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Gearing Up for the Big Search for XMRV - WSJ Article

C

Cloud

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I think that's a very optimistic belief at best. The 'serious science' can't even get its collective head around the cohort criteria. The only people making noise about that appear to be patients and other advocates. THAT'S odd in the least.

Add to that noises about defining 'once and for all' and we've got some real odd 'science' going on.

As Cloud says, selection criteria for replication should be the number 1 priority. I think the focus on contamination and lab procedures etc are either red herrings or, it is possible they just do not understand the complexities and flaws in the diagnoses of exclusion.

Think about using AIDS patients for research, who don't exhibit cardinal symptoms/signs of AIDS! That's what the 'failure to replicate' Lombardi et al is analogous to.
Giving them the benefit of the doubt, I would have to agree.....but looking at it realistically, how could they not know? And if they really don't understand these complexities and flaws, they need educated immediately.


"As a starting point, everyone had to agree on how to define a CFS patient for the purposes of the study. The issue has been highly contentious and Lipkin says they tried to agree to criteria for patient selection that “includes everyone’s viewpoints.”

"Tried to agree" is not good enough. It needs to be consensus by those in the know.
"Everyone" also needs to be those in the know.

"The solution: the study will seek to enroll people who in addition to meeting criteria for two widely used, symptom-based definitions of CFS, showed signs of infection — such as a sore throat or tender lymph nodes — around the time they developed CFS. The thought is that if there is a viral link to CFS, it’s most likely to show up in those patients".

Great as long as one of the "two widely used symptom based definitions" is the CCC.

Signs of infection around time of onset? Many of us did not have an infectious onset.
 

Otis

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Since I saw the video of Singh's talk, and also learned that the Lipkin study will be using the Fukuda and Canadian definitions, I have become a lot more confident they will find something
Amy replied to comments on the blog with the following:

This is Amy Dockser Marcus, the author of the blog item. The study will use the Fukuda and Canadian definitions.
This makes me feel better as long as this isn't a "Revised Fukuda" bait and switch. I'm sure that was an interesting meeting.

So now my main concern is this "once and for all" nonsense.
 

asleep

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Lipkin's notion that his study will conclude the science is both unscientific and perversely dangerous. It is a statement that can only be made after the fact, and pertaining to aspects of his study that provide reproducible explanations for discrepancies.

I really hope that the WPI has a very concrete grasp of the precise mechanisms driving the postive/negative differences (as Judy alluded to by saying they thought processing was key). Without this trump card up their sleeve, I can very easily see the WPI being quietly swept aside behind the scenes in a landslide of ignorance and bias.

As for odds, I would say 95% in favor of (co-)causation. At the end of the day, the two positive studies are still very strong and indicate strong association between HGRV and CFS. The WPI demonstrated that XMRV is both infectious (and produces an immune response) and not endogenous (via sequencing and blasting). Both studies taken together provide strong evidence of a genetically diverse infectious human retrovirus. Both studies also went to great lengths to rule out contamination. Additionally, the pathogenetic model of retroviral infection in humans (and MLV infection in animals) fits CFS like a glove.

The only countervailing evidence is a set of 0/0 studies that prove nothing more than their collective inability to find the virus. Not one of them provides any explanatory evidence that either positive study is a "false positive." Thus far, the only hypothesis proffered as potential explanation for "false postives" is contamination. And this hypothesis has vastly more evidence stacked against it (checks/controls in both postive studies; vastly higher percentage found in CFS than controls, consistent across positive studies; antibody response; genetic diversity of strains found, suggesting true infectivity; Coffin's failure to find XMRV in any of 70 species of mice, i.e. from whence doth thy contamination spring) than for it (is there any evidence beyond "well, we've arbitrarily chalked up similar discrepancies in the past to contamination"?).


Researchers have no reason to try and not find something, everyone wants to be the first one to replicate the results.
This seems to be the overarching theme repeated ad nauseam on this forum, despite the fact that there is a surfeit of historical evidence (regarding both CFS and other diseases) against this rosy notion. Furthermore, how can you logically claim "everyone wants to be the first one to replicate the results" when absolutely nobody (except the Alter study) has even attempted a replication study? Can someone who, at the crack of the starting gun, wanders into the infield to sit and play with dandelions really be accused of "wanting to win the race"?

I also know that while science (and certainly the politics surrounding it) can move painfully slowly, and that we have paid a terrible price for that, I still would much prefer they took a little longer and got the answer on XMRV right.

Actually, I think things are moving at a reasonable pace, considering what is at stake. This issue goes way past ME/CFS patients, it is potentially one of the most serious disease factors in human history. For everybody's sake, including ours, we must allow the basic science of XMRV (et al) to be firmly established. We must be able to clearly define and detect the relevant organism(s), before we can do anything else, including serious clinical trials.
I agree that being careful and thorough is important. I think, though, that much of the frustration with the pace of research is very legitimately derived from an obvious lack of haste and funding from the relevant government agencies. Why did it take a full year to form and fund operations like the BWG and Lipkin study? It took no time for the CDC to fire off a shoddy 0/0 study, yet a full year later even modest research funds are not forthcoming to the WPI and other, dare I say, competent researchers. That is not being careful. This is being deliberately slow.
 

redo

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Apart from the ridiculous statement about ending the debate about association with CFS or not, my other concern is about the two 'widely used' criteria. Fukuda and Reeves? Fukuda and Oxford? What about that pesky Canadian Guidelines? If THOSE are NOT used, then we've got trouble ahead.

Science is not a rational self-correcting system. It's performed by scientists, who are as much social actors as anyone. Like the market, it cannot be left to its own devices without challenge. If scientists are shackled by 'bounded rationality' to the extent they're going to ignore the importance of the Canadian Guidelines for identifying the proper research cohort to replicate the WPI findings (it's too complicated for them?), but still think they can 'end the debate', then you all really are screwed.

If that seems a little apocalyptic and hysterical, please bear in mind, all these scientific dudes who can't get their little heads around the use of Canadian Criteria, and therefore can't replicate the WPI study, because that's what been happening!
Good post!

Why not send Lipkin an email?

It's better that he knows about it beforehand. If we come (as they would put it) "screaming" about it afterwards, we'll be dismissed.
 

Cort

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If that seems a little apocalyptic and hysterical, please bear in mind, all these scientific dudes who can't get their little heads around the use of Canadian Criteria, and therefore can't replicate the WPI study, because that's what been happening!
I don't think it can all be all the cohort. The WPI said their patients are not atypical and 50% or whtever it is of VIP Dx samples are positive and god knows where they are coming from. Plus we have failed studies from Joliceur, Felsenstein and Huber (who used Levine) - all of whom knew CFS patients. Besides while Fukuda is no ones favorite researchers have been able to document RNase L, NK cell, brain lactic problems, blah, blah, blah usinf it - if anything is widespread in CFS - it should at least show up in Fukuda classified patients and then more so in CCC classified patients.
 

Cort

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I don't think it can all be all the cohort. The WPI said their patients are not atypical and 50% or whtever it is of VIP Dx samples are positive and god knows where they are coming from. Plus we have failed studies from Joliceur, Felsenstein and Huber (who used Levine) - all of whom knew CFS patients. Besides while Fukuda is no ones favorite researchers have been able to document RNase L, NK cell, brain lactic problems, blah, blah, blah usinf it - if anything is widespread in CFS - it should at least show up in Fukuda classified patients and then more so in CCC classified patients.
Really for me all they need to do is find is some people - 10-20% would be great...just not zero
 

Cort

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Clinicians who treat patients in different regions of the country, including Miami, Boston, Palo Alto, and Salt Lake City, will be collecting the blood from both healthy people and CFS patients.

Lipkin tells the Health Blog that the study focuses on whether XMRV or other viruses in the same family are found in higher frequency in patients with CFS.

As a starting point, everyone had to agree on how to define a CFS patient for the purposes of the study. The issue has been highly contentious and Lipkin says they tried to agree to criteria for patient selection that “includes everyone’s viewpoints.”
We know who those physicians are, right? That's Dr. Klimas, Dr. Komaroff, Dr. Montoya and Dr. Bateman... There's no way any of these physicians are going to use the Oxford or Empirical Definition. (Nobody other than the CDC has ever used the ED so far as I can tell and has any researcher anywhere in the US ever used the Oxford criteria? (The answer to that is probably 'no' - and they certainly wouldn't start using a British Definition now. )).

They are going to require that they meet the Fukuda and the CCC and they're going to have infectious onset. Even if not everyone had infectious onset - but those are the type of patients Dr. Peterson tended to see and they make up the bulk of CFS patients. If XMRV is in CFS they should be able to find it in them....

I realize there's alot of mistrust but I think if you read a little between the lines this is exactly the study the CFS Community wants....

The big studies are actually very much taking researchers considerations into account. The only positive blood samples the BWG is using are from the WPI and the WPI has been included in all steps of the process. Now Lipkin is using top CFS physicians and he is requiring patients meet both criteria and he is using the WPI and Dr. Alter's lab (and the CDC).....Dr. Singh is collaborating with Dr. Bateman. The CAA/GSK study is requiring infectious onset.....let's forget about the little studies, the big studies all look really good to me...
 
C

Cloud

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Thanks for the positive perspective Cort. I will add that I am not infectious onset and in the CAA/GSK study (last I heard anyhow).
 
C

Cloud

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So Cloud, do tell us - have you heard anything from them? Any time lines? I guess you're not going to find out your results????
I haven't and it's been really difficult to get information on this. I really need to pin Dr P down on this next trip over. He plugged me into it back in like May, I did all the paperwork, bloodwork, and more bloodwork, and then never heard another word. I thought it was going to involve more than just studies on my profile and blood....I thought we would see clinical trials, possibly with drugs. I'll get the news next trip to Tahoe, unless they contact me before.

Also Cort, as far as infectious onset criteria....I just meant that I didn't have the typical flu like illness that most get with onset....but I did have brewing chronic infections and maybe that's how I qualify. Or maybe I got the boot and that's why I haven't heard anything. Find out soon.
 

Cort

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So Dr. P is providing patients to the BioBank? Good for him.

I think the onset question is so interesting. Sudden acute infectious onset....or a series of colds that just drag you down (into the abyss) or sudden onset non-infectious...or gradual (but not actually all that gradual -a month or two? in my case) without infection.......so many different types.
 

free at last

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So Dr. P is providing patients to the BioBank? Good for him.

I think the onset question is so interesting. Sudden acute infectious onset....or a series of colds that just drag you down (into the abyss) or sudden onset non-infectious...or gradual (but not actually all that gradual -a month or two? in my case) without infection.......so many different types.
Something you said there really made me think, and its something ive never really thought a lot about, and actually seems very surprising. Normally when one has typical flu symptoms temperature aching all over banging head, chest infection so forth, they usually are very much infectiouse, even if the virus symptoms ( and bacterial or otherwise ) are not the flu virus but something else. Not once did any member of my family catch this illness onset. And i had it enough times severly ( temperatures ect ) for there to be more to this than my family getting lucky. Either i wasnt infectiouse ? or they already had immunity. wonder what this observation means, as it certianly appears to me that i should have been infectiouse. Not once did they come down with the flu like illness. Call me dim but your words Cort really made me think about that for the first time properly. I did realize in the past no one caught my ME symptoms when it had turned chronic ( now without temps ) that seemed believable. but to avoid those many seriouse temperature flu like onset epsisdes that i had, strikes me as rather odd. And really must mean a great deal, a clue if you will. Wonder how that connects to a XMRV question ? damm weird if you ask me, they should have got ill at some point naada and i know this wasnt kind of re occuring food poisining like salmonella no constant vomiting ?
 
C

Cloud

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So Dr. P is providing patients to the BioBank? Good for him.

I think the onset question is so interesting. Sudden acute infectious onset....or a series of colds that just drag you down (into the abyss) or sudden onset non-infectious...or gradual (but not actually all that gradual -a month or two? in my case) without infection.......so many different types.
Yep, he sure is.....He had a girl there from the CAA signing people up for quite some time. He seems to be somehow involved in this collaborrative study beyond just referring patients.
 
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I don't think it can all be all the cohort. The WPI said their patients are not atypical and 50% or whtever it is of VIP Dx samples are positive and god knows where they are coming from. Plus we have failed studies from Joliceur, Felsenstein and Huber (who used Levine) - all of whom knew CFS patients. Besides while Fukuda is no ones favorite researchers have been able to document RNase L, NK cell, brain lactic problems, blah, blah, blah usinf it - if anything is widespread in CFS - it should at least show up in Fukuda classified patients and then more so in CCC classified patients.
But you agree the cohort is a VITAL issue though?
 
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Good post!

Why not send Lipkin an email?

It's better that he knows about it beforehand. If we come (as they would put it) "screaming" about it afterwards, we'll be dismissed.
If you have his email address, I'll do it. I can be a 'screaming' harassing carer advocate beforehand lol!
 
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Giving them the benefit of the doubt, I would have to agree.....but looking at it realistically, how could they not know? And if they really don't understand these complexities and flaws, they need educated immediately.


"As a starting point, everyone had to agree on how to define a CFS patient for the purposes of the study. The issue has been highly contentious and Lipkin says they tried to agree to criteria for patient selection that “includes everyone’s viewpoints.”

"Tried to agree" is not good enough. It needs to be consensus by those in the know.
"Everyone" also needs to be those in the know.

"The solution: the study will seek to enroll people who in addition to meeting criteria for two widely used, symptom-based definitions of CFS, showed signs of infection — such as a sore throat or tender lymph nodes — around the time they developed CFS. The thought is that if there is a viral link to CFS, it’s most likely to show up in those patients".

Great as long as one of the "two widely used symptom based definitions" is the CCC.

Signs of infection around time of onset? Many of us did not have an infectious onset.
Re the 'infectious onset' - this relates to the problems of trying adequately define and quantify a 'sudden' onset against a 'non-sudden' onset, by retrospective self reports, in ill people subject to disbelief and social exclusion, some for many years.

Pretty much impossible.

Unfortunately, even Oxford criteria allow for a self report of 'infection' at onset, even if it was the FLU!

What a mess. The brightest stars in the heavens still can't get their heads around this even!
 

lancelot

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But you agree the cohort is a VITAL issue though?
Yes it is vital to all CFS/ME study. If a CFS/ME study is not using the Fukuda and/or CCC definitions, then their study has already failed before it even begins. Fortunately, the Lipkin study is using the Fukuda and CCC definitions to choose their cohort so this is a non issue here. This study will finally settle the debate. We will either have to accept XMRV/MLV's as the cause or abandon it. The truth is near!
 
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Yes it is vital to all CFS/ME study. If a CFS/ME study is not using the Fukuda and/or CCC definitions, then their study has already failed before it even begins. Fortunately, the Lipkin study is using the Fukuda and CCC definitions to choose their cohort so this is a non issue here. This study will finally settle the debate. We will either have to accept XMRV/MLV's as the cause or abandon it. The truth is near!
Hi Lancelot,

Are you SURE the CCC are being used? How do you know that? If it is true, then this is great news. But I could see no indication of that.