Article: The CDC XMRV Study: How Not to Find XMRV?
- Thread starter Phoenix Rising Team
- Start date
It looks to me like the authors of the paper probably didn't want to find the bug.
But when some big kahuna at the DHHS heard about the FDA/NIH study he realised he had been asleep at the switch for the past nine months while a major discovery was unfolding.
Now Mr.Bigkahuna is frantically trying to buy a bit of time and patch up a bunch of holes as this unfolds.
There is no chance in hell of burying this thing at this point. Wall Street Journal, Nature, etc... this cat is out of the bag.
But when some big kahuna at the DHHS heard about the FDA/NIH study he realised he had been asleep at the switch for the past nine months while a major discovery was unfolding.
Now Mr.Bigkahuna is frantically trying to buy a bit of time and patch up a bunch of holes as this unfolds.
There is no chance in hell of burying this thing at this point. Wall Street Journal, Nature, etc... this cat is out of the bag.
I agree, Julius. The cat is out of the bag and there is no way the CDC can put it back in, no matter how hard they try. All they can do is slow the progress of research and make fools of themselves.
I think that's exactly what happened - they were asleep at the switch. I guess its possible that they never suspected that there would be a positive paper out there - so they never really kept an eye on things.
How TO FIND XMRV - Do Not Forget To STIR!
Cort, this has probably been discussed at length (and I missed it) but today, someone (Gracenote?) posted a link to the very detailed "Finding XMRV for Dummies" article by Mikovits that is posted on the IACFSME web site:
http://www.iacfsme.org/BULLETINSPRING2010/Spring2010MikovitsLetter/tabid/427/Default.aspx
Simply add a clinician that knows a CFS patient from a depressed patient (and some age/gender/geographically matched controls), $200-300K(?), stir*, and you have something very close to a replication study.
Sorry if I'm revisiting a well worn topic. I just hadn't seen this description of how one tests for XMRV before.
* Don't forget to stir! IT WON'T WORK if you don't and millions of people will remain sick and some will die. You, on the other hand, will simply look silly when people figure out you omitted the simplest step. The clinician will make a difference but in a pinch you can omit the clinician and still get some results (we can't recommend deliberately removing all CFS patients and then making up your own definition of a CFS patient as your results will not be comparable to any other cohort).
Cort, this has probably been discussed at length (and I missed it) but today, someone (Gracenote?) posted a link to the very detailed "Finding XMRV for Dummies" article by Mikovits that is posted on the IACFSME web site:
http://www.iacfsme.org/BULLETINSPRING2010/Spring2010MikovitsLetter/tabid/427/Default.aspx
Simply add a clinician that knows a CFS patient from a depressed patient (and some age/gender/geographically matched controls), $200-300K(?), stir*, and you have something very close to a replication study.
Sorry if I'm revisiting a well worn topic. I just hadn't seen this description of how one tests for XMRV before.
* Don't forget to stir! IT WON'T WORK if you don't and millions of people will remain sick and some will die. You, on the other hand, will simply look silly when people figure out you omitted the simplest step. The clinician will make a difference but in a pinch you can omit the clinician and still get some results (we can't recommend deliberately removing all CFS patients and then making up your own definition of a CFS patient as your results will not be comparable to any other cohort).
I object to calling any of the participants in the study CFS patients. By the CDC's created definition they look at generalized fatigue. That may be a good subject for research but should not use CFS dollars or be compared to CFS studies.
They are using goat blood for a positive control because they wouldn't accept the WPI positive samples, so they have to use different chemicals from the human blood samples. The whole thing seems skewed to me around not using a positve human blood sample for control. There is no evidence that they could get a positive reading on a positive human blood sample. It's all test tube constructed substitutes. Koch Institute came closest to what we've heard they need to do using the env protein. Maybe they were seeing something and called it negative. I'm not sure their other test was more sensitive, since they didn't culture they weren't using cells that were reproducing virus. I want to read more about the ug numbers. Not a professional, just a reader, but it doesn't sound over to me.
They did say XMRV is very like polyclonal MulV which I think is very dangerous. They may be taking that back later.
We really need to get the CDC to dump that stupid definition. Everyone at the CFSAC meeting was so polite to the new CDC officer, but enough is enough. They can't go on with years of bad research. Just call them fatigue studies and give us our money back.
They are using goat blood for a positive control because they wouldn't accept the WPI positive samples, so they have to use different chemicals from the human blood samples. The whole thing seems skewed to me around not using a positve human blood sample for control. There is no evidence that they could get a positive reading on a positive human blood sample. It's all test tube constructed substitutes. Koch Institute came closest to what we've heard they need to do using the env protein. Maybe they were seeing something and called it negative. I'm not sure their other test was more sensitive, since they didn't culture they weren't using cells that were reproducing virus. I want to read more about the ug numbers. Not a professional, just a reader, but it doesn't sound over to me.
They did say XMRV is very like polyclonal MulV which I think is very dangerous. They may be taking that back later.
We really need to get the CDC to dump that stupid definition. Everyone at the CFSAC meeting was so polite to the new CDC officer, but enough is enough. They can't go on with years of bad research. Just call them fatigue studies and give us our money back.
Well, I'm still re-reading the paper so it can sink in and I have to go back and look at the populations they used again.
But, Cort, you are right that the CDC papers are usually more subtle than their headlines and if you read the papers, you find lots of interesting bits. Unfortunately or intentionally though, the headlines and press releases often are constructed to close the door on honest CFS research and investigation.
By saying at the end of the paper, more or less, that the CFS they were looking at is not the same one that the WPI is looking at, they are admitting they are studying the wrong group but their headlines seem to imply otherwise. I would like to see someone find out the percentage of people currently diagnosed with CFS by healthcare staff who also fit Canadian Criteria. My guess is that most of us will; it's just that the CDC has ignored people's symptoms. "The greatest trick the CDC ever pulled was to make you think CFS didn't exist" -- first it was merely a bunch of depressed middle-aged yuppies, then it was childhood sexual abuse victims, now it's NOT what people diagnosed by their physicians with CFS have. The CDC has once again misappropriated funding.
And speaking of cohorts, 2 can play at this game. With the Wichita dial-up cohort, which composed 11/51 of the CFS subjects in this current study, which 11 were these?
In the 2003 article below, the CDC states that with three years of Wichita cohort follow-up,
- only 3 out of 65 total had 2 consecutive visits where they still diagnosed with CFS.
-- at one year, only 1/3 were still diagnosed with CFS
--at years 2 and 3, only 21% were classified as CFS
-- over 3 years, 23% were diagnosed with excluded conditions and no longer fit CFS
-- "Since only 13.9% had ever been treated or diagnosed with CFS, the majority had either not perceived their status as an illness or had not undergone evaluation for identifiable causes of fatigue."
-- median hours worked -- 40!!! hours a week
-- 77% gradual onset
Were these 11 people who worked 40 hours a week? Were they folks who were later excluded as having CFS? Did they sustain the CFS diagnosis only for a year?
http://www.hqlo.com/content/1/1/49
[Note to WPI: they should have released characteristics of their cohort into the scientific press as soon as possible, more than just presenting it at the CFSAC 10/2009 conference. By the time it was written up in Science, it was too late. Give the CDC an inch and they'll take a mile.]
But, Cort, you are right that the CDC papers are usually more subtle than their headlines and if you read the papers, you find lots of interesting bits. Unfortunately or intentionally though, the headlines and press releases often are constructed to close the door on honest CFS research and investigation.
By saying at the end of the paper, more or less, that the CFS they were looking at is not the same one that the WPI is looking at, they are admitting they are studying the wrong group but their headlines seem to imply otherwise. I would like to see someone find out the percentage of people currently diagnosed with CFS by healthcare staff who also fit Canadian Criteria. My guess is that most of us will; it's just that the CDC has ignored people's symptoms. "The greatest trick the CDC ever pulled was to make you think CFS didn't exist" -- first it was merely a bunch of depressed middle-aged yuppies, then it was childhood sexual abuse victims, now it's NOT what people diagnosed by their physicians with CFS have. The CDC has once again misappropriated funding.
And speaking of cohorts, 2 can play at this game. With the Wichita dial-up cohort, which composed 11/51 of the CFS subjects in this current study, which 11 were these?
In the 2003 article below, the CDC states that with three years of Wichita cohort follow-up,
- only 3 out of 65 total had 2 consecutive visits where they still diagnosed with CFS.
-- at one year, only 1/3 were still diagnosed with CFS
--at years 2 and 3, only 21% were classified as CFS
-- over 3 years, 23% were diagnosed with excluded conditions and no longer fit CFS
-- "Since only 13.9% had ever been treated or diagnosed with CFS, the majority had either not perceived their status as an illness or had not undergone evaluation for identifiable causes of fatigue."
-- median hours worked -- 40!!! hours a week
-- 77% gradual onset
Were these 11 people who worked 40 hours a week? Were they folks who were later excluded as having CFS? Did they sustain the CFS diagnosis only for a year?
http://www.hqlo.com/content/1/1/49
[Note to WPI: they should have released characteristics of their cohort into the scientific press as soon as possible, more than just presenting it at the CFSAC 10/2009 conference. By the time it was written up in Science, it was too late. Give the CDC an inch and they'll take a mile.]
Can't we just call our illness CCCFS (Canadian Criteria Chronic Fatigue Syndrome) and clarify that this is a different illness from CDCCFS (Centre for Disease Control Chronic Fatigue Syndrome)?
It is already proven that XMRV is connected with CCCFS (WPI study, cf. selection of patient cohort), and that it is not connected with CDCCFS (Kings college study, Dutch study).
We need to get the separation of patient cohorts publicly established and accepted, and stop going along with the charade of pretending two completely different illnesses are one. I actually wish the WPI had come straight out saying that they had discovered that some patients incorrectly diagnosed with CFS actually had a new, distinct illness called XAND and thus we could have avoided all this sheer nonsense.
It is already proven that XMRV is connected with CCCFS (WPI study, cf. selection of patient cohort), and that it is not connected with CDCCFS (Kings college study, Dutch study).
We need to get the separation of patient cohorts publicly established and accepted, and stop going along with the charade of pretending two completely different illnesses are one. I actually wish the WPI had come straight out saying that they had discovered that some patients incorrectly diagnosed with CFS actually had a new, distinct illness called XAND and thus we could have avoided all this sheer nonsense.
strategic pause
There's always the possibility that this paper is Reeves' last gasp and it had to be published.
Maybe Alter's study is being held back to provide a 'strategic pause', as it says in 'Nature', before utterly contradicting the 'Reeves' study and re-directing the CDC's research into M.E.
Yes, optimistic, I know...
http://www.nature.com/news/2010/1007...tml?s=news_rss
There's always the possibility that this paper is Reeves' last gasp and it had to be published.
Maybe Alter's study is being held back to provide a 'strategic pause', as it says in 'Nature', before utterly contradicting the 'Reeves' study and re-directing the CDC's research into M.E.
Yes, optimistic, I know...
http://www.nature.com/news/2010/1007...tml?s=news_rss
On their website http://www.cdc.gov/ncidod/dhqp/bp_xmrv_overview.html the CDC states:
This is simply untrue. They need to be held accountable for this perversion of science.
This is simply untrue. They need to be held accountable for this perversion of science.
Its a formaility of scientific research that you have your hypothesis and the opposite null hypothesis. A properly designed study must allow equal opportunity for either to be true.
I'm sure the world at large will view the CDC paper as a bona fide attempt to test the hypothesis that XMRV is associated with CFS - but this hypothesis is predicated on the pre-condition that CFS may be an organic illness. Its clear to me that (leaving aside other failings) the hypothesis was never properly tested because the CFS cohort excluded anyone with any evidence of organic illness.
We all know however that Reeves' hand is all over the CDC study design and cohort selection. We also know that Reeves believes CFS to be psychosomatic.
Its obvious from the details of the cohort that they have very carefully screened the 'CFS' cohort, and probably the controls, to eliminate any possibility that these folk were anything other than either mildly fatigued or had a psychosomatic illness. I mean fatigue for one month or more, plus one other symptom including unrefreshing sleep? Would that not cover the whole Atlanta population during high summer?
Switzer and all then criticise the WPI cohort as failing to exclude those with neurological symptoms which are "clearly exclusionary for CFS"? Yet they also suggest the possibility that the WPI cohort is a subset of CFS? Surely the former statement logically negates the latter
Perhaps we should be very grateful to CDC for finally spelling out in detail that the Reeves CFS they are studying is a completely different disease from ME/CFS.
If both the CDC and CCC definitions were watertight (i.e. that the CDC definition of CFS/Reeves Disease excludes anyone with organic illness and that the CCC definition excludes psychosomatic illnesses) then the two definitions are mutually exclusive.
The bottom line is that CDC and WPI were studying two entirely different illnesses. One being ME – an organic neuro-immune disease and the other Reeves CFS – a somatoform disorder.
ME is not a subset of CFS. Rather ME and Reeves CFS can only be considered as both subsets of 'Conditions with fatigue as one of perhaps many symptoms'.
If I lived in the states and had a diagnosis of CFS and could demonstrate immune abnormalities, POTS, orthostatic intolerance etc, on the basis of the CDC description of CFS, I'd be kicking up hell over mis-diagnosis.
Ironically the CDC paper could be the final breaking point that seperates out ME/CFS or XAND from the wastebasket CDC and Oxford idiopathic fatigue.
Bring it on!
I'm sure the world at large will view the CDC paper as a bona fide attempt to test the hypothesis that XMRV is associated with CFS - but this hypothesis is predicated on the pre-condition that CFS may be an organic illness. Its clear to me that (leaving aside other failings) the hypothesis was never properly tested because the CFS cohort excluded anyone with any evidence of organic illness.
We all know however that Reeves' hand is all over the CDC study design and cohort selection. We also know that Reeves believes CFS to be psychosomatic.
Its obvious from the details of the cohort that they have very carefully screened the 'CFS' cohort, and probably the controls, to eliminate any possibility that these folk were anything other than either mildly fatigued or had a psychosomatic illness. I mean fatigue for one month or more, plus one other symptom including unrefreshing sleep? Would that not cover the whole Atlanta population during high summer?
Switzer and all then criticise the WPI cohort as failing to exclude those with neurological symptoms which are "clearly exclusionary for CFS"? Yet they also suggest the possibility that the WPI cohort is a subset of CFS? Surely the former statement logically negates the latter
Perhaps we should be very grateful to CDC for finally spelling out in detail that the Reeves CFS they are studying is a completely different disease from ME/CFS.
If both the CDC and CCC definitions were watertight (i.e. that the CDC definition of CFS/Reeves Disease excludes anyone with organic illness and that the CCC definition excludes psychosomatic illnesses) then the two definitions are mutually exclusive.
The bottom line is that CDC and WPI were studying two entirely different illnesses. One being ME – an organic neuro-immune disease and the other Reeves CFS – a somatoform disorder.
ME is not a subset of CFS. Rather ME and Reeves CFS can only be considered as both subsets of 'Conditions with fatigue as one of perhaps many symptoms'.
If I lived in the states and had a diagnosis of CFS and could demonstrate immune abnormalities, POTS, orthostatic intolerance etc, on the basis of the CDC description of CFS, I'd be kicking up hell over mis-diagnosis.
Ironically the CDC paper could be the final breaking point that seperates out ME/CFS or XAND from the wastebasket CDC and Oxford idiopathic fatigue.
Bring it on!
Certainly a novel solution!
I like the Definitions Athene. (big grins)
Well, the "managing" by the DHHS has got the boys up in arms for sure. Even Dr. Rancello seems pissed and he is pretty polite all in all. One one side we have the well respected trio of Dr. Coffin, Dr. Goff, Dr. Ruscetti and their supporters. and on the other side we seem to have the gov'ment trying to play big brother. I don't think these guys appreciate their fellow college Dr. Alter being 'managed'. (big grins)
It should make for an interesting summer.
Well, the "managing" by the DHHS has got the boys up in arms for sure. Even Dr. Rancello seems pissed and he is pretty polite all in all. One one side we have the well respected trio of Dr. Coffin, Dr. Goff, Dr. Ruscetti and their supporters. and on the other side we seem to have the gov'ment trying to play big brother. I don't think these guys appreciate their fellow college Dr. Alter being 'managed'. (big grins)
It should make for an interesting summer.
The CDC have a difficult problem on their hands: how to make the disease go away without losing the funding, which they have repeatedly misappropriated in the past - as revealed in official testimony about doing better in the future. The way out of this is to maintain confusion, which they have succeeded in doing.
At a technical level, there are lacunae in this paper which invite speculation. (This could be my own problem due to cognitive impairment from this disease I imagine I have. I'm hoping someone will clarify things I've missed.)
The statements about the diagnostic criteria employed generate confusion, as above. Can they point to any published criteria they are actually using as published? My reading of the Fukuda definition leaves me in doubt that this is actually what was used in the study. The statement indirectly attacking the Canadian Consensus Criteria is ingenuous (not ingenious, except possibly as a diversionary tactic). We are left with the impression any solid physical characteristics are exclusionary. This should be clarified.
A series of papers early in the year attracted criticism about their failure to validate their tests against samples drawn from living infected human beings. This paper is no exception, despite months of prior opportunity. Spiking samples will not necessarily produce anything like you get from an infected person. The only evidence that this was taken into account is a paragraph about the lack of the availibility of a control panel. Why didn't CDC researchers address this issue before wasting time in the laboratory, let alone publishing? Is this potential pathogen peculiarly outside their scope?
While there is a statement that CDC laboratories were able to detect XMRV in samples from people they trusted, there is no supporting data to show how well they can detect virus if the sample is not labeled positive. This amounts to saying, "yes, we know how to detect this virus, trust us." We have no idea how close to the margin their results are. A double-blind study independent of CFS/ME is called for. Blinding should not be controlled by a group which has a demonstrated record of nonfeasance, misfeasance and malfeasance involving millions of dollars, plus Congressional testimony about same approaching perjury.
Among the criticisms of previous papers easily available prior to this publication, there were very specific statements about activating cells in the samples, then allowing these to divide several times, in order to raise the number of copies available to PCR. This paper does not appear to address these concerns in any way. Have I missed something, or is this an attempt to ignore opponents and proceed by sheer bluff?
In assessing sensitivity of tests it is important to consider the number of cells available at the start. We already know very few cells in the blood will show active infection. The difficulty of finding this may not bother those with highly specialized backgrounds, who can read between the lines. For me, this is a mystery. I also wonder about the relation between numbers of cells and amounts of DNA, as this can give an idea of the effectiveness of techniques for processing samples and extracting DNA prior to PCR. Why were such simple measures omitted? It is far too easy to think this was deliberate obfuscation. Responsible researchers should take pains to dispel such doubts.
It is clear that researchers working on this virus in relation to prostate cancer are also working at the limits of the state of the art. They have not been subject to the kind of prejudgment apparent here.
Had prostate cancer been treated like this one can imagine a senior researcher speaking off the record with the following statement:
"Just between you and me, this whole business stinks. All these complaints involve sexual organs, and when we check, we find none of these people have healthy sex lives. We have reason to believe they were sexually molested as children."
At a technical level, there are lacunae in this paper which invite speculation. (This could be my own problem due to cognitive impairment from this disease I imagine I have. I'm hoping someone will clarify things I've missed.)
The statements about the diagnostic criteria employed generate confusion, as above. Can they point to any published criteria they are actually using as published? My reading of the Fukuda definition leaves me in doubt that this is actually what was used in the study. The statement indirectly attacking the Canadian Consensus Criteria is ingenuous (not ingenious, except possibly as a diversionary tactic). We are left with the impression any solid physical characteristics are exclusionary. This should be clarified.
A series of papers early in the year attracted criticism about their failure to validate their tests against samples drawn from living infected human beings. This paper is no exception, despite months of prior opportunity. Spiking samples will not necessarily produce anything like you get from an infected person. The only evidence that this was taken into account is a paragraph about the lack of the availibility of a control panel. Why didn't CDC researchers address this issue before wasting time in the laboratory, let alone publishing? Is this potential pathogen peculiarly outside their scope?
While there is a statement that CDC laboratories were able to detect XMRV in samples from people they trusted, there is no supporting data to show how well they can detect virus if the sample is not labeled positive. This amounts to saying, "yes, we know how to detect this virus, trust us." We have no idea how close to the margin their results are. A double-blind study independent of CFS/ME is called for. Blinding should not be controlled by a group which has a demonstrated record of nonfeasance, misfeasance and malfeasance involving millions of dollars, plus Congressional testimony about same approaching perjury.
Among the criticisms of previous papers easily available prior to this publication, there were very specific statements about activating cells in the samples, then allowing these to divide several times, in order to raise the number of copies available to PCR. This paper does not appear to address these concerns in any way. Have I missed something, or is this an attempt to ignore opponents and proceed by sheer bluff?
In assessing sensitivity of tests it is important to consider the number of cells available at the start. We already know very few cells in the blood will show active infection. The difficulty of finding this may not bother those with highly specialized backgrounds, who can read between the lines. For me, this is a mystery. I also wonder about the relation between numbers of cells and amounts of DNA, as this can give an idea of the effectiveness of techniques for processing samples and extracting DNA prior to PCR. Why were such simple measures omitted? It is far too easy to think this was deliberate obfuscation. Responsible researchers should take pains to dispel such doubts.
It is clear that researchers working on this virus in relation to prostate cancer are also working at the limits of the state of the art. They have not been subject to the kind of prejudgment apparent here.
Had prostate cancer been treated like this one can imagine a senior researcher speaking off the record with the following statement:
"Just between you and me, this whole business stinks. All these complaints involve sexual organs, and when we check, we find none of these people have healthy sex lives. We have reason to believe they were sexually molested as children."
Can this be pursued as a crime of deception or conspiracy with intent to deceive? They have clearly not used the same methodology cohort group etc
Can this be pursued as a crime of deception or conspiracy with intent to deceive? They have clearly not used the same methodology cohort group etc
Link to Nature
DotDot posted a link to an article in Nature. I couldn't get that link to work. Here is the link to what I presume was the intended target: http://www.nature.com/news/2010/100702/full/news.2010.332.html
DotDot posted a link to an article in Nature. I couldn't get that link to work. Here is the link to what I presume was the intended target: http://www.nature.com/news/2010/100702/full/news.2010.332.html