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Different treatment of CFS vs control samples in XMRV studies

Discussion in 'XMRV Research and Replication Studies' started by Sasha, Sep 28, 2010.

  1. Sasha

    Sasha Fine, thank you

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    In today's XMRV Buzz, Cort wrote (my bolding):

    "'Living with CFS' basically got Dr. McClure to get down to the nitty gritty about XMRV in a series of emails. Dr. McClure believes the WPI's results and presumably Dr Alter's results (and Dr. Hansen's results? and the UK Mikovits study results?) are probably due to contamination and were confounded by the fact that blinding/randomization was not done and that not all the samples were treated 'in the same way and at the same time'. Of course she has her points - she is a published retrovirologist - and we shall see. Dr. Singh is in the middle of her study which is designed to answer all of Dr. McClures concerns and, of course, the DHHS and NIH studies will as well."

    At the XMRV workshop, a lot seemed to be being said about XMRV/MLVs being very sensitive to how the blood samples were collected and stored. I had the impression that in at least some studies, CFS samples were from banked collections and control cases were recently collected especially for the study; and vice versa. My memory on this is foggy and my reading superficial so I could be dead wrong, but Dr McClure seems to be saying this.

    This is a different argument from that involving contamination; the suggestion presumably is that if you treat blood collection differently in the case & control groups, differences in the apparent rate of XMRV+ is due to differences in how the blood has been treated, not the underlying prevalence of XMRV in the two groups.

    The implication would be, of course, that XMRV must be very prevalent in the general population because if contamination isn't an issue (as I gather other research has indicated that it is not) then XMRV would be as prevalent in the control as the CFS groups (where it is showing up in 50%+ of cases in studies that have proved capable of detecting it at all).

    My question: am I wrong that the blood in the CFS and control groups has been collected/treated/stored differently in those studies that have found a difference between CFS & control groups? :confused:
     
  2. acer2000

    acer2000 Senior Member

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    The studies in the Science paper were blinded. It says so in the "response to comments" from Dr. Mikovitz in Science. Not only was the study blinded, the samples were divided up and tested independently at 3 labs, the NCI, the WPI, and the CC.

    From paragraph 5 in "Response to Comments on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"
    Judy A. Mikovits1,* and Francis W. Ruscetti" Science 14 May 2010: Vol. 328. no. 5980, p. 825 DOI: 10.1126/science.1184548

    From paragraph 5

    As far as the Lo, alter paper... I suppose its possible that there was a difference in processing the samples between the cases and controls that accounts for the results, but it seems unlikely.

    Think about it, 7/8 of the people were still positive 15 years later on a fresh blood draw, but not the controls. So even if you claim that the tubes they used in the early 90s were contaminated (cases) and the new ones weren't (controls), it doesn't make much sense unless they used different tubes on the 8 cases they retested recently from the tubes in the controls also tested recently.

    I dunno... why doesn't McClure prove the contamination theory, instead of just alleging that is the case? If she knows the cause of the contaminant, publish a paper on it?
     
  3. Sasha

    Sasha Fine, thank you

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    Sorry, acer, I don't think I made my question very clear! I wasn't talking about the contamination issue but the suggestion that I've seen (from Dr Mikovits? Coffin?) that it's important to collect blood samples in a very particular way - quickly freezing it as soon as it's been collected from the patient, storing it in certain kinds of test tube, etc. - in order to give XMRV a chance of being detected. If in a study, the CFS samples are taken from a collection banked some years ago while control samples are collected fresh (or vice versa) that would mean that the treatment of blood at that stage could affect XMRV's chances of being detected and make it different between the two groups. Contamination or blinding aren't relevant to that particular scenario.

    In the Alter paper, for example, do we know that the blood samples of cases (the modern samples) and controls were collected in identical ways - same time delay between being drawn from the patient and being stored, being stored under the same conditions and in identical containers, etc.?

    The notion that the detection of XMRV might be very sensitive to such differences seems to have come up in recent months as a possible explanation of differences between studies but lately it seems to have been raised as a possible explanation of differences within studies. I hadn't thought until recently about the issue that studies weren't necessarily collecting from cases and controls under similar conditions.
     
  4. Sasha

    Sasha Fine, thank you

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    Cort reports that Dr Singh and others are stressing the importance of treating blood samples in the same way at the collection and storage stage here in his article on the OFFER meeting (very interesting).
     
  5. eric_s

    eric_s Senior Member

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    I think in the Alter and in the Mikovits UK study there was a difference between cases and controls regarding how the samples where drawn etc.
    I don't know about the Lombardi et al. Science paper from last October.
    But since we've seen both, "old" samples for cases and new ones for controls and the other way round in another study, i don't think this has led to false results.

    Thanks acer2000, for showing that Lombardi et al. blinded the samples, i thought i read somewhere else that they hadn't.
     
  6. Esther12

    Esther12 Senior Member

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    The exact deatils as to how/when the samples for the Science study were blinded would be great.

    You would assume that the WPI would be paying attention to any difference in XMRV rates which seem to tie to different sample procedures. Is it normal to do this sort of analysis?

    I wonder when we'll hear about the results of the Singh study.
     
  7. Megan

    Megan Senior Member

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    Tere is another issue here that doesnt seem to have been picked up in this thread. The following quotes appear in the presentation by the Blood Working Group at the XMRV conference:

    On page 12:
    On P14 under heading Phase II Setup:
    In the BWG abstract 20 from the conference it says:

    I find the above quotes more concerning than the suggestion of contamination. If it's true that the level of virus present degrades in the time prior to freezing then this would seem to me to be a more sensible alternative explanation of why less positives may be found among controls than patients in the positive studies, assuming most studies are using blood donors as controls. Of course it doesn't explain the results of the zero/zero studies. But it begs the question, what is the prevalence rate among healthy controls if their blood is frozen without waiting several days?

    If the prevalence rate among healthy controls jumps to a much higher number than previously quoted for XMRV, we may lose the high degree of association between CFS and XMRV, and hence the possible evidence for causation?

    Then there have been the comments about heparin tubes.

    I find it hard to believe that the BWG and thw WPI don't already have some idea of the answers to the above questions. It seems they are holding their cards close to their chests.
     

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