Bad science fails to cast doubt on XMRV research. John Anderson Feb 27 10

[leelaplay]

John Anderson posted this to co-cure today.

This article, to me, does a good job of explicating why the Uk and Dutch studies only show that the methods and CFS definitions used are unable to find XMRV; NOT that XMRV is not there.

This is not the normal post to co-cure as I don't see that it has been posted anywhere else. I hope John is flogging it to different media and patient organizations to get it published.

Bad science fails to cast doubt on XMRV research

Absence of evidence is not evidence of absence those speculating on the failed XMRV
studies and claiming they cast doubt on the Science paper should understand the
difference between exact replication studies and quick and dirty
approximation studies that did not replicate the exacting protocols employed by
the Whittemore Peterson Institute, National Cancer Institute and Cleveland Clinic.

Information from the Science paper discloses the very strict criteria and additional tests
used to characterise severely affected neuro-immune CFS patients, while the
approximation studies used loose chronic fatigue criteria that were
influenced by psychiatrists and fail to distinguish between neurologically
impaired patients and those suffering chronic fatigue from a variety of causes.

These approximation studies only prove the failure to use precise scientific
replication methodology and therefore have no bearing on the status of XMRV
infection in CFS patients and the 4% positive population controls. The Science
paper stands and ongoing scientific research is being conducted to replicate
the findings and clarify the relationship between XMRV and human disease.

The Department of Health and Human Services is conducting studies on the prevalence of XMRV in the blood donor population and whether it is transmitted by blood transfusion, WPI is conducting a study on blood transfusion recipients, and the National Cancer Institute is studying models of mouse retroviruses that cause cancer and neurological disease, and potential anti-XMRV treatments. Furthermore Prof. Malcolm Hoopers press release Magical Medicine, his formal complaint to the Minister for Science overseeing the MRC and letter to the Chairman of NICE, including a 442 page report of an extensive and fully referenced review of the literature on ME - which casts serious doubts about the psychogenic model of 'CFS/ME' filtered to the media - have significant medico-legal consequences.

 

[Sing]

That's a good hard punch! We are watching a boxing match, I think. Our side has to step well and throw some strong punches. I'm pleased to see this one.

Thanks IF !

Sing

 

[rebecca1995]

I'm happy to see this too, especially given Vernon's tepid offering that spent a lot of space defending the three negative studies.

 

[Dr. Yes]

"Tepid"!! That's the word I was looking for!

 

[justinreilly]

Weak European XMRV studies cast no doubt on WPI/NCI/CC Science Paper

'Tepid"- yes. Some of it was full-on tepid esp. characterizing the Oxford definition as "widely accepted" or something to that effect. It's hard enough to battle our abusers/oppressors without CAA helping them out by echoing their nonsense. But this is nothing new.

A note on the co-cure post- Only the Netherlands study used the Oxford definition, not the other two. Although I must say Wessely's study was typical for him- ie a POS. Dr. Kerr's study does give me a little pause, but they had some Wessely school people involved in it who easily could have thrown some monkey wrenches into the works to skew the results. All in all, WPI, NCI and CC's study is far more credible than the combination of the three negative studies. We just need to wait for the actual replication studies and be vigilant in calling out the charlatan's like Wessely who publicize their erroneous views that their studies 'cast doubt' on the Science paper. Beotch Please!

 

[justinreilly]

I can't believe I put an apostrophe in 'charlatan's'. As I say, You shouldn't use an apostrophe just to let someone know an 'S' is coming up. I should follow my own advice.

 

[leelaplay]

I can't believe I put an apostrophe in 'charlatan's'. As I say, You shouldn't use an apostrophe just to let someone know an 'S' is coming up. I should follow my own advice.

ah - it's just a typo - don't worry.

But following our own advice - with you on that - funny how often we need to do it!

Forgot to say in my original post that I love the title of the article - very strong. I do hope he gets it published somewhere. It's the type of title that sticks in people's minds.

Bad science fails to cast doubt on XMRV research.

ETA: and your title is excellent too:

Weak European XMRV studies cast no doubt on WPI/NCI/CC Science Paper

 

[justinreilly]

Speaking of titles, what's with Dr. Vernon's title for the article we've been discussing- "Playing a Weak Hand Well." Is she saying the WPI study is weak evidence and we have to exaggerate it to maximize the scientific community's and wider world's response to it? If so, I disagree. If not, what does it mean.

I found it weird that she ended the article basically saying we're wasting a lot of time and money on XMRV. It seemed she was also implying that the WPI study was not well designed. If so, I disagree on these points too.

She kind of echos Reeves point that WPI did not fully disclose the demographics/ relevant characteristics of the study cohort. Is this true? I don't have much of a science background.

 

[oerganix]

Speaking of titles, what's with Dr. Vernon's title for the article we've been discussing- "Playing a Weak Hand Well." Is she saying the WPI study is weak evidence and we have to exaggerate it to maximize the scientific community's and wider world's response to it? If so, I disagree. If not, what does it mean.

I found it weird that she ended the article basically saying we're wasting a lot of time and money on XMRV. It seemed she was also implying that the WPI study was not well designed. If so, I disagree on these points too.

She kind of echos Reeves point that WPI did not fully disclose the demographics/ relevant characteristics of the study cohort. Is this true? I don't have much of a science background.

She may be just covering her behind, but I don't trust her.

This was posted on the Sandman's Blog: http://dancingwiththesandman.blogspot.com/2010/02/comments-on-netherlands-xmrv-study.html another CoCure repost. An excerpt:

....Yet all three studies obtained significant and totally co-ordinated 0%
outcomes and publicity across the International media with the sole
intention of casting “serious doubt” on the original study published in
Science during October 2009.

Those in the profession of liaison psychiatry and Governments pursuing
CBT/GET agendas (i.e. the PACE Trial in the UK) with vested interests in
finding a 0% association between XMRV and CFS are the only people currently
benefiting from "quick and dirty" 0% non-replication findings.

The jury is therefore still well and truly out.

Sincerely,

Stephen Ralph DCR(D) Retired.

 

[usedtobeperkytina]

Actually, I think she says that since WPI did not give enough info to begin with, the time and money is being wasted. I don't think she was saying that WPI wasted money on XMRV.

Tina

 

[leelaplay]

2nd draft of article it seems

this was just posted to co-cure - same article "with corrections":

Bad science fails to replicate XMRV research

Absence of evidence is not evidence of absence – those speculating on the failed XMRV
studies and claiming they cast doubt on the Science paper should understand the
difference between exact replication studies and dubious approximation studies
that did not replicate the exacting protocols used by Lombardi et al from the
Whittemore Peterson Institute, National Cancer Institute and Cleveland Clinic.

Information from the Lombardi et al study discloses the very strict criteria including comprehensive
immunological tests to characterise severely affected neuro-immune “CFS”
patients, while the approximation studies used loose “chronic fatigue” criteria
influenced by psychiatrists that fail to distinguish between
neurological/immune dysfunction and severe chronic fatigue from various causes.

The Lombardi et al research used very specific testing methods a) PCR on nucleic
acids from un-stimulated and 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. Refinement of the PCR method
was necessary to detect the very low levels of XMRV in the blood, PCR alone is
inadequate.

The approximation studies only prove the obvious failure to replicate the precise
scientific methodology required and therefore have no bearing on the status of
XMRV infection in “CFS” patients and the 4% of the population positive for XMRV.
The Science paper stands and ongoing scientific research is being conducted to
replicate the findings and clarify the relationship between XMRV and human
disease.

The Department of Health and Human Services is conducting studies on the prevalence
of XMRV in the blood donor population and whether it is transmitted by blood
transfusion, WPI is conducting a study on “CFS” affected blood transfusion
recipients, and the National Cancer Institute is studying models of mouse
retroviruses that cause cancer and neurological disease, and potential
anti-XMRV treatments.

Furthermore Prof. Malcolm Hooper’s press release “Magical Medicine”, his formal complaint
to the Minister for Science overseeing the MRC and letter to the Chairman of
NICE, including a 442 page report of an extensive and fully referenced review
of the literature on ME - which casts serious doubts about the psychogenic
model of 'CFS/ME' filtered to the media – indicate a potential culture of
denial.

Millions of patients are suffering from hidden neuro-immune diseases which have not been
appropriately investigated due to a questionable lack of funding. WPI is
investigating the encephalomyelitic diseases Myalgic Encephalomyelitis (or equivalent
WHO-ICD CFS), Atypical Multiple Sclerosis and neurological Lyme disease, and the
related diseases Fibromyalgia and Multiple Chemical Sensitivity.

Collectively these patients have been denied their basic human rights under the prevailing
culture, it is time for good science to prevail and alleviate this unacceptable
level of human suffering and despair.

 

[cfs since 1998]

Speaking of titles, what's with Dr. Vernon's title for the article we've been discussing- "Playing a Weak Hand Well." Is she saying the WPI study is weak evidence and we have to exaggerate it to maximize the scientific community's and wider world's response to it?

I agree, the title is downright offensive. Unless that's not what she meant, but should have realized it would be interpreted that way. I continue to be more and more disimpressed with the CAA every day.

 

[Anika]

Commenting on the Vernon piece - the title is interesting. I don't think she's saying WPI / NCI / CC have a weak hand - more likely, that other groups have done well in getting bang for their little buck. But I think the title is ambiguous, perhaps deliberately to be polite to those like Kerr who are part of the authors of the "other studies". Let's face it, the first UK study and the editorial on the Dutch study have come out of what could be called a Medical Media Manipulation factory. It's a game they play well - even when they have a "weak hand."

I shared the feeling that Vernon was frustrated with cohort description. The other studies were actually less descriptive. I think they all leave something to be desired.

I think the Science authors do need to clear up some questions about cohort that come up repeatedly - and that means WPI, which is responsible for cohort. We've got a number of posts about Canadian vs Fukuda etc. The Science paper implied - well, actually stated, since they used "and" instead of "or" - that everyone met both Canadian and Fukuda. But I think that might have been an unintended grammatical error - that they really meant either / or - which is a common error among non-English majors. I haven't seen a confirmation on that point - in fact, I think one casual statement may have said one or the other criteria was met, but I wouldn't accept a casual verbal comment as definitive. There could be a clarification that they are hoping to make with a subsequent study publication. But, given that they had samples from various sources, and that Canadian criteria haven't been used for many research studies to date, it seems to me a major point if they did somehow verify that all patients from whom samples were used did meet Canadian criteria.

If someone has seen a definitive confirmation outside of the Science paper, I would appreciate the reference - I have tried to keep reasonably up to date, but it's not easy (and, it's good that things are happening at more than a snail's pace).

When Vernon and other respected scientists in virology (like Vincent Racaniello? may not be spelled right) have made comments to the effect that there needs to be some cooperation and sharing of samples etc., I do get the sense that there's frustration among some of the people who are close to the reality of what's going on - but it's not entirely clear that they're directing their comments at one research group, whether WPI or one of the others. I think they're just being scientists.

Personally, I am very supportive of both WPI's and CAA's efforts - but neither of them is exempt from criticism or constructive suggestions, and I don't think they would want to be. I absolutely want the best efforts, including criticism, from every quarter. I will give editorial comments (like those of SW in the BMJ) the credit they deserve (imo, or imho, depending on the moment...;-).

 

[Angela Kennedy]

I'm happy to see this too, especially given Vernon's tepid offering that spent a lot of space defending the three negative studies.

Yes that was pretty amazing. The criticising of the WPI for not including enough info about their cohort in particular made me laugh, in a pained, bitter way. Has she SEEN the CFS research literature over the years? Did she LOOK at the information contained in the three NEGATIVE' papers about the patients tested? The supplementary material provided by the WPI courtesy of Science actually gave more information on their patient cohort than any I've ever seen, especially in literature supporting a psychiatric paradigm.

 

[Angela Kennedy]

Commenting on the Vernon piece - the title is interesting. I don't think she's saying WPI / NCI / CC have a weak hand - more likely, that other groups have done well in getting bang for their little buck. But I think the title is ambiguous, perhaps deliberately to be polite to those like Kerr who are part of the authors of the "other studies". Let's face it, the first UK study and the editorial on the Dutch study have come out of what could be called a Medical Media Manipulation factory. It's a game they play well - even when they have a "weak hand."

I shared the feeling that Vernon was frustrated with cohort description. The other studies were actually less descriptive. I think they all leave something to be desired.

I think the Science authors do need to clear up some questions about cohort that come up repeatedly - and that means WPI, which is responsible for cohort. We've got a number of posts about Canadian vs Fukuda etc. The Science paper implied - well, actually stated, since they used "and" instead of "or" - that everyone met both Canadian and Fukuda. But I think that might have been an unintended grammatical error - that they really meant either / or - which is a common error among non-English majors. I haven't seen a confirmation on that point - in fact, I think one casual statement may have said one or the other criteria was met, but I wouldn't accept a casual verbal comment as definitive. There could be a clarification that they are hoping to make with a subsequent study publication. But, given that they had samples from various sources, and that Canadian criteria haven't been used for many research studies to date, it seems to me a major point if they did somehow verify that all patients from whom samples were used did meet Canadian criteria.

If someone has seen a definitive confirmation outside of the Science paper, I would appreciate the reference - I have tried to keep reasonably up to date, but it's not easy (and, it's good that things are happening at more than a snail's pace).

When Vernon and other respected scientists in virology (like Vincent Racaniello? may not be spelled right) have made comments to the effect that there needs to be some cooperation and sharing of samples etc., I do get the sense that there's frustration among some of the people who are close to the reality of what's going on - but it's not entirely clear that they're directing their comments at one research group, whether WPI or one of the others. I think they're just being scientists.

Personally, I am very supportive of both WPI's and CAA's efforts - but neither of them is exempt from criticism or constructive suggestions, and I don't think they would want to be. I absolutely want the best efforts, including criticism, from every quarter. I will give editorial comments (like those of SW in the BMJ) the credit they deserve (imo, or imho, depending on the moment...;-).

I do agree Anika, wholeheartedly, that the WPI should NOT be exempt from criticism or constructive suggestions. Having said that, the three negative papers and Wessely and McLure's editorial in the BMJ are full of problems: scientifically and ethically. And some of the 'criticisms' made about the WPI have not been constructive at all. McLure has said some pretty stupid things - like the "1000% correct" comment, and her and Wessely's comments about patients in the BMJ editorial were outrageously inflammatory, as just two examples.

I think we have to accept, actually it's vital that we the community accept it, that 'scientists' are not just 'scientists', they are human beings subject to the same ideological and political forces as anyone else, which is why there is academic study of the philosphy and sociology of science. Vernon's piece does seem rather slanted against the WPI, and knowing something about Vernon's own positions on 'CFS', her piece is flawed and not neutral in position.

 

[Cort]

Dr. Vernon's positions on CFS?

Check out the CAA's research program or her own multi-year work on gene expression in CFS. She's fully committed to a physiological explanation of CFS and her research program at the CAA demonstrates that.

Playing a Weak Hand Well for me had nothing to do with the WPI. Her piece suggested that she felt the WPI is not playing their hand well by presenting conflicting information about that original cohort and then not clearing it up. She's afraid that that was a very select group of patients and that XMVRV is found in their blood and the whole thing is going to go belly up unless researchers focus on those patients. She also considers the fact that XMRV could be in the blood of very ill patients and the tissues of not so ill patients.

The article was about the Dutch study; Playing a Weak Hand Well meant to me that the Dutch study - with its very small sample size and the old samples and the Oxford cohort problem neverthless played that weak hand well by using sophisticated techniques to search for the virus.

I believe that CFS patients will be found in the Oxford cohort; except for the fact that it doesn't require certain symptoms its very similar to the Fukuda or CDC cohort which has been used in virtually all ME/CFS research studies.

 

[rebecca1995]

Justin:

'Tepid"- yes. Some of it was full-on tepid esp. characterizing the Oxford definition as "widely accepted" or something to that effect. It's hard enough to battle our abusers/oppressors without CAA helping them out by echoing their nonsense. But this is nothing new.

I thought the CAA's response to the first two papers was reasonably strong, but the latest response is definitely disappointing. We're going to have to keep our eye on the CAA to make sure their actions are appropriate for an advocacy organization. If there's another weak response to the next negative paper, we need to revisit hvs's excellent points from her December post.

Cort:

She's afraid that that was a very select group of patients and that XMVRV is found in their blood and the whole thing is going to go belly up unless researchers focus on those patients.

It may be true that XMRV is only associated with a subset of what has been called "chronic fatigue syndrome", but distinct cohorts have never bothered Dr. Vernon/ the CAA before. Case in point: CB"T" and GE"T" may be innocuous or even helpful for a subset of patients, but these treatments are endorsed by the CAA for the entire CFS population. Their literature contains numerous positive references to these regimens with no caveat for the large subsets--perhaps the majority--of CFS patients who have experienced disastrous decline in their health following these "treatments".

Personally, I'd like Dr. Vernon to focus on characterizing those patients who are harmed by CB"T"/GE"T". What are the features of this cohort? In fact, there may be substantial overlap with the cohort she claims was not well-characterized by the WPI/CC/NCI.

 

[Angela Kennedy]

Cort, Dr Vernon's position on CFS is exemplified by her co-authorship of the much criticised 2005 'empirical' criteria paper, her close collaborations with Reeves and Heim, her part in the 'pharmocogenomics' series of articles which focused on new, incorrect use of terms like allopathic loads and interoception synthesised in a psychogenic context, and focused in psycho-social stressors, her interest in 'early life experiences' and the determination to make 'early stress' the most prominent explanation for 'CFS' and changes in gene expression.

Now you many think they are reasonable positions that exclude psychogenic explanations. I think, from the evidence available and the flaws in the research and theoretical concepts, that they are not. There seems to be a marked determination to make 'stress' a predisposing factor in developing 'CFS', even though the correlations are weak at best, even after the massive flaws in methodology are accounted for.

Vernon obviously has never come out, to my knowledge, and said "well we should have Canadian crtieria cohorts as well as my empirical bunch". She promotes a case definition that weeds out severely impaired with neurological signs for example (something many 'CFS' ers have in Britain at least). So her concerns about being exclusionary, as you've narrated them, seem somewhat discrepant, when seriously impaired people with signs of organic dysfunction are excluded from research, but have to suffer the consequences of inappropriate extrapolation, as in CBT/GET studies (Rebecca's expressed this better than I). Her positions of CFS therefore were reflected in her article, and no, she's not neutral. She's not the only one of course, but it was her article we were discussing.

Indeed, one flaw in ALL ME/CFS research is indeed the use of Oxford and Fukuda. When Cleare, Wessely and another co-author responded to criticisms on the plos one paper, we actually got to see the extent of exclusion of anyone with organic dysfunction in their research cohort (actually not in the article itself, i had to go hunting). My response is on Plosone too. The testing to exclude organic illness is not given to clinical patients in CFS in Britain, but research cohorts get it, but ONLY to exclude 'organic illness'. The vagaries of Fukuda explains to a certain degree how the research community has managed to get some work done on establishing certain abnormalities in certain groups, but it's been pretty subject to luck not scientific precision!

It's about time proper Canadian research cohorts are established so that severely impaired patients don't continue to be treated like those with no organic dysfunction. The fact many of the scientists continue to ignore this is extremely significant, and worrying. They can't even be bothered to acknowledge in limitations of study sections in their papers about the Canadian criteria.