The Fight is on...Imperial College XMRV Study

[MEKoan]

I find this concept very slippery so please bear with me.

If the Imperial College intentionally screened out anyone with signs and/or symptoms of ME/CFS, which seems to be the case and their modus operandi in general, and they found 0 XMRV, does that not bolster rather than weaken the case for a connection?

If XMRV exists in between 2 and 3.7% of healthy controls, who may go on to develop ME/CFS and who may have biomarkers indicating that they are at risk, mightn't a 0 result from Imperial simply indicate that their samples had been pre-screened, deliberately yet inadvertently, for said marker.

So (squishy, squishy) what I'm trying to say is, given the statistical problem of finding 0, isn't it more likely that in their choice of cohort they have identified and excluded one or more relevant indicators of XMRV infection?

Might that not be a good thing?

 

[fresh_eyes]

*smacks forehead*
Good thinkin', Koan!

 

[MEKoan]

thanks! My brain hurts.

 

[fresh_eyes]

Brain cramp! Brain cramp! But you're absolutely right - because healthy people who are XMRV+ may have 'organic abnormalities' due to XMRV that would have excluded them from this study, even if they're not (yet) ill.

 

[MEKoan]

Brain cramp! Brain cramp! But you're absolutely right - because healthy people who are XMRV+ may have 'organic abnormalities' due to XMRV that would have excluded them from this study, even if they're not (yet) ill.

Preciselioso!

Given what we have been told about how they cherry pick patients for studies this seems the logical conclusion.

ETA Someone, somewhere, said that they could not have prescreened for XMRV to rig the results but they may have prescreened for something which is linked with XMRV infection in every case but is not yet known to be.

Yes: brain cramp!

 

[Hope123]

Ah, but there is still the question of whether or not they tested healthy controls at all. It may have been a reporter misinterpretation or a slip from McClure - but they were mentioned in the press.

I still say that they might have found XMRV in the healthy controls and threw out that data to make their point.

At least as stated in the paper, NONE of the samples were from healthy controls.So there was no healthy comparison group.

 

[Orla]

Dr yes wrote:

If it is established on the record that patients with orthostatic intolerance, abnormal white cell counts or any other physical abnormalities were excluded from the study, I think we will have all we need to make this study fade from both public and scientific memories

Most patients in the UK only get very basic tests done. I would expect this testing to include white cell counts but not orthostatic intolerance testing.

The authors wrote:

"All patients had undergone medical screening to exclude detectable organic illness"

But because most patients were likely to have had only minimal testing, the study could have included people with organic problems, just that the researchers probably didn't check for the type of abnormalities typlically seen in ME/CFS patients (and probably any patients who happened to have abnormal tests from elsewhere, or came up abnormal on what they checked for, would have been excluded, from my reading of it)

Orla

 

[Dr. Yes]

So, re the rest of your post, it all boils down to one question, yes? Did they actually exclude all those with any sign of organic disease? Seems like an easy enough question to answer. Have you considered posting it in the comments section? Some comments/questions are getting answered.

Hey Fe,

It is an easy enough question to answer, but getting it answered is the tricky part. I checked out the journal comments page again just now and the authors still haven't responded to any questions except one -- from a fellow molecular biologist/ virologist (McClure even agreed to run an extra test that he suggested). The other excellent questions (none from scientists) have been ignored, so far. (McClure did deign to say 'thanks, you're very smart' to one respondent who wrote in just to defend their study.)

So I still think the best way to get this question actually answered, and answered seriously, is to have a scientist correspond with them. I really hope Dr. Vernon would see the importance of doing so. I really hope she gets the message.. I could always try to write her, but writing something 'official' is a little harder on me than posting here (more concentration on the 'presentation')... but if I don't hear back from Jennie S. by tomorrow I probably will anyway.

The other possibility is of course, as we mentioned earlier in this thread, to write to Wessely directly ourselves (jointly, en masse, whatever). It may get a response, but I'm concerned that we would get the "handled" response -- friendly but soft on details, and still unclear. Or just bullsh**. Wessely in particular seems to be good at that. McClure and the others, if they responded, would at best refer us back to him for that information.

Hopefully Jennie S. and the CAA will have some good news for us. Otherwise, we'll have to try emailing ourselves, probably by the end of next week. Does anyone know of another possibility?

 

[ashes]

Hi there,

This is my first post but I've been lurking on the boards since the XMRV news broke.

Ok, I'm confused, so if they screened out anyone with any evidence of organic disease and they had no healthy controls, who exactly were they testing? If they have no organic disease doesn't that make these people, by definition, HEALTHY (at least in their minds)? Or, alternatively, by screening out people with organic disease, and eliminating "healthy" people, were they just trying to analyze the "depressed people" (i.e. those with no abnormal lab results but who complain of issues). I'm not saying those people are necessarily healthy (they may have their own undiagnosed issues) but it certainly seems that they hand-picked people that had no measurable symptoms, which means they don't have ME/CFS. Right?

 

[_Kim_]

Hi ashes

Hi there,

This is my first post but I've been lurking on the boards since the XMRV news broke.

Ok, I'm confused, so if they screened out anyone with any evidence of organic disease and they had no healthy controls, who exactly were they testing? If they have no organic disease doesn't that make these people, by definition, HEALTHY (at least in their minds)? Or, alternatively, by screening out people with organic disease, and eliminating "healthy" people, were they just trying to analyze the "depressed people" (i.e. those with no abnormal lab results but who complain of issues). I'm not saying those people are necessarily healthy (they may have their own undiagnosed issues) but it certainly seems that they hand-picked people that had no measurable symptoms, which means they don't have ME/CFS. Right?

Welcome to the forums!!

You're confused I'm confused the only one who isn't confused is Simon Wessely :Retro mad:

 

[froufox]

Yes I agree with you Orla and I was going to post about this issue too. All the tests that were mentioned that the participants underwent eg thyroid, morning cortisol, liver function, electrolytes, urea, full blood count etc are very very basic and generally do not pick up abnormalities that people with CFS have. I have had these tests done several times and they are always 'normal', though I would dispute what is normal for thyroid as the ranges they use are too wide, and for cortisol they only test serum, not saliva, ...my saliva cortisol is down in the dumps all day but my morning blood cortisol is 'ok'. Also my white blood cell counts I think are on the low side but they are always in range. The only thing that is apparently wrong with me is that I have low ferritin! So the fact that these people have tested normal on these tests means nothing...they might well still have a lot of abnormalities undetected by the tests like in my case.

Most patients in the UK only get very basic tests done. I would expect this testing to include white cell counts but not orthostatic intolerance testing.

The authors wrote:

But because most patients were likely to have had only minimal testing, the study could have included people with organic problems, just that the researchers probably didn't check for the type of abnormalities typlically seen in ME/CFS patients (and probably any patients who happened to have abnormal tests from elsewhere, or came up abnormal on what they checked for, would have been excluded, from my reading of it)

Orla

 

[MEKoan]

It says that the 186 were selected from consecutive attenders at a NHS clinic, but if you read the references it is clear that these were bloods stored from previous research papers. The statement is disingenuous as the impression is that it was consecutive attenders that were used but they were SELECTED from this group, which is not the random choice it seems. In fact the consecutive bit should have been left out as it is meaningless when you don't use them all.

Going to those previous papers, the patients were screened and excluded if they had any organic disease or positive results from the minimal blood tests. SW's definition of CFS excludes anyone with neurological signs so they would be out too.Then they were then given a questionnaire and only if they gave the right answers to that were they deemed to have CFS.

I find this concept very slippery so please bear with me.

If the Imperial College intentionally screened out anyone with signs and/or symptoms of ME/CFS, which seems to be the case and their modus operandi in general, and they found 0 XMRV, does that not bolster rather than weaken the case for a connection?

If XMRV exists in between 2 and 3.7% of healthy controls, who may go on to develop ME/CFS and who may have biomarkers indicating that they are at risk, mightn't a 0 result from Imperial simply indicate that their samples had been pre-screened, deliberately yet inadvertently, for said marker.

So (squishy, squishy) what I'm trying to say is, given the statistical problem of finding 0, isn't it more likely that in their choice of cohort they have identified and excluded one or more relevant indicators of XMRV infection?

Might that not be a good thing?

 

[fresh_eyes]

So, guys, check out this thread of comments on the PLoS ONE paper:

http://www.plosone.org/annotation/l...notation/6bfbac4a-5ace-4a2d-a9bb-60f017ae24d8

McClure is jumping to do the testing the commenter suggested ASAP, results by Monday. Does that strike anyone else as kind of strange? Like practically an admission of having made a mistake?

 

[MEKoan]

Even with only minimal testing is it not possible that there is a consistent yet not, on the face of it, startling abnormality which shows up in all who are infected with XMRV and which excluded them from participation in a Wessely related study?

If that is the case, might that not, at the end of the day, prove to be a very useful finding?

 

[Lily]

I kinda think that we may be misinterpreting what "eliminating those with organic disease " means. I think what they mean by that is that they did not include anyone with any confirmed diagnosis such as MS or say diabetes, lupus, hashimotos or any number of other diseases that can be confirmed diagnostically. And that they included only those who had been seen for chronic fatigue, who also had basic routine blood chemistries that were within normal ranges. The anomaly there is that cortisol test, which doesn't fall into any "routine" evaluation I've ever seen, and that is particularly interesting to me. I'd like to see someone inquire about that.

To me, that does not mean that they excluded those with say, orthostatic intolerance for instance. Orthostatic intolerance is a symptom - the cause is not found in many cases and so it is attributed to dysautonomia, or sometimes a cause may be identified such as of cardiovascular disease. If a cause is identified/verified, then these people would have "organic disease" and not be included.

I'm sorry I cannot explain this better. It seems so clear to me until I attempt to put it into writing here. If I could talk, instead of write I'd do a better job.

A lot of what we all have are "symptoms" that cannot be confirmed to be associated with organic disease. If they truly did rule out everyone with any symptoms other than fatigue, then they surely did do some very nice cherry picking, and I don't see how anyone could possibly take them seriously. That would make it just too easy for their study to be discounted, so I don't believe that's what they did.

Doesn't the CDC criteria exclude other organic disease? It's been a long time since I reviewed the various criteria sets, but I thought one of them did.

Don't misunderstand me - I certainly don't think they performed a valid replication study. I'm only speaking to the "exclusion of those with organic disease" thingee.:Retro smile:

 

[MEKoan]

Hi Loldershaw,

Prof. Wessely has a very distinct idea of what this means and it is more of a political than a semantic problem we grapple with.

ETA this cherry picking was not done for this study which, as you say, would be far too blatant. The cohort was defined long ago in other Wessely studies and the blood was simply passed along for this one.

P Wessely could rush this blood along to any lab quite confident that no sick people had been included.

 

[Katie]

IDEA!

You know all the stuff about UNUM, you know who really loves that kinda story, and any dodgy business like that - Private Eye.


UK folk, what do you think? Worth emailling them at the very least. They've printed stuff about Phil Parker threatening people with libel so they are aware of some controversy surrounding ME. Any thoughts?

 

[thefreeprisoner]

Parvofighter, have you seen the way that if you Google "xmrv economist" your awesome comment comes out top, not the original Economist article itself?!! LOL.
Brilliant work...

 

[MEKoan]

Oh yes, I am well aware of all that.

Sorry, loldershaw, of course you are.

 

[fresh_eyes]

Parvofighter, have you seen the way that if you Google "xmrv economist" your awesome comment comes out top, not the original Economist article itself?!! LOL.
Brilliant work...

OMG! Parvo, you're famous! Good on ya! Thanks for pointing that out, freeprisoner (& by the way, welcome!).