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

As per my personal message to you DecodeME are in contact with the lead on the Dutch GWAS study [Dr Cindy-Boer]*

*"[Sonya Chowdhury - Action for ME] Thanks Francis. We are in discussion with Cindy [dr Boer] and met before their application and are due to meet imminently so will have a clearer understanding of how this might fit afterwards and happy to report back" https://www.researchgate.net/profile/Cindy-Boer

Well hope the patient community are responding to highlighting the need to ensure that the Dutch GWAS selection criteria mirror the DecodeME criteria i.e. so that the studies can be combined.

EDIT - Speculation but maybe the researcher wants to do the right thing and would appreciate some "assistance/backup" from the patient community - so ask for the criteria to be aligned formally/publicly! @Arvo

 

O yes, absolutely. I was talking about the GWAS study alone.

I also find it strange that a serious biomedical researcher would work with Rosmalen as project leader. Are they fine with the project leader calling the serious biomedical illness they're studying a "maladaptive response to physical complaints"? Or with being used to further their project leader's psychosomatic agenda? Or are they unaware?

 

Yes, this looks good. dr Boer also has an interesting publication history in general (osteoarthritis, gut microbiome, genes), and there's no psychosomatic claptrappery.

I do hope that if there is going to be a collaboration that here will be solid guarantees that there will be no psychosomatic angle, an appropriate study group selection that is not just using the Lifelines participants, and if necessary taking a stand against disableist/psychosomatic framing within the ME/CFS Lines project. Assuming dr Boer is wonderful (she might very well be) then I still don't trust Rosmalen. And I'm rather done with having to protest things after the fact.

 

It's also potentially 'entryism' https://en.wikipedia.org/wiki/Entryism particularly when you think about the tendency of those from BPS background to focus on climbing their way up through the committee and admin positions and collecting power.

but I know what you are getting at and I struggle for the specific term, I've probably used 'wrapping oneself in someone else's flag of goodness' type thing. Basically she is trying to hide her agenda under the pretence that it wouldn't have been accepted by x (who is good and real) if there wasn't something to it. Such organisations/people who might think teaming up can't cause that much harm etc might want to think about the information-sharing and data-sharing and strategy sharing type inside info these people would get from joining up with them - even if they don't think it is much they are giving away, because nice normal people wouldn't be using things in such ways due to the more collaborative or 'in same vein' nature of others they might work with in the same field.

 

Perhaps DecodeME would consider publishing what they consider to be the core criteria for any project to provide data that can usefully be combined with their own. This would provide clarity for other researchers and reassurance for patients.

Apologies if I posted this before - a little PEM deja vu this morning.

 

I looked around a bit on dr Boer's Twitter page.

Spoiler: Tweets and quotes from articles dr Boer recommends about her study.

Here is her reply to someone posting about her study.

On 5th of May: "I will work together with DecodeME."

https://twitter.com/user/status/1654409342811078657


In another tweet, she refers to this article as "a short summary of our new research project into ME/CFS" (article GT english)

Some quotes:
"Virtually nothing is known about the biological processes in the body that cause ME/CFS"
"Although many patients have the following symptoms in common: pain, sensitivity to light and sound, concentration and memory problems and severe fatigue."[Note, no PEM mentioned!]
"ME/CFS is also called an exclusion diagnosis: you get that diagnosis when many other conditions have been ruled out. That makes ME/CFS a nasty disease." [Erm, that's not what makes ME/CFS a nasty disease... And in The Netherlands there is no ruling out of "many other conditions" as that is advised against.]
"The ME/CFS Lines Consortium uses data from a population study with the health data of more than 160,000 Dutch people from the north of the country. 'In that Lifelines study, many measurements have already been made in people with ME/CFS, even when they were not yet ill,' says Cindy Boer, principal investigator of the 'ME/CFS & genetics: research into the biological cause' subproject."

In reply to her tweeting it, someone asks: "Hopefully, a thorough selection of patients will precede, using CCC or ICC criteria, including PEM as a symptom. Based on Fukuda and without PEM (Lifelines), another over-inclusive mess is being investigated."

Dr. Boer answers: "Certainly! this is also stated at the ME/CFS lines consortium:
"In addition to the CDC, the IOM, ICC and CCC criteria sets will also be mapped out for these participants, after which they will be related to various biomedical mechanisms in sub-projects" and refers to the ZonMw page.
But, as stated earlier, this is opaque wording instead of a clear statement to have the GWAS participants physician diagnosed and fitting ICC or CCC (or IOM) criteria. It looks like they're using Lifelines patients and will see how all four criteria sets apply to the studied group after the study is done. So the GWAS will be done on a mixed bag of self-reported patients with chronic fatigue, with only a portion of them having ME/CFS (with PEM as a needed feature).

https://twitter.com/user/status/1650808980044750848


With the text "A nice/beautiful descriptio of the ME/CFS Lines consortium", she also shares this article (GT eng) by the ME/CVS Stichting, the organisation that's collaborating with ME/CFS lines while all other patient orgs are shut out, and in doing so helps ME/CFS Lines to hold up the mirage that they collaborate with the patient community.

Some quotes:
" According to previous measurements, approximately 2500 participants meet the ME/CFS criteria, but that data has not been further investigated. A wealth of data awaits here. Pre-ME/CFS information is also available for about 400 of them. Lifelines is the only cohort worldwide that has this type of data. It offers a unique opportunity to research the cause of ME/CFS."

"MeCfs Lines is building a separate cohort with biobank² to conduct further research into these 2500 participants. 800 patients are being analyzed in extra depth in the field of systems biology. Then you should think of “big data” research into proteins, into products from the metabolism in cells and from the immune system, and into the microbiome³ that is present in the gastrointestinal tract. The research takes place in the sub-projects. A separate project focuses on the genetics in ME/CFS. An international partnership is being set up for this purpose.

Comparison of the patient data with the other consortium becomes possible. The MeCfs Lines biobank is being harmonized with that of NMCB, taking much of it from the UK ME/CFS Biobank. Both consortia use the extensive DePaul questionnaire, so that patients can be properly compared and classified on the basis of the four well-known criteria sets Fukuda/CDC, IOM, CCC and ICC. Where possible, there will also be cooperation with NMCB at project level."

https://twitter.com/user/status/1651136597964861441

So, circumstantially, this already does not look good. She doesn't seem to understand ME/CFS very well yet, does not recognise PEM as a cardinal feature -or even at all- and refers to the same opaque language that indicates patients will be pulled from Lifelines without filter and then something something IOM, CCC ànd CDC after the studies are done.

At this point I don't think she's untrustworthy, it looks to me like she just isn't very knowledgeable about ME (yet) -what it is, what it's not, and what its criteria should be per international standards- so doesn't see the issues with the Lifelines and Rosmalen, who tell her they have an ME/CFS collection ready to use. Of course this unfamiliarity with ME and the surrounding issues still is bad. (And I can be mistaken in her intentions of course.)

I am also surprised by her 5th of May message that the collaboration with DecodeME is a done deal.

But there's more....

 

And I'm making this a follow-up post to post #206 as this needs separate mention. The ME/CVS Stichting posted a link to an attachment from Judith Rosmalen's grant request to ZonMw.

First of all, this shows that the ME/CVS Stichting has access to that, and afaik the other patient orgs haven't? (The grant requests were part of the FOI request sent to ZonMw by ME/CVS Vereniging on april the 8th.)

But more importantly, it looks like it unequivocally states the use of CDC '94 criteria for the GWAS study. (Which is not according to the ME/CFS biomedical research plan, which ZonMw blacked out of their FOI request reply.) No mention on having used self-report.


Table 2: In the row "genetics", sample: "All participants fulfilling CDC criteria in wave 2 (2,500 cases) or wave 3 (currently 400 extra); genetic data already available in N=1,400 cases and 48,000 controls; Power considerations: "Genetic data will be collected in all participants fulfilling the CDC criteria; genetic analyses will be performed on several ME/CFS cohorts combined."


You can also see the claim ME/CFS Lines makes that they have "2,500 individuals meeting the diagnostic criteria of ME/CFS" black on white. They don't of course. Apart from all the other problems, per the Biomedical Research Plan the international standard has PEM as a cardinal feature.

You can also see under "power considerations" that Rosmalen has solved her problem of the Lifelines CFS data (that she has advised the collection criteria for) being crap and not aligned with the current international standard for ME/CFS by simply deciding CDC'94 as an equal among 4: "ME/CFS Lines be the first population-based patient cohort in which the four widely used diagnostic criteria sets and their overlap will be assessed." I'll look it up, but I'm pretty sure that this is not in line with the program or its aims, and it states that you have to choose criteria (indicating it is between ICC, CCC and possibly IOM) and motivate your choice.

Anyway, there are people here who can do much more with this than I can.

Included the PDF and a screenshot so you can see the header online that this is indeed an attachment from Rosmalen's grant request. (Tagging @Andy and @dave30th as I think you'll want this doc.)

 

"I am also surprised by her 5th of May message that the collaboration with DecodeME is a done deal."
Perhaps welcome Dr. Boer's message - publicly - and ask for more details e.g. how many participants are there in the Dutch GWAS study and will they all meet the criteria used in the DecodeME study. The lifelines cohort is already pretty small i.e. 2.5K (correct? - DecodeME is 25K equivalent to approx 6.5K in Holland) so if e.g. only a portion met DecodeME criteria then the Dutch study won't add much --- pity.

I'd PUBLICLY (VIA SOCIAL MEDIA ETC.) highlight your concerns to the:

• "sponsor" Government Department i.e. who provided the funding. Their ultimately responsible for allocating public funding;
• scientists - Dr. Boer et al. If Dr. Boer was my colleague/child --- then I'd be concerned that checking out their CV would highlight a highly contentious flawed study --- would you want that on your CV? Also, consider that they might want to do the right thing for people with ME - they might just need some public assistance from the patient community.

 

That message is in English so I'd say it's open for anyone to chime in. I won't on this particular message because of reasons.

 

Anyone got a link?

EDIT - found it* & replied - suggest others do the same --- think there are only two replies!
"Criteria used in the DecodeME available online -Google - are you using the same criteria i.e. so that the two studies can be combined?
In Dementia they needed to combine GWAS studies to gather sufficient data to find genes.
How many participants will meet DecodeME criteria?"

*https://twitter.com/user/status/1654409342811078657

 

Problem is e.g. in Dementia they needed large [GWAS] studies to find the second & third gene. They did that by combining several GWAS studies -- probably multiple times the size of DecodeME. So we need any future GWAS studies to use the DecodeME criteria.
Great to see DecodeME team are in contact with those running the Dutch study --- hopefully the Dutch data will be collected using the same criteria.

 

Yea I fully agree i.e. DecodeME won't use data that isn't collected in an appropriate/compatible way (criteria).

So the real risk is a useless Dutch (GWAS) study --- which appears to still be a risk despite comforting words from the researcher - Cindy G. Boer, PhD - "If you want, I do not mind walking you though details of my project - For example, I will work together with DecodeME, - or answering questions about it. send me a message."

 

Tweets --- too short --
I responded to Cindy G. Boer, PhD i.e. encouraging her to provide usable data & trying to highlight that her/Dutch study might stand out for being unusable!
"
Hi [Cindy Boer] as per my response to Siebe.
@PatientPersists
NIH etc. are in discussions which will likely lead to further GWAS studies i.e. which will be combined [DecodeME criteria]. Patients need usable data from "your" project i.e. can be combined DecodeME.
"Your" project - usable data?"

I'd also responded to a Tweet by
"Siebe.
@PatientPersists"
who seems to be part of long covid community --- & who responded to Cindy Boer's offer to explain their methodology. Good to see that
interest from long covid community.
I couldn't find my tweet though!

 

I'm sorry, I don't follow why I would want this document?

Mod note: this response was prompted by a suggestion that S4ME as a whole responds to the issue (since deleted due to some confusion about how to contact S4ME administration)
If you would like the social media accounts to help in this situation then I would recommend posting any blogs or other publicly shared communications that point out the flaws in what has occured in this thread. It would then be highly likely that they would make it into the News in Brief posts, which I then base the forum's ME Awareness Hour posts on.

An additional possibility is the wording of an open letter could be proposed to the forum's management team, with the idea that the eligible membership of the forum would be asked to vote on whether they support it or not. If it was supported in this way then it would represent an official forum document. An example of such a vote can be seen here, https://www.s4me.info/threads/letter-to-nice-concerning-the-gdg-committee.6618/, examples of previous forum open letters can be found in this sub-forum, https://www.s4me.info/forums/open-letters-and-replies.100/

 

I hope that in case the Dutch GWAS won't be transparent about it, then DecodeME will be open about the type of "collaboration" they are doing. I trust DecodeME to do the right thing (it seems like a knowledgeable and well set-up project), but I'm not sure if they would have noticed the pitfalls of even superficially working with a project that is based on Lifelines data, well-intentioned as it would be. For example, they will probably not have had access to the dutch ZonMw Research Program for ME/CFS and its requirements. And how clear would the ME/CFS Lines GWAS project, if they will use unfiltered Lifelines data, have been about their data being based on self-report, questionnaires, questionnaire "diagnosis" by Lifelines etc. that is bloated? The attachment in Rosmalen's grant request proudly states "Even in the current patient set, we have 2,500 individuals meeting the diagnostic criteria of ME/CFS", which just isn't true: how well would DecodeME have been able to check that?

Again a reminder that the dutch GWAS study needed international collaboration and alignment for the grant. If the ME/CFS Lines GWAS project is indeed using pure Lifelines material like it seems to do (based on ample sources), without proper clinical assessment and using well-motivated and proper criteria (as per the ME/CFS research program and scientific necessity), then I fear that DecodeME might have unwittingly given them validation.

(Also as a sub-project of ME/CFS Lines, the dutch GWAS is getting a maximum of 499,846 euros for a 48 month project, under a requirement of international collaboration and alignment. Any signed collaboration agreements with a third party had to be submitted within 2 months after the grant approval, and ZonMw could then still cancel the grant if they didn't approve of it. So I hope that if DecodeME signed a collaboration agreement, then they did so under strict conditions that can be made public.)

 

Because of post #39 I thought you were connected to DecodeME or another project that was considering collaboration with the Rosmalen-group:

reply

(one of these days I will learn how to do the quote-in-quote thing)

As this doc is marked on the ME/CVS Stichting page as an attachment from the ME/CFS Lines consortium grant request ("Judith Rosmalen Consortium aanvraag"), and it tables characteristics of its patient cohort and biobank, I though you'd be interested.

I've found it on the site of the ME/CVS Stichting, here (GT eng), when you click on "summary of it in tabular form".

I'm sorry if I was mistaken or unclear. (It would have been better worded as "I thought that you might be interested in this doc" - wonky brain.).

 

Cross-posted with Arvo's post immediately above.

In my opinion, way too much is being made of the word collaboration in this situation.

As we (DecodeME) are a project that is as open as possible, we are, and always have been, willing to share with whoever is interested:
our selection criteria, questionnaire and algorithm, with the proviso that our full criteria will only be publicly revealed at publication of our results, in order to avoid biasing our own recruitment,
the technical process that our samples went through as the ideal for potential comparisons of different sample sets is if they have been processed in the same way,
and once we have published our results, the full, anonymised data will be available to researchers who have ethics approval for their own project.

So our sole previous conversation, and any we might have in the future, will cover this. Emphasis in any conversation will obviously be put on the desirability of alignment of selection criteria to enable any future meta analyses, and as we have the larger data set it is by far the best idea if smaller data sets conform to the same selection criteria as ours. I don't want to speak for my fellow DecodeME management team members but I personally don't really see much scope or capacity for collaboration beyond sharing methods and criteria; DecodeME is funded for around another 15 months and we have got plenty to do already in that time.