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CDC Multi-site Study - An interview with Beth Unger

Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, Jan 31, 2014.

  1. Ember

    Ember Senior Member

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    Subgroups presuppose groups, and identifying them may not be ground-breaking:

    Optional Considerations
    By insisting that Dr. Unger "assess data with an open mind, looking for unexpected patterns," are you denigrating the time-honoured practice of hypothesis testing?
    Last edited: Feb 3, 2014
  2. SOC

    SOC Moderator and Senior Member

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    The CPET test is not the same test as the walking cardiac stress test.

    The CPET is done on a bicycle, not a treadmill. The bicycle does not force a particular speed on the patient the way a treadmill does. The cardiac stress test only records EKG and BP. The CPET also includes pulmonary gases, so the tester knows when the patient has reached his/her anaerobic threshold and can adjust the test accordingly so as not to severely overwork the patient. The cardiac stress test has all patients exercising at the same speed and incline, healthy or ill. That can be a serious problem with PWME. The CPET (properly performed for PWME) allows for adjustment of work depending on the capability of the patient.

    I suspect that the CPET test (properly done for PWME) is not as severe as many PWME fear. I've done it (the one day test) twice now and neither time was it as terrible as I expected. Both times it was done in the office of an ME/CFS specialist by people who understand the illness. The test ran about 8 minutes. The pedaling resistance was set so easy that it was like waving my legs around, not pushing with any power at all. I didn't feel great afterwards, but I didn't have a massive crash, either.

    I do not have mild ME/CFS. I'm about 5/10 on most scales. I couldn't walk more than 100 ft without PEM the last time I did the test, so it's not like I'm not susceptible to PEM or have a high threshold for PEM.

    I'm not saying the test is trivial for all PWME. I think many of us have some (relatively small) consequence such as several days to a week of moderate PEM, but not a long-term crash. It's important to note that it is NOT the same test as the cardiac stress test most people imagine, which would probably seriously crash most of us, especially when done by technicians unfamiliar with the limitations of PWME.
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  3. Bob

    Bob

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    I think there's a wide consensus that CFS and CFS/ME are heterogeneious, and that ME might be heterogenous.
    I personally think it's absolutley essential to use data to attempt to identify subgroups, in order for research to advance.

    Yes, there are various subgroups that are already defined, but Unger is carrying out a massive data analysis, and perhaps she may find unexpected groups, based on the data. I hope she is cross-referencing with already-defined subgroups, such as the ones you've identified here.

    I think it would be narrow minded if the only hypothesis being tested was whether patients fit into currently defined diagnostic criteria. I hope that Unger is testing the collected data against Fukuda and the CCC/ICC. But I think many of us agree that CCC and ICC, although vastly preferable to Fukuda, are not set in stone.
    Last edited: Feb 3, 2014
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  4. Bob

    Bob

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    There have been times during my illness when 8 minutes of the mildest exercise would have caused me a severe relapse, lasting for months. I was especially reactive during my first 3 years of illness. I'm more stable now, after discover pacing and implementing it strictly, but my last relapse was severe for about 6 months, and then continued moderately for months after that.
    I'm not sure how I'd currently react to an 8 minute maximal CPET test, but I'd be too cautious to attempt it, unless going through a prolonged stable spell.

    If anyone is brave enough to attempt such a test in the name of science, then I'd be very grateful to them, but I think we've all got to be honest with ourselves that such a test could potentially be damaging to patients. I know we are desperate for answers, but we've also got to protect each other.

    Patients have got to go into such a test with eyes-wide-open, and being fully informed and fully aware of the potential for adverse effects.
    Personally, I'd recommend that new patients are not put through such a test, as they wouldn't have a full insight into the nature of their post-exertional reactions, and so can't make an informed decision about it.
    Last edited: Feb 3, 2014
  5. SOC

    SOC Moderator and Senior Member

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    Keeping an open mind while looking as what's going on and searching for patterns is the first step in science. It is called observation. It comes before the formation of a hypothesis. It's what hypotheses are based upon. First you have to develop the hypothesis, then you test it.
  6. SOC

    SOC Moderator and Senior Member

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    I understand that many patients are afraid of the test. Exercise can be very risky for us. I'm simply suggesting that absolute rejection when you've never even seen the test done might be counterproductive.

    An 8 minute maximal CPET test is not 8 minutes of maximal exercise, btw. It's only maximal (your own maximum) at the end.

    I wonder if it might be informative to have a poll or some way of gathering info that would allow all members who have had the test to report the consequences they suffered. That might give us a better sense of whether it is truly dangerous for PWME and whether we should therefore discourage it's use... or conversely, whether patients are not reporting serious consequences and the test can safely be used a valuable objective measure for research studies.
  7. Ember

    Ember Senior Member

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    Can you articulate Dr. Unger's study design? Is she proceeding without research questions or hypotheses? Notice that she rejects Dr. Klimas' suggestion in the first 75 seconds here:



    This quotation from “Research questions, hypotheses and objectives” may provide a useful commentary on Dr. Unger's "data-driven" approach:
    A good hypothesis should precede and drive a study's data collection.
    Last edited: Feb 3, 2014
  8. Bob

    Bob

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    I'm not sure that would be helpful. Just because either a minority or a majority of patients have found the consequences of a CPET test to be acceptable for themselves, does not mean that it would be safe for everyone.

    I'd rather have open honest discussions about it and allow individuals to decide for themselves whether or not it would be safe for them.

    Some of us will decide it would be relatively safe for us to participate while others will decide it would be dangerous or potentially dangerous for us.
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  9. roonie

    roonie

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    i think we should all do what Jim Wilson did with lyme here in Canada......raise a few dollars .....open up our own labs....hire our own docs.....get er done! There is now a treatment center in his province of British Columbia to treat lyme and other associated illnesses......even cfs/fibro.
  10. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    If they just tested dam people who fit the ccc for nk function, rnaseL, 2 day exercise test. Im sure klimas and co have some kind of research on cytokine patterns. Check for viral reactivations and common bacterial infections.

    Come on how dam hard is it? Theres 30yrs of research and we have biomarkers just have to use the dam things.

    It seems like they just want to invent the dam wheel. Aarrgghh! !!!
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  11. taniaaust1

    taniaaust1 Senior Member

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    To me avoidance of doing 2 day exercise tests is to try to play the illness down as much as the CDC can do. It shows lack of change (I believe they are only doing what they currently are doing due to public pressure, they will keep doing as little as they can do)
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  12. taniaaust1

    taniaaust1 Senior Member

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    oh boy.. sorry all, the two above posts above over state disability service werent suppposed to be on this thread (they were meant to be on my thread). Brain fog. I'll get a mod to move them.
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  13. alex3619

    alex3619 Senior Member

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    Chicken and egg. What data do you collect, by what methods? In order to figure that out you need some idea of what to look for: one or more hypotheses. There are millions of possible tests, nobody is going to do them all.

    There is a difference between an exploratory study, in which hypothesis testing is not the goal, and a rigorous study of mechanisms, treatment etc, in which hypothesis testing should be the goal. Exploratory studies are about getting data, yet as I said you can't do that unless you have some notion of what data you want: you have to have some kind of hypothesis.
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  14. Ember

    Ember Senior Member

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    This seems to have been Dr. Unger's research question: “The question being asked over and over is, how do the patients differ in people's practices.... Is that why the findings in the laboratory are not always translatable?” To investigate the presumed heterogeneity among practices, Dr. Unger undertook “to collect standardized data on all the domains of illness included in the Canadian Consensus Criteria of CFS/ME (sic), the 1994 CFS definition and the newly proposed International ME definition.”

    But Dr. Unger's interim analysis showed more heterogeneity within the patient population than among the clinics, and her questionnaires failed to identify robust subgroups:
    Nevertheless, Dr. Unger is refusing to use credible biogenic correlates to better define subgroups.

    In addressing the IOM Committee, Dr. Unger presented her study's objective this way: “To describe what the patients in these clinical practices actually look like. And so to provide data both to address how case definitions might work as well as to identify subgroups that we could find from these patients.” Dr. Unger freely expresses her opinions about how case definitions might work:
    But beyond describing "a broad umbrella with various degrees of severity," and despite having the relevant data, Dr. Unger isn't prepared to use either Fukuda, the ICC or the CCC to better characterize her study's cohort.
    Last edited: Feb 5, 2014
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  15. Bob

    Bob

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    Unger is pro-actively looking for subgroups based on the data. I'd be surprised, and disappointed, if she wasn't using existing CFS & ME definitions to see if her data matches those subgroups. However it works out (i.e. if the data either matches or doesn't match the existing criteria) then that will give us helpful new information. (As long as the study is carried out competently, honestly and comprehensively, which isn't guaranteed of course.)

    That's exactly what we want her to do, isn't it?
  16. Bob

    Bob

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    I had forgotten the content of this video. I think perhaps it's the best review of the study that Unger has presented so far:
    http://www.tvworldwide.com/events/f..._archive.cfm?gsid=2251&type=flv&test=0&live=0

    @Simon reviewed it in his health-rising article:
    http://www.cortjohnson.org/blog/201...c-chronic-fatigue-syndromemulti-clinic-study/

    Unger starts the presentation @86.00

    Some snippets:

    Collected clinical data includes:
    Basic Demographics.
    History of illness (e.g. age of onset.)
    Medical history.
    Lab and other diagnostic tests.
    Family history.
    Infection/immunization history.

    Mental health and role emotional scores are 'preserved' in CFS in all of the clinics. (i.e. CFS patients have normal outcomes for mental health scores.) (This is a novel conclusion for the CDC.)

    Unger is testing the DePaul Symptom Questionnaire, along with the various diagnostic criteria.

    Unger mentions that the study demonstrates that the MFI general fatigue scale is not useful for research into CFS because 40% of patients had the maximum possible score.
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  17. Ember

    Ember Senior Member

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    In the first 75 seconds of the IOM Committee's Q & A, Dr. Unger indicates that she isn't prepared to use existing CFS & ME definitions. She claims that she doesn't know “how to set the criteria for each of the various points of the disease criteria. In other words, there's not a cut point for any of these.”

    Her description of “a broad umbrella with various degrees of severity” isn't supported by the ICC. It identifies a subgroup that needs to be removed based on much more than severity. Dr. Unger would risk identifying such an ME subgroup were she to use the 2-day CPET.
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  18. Gemini

    Gemini Senior Member

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    Agree. Would like Dr. Unger to build on the existing science & incorporate biomarker candidates in her study.

    NIH State-of-the-Knowledge Workshop (2011) identified 5 biomarker candidates [with qualifications]:
    1. NK cell function [methodological issues?]
    2. Perforin [by flow cytometry, a surrogate for NK cell function]
    3. Dipeptidyl peptidase-4 (CD26) [an excellent cell membrane biomarker candidate]
    4. Neuropeptide Y [correlates with severity of illness]
    5. Cytokine panels

    Byron Hyde's SPECT Scan test & the Duffy/Komaroff EEG Spectral Coherence test are additional candidates.

    Perhaps a group here on PR could compile a biomarker list to suggest to Dr. Unger?

    Sources:
    1. "NIH ME/CFS State-of-the-Knowledge Workshop Report,""Diagnosis & Biomarkers" section, p13-4, April 7-8, 2011
    http://orwh.od.nih.gov/research/me-cfs/pdfs/ORWH_SKW_Report.pdf

    2. "Missed Diagnoses: Myalgic Encephalomyelitis & Chronic Fatigue Syndrome," Bryon Hyde, MD, Second Edition, 2010
    http://www.lulu.com/us/en/shop/byron-hyde-md/missed-diagnoses-myalgic-encephalomyelitis-chronic-fatigue-syndrome-second-edition/paperback/product-18463888.html

    3. http://www.ncbi.nlm.nih.gov/pubmed/21722376

    Edited to add links to sources
    Last edited: Feb 5, 2014
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  19. Bob

    Bob

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    This has just come through on the CFSAC email list...

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  20. Bob

    Bob

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    I wonder if Dr Unger has seen Lenny Jason's recently published research that distinguishes CFS, CFS/ME and ME patients from healthy controls by using frequency and severity of certain symptoms:
    http://forums.phoenixrising.me/inde...e-learning-and-featu.27975/page-2#post-427215

    Agreed. But she is correct to say that the CFS cohort is a broad umbrella, etc. (And her remit is to study the entire CFS population.)

    But even if looking purely at the CCC or ICC population, then there will probably be heterogeneity. We don't know if all ICC patients have the same disease. All we know is that the characteristics of their illness/es are similar. Data and research is needed to investigate it further.

    I absolutely agree that the CDC needs to include proper and comprehensive biomedical research in its study, including all the tests & research that have been mentioned in this thread.
    I'll be deeply frustrated if they haven't started doing this before the end of 2014. But I think it seems quite sensible for them to gather clinical and demographic data for such a large study before they move towards collecting more specific biomedical research data.

    I also agree that Unger's use of language, apparent failure to engage with the community, and an apparent lack of insight into the differences between CF and ME, is deeply disappointing and frustrating.

    We need the ME research community to attempt to use data to distinguish subgroups.
    The CCC/ICC are a helpful guide while more research is being undertaken.
    They're helpful, but they are not going to lead to answers for us in themselves.
    We need more research and more data.
    I'm hoping that Unger is focusing on PEM and other symptoms used in the CCC/ICC, to measure her data against in attempt to distinguish subgroups.
    And I hope that she understands the difference between fatigue and ME. Otherwise it's going to be another dead-end at the CDC.
    Last edited: Feb 6, 2014
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