UK: MRC and NIHR announce ME/CFS workshop, November 2019 & ME/CFS Biomedical Partnership FAQ

[Trish]

I don't think we know enough yet to comment on the differences. I hope the GWAS gets funding. And I hope expansion of the biobank gets funding. Who from and how each of these might happen is so far outside my experience I would just be speculating. All I know is I trust Chris Ponting to know what he's doing, and I didn't trust EC and therefore didn't support MEGA.

 

[Russell Fleming]

I don't think we know enough yet to comment on the differences. I hope the GWAS gets funding. And I hope expansion of the biobank gets funding. Who from and how each of these might happen is so far outside my experience I would just be speculating. All I know is I trust Chris Ponting to know what he's doing, and I didn't trust EC and therefore didn't support MEGA.

Fair enough, although Prof. Ponting would have been doing the 20,000 GWAS attached to MEGA

 

[Jonathan Edwards]

I find it very strange that nobody has commented on the apparent removal of the proposed expansion of the M.E. Biobank from this project. This was a key (but not the only) distinction between what was MEGA and this new venture and it offered considerable scope for future research. It seems very odd that the expansion plans are no longer part of the project.

What document are you using this on?

My understanding is that the ME Biobank will be involved in the project.

 

[Adrian]

I find it very strange that nobody has commented on the apparent removal of the proposed expansion of the M.E. Biobank from this project. This was a key (but not the only) distinction between what was MEGA and this new venture and it offered considerable scope for future research. It seems very odd that the expansion plans are no longer part of the project.

Having been to the meeting last week I think this is a really good opportunity to get some funding of a bio ME research project. I like the idea of the GWAS study which could give good indications as to mechanisms behind ME. To do that it need to be really well powered with large numbers of patients samples. One of the things I found interesting was talking with people who didn't know much about ME but knew a lot about genetics and GWAS studies and they described GWAS as transformative in understanding other diseases.

 

[Russell Fleming]

What document are you using this on?

My understanding is that the ME Biobank will be involved in the project.

"It was agreed that we need to craft a scientifically robust GWAS application but the more detailed costs now available most likely mean that we cannot also expand the biobank with samples other than saliva.

"There was consensus that we need to prioritise the GWAS work. There were lots of other suggestions and recommendations from individual participants which the Biomedical Partnership Management Group will now consider.

"At the end of the workshop, the importance of this invited application to not only deliver a high-quality genomics project but to also create a new pathway for future research and research funding in the UK was re-stated."

This was from the summary report now published by Action for M.E. and ME Association following the Workshop last week.

Sure the Biobank team will I presume remain involved, but the expansion plans for the M.E. Biobank (whereby c.1,000 patients would be clinically assessed and have blood etc. samples taken) appears to have been dropped.

 

[Jonathan Edwards]

Thanks Russell (@Russell Fleming)

I have been involved in various ways along the road from the first suggestion of this MRC bid. The emphasis, as I have understood it, has always been on a GWAS study. I was very pleased to see the Cure ME team involved and there have been discussions about a broader package if possible but since the GWAS, to be done thoroughly, seems to need most of the funding available I think adding anything major in is unrealistic. From what I saw the Cure ME team would get a significant tranche of the funding, although the biggest slice goes just on the genetic assays themselves.

I think this is absolutely the right priority for the Cure ME team at present because it realises the basic aim of the ME Biobank - that whenever a first class project gets put together the Biobank resource is drawn on if at all possible. I think a 400-500 cohort would be adequate for a second pass confirmation of initial GWAS findings. I have not so far seen any specific power calculations relating to a need for a larger cohort either for this or other purposes.

The basic problem the applicants are faced with is that the MRC puts a limit on the money available for any single application of this sort. I agree with Stephen Holgate that focusing on the GWAS should not be seen as closing doors to further applications.

 

[Adrian]

- that whenever a first class project gets put together the Biobank resource is drawn on if at all possible. I think a 400-500 cohort would be adequate for a second pass confirmation of initial GWAS findings. I

I'm not sure I understand your point. I assume you are suggesting that the blood samples could be used in an omics project to look at the areas of mechanism pointed to by the GWAS study?

I agree with Stephen Holgate that focusing on the GWAS should not be seen as closing doors to further applications.

I think Stephen Holgate was being stronger than saying that it wouldn't close doors to other applications. I thought he was suggesting that good progress on one project like the GWAS one would help in getting backing for other projects.

 

[Jonathan Edwards]

I'm not sure I understand your point. I assume you are suggesting that the blood samples could be used in an omics project to look at the areas of mechanism pointed to by the GWAS study?

What I am suggesting is that if the GWAS comes up with some linked gene alleles in a 20,000 cohort that is needed for statistics but might generate spurious confounding links, then a 500 ME Biobank cohort, if also screened by GWAS (which I presume everyone assumes will be done) can provide a confirmatory sample with a much reduced Bonferroni correction, that would hopefully weed out spurious hits because it has been recruited on a population basis and diagnosis has been confirmed by clinical assessment.

There is a lot of debate about what relative risks associated with gene alleles are worth chasing. My experience suggests that helpful pointers will be alleles with quite substantial relative risks. They ought to show up in a 500 cohort with small risk of false positive if you are, for instance, limiting yourself to the five strongest signals.

I think Stephen Holgate was being stronger than saying that it wouldn't close doors to other applications. I thought he was suggesting that good progress on one project like the GWAS one would help in getting backing for other projects.

Yes, very much so. I very much agree with what he is saying.

 

[Chris Ponting]

Fair enough, although Prof. Ponting would have been doing the 20,000 GWAS attached to MEGA

Hi. For information, I had only a minor role in MEGA. There were no posts and no funds proposed to come to my team. I wasn't down to do the GWAS - I think Bristol was going to do that. The biggest difference between this GWAS and MEGA's are in the recruitment strategies: via clinics versus spit-and-post.

 

[Chris Ponting]

Thanks Russell (@Russell Fleming)

I have been involved in various ways along the road from the first suggestion of this MRC bid. The emphasis, as I have understood it, has always been on a GWAS study. I was very pleased to see the Cure ME team involved and there have been discussions about a broader package if possible but since the GWAS, to be done thoroughly, seems to need most of the funding available I think adding anything major in is unrealistic. From what I saw the Cure ME team would get a significant tranche of the funding, although the biggest slice goes just on the genetic assays themselves.

I think this is absolutely the right priority for the Cure ME team at present because it realises the basic aim of the ME Biobank - that whenever a first class project gets put together the Biobank resource is drawn on if at all possible. I think a 400-500 cohort would be adequate for a second pass confirmation of initial GWAS findings. I have not so far seen any specific power calculations relating to a need for a larger cohort either for this or other purposes.

The basic problem the applicants are faced with is that the MRC puts a limit on the money available for any single application of this sort. I agree with Stephen Holgate that focusing on the GWAS should not be seen as closing doors to further applications.

Thanks for this. Just to mention that the MRC's emphasis on a GWAS is not new, and goes back to their Strategy Board's comments (25 March 2019) when they said: "Overall, the Genome Wide Association Study (GWAS) component of the study was considered to be a good agnostic starting point and members noted that the proposal had been enhanced to bring together a more unified case definition in this joint proposal."

 

[It's M.E. Linda]

The biggest difference between this GWAS and MEGA's are in the recruitment strategies: via clinics versus spit-and-post.

I consider the above to be a major improvement. Clinics would only have supplied people from the current cohort attending appointments and would have very few long-standing (lying), long-term ‘patients’. e.g. I was discharged Jan 2015 and have had no follow up from the Clinic.

Excellent that Cure ME (UK ME/CFS Biobank) will still be involved with the Surveys/Criteria checking the spit-and-post donors and, if the correct authorities are obtained from donors at the start, then future follow up studies can expand into the taking of blood (additional research funds can be sought) and then the expansion of the Biobank.

 

[MEMarge]

Another advantage will be that without the BPS slant there won't be time, effort or money wasted on pointless questionnnaires like the Chalder FQ etc.

 

[rvallee]

I consider the above to be a major improvement. Clinics would only have supplied people from the current cohort attending appointments and would have very few long-standing (lying), long-term ‘patients’. e.g. I was discharged Jan 2015 and have had no follow up from the Clinic.

Excellent that Cure ME (UK ME/CFS Biobank) will still be involved with the Surveys/Criteria checking the spit-and-post donors and, if the correct authorities are obtained from donors at the start, then future follow up studies can expand into the taking of blood (additional research funds can be sought) and then the expansion of the Biobank.

It's sad but remarkable that to get better outcomes, it is actually preferable to work around current official clinical "expertise" as it is more likely than self-reported diagnosis to pollute the data with invalid cases. There will still be such cases but there will be fewer.

Seriously this warrants some discussion in medical literature. We are essentially talking about a decades-long process that created "specialist" clinics, training and guidelines that are as a matter of fact less reliable than patient self-reports with no such "expert" input is involved. This is "expertise" promoted within every public health and medical institution in the country, including official training and internal documentation.

It's hard to give proper framing for just how catastrophically bad this is. Especially that it's well-documented, consistently raised by thousands and was accurately predicted at the time. And that it's happening independently in many other countries for the very same reasons.

There is a good case to make that politics would likely do just as well, if not better, if representatives were randomly selected. In large part this is because of the corrupting effect of power and money, not because of any particular skills. To find the same in medicine, where training, skills and expertise are everything, is just about the height of incompetence and malpractice. I don't think there is anything comparable in any other skilled profession. And the people responsible are still doing the very same thing, awarded plenty, while complaining about not being celebrated enough.

 

[MEMarge]

Seriously this warrants some discussion in medical literature. We are essentially talking about a decades-long process that created "specialist" clinics, training and guidelines that are as a matter of fact less reliable than patient self-reports with no such "expert" input is involved. This is "expertise" promoted within every public health and medical institution in the country, including official training and internal documentation.

As Carol Monaghan said in Westminster, PACE is likely to be
“one of the greatest medical scandals of the 21st century”

 

[Cheshire]

Posts about the feedback on the UK GWAS project have been moved to a new thread.