The Netherlands - €28.5 million ME/CFS research program - ZonMW funding awards announced April 2023

[Solstice]

I think this is a central question. Lifelines has previously published on CFS but this was based on self-report which is probably not very reliable. I would assume that the funding allocated by ZonMW was meant to do a full clinical examination on these patients to have more reliable ME/CFS diagnoses.

If not that is not the case, than this might be a bigger problem than having Rosmalen as the project leader. The studies themselves sound promising but if the samples these researchers get are only self-reported CFS than the analyses might not be reliable.

The description is not very clear about this. It reads: "In 2018, 2,500 Lifelines participants met CDC criteria for ME/CFS. Since then, at least another 400 people have developed ME/CFS within the Lifelines cohort. Among these participants, in addition to the CDC, the IOM, ICC and CCC criteria sets will be mapped, and then related to various biomedical mechanisms in subprojects."

It's the two points we should be hammering home really. Funding Rosmalen is a slap in the face of ME-patients. Selecting people based on fatigue-questionnaires is a recepy for failure. I lined that out in my mail, but I do think every additional mail sent, especially from big collectives puts extra pressure on ZonMW and makes it clear that there will be heavy scrutiny not just from the Netherlands. So I'd consider that a good thing, circling back to a question @Hutan previously asked.

I'd like this sort of international collaboration of patients, ME-friendly researchers and physicians, organizations and journo's to be the norm. As it does influence us all. I think a lot of people abroad held their breath when NICE was delaying their guidelines to be published and a lot of people internationally have written in.

As @Arvo pointed out, if Rosmalen conjures up findings based on faulty cohort-selection it will prolong our struggle everywhere. Just as the situation in Scandinavia atm is probably problematic for us all. On top of that, 4.4 million is a lot of money and if properly spent a lot of good could be done with it. So I'm all for everyone that feels compelled to chime in to actually do so.

I don't know of the ME Den Haag team still exists, maybe @Grigor or @Arvo knows if things could be coordinated with people in NL.

 

[Arvo]

One thing that concerned me is whether they propose to gather objective data i.e. re psychological interventions?

Not at the moment, but my worry is that there will be psychological/psychosomatic/functional disorder studies done by ME/CFS Lines in a next phase, during the use of, or after they have used, the current ZonMw funds to get set up. The ZonMw text of Rosmalen's project speaks of training researchers and building a "multidiscliplinary research structure", while it remarkably makes no commitment whatsoever to further biomedical research beyond the first 4 studies.

One of Rosmalen's current studies is looking at "the predictors and consequences of receiving a diagnostic label" of CFS, using the Lifelines CFS cohort that will be the ME/CFS Lines group.
And she's for example also looking at the heredity of "internalizing and functional disorders", which personally gives me the heebie-jeebies.

CBT industry research is a two-step:
1. produce papers claiming ME patients have lots of depression/are somatising/have beliefs about their illnes/are too focused on their illness.... whatever is needed to claim their illness has a strong and significant psychiatric influence and that therefore psychiatric intervention is justifyable
2. produce the intervention papers.

At this point (I'm way more at home in the UK situation in the last century than the current one in my own country) it looks to me like Rosmalen covers step one, while Knoop covers step two.

if the intention is to fund psychological research then make sure it's objectively assessed - the objective evidence so far indicates that these interventions don't work

That would be a next line, if the grant isn't retracted or changes made, and this turns up, but I'm not sure if "making sure" can or will happen effectively, even when patients try.

These guys have a lot of room for their actions: Knoop for example refused to publish his research protocol for ReCoVer (I believe he has done later?), and you see that Rosmalen has the audacity to present herself as an ME/CFS biomedical champion while simultaneously running a study where the Lifelines CFS cohort is presented as functional somatic symptoms.

 

[Andy]

Personally I think I could live with including people who have fatigue but don't meet all of the criteria for ME/CFS --- e.g. I think PEM is based on a questionnaire?

You perhaps could; the vast majority of the ME/CFS patient community couldn't, and many have had to spend a lot of energy and time arguing against this very idea. The fact that you seem to consider PEM optional because it is 'based on a questionnaire' is staggering to me.

 

[Trish]

Personally I think I could live with including people who have fatigue but don't meet all of the criteria for ME/CFS --- e.g. I think PEM is based on a questionnaire? Obviously there are limits e.g. where fatigue is attributable to another condition.

Then we have a very different view of ME/CFS and the whole point of research needing to have a well defined cohort. Otherwise how can anyone interpret the results?
Can you imagine migraine researchers including anyone with any type of headache, or Parkinsons' Disease researcher including anyone with any type of tremor, or Dementia research including anyone who self reports as rather forgetful.
I'm sorry, but your comment is ridiculous.

 

[Andy]

This situation is starting to look more and more like the one we previously had in the UK with MEGA (the forerunner to what turned into DecodeME). While MEGA had elements that were worthy of support, principally a proposed GWAS, it also had the issues that Esther Crawley was project lead, and long before the GWAS would happen she would be in charge of gathering a cohort together that she would then be asking various questionnaires of. The concern was that even if the GWAS did go ahead, there would be a stream of publications on how the questionnaire responses from the MEGA cohort all indicated that we just needed some CBT due to our anxieties and depression.

Fortunately MEGA hadn't secured funding, so after it became clear that there was significant UK patient objections to it, changes were made which eventually led to DecodeME. With the Rosmalen situation I can see a big challenge is that she has been awarded the funding already.

 

[Arvo]

PEM has been the core feature as part of expert descriptions (of those with actual ample clinical experience) since the 80s, for UK examples see here, for the US see Johnson's "Osler's web", where she describes it is accepted as a cardinal feature by prominent experts since the very early 90s (or even earlier, I'd have to check).

"fatigue" as in "tiredness" (instead of muscle fatiguability) became dominant due to a bunch of US officials (CDC/NIH)- who didn't actually believe that ME was a disease, and who mocked the patients behind their backs (that they were often women played a big role in that), regarding them as neurotic (neurasthenic, hysteric)- and the UK psychiatry efforts, who stuffed ME into a neurasthenia/hysteria framework -which got absorbed by The Netherlands.

PEM is the cardinal feature of ME that should be part of a small group of other core symptoms, like e.g. Ramsay's diagnostic triad PEM+dysautomnia+cognitive dysfunction. ME/CFS research criteria have to have it.
(And it needs to be asked after properly, not some weak "do you have symptoms after exertion" because everyone will say yes to that - think tiredness or muscle aches after a long walk/sports, it's not the same as "exertion makes me very sick".)

 

[Solstice]

This situation is starting to look more and more like the one we previously had in the UK with MEGA (the forerunner to what turned into DecodeME). While MEGA had elements that were worthy of support, principally a proposed GWAS, it also had the issues that Esther Crawley was project lead, and long before the GWAS would happen she would be in charge of gathering a cohort together that she would then be asking various questionnaires of. The concern was that even if the GWAS did go ahead, there would be a stream of publications on how the questionnaire responses from the MEGA cohort all indicated that we just needed some CBT due to our anxieties and depression.

Fortunately MEGA hadn't secured funding, so after it became clear that there was significant UK patient objections to it, changes were made which eventually led to DecodeME. With the Rosmalen situation I can see a big challenge is that she has been awarded the funding already.

It all seems pretty deliberately done. I don't think they knew this particular stream of funding would become available when they started to identify fatigue patients in the Lifelines-project but it did all come together brilliantly for them. Now they've got a lot of scope for fuckery with a nice big set of patients and a big chunk of money. Otherwise it would've probably been a smaller chunk of money but the same would still happen.

Ignoring the input from patients in awarding this project I consider to be sabotage. Sabotage of their own commitment to patients, awarding the project is sabotaging their commitment to biomedical research into ME. Now that the decision has been made they'll probably try to ride out the wave of negativity, but they might be sorely mistaken in that department. I think too many people have woken up to the fact they have been had by the BPS-crew, not just patients. Patients with other diseases also have a stake in this and are getting more aware of how one situation affects the other, in general.

 

[FMMM1]

Then we have a very different view of ME/CFS and the whole point of research needing to have a well defined cohort. Otherwise how can anyone interpret the results?
Can you imagine migraine researchers including anyone with any type of headache, or Parkinsons' Disease researcher including anyone with any type of tremor, or Dementia research including anyone who self reports as rather forgetful.
I'm sorry, but your comment is ridiculous.

My family member has had one experienced neurologist indicate "ME" as a potential diagnosis --- as for other "diagnosis" ---
As you know, it isn't like e.g. diabetes --- high blood sugar ---
If anyone has been diagnosed (with a high degree of confidence) with a disease which could be responsible for their disabling fatigue then they shouldn't, in my view, be included in an ME/CFS research cohort. I'm personally concerned about excluding people who e.g. are labelled as having pre-existing "anxiety" or "depression" i.e. a potential psychological cause of their disabling fatigue --- although I accept that it may be reasonable to do so.

Dementia seems to be an excellent analogy --- GWAS studies initially found one gene [APOE gene?] and it took larger studies to find further genes --- although they all seem to be immune related(?). So maybe dementia has different immune related pathologies --- same outcome. OK clean the ME/CFS data, by selecting/excluding participants -- as much as you can --- but that seems difficult -- at least at this stage. Dementia offers a +ve - OK it's taken larger studies but target genes have been identified -- therefore it's doable in ME/CFS.

 

[Trish]

I sympathise with people who have disabling fatigue that is not ME and for which another cause hasn't been identified. I know someone in that position - they are unable to do a full time job, but definitely don't get PEM, so they don't have ME. I would support research about people in that position, but they should not be mixed in with ME. That would not be helpful to either group.

 

[Wyva]

I don't want to exclude the possibility that the disease is more of a spectrum and that there may be people who for some reason don't have PEM but still suffer from this disease. However: the criteria where PEM is not required to have are simply too wide or inclusive and for example people with mental disorders like depression may get included too. Not to mention that there seem to be a not insignificant number of people who eventually turn out to suffer from some other, undiagnosed or possibly rare disease that causes debilitating fatigue. This happens even with PEM, btw, but the wider the criteria, the more likely it is to happen. So the point is that the narrower criteria with compulsory PEM are necessary in order to make it as sure as possible that the studies are about ME/CFS indeed. Even if there may be people suffering from this disease but without PEM. This is even in their interest because it makes finding a biomarker easier (and then the biomarker will likely show who has the disease with or without PEM).

 

[Arvo]

Aside from letters from individuals to ZonMW and the Ministry of Health, are there other things that can be done by the international ME/CFS community to try to stop this? Would a letter from the World ME Alliance, with international patient groups as signatories be of any use?

I do think every additional mail sent, especially from big collectives puts extra pressure on ZonMW and makes it clear that there will be heavy scrutiny not just from the Netherlands. So I'd consider that a good thing, circling back to a question @Hutan previously asked.

I'd like this sort of international collaboration of patients, ME-friendly researchers and physicians, organizations and journo's to be the norm. As it does influence us all. I think a lot of people abroad held their breath when NICE was delaying their guidelines to be published and a lot of people internationally have written in.

As @Arvo pointed out, if Rosmalen conjures up findings based on faulty cohort-selection it will prolong our struggle everywhere.

I agree with @Solstice.

I think the ME/CVS Vereniging and @Lou Corsius would probably be good contact points to discuss coordination and content, as they have been closely involved in the process to set up the ZonMw Research program and know it well. (Of course there are others as well.)

Note that the ME/CVS Vereniging has a FOI request running regarding the grant approval, so I would at least ask if it's best to await the results of that before a response. (Or if it's best to send one now, strike the iron while it's hot to move ZonMw to do the right thing as there's international scrutiny, and optionally have a follow-up if the outcome of the FOI warrants it.)

 

[Arvo]

I sympathise with people who have disabling fatigue that is not ME and for which another cause hasn't been identified.

Me too! It's a bad situation for all the patients who have been thrown in the chronic fatigue bin, including those with disabling fatigue without PEM. It's not just ME patients whose medical research has been stalled by this for decades. And we should support eachother, I don't want patients with disabling fatigue without PEM to be theoretically left behind in the psychosomatic fatigue bin - their illness mechanism could be related or could be completely different, it doesn't matter, as long as it's figured out what is actually happening.

 

[Solstice]

Me too! It's a bad situation for all the patients who have been thrown in the chronic fatigue bin, including those with disabling fatigue without PEM. It's not just ME patients whose medical research has been stalled by this for decades. And we should support eachother, I don't want patients with disabling fatigue without PEM to be theoretically left behind in the psychosomatic fatigue bin - their illness mechanism could be related or could be completely different, it doesn't matter, as long as it's figured out what is actually happening.

Should probably be some sort of alliance against bad research or for good research.

 

[Solstice]

I agree with @Solstice.

I think the ME/CVS Vereniging and @Lou Corsius would probably be good contact points to discuss coordination and content, as they have been closely involved in the process to set up the ZonMw Research program and know it well. (Of course there are others as well.)

Note that the ME/CVS Vereniging has a FOI request running regarding the grant approval, so I would at least ask if it's best to await the results of that before a response. (Or if it's best to send one now, strike the iron while it's hot to move ZonMw to do the right thing as there's international scrutiny, and optionally have a follow-up if the outcome of the FOI warrants it.)

Hadn't thought about Lou actually posting here, but he'd be the guy to contact I suppose.

 

[FMMM1]

I know someone in that position - they are unable to do a full time job, but definitely don't get PEM, so they don't have ME.

I wonder how accurately PEM can be diagnosed ---give 100 doctors the same patients and see who gets the PEM label. I think my family member would be classified as having PEM by the way.

This is even in their interest because it makes finding a biomarker easier (and then the biomarker will likely show who has the disease with or without PEM).

Yea there's a bit of me that thinks the narrower cohorts (include PEM, exclude anxiety or depression or whatever) can be used to e.g. find a biomarker and then the wider group can be tested for that.

 

[FMMM1]

CBT industry research is a two-step:
1. produce papers claiming ME patients have lots of depression/are somatising/have beliefs about their illnes/are too focused on their illness.... whatever is needed to claim their illness has a strong and significant psychiatric influence and that therefore psychiatric intervention is justifyable
2. produce the intervention papers.

At this point (I'm way more at home in the UK situation in the last century than the current one in my own country) it looks to me like Rosmalen covers step one, while Knoop covers step two.

Yea, recall Jonathan asking whether these folks deliver anything a caring health professional wouldn't do i.e. alongside their professional bit --- and my view is there's no evidence they do. E.g. the home help might help with your food and do a whole lot of other life enhancing things --- versus pinning the blame on you.
I think it's clear from the last point what my views are and my hopes of meaningful progress are directed towards GWAS and any biomedical clues we can research.
I simply don't have the lived experience you guys have.
I appreciate the tone of the conversation here, it's an opportunity to discuss these things --- perhaps I'll even learn but even I'm not that confident of that ----

These guys have a lot of room for their actions: Knoop for example refused to publish his research protocol for ReCoVer (I believe he has done later?), and you see that Rosmalen has the audacity to present herself as an ME/CFS biomedical champion while simultaneously running a study where the Lifelines CFS cohort is presented as functional somatic symptoms.

Yea so far my views are that these folks are most useful when they facilitate things like GWAS --- if they insist on doing research then please treat those who are ill, and the public funders, with respect --- measure objectively --- don't present a pile of (subjective - EDIT /"very low quality evidence") useless crap and then defend it. Some of this is probably inappropriate.

 

[Grigor]

This situation is starting to look more and more like the one we previously had in the UK with MEGA (the forerunner to what turned into DecodeME). While MEGA had elements that were worthy of support, principally a proposed GWAS, it also had the issues that Esther Crawley was project lead, and long before the GWAS would happen she would be in charge of gathering a cohort together that she would then be asking various questionnaires of. The concern was that even if the GWAS did go ahead, there would be a stream of publications on how the questionnaire responses from the MEGA cohort all indicated that we just needed some CBT due to our anxieties and depression.

Fortunately MEGA hadn't secured funding, so after it became clear that there was significant UK patient objections to it, changes were made which eventually led to DecodeME. With the Rosmalen situation I can see a big challenge is that she has been awarded the funding already.

Sums it up pretty well indeed. I wish we could get a better/more receptive project leader. She's not as bad as Crawley, but there are definitely some similarities. Or let me rephrase that and say that she's more nuanced which makes her more slippery.

 

[dave30th]

Or let me rephrase that and say that she's more nuanced which makes her more slippery.

This seems like the pertinent point.

 

[Sean]

Sorry if this is annoying, ignore if wanted of course,

This kind of stuff is exactly what S4ME is for. Go for it. You are doing fine.

So... the group from Lifelines presented as a solid ME/CFS research cohort:

• is based on self-report
• is diagnosed as having "CFS" by the biobank itself (based on the symptom of "fatigue", using Fukuda & -optionally?-a psychiatric questionnaire), not by a physician and/or in person.
• includes patients undiagnosed by a physican
• includes patients that didn't initially self-report as having ME/CFS or CFS (and note that "CFS" in The Netherlands is often understood as "being chronic fatigued", it's broad), it was Lifelines who added them to the group
• is considered to be having a collection of functional somatic symptoms that are bundled as the functional disorder CFS by the Lifelines scientific advisor. (And is collected as such.)

What a mess.

 

[Sean]

One of the most powerful tools we have is making sure the BPS club (and their clients and funders) know that very close and public attention, including on the formal record, is increasingly being paid to their choices and actions, and that patients in particular will not be silenced about shabby science and poor ethics. We are in this for the long haul, because we have no choice.

I agree with trying to stop Rosmalen's project as the first step. Failing that, then demanding at the very least she be required to use appropriate objective outcome measures, and as primary measures, not secondary.

Also agree with the comments about why PEM is essential to helping unravel all this. Being able to (reliably and safely) detect, quantify, and characterise PEM would bring sorely needed clarity and progress, including for those who do not have PEM. It would be a win/win for all patients.

–––––––

FND, MUS, PPS, whatever, is a classic example of what happens when Occam's Razor is ignored, and unnecessary elements are introduced into a causal model. The (current) BPS model is stuffed full of them.