Development and validation of blood-based diagnostic biomarkers for [ME/CFS] using EpiSwitch®… 2025, Hunter et al. (Oxford Biodynamics)

Jonathan Edwards said:
I am well aware that many people think that way but the more people with ME/CFS and advocacy organisations for ME/CFS call for and fund projects focused on this sort of diagnostic test the longer the disease will remain in limbo with researchers churning out useless analyses of what might otherwise have been valuable data.

At least Robert seems to understand that !

Look at inflammatory rheumatic disease - we went from total ignorance to having highly effective treatments for all of them without ever bothering with a diagnostic
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I was agreeing with you.
Are you disagreeing with me or….?
 
Hmm. We have been homing in on particular signals like interferons (1 and 2) and DecodeME has pulled up CA10, OLFM4 and BTN2A2 etc. - without any presuppositions about cell types in either case, just disease dynamics and DNA data.

This study picks out IL-2, CD4, maybe HLA-DR, IL-10 in PBMCs, which are all about things like IL-2, CD4, HLA-DR and IL-10. It's a bit like saying we looked at white cells and found a major focus on white cell gene products.

IL-2 could be relevant, as an indicator of T cell activity. But we have already found studies that show that physical activity shifts T cell behaviour.

The comparison of disease and drug 'networks' smells to me of AI fairyland stuff - which we have seen before and not known what on earth to make of. Give me an old-fashioned GWAS any day.
 
The issue with this test is very simple in practical terms:
There are loads of reasons for why someone would be flagged by this test that has nothing to do with their ME/CFS.
There are also loads of reasons for why someone with ME/CFS would not be flagged by this test.

This is mainly caused by two factors:
The lack of a closely matched control group and no grounding in biological processes known to be causally involved in ME/CFS.

Therefore, this test can’t ever validated a diagnosis.

Using this test to validate a diagnosis is just as nonsensical as using CPET to validated the disability for disability benefits, or using a tachycardia upon standing as a diagnostic feature for OI in general or the (very flawed concept of) POTS.

Edited for clarity.
 
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Utsikt said:
The issue with this test is very simple in practical terms:
There are loads of reasons for why someone would be flagged by this test that has nothing to do with their ME/CFS.
There are also loads of reasons for why someone with ME/CFS would not be flagged by this test.

This is mainly caused by two factors:
The lack of a closely matched control group and no grounding in biological processes known to be causally involved in ME/CFS.

Therefore, this test can’t ever validated a diagnosis.

Using this test to validate a diagnosis is just as nonsensical as using CPET to validated the disability for disability benefits, or using a tachycardia upon standing as a diagnostic feature for the (very flawed concept of) POTS or even OI in general.
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Why are POTS and OI in general flawed concepts?
 
Ash said:
Why are POTS and OI in general flawed concepts?
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Sorry, only POTS is.

POTS implies that there exists a syndrome where tachycardia upon standing is key to the syndrome. That doesn’t seem to be the case, and regardless it’s pure speculation.

OI is just «intolerance to not being horisontal». The use of HR to measure OI is flawed for much of the same reasons as for POTS - HR might not be relevant at all.
 
Utsikt said:
Sorry, only POTS is.

POTS implies that there exists a syndrome where tachycardia upon standing is key to the syndrome. That doesn’t seem to be the case, and regardless it’s pure speculation.

OI is just «intolerance to not being horisontal». The use of HR to measure OI is flawed for much of the same reasons as for POTS - HR might not be relevant at all.
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For OI, one could have symptoms other than raised HR or in addition to this, but is HR not measured because it can be measured and it is a common symptom that some or perhaps many people find tracks well enough with their other symptoms for it to be worth paying attention to?

As for POTs I am confused by this category generally. But is it not useful to have over not having it because so many people find medications and lifestyle changes associated can help them to expand their capacity for activity and living life rather than lying down and suffering?

Or do you mean it’s been sufficiently studied to discredit it whatever ‘it’ is supposed to be?

Or if it’s just that ‘it’ had no business emerging as a construct, then is that the problem itself?

Or maybe patients could get to something better a better more solid outline of what’s wrong without it do you mean, like a neurological immunological or cardiovascular disease etc identified?
 
Jonathan Edwards said:
There is no point in developing a diagnostic test that correlated 100% with a syndrome. If it does, you know you already had a 100% method of recognising the syndrome so the test is unnecessary.
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It could still be useful if we are moving from the diagnosis of exclusion, which often takes years, to a positivity test that takes days. This particular test, however, smells like a marketing job. For all we know, they might have had exactly the same result if they mixed ME/CFS cases with flu cases.

Jonathan Edwards said:
The pathways section looks to me just like a random bucketful of the usual suspects.
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This was exactly my first thought, a marketing job.
 
Ash said:
For OI, one could have symptoms other than raised HR or in addition to this, but is HR not measured because it can be measured and it is a common symptom that some or perhaps many people find tracks well enough with their other symptoms for it to be worth paying attention to?
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We have no indication whatsoever that this is the case. It’s pure speculation.
Ash said:
As for POTs I am confused by this category generally. But is it not useful to have over not having it because so many people find medications and lifestyle changes associated can help them to expand their capacity for activity and living life rather than lying down and suffering?
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Every single trial for POTS interventions have failed or been subject to so much bias that it’s impossible to get anything meaningful from it. People are eager to interpret causality into everything they do. If we’re to listen to that we should also listen to those that say that their medallion helped them.
Ash said:
Or do you mean it’s been sufficiently studied to discredit it whatever ‘it’ is supposed to be?
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The burden of proof goes the other way. The proponents of POT as a syndrome are the ones that have to argue why it must be. They have not.
 
InitialConditions said:
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To be fair lots of low cap biotech are ripping today, and the market in general though not 40%…. Though the amount of press for this is for sure a pump.


They were trying to fundraise beginning of this year they seemed to be in a bad position. I would not be surprised if this is a last ditch effort to garner some capitol.


Proposed Fundraising - 16:35:00 14 Jan 2025 - OBD News article | London Stock Exchange
https://www.londonstockexchange.com/news-article/OBD/proposed-fundraising/16852409
 
Ash said:
For OI, one could have symptoms other than raised HR or in addition to this, but is HR not measured because it can be measured and it is a common symptom that some or perhaps many people find tracks well enough with their other symptoms for it to be worth paying attention to?
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In the commonest form of OI, with fainting, the heart rate slows. In POT it speeds up, but it does not seem clear why or if the speeding up is a problem in itself, rather than the OI.

Ash said:
But is it not useful to have over not having it because so many people find medications and lifestyle changes associated can help them to expand their capacity for activity and living life rather than lying down and suffering?
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Do we know that these treatments actually work though? Lot of people take supplements and homeopathic remedies and say they expand their capacity etc. when we have no good reason to think they do.
 
Utsikt said:
The burden of proof goes the other way. The proponents of POT as a syndrome are the ones that have to argue why it must be. They have not.
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I think that was the note that I finished with, I understand the requirement.

I was just wondering since medicine often doesn’t meet such requirements, why this particular category specifically was problematic.

I’ve read a fair amount about POTs and I still don’t understand what it’s supposed to be exactly.

I’ve also read a fair few people dissecting POTs, and dismissing it, I think that where I’d stand.

But, I struggle to retain any of this information. I’m not in disagreement with your initial statement, I really couldn’t remember the info on this category.
 
Utsikt said:
Then it wouldn’t be a replication. Replication is to do the same thing in a different lab by a different team and seeing if it gives the same result.
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Is that the case? I thought it meant replication of results, but allowed for variation in methodology, including up to completely different methodology. The idea is to make the findings more robust.
 
SNT Gatchaman said:
Is that the case? I thought it meant replication of results, but allowed for variation in methodology, including up to completely different methodology. The idea is to make the findings more robust.
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The open science movement, which was the 1st to push replication hard as a solution for life science problems, has defined it broadly to include both direct replication of methods and trying to replicate the overall findings more generally. The first approach includes taking the original method and improvingo upon obvious weaknesses, such as a small sample size. .
 
Ash said:
I think that was the note that I finished with, I understand the requirement.

I was just wondering since medicine often doesn’t meet such requirements, why this particular category specifically was problematic.

I’ve read a fair amount about POTs and I still don’t understand what it’s supposed to be exactly.

I’ve also read a fair few people dissecting POTs, and dismissing it, I think that where I’d stand.

But, I struggle to retain any of this information. I’m not in disagreement with your initial statement, I really couldn’t remember the info on this category.
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I don’t really care too much about what’s become standard. I only care about what’s logically sound. And POTS is not. I just used it as an example of similarly bad practice.
SNT Gatchaman said:
Is that the case? I thought it meant replication of results, but allowed for variation in methodology, including up to completely different methodology. The idea is to make the findings more robust.
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I was under the impression that replication was about trying the same thing to see if it gave the same results. But that might be «replication of the study» and not «replication of the results». So I can see that there might be room for a different understanding.

I think that if you were to fix all of the weaknesses of this trial, it would be so substantially different that it can’t reasonably be called a replication of the original study.

And I’m not sure what such a study would be looking to replicate. Would they try to use the same biomarkers in new cohorts? Or is it the analysis to identify the biomarkers? Both? Something else?
 
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