, moving on to somewhere that does promise to fix them with some fancy stem cells or spine surgery or something, or sinking into resignation back in their now down-sized home, making followup or long term tracking impossible.

The better approach is to encourage the development of centres of good care around the world that are independent of the institute.

And that can be done by our imagined institute offering very generous research grants but requiring the researchers to partner with organisations that have a track record of providing care to people with ME/CFS and who clearly understand the disease and have the capacity to diagnose. Maybe that means taking experienced clinicians to places like Uganda, to train up local clinicians for a clinic and, in the process diagnosing a study cohort. Or working with a (rare) reputable and sensible clinician who already has a thousand patients in their database. Maybe it means multi-site studies - those have the benefit of perhaps uncovering different types of 'ME/CFS'.

And it means biobanks of various sorts of human samples and registries of well diagnosed patients so that the expertise of good clinicians benefits many researchers.
 
Last edited:
Hutan said:
Well, we are fairly sure that they are pretty much everywhere.
Click to expand...

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

Hutan said:
Those patients would be either very fortunate to have lots of money to get there, or have mortgaged their house and are teetering on bankruptcy because they can't work, or they have used all their social capital fundraising on the internet.
Click to expand...

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.
 
Last edited:
strategist said:
For a doctor to justify seeing patients with ME/CFS, some useful treatment or diagnostic procedure needs to exist that can be used.
Click to expand...

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.
 
You must log in or register to reply here.
Back
Top Bottom