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

Discussion in 'General ME/CFS News' started by Sasha, Aug 24, 2015.

  1. Sasha

    Sasha Fine, thank you

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    In the context of Cort's very interesting article about all the NIH ME/CFS grants of 2015 (which go well beyond just the Lipkin/Klimas/Hanson grants), I'm wondering if there's a difference in focus and scale of research in the US and UK and if so, why.

    In the US, research focusing on autonomic and exercise challenge (and its immune and other effects on PWME) seems common: do we not get this in the UK because of the BPS school's influence or is it going on and I don't know about it?

    And 'Big Data' - this thing that Ron Davis and the OMI go in for of going in hypothesis-free and using the new techniques involved to look at everything that's happening at a gene expression level (if I've got that right) and comparing PWME and healthies to determine what's going wrong - we seem to see that in the US work but not the UK work.

    Is this just my ignorance of the field talking or are there differences between the US and the UK here? And if so, why?

    Discuss. :)

    Again, @Simon, @Jonathan Edwards.
     
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    The biggest research programme in the UK looks at autonomic dysfunction and exercise too, and effects on the immune system - Julia Newton's programme. I think it is worth remembering that the USA is five times the size of UK and probably nearly ten times as rich in money terms. It has been said that the US government spends $5M p.a. on ME. I think the UK government probably spends more than $1M.

    As for big data - I have never been very impressed by trawling everything. Without some sort of hypothesis you end up with so many bits of data you are bound to find some spurious p value of less than 0.05. If you have no leads then trawling is sometimes all you can do, but I see no justification for deliberately taking a trawling approach by preference. I tend to go more for the UK Biobank approach - which very carefully builds up a cohort of PWME and controls with as little bias as possible (I don't see that in the US so much) and then plans to 'selectively trawl' on the basis of things that we already have some hint might tell us something.
     
  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    What of course is intriguing is that the UK Biobank is funded by one of the largest NIH grants.
     
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  4. Sasha

    Sasha Fine, thank you

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    I hadn't realised she combined the two. I've clearly not been reading properly.

    I didn't realise they were ten times as rich, which would explain a lot.

    I agree that a big trawl can come up with loads of spurious stuff that won't replicate - there was a lot of that starting up in the early 2000s and it looked rubbish - and the field seemed to be the Wild West, with all the problems of lack of study pre-registration and post-hockery of clinical trials but writ larger.

    But I think that if you have people like Ron Davis doing it, who are well aware of the problems of spurious findings, it makes sense in a disease that's poorly understand and multi-system in nature.

    Solve ME/CFS in the US have a biobank and people are using it - I don't know how unbiased it is. I thought it weird that the NIH would fund the UK biobank.
     
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  5. alex3619

    alex3619 Senior Member

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    The way I see it Big Data approaches do not generate answers. What they do is generate hypotheses, things that can be investigated using more targeted approaches.
     
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  6. voner

    voner Senior Member

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    Jonathan, could you explain in more detail what you mean by "carefully builds up a cohort". was such a poorly defined disease, how do you get "with as little biased as possible".
     
  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    By identifying a primary care based population and trawling directly from primary care sources and then re-assessing all potential cases using several sets of criteria - which I think is what Nacul and colleagues did in their original epidemiology paper. With several sets of criteria you can go back and compare with studies using different ones. Clearly there is always room for bias but I worry about studies done on cases recruited through the internet because they may be quite atypical of the ME population as a whole. All you need is for some correlated variable to bias recruitment and you can get spurious p values for everything even if the bias is quite small.
     
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  8. voner

    voner Senior Member

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    i'm a bit confused. Previously I've seen you express your concerns with the United States method of using patients from well-established "ME/CFS doctors", because of potential bias. also, in a perfect world, this methodology you desire would be great, but were far from a perfect world in this field. So you have to muddle along. How do you do it with very limited monetary resources...??
     
  9. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    It has been done, quietly and methodically, by the UK Biobank team. That is the point. They have nearly a complete set of samples and controls.

    The problem with patients under specialists is the same as for those recruited via the internet - it can be biased by referral practices. What is needed is a cohort that has not even been referred.
     
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  10. Nielk

    Nielk

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    How are they then chosen? What set of criteria are being used?
     
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  11. charles shepherd

    charles shepherd Senior Member

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    You might find it helpful to look at the last Report from the UK ME/CFS Biobank

    The sample numbers, incidentally, have increased since then

    Report:
    http://www.meassociation.org.uk/wp-...ank-Report-Executive-Summary-Nov-14-final.pdf

    Inclusion and Exclusion criteria are on pages 7 to 8:

    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. Compliance with study criteria was confirmed by a clinical member of the research team (doctor) after reviewing the results of a range of laboratory tests used to exclude alternative diagnoses.
    Healthy controls: informed consent, 18 to 60 years old, no past or present fatiguing illnesses and/or other major morbidity such as cancer or coronary heart disease.

    Exclusion criteria

    Cases: Recent use (in the preceding 3 months) of drugs known to alter immune function (e.g. azathioprine, cyclosporine, methotrexate, steroids); anti-viral medications and vaccinations; history of acute and chronic infectious diseases such as hepatitis B and C, tuberculosis, HIV (but not herpes virus or other retrovirus infection); other severe illnesses and severe mood disorders. Pregnant women and those within 12 months post-partum and/or currently lactating are excluded.

    Healthy controls: all of the above, in addition to the presence of any fatiguing illnesses and other conditions that would exclude a diagnosis of ME/CFS (in those with fatigue), present or past.

    Potential participants were invited to join the study by their doctor (affiliated with a collaborating NHS site) or by ME/CFS Disease Register staff if the patient was enrolled in the ME/CFS Disease Register. The LSHTM research team provided invitation packs to the participating NHS sites, which posted them to the potential participants identified in the database search. The invitation pack included an invitation letter from the health service, information about the study (with separate information sheets for cases and controls), a “Symptoms Assessment” form for determining case definition compliance, a consent form, a refusal form, and a stamped self-addressed envelope.

    Because people severely affected by ME/CFS (that is, bed- or home-bound) often do not, or cannot, visit NHS services, and are particularly under-represented in ME/CFS research, information sheets and invitation packs were sent to support groups in the Greater London area for identification of and distribution to interested individuals in this segment of the ME/CFS population. Unfortunately, those very severely affected by the disease would be unable to participate because of the need to complete a half-hour clinical assessment and to provide a blood sample. 8 | P a g e
    Potential participants with ME/CFS were also asked to invite a friend to participate as a healthy control and so invitation packs were provided to them for this purpose. Additionally, information packs were made available at NHS sites and at LSHTM to supplement healthy control recruitment.

    When the signed consent and “Symptoms Assessment” forms were received by the research team, they were reviewed by the clinical researcher to confirm compliance with the inclusion and exclusion criteria for cases and controls. All potential cases would have received a diagnosis of ME/CFS at some time in the past. The clinical staff then assessed the diagnosis of ME/CFS according to the study’s protocol, which requires compliance with the Canadian Consensus Criteria (1) and/or the CDC-1994 criteria (2). Cases meeting the former have been shown in most cases to also meet the latter criteria (4), and the former seems to characterise those who are most severely affected. Comprehensive phenotyping of patients at baseline also enabled categorisation of individuals according to other clinical criteria, such as the London (7) and International Consensus (8) criteria, although these definitions were not used to determine enrolment eligibility.

    Once eligibility was established, the research team booked appointments for participants for clinical assessments and blood sample collection. Participants in the Greater London area with severe disease and/or mobility restrictions were seen at their homes. Consenting respondents ineligible according to the screening questionnaire were thanked by the research team and told that their ineligibility was based on the exclusionary criteria.

    We have just put out an appeal for more people with severe ME/CFS and for some healthy controls:
    http://www.meassociation.org.uk/201...lood-samples-to-be-stepped-up-21-august-2015/

    This is the work that is being done with the US/NIH grant:
    http://blogs.lshtm.ac.uk/news/2013/06/28/uk-mecfs-biobank-project-awarded-1-million-grant/

    Dr Charles Shepherd
    Chairman, UK ME/CFS Biobank Steering Group
     
    Last edited: Aug 24, 2015
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  12. voner

    voner Senior Member

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    So, is this Biobank available to United States researchers also/researchers from all over the world, or just the UK?

    if it is, who is using it (UK and non UK researchers)?
     
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  13. jimells

    jimells Senior Member

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    Does the OMI study on severe/very severe ME patients qualify as a good study cohort? I don't remember any mention of controls or comparison groups. It also sounds a bit like a trawling expedition - $25,000 in diagnostics for each patient, as I understand it.
     
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  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Charles is the best person to answer but my understanding is that the more research groups take advantage of the resource the better. Nobody is using the material just yet because the sample set needs to be complete and made ready for access. Nobody will want to delay things unnecessarily but it is important to get the conditions of access formalised so that everyone involved gets a fair deal.
     
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  15. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Severe cases present a slightly different balance of priorities when it comes to setting up a cohort, because of logistic difficulties. The UK group are recruiting differently for severe cases. I do not know enough about the OMI cohort to comment specifically.
     
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  16. Nielk

    Nielk

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  17. voner

    voner Senior Member

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    @Jonathan Edwards ,

    would you also define what you mean by the term "Cohort".. when I tried to look up the term on the Internet I got references to longitudinal studies and I don't think that's what you meant?

    so much of communication problems is just that we have different assumptions of what various different terms mean. I guess that's One thing formalized schooling does, it gives everyone involved a common set of accepted terminology ..
     
    Last edited: Aug 24, 2015
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  18. charles shepherd

    charles shepherd Senior Member

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    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
     
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  19. Nielk

    Nielk

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    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?
     
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  20. jimells

    jimells Senior Member

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    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."

    :bang-head::bang-head::bang-head:
     
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