US vs UK research: is there a difference in focus and scale?

[Nielk]

Inclusion criteria

ME/CFS cases: informed consent, 18 to 60 years old, and clinical diagnosis of ME/CFS according to Canadian (1) or CDC-1994 (2) criteria.

Canadian or Fukuda? As if both of these criteria select the same cohort?

 

[voner]

Having collected all these blood samples from people with ME/CFS (including severe ME/CFS), healthy controls and people with MS, we are almost in a position to open up the UK ME/CFS Biobank to researchers - here in the UK and overseas - who want to make use of the samples, alnog with the very detailed (and anonymised) clinical data that is attached

As soon as the funding contract has been agreed and signed, which is currently in progress, we will be appointing an additional member of staff and making an announcement that covers all aspects relating to the supply of samples - application procedures, peer review of applications, ethical approval etc etc

The three year study that is investigatingg the virology and immunology of ME/CFS is being funded by the NIH. This has involved the collection of yet more samples

At the Biobank Steering Group meeting last week we were discussing plans for the next NIH site visit and the possibility that there will be another public meeting where the NIH representatives can speak about their work in relation to ME/CFS

This type of international co-operation is very encouraging and helps to demonstrate that the UK Biobank is well respected new item of ME/CFS research infrastructure

Charles, thank you. that is indeed good news. thanks to everyone involved.

 

[charles shepherd]

So the US/NIH s funding a ME/CFS biobank in the UK but none in the US?

My understanding is that the NIH is funding ME/CFS research in the US (you could check their website for specific details) but I don't think they are funding any other biobank work.

These are the powerpoint slides from Chris Biesel's public lecture on NIH funding for ME/CFS research that took place at the London School of Hygiene and Tropical Medicine in September last year:

http://www.lshtm.ac.uk/itd/crd/rese...nih_public_outreach_session_sept__8__2014.pdf

 

[charles shepherd]

Canadian or Fukuda? As if both of these criteria select the same cohort?

The biobank is assessing (in some detail) whether the people who are being recruited meet Fukuda criteria, or Canadian Criteria, or both. As we are collecting a large amount of clinical data (more than for a routine clinic diagnostic assessments) we can also, if necessary, find out if people meet other diagnostic criteria. This information, could, of course, be very helpful when it comes to looking at sub-grouping under the ME/CFS umbrella.

 

[jimells]

The three year study that is investigatingg the virology and immunology of ME/CFS is being funded by the NIH. This has involved the collection of yet more samples

At the Biobank Steering Group meeting last week we were discussing plans for the next NIH site visit and the possibility that there will be another public meeting where the NIH representatives can speak about their work in relation to ME/CFS

Is there a rogue group at NIH running this operation under the nose of Collins? It just seems so totally bizarre that an important project like this, that patients and researchers have been begging for decades, is totally, completely ignored at this past week's CFSAC meeting.

Instead of hearing about all the great things NIH is doing, we were subjected to yet another diatribe about how only a handful of stupid inexperienced researchers apply for their grants.

Can NIH reps to CFSAC really be so completely and totally incompetent that they have to come to PR to find out what their own agency is doing regarding their own specialty?

 

[charles shepherd]

My understanding is that the NIH is funding ME/CFS research in the US (you could check their website for specific details) but I don't think they are funding any other biobank work.

These are the powerpoint slides from Chris Biesel's public lecture on NIH funding for ME/CFS research that took place at the London School of Hygiene and Tropical Medicine in September last year:

http://www.lshtm.ac.uk/itd/crd/rese...nih_public_outreach_session_sept__8__2014.pdf

PS: My understanding is that the main interest in ME/CFS research at NIH centres around the Allergy and Infectious Disease division.

 

[voner]

The biobank is assessing (in some detail) whether the people who are being recruited meet Fukuda criteria, or Canadian Criteria, or both. As we are collecting a large amount of clinical data (more than for a routine clinic diagnostic assessments) we can also, if necessary, find out if people meet other diagnostic criteria. This information, could, of course, be very helpful when it comes to looking at sub-grouping under the ME/CFS umbrella.

Charles,

what potential subgroupings are you looking at or trying to make sure there is baseline information for subgroups..... for example, autonomic dysfunction, fibromyalgia, "severe CFS".....

 

[jimells]

My understanding is that the NIH is funding ME/CFS research in the US (you could check their website for specific details) but I don't think they are funding any other biobank work.

These are the powerpoint slides from Chris Biesel's public lecture on NIH funding for ME/CFS research that took place at the London School of Hygiene and Tropical Medicine in September last year:

http://www.lshtm.ac.uk/itd/crd/rese...nih_public_outreach_session_sept__8__2014.pdf

That was an interesting presentation. Thank you for the link. I see that Dr Fauci's fiefdom, the NIAID, the institute that use to run the "CFS" program, gets over half the money.

I love the chart showing HIV/AIDS get the most funding, and our illness gets almost the least. I can't imagine that the NIH public relations dept would approve.

The presentation also shows how there is no currently active Program Announcement. That is still true today. It also shows there has not been a new RFA for TEN YEARS!

And all the non-US finding. Who knew?

Overall, this does not look like a presentation singing the praises of NIH. It looks more like criticism of the leadership.

 

[Jonathan Edwards]

Can you please explain this statement? How is it that if one has already been referred to a specialist, they are considered biased? Does that apply to cohorts of all diseases?

Yes it applies to all cohorts of all diseases. The point is that in a population of say 1 million people, there will be, say, a thousand people with disease X. If we want to understand the mechanism of disease X it is useful to compare test in people with X with people who are otherwise as identical as possible to those patients - by age, sex, social status, etc etc. Of those thousand it is likely that maybe only four hundred get referred to specialists, or that only a hundred will volunteer through the internet, or whatever 'referral' process one can think of. And the trouble is that the people who get diagnosed or go on the internet may well be different from the others in important respects. The standard one is that people who already have another disease or some positive tests for other reasons are more likely to get referred or to refer themselves because they have already got into the medical care system. So it might seem that more people with ME have thyroid disease or positive thyroid antibody tests because people with those things are more likely to get into the cohort.

So any referral system that only brings to light a proportion of patients has a risk of bias. This is not 'bias' in the sense of somebody being prejudiced, it is just a weighting on probability of getting a result that suggests that there is a difference. Any referral system is almost bound to weight the cohort slightly one way or another for almost anything tested. And since the search for biomarkers relies on looking for statistical differences in such tests, if you have a big enough sample almost everything will look to be a biomarker for ME in a pre-referred cohort.

This is the reason why all the big studies on causes of heart disease and arthritis and stroke etc. are done on primary care based populations like the Framingham study or the Norfolk Arthritis Register.

 

[Jonathan Edwards]

Well here is one gigantic difference between US and UK research: after the Lipkin XMRV replication studies ended, there was a well-defined cohort (and controls?) complete with biologic samples. I was reading just yesterday how the community asked to have this important resource made available using a well-defined process designed to get the most out of the biobank. Dr Unger's response was, "It will be made available on a first-come, first-served basis."

I am not sure what difference you are suggesting? The UK Biobank samples will be made available on a first come first serve basis I think. That is to say that any bona fide research group can ask for samples until they run out. The difference may be that the UK Biobank, as I understand it, is keen to re-invest in restocking the Biobank on a rolling basis.

 

[charles shepherd]

Charles,

what potential subgroupings are you looking at or trying to make sure there is baseline information for subgroups..... for example, autonomic dysfunction, fibromyalgia, "severe CFS".....

We aren't specifically looking at either clinical (or possibly pathological sub-grouping) at the moment

The main priority at the moment is to get everything in place so that we can open up the biobank to researchers who want to make use of the samples

 

[jimells]

I am not sure what difference you are suggesting?

It's the difference in attitude. The UK approach comes across as methodical. The CDC approach seems casual, and indifferent to the concerns of researchers. I guess I need to quote a reference here, but I'm coming up empty at the moment.

 

[charles shepherd]

I am not sure what difference you are suggesting? The UK Biobank samples will be made available on a first come first serve basis I think. That is to say that any bona fide research group can ask for samples until they run out. The difference may be that the UK Biobank, as I understand it, is keen to re-invest in restocking the Biobank on a rolling basis.

Hi Jonathan - yes, the intention is to make sure that part of the cost recovery process provides for the restocking of blood samples.

Fortunately, we are not short of people here in the UK who are keen to donate blood samples to the biobank and we have a very enthusiastic research group at the London School of Hygiene and Tropical Medicine and the Royal Free Hospital.

 

[jimells]

I guess I need to quote a reference here, but I'm coming up empty at the moment.

Hmm, yes. Note to self: search first, write later, especially to professors. I got a few details not quite right. And maybe the case is overstated a bit. This is from Mary Dimmock's "Thirty Years of Disdain"

NIH has squandered other opportunities to advance the field. For instance, as a product of his XMRV study, Dr Ian Lipkin... established a biobank of 147 well-characterized patients and 146 matched controls. Patients had to meet both the Fukuda and Canadian definitions, had to meet well-‐defined exclusion criteria, and had to have a viral-‐like onset consistent with an infectious disease.794 Because of the rigor of characterization, these samples have strategic value for their potential to advance key research questions like biomarkers.

As discussed in an interview with Dr. Vincent Racaniello in 2012, Lipkin stated that funds would be set aside to study these samples. Further, in the 2014 U.S. Senate appropriations report, congressional leaders stated that these samples could “help speed diagnostics and a better understanding of the pathophysiology of this severely disabling condition” and specifically requested “a special funding opportunity to spur research into ME/CFS.”795

But the NIH did not set aside funds for these samples. Further, in a personal email, NIH staff stated that the samples would be distributed on a first-‐come, first-‐served basis. 796 How much opportunity has been wasted by not issuing an RFA for these samples and by not using a more strategic approach in deciding how these samples were consumed?

The point here is not the disposition of one particular set of samples... Rather, these examples demonstrate a pattern of behavior that appears to be unfocused, uncommitted, and ultimately misguided. Meandering at best.

My apologies, Dr Unger. The email referenced in footnote 796 involved Dr Maier.