MRC/NIHR DecodeME Showcase meeting online and in person Nov 6th

Katherine Seton talked about a preliminary study of the feasibility of a red light therapy trial, justified by something to do with oxidative stress and mitochondria. I could not make much sense of it. It was mostly about how patients managed with the treatment and outcome scoring as far as I remember.
 
Audrey Ryback talked about her work on electronic health care records in Lothian. This is impressive. They appear to have a genuinely population based cohort. The prevalence was up at 0.8% - 7,000 cases out of 900,000 people. In other words everyone with ME/CFS in a defined area. This begins to look like solid population data. (And I suspect GPs in Lothian are relatively good about coding ME/CFS compared to some places.)

The data provide a variety of measures of disease dynamics. Audrey stayed with us Wednesday night and also showed me work she has been doing with Simon on age of incidence profile which are to me pretty mind-blowing. Clues from the old Norwegian study look as if they are replicable. We should set up a thread if Simon is happy for us to dig in to this (it may not quite be ready). To me it looks as if there is a totally novel aspect to ME/CFS disease dynamics worth a very deep look at.
 
Sasha said:
What do you think would be more informative, and what should the MRC be doing differently (and/or how should we be trying to influence hte MRC)?
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Nothing is more informative - other than reading the reviewers' reports. You cannot do numbers on stuff like this. The parameters are quite different for different research fields. The MRC need to stop using ignorant reviewers. Which means that physicians need educating and need to care. How you achieve that goodness knows but we will try. I already have a new academic physician interested today - and he is the first one I have tried. The gene stuff is trendy, so it is reasonable to hope that people will bite.
 
Sonya Chowdhury talked very openly and sensibly about funding and indicated that they were hard at work trying to raise funds for Sequence ME, at present from the USA. It sounds as if the project may be broken up into modules so that funding for at least some can get started although that was not clear. My gut feeling is that this will get funded but it will need creativity - which I think the team have plenty of.
 
Jonathan Edwards said:
Nothing is more informative - other than reading the reviewers' reports. You cannot do numbers on stuff like this. The parameters are quite different for different research fields. The MRC need to stop using ignorant reviewers. Which means that physicians need educating and need to care. How you achieve that goodness knows but we will try.
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Thanks, that's interesting. So if it's all about the MRC using ignorant reviewers, do we know why they're doing so? Dom't we have potential reviewers who aren't ignorant? Do they need to be putting themselves forward? Are there enough of them? Or do we need to cultivate new people like this guy:

Jonathan Edwards said:
I already have a new academic physician interested today - and he is the first one I have tried. The gene stuff is trendy, so it is reasonable to hope that people will bite.
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This is very good news! Let's hope that's the start of a trend.
 
The Precision Life presentation I found interesting. I think it was stuff we have seen before but the presenter was clear and I got a bit more of an idea what it was about.

I think they have been doing roughly what I hoped Chris would set up when I first saw the results - looking for which risk-associated SNPs clustered together, if they did. The rationale Precision Life use is I think misguided. They find clusters of SNP associations and assume that these tell them what the disease pathways are involved in those cases. I don't think it will work like that. A disease mechanism will involve tens of thousands of gene products along the way and any one of those could tip it one way or another. Risk genes are likely to be more central to pathways but you cannot say that Ms X with SNP G has a particularly G involving disease. The influence of the genes is statistical and for most of those in DecodeME fairly slight. The main reason why Ms X and not Ms Z got ME/CFS is probably entirely random - something everyone seems to forget.

Nevertheless, the method of looking for clustered SNPs might tell us something very useful about how risks interact or don't. What I would like to see is an analysis of their sort just on the 8 main regions for DecodeME. They include a whole lot of other genes that presumably have lower level signals. They may be relevant but I want to know, for instance, whether OLFM4 clusters with BTN2A2 and not RABGAP or whatever. I guess they have those data.
 
Jonathan Edwards said:
Katherine Seton talked about a preliminary study of the feasibility of a red light therapy trial, justified by something to do with oxidative stress and mitochondria. I could not make much sense of it. It was mostly about how patients managed with the treatment and outcome scoring as far as I remember.
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It could be interesting from the perspective of experience in running trials with ME with patients at home. She is from the quadram inst. (Simon Carding) and I think they are trying to do some trial (can't remember what on)
 
Sasha said:
Dom't we have potential reviewers who aren't ignorant?
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No we don't I suspect. There just isn't anybody who sees the nature of the problem. I can maybe think of one or two. But the one thing you can be sure about with MRC is that it is an inbred clique. The situation can change if the word gets about that there are brownie points to be had for ME/CFS biology but we need a sea-change.
 
Jonathan Edwards said:
No we don't I suspect. There just isn't anybody who sees the nature of the problem. I can maybe think of one or two. But the one thing you can be sure about with MRC is that it is an inbred clique. The situation can change if the word gets about that there are brownie points to be had for ME/CFS biology but we need a sea-change.
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Surely people don't go on review panels just for brownie points, though! I can't believe everyone is quite so self-serving.

Could it be just a matter of tapping the right people on the shoulder, like you've started to do? We can't afford to wait for a sea change. We need things like Sequence ME & Long Covid funded now. If the right people are there, and they want to be reviewers, can they put themselves forward and expect to be able to serve as MRC reviewers for ME/CFS proposals, or will they encounter resistance?

I feel we need a plan! I hate to just sit here when we can see what the problem is and there might be ways to solve it. This is a hugely important issue. We're talking about turning on the tap of UK government funding for ME/CFS.
 
Jonathan Edwards said:
It sounds as if the project may be broken up into modules so that funding for at least some can get started although that was not clear.
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I wondered if they'd divided up aspects of the work so they could target different grant programmes, though I might be reading in. It's a bit frustrating when presenters are as pressed for time as they were today, it feels as if there are half-finished sentences that you'd like to have heard the end of.
 
Jonathan Edwards said:
He also pointed out that a number of genes are replicating across studies although not for some cohorts, which probably indicates that there are still problems with subject selection
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We don't know which method of selecting patients gets us the closest to a pure cohort. The strength of disease signals that emerge from each individual study can tell us something about how good the patient selection was but we don't know what exactly is being selected for.

An inconsistency might just indicate an improvement over previous studies.

A similar argument could be made for a diagnostic test. A diagnostic test at this point, when cohorts are almost certainly not close to pure, cannot possibly reach high accuracy and specificity. The tests that reportedly are reaching high accuracy and specificity are probably too good to be true.
 
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Jonathan Edwards said:
It sounds as if the project may be broken up into modules so that funding for at least some can get started although that was not clear.
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Perhaps if this happens some of the modules then some of the modules without funding could be funded through charity fundraising?

Perhaps they are planning to do at least some of the analysis with the ME/CFS samples with whatever funding they've secured now and then do the long covid part and compare the two when they can? That occured to me the other day as a possible logical move.

It would also mean the MECFS data wouldn't be tied to the logistics of collecting the LC data.
 
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