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CAA - WPI only lab reporting false positive result. (Is this correct?)

Discussion in 'General ME/CFS News' started by V99, Aug 1, 2010.

  1. V99

    V99 *****

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    http://www.cfids.org/xmrv/default.asp

    The CAA reported the following on their XMRV page:
    A number of question have been raised by various people about this statement. Is it correct to say that the WPI was the only lab. Firstly, the chart next to this statement shows the FDA to also have found XMRV in the sample that was not spiked. Secondly, the test was to look for spiked samples, not real live XMRV virus. Therefore the sample that was not spiked may actually have XMRV, but would not be detected by tests which use primers and probes set for an artificial clone.
  2. Otis

    Otis SeƱor Mumbler

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    Thanks V. If I survive this plane trip I'll check FB. :^ )
  3. V99

    V99 *****

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    Where are you?
  4. Esther12

    Esther12 Senior Member

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    Hmmm...

    Is there a copy of that chart which is easier to read than the tiny one?

    Will be interesting to see what happens here, but currently I'm more interested in seeing the NIH paper.
  5. V99

    V99 *****

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    I'm not sure if there is, but if you look at the top row, where the sample is, only two groups have this painted green. The FDA (Lo) and the WPI
  6. Esther12

    Esther12 Senior Member

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    Here it is for people.

    [​IMG]

    Thanks for posting this V99. It is a bit worrying that the WPI got a false positive - but you're right that it seemed the FDA did too. Maybe this is why (some guy - forgotten his name) was talking about the possibility that identifying XMRV from patient samples is different to spiked samples? It would be extraordinary if they sent out a XMRV positive sample in a sample that was meant to be clean, but who knows at this point. If the FDA and WPI picked out the same sample, but that is what happened.

    Were the FDA involved with the positive study we're waiting for? I'm getting my three letter acronyms mixed up - FDA, NIH, NCI...

    If both positive studies were properly blinded, it would be strange that the contamination would be consistently more likely with the CFS samples.

    ps: The CDC kicked arse at the spiked samples.
  7. omerbasket

    omerbasket Senior Member

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    Okay, I have e-mailed Dr. Mikovits and her reply explains it all!
    This is what she said:

    So there is your answer: These tests have not been done by the WPI in the science paper or later, until now. It says absolutley nothing, zero, about the validity of the findings in Science, which were confirmed by many tests - and the best evidence for this in my view is that such a prestigous magazaine, "Science", after a rigorous peer-review, published it.

    It is sad, very sad, that the organization that is supposed to help us, the CAA, chose not to mention these stuff and to cause people to believe, falsely, that perhaps the WPI found XMRV so many times when it was not actually there (but in the helathy cohorts the false positives didn't come near as much... but that is something the critics don't want to address...).

    People, can you update the title of this thread so that people would know that there is an explanation for all of that in the 4th page? Or perhaps it's even possible to put that message inside the first message or something?
  8. V99

    V99 *****

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    If there is no official test, it is definitely possible that this sample does have XMRV. Especially when the prevalence rate could be 3% to 7%. These samples will have been confirmed negative with synthetic XMRV, not the real thing. Therefore it cannot be claimed it was a false negative.

    Yes, the FDA lab in question is the one involved in the positive study, under Dr Lo. There is another FDA lab also taking part in this testing process.

    That's very true, but again not the same as real samples.
  9. anciendaze

    anciendaze Senior Member

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    With a reported 3% to 7% background rate, the chance of having a positive in an assumed negative control cannot be dismissed out of hand. With rapid mutation taking place in infected individuals, due to action of APOBEC3, spiked samples may well present an easier target.

    We're back to the question of starting with a panel of infected individuals, which some involved deny exist. Couldn't they begin with asymptomatic infected, for which part of the controversy disappears?
  10. Esther12

    Esther12 Senior Member

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    Thanks for that Omerbasket. I didn't think the CAA were being as alarmist as Mikovits implied - the CAA didn't really do any interpretation for there to be a misinterpretation (other than not mentioning the apparent FDA positive). I understand it being a touchy issue though.

    Still though - if it was a false positive, it does raise concerns about contamination while things are so uncertain.

    If there are two independent blinded studies, I'm not too worried - I just want to see this new one!
  11. V99

    V99 *****

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    Officially no on would know if it was a negative sample.
  12. bakercape

    bakercape Senior Member

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    If there is no standardied test

    How can anyone know if a blood sample was neg. To begin with. Maybe the WPI test was more sensitve and picked up the virus. Isn't that a possibility?
  13. V99

    V99 *****

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    This is what the CAA said:
    But the FDA (Lo) also detected xmrv in this sample, and the result cannot be said to be a false negative, if they, as yet, have no way of knowing if it contained xmrv.
  14. Esther12

    Esther12 Senior Member

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    That's all true.

    I wonder how these samples were created?

    They could have all been from the same individual's blood?
  15. VillageLife

    VillageLife Senior Member

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    Perhaps they should have said, although WPI got a false positive, it doesnt matter because actually The phase I study was not designed or powered to evaluate specificity. (that would of been better!)

    Instead its a short comment which implies many things and leaves us all thinking WPI have indeed done something seriously flawed! which of course they haven't.
    hope it can be edited!!:cool:
  16. jspotila

    jspotila Senior Member

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    I am seeking clarification of what was reported at the meeting, the diagram on the Association's website, and the details of this phase 1 study of the analytic panels. The Association always seeks to provide accurate information, so if there is an error or miscommunication then that will be cleared up and corrected as necessary. I appreciate everyone's patience while I do this.

    Edited to add: The statement on the Association site says that there WPI reported only one false positive in this phase 1 study. The Association did not say anything about WPI's testing of samples in general. There was some confusion on another thread because the statement says 1 false positive but the diagram looks like FDA had a false positive as well. As I said, I am seeking clarification of all this.

    Patient Heidi Dunlap-Bauer provided a summary of the FDA meeting on her Facebook page. Here is what she said about the Working Group phase 1: "Next up was the Blood XMRV Scientific Research Working Group report by Graham Simmons. This group has just about all the names we are familiar with and then some: Harvey Alter, Jerry Holmberg, Frank Ruscetti, Roger Dodd (you remember him from the May transcripts referring to the perception of an XMRV emergency rather than a real emergency), Suzanne Vernon, Judy Mikovits, John Coffin, Shyh-Ching Lo, Bill Switzer, etc. Presently, the main thrust of this group seems to be to find agreement on an effective assay. Graham Simmons concluded that the study was "too small to conduct meaningful statistical comparisons" and "more work on analytical panel development will need to be performed." The main labs in this group are WPI, FDA (Lo), FDA (Hewlett), NCI and BSRI."
  17. ukxmrv

    ukxmrv Senior Member

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    Thank you, jspotila
  18. Dr. Yes

    Dr. Yes Shame on You

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    Thanks Jennie. This matter concerned me as well.

    Without knowing what kind of assays, nor even what kind of samples (how they were screened, strain of XMRV, etc) were being used, this was a meaningless piece of information from the CAA. Given this, and the fact that so few samples appear to have been tested, reporting on a single 'false' positive at this stage was premature, except perhaps to have a 'scoop', but the only effect it could have is to unjustly cast doubt on the WPI (and perhaps make the CDC look better). Not mentioning the apparent 'false' positive at the FDA lab was a strange omission as well. We would need more information than this out-of-context snippet, particularly about the means by which samples are initially determined to be negatives. I think it was inappropriate and irresponsible for the CAA to release that tidbit of information to begin with, even leaving aside the question of whether it was a misinterpretation.

    These labs are evaluating their assays on spiked blood, so at this stage they are basically just repeating the calibrations used in the individual studies. More technically 'sensitive' PCR as determined by spiked samples does not necessarily equal effective PCR in detecting XMRV in CFS patients. Essentially the assays are being tested for their sensitivity in detecting a synthetic clone of prostate cancer strain XMRV in whole blood, not on their ability to detect XMRV in vivo in PBMC from CFS patients (who have strains of XMRV that differ genetically from the prostate cancer strain). And how one determines that any blood sample is truly XMRV negative in the first place is a good question.
  19. eric_s

    eric_s Senior Member

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    I think they explain the Lo lab's false positive. In the top right corner of the top cell in the Lo column there seems to be an asterisk and at the bottom of the picture there's probably text eplaining it. Unfortunately it's too small for us to read.
  20. V99

    V99 *****

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    It may explain why the FDA (Lo) box is green, but the idea of a false negative cannot be testable at this stage.

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