CAA-XMRV: Tell Me What It Means To ME? My deepest apologies to Aretha Franklin. I couldnt help it. Im out to give you all my money, but all Im askin In return honey, is to give me my proper respect ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The first item that appeared in my Saturday morning email was the CFIDS Associations notice of Dr. Suzanne Vernons latest blurb, Playing A Weak Hand Well. I had no doubt in my mind that this would be some kind of response to the latest failed XMRV pseudo-replication study, and was hoping that the rapid response by the CAA was indicative of change..in light of the recent conversations with the advocacy group as a result of Whassup With the CAA, and in light of some even more recent failed response to the DSM5 circus. (Well get to that further down in this blog.) It was not. I read the article and my brain shorted out on the spot. I dont know how Mary Schweitzer pulled off such a rapid and beautifully perfect response on her blog, but I thank Goodness that she did. I went into overload. In the Weak Hand article, Dr. Vernon states, With the third negative study published in just 51 days, it is now harder than ever to explain the negative results based on CFS patient characteristics and methods alone. The implication is that XMRV is likely to explain a subset of CFS rather than all cases defined as CFS (using any of the seven existing definitions). Harder than ever to explain? Really? Lets break this down. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ With the third negative study published in just 51 days. Stop. Right there. How have these so-called replication studies been handled so far? Does the fact that THREE of them have been completed in just 51 days ring any bells? It should. It smacks of hurried, slap-dash, agenda-driven pseudoscience.the type that occurs when we hold to the concept that science is a social effort, and not that science is, er, science. And lets take a look at the driving forces behind these studies, Simon Wessely in particular. The first of these three biopsychosocial nonreplication replication studies came to us straight out of Imperial College, UK, patients courtesy of Simon Wessely himself. The percent of samples found to have XMRV iszero. Not even a token XMRVer in the bunch. The methodology was questionable at best, and even the CAA admitted that this should not be considered to be a valid attempt at replication. That being the case, why is it included as a part of Dr. Vernons argument that it is now harder than ever to explain the negative results? How can we even count this as a negative study, if we deny its validity in the first place? Stephen Ralph DCR(D) retired, wrote an excellent piece describing the irrelevance of the three negative studies that seem to concern Dr. Vernon, called Exposing More Anti-XMRV Spin In it, he says, So in closing, we have now had three post-Lombardi et al studies 2 in the UK, and 1 in the Netherlands. * None of them bothered at all to replicate Lombardi et.al. * None of the three studies used Fukuda and Canadian criteria to specifically select all their patients using the detailed outline of patient selection given in the Lombardi et al paper (see above). * None of the three null studies validated their test against samples from CFS patients already known to be XMRV positive * None of these three studies even conceded that there is a growing population of CFS XMRV positive patients across the world including the United Kingdom. * None of these three studies made any attempt to carry out the full range of testing methods specifically used by the Lombardi et al research ie: a)PCR on nucleic acids from un-stimulated white blood cells; b)XMRV protein expression from stimulated white blood cells; c)Virus isolation on the LNCaP cell line; and d)A specific antibody response to XMRV. (Note: It should also be emphasized that all four methods were needed for very good reasons and not just for the sake of wasting time and money. You can find out why by reading the Lombardi et al papers cited in this article.) ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The implication is that XMRV is likely to explain a subset of CFS rather than all cases defined as CFS (using any of the seven existing definitions). Why is there no discussion here about the seven existing definitions? Surely this is CFS history 101. What about Oxford? Do we find it reasonable in ANY scenario for XMRV replication attempts to be based on OXFORD? Why is there no reiteration of the inherent flaws in Oxford, and how it came to beas a direct response AGAINST the biology of the disease, driven by the psychologizing movement. Why, in this statement alone, is the CAA once again expediently reclassifying the very cohort that earned us the CFS brandas a subset? Why does the CAA NOT defend Holmes and instead follow the political trail to psychology by not doing so? Mary Schweitzers blog does an excellent job of addressing the Oxford Criteria question. PLEASE read it if you havent already! There are so many flaws, faux pas, and political red flags in this one paragraph alone that I almost didnt read the rest of the article. But I did. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Lets talk about the WPI samples. Further in her paper, Dr. Vernon argues that the study by Lombardi, et al, published in Science showed that XMRV could be detected in samples from the WPI repository. Unlike the negative XMRV studies where results and characteristics of these CFS cohorts have been the subject of numerous earlier publications, little is known about the patient samples stored in this repository. The Science papers supplement refers to a variety of abnormalaties without defining how they were measured or how uniformly they show up among patients whose samples are stored there. The supplement makes reference to DeFrietas PNAS publication. Does this mean that WPI tested the same samples as DeFrietas, et al, or that they were obtained from the same cluster outbreaks mentioned in her paper? We do not know. This seems like idle speculation. In another, earlier paper written by Dr. Vernon, she states that samples from the CFS patients in the Science paper were gathered from several regional physicians practices, according to information on the Whittemore Peterson Institutes website. http://www.cfids.org/xmrv/021510study.asp. Other than the inferences about the sample selection, lets not forget that the original study was done in conjunction. The three major players were the WPI, AND the Cleveland Clinics, AND the NCI. This was not a fluke, nor a fly-by-night 51-day wonder. I stand confused. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ More on DSM5, as promised. Why, WHY, is the CAA so quick to jump on anything that seems to denote a negative connotation for WPI, when it comes to anything XMRV? Especially when issues that are genuinely threatening to the CFS community take a back seat? Two weeks ago, on Facebook, we asked the CFIDS Association what their position was regarding the DSM5 drafts, under their discussion topic, Questions for the CAA. (See DSM-5: Ticket Back to Reevesville for more information on DSM5) Several of us were asking questions. Here are the questions, and the responses we got: Question: What is the CAA doing to combat the DSM5 drafts? The CFIDS Association of Americas response: Have you inquired with the IACFS/ME? Their organization is led by a psychologist (Fred Friedberg) and has the professional expertise to navigate DSM criteria and the APA process for revising/adopting it. Question: The point wasnt what anybody else was doing, though., it is what are YOU doing, CAA? This is a key, critical , end-of-the-rope advocacy issue. Supporting the science and combatting the psychobabble is what our advocacy group should be doing, first and foremost. If there is a more Custers-Last Stand-type scenario that is going on at the moment, diverting our advocacy groups attention, Id like to know what it is. The CFIDS Association of Americas response: Understanding and influencing proposed new DSM disorders and their consequences for ICD coding and clinical care require consultation with professionals who have expertise in the processes employed by the American Psychological Association and World Health Organization. Were aware of the issues, but cant provide an immediate and definitive answer about how to effectively intervene. Validation of biomarkers for CFS would substantially reduce the impact of the CSSD proposal and validating CFS biomarkers is our top priority. Question: CAA, will you not hold up the Holmes 88 criteria and SHOW the authors of the DSM the part where it says psychiatric disease is excluded under the Major Exclusion portion of the criteria? http://www.cfids-me.org/holmes1988.html What possible reason is there to be anything less than adamant on insisting upon the intended meaning of this Major Exclusion? Question: I understand that you have Katrina Berne, Ph.D, (Psychologist) on your Board. Couldnt she take a look at the DSM5 proposals and tear apart their intent? She has been a PWC for years, so I feel she must be very interested in this continuing debacle at the CDC. The CFIDS Association of Americas response: The DSM changes were posted last week and the public comment period is open through April 20. Rather than act hastily, we need to undertand all the factors involved with these proposals and how to most effectively influence the final decisions. We have a tradition of being deliberate and thorough in our actions that we intend to uphold. The CFIDS Association of Americas response: We were working over the weekend on this and other issues, but administrative access to our Facebook account was blocked by Facebook for site mainenance for several hours on Saturday and Sunday, preventing us from making any posts. Question: If the mission statement is to promote awareness, wouldnt that include issues of great concern to CFS patients. While acting with deliberation and without undue haste is laudable, shouldnt the CAA at least be making CFSers aware that the DSM revision process is occurring, and that CFSers would do well to scrutinize it? Question: Secondary to that, how about a statement of concern regarding Sharpe and company being on the panel? The CFIDS Association of Americas response: No further response. (It needs to be pointed out that the CAA never bothered to actually visit the questions thread long enough to post answers. These questions had to be asked again and again on different threads, and then when answers were received elsewhere, posted by us into the q&a.) ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ So in answer to the very appropriate Holmes 88 criteria questions, and all other criteria questions, it appears that we will get no answer from the CAA. It does not appear that they will hold up the original Holmes in our defense, whether it be against psychobabble, or in response to improper replication testing of a potential biomarker. Im reminded of my last visit to Kentucky Fried Chicken, over 10 years ago. I asked for all white meat. They said it couldnt be done, as theyd haveta COOK that! I eat at Popeyes now.