[UK] A proposal for an ME/CFS, Long Covid, and Post-Infectious Disease research platform

If I'm interpreting you correctly, you think the science will start moving fast soon - you've said the right people are interested, you and Jo Cambridge and Jackie Cliff will be putting up your paper, we'll find out if DecodeME shows anything - so what if a solid drug candidate pops up based on this science? If that happened tomorrow, where would we get a patient cohort from and how long would that take? Are there things we should be doing now to make sure that any such trial could hit the ground running?

We don't have time to lose.

 

All we need is for the medical research 'received wisdom' on ME/CFS biology to shift to belief mode. Then projects will be funded and even before they are there will be researchers wanting a piece of the action. The only thing I can think of that will change things is an experimental result. No other lobbying or explaining will change minds. The Fluge and Mella data and the Zhang data very nearly do that but not quite it seems. But we will get there.

 

No sweat, Sasha. Oystein Fluge will have done it before you have time to write your forum post. The Norwegians are seriously get things done people - I would take all my hats off to them if I had any.

 

Are we sure? What if they answer questions and clarify the fuzzy stuff? One of us has posted a question on MedRxiv (currently in moderation).

 

That's excellent news but why can they do it when the UK can't?

 

In my opinion: Yes. They are good at running trials, good at getting funding from many different sources, and have a very high standing among thousands of patients in Norway. Recruitment won’t be bottle neck.

 

I didn't say we can't. But we need physicians who are seriously bright, honest, humble, and very committed to ME/CFS. There aren't that many people around like Oystein and Olav. It doesn't matter anyway, does it? I had ethical committee approval for a trial in ME/CFS but closed the project because the Norwegians had it in hand.

It has nothing to do with not having resources in the UK. It is all to do with people knowing what they are doing and being passionate about getting it done. That is why I don't see discussions of superstructure being of any real interest.

 

We're extremely lucky to have them in the field but they've got a day job and what if there's more than one drug candidate? How likely is it that it will be a 'one and done' situation as it was (I think?) with rituximab? Might we not need several trials going on in parallel?

 

We do, but getting physicians to take ME/CFS seriously is not that easy it seems.
One of the problems I see is that doctors only ever come across patients in the interview situation in the clinic where attitudes are already firmly in place. I have, over the years, found it very useful to join patient groups as someone who is not expected to provide a solution to a personal problem and who can expect to be argue with because no personal outcomes are at stake. So few of my colleagues seem to want to do this.

 

How do we get out of this situation? Is it a matter of identifying doctors whose attitudes aren't already in (the wrong) place? Or should we be trying to persuade doctors wholesale, hoping that some among them will take us seriously and get interested in helping?

I don't know what would even seem persuasive. With Covid, there seem to be plenty of doctors who don't believe ME is real until they get it themselves, and even then, their colleagues don't believe them.

It doesn't seem to be enough to see patients profoundly disabled, given that if you look through a BPS lens, that disability is self-inflicted and imaginary.

Would inviting doctors here to talk with patients who can talk freely without fear of repercussions help?

We need a way forward but we've never been able to find one.

 

Actually we did find one. And it is working through. We will have a way forward when we have data that make the biological basis clear. It will come, I am confident.

 

Maybe other countries will find their Oysteins and Olafs when we have something to chew on?

After all, the extent of BPS influence in Norway made it look like a very unpromising environment for ME/CFS research, yet the Bergen team still emerged.

They found something interesting and followed it up. The existence of a whole ecosystem of BPS-focused research and provision was irrelevant to them because it had no bearing on the theory they wanted to test.

It's possible similar things could happen elsewhere when good leads are found: scientists working in other areas seeing a relevance to their own work, people remembering questions they once asked but never got answered.

Yet they still started their ME/CFS work, and all of it has been very good. I guess it's an another argument against putting large sums of money into infrastructure. When bright people are onto something, they tend to find ways of following the scent.

 

So in summary…is the the message to send

• Don’t waste money on the current clinics in the NHS, they’re crap
• Don’t waste time building big funding pipelines, they’re crap
• But be ready to get behind good science when it comes

Because I agree with all that. But feel we need to work on the third bit given how long it takes to persuade politicians, funding bodies, medical organisations from GP practices through hospitals…

I have less faith than some seem to have that it will just magically all happen and fall into place. I believe that a scientific discovery will help. But everything beyond that does seem to be another set of hurdles we are going to need to work on.

 

Why do we have to convince anyone but the funding bodies when it comes to research funding?

 

Because of who gives the money to and sets up the funding bodies, who sits on them and advises them, because of all the other points we’ve talked about in this thread…

 

To expand a bit, the funding bodies have their funding allocated by politicians, their frameworks and remits set by them too. Problems there have been highlighted and influence them involves others outside those bodies. We’ve also discussed the need for clinical changes, these can be influenced by others. There’s a whole load of interconnected people and organisations.

I get that you can’t easily make change in those areas without a change in the science, the evidence. A catalyst if you will. But I find it hard to accept that that change alone does all the work. I’ve never seen that happen in the real world. There is always more.

I’m not sure if I’m misunderstanding people or explaining poorly. Or just have a different world view from others.

I see the scientific development or breakthrough expected as a seed
That seed will not just grow though, it needs earth, water, sun…
I am talking about that, what is needed to create the best environment to support and nurture it

 

I do take the point, but the funding bodies are already set up and already funded, so we've no influence there.

The questions is, how will they respond to applications once there's something concrete to follow up? We haven't got a proper sense of that yet, as we've been short of projects that could compete in funding rounds against applications with a stronger evidence base.

It might turn out to be as bad as you think in Britain, at least at the outset. But there's more than one medical research council in the world.

There will be, but maybe we'd get the most benefit from our efforts by looking to that.

If a group made a breakthrough convincing enough that people started designing experiments or thinking about drug candidates, perhaps we should be thinking about the larger trials that would follow if it panned out.

We can help researchers make sure they're recruiting well defined cohorts, creating access for as broad a range of severities as possible, and identifying and measuring outcomes that would give them the evidence they need to convince doctors and healthcare systems.

That's probably where most of our power to effect change lies.

 

I think it does happen. At some point around 1990 'going senile' became 'Alzheimer's disease' because there was some new science on neurofibrillary tangles and amyloid and Tau protein. That fed through directly to all old people getting scans and getting diagnosis and new drugs being licensed - even if they don't do much.

When Ravinder Maini worked out that he should try anti-TNF for RA (I had too but he had access to a safe antibody) and others of us followed with other biologics RA went from a Cinderella disease with little clinical funding to having the biggest drug budget of any disease almost overnight. The discovery of H pylori revolutionised ulcer management very quickly too.

We need the people who referee grants to understand that this is a real biological problem. Once that has happened I see nothing stopping the process. Finding effective therapies may turn out to be hard but to some extent I see the central goal as having the disease recognised socially for what it is. I think that will happen quite quickly.

 

I’d say focus on firming up the definitions and understanding that when people suggesting making it fuzzy claiming ‘inclusive’ that it’s actually leading to something that again excludes those with me/cfs from their own category , and because PEM and me/cfs are so counterintuitive vs fatigue on its own it also creates a grim dystopia where we are at risk of being called mad and/or driven mad. But also so that it becomes a defined ‘problem’ that can be worked on and any possible groups or differences within that can provide clues. Rather than us disappearing again into some bucket of ‘people who get tired asking for awareness but not putting across well precisely the gist of it as an illness/what the mechanism is that is specific’

I think there are some important ideas and aspects such as PPI that the detailed of how it can be used for good and to provide proper representation (not the illest getting judged out and spoken over so disappearing) in samples so the proper disease is studied not the spectrum cut as usual, is important. But it’s that detail of where the issues are not constructing necessarily a different format that could still be played because it doesn’t have the real problem points focused on.

and it needs to move towards people who are long experienced and aren’t out in a position where they will be coerced or told to ‘be nice’ meaning say what people want to hear as the answer and not do their job of critiquing. Whereas at the moment it’s people who spent six months in a fatigue clinic who were compliant in saying the right things who don’t have much experience as they are at best a few years in. Getting drafted in to have a nice old time being nice about someone’s work with the same eg bacme mindset. Which leaves us stuck in the perception of the illness being what they’ve been taught to perceive their pattern of symptoms as. Rather than the many years on of living deteriorations after doing x or going through y.

there are many other bits named that are also good to be tackled and elucidated this way.

and whatever the system or initiative need to be being done.

they aren’t the side issues to be worked out later but the difference in whether anything goes the wrong way or the right way