Time for the Big Talk. How's the CAA doing?

[hvs]

However, I believe future XMRV research will likely bring in many new players (individuals and/or organizations) and eventually overshadow some of the major players that have been prominent in the past. Past players who have been able to often unduly shape public policy and perception on ME/CFS.

So even though I've enjoyed this thread and have learned a lot, I don't know how relevant it will all be going forward. Individuals and/or organizations that may not have always acted in our best interests (probably often innocently so), just won't have as much clout going forward.

Like Summer, I think you're on to something here, Wayne. And it's one of the reasons I'm monitoring what the CAA says so closely. What will this institution do now?

I suspect the nature of being a CFS patient will change drastically when we all become XAND patients. The CAA has been used to advocating for patients, frankly, w/o much hope. They worked on awareness and validation and so on. (Only recently did they get into the act of directly funding research.) We're all about to become people with a lot hope, but facing a tough, life-long disease the taming of which is going to take some hard-hitting medicine. We are now and will continue to look to the WPI (and other researchers) or answers and guidance for treatment.

Again, what will this institution do in the face of this constitutional challenge? Which way will they go?

My proposition was that they receive poor marks for their performance in the first few weeks of this new era. Instead of preparing everyone to be great critics of the inevitable Reeves hatchet job of replicating the unimpeachable WPI study, they offered their "cautionary tale" which was hamfisted, at best, and many folks interpret it as worse. Reasonable people can disagree, but Vernon's objections to not having certain data published in the _Science_ article in my opinion were not scientifically sound. Since I think they had no sensible basis in science, I have to guess at the real basis.

 

[The Phantom]

I agree with Wayne that Reeves currently has the most ability to throw a monkey wrench into XMRV research. I also agree that science is going to ultimately sweep aside many of the current players, including Reeves, because a lot of people are going to want to study a new retrovirus. However, in the short run, it will be a bad thing if Reeves publishes a study, using patients who meet the Reeves definition, that finds XMRV in, say, 20 percent of that cohort. (This will be the approximate result if 75% of his sample doesn't have CFS, which is what is suggested by his prevalence numbers, and the 25% who do have CFS have a 67% positivity rate for XMRV). He will then go to the New York Times, etc. and claim WPI is unreliable. This is not insurmountable, but it will take time to straighten this out. I think most of us would like to see the science progress as quickly as possible.

By the way, if you want to see the scientific review process gone awry, check out the review of the original publication of the Reeves' definition. You can find it at the end of the downloadable pdf of the paper (although I hesitate to suggest clicking on the pdf of the paper, because every click gets recorded and used to support the validity of the paper). There was a single reviewer, Tony Komaroff, and no statistical review! The statistical method they used, called, ironically, the Monte Carlo analysis has been mostly used in derivatives trading. Google it. Suzanne Vernon is, unfortunately, a co-author of the Reeves' definition. I think she's a sincere scientist, but, geez Suzanne, you really blew it on this one.

Anyway, what I really want to make sure everyone does is sign Tom Kindlon's petition about the Reeves' definition. Since my guess is that most people on this forum have already signed, I'm hoping you'll get all your friends and relatives to sign, too, if you haven't already done so.

This is the email I sent to anyone I thought might sign. First I said hi and caught them up on my news if I hadn't been in touch for a while, and asked about theirs. Then I said:


By the way, I'm emailing everyone I can think of to see if anyone is willing to sign a petition about the definition of Chronic Fatigue Syndrome (which I, along with many other people, call Myalgic Encephalomyelitis or ME/CFS). It's a pretty esoteric thing to have to have a petition about, but, unfortunately, it's important. Basically, since there's now a lot of data about infectious and other possible causes for CFS, in 2005 Dr. Reeves of the CDC decided to redefine it (CFS) so it would better fit his theory of a psychological cause. Dastardly! Anyway, there's an online petition against the definition. It's a bit of a slog to get through: there's the petition, then there are references, then there's an explanation, then there are a bunch of additional notices, then there's the place where you "sign". They do want your email address, but you can check a box saying you don't want to be notified about any additional related petitions, and I've never been spammed by them to my knowledge. You can also check a box if you don't want your name showing up on the internet. It only takes a couple of minutes.

You may have heard about the new data that suggests that ME/CFS may be caused by a retrovirus called XMRV. Given that a retrovirus was suggested as the cause in the early 90's but rejected by the CDC, a lot of people think this is a good time to discuss why the science has been so bad. Hence, the petition. If you want more information before considering whether or not to sign, call, email or shout loudly and I'll be happy to explain further. If you know anyone else who might be willing to sign it'd be great to pass it along.

Here's the link: http://bit.ly/nYHy5



If you're able to, please copy & paste, then email this to anyone you can think of. Feel free to alter it, add to it, improve it in any way you can think of, yell at me, whatever. The last time I looked (& I'm embarassed how often I do look) there were about 1750 signatures. It would be great to get to 2000 or beyond. You don't have to be from the U.S. to sign. Tom posted the petition from Ireland. This affects all of us.

Thanks to Cort for providing this forum and to everyone who contributes. I learn so much here.

 

[kolowesi]

Typical

I'm really confused. What's typical, what's mild, what's moderate?

We can't go by diagnosis, that's a moving target. The surface has been scratched in gene expression, but it's hard to determine cause and effect there as well. How many of us have had a full array of testing?

My local neurologist and Dr. Garth Nicolson found active mycoplasma in over 50% of fibro patients. I wonder if these patients are immunocompetent? How many of them have reactivated viral infections, but have never been tested?

I'm wondering if the pool of people with XMRV is actually much larger than the sickest CFIDS patients.

Not everyone has reactivated viruses, stealth bacteria, high RNase-L, low Natural Killer Cell function. But is it really true that only 20-25% of ME/CFS patients have immune system dysfunction? I'm getting the 20%-25% figure from those who say that's the number of people with an infectious component (I've read it several places, but probably can't find it).

If so, what the heck is going on with the other 75%? And I'm not talking about Dr. Reeve's cohort either.

I look forward to being enlightened on this. I think it is central to the validation studies. Can someone point me to a definition of "mild CFS," "moderate CFS," "typical CFS" as the researchers and CAA are using the terms, not as the CDC would use them.

The CAA is protecting us from thinking there might be an answer out there and being disappointed later. Even if XMRV turns out to be another co-infection rather than a cause, it's not worth getting excited over?
I read elsewhere that the 20 or so cancer patients were people who had been sick for 20+ years. HHV-6a is found in cancer and MS, even EBV is known to cause cancer. The other exogenous retroviruses cause cancer, (I realize it's not known whether XMRV is endogenous, but the 4% of controls doesn't seem enough for something that's been around for generations.)

I hope the CAA will continue to improve as representatives of this heterogeneous (and in my case, cranky) population. My opinion for many years was that they were playing for the same team as the CDC, not the team of those who search for answers to an organic disease.

I will have an open mind, as Cort and others insist they are on our side. If they must be political and protect us from panicking, I will try not to be irritated. If the CDC has blown it by ignoring us, I suspect the real panic will be elsewhere than in the patients' minds. We already know how bad this is.

Kelly

 

[Dolphin]

I agree with Wayne that Reeves currently has the most ability to throw a monkey wrench into XMRV research. I also agree that science is going to ultimately sweep aside many of the current players, including Reeves, because a lot of people are going to want to study a new retrovirus. However, in the short run, it will be a bad thing if Reeves publishes a study, using patients who meet the Reeves definition, that finds XMRV in, say, 20 percent of that cohort. (This will be the approximate result if 75% of his sample doesn't have CFS, which is what is suggested by his prevalence numbers, and the 25% who do have CFS have a 67% positivity rate for XMRV). He will then go to the New York Times, etc. and claim WPI is unreliable. This is not insurmountable, but it will take time to straighten this out. I think most of us would like to see the science progress as quickly as possible.

By the way, if you want to see the scientific review process gone awry, check out the review of the original publication of the Reeves' definition. You can find it at the end of the downloadable pdf of the paper (although I hesitate to suggest clicking on the pdf of the paper, because every click gets recorded and used to support the validity of the paper). There was a single reviewer, Tony Komaroff, and no statistical review! The statistical method they used, called, ironically, the Monte Carlo analysis has been mostly used in derivatives trading. Google it. Suzanne Vernon is, unfortunately, a co-author of the Reeves' definition. I think she's a sincere scientist, but, geez Suzanne, you really blew it on this one.

Anyway, what I really want to make sure everyone does is sign Tom Kindlon's petition about the Reeves' definition. Since my guess is that most people on this forum have already signed, I'm hoping you'll get all your friends and relatives to sign, too, if you haven't already done so.

This is the email I sent to anyone I thought might sign. First I said hi and caught them up on my news if I hadn't been in touch for a while, and asked about theirs. Then I said:


By the way, I'm emailing everyone I can think of to see if anyone is willing to sign a petition about the definition of Chronic Fatigue Syndrome (which I, along with many other people, call Myalgic Encephalomyelitis or ME/CFS). It's a pretty esoteric thing to have to have a petition about, but, unfortunately, it's important. Basically, since there's now a lot of data about infectious and other possible causes for CFS, in 2005 Dr. Reeves of the CDC decided to redefine it (CFS) so it would better fit his theory of a psychological cause. Dastardly! Anyway, there's an online petition against the definition. It's a bit of a slog to get through: there's the petition, then there are references, then there's an explanation, then there are a bunch of additional notices, then there's the place where you "sign". They do want your email address, but you can check a box saying you don't want to be notified about any additional related petitions, and I've never been spammed by them to my knowledge. You can also check a box if you don't want your name showing up on the internet. It only takes a couple of minutes.

You may have heard about the new data that suggests that ME/CFS may be caused by a retrovirus called XMRV. Given that a retrovirus was suggested as the cause in the early 90's but rejected by the CDC, a lot of people think this is a good time to discuss why the science has been so bad. Hence, the petition. If you want more information before considering whether or not to sign, call, email or shout loudly and I'll be happy to explain further. If you know anyone else who might be willing to sign it'd be great to pass it along.

Here's the link: http://bit.ly/nYHy5



If you're able to, please copy & paste, then email this to anyone you can think of. Feel free to alter it, add to it, improve it in any way you can think of, yell at me, whatever. The last time I looked (& I'm embarassed how often I do look) there were about 1750 signatures. It would be great to get to 2000 or beyond. You don't have to be from the U.S. to sign. Tom posted the petition from Ireland. This affects all of us.

Thanks to Cort for providing this forum and to everyone who contributes. I learn so much here.

Well done, The Phantom.

2000 signatures would be great.

It'd be great if some people tried writing to others.

Lots of people are enthusiastic e.g. they signed twice and I deleted a signature (in case you wonder why the figures are odd e.g. I deleted around 20 on Monday - duplicates that came in in the last couple of weeks).

But I get the impression it has not been E-mailed around as much as it could be. Or linked to, etc.

 

[_Kim_]

Since my guess is that most people on this forum have already signed

I didn't know about the petition (I just signed it, I'm #1756). I wouldn't assume that all of the members of this forum know about it either. Maybe you could repeat the details (above) as a new/separate thread?

 

[kolowesi]

petition on Facebook

Tom,

I joined the CAA on facebook and put the link in a comment saying we need to fix this.

Hope that's OK!

 

[Advocate]

So there should be at least two types of studies; one on the original cohort and one on more typical patients.
.

Cort, who will define "typical?" What is your idea of "typical?"

 

[The Phantom]

I didn't know about the petition (I just signed it, I'm #1756). I wouldn't assume that all of the members of this forum know about it either. Maybe you could repeat the details (above) as a new/separate thread?

You're right, Kim. I'll do that. I'm not sure where to put it, but most people seem to be looking at the XMRV/XAND forums & it is relevant to future XMRV research, so I'll put it there. Maybe I'll start a new thread in advocacy, too. If anybody else wants to start a thread somewhere else, please feel free to copy & paste--we need every signature we can get. Thanks to Kolowesi for getting it on Facebook. I'm not on it. Anybody on MySpace? Anybody Twitter? I've only heard about these things, but if anyone knows how to do it, go for it!

 

[Aftermath]

Dr. Vernon and Reeves' Empirical Definition

...
Suzanne Vernon is, unfortunately, a co-author of the Reeves' definition. I think she's a sincere scientist, but, geez Suzanne, you really blew it on this one.

...

Wow. If this is correct, she definitely blew that one. Do you have any citation for the paper in which this definition was chronicled?

 

[cfs since 1998]

Chronic fatigue syndrome--a clinically empirical approach to its definition and study

Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C.

 

[Dolphin]

Chronic fatigue syndrome--a clinically empirical approach to its definition and study

Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C.

She was a CDC employee at that stage. I think they might have been "following orders" so to speak.

Here's my theory on what happened (copied from something I wrote before):

[Aside: A lot of people have made suggestions to me speculating why the CDC broadened the criteria in the way they have done. I do not know the answer. The most plausible theory to me is the following: The CDC followed patients in the community in 1997, 1998, 1999 and 2000. Between December 2002 and July 2003, they were brought in for intensive testing. In total, 227 people were invited in, including 70 who had previously been diagnosed with CFS. These people went through very expensive testing the whole exercise cost $2m. However, unfortunately, only 6 out of the 70 cases of CFS satisfied the Fukuda definition when they were brought in. Also 4 more of the other individuals also satisfied the definition. If one only excludes people who currently have Melancholic Major Depressive Disorder (MDDm) (which was not the recommendation of the International CFS Study group), one can get the numbers who satisfy the Fukuda definition up to 16. The CDC admit this in their paper (Reeves, 2005). However 10 (or 16 if one allows all the MDDm cases) people with CFS would not be enough for the CDC to publish CFS studies with a lot of the data they have. For some of the experiments, people would not have been suitable for one reason or another e.g. they were on medication. Also, often data is not complete or tests become corrupted so a percentage is lost. For some of the experiments, gender might make a difference and one may end up excluding the men as there might not be enough patients. So 10 or 16 CFS patients is not enough to publish CFS papers using this data. But $2m of the CFS fund had been spent on this experiment and it might look like a waste of taxpayers money if papers were not published. The CDC had already gotten into trouble for misusing the CFS budget in the past. So the definition of CFS was expanded so that CFS papers could be published. So thats one plausible theory although one does not need to accept that to believe that the empirical definition is flawed].

 

[Advocate]

So thats one plausible theory although one does not need to accept that to believe that the empirical definition is flawed].

Do you think we should refer to it as the Reeves definition or the "empirical" definition? Which term suggests more clearly the arbitrary nature of the various definitions?

 

[Dolphin]

Do you think we should refer to it as the Reeves definition or the "empirical" definition? Which term suggests more clearly the arbitrary nature of the various definitions?

I've got into the habit of calling it the empiric/empirical definition from writing to medical journals (mainly just online comments).

But a proper "empirical" definition is where one would get the thresholds using sophisticated mathematical/statistical techniques.

While all they did was pick numbers out of the air e.g. the median for the MFI-20 scores in their sample (not even based on a population sample).

The paper looks scientific because they then use some mathematical/statistical techniques to show the thresholds are better than nothing, but that's not really much of an achievement. Pretty much anyone can up with something than is better than nothing/better than random numbers.

So "Reeves' criteria" best. Possibly best not to say Reeves definition as he tries to claim it's not a new definition, that he has just picked out thresholds for the Fukuda definition. But the numbers are so odd! So Reeves criteria (or Reeves definition) best I guess.

 

[Dolphin]

I see I used the term "empirical definition" rather than "empirical criteria" in the petition!

Anyway, at the start, I didn't want to make it too personal about Reeves.

But I think to mobilise the ME/CFS community, calling it the Reeves' criteria is probably best as well as the point I made about calling it an "empiric"/"empirical" definition being a bit misleading.

 

[Andrew]

I think Vernon was a little less upbeat than some other researchers, but her cautions were no different than the cautions we've been giving each other here. And her tone is really no different than the members of my local support group that I've heard from.

FWIW, I still don't trust the CAA. My distrust began with their newsletter, which seemed to be little more than patting themselves on the back. And then their "faces" campaign, which I found insulting.

 

[MEKoan]

What about "CDC criteria"?

When I read "empirical" I cannot help but think, altough I know better, that it is logical and a response to other criteria which is not. I know that's not the case but, each time I read it, I must do a little mental correction: it doesn't mean what it says it means.

I would imagine that people who do not know the history must ask themselves why we are complaining about criteria which is "empirical".

I also understand not wanting to make this some kind of personal thing with Reeves. I think "CDC criteria" is the most straightforward and clear especially is teamed with some kind of modifier: cockamayme CDC criteria, erronious CDC criteria, concocted CDC criteria... or, something more reasonable if you must.

Peace out,
Rafiki

 

[Dolphin]

What about "CDC criteria"?

When I read "empirical" I cannot help but think, altough I know better, that it is logical and a response to other criteria which is not. I know that's not the case but, each time I read it, I must do a little mental correction: it doesn't mean what it says it means.

I would imagine that people who do not know the history must ask themselves why we are complaining about criteria which is "empirical".

I also understand not wanting to make this some kind of personal thing with Reeves. I think "CDC criteria" is the most straightforward and clear especially is teamed with some kind of modifier: cockamayme CDC criteria, erronious CDC criteria, concocted CDC criteria... or, something more reasonable if you must.

Peace out,
Rafiki

People can use whatever descriptions they like in E-mails, etc.

My point about using the world empirical (which I didn't choose as such - it's a term the CDC use in the paper) rather that, say, "CDC criteria" is most researchers think of CDC criteria as the Fukuda definition. So this was to distinguish between the two.

The CDC team are trying to say they are just using the Fukuda definition. And if you don't look at their papers very carefully, it looks like that is what they're doing. Sometimes they don't even reference the 2005 paper. So part of the aim of the petition is to highlight that the definition/criteria they are using is different. Personally I don't think the Fukuda are great by themselves. But what the CDC is so much worse.

But people can use whatever language they want when trying to raise awareness on the issue.

 

[The Phantom]

She was a CDC employee at that stage. I think they might have been "following orders" so to speak.

Here's my theory on what happened (copied from something I wrote before):

[Aside: A lot of people have made suggestions to me speculating why the CDC broadened the criteria in the way they have done. I do not know the answer. The most plausible theory to me is the following: The CDC followed patients in the community in 1997, 1998, 1999 and 2000. Between December 2002 and July 2003, they were brought in for intensive testing. In total, 227 people were invited in, including 70 who had previously been diagnosed with CFS. These people went through very expensive testing the whole exercise cost $2m. However, unfortunately, only 6 out of the 70 cases of CFS satisfied the Fukuda definition when they were brought in. Also 4 more of the other individuals also satisfied the definition. If one only excludes people who currently have Melancholic Major Depressive Disorder (MDDm) (which was not the recommendation of the International CFS Study group), one can get the numbers who satisfy the Fukuda definition up to 16. The CDC admit this in their paper (Reeves, 2005). However 10 (or 16 if one allows all the MDDm cases) people with CFS would not be enough for the CDC to publish CFS studies with a lot of the data they have. For some of the experiments, people would not have been suitable for one reason or another e.g. they were on medication. Also, often data is not complete or tests become corrupted so a percentage is lost. For some of the experiments, gender might make a difference and one may end up excluding the men as there might not be enough patients. So 10 or 16 CFS patients is not enough to publish CFS papers using this data. But $2m of the CFS fund had been spent on this experiment and it might look like a waste of taxpayers money if papers were not published. The CDC had already gotten into trouble for misusing the CFS budget in the past. So the definition of CFS was expanded so that CFS papers could be published. So thats one plausible theory although one does not need to accept that to believe that the empirical definition is flawed].

I don't mean to be very critical of Suzanne Vernon's co-authorship of the Reeves criteria, just a little critical. The convention with scientific articles is to put the person actually writing the article as the first author, and the senior supervising scientist as the last author. The middle group of people are usually listed in order from the most involved to the least involved. Dr. Vernon's position in the list implies she was the least involved. I think tomk's scenario is very plausible. It's possible this article is one of the reasons she left the CDC--we don't know. Still, her name is on the article, so, for me, that means I need to be a bit wary of her opinions. She may have been following orders, or she may simply not have understood the whole picture at that time. She may have a better understanding now.

As to what to call the Reeves definition/criteria/fiasco, I also think it doesn't matter. Hopefully, if we make enough noise about it, it will be appropriately discredited and we won't have to call it anything. It will just disappear. You don't hear much about the Oxford criteria any more. Unfortunately, there are still studies that used the Oxford criteria that are referred to by other studies, but at least people aren't doing new studies using Oxford.

Then there's the question about whether we need to focus on the NIH rather than the CDC, given that the NIH has more money for research. My thought is we do need to keep our attention on the CDC right now. The NIH has mostly PhD researchers, not doctors. They are interested in the virus, not the patients. Many of them will not pay attention to clinical criteria; they will leave that to the CDC. Please note that the journal Science didn't even want to publish clinical information about the control group in the Mikovits study--that information was offered to them, but it wasn't worth the column inches to them. This has been a criticism levelled by the medical community, but the scientific community doesn't really care. My guess is the NIH will pursue research on XMRV, because it's an interesting new virus. But they may not pursue research on XMRV in people with ME/CFS if the CDC publishes a paper saying they're not finding the same levels of XMRV in CFS using the Reeves definition. They may not know anything at all about the problems with the Reeves definition, and they may not have the time or the interest to find out. They're busy. They trust the CDC to do the right thing clinically. They don't know they're not trustworthy; we do. It's a potential problem which we need to avoid.

 

[Dolphin]

I don't mean to be very critical of Suzanne Vernon's co-authorship of the Reeves criteria, just a little critical. The convention with scientific articles is to put the person actually writing the article as the first author, and the senior supervising scientist as the last author. The middle group of people are usually listed in order from the most involved to the least involved. Dr. Vernon's position in the list implies she was the least involved. I think tomk's scenario is very plausible. It's possible this article is one of the reasons she left the CDC--we don't know. Still, her name is on the article, so, for me, that means I need to be a bit wary of her opinions. She may have been following orders, or she may simply not have understood the whole picture at that time. She may have a better understanding now.

I think this might be one of the reasons why the CAA have been relatively quiet on the issue at least until the last few months.

After the Georgia study came out around June 2007, with a prevalence rate of 2.54%, a lot of us woke up that the CDC were doing something strange. Mary Schweitzer seem to have noticed before that and there might have been the odd other person but few people had said much anyway.

So anyway I thought things would move after that and was disappointed that the CAA weren't bringing it up more.

Eventually by April 2009, I decided I was fed up waiting and set up the petition.

I think the petition and people complaining more have nudged the CAA to do something.

So I think things are going in the right direction in some ways.

But we need to keep complaining about the Reeves/empiric/CDC definition as nobody including no researchers (except Leonard Jason) are making much of a fuss about it. It might be because that 2005 paper is so hard to read. One person said to me they thought it was deliberately hard to read.

 

[dkesh]

CAA's job is to get funding

I think that the discussion here is somewhat misguided. In a well-organized effort, it's not really the CAA's job to pick out winners and losers from the research. Their job should be to, by whatever means necessary, increase the size and diversity of the funding pool for CFS research, treatment, and education.

Their most important job is and always will be lobbying the government to increase funding. It doesn't really matter whether Suzanne Vernon thinks that XMRV is the answer or not; what matters is whether the organization uses the XMRV research as an excuse to increase funding by whatever means necessary. Even if XMRV turned out to not be the answer in terms of research, the CAA would've done a terrible job if they don't make XMRV the answer in terms of funding. Interest has never been higher. The job of patient advocates is to translate that interest into research dollars.