Biomarkers for ME/CFS - discussion thread on the next steps for testing biomarkers, and why we need them

AknaMontes

AknaMontes

Senior Member (Voting Rights)
Posts moved from UK: DecodeME recruitment open (online questionnaire, postal spit kit), 12pm 12th Sept 2022

I think they need to scale up the decode project and collect blood samples, then run a set of tests to look for as many as possible of the potential biomarkers different researchers have announced. They could reduce the number of tests as they proceed by dropping the less successful ones, and the outcome could finally be - perhaps - a clearly established biomarker or panel. This makes more sense to me than the continuing process of very limited available funding dribbling out to support small studies that will never be replicated or scaled up. If MRC paid for some of it they would surely get a better ROI ? They would have blood test results to compare with the DNA and histories collected, researchers would finally have a way to gather homogeneous research subjects, and the patients would have biomarkers, both for clarity for their own healthcare and to try to help stop the abuse of children with ME being put in locked psych wards and false accusations of FII etc.
 
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AknaMontes said:
I think they need to scale up the decode project and collect blood samples, then run a set of tests to look for as many as possible of the potential biomarkers different researchers have announced. They could reduce the number of tests as they proceed by dropping the less successful ones, and the outcome could finally be - perhaps - a clearly established biomarker or panel. This makes more sense to me than the continuing process of very limited available funding dribbling out to support small studies that will never be replicated or scaled up. If MRC paid for some of it they would surely get a better ROI ? They would have blood test results to compare with the DNA and histories collected, researchers would finally have a way to gather homogeneous research subjects, and the patients would have biomarkers, both for clarity for their own healthcare and to try to help stop the abuse of children with ME being put in locked psych wards and false accusations of FII etc.
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There is an enormous amount of potential ME research and also a large number of small scale projects that remain un replicated and requiring follow up. However DecodeME is asking a specific question, are there any genetic patterns relating to ME? A successful conclusion to this study will then lead on to hopefully more targeted research of the type you discus, @AknaMontes, but that is then separate research beyond the current scope of DecodeME.
 
I hope enough shows up in the genetic data to justify very large future funding allocation for such next steps.[/QUOTE]

I'm pretty sure pwME are desperate enough to contribute to the cost of tests. For example, I gather Prusty's suggested biomarker tests will be available shortly in one of the private clinics in the UK. If people had somewhere to send their results data would accumulate over time rather than going just to individuals. I mean why are we not collecting that data already somewhere? Surely an AI can do most of the work analysing it? Why does it need millions in funding? People just get tests over time as and when we can afford them, using a few approved labs perhaps, and send in results which slowly stack up. Maybe we are making the research far more expensive and laborious than it needs to be? A crowdfund could speed the process up.
 
The trouble with individuals paying for tests that haven't been validated by replication studies is that you don't necessarily get useful data. Look at the XMRV mess, and the tests maverick UK doctor Sarah Myhill used that turned out not to replicate.
 
AknaMontes said:
I hope enough shows up in the genetic data to justify very large future funding allocation for such next steps.

I'm pretty sure pwME are desperate enough to contribute to the cost of tests. For example, I gather Prusty's suggested biomarker tests will be available shortly in one of the private clinics in the UK. If people had somewhere to send their results data would accumulate over time rather than going just to individuals. I mean why are we not collecting that data already somewhere? Surely an AI can do most of the work analysing it? Why does it need millions in funding? People just get tests over time as and when we can afford them, using a few approved labs perhaps, and send in results which slowly stack up. Maybe we are making the research far more expensive and laborious than it needs to be? A crowdfund could speed the process up.
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Setting up a biobank is important for sure but just logistically collecting serum is harder than collecting spit. It requires a phlebotomist to travel around collecting blood, and the blood needs processed the same day which requires basic lab things and a centrifuge to spin down the clot, and then a -80C freezer for long term storage. Moving samples around the country requires dry ice.

Replicating these biomarkers is also time in the wetlab doing thousands of ELISAs - which aren't hard to do to be fair (something like a covid LFT). Other biomarkers are of a different nature like miRNAs would need a different technique like a blot or probably a microarray.

Once you actually have the data you don't need an AI to analyze it. The data analysis isn't the hard part it's the collecting the right type of data that's difficult.
 
Trish said:
The trouble with individuals paying for tests that haven't been validated by replication studies is that you don't necessarily get useful data. Look at the XMRV mess, and the tests maverick UK doctor Sarah Myhill used that turned out not to replicate.
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And would potentially skew the participant demographic, with the attendant bias that might come with that, because only those able to afford the tests would be included.
 
AknaMontes said:
For example, I gather Prusty's suggested biomarker tests will be available shortly in one of the private clinics in the UK.
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I wouldnt waste my money...
Dr Charles Shepherd from the MEA on MEA facebook said:
The findings in this pre-print paper (meaning that the research has not yet been peer reviewed) have become the subject of widespread internet and twitter discussion
Some people are concluding that a diagnostic biomarker for ME/CFS has been found and will soon be available to use
This is not correct
There is a long journey between publishing interesting but rather complex preliminary findings like these in a small group of people with ME/CFS and getting these findings confirmed in much larger numbers of people with ME/CFS (and not being found in people with other conditions that can produce ME/CFS like symptoms) by other research groups before concluding that a diagnostic test that is both specific and sensitive to ME/CFS has been found
Given all the effort that is being put into finding a diagnostic biomarker by various research groups (including those using samples from the ME Biobank in London which is funded by the MEA Ramsay Resach Fund) it is possible that one will emerge
But in our current state of knowledge this is unlikely to occur this year
Dr Charles Shepherd
Hon Medical Adviser, MEA
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Barry said:
And would potentially skew the participant demographic, with the attendant bias that might come with that, because only those able to afford the tests would be included.
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What different characteristics would people with ME/CFS who had paid for a test have over those who did not? I could understand that possibly being an issue with a large population study but most ME/CFS studies use convenience samples and it's unclear to me what the different characteristics would be in a scenario like this.
 
JemPD said:
I wouldnt waste my money...
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I think people will be making their own minds up about the fibronectin tests, and what matters right now isn't whether or not people do have the tests but whether the results can be gathered centrally. It would seem sensible to ensure cost isn't a limiting factor for people who would like to have the test - a crowdfund to ensure everyone has access makes sense. But first we need a database for the collected results?
 
AknaMontes said:
I think people will be making their own minds up about the fibronectin tests, and what matters right now isn't whether or not people do have the tests but whether the results can be gathered centrally. It would seem sensible to ensure cost isn't a limiting factor for people who would like to have the test - a crowdfund to ensure everyone has access makes sense. But first we need a database for the collected results?
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And what if it turns out the test is flawed. Maybe everyone with chronic disease comes up positive, or it's related to inactivity or something. We have been down this road before.

Sure some people will have the test, but any results gathered centrally will include all sorts of confounders like people self diagnosed who don't have the disease, people with all sorts of comorbidities, etc. so any collated results will be pretty meaningless.

I don't think it would be ethical to ask people for money via crowdfunding to pay for people to have an unreplicated unvalidated test.
 
Barry said:
And would potentially skew the participant demographic, with the attendant bias that might come with that, because only those able to afford the tests would be included.
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At least 'maverick' doctor Sarah Myhill was trying to get something done, and her instinct on mitochondrial involvement was bang on. I'm a completely beginner as a science student, but surely history suggests that progress needs both mainstream people and methods AND people who think and work outside the box? Good point on economics which could influence results. But then how many studies have relied on patients being able to get to a hospital or surgery? And still do? Exclusion of those of us who are Severe is routine. There's not going to be any such thing as a perfect cohort of participants, maybe it just needs to be good enough for the degree of error possibly caused by selection factors to be outweighed by the clarity of results? I don't mind risking the cost of a blood test personally, but would rather be tested for a bunch of biomarkers and have a potentially useful database to which to send the results. That would motivate me to have the tests.
 
chillier said:
Setting up a biobank is important for sure but just logistically collecting serum is harder than collecting spit. The data analysis isn't the hard part it's the collecting the right type of data that's difficult.
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So what are the possible work arounds? It must be possible somehow. (Envisages a lab in an adapted ice cream van playing the panorama theme tune visiting all the major towns and cities...I was hearing yesterday of an ME researcher so utterly fed up with the barrage of obstructions to his university research by the psych activists he's set up a lab in his garage and is ploughing on regardless.) Does anyone remember those enormous science lab kits sent out by the Open University to their science students back in the seventies? Happy days. I think I've still got some of the bits somewhere. Of course it does need to be done in a credible way - a recognised lab, and properly collected samples. Many of us could get a blood draw done locally, sending a sample sounds complex. Has anyone made a list of all those published potential biomarkers to find the simplest to test first? And didn't someone say a couple of years ago that subtle signs of ME could be seen in regular blood tests? What happened to that? Can't recall where I heard it.
 
AknaMontes said:
At least 'maverick' doctor Sarah Myhill was trying to get something done, and her instinct on mitochondrial involvement was bang on. I'm a completely beginner as a science student, but surely history suggests that progress needs both mainstream people and methods AND people who think and work outside the box?
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These people are not 'thinking outside the box' @AknaMontes. Their ideas about mitochondria, autoimmunity, clotting, viral reactivation etc. are old stories from decades ago recycled by people who have no understanding of the complexity of the biology. These people are so deep down at the bottom of a an old box in the backyard that they will never get out.

We need rigorous scientific methodology because biology is complicated that otherwise you just get coincidences flagged up as meaning something - or worse. No way should there be crowdfunding for collecting rubbish lists of data. And as far as I can see we can tell already from the result on fibronectin that for an individual person the result means zilch, zero, nada - a complete waste of money.
 
AknaMontes said:
At least 'maverick' doctor Sarah Myhill
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I’d have put the scare quotes around ‘doctor’ instead myself, considering that she’s currently on a nine month GMC ban for pushing, inter alia, ivermectin, and intends to market herself in future as a naturopath.

https://www.bbc.co.uk/news/uk-wales-64457153


Sorry, I don’t mean to keep having a pop at you, it’s just the coincidence of some surprising posts at a time when I’m feeling particularly tetchy.
 
@AknaMontes I agree with your basic idea that we need more work done on the possible biomarkers that have been flagged up by various researchers, but as far as I can see most of those biomarkers are only testable in labs that have specific sophisticated equipment, like the work Morten is doing with Raman spectroscopy, or with equipment that hasn't been manufactured at scale yet, like Ron Davis's nanoneedle where research seems to have stalled, or some may only work on freshly collected blood, so the patient needs to go to the lab for the blood draw.

So it's not just a case of collecting lots of blood samples and sending them off to an ordinary blood testing lab.

There are already frozen samples from properly diagnosed patients in biobanks such as the UK ME/CFS biobank that they can send anywhere in the world for researchers to use. I hope where possible that resource will be used to do replication studies on possible biomarkers.
 
AknaMontes said:
So what are the possible work arounds? It must be possible somehow.
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The set up is probably available. The UK ME Biobank has a well documented set of samples and controls. If someone comes up with a suggested biomarker the obvious next step is for them to request a set of samples and controls blinded from the ME Biobank and see if they can replicate their findings in that way. Not many people have done that and I am not sure we have seen anything replicated that way.

Very little that looks as if it is worth replicating in the way of blood test has shown up in the last ten years as far as I am aware. The finding on MAIT T cells at CureME looked worth repeating but that was done on the Biobank samples in the first place.
 
Another thought, while my mind is focused on this.

A study may find that there is a statistically significant difference between the mean value of substance X in the blood of pwME and the blood of healthy controls. This doesn't necessarily mean substance X is a biomarker for ME/CFS.

Differences between means may be statistically significant in groups where there is a lot of overlap. To take a daft example, there is a statistically significant difference between the mean height of adult British men and adult British women. But measuring an individual's height is not a good way of determining whether that individual is male or female.
 
Shadrach Loom said:
Same source as the axed Panorama, by any chance? More detail would be useful there, too.
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I'm not going to land my source in it without checking with them first. Currently they are not well, so will catch up at some point. I was only told because I was putting hours into writing to Panorama asking them to make an up to date programme on the crisis over children caught up in care proceedings, denial of nutrition and hydration in very severe, and NG206 implementation. The person involved wanted to save me wasting time.
 
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