Nature.com report that Alter paper reviewers want "additional studies"

[Levi]

Following Anika's post, this is what they say at pages 19-20 of the provisional pdf at:
http://www.retrovirology.com/content/pdf/1742-4690-7-57.pdf

(In relevant part it says

and 22 of 32 persons with CFS and 30 of 51 healthy controls from Georgia....Clinical and demographic characteristics of subjects with specimens available for this study did not differ from those persons who did not have ample specimen volumes and case-control matching was maintained.

If case control matching was truly maintained those 22 persons with CFS from the Georgia dial-up survey will have exactly the same proportion of cortisol levels as the larger group in Reeves' prior CFS cortisol study in Reference 2. This should be easy to prove or dis-prove, and it would be fun to see if they are lying about this. After all, the cortisol testing had already been done prior to this new paper, and is part of the patient's medical history.

 

[Angela Kennedy]

Hiya Levi,

I think your comment about 'when the smoke clears' is probably one of the most important things that can be said about this whole thing. There's a whole lot of thick black noxious smoke enveloping 'CFS' research, and impossible to pick out lots of issues because of that (It should get a prize for apt metaphor of the week!)

I have to call you on the 'prickly' thing though. I'm arguing logically - even when my language is conversational and facetious. I am basing my arguments on my own research and deep analysis of MANY 'CFS' papers over the years (like a lot of us), and 'prickly' makes me sound over-sensitive, which I'm not. And I've had people liken me to terrorists and publicly claim I personally harassed Simon Wessely, which was MASSIVE libel! I've had to develop a thick skin if anything. (Also I'm not ill with 'CFS/ME', my daughter, now adult, is.)

 

[Hope123]

It would be interesting to know in the Wichita cohort WHEN the blood was taken as many subjects dropped out during the 3-year follow-up (65 initially to 39 to 24 at 3 years) and only 3 subjects sustained a diagnosis of CFS over 2 consecutive follow-ups. Dr. Vernon mentioned this in her commentary when she was wondering if the Wichita cohort was the initial cohort or the follow-up cohort.

http://archinte.ama-assn.org/cgi/content/full/163/13/1530 (2003)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC269990/ (2007)

From what I understand, Wichita cohort was originally assembled using 1994 criteria but it looks like the CDC had the subjects also take the MFI/ SF-36. Later, using the MFI/ SF-36 data they selected those who fit the new Reeves criteria after-the-fact. Haven't read it yet but "There was minimal association between the empirical classification and classification by the surveillance criteria." (???) from:

Reeves criteria development from Wichita: http://www.biomedcentral.com/1741-7015/3/19

For those interested in the Georgia community-based cohort, read comment #21 from this older article by Mary Schweitzer who gives links also:

http://www.atlantaunfiltered.com/2010/02/05/cdc-reeves/

Dr. Jason's take: http://www.iacfsme.org/IssueswithCDCEmpiricalCaseDefinitionandPrev/tabid/105/Default.aspx

I haven't read through all of these but let's follow those subjects and the twists and turns of their classification (or not) of CFS.

*If anyone was actually a participant in these studies, I'd like to hear your take on what went on.

 

[Anika]

Hope, thanks for pulling these references together so we can look over them. I've looked at some of them before but only have some general impressions.

The Reeves/empiric criteria should get their due examination and criticism again now that more people are actually looking at CFS studies. We need to keep bringing this up as long as the CDC keeps ignoring the issues.

There should also be some explaining about why the 2008-2009 Georgia study only has specimens for 60-70% of CFS patients and controls - who's minding the store?

 

[anciendaze]

...
So, when Reeves and CDC now talk about Fukuda criteria in current publications, they mean the Reeves / empirical criteria, which they rationalize as simply "operationalizing" Fukuda - though they have done absolutely no studies to validate that assertion...

Every time I hear that term I think about a tomcat who got "operationalized".

Leaving aside the linguistically-challenged aspect of the statement, I think the claim is that the questionnaires and protocols used in the Wichita study implement diagnosis according to the Fukuda definition. My understanding of the Canadian Consensus Criteria is that they also implement the Fukuda definition, in a fairly restrictive way. Now, reading that physical signs in the CCC may lead to exclusion under the empirical definition, I wonder how a more restrictive definition can ever be exclusionary. This parting shot is practically certain to increase diagnostic confusion, a persistent feature of information emanating from this group.

There is a logical contradiction in the way this has apparently been put into practice. We have a condition like MS, with unknown etiology and diagnostic overlap, being exclusionary. It is hard to come up with any physical sign which is not. This constructed cohort without physical illness is then used to test an hypothesis about an infectious agent.

At this point one wonders about cognitive deficits at the top end of the stethoscope.

Added: In reference to my analogy about prostate cancer, where the virus was first found, I've just confirmed one guess. There was a sharp increase in prostate cancer diagnoses in the late 1980s. Part of this was due to better diagnostic tools. This increase leveled off and even declined in the 1990s. This is the kind of behavior you expect when new tools make you aware of more cases. There is an initial surge as you clear out a backlog of missed diagnoses, followed by a steady rate. This new rate remains about twice the rate prior to 1985.

To decide if there was an actual surge in incidence you need more detailed demographic data. At this point, nothing contradicts a hypothesis of a parallel rise in PC and XMRV infection starting around 1985.

 

[Hope123]

Aside from definition, the problem with many CDC studies (not counting Georgia registry here where MD referred patients) is that they mostly focused on "new" subjects rather than studying people who already had CFS. Less than 15% of the past cohorts already had a physician diagnosis of CFS. Perhaps they thought people who already had CFS would "contaminate" their studies??!! It doesn't make any sense; sure, community-based studies are needed to look at the epidemiology but shouldn't researchers also study the people who ALREADY have the illness? That's the usual process for other illnesses where both types of studies are undertaken.

 

[SOC]

What if we don't have CFS

Aside from definition, the problem with many CDC studies (not counting Georgia registry here where MD referred patients) is that they mostly focused on "new" subjects rather than studying people who already had CFS. Less than 15% of the past cohorts already had a physician diagnosis of CFS. Perhaps they thought people who already had CFS would "contaminate" their studies??!! It doesn't make any sense; sure, community-based studies are needed to look at the epidemiology but shouldn't researchers also study the people who ALREADY have the illness? That's the usual process for other illnesses where both types of studies are undertaken.

I'm starting to wonder if the CDC isn't (consciously or unconsciously) trying to redefine "CFS" so that their assertion that CFS patients don't have a physical illness doesn't look moronic in hindsight. Sort of a rewriting history thing. In other words, what if what the CDC is working up to say is not that we don't have XMRV, but that we don't have "CFS".

By this completely hypothetical argument, they will not ultimately deny that people with neuro-immune illnesses have XMRV (or whatever), but that we were never the people they were talking about. We were just "misdiagnosed" with CFS. That means they may have to creatively ignore the Incline Village cohort for which the name 'CFS' was originated, but hey....

Extending my (again, completely hypothetical) argument, the CDC can claim the FDA/NIH study is "fundamentally flawed" because it didn't test "real" CFS patients, it tested people with idiopathic neuro-immune illnesses and then drew conclusions about CFS patients. If the CDC's patients were treated as persons with a serious retrovirus, that would be a great disservice to them.

I'm not suggesting this is true. Let's call it another way to look at the craziness of what's going on that might clue us in to what the real situation is.

Sorry if this is not fully coherent -- bad fog today -- but I think there's something interesting here....

BTW, why cant' the CDC use ME/CFS, which is supposed to (I think) be the official (American, anyway) name of this illness?

 

[Hope123]

I'm starting to wonder if the CDC isn't (consciously or unsconciously) trying to redefine "CFS" so that their assertion that CFS patients don't have a physical illness doesn't look moronic in hindsight. Sort of a rewriting history thing. In other words, what if what the CDC is working up to say is not that we don't have XMRV, but that we don't have "CFS".

By this completely hypothetical argument, they will not ultimately deny that people with neuro-immune illnesses have XMRV (or whatever), but that we were never the people they were talking about. We were just "misdiagnosed" with CFS. That means they may have to creatively ignore the Incline Village cohort for which the name 'CFS' was originated, but hey....

Extending my (again, completely hypothetical) argument, the CDC can claim the FDA/NIH study is "fundamentally flawed" because it didn't test "real" CFS patients, it tested people with idiopathic neuro-immune illnesses and then drew conclusions about CFS patients. If the CDC's patients were treated as persons with a serious retrovirus, that would be a great disservice to them.

I agree with your thoughts. They're using semantics now as an excuse for their poor track record of CFS research. Even if XMRV is not the cause of CFS, they will try to use this as an excuse when others find the etiology (-ies) behind CFS. This part says it all:

"The 1994 International CFS case definition and
the Canadian Consensus Criteria are different and do not necessarily identify similar
groups of ill persons. Most notably, the Canadian Criteria include multiple abnormal
physical findings such as spatial instability, ataxia, muscle weakness and fasciculation,
restless leg syndrome [CDC - this is not a physical finding - it's a diagnosis], and tender lymphadenopathy. The physical findings in persons meeting the Canadian definition may signal the presence of a neurologic condition
considered exclusionary for CFS and thus the XMRV positive persons in the Lombardi et
al. study may represent a clinical subset of patients [11].

CCC by the way was developed by clinicians who have followed CFS patients (yes, including those from which the original CDC CFS definitionw as created!) for more than 2 decades, not researchers who only see subjects one time or for a few scant exams.

 

[Dolphin]

It would be interesting to know in the Wichita cohort WHEN the blood was taken as many subjects dropped out during the 3-year follow-up (65 initially to 39 to 24 at 3 years) and only 3 subjects sustained a diagnosis of CFS over 2 consecutive follow-ups. Dr. Vernon mentioned this in her commentary when she was wondering if the Wichita cohort was the initial cohort or the follow-up cohort.

http://archinte.ama-assn.org/cgi/content/full/163/13/1530 (2003)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC269990/ (2007)

From what I understand, Wichita cohort was originally assembled using 1994 criteria but it looks like the CDC had the subjects also take the MFI/ SF-36. Later, using the MFI/ SF-36 data they selected those who fit the new Reeves criteria after-the-fact. Haven't read it yet but "There was minimal association between the empirical classification and classification by the surveillance criteria." (???) from:

Reeves criteria development from Wichita: http://www.biomedcentral.com/1741-7015/3/19

Don't forget that the patients who were followed from 1997-2000 were invited in for 2 days of testing in 2002/2003. They used the SF-36, MFI, etc on these patients. There is a tiny chance that the blood is from 1997-2000 but it looks very much to me like this was taken from the empiric criteria patients in 2003.

 

[Dolphin]

I agree with the comments about cortisol. Cortisol can fluctuate a lot during the day, can be affected by many factors, and must be tested carefully. Also, there have been conflicting studies about cortisol in CFS in the past if I remember right.

Also, nowhere in the current Retrovirology papers is cortisol mentioned as a criteria for how they selected their subjects in any of the cohorts (Wichita/ Georgia community/ Georgia Bibb registry) used in the study. Instead, the Reeves Empiric Criteria (which doesn't include any labs at all) is used.

Not everyone in the Georgia community study had low cortisol either.

Also, when the WPI paper came out, scientists were asking why the WPI didn't test all 101 CFS subjects nor all the controls with all the tests available. E.g. why were only the 33 PCR (-) tested using antibody/ Western Blot, etc.? The same question could be asked of the CDC:

There were 292 CFS patients identified by Georgia community and 65 CFS in Wichita. But the CDC only used 33/292 from Georgia and 11/65 from Wichita in the current study? Why were these specific patients selected? Did they fit the Reeves Empiric? (in which case it's a small percentage from each study) Were these the only people who had blood stored? Were they selected randomly? Inquiring minds want to know.

There were only 113 CFS patients identified in the Georgia sample. http://www.pophealthmetrics.com/content/5/1/5 292 is the number of CFS-like cases but 141 were found to have a medical or physical exclusion and 1 record was lost. One can see how the 150 fared in Table 2.
But the language and what they are doing can be a bit confusing in these CDC papers.
And as I said in the previous post, it very much looks like the Wichita patients are the ones who took part in the follow-up study so 11/43 which they say in the paper. They say 22 of 32 Georgia CFS patients - not sure where the 32 came from.

 

[biophile]

I think your comment about 'when the smoke clears' is probably one of the most important things that can be said about this whole thing. There's a whole lot of thick black noxious smoke enveloping 'CFS' research, and impossible to pick out lots of issues because of that (It should get a prize for apt metaphor of the week!)

The "smoke" may never "clear" on its own either. There's just too much smoke to even see the exhaust pipe, like the car in the movie where John Candy played "Uncle Buck"!

 

[biophile]

Seek and you will find

The CDC are determined to study "chronic unwellness" as a result of psychological stress. That is what they are looking for and that is what they will find. It doesn't matter to them if it deviates away from what they are originally supposed to be studying. The recent Heim et al 2006/2009 studies are case in point: the prevalence estimates jump several fold and various childhood abuse now emerge as major factors, contrary to previous research using different CFS criteria.

 

[Bob]

The CDC are determined to study "chronic unwellness" as a result of psychological stress. That is what they are looking for and that is what they will find. It doesn't matter to them if it deviates away from what they are originally supposed to be studying. The recent Heim et al 2006/2009 studies are case in point: the prevalence estimates jump several fold and various childhood abuse now emerge as major factors, contrary to previous research using different CFS criteria.

I would probably find it hard to believe that this sort of thing could be going on within the CDC if I didn't know how true it is.

The Guardian journalist called the ME/CFS community 'conspiracy theorists'... The only issue I'd have with that is that it's not a 'theory', but the evidence for conspiracy has laid out in front of us, for public scrutiny for the past 30 years. I think the journalist needs to read Osler's Web... Maybe we should send her a copy.

 

[RustyJ]

The CDC are determined to study "chronic unwellness" as a result of psychological stress.

Call me niaive or ME addled, but I still don't understand their stance. Okay they make a series of bad calls, but it is a relatively easy shift for them to shelve everyone into the 'chronic unwellness' drawer and get on with looking at XMRV. At the end of the day there is still XMRV floating around. Whether or not XMRV is a major factor in ME is a secondary issue to the main one: XMRV is out there and it is causing harm and it is spreading. I thought it was their job to nail things like this.

 

[Bob]

Call me niaive or ME addled, but I still don't understand their stance. Okay they make a series of bad calls, but it is a relatively easy shift for them to shelve everyone into the 'chronic unwellness' drawer and get on with looking at XMRV. At the end of the day there is still XMRV floating around. Whether or not XMRV is a major factor in ME is a secondary issue to the main one: XMRV is out there and it is causing harm and it is spreading. I thought it was their job to nail things like this.

Hi Rusty,
I think this is more to do with careers than science... Some of these people have made careers, and reputations, for themselves by becoming 'experts' on CFS and denying that CFS has any biomedical basis at all... They've always denied that there are real physical symptoms, bio-markers, or any pathogens involved in CFS... This denial has been going on for 30 years or so... So after all of this time, I would think that they are more interested in protecting their reputations, status, careers and income than in finding out about the science...
Luckily for us, I think, this research now moves across to the scientific heavy-weights who deal with viruses, retro-viruses and other pathogens. Research is being carried out on XMRV, including within the CDC (for example; they are working on a standardised test for XMRV which the WPI is involved with), but these old-school CFS 'experts' will continue to kick up a heck of a lot of fuss while it goes on. There may well be some people within the CDC who are successfully working on XMRV, outside of the CFS department, but I'm just speculating here... I don't have any info on that.

 

[*GG*]

The CDC are determined to study "chronic unwellness" as a result of psychological stress. That is what they are looking for and that is what they will find. It doesn't matter to them if it deviates away from what they are originally supposed to be studying. The recent Heim et al 2006/2009 studies are case in point: the prevalence estimates jump several fold and various childhood abuse now emerge as major factors, contrary to previous research using different CFS criteria.

Seems like they just want big Gov't to put us on pysch meds and have more control over our lives, please protect the weak and fragile!

Just makes me think that many on the Right are right! Progressives just want to re-write history and ignore what is going on right in front of us! Please media do your damn job!! Otherwise you will become obsolete!

 

[ahimsa]

I'm starting to wonder if the CDC isn't (consciously or unconsciously) trying to redefine "CFS" so that their assertion that CFS patients don't have a physical illness doesn't look moronic in hindsight. Sort of a rewriting history thing. In other words, what if what the CDC is working up to say is not that we don't have XMRV, but that we don't have "CFS".

Agreed. They did the same thing with autonomic dysfunction. In this study they report that they found it more often in healthy controls than in their set of "CFS" patients: http://www.cdc.gov/cfs/publications/causes_30.htm

I guess the CDC conclusion was, sure, there are people out there who have various kinds of autonomic dysfunction, but it has nothing to do with "CFS." At least, not our idea of "CFS."

And yet, they never revised any of their "CFS" definitions to make orthostatic intolerance an exclusionary condition (which might be one way to interpret the data). Nor did they say that this problem can be a co-morbid condition. Nor did they say that this is a sub-group of patients that could be studied separately. (and there may be other options that I can't think of right now)

Instead, they completely ignored orthostatic intolerance (POTS, NMH). And then, poof, as if by magic, a measurable group of symptoms found in a subset of patients simply no longer exists as far as the CDC definition of "CFS" is concerned.

And yet, every ME/CFS patient online forum (or support group meeting) that I have visited always includes a good sized subset of folks who have these problems. No one is saying that every patient has these symptoms but it is not a tiny fraction that should be ignored.

The 2003 ME/CFS Canadian Case definition did the exact opposite and listed autonomic manifestions as one possible group of symptoms.

By this completely hypothetical argument, they will not ultimately deny that people with neuro-immune illnesses have XMRV (or whatever), but that we were never the people they were talking about. We were just "misdiagnosed" with CFS. That means they may have to creatively ignore the Incline Village cohort for which the name 'CFS' was originated, but hey....

I would love to read the CDC's logic for this....it might be amusing!

 

[biophile]

The CDC are part of the problem

The CDC's actions can be explained by the beliefs and attitudes of their employees. They went skiing and gambling when they should have been investigating the Lake Tahoe cohort more seriously. They coined "CFS" and unofficially made fun of patients. They don't believe "ME/CFS", as we patients understand it, actually exists. They consult with self-appointed mind-body "specialists" and "experts" who insist the symptoms are part of a psychosomatic functional illness, which is a flawed ideological persuasion all on its own. They have redefined CFS in ways which is not accepted. They are unable to confirm the basic findings of other researchers. They keep ignoring the flaws pointed out to them. Most recently they are unable to detect XMRV in CFS patients and don't believe XMRV is significant.

I recently watched the film "And The Band Played On". In the early 80's the "higher ups" in the CDC and other figures responsible for the blood supply were at first stonewalling on "GRID"/AIDS, but at least their small underfunded group of researchers working on AIDS connected some important dots and contributed to progress.

When it comes to ME/CFS in 2010, over 25 years and $100 million later the entire CDC (including the higher ups and especially the small underfunded CFS division) have proven themselves to be part of the problem not the solution, prone to administrative scandals and can't even define CFS properly yet alone research it adequately. Their incompetence and indifference is dangerous and is perpetuating suffering.

The ~100% mortality rate of AIDS in the 80's obviously went a long way to force the urgency of the situation. Whereas the mortality rate of ME/CFS is relatively low, people don't think it is urgent and they care even less for alleged "psychosomatic" illness. At the CDC we do not have the equivalent of a proactive Dr Don Francis working for us as he did on AIDS. We have people like William "XMRV is ubiquitous but we still won't find it" Reeves supplying the chronic unwellness patient samples and Walid "I don't want my career stained with CFS" Heneine heading the virology in their XMRV study.

The CDC already have nearly zero credibility in the ME/CFS/CFIDS communities. If XMRV turns out to be significant (which at this stage looks like it will), the CDC are going to look like incompetent fools even to the general public. Their CFS division needs a serious shake up, the good kind, not Reeves' coup d'etat of last time. Failing that it needs to be shut down so other researchers like the WPI can put the money to better use.

I doubt ME/CFS will be as simple as HIV/AIDS, but I agree we are witnessing the start of a power shift, the beginning of the end in the battle of different schools of thought. The "gay" stigma of AIDS remained for many years after it was disproved. Similarly, the "neurotic" stigma of CFS remains despite being disproved as well.

 

[Sean]

Similarly, the "neurotic" stigma of CFS remains despite being disproved as well.

Not necessarily. Look at how fast things changed for stomach ulcers. They were supposedly the archetypal stress caused psycho-somatic disorder. Well, that didn't last long once they realised they could cure it easily, quickly, and permanently with basic antibiotics.

 

[Levi]

There will be no power shift

If you rule out conspiracy theories, then the most plausible explanation for the charted course CFC has taken is that they believe it is fun to mess with CFS patients and listen to them squeal;

"Lets see guys, don't we have some blood left in some of those old vials we used for all those CFS cortisone studies? I know, lets do an XMRV study with it and drive home another Zero/Zero result to put on top of Simon Wessely's hit job!! THAT will set their little heads spinning . . . I'll write it up myself."

If we start taking heat for bad research, we can always change the name of the syndrome again to divert criticisms."

They coined "CFS" and unofficially made fun of patients.