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

Could this be a discussion point that is set up as a thread in itself?

I have a sense this isn't the only place where this sort of stat/suggestion of bringing in LC stats has come up recently.

I think/seem to remember eg @Hutan often has some good insight on the research and comparison of long covid vs ME/CFS

this seems an increasingly important area to clarify the language of/what is meant under some of these terms. But also to just list some of the latest data, and maybe some of the older suggested ones that might still be being thrown around so we can wind back what comes from what source at what point - as I'm getting a bit confused

e.g. where did this suggestion of 50% originally come from? and when it is 'of pwlc' what is meant by that, or is it 'pwlc who fit an ME diagnosis'?

It is hard to comment on and think whether it is true without knowing whether we are talking about 50% of the lc people who might have been designated at the point in time when symptoms (of any kind, so could include sense of smell being lost) for more than 4-6 weeks was being used for lc, or soemthing else. And the who fit an ME diagnosis sounds better but it would be good to confirm whether we mean that in an official sense ie certain criteria etc?

Basically I don't know what group we are talking about being half of what other group currently, and am used to here commenting on quite specific papers etc.

 

Interesting point. I'm guessing there is a difference, given that a call for just ME/CFS would mean that those with or studying pwME from lc or infectious diseases would be included anyway and it wouldn't preclude studying eg covid to see how many ended up with ME/CFS

It seems like given how on the back foot things are and other aspects about ME/CFS (eg bucketing and it not yet sitting obviously under 'one body part/system/specialty') that alone is a rather broad area/remit?

On the other hand I'm interested because there might be very good reasons behind this that I haven't had enough time yet to spot?

 

I guess we have to admit that this is one of the issues at the nub of the conundrum.

@Kiristar that's fascinating that you did the research into the Grand Challenge document and know about the German situation.

Can you provide any detail on this question for those ie the control mechanisms/who is able to be in charge of making those decisions on who gets the money and is allowed into/chosen for the consortium?

I think that this would be the really reassuring part to be able to hear about and discuss.

 

Here are my overall thoughts. Quotes are from the proposal.

What is «low critical mass»?

Regarding funding: Which concrete studies have not been funded the past 5 years? Were these studies worrhwhile?

Which projects (biobank, etc.) lack funding for the barebones operation in the future?

What does synergy mean?
To me, synergy is a buzzword - as a management consultant it’s what we say when we want people to «work together» because that’s supposed to somehow produce a better outcome.

Repeat of the above: are there concrete projects that have not been funded?

Is the assumptions that more would produce a better outcome?

This reads like more buzzwords to me. Why is this what is needed? I don’t think it is self-evident.

This is a good point for why more funds should be available, in general.

What does «take full advantage of» mean? My understanding is that the by far most important thing is that the samples are preserved and not destroyed. But that can be done with skeleton funding and crews.

Using them is not a priority. The important thing is to have them available for when they are needed for a really good project, whenever that will be.

What is the purpose of focusing on PEM in isolation, when we don’t know if PEM is all of ME/CFS or its own thing?

The thing that might be needed with regards to PEM is a large collection of accounts of PEM to get a better understanding of the «behaviour» that we can observe and quantify. Maybe that’s what «clinical» means?

This could be used to inform future studies that tries to dissect the underlying mechanisms.

Everyone want drugs and treatments. But we need to understand the mechanisms before we can start with the drugs - trying things based on hunches (which is all we’ve currently got) is very unlikely to yield and results.

«Innovate treatments» is just another buzzword. And we have no idea if we actually have to do something new - because we don’t know what we’re supposed to treat.

This is just «try to figure out what’s going on». Which makes sense as a priority. I don’t get why the tools are listed in this section only?

It is not clear to me what this is about and how it relates to ME/CFS.

There is no ME/CFS-infection that we know of, so presumably this is about infections in general? But which ones are we supposed to focus on - and how is that supposed to advance the research into ME/CFS?

ME/CFS does not appear to be an infection issue per se, but rather an issue of something getting something out of whack.

I don’t see why the causes and treatments for severe and very severe are singled out. Any research into ME/CFS should ideally account for all severities. Unless there is a specific reason to believe that severe+ is a distinct pathological entity?

What could have been singled out, is how to provide adequate care for the severe to extreme. Although it would overlap with general care for anyone with ME/CFS.

—————

It’s certainly possible that my failure to understand is a me problem. And it’s always challenging to distill what has undoubtedly been a lot of discussions into just a couple of pages.

My worry here is that the reasoning doesn’t shine through. We’re mostly told what the conclusions are. And if it isn’t obvious to us - how is it going to be clear enough for the intended recipients and decision makers?

And maybe even more importantly - how is it going to serve as a foundation for the governance of the implementation of this project?

 

From the ME Association write-up of the last CureME Bioback steering group update. Samples do age!

The lab team is the Brunel team under Jackie Cliff studying HHV6 with NIH/NIAID funding. The continued funding of that team is in question due to the research situation in the US.

 

I think that understanding PEM is really important (and certainly not doing it with the word 'behaviour' involved) because of the potential for it to produce limitations and its own effects in trials or experiments. I remember the old days of eg chemistry lessons where the last section of a report had to be describing the limitations of what you'd done and what needed to be borne in mind as a factor to be controlled for next time.

We are currently in a situation where most experiments still involve groups of people approximately selected based on definitions of symptoms being asked to then attend a location that could be at varying distances/difficulty of journey at times that could be of varying convenience to their other committments or patterns.

And that is before we think that someone could theoretically be I guess 'mild' but get quite extreme PEM - and by that do we mean how much it is triggered by, or how much the symptoms or 'total debility' are or how long they last. Basically even if we had a perfect scale or way of assigning people into severities or % severity re: their ME/CFS then there is this other factor, which is perhaps a bit more independent than we acknowledge. What people can 'do' as a one-off (after radical rest) vs how ill they are afterwards is more complicated than that across a population of people. I think there is even a Workwell paper noting that pwme aren't 'unfit'.

We can probably assume that most will be in PEM by some point after doing the experiment ironically, but the idea of 'being not in PEM' is almost a philosophical conundrum for pwme. And as things are triggered by cumulative exertion, and we have fatiguability and other pains etc even expert patients are making complex calculations working out how much PEM they might be in and where in their threshold (for the day and for the month) they happen to be when doing something.

Hence why I guess the CPET idea was a good start point simply because of the idea of a short-term 'max' that for once wasn't an arbitrary amount like a 6min walk or doing 20 hand grips. But still all we can know is that we are probably thrusting everyone who does it into PEM at some point if they get PEM. The issue is that the same package that might break and be very dangerous and unnecessary overload just to trigger PEM for one might not be doing the same for another.

Vice versa even if we were even just doing blood draws at home for a group how do we know who is in PEM or still recovering from a massive PEM. It might turn out to be really useful to know, particularly if we are doing before and after type trials and so a snapshot bloodtest when what is being looked at in the blood is the sort of aspect that varies

Currently we have no idea of what 'dose' a person is getting, or even able to control for the other things adding to said dose given that cumulative exertion and sensory leading up and after and around whatever 'controlled task' are still adding to the same thing. Plus of course people have joked in other trials about someone being on a wobbly chair in a cold room after a bad night sleep and needing a wee whilst doing eg a test like the EFfrt test. On the other hand someone doing behavioural self-report how do you feel surveys inviting people to come in for their follow-up at a time that suits them better, with better parking arrangements, free strong coffees and comfy chairs in a quiet lounge compared to their 'before' questionnaire environment will also affect most pwme in the same direction. But PEM is what people have been doing in the week leading up to it all.

I agree that PEM and worsening could simply be associated rather than causal - the 'underlying thing' is what causes both + exertion that is cumulative. And it could be that there isn't something important about PEM. But we might need to understand it better in order to work out what level of 'acute' symptoms for them someone is under whilst being tested simply to have a better chance of like with like.

And on the like with like note then it might help to ensure more homogenous samples - even if that is done by within subject variance ie catching everyone on a similarly well-rested (or not) day to when they did their 'before'.

 

Bit of an aside, but one of the things I'm not clear about is where the money for projects like this would come from. I've experience with grants and funding (it was part of my job), but it was in a very different field.

I imagine research teams usually bid for funds from one of whichever public programmes are currently open. It will probably have priorities that limit who can apply, where, and for what, and applications will have to be tailored closely to the criteria.

It seems unlikely the proposed consortium would apply to one of those, as the chances of a scheme that's a good fit happening to be open at the right time are quite low. Trusts and foundations might be an option, as they're often less rigid than public funders. Most have less money available though.

Are there other potential funding sources? Governments don't usually hand over money outside of existing funding programmes, but there might be other options that I'm not aware of.

The reason it's piqued my interest is that we had to come at it from the opposite direction. We looked at the programmes available and our chances of success before we started designing a project; the trick of getting bigger ones off the ground was in finding a good compromise between what we wanted to achieve and what funders were interested in supporting.

 

I agree that there is a separate issue elsewhere where it seems some seem to talk about those who are more severe as if they have a different illness. It is particularly concerning when you hear some grim remarks like 'it can't be ME/CFS as it doesn't get that bad' etc.

I absolutely agree that I'd want reassurance people understand that it really is a continuous spectrum.

On the other hand I can see from my own experience and the fact that without having this those most severe are those most excluded and spoken for and least prioritised and heard that doing this is actually required. At the end of the day 'getting worse' is often what those who are milder warn about happenning to them, but it is only those who it has happenned to who can confirm and evidence that. And if the set-up of research and funding (because I imagine it is harder and more costly to design things to be careful and recruit those who are more severe and do things remotely etc) isn't designed to be accessible to the illest it can't include them, so that part of the spectrum stays invisible and unevidenced.

I'd be really worried that there is particular safeguards being taken however on protecting this group though. And the ethical side of things absolutely needs a group of highly expert patients working with a small trusted group of staff to be put together. There is so much room for harm here. And coercion, sometimes inadvertent, has been such a problem in general with ME/CFS, but would be at a desperate level for those who are severe and very severe.

The mere threat of being sent into maltreatment is immediately life-threatening and completely present, and yet currently those who would in normal illness protect from such absolutely believe those suggesting it. So how on earth can we put something together that is a charter making sure that researchers know and are aware of what they need to do transparently to be able to confirm their research was done under conditions where people did not feel any perceived threats (like I'd imagine those in clinics where reports might be sent off to GPs would be possible).

Those who themselves have experienced different levels of this can indeed I think be the only ones who can speak to this, and I'd say it feels very obvious when you are in it. In fact you don't notice you are now 'at a new level' other than by hindsight that you aren't coming out of that crash given it has been a year, or two, it is so 'the same thing'.

But there sometimes do seem to be other things that 'drop off' or deteriorate which might just be because as whatever ME/CFS is and the bits it involves (which might be different things getting worse at different rates or combining with other different weaknesses in their system in other peopel) as things get worse too. Things that can be helped by good clinical care. Things that might be clues.

That naughty phrase of turning no biomarker that is consistent across everyone bucketed into CFS to infer that noone with ME/CFS has anything flagging on blood tests as not normal is something that has always got to me from the bps. like as soon as they put a label on someone these facts disappeared in them.

And even if not these people are more ill, and currently excluded from being seen by anyone - so are cut out of the spectrum that way. And yet research can't possibly be inclusive if it is based around the cost-base and normal set-up of researchers or even other illnesses (which don't have the same sensory issues and 'envelope' - I can't help remark on the mindset of an HCP eg an OT who tries to get PEM and that the disability is this cage of 'this is how much energy you can use cumulatively' but is then flummoxed by the 'but you could walk up the stairs if you needed to'... although by that we mean probably by resting for several days in order to) unless it is focusing on being inclusive and accessible to the most ill then it won't be including them. It's like a friend sending a severe person an invite to their wedding. vs a relative designing what they can do with their wedding to make the important parts involve the severe person.

So I think it probably is necessary. I also hope that the PPI will be ensuring that it is very differently done in order that those who are severe are probably getting a voice and heard and not just having others speaking for them or interpreting them (it seems like DecodeME did this well, it really isn't as good a case with other things as those involved often think they are offering). Because again just leaving the odd place for someone severe or their carer without checking that carer actually could consult with the severe person, or being able to shift the timing of a meeting if that person had been ill for the fortnight and couldn't provide said input, and putting that one person on their own round a table of people with more power to out-energy and no experience of severe (whilst severe has experience of milder) isn't that - it's a stitch up.

For a start how is it appropriate that you've only one or two people to cover the entire workload of the whole world that the rest of the table have no lived experience of whatsoever. And that is incredibly hard to remember and then work out how to communicate to potentially credulous individuals? Who have exponentially smaller non-spare energy. Moderate being maybe 4 good hrs a day, but bottom end of severe 4 a month - except those are just 'better ones' that people time for must-do like appointments, eating, teeth. So why aren't people backed up by being able to be a team of 20 to answer the bigger workload of question, given they'll have more symptoms, impact and experience to report on anyway? And because they have far less control of when they will have anything spare so need a pool of people anyway. But also it is the feeling of being outnumbered given the experiences they are going to need to communicate.

What methods might work for the rest as more convenient can exclude those severe. And who wants to be the one person vs a whole table of people who are all stronger and can war of attrition so if the conversation keeps going it's no issue to them, and they can speak louder for longer etc. People might want to get something done faster rather than making sure it is right and includes people being able to contribute on their best days. Where there is disagreement noone is yielding to it being because the other person perhaps hasn't had the experience yet so actually isn't qualified to be sure x doesn't happen or isn't a problem.

The experience of being more severe is sometimes not even sought to be believe by other pwme who are milder (that seems to be a common assumption both laypersons and pwme have that 'because we all have the same thing'), ie the disbelief can often be the same or the source of where they have differences in experience being misattributed eg so disagreeing rather than seeking to understand if they don't get something said 'because it doesn't fit their experience', or thinking because someone whose illness isn't invisible and is more extreme is now more obviously badly treated by others can't be true because those said others have been perfectly nice to the milder person.

 

Agree, this is a really important point. People engage because they care. That care sometimes comes out in different ways. There’s good advice for us all here.

I’m not sure exactly what the situation is now with the current structures but as I understand it in the past regions (so trusts and foundations) often used to work with particular institutions. There were formal links between them and particular medical schools or universities but also informal ones. And I’m sure there’ll be at least a hangover from this. There can be systems and processes but if people know particularly people can do something they favour them. We all do it. Even on here we talk of favouring people and teams we know and trust.

It’s a good point and so very common. Fitting a proposal to what those with the purse strings are looking for is common in all sectors I think. And I guess an argument for having as ‘light’ a process as possible if we want as broad a range of potential things investigated. Or to be open to what may happen in the future.

 

Agree. But equally (as I think I said before) we need to prepare, to ensure we are ready to do trials when we have the mechanisms. It is possible to do some things in parallel. If we only think about these things after we have the answers we will face potentially needless and long delays.

I think they’re singled out because we have seen severe people regularly not included in research. This has been discussed frequently on these forums. There are specific challenges and we need to address them.

That’s my take/interpretation of a couple of areas anyway. There’s lots of good points made here. Maybe some of the issue is the words or phrases used. Perhaps a case of the wording allowing different interpretations or working to different goals or people, I’m not sure. But getting consensus from groups of people/committees is very hard and working with big organisations often ends with this sort of language doesn’t it?

 

I am not sure that any preparation is needed other than having patient cohorts ready under clinical care - which is the one thing absent from the proposal.

When I suddenly wanted to do a trial, having been working in the lab, there was nothing needed to be done other than get hold of the drug.

I am sceptical about setting up all sorts of resources in lab terms. Expertise in science is all around us and there is free access, unlike in business. If access to expertise on cell sorting is needed there are plenty of people with that expertise to go and talk to. Knowledge from research doesn't belong to anyone. It is shared openly. This is why I do not really follow the need for a 'consortium'. We are not talking about intellectual property, or at least we shouldn't be.

At one point I suddenly wanted to have access to expertise on the molecules VCAM-1 and CD55. I had no idea in advance that these would be the ones of interest. So I went and talked to people who knew about them. I didn't have to find £1M a year to support their labs.

 

Thanks @Jonathan Edwards that’s really useful insight. And yes I meant all the surrounding supporting stuff rather than lab resources. I’m coming at this in a sense of, the people and processes and all that side of things are hard and time consuming so why not get prepared there. We want to have patients ready and able to participate in a safe and supported way. Maybe I’ve been assuming this would be a new thing rather than just under clinical care as clinical care seems like such a challenge! Putting it as you do makes a lot of sense.

 

«Behaviour» was intended to mean how PEM behaves, not how the patients behave. It might have been a mixup in translation on my part.

 

I wonder if we can flip this around from thinking about what structures need to be built. So here’s my question

What obstacles need to be removed to enable high quality research into ME/CFS in the UK?

Or even if we wanted to sell it to politicians..
What obstacles need to be removed to enable the UK to be a world leader in ME/CFS research?

I’m thinking along the lines of, we need to

• remove negative perceptions of ME/CFS as a viable research career
• remove barriers for patients, particularly severely affected, to take part in research
• remove challenges in getting a diagnosis to increase potential participant pool
• remove stigma within medical community which prevent patients from coming forward or being supported in any research or trials
• remove the problem within the NIHRC/MRC (which I don’t fully understand, if someone can explain that would be useful)

Would a few points along these lines this help communicate our asks to those that need to hear?

 

the problem there is people in power making assumptions, based on overwhelming prejudice to female patients.
I concur regarding Stephen Holgate. I’ve also not seen explanation of why Stephen Holgate chose To do a JLA PSP for his field asthma, immediately, as became available in 2004 and yet for pwME. he had been leading the MRC expert groups on ME/CFS since 2007, it wasn’t offered until 2020.

 

Other than the access to patients part - the design shouldn’t take long to figure out from scratch.

Ideally, they would join here and we could hash out a design in a month or two tops.

And I’m not sure there is much else that can be prepared for - because we wouldn’t know what we would be testing!

Yes, but most of them are about how to include the severe+ in research, are they not? Do we need a «hub» for that?

Yes, which is why it might have been predictable that this would have happened.

We saw the same thing with a consensus statement about LC recently. The problem is that when you need consensus - you end up including opinions that are less «right» because it’s difficult to get people to change their minds. So everyone pleases everyone, and it becomes so watered down that it’s difficult to figure out what they have actually agreed upon.