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A Multicenter Blinded Analysis Indicates No Association between CFS/ME and either XMRV or pMLV

Discussion in 'XMRV Research and Replication Studies' started by Firestormm, Sep 18, 2012.

  1. SOC

    SOC Moderator and Senior Member

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    Many legitimate ME/CFS patients have comorbid fibromyalgia, hypothyroidism, OI, viral infections, pain conditions, sleep disturbances, IBS, etc

    If you rule out all patients with comorbid (as opposed to genuinely exclusionary) conditions, you eliminate many legitimate ME/CFS patients. That is not a "good" cohort.

    Dr Hyde is an excellent diagnostician, but he is not the unique definer of what makes ME/CFS.
    beaker likes this.
  2. rlc

    rlc Senior Member

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    Hi SOC, what I’m saying is that if they are going to be successful in finding bio markers for ME, if they include patients that have co morbid conditions in the studies these co morbid conditions cause bio medical changes in the body that are different to those that will be found in people who just have ME, so these co morbid conditions will causes the results of the study to be distorted and make it very difficult to reach any useful conclusions from the results. An example of this is thyroid diseases they have already been proven to dramatically alter immune function see http://online.liebertpub.com/doi/abs/10.1089/thy.2010.0429?journalCode=thy as they are planning to look at immune function to try and find a bio marker, having patients with hypothyroidism in the study, which is bound to happen if they are using the out of date TSH reference ranges is going to distort the results dramatically and make it impossible to work out what is going on. So they will then have to repeat the study minus any patients with thyroid conditions wasting lots of time and money. And the patient community will have to suffer longer.

    There is nothing way out about what I’m saying, it is standard scientific practice when studying any disease to one, make sure that all the patients have the same disease and two, to not let patients with co morbid conditions into the studies because it will dramatically alter the results. It is how studying diseases is done.

    I’m not saying that Dr Hyde is a unique definer of ME/CFS at all, I’m using him as an example that if doctors do a lot more tests then have been used in this study what they find is that extremely large amounts of patients who fit the diagnostic criteria’s like Fukuda and CCC are actually misdiagnosed and don’t have ME at all. The testing that was used in this study was so small that it would only pick up a tiny fraction of the misdiagnosed patients, which will leave them with a mixed cohort of patients with many different diseases any attempt to find the cause of ME amongst a mixed cohort is guaranteed to be futile and a complete waste of time and money, as it has been so many times in the past.

    I must admit to being shocked at how poor the testing they did to rule out other diseases in this study is, from my understanding the doctors that selected the patients for it are, Dr Anthony Komaroff, Dr Dan Peterson, Dr Nancy Klimas, Dr Jose Montoya, Dr Sue Levine, and Dr Cindy Bateman. I would assume as they are the Doctors and the rest of the participants were Virologists, that the doctors were mainly responsible for chosing the tests to be done? As I would imagine that these doctors choose the patients for this study from their own patients? I find it somewhat disturbing that some of these patients were excluded from the study for failing the extremely limited set of tests used in the study. Why had these doctors not already tested them for these things??

    All I’m asking for is correct scientific procedure to be followed; they have to make sure that all the patients they are studying have ME. Because there is no diagnostic tests for this disease and it is officially a disease of exclusion we should be demanding that they exclude all other diseases before deciding that the patients have ME. Otherwise all the planed future studies will be a waste of time, they will be well paid and get to go to all the conferences etc, but we will be the ones that suffer when the results come back completely inconclusive, just as all the other previous studies on mixed cohorts have been.

    As a community we should be demanding a better standard of science then the testing that they used in this study, they have deemed that all these patients in this study have ME/CFS without doing anywhere near enough testing to see if these people have other diseases, samples from this study are already going to be used in further testing, the results are very likely to be meaningless because they have not done everything that can be done to make sure that all the patients actually have ME.

    All the best
  3. SOC

    SOC Moderator and Senior Member

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    rlc -- I agree with your point and generally agree with it. The only point I want to make is that some of these common-to-ME comorbid conditions may be caused by ME. Eliminating patients with those conditions would skew the patient cohort.

    However,patients with independent additional conditions should indeed be removed from a clean patient cohort for just the reasons you mention.

    For example, a patient with pre-existing, well-treated depression who still has ME should not be in a clean patient cohort. The condition existed before ME onset and is therefore unlikely to be caused by ME. Whatever is causing the depression -- let's assume it's physiological, not psychological -- might confound study results.

    On the other hand, a patient with OI that developed after (or along with ME) and is well-treated for OI but still has ME should not be eliminated from a clean cohort because the ME could be the cause of the OI and eliminating those patients from the cohort would eliminate a legitimate subset of patients thereby skewing results.
  4. rlc

    rlc Senior Member

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    Hi SOC, I agree with conditions like OI/POTs there is considerable evidence that this can be caused by ME, so if these conditions have developed at the same time as the ME symptoms started or sometime after there is a strong likely hood that ME has caused the OI/POTs. However there are many other causes of OI/POTs and almost all of them will give similar symptoms as those attributed to ME and almost all of these other causes of OI/POTs will have been missed by doing the very limited amount of testing that has been done in this study see http://www.dinet.org/what_causes_pots.htm

    If a study was being done properly and all the other possible causes of the patients OI/POTs or any of their other symptoms have been ruled out and they don’t have any of the other known diseases that could causes these symptoms, then they should be included in the study.

    If the science is done properly and all other diseases are ruled out first, one of the first immediate benefits will be that they will be able to say for certain what the symptoms of ME are because for so long what has been said to be the symptoms of ME has been based on mixed cohorts of patients. Once they have a pure cohort with modern technology I doubt it would take very long at all to get this mystery of what causes ME solved, and treatment could be found.

    But unfortunately the people involved in this study and who are also involved in the CFI studies are showing no signs of wanting to test patients properly to make sure that there is a pure cohort, or of knowing what tests should be being done. If they continue to select patients in the way they have in this study, and use samples from patients in this study who have not been properly tested to rule out other diseases. We are all going to be very disappointed with the confusion that will follow and the massive wasted opportunity of the money that has been given to the likes of the CFI being wasted on testing mixed cohorts.

    I must say I’m very disappointed, I can’t believe how many of the common diseases that cause ME like symptoms that they have not tested the patients in this study for. Hopefully someone can manage to get them to start testing the patients properly soon.

    All the best SOC
  5. joshualevy

    joshualevy

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    [and also Sean's post #19, which makes a similar point.]

    That is the goal of most research, and I agree that this was a very well done study.
    However, the goal of this particular study was clearly to convince the very last few stragglers that XMRV (no matter what name is used) is not a cause of CFS/ME. For that purpose it failed, because it could not succeed. Anyone who recently believes that XMRV causes CFS/ME has ignored so much science, that one study, even a really well done study, would be ignored as well.

    Put another way. A study must tell us something that we don't already know. It must add to the knowledge (not just be well designed, etc.) This study told us the same thing that 30 other studies had already told us. Would you rather spend a few million dollars on the 30th study showing XMRV has nothing to do with CFS/ME, or spend that money on something else?

    That was the point of my central question: Did this study change even one person's mind? I doubt it.

    Joshua (not Jay!) Levy
  6. FancyMyBlood

    FancyMyBlood Senior Member

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    Yes it did. Many people on this and other ME/CFS forums still believed in XMRV/PMLVS/HGRVS as a cause of ME/CFS, even after all the negative studies. Personally, it frustated me because the science was clear a long time ago.

    Now, I've yet to see one patient that still believes in a connection (outside the twisted minds at peoplewithme.com), so this event definitely had a major impact on the believes of a substantial group of patients. Although I don't think it's the study itself that convinced these people, but the presence and statements of Mikovits and Ruscetti. Lipkin is a very smart man and my respect for him grows each day.

    From a scientific point of view, this study was probably a waste of money indeed. But the whole XMRV fiasco raised much awareness and because of this study we now have a great set op blood samples that can be used to explore other avenues. Ironically, XMRV (and the rituximab paper) is/are the best thing that could ever happen to ME/CFS research, so it's not a total waste of money. And please excuse us for not really caring about the financial aspect of this study when this disease has been underfunded for the last two decades.
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  7. Bob

    Bob

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    Lipkin doesn't think that the study was a waste of time or money. He has stated that very clearly. He has also said that a large proportion of the money spent has given us a valuable high-quality and well-defined supply of patient and control samples that can be used in future ME studies, by various researchers. So the funding has created a valuable asset that can be used again.

    Also, XMRV research has stimulated further biomedical research, and brought Lipkin, Alter and Levy into the field of ME. That's worth any amount of money, in my opinion.
  8. ixchelkali

    ixchelkali Senior Member

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    I disagree with you on a couple of counts. First, if the study was aimed at convincing ME/CFS patients, it may not have been aimed at the diehard true believers, who as you say probably will not be convinced by any evidence. It may, instead, have be aimed at patients like me, who thought that the weight of evidence looked as though XMRV isn't associated with ME/CFS, but who wouldn't feel sure about it until at least one good replication study was done. I'd also point out that this study was started before some of that negative evidence came in.

    I also disagree that this study told us the same thing that other studies had. None of the other studies told us that if you used the techniques developed by the original study's authors, stringently guarded against contamination, had a well-defined patient cohort, and carefully handled patient's and healthy control's samples the same way, you wouldn't find XMRV infection.

    Personally, I think it's almost as bad to be willing to be completely convinced by incomplete evidence as it is to be unwilling to be convinced no matter what the evidence. But I guess it depends on what you consider complete evidence. I'm just happy that Ian Lipkin's idea of complete evidence agrees with mine, so that I don't have to go through the rest of my life wondering if we really do have XMRV and they missed it because they weren't thorough enough. I wanted to know that they didn't find it because it isn't there, not because they didn't use the right technique to look for it.

    But I hope that the study wasn't done because of patients like me. I hope it was done because that's how good science should be conducted. I'm much more worried about them wasting precious research dollars on schlock pseudo-science and/or sloppy science (including some of those 30 prior studies you mentioned) than I am about negative results from a well-conducted study.
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  9. ixchelkali

    ixchelkali Senior Member

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    !!!!!!!!
    :thumbsup:
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  10. ixchelkali

    ixchelkali Senior Member

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    You're right, and I intended to be referring to XMRV and those pMLVs, but I didn't make that clear. Thank you for the correction.
    jace likes this.
  11. SOC

    SOC Moderator and Senior Member

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    rlc -- I don't think we are disagreeing in general. :) A good study cohort should exclude people that have additional conditions that would cloud the results of the study. We've suffered with the problem of lousy research cohorts for decades. That needs to stop immediately.

    The place where we do disagree, I think, is in our assessment of the ability of the likes of Drs Petersen, Klimas, Bateman, etc to select a clean cohort from among their patients. I believe that when they identified patients for this study as ME/CFS patients, they did not send people with other readily treatable conditions. I would NOT be saying this if the patients were selected from, say, the "CFS" patients of general practitioners, however.

    To me, vetting by top ME/CFS specialists + meeting CCC means we have a darned good cohort.
  12. Sea

    Sea Senior Member

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    Low ESR is within the normal range. The normal range for ESR starts at 0. Nobody yet knows what the signifigance of a low ESR is, they're only looking for high or not. So even though we know it is another anomaly that people with ME test low on ESR, it isn't used for anything yet and wouldn't have affected this study cohort.
  13. rlc

    rlc Senior Member

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    Hi SOC, nice we agree on some things, however you say that the patients met the CCC, this study did not demand that the patients had the Cardinal symptom of the CCC PEM, it did not give the patients all the tests that are required by the CCC, or have all the diseases that are required by the CCC to be ruled out, ruled out. So from a scientific point of view it is not possible for these patients to have met the CCC. There is also the important point that the principle writers of the CCC Dr Carruthers etc have rejected the CCC as flawed and have written the ICC to replace it, in which there are far stricter criteria that have to be met for the patient to have ME. Dr Carruthers is on record as saying that only 10% of CFS diagnosed patients have ME. So why have they chosen to use the CCC when its own writers do not consider it good enough. The patients for this study would also not have met the new ME/CFS primer because it demands extensive testing to rule out other diseases before a patient is diagnosed, which this study has failed to do.

    Now I’m going to say something that some people may take offence to, but this is not my intention, I’m just trying to argue my point from the point of provable science, so please don’t take offence. The virologists who were part in this study are experts, they have been through years of training, are highly qualified and have been constantly tested to make sure they know there subject and what they have learned is based on proven replicated science therefore scientific facts, and I have no problem with their virology work in this study it is very well done and impressive.

    Again please don’t take offence to this; you use the term “top ME/CFS specialists” because there is almost no replicated science in the field of ME and CFS there is nothing to tests if peoples knowledge is good or bad on, there is no tests that can be given to a doctor to see if they really know this subject or not, so there is from a medical and scientific point of view no facts to say that someone is a top specialist in ME/CFS or not, it is a matter of opinion, this is not science! The reality is that CFS specialists have just decided to appoint themselves CFS specialists there are no controls on who can do this or what they should be doing or know to be a CFS specialists. The reality is any doctor can declare that they are a CFS specialist and start quoting any of the large amounts of un-replicated therefore unproven science, which is often based on mixed cohorts to support whatever theory they have decided they are an expert in. There is no replicated science that says exactly what symptoms CFS patients have, all the Criteria are different, so any CFS doctor can just decide whatever symptoms they want constitute CFS. So there are no controls on CFS doctors because there is no evidence to base controls on. In other medical specialties, such as say endocrinology, it is all based on proven replicated science, so the Endo’s are controlled by this they can’t just say something is something because they feel like it, they would get struck off. In the field of CFS there is no replicated science so a CFS doctor can basically make it up as they go along.

    If you look at what CFS specialists do, without naming any names, this is just generalized comments about CFS specialists. They normally start by charging their patients an obscene amount of money, for which the patient get what is often a very minimal amount of testing to rule out other diseases, which will almost certainly miss many underlying health conditions. Which the patient could have got for free from their doctor anyway, they are often charged large amount of money for various immune function tests which again can often be done for free, my local hospital did mine! These tests have no diagnostic value on their own because so many known diseases cause these kinds of anomalies. There is as yet no replicated science based on pure cohorts that shows that these immune function tests have anything to do with ME, but they will often tell the patients that these results prove that they have ME, but there is a vast amount of replicated science that shows that many of the conditions that these CFS doctors don’t test for do cause these immune anomalies. Low Nk cell results have been proven to be caused by not sleeping well. They often also charge for experimental tests that that have not been independently verified as having anything to do with CFS by science. They will often also charge for a large amount of assorted viral tests which can also normally be done for free elsewhere, and often tell the patient that high titers in a certain virus proves this is the cause of the patients problems despite the fact that replicated science shows that high titers are found in perfectly healthy people and basically prove nothing.

    Their treatment will normally consist of a mixture of change diet, rest more and don’t over exert yourself, take a vast array of assorted vitamins and minerals and other supplements, which they often charge for, give immune boosters, and sometimes antiviral as well.

    The problem with these treatment regimes is that they would often make anyone with any chronic disease feel a bit better, and because they often give so many things at once nobody knows which treatment is helping, or often because of a lack of extensive testing for other diseases, what disease it is helping with. Because there is a lack of replicated science that say’s that any of these things do certainly help with CFS, the patients of these specialists are taking a big risk in following these treatment regimes and are basically paying large amounts of money to be used as guinea pigs to see if the CFS specialists theory works.

    So because of the lack of controls on CFS specialist and the lack of replicated science to base controls on. To say someone is a top CFS specialist is just a matter of faith; it’s not science because the science hasn’t been done to base it on.

    The one thing that all these CFS specialists do is to say all the right things, they are very sympathetic to the patients and make many public statements about how terrible it is that this diseases isn’t funded properly and research isn’t being done etc, which is why the patient community loves them. But this doesn’t prove that they are good or know what they are doing. There is no replicated science to test them against.

    If one was to be cynical one could say that there is no need to charge the patients the ridiculous amounts of money a lot of them do, which is not justified by what they are doing and very often can be done for free or at least a lot less expensive elsewhere, and that supportive statements to the CFS community it is just good PR to get them more patients, and to get grants off governments, universities and private donors, and that they are living the high life, while their patients are forced to mortgage their houses and live in poverty to pay these doctors exorbitant fees for appointments and experimental treatments that frequently leave the patients only feeling mildly improved, no improvement at all and often a lot worse and in some cases they have almost killed the patient.

    So who’s a good CFS specialist and who isn’t, well nobody knows, nobody is curing their patients and there is no science to judge the CFS specialists on. Because there is no replicated science you can’t so oh but so and so has been doing this for twenty years, they could have been doing it completely wrong for twenty years and nobody can prove otherwise.

    But what we do know is that the twenty five writers of the ICC would not agree with them using Fukuda and CCC to assess the patients in this study they think that the ICC is better, the writers of the ME/CFS primer would not have supported the testing requirement used in this study because they say far more extensive testing needs to be done. And I would imagine that Dr Hyde would have told them they were completely bonkers to only do the few tests they did to assess the patients for other possible diseases.

    So whichever of the CFS doctors people decide they have faith in is just exactly that faith it is not science.

    So if things are to be done scientifically, which is the only way that they are ever going to get a pure cohort to study. It has to based on science not unproven faith that whichever CFS specialist it is, is good, because this is impossible at the present time to be proven scientifically. But what we do know is that ME is a disease with no known cause and that it has symptoms that are also caused by many other diseases or combinations of diseases.

    So from a scientific point of view we can’t rely on what is an unproven opinion of a CFS specialist that the patient’s symptoms are caused by ME. What has to be done is that they need to remember that it is a disease of exclusion and test the patent cohort for all the other disease that can cause these symptoms which will leave only the patients with these symptoms and no known cause and they can then be studied to find the cause. This is something that they have failed spectacularly to do in this study; the testing requirements are so minimal that it’s what you would expect from Wessely, if it is these CFS specialists that came up with these testing requirements, it is scientifically right to say that they have failed to come up with tests that will rule out all other possibilities! As an example of how bad the testing is in this article by Dr Mirza he suggests a set of tests which will find 90% of the misdiagnosed patients assuming that they did not use the new TSH reference range in this study they have failed to do every single one of the things that he says should be done!!! See http://www.bmj.com/rapid-response/2011/11/01/myth-chronic-fatgue-syndrome

    So the only way forward is to get diagnostic experts not CFS specialists who have not been trained in this. To make a list of the disease to be ruled out because they have the same symptoms and what tests need to be done to rule out these diseases. Then the CFS specialists can but forward which ever patients they think have CFS, these patients can then be given all the tests recommended by the diagnostic experts, and all the ones that are shown to have other diseases can be ruled out of the studies.

    This will create a two tiered system, which will double check the opinions of the CFS specialists on who has CFS and who, doesn’t.

    As an example of why it is so important that the patients are tested properly to rule out other diseases, if you take just one possibility that they didn’t test for Vitamin D deficiency. It’s estimated that as many as twenty percent of the population have vitamin D deficiency amongst people with chronic illnesses that rate is far higher due to them not being able to get out in the sun. So statistically it is very likely that a very high percentage of the patients in this study have some level of vitamin D deficiency. Because Vitamin D is a vital component of the immune system any attempt to study the immune system in this patient cohort is going to be finding the anomalies caused by vitamin D deficiency as well as ME. This will totally confuse the results and waste years of time, Also because it has recently been proven that the immune system is unable to fight infections without sufficient amounts of Vitamin D, this means that vitamin D deficient patients get all kinds of different infections, so if they do a pathogen search on these people they will find all these infections as well and won’t be able to tell which infection is responsible for ME. So lots of time money and effort will be wasted and everyone will have to suffer longer.

    Like I say I mean no offence to anyone with my opinions on CFS specialists, I’m just saying that because there is no replicated science in this field to judge them on it is impossible to say whether they are any good or not, but if the CFS specialists involved in this study are responsible for coming up with the list of tests to do to rule out other diseases they have failed spectacularly to come up with a list of tests that will rule out all other causes of CFS/ME symptoms!! Which endangers the chance of anything useful being found from further study of the patient samples from this study.

    All the best




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  14. rlc

    rlc Senior Member

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  15. ixchelkali

    ixchelkali Senior Member

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    I disagree with your reasoning. They said that the patients met the Fukuda and Canadian Consensus Criteria. If that is true, then the clinicians would have ensured that they did, meaning that they would have performed the tests, found the symptoms, and ruled out the other diseases, to meet the criteria of those two definitions. THEN, having selected patients that met the two case definitions, the study subjected them to a battery of lab tests and further exclusions.



    I assume they used the Fukuda and Canadian Consensus Criteria because that’s what the 2009 Science paper used, and this was intended to be a replication study.



    It’s true that there is no recognized medical specialty for ME/CFS doctor. There are no board qualifications, so that you can see that this individual doctor has met standardized minimal requirements. As scientific evidence, these clinicians could have been Dr Joe Schmo selecting patients who met the criteria. And yet it is also true that these clinicians were not Dr Joe Schmo diagnosing patients from what he reads on a website. While there may be no official standard for ME/CFS specialist, there are, in fact, doctors who are particularly knowledgeable about the biomedical research on ME/CFS and who have years of experience treating real, live patients. Doctors who are not quacks preying on desperate sick people. And people who follow the ins and out of ME/CFS know who they are. It doesn’t meet a standard of scientific evidence, and yet it is true nonetheless.
    SOC likes this.
  16. rlc

    rlc Senior Member

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    Hi ixchelkali, RE

    Scientific papers such as this contain all the information on what tests were done. They contain the scientific facts, people can’t just decide that they MUST have done other tests; if they had done other tests it would have been included in the paper.

    In this interview http://www.mecfsforums.com/wiki/Dr._Ian_Lipkin,_9/18/2012,_TWiV Dr Lipkin explains

    we looked at, you know, a wide range of parameters that we thought might be important as exclusionary diagnoses, and I’ve mentioned some of these already, like evidence of liver disease…

    RACANIELLO: Right.

    LIPKIN: …and so forth. …

    RACANIELLO: Other viruses…

    LIPKIN: But Table 1 has a whole series of different things that WE THINK are important.

    So Lipkin is stating that the tests in Table 1 are the tests that they decided to do because they thought they were important, not because they were following the CCCs recommendations.

    The tests that they decided on, are not the same tests that the CCC recommended and certainly do not rule out all the diseases to be ruled out in the CCC, and because the CCC is badly written its own testing requirements also will not rule out all the disease that the CCC says should be ruled out, not to mention the fact that both the CCC and Fukuda have failed to include numerous common diseases that can cause these symptoms that should be ruled out, so even if they had done the tests in the CCC which they state they didn’t they did the tests they decided on, it still would not have ruled out other common diseases that can cause these symptoms e.g. the CCC does not say to tests for Vitamin D etc, etc

    Scientific papers contain the scientific facts, the facts are that the tests that they say they did in this paper are the only tests that they gave all the patients who participated in this study. These tests do not even come close to ruling out all the illnesses that can cause these symptoms.

    The authors of this scientific paper who decided amongst themselves on the testing requirements for it are,

    Alter, Mikovits, Switzer, Ruscetti, Lo, Klimas, Komaroff, Montoya, Bateman, Levine, Peterson, Levin, Hanson, Genfi, Bhat, Zheng, Wang, Li, Hung, Lee, Sameroff, Heneine, Coffin, Hornig and Lipkin.

    Now it is understandable that the Virologists who were involved in this study would not be experts in what other diseases cause the same symptoms as CFS and what the tests need to be done to rule out these diseases are, it is not their field of expertise. But for the CFS specialists, Anthony Komaroff, Dan Peterson, Nancy Klimas, Jose Montoya, Sue Levine and Cindy Bateman to have agreed with this incredibly minimal and completely full of holes testing regime is just totally unacceptable.

    Which goes back to the question, how do you know if a doctor is a CFS specialist, other than they have declared themselves one? The truth is there is virtually nothing to test them on!! Although people are very fond of saying that there is biomedical research in ME/CFS, the truth is that there is almost no replicated scientific evidence of anything in the field of ME/CFS, Just as with XMRV were so many people convinced themselves that the original study meant that XMRV was the cause of CFS, when proper replicated science was done the original findings turned out to be totally bogus. This happens with the majority of scientific findings when properly replicated they turn out to be bogus. All we have is a large amount of un-replicated studies, which are very likely to turn out like the original XMRV study to just be useless pieces of paper. The majority of ME/CFS studies are based on numbers of patients that are often so small the results are meaningless, almost all of them are based on not having ruled out other diseases in the patient cohorts so the patients could have had anything, and all these studies show vastly contradictory results, and for every study that say’s they have found biomedical evidence of something there is another one that said that they couldn’t find it at all, So in short there is no such thing as proven replicated Biomedical evidence of anything in this disease. There is just a bunch of unproven hypothesis and a lot of hypothesis that have been proven to be wrong that people are still holding on to. It is for this reason that the CFI research has been set up in the first place!!

    So there is no such thing as someone who is particularly knowledgeable about the biomedical research on ME/CFS, it is impossible because there is virtually no replicated independently verified biomedical research in this field, and anyone that says they are an expert in something that doesn’t exist, could I feel only be described as delusional.

    You can’t tests someone on what the symptoms of ME/CFS are, because all of the diagnostic criteria say very different things, you can’t tests some one on their knowledge of what tests confirm a ME/CFS diagnosis, because there is no replicated scientific proof that any tests do actually confirm a diagnosis of ME/CFS which is one of the reasons that the CFI has been set up. And you can’t test someone on what treatments should be given to ME/CFS patients because there is no replicated science that shows that these treatments work or are safe for ME/CFS patients.

    There is however one area of medicine that someone claiming to be a CFS specialist can be tested on. And that is there knowledge of what other diseases have these kinds of symptoms and what the tests are to rule out these other diseases are. If the CFS doctors involved in this study were tested on this and wrote down that the testing that they have agreed to be used in this study is all the testing that should be done to rule out other diseases, they would get an F, fail the test and not be allowed to be a CFS specialist. It is a great shame that someone can say that they are a specialist CFS doctor without having to be tested on this first.

    So when you say

    There is no independently replicated biomedical research on ME/CFS to be knowledgeable about, this is why the CFI was set to try and provide some. And you say

    The above CFS specialists involved in this study have agreed that the extremely woeful amount of testing done in this study is acceptable to rule out other diseases that cause the same symptoms as CFS despite the fact that almost any average GP would immediately start seeing holes in it. If they think that this is an acceptable amount of testing to use in a very important study like this, it would be reasonable to assume that they are also using these same tests to check if there patient have other diseases. Which raises the strong possibility that they are in fact seeing large numbers of people with a vast assortment of diseases that they are not testing them extensively enough to correctly diagnose. Statistically as so many of the diseases that they are not going to be able to diagnoses with this set of tests are very, very common and ME has always been very rare, it is very likely that the large majority of their patients that they think have CFS don’t have it.

    As these doctors do not to the best of my knowledge make their testing regimes available for us to check, we can’t confirm that these are the tests that they do. But as these doctors have never made any public statements about finding large numbers of misdiagnosed patients, and other doctors who do extensively test their patients for other diseases report finding 80-90% of their patients have been misdiagnosed with CFS when they really had other known diseases. This leads me to seriously question if they do have years of experience of treating real live ME patients. Because if they are using the same kinds of tests to rule out other diseases that they have agreed to be used in this very important study then the only possibility is that the overwhelming percentage of their patients will be misdiagnosed and not have ME.

    So there is nothing to tests CFS specialists on as there is no replicated science on which to test them on. The only thing that you can test a CFS specialist on is there knowledge of what other diseases have to be tested for and what these tests are, which like I say if these doctors involved in this study were tested on this and said that the tests that they agreed to be used in this study were the correct tests to use they would have failed spectacularly and not be allowed to be a CFS specialist.

    So the only measurable thing that CFS specialists are actually excelling at is their bed side manner and making public statements about how badly CFS patients are being treated, which gets then a lot of support from the patient community and more patients, none of which means they are a good doctor, or is something to pay exorbitant fees for.

    Like I say I’m not trying to offend anyone and I know some members of the community have a lot of faith in certain of the CFS specialists, but what I’m trying to point out is, that is all it is, faith, the CFS specialists say they are good and people believe them. But from a scientific point of view there is almost nothing to measure the standard of these doctors on because there is no replicated science to test them on. The only thing that they can be tested on is there knowledge of the other disease that can cause the symptoms of CFS and what the tests for these diseases are. The CFS specialists involved in this study have shown by agreeing to the testing requirements of this study that their knowledge of this is very poor, and if they are doing the same kind of testing on their own patients statistically this can only mean that the vast majority of their patients don’t have ME in which case the experience that they think they have on this disease is actually largely based on patients that don’t have it.

    So any way what diseases has this study failed to test for that can cause the same symptoms as CFS, well here’s a few of the top of my head.

    Celiac disease
    Vitamin D deficiency
    B12 Deficiency
    Folate deficiency
    Magnesium Deficiency
    Central sleep apnea
    Obstructive sleep apnea
    Hemochromatosis
    Primary, secondary and tertiary adrenal insufficiency (Addison’s etc)
    Cushing syndrome
    Iron deficiency
    lupus
    Wilson’s disease
    Acute intermittent Porphyria
    Porphyria cutanea tarda
    Porphyria variegata
    Crohns disease
    Tuberculosis
    Pituitary tumors

    Brucellosis

    Giardia

    Leptospirosis

    Toxoplasmosis

    Chiari malformation

    Sarcoidosis

    Amyloidosis

    Brain tumors and tumors of the central nervous system

    Many forms of Cardiac disease, they have not even tested Homocysteine a basic screen for heart disease.

    If they have used the out of date reference range almost all labs still use for TSH, so it is the most likely option, they will have missed cases of hypothyroidism.

    Pre diabetes

    Intestinal parasites such as hook and tape worm

    Etc, etc, etc

    So apart from the fact that because they haven’t tested for these diseases and that many of these diseases are so common that there has to be people with these illness in the patients that they have selected. Which means they will be studying a mixed cohort and the results will be confusing and totally meaningless.


    I’d like to paint a picture of how because of this the 10 million dollars of donated money for the CFI research will effectively be flushed down the toilets. If as is planned samples from this study are used for further research or more patients are selected using the same minimal testing which is the most likely option as it is the same doctors that are involved in the CFI research.


    If when they have done their research and decide to announce their results in a press conference, if there is anyone there who even has a rudimentary knowledge of fatigue causing illnesses at the press conference, it is likely to go something like this.


    Interviewer. Dr Lipkin you say that samples were taken from carefully selected patients, but I see that in the tests you did on these patients ANA has not been tested, as this test is used to detect lupus a disease that can cause the symptoms of CFS how do you know that some of these patient you selected didn’t have lupus?

    Lipkin. um er well no we didn’t test ANA so um that could be possible.

    Interviewer. Dr Lipkin, you also haven’t tested these patients for very common conditions that can cause these symptoms such as Celiac disease, Hemochromatosis, sleep apnea, b12, folate, Vitamin D deficiency, iron deficiency, common causes of heart disease and pre diabetes, not to mention rarer conditions such as Addison’s, Pituitary tumors and Porphyria how if these diseases are capable of causing the symptoms of CFS is it possible that you can say that these patients you have selected have CFS, when you haven’t tested them to ensure that they don’t have one of these diseases instead of CFS, after all the medical literature says that CFS is supposed to be a disease of exclusion were patients have to have all these diseases ruled out before they can be diagnosed with it?


    Dr Lipkin, um er um shuffles nervously in his seat, well what your saying is true we haven’t tested the patients for those conditions so theoretically it is possible that these patient do have these other conditions um not CFS.


    Interviewer, Dr Lipkin so what your saying is that there is no evidence that these patients that you are claiming to have found these results in actually have CFS because they haven’t been tested for so many other diseases that cause the symptoms of CFS and these results could equally well have come from a group of patients that have a large collection of other diseases.


    Lipkin er, um, er well yes we didn’t test the patients for those other conditions so er that could be possible. But we did make sure that they all had the symptoms attributed to CFS.


    Interviewer, surely as many diseases are known to have the same symptoms as CFS and you haven’t tested for a large number of disease that do have these symptoms, by just saying that the patients had the symptoms of CFS, this just means that you are guessing whether the patients had CFS because nobody has proved that they don’t have all the other diseases that cause these symptoms that you haven’t tested the patients for?


    By this time everyone involved in the CFI research are going to be the laughing stock of the entire scientific and medical community, it will be obvious that the patients they selected could have anything, that they have failed to follow the first rule of studying any diseases (make sure that the patients you are studying actually have the disease you are studying) and all their research time and effort and all the money that has been invested in it will be flushed down the toilet. And there will be very little chance of them getting any more money to sort out the colossal mess they have made.


    This might not happen at the press conference but it certainly will happen, the scientific community will do its job and pick whatever research they have done apart and it will very quickly be reveled that they have no proof whatsoever that the patients they selected have CFS because they haven’t tested the patients for the other diseases that cause these symptoms. Therefore the results will be totally meaningless and they will be ridiculed for poor research.


    Anyway I have said all I need to say on this subject and pointed out that their scientific methodology for selecting patients is flawed because they have not tested these patients for a very large number of the diseases that cause the symptoms of CFS. If people want to keep having faith that these doctors are doing it right, despite the fact that the testing that they did in table 1 of this study shows that it is statistical impossible that they haven’t selected a mixed cohort that is their choice.


    The good news is that if people do want what they claim they want good scientific research done into ME, Dr Lipkin has shown that he is very influenced by the views of the patient community, so if enough people contact him and demand that the patient cohort is properly tested to rule out all the other diseases that cause these symptoms there is a chance he may introduce more testing.


    But if the patients are not going to be tested properly all the future research is going to be a waste of time, and the patients will be left to suffer for the rest of their lives and are very likely to be reclassified under the new DSM as being mentally ill. So it’s up to the patient community to demand better science or suffer the consequences.


    All the best








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  17. biophile

    biophile Places I'd rather be.

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    I would like to summarize some of rlc's excellent points, mostly for myself, but also for anyone else who, like me, often struggle to get through multiple large posts at once and are tempted to gloss over them instead.

    [subject to editorialization and further modification]

    The recent study on XMRV/pMLV, irrespective of the quality of the virology, did not do enough to exclude known medical conditions from the ME/CFS cohort (the list of tests performed can be found in Table 1 of the paper: http://mbio.asm.org/content/3/5/e00266-12/T1.expansion.html). Unfortunately, this is a very common problem in the research literature on ME/CFS, which is primarily comprised of small studies without adequate confirmation or follow-up attempts at replication.

    There are many different and conflicting criteria for ME and/or CFS, which makes it difficult to define it for research and has lead to mixed cohorts. A start would be thoroughly excluding all patients with other diseases by extensively testing the study candidates (although it is also important not to accidentally exclude those with clinical characteristics previously associated with ME/CFS eg OI). Without taking all these cautions, efforts into projects such as the CFI will be wasted. We also cannot assume that when a research group uses a stated criteria, that all the tests suggested by those criteria were actually done.

    It is difficult to judge a "top ME/CFS expert", because there is no reliable standards to compare with, and little established/replicated science on the issues of testing and treatment. Anyone can present themselves as an expert or be accepted as such, by being familiar with much of the (unreplicated) research and demonstrating great sympathy towards patients, but are often very expensive and not necessarily effective doctors.
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  18. Bob

    Bob

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    Ian Lipkin is very hot on sub-groups. He has said that he expects his research to identify sub-groups. So maybe a heterogeneous cohort might not be such a problem in his research.
  19. user9876

    user9876 Senior Member

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    I think it is a good idea to have a heterogeneous cohort since to subdivide is to make assumptions about how that division should go. You need to then do the analysis when you find something wrong as to which symptoms and signs relate to that observation. However it could be there are differetn mechanisms each leading to similar sets of symptoms.

    I would have thought however that as the variability of the cohort grows the size of the sample set should also grow. In optimisation for every additional parameter in the model you are fitting you need to roughly double the number of samples you deal with. Sample theory is not something I can remember anything about but I would have thought pulling samples from a more complex set of patients would imply you need more.
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  20. Bob

    Bob

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    Yes, I would have thought that is the case.

    Something else I've just thought about, which might have been mentioned before, is that Lipkin has narrowed down his cohort using what seems like quite arbitrary criteria, such as night-sweats, so it could be possible that he is actually excluding ME patients.

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