Article: Who is Dr. Elizabeth Unger?

Article: Who is Elizabeth Unger?

You can view the page at http://forums.phoenixrising.me/content.php?413-Who-is-Elizabeth-Unger-CDC-cfs-chief

 

If she continues to believe the BS definition that is in effect Reeves Disease (ie affects most of the population) then that says it all in my opinion. Studying people with nothing in common with each other will continue to generate more questions than answers. The first thing she should be held accountable for is her support for the Empirical Definition. There is very little benefit from many random numbers that have nothing in common...statistical power, yeah right!!!

Perhaps we should send her a phone book for New York City. There will be plenty of people that she can pick at random who are "fatigued" and will provide her with plenty of "statistical power". Even better she might be able to take the mantle back from the Brits who have recently been blowing the CDC out of the water for producing expensive and completely useless studies. It's high time the CDC gets back to the days of "Dear Sir" and Dr. Unger seems like the person to do it!

 

Which Journal did she help found? It doesn't appear to be those which she is currently on the editorial board.

She might have leadership qualities, but she isn't demonstrating much leadership with regards to CFS. The recent CDC economics costs study was an elephant in the room with respect to how much research funding CFS gets, but she doesn't appear to have much interest lever aging this.

She might be better than previous heads of the group, although that isn't saying much given their history.

I actually have a slightly different opinion on the empirical definition. An empirical approach is not as terrible as it sounds, especially if it involves objective measures of symptoms or activity levels. But the so-called empirical approach was not actually empirically determined. The cut-offs in terms of the SF-36 scores etc were a priori determined. Whereas they should have been optimised such that the size of the group that it captures is the same (and not ten times larger) than the Fukuda definition that it was supposed to match. But the thresholds could also be optimised to match that of the CCC. Eg take the existing Witchita group, find out how many match a strict CCC definition and then optimise the cutoffs of the various empirical instruments until there is a high correlation between the definitions.

Yes there is going to be an arbitrary cut off between moderate-severe and mild patients. But in terms of research, it is the more severely affected patients that should be concentrated on.

 

did you read the Jason critique of the "Empirical" "definition", Snow Leopard?
www.cfids-cab.org/MESA/Jason-10.pdf

I agree that there's nothing wrong with what they were ostensibly trying to do with the Reeves inclusion, but the result of it was that (from reading the actual "Empirical" criteria as compared to Fukuda):

instead of debilitating exhaustive fatigue; you can have limiting fatigue, or fatigue and depression

instead of severely reduced activity because of the disease at hand; you can have slightly reduced activity from any cause, or depression

instead of 4 or more symptoms all constant or recurring and of 6 month's or more duration and related to the disease at hand; you can have 4 or more symptoms over the previous 1 month, only a few of which need be significant (as to continuous, recurring, or severe), and which do not need to be related to the disease at hand

edit: what I'm trying to say is that it isn't merely the parameters (how many people are included based on what percentage of the population is considered abnormal) but also how things are looked at (i.e. which subscales of the SF-36 are used, because depression able to substitute for a number of non-depression criteria... how the 4/8 symptoms are assessed in relation to the disease at hand... how debility is assessed in relation to the disease at hand).

You cannot merely change the parameters, because you will still have the problems of debility and 4/8 symptoms not being related to the disease at hand, and depression being able to substitute for severity of fatigue and for debility. You have to start over from scratch. /edit

Probably nobody from the Empirical groups match CCC, because CDC has become suspicious of symptoms such as tender lymphs (!), ataxia, and such, as indicating the patient likely does not have CFS but has some alternate disorder. (see Switzer et al., for example). Many of their patients do not even match strict Fukuda (see the CDC's OI study, for example).

Better to operationalize Canadian, as Jason has done: http://www.scipub.org/fulltext/ajbb/ajbb62120-135.pdf

Or start over and don't revise the Fukuda to make it less strict; revise it to make more strict--require PEM and add nausea as a diagnostic-contributory symptom.

Or, require PEM and cognitive dysfunction, and perhaps low NK cell function, and make the following diagnostic-contributory: abnormal SPECT, abnormal PET, punctate frontal lobe MRI lesions, low blood volume, abnormal repeat cardiopulmonary test, etc.

 

I actually have a slightly different opinion on the empirical definition. An empirical approach is not as terrible as it sounds, especially if it involves objective measures of symptoms or activity levels.

Really how do you have "objective measures" of symptoms or activity levels? Everybody has different tolerances and "beliefs" as to the severity of their symptoms and they can be manipulated easily by the ridiculous forms and questionnaires that are created. Isn't this obvious from the PACE studies? The only way forward is to insist on clear cut diagnostic tests such as NKC function, Spect Scans, cytokine panels, etc. as screens for cohort studies.

 

Cort you mention the following studies which Unger has overseen. I'm assuming the G. Broderick in all three of these, is the same Gordon Broderick who presented at the SoK meeting a couple of weeks ago?

Is this a positive sign?

"The studies that she has overseen have been highly technical explorations on the cutting edge of gene expression and other research such as....
Exploration of statistical dependence between illness parameters using the entropy correlation coefficient.Craddock RC, Taylor R, Broderick G, Whistler T, Klimas N, Unger ER.Pharmacogenomics. 2006 Apr;7(3):421-8.
Identifying illness parameters in fatiguing syndromes using classical projection methods. Broderick G, Craddock RC, Whistler T, Taylor R, Klimas N, Unger ER.Pharmacogenomics. 2006 Apr;7(3):407-19.PMID: 16610951
Gene expression correlates of unexplained fatigue.Whistler T, Taylor R, Craddock RC, Broderick G, Klimas N,Unger ER. Pharmacogenomics. 2006 Apr;7(3):395-405."

 

If she continues to believe the BS definition that is in effect Reeves Disease (ie affects most of the population) then that says it all in my opinion. Studying people with nothing in common with each other will continue to generate more questions than answers. The first thing she should be held accountable for is her support for the Empirical Definition. There is very little benefit from many random numbers that have nothing in common...statistical power, yeah right!!!

Thus far it seems like she's sticking with the ED in the form it is - which honestly I think is a disaster for her personally as no one outside the CDC has used it and I can't imagine that they will - so why keep isolating your program? Why not re-open the subject - get buy-in and start again? I believe they promised a definitions conference....so may be that will happen.

 

Which Journal did she help found? It doesn't appear to be those which she is currently on the editorial board.

She might have leadership qualities, but she isn't demonstrating much leadership with regards to CFS. The recent CDC economics costs study was an elephant in the room with respect to how much research funding CFS gets, but she doesn't appear to have much interest lever aging this.

She might be better than previous heads of the group, although that isn't saying much given their history.

I actually have a slightly different opinion on the empirical definition. An empirical approach is not as terrible as it sounds, especially if it involves objective measures of symptoms or activity levels. But the so-called empirical approach was not actually empirically determined. The cut-offs in terms of the SF-36 scores etc were a priori determined. Whereas they should have been optimised such that the size of the group that it captures is the same (and not ten times larger) than the Fukuda definition that it was supposed to match. But the thresholds could also be optimised to match that of the CCC. Eg take the existing Witchita group, find out how many match a strict CCC definition and then optimise the cutoffs of the various empirical instruments until there is a high correlation between the definitions.

Yes there is going to be an arbitrary cut off between moderate-severe and mild patients. But in terms of research, it is the more severely affected patients that should be concentrated on.

Sounds like a great idea about the ED....We'll see if she demonstrates real leadership. Dr. Reeves, apparently, was a top down kind of leader. She doesn't seem like the kind of person who is a strong leader but you never know...she has started some things in the past....will she forge her own path with CFS? Or is she satisfied with where they are at?

I can't imagine that she is...even the researchers tend to dislike the program greatly and they don't seem to be leading....

She also has the problem of really poor funding...funding that has actually dropped over the past 10 years - and the need to increase it. On that level dynamic leadership is needed to dig more dollar out of the CDC.

 

Cort you mention the following studies which Unger has overseen. I'm assuming the G. Broderick in all three of these, is the same Gordon Broderick who presented at the SoK meeting a couple of weeks ago?

Is this a positive sign?

"The studies that she has overseen have been highly technical explorations on the cutting edge of gene expression and other research such as....
Exploration of statistical dependence between illness parameters using the entropy correlation coefficient.Craddock RC, Taylor R, Broderick G, Whistler T, Klimas N, Unger ER.Pharmacogenomics. 2006 Apr;7(3):421-8.
Identifying illness parameters in fatiguing syndromes using classical projection methods. Broderick G, Craddock RC, Whistler T, Taylor R, Klimas N, Unger ER.Pharmacogenomics. 2006 Apr;7(3):407-19.PMID: 16610951
Gene expression correlates of unexplained fatigue.Whistler T, Taylor R, Craddock RC, Broderick G, Klimas N,Unger ER. Pharmacogenomics. 2006 Apr;7(3):395-405."

Yes, that is the same Broderick and she clearly has strong interests in this area. The CDC under Dr. Reeves cut back on that type of research. I'm not positive but my guess is that they have not published a paper on that kind of research in several years...

Might we see a Broderick, Klimas, Fletcher, Vernon, Unger collaboration? Theoretically we SHOULD - because everybody accept Unger is working with the others and really this is kind of odd because some of the tools to do this were developed at the CDC.

This is a big problem with them - they're doing their own thing in their own group and they're just not connected...

Outside of them you see researchers from different groups collaborating all over the place.

 

I'm not sure which Journal she founded - not sure where I got that from but check out the Association she helpef found http://www.amp.org/. This organization is a monster now... I look at it and dream about the little IACFS/ME..... Maybe someday....

 

Really how do you have "objective measures" of symptoms or activity levels? Everybody has different tolerances and "beliefs" as to the severity of their symptoms and they can be manipulated easily by the ridiculous forms and questionnaires that are created. Isn't this obvious from the PACE studies? The only way forward is to insist on clear cut diagnostic tests such as NKC function, Spect Scans, cytokine panels, etc. as screens for cohort studies.

that's eminently true, and the "severity rating" of symptoms changes even without intentional manipulation just based on how many other symptoms one has, what other life events are going on, mood, sleepiness, current efficacy of coping, etc. It's a great myth that assigning a number to something makes it objective or quantifiable.

 

did you read the Jason critique of the "Empirical" "definition", Snow Leopard?
www.cfids-cab.org/MESA/Jason-10.pdf

That one actually had a few minor differences to the CDC criteria. The better Jason paper is this one:
http://www.scirp2.org/journal/PaperInformation.aspx?paperID=1622

instead of debilitating exhaustive fatigue; you can have limiting fatigue, or fatigue and depression

instead of severely reduced activity because of the disease at hand; you can have slightly reduced activity from any cause, or depression

instead of 4 or more symptoms all constant or recurring and of 6 month's or more duration and related to the disease at hand; you can have 4 or more symptoms over the previous 1 month, only a few of which need be significant (as to continuous, recurring, or severe), and which do not need to be related to the disease at hand

The CDC was trying to capture all with 'fatigue' lasting 6 months or more. My goal would be to capture those with severe fatigue for 6 months or more, for the purpose of research (at least a preliminary group before further subtyping). I would also exclude those who are obese (BMI over 30). (I'm willing to trade sensitivity for specificity)

The issue of physical functioning can be resolved by imposing a tight SF-36 PF requirement.

The problem with the existing empirical criteria is that it only required:

physical function (? 70), or role physical (? 50), or social function (? 75), or role emotional

I'm sure we can guess the result.

Secondly, instead of the MFI which is far too vague, we could choose one from:
http://www.dsq-sds.org/article/view/1375/1540 and refine the cutoffs.

The symptom inventory could be changed to include a mandatory question to capture reduced activity for at least 2 days as a result of PEM. Activity levels demonstrating such could also be measured objectively if needed...
The symptom measures could be captured in two stages, the first whether the symptoms have persisted for over 6 months and the second about the frequency or severity of the symptoms. The choice of symptoms to use could be determined empirically as well.

Obviously the gold standard would be biomarkers, but it would lower costs if the cohort could be reduced before requiring expensive testing, such as MRI scans.

 

Obviously the gold standard would be biomarkers, but it would lower costs if the cohort could be reduced before requiring expensive testing, such as MRI scans.

Again, including people with no OBJECTIVE biomarker/test or whatever is pointless. It's a completely biased sample depending on who is asking the questions, who is filling out the forms and how those people felt on THAT day. If studies can't be done right they shouldn't be done at all.

I checked out those fatigue scales. Talk about absurd. Most people with CFS would start filling in random ovals after the first question.

Also, PEM is not necessarily related to reduced activity. And PEM is hardly an objective marker either.

Those asinine forms and questionnaires must go!!!!!!

 

that's a good paper, Snow Leopard, thanks for posting (and I didn't realize the first one had some inaccuracies; maybe I should read it again)

ok, so we're agreed that the methods of assessing symptoms and disability need to be totally redone, in addition to tightening how severe the debility needs to be. I feel much better now.

also we agree that the ostensible theoretical idea behind the "Empirical" inclusion is ok as an interim meausure (although I still feel assigning a number to something doesn't really do a lot to help assess it, but I do agree that it's good to attempt to record what symptoms are recurrent, moderate, severe, etc.); it's just that the way it was worked out in this instance (Reeves et al.) was inaccurate and did not select appropriate patients

 

I'm pretty sure we have blood-based biomarkers available. MRI is a nice thing to suggest as an aid, but it's not going to show lesions in the majority of patients anyway.

NK cell function is the way forward, and this is blood-based, therefore, will become relatively inexpensive once it's needed for 1 million patients.

 

I hope Dr. Unger reaches out to clinicians who deal with ME/CFS patients regularly and takes their input seriously. My experience has been that pathologists are smart people but they interact usually with other doctors, lab staff, medical staff rather than patients directly. So it behooves her to try to get patient or clinician input as much as possible; I know she is meeting with patient groups in the near future and I appreciate that.

Snow Leopard's point is well-taken. The way that the "Emprical Reeves Definition" has been constructed is questionable. In other areas of medicine, empirical definitions have been and still are used but they are often derived carefully from clinical observations and arbitrary cutoffs, if made, have to been tested to see if they truly reflect reality. That is there is often a derivation cohort (from which definitions are developed) and a validation group (to see how well or not the definition works). I don't know if the Reeves or other definitions have had these cohorts. Definitions are also refined over time and are not static, unlike the situation we have had for so long with Fukuda. Fukuda itself was meant to be a working and not final definition.

 

Snow Leopard's point is well-taken. The way that the "Emprical Reeves Definition" has been constructed is questionable. In other areas of medicine, empirical definitions have been and still are used but they are often derived carefully from clinical observations and arbitrary cutoffs, if made, have to been tested to see if they truly reflect reality. That is there is often a derivation cohort (from which definitions are developed) and a validation group (to see how well or not the definition works). I don't know if the Reeves or other definitions have had these cohorts. Definitions are also refined over time and are not static, unlike the situation we have had for so long with Fukuda. Fukuda itself was meant to be a working and not final definition.

There has been no validation group with the "empiric" criteria (Reeves et al., 2005) (I don't like calling it an empiric/empircal criteria, even though I've used the phrase as much as anybody, because it wasn't derived by observation but basically arbitrarily).
The 2005 paper had a small validation component where they looked at other subscales of the SF-36 within the same sample; but SF-36 subscale scores tend to correlate together. All they basically showed as I recall is that what they did was better than completely random cut-offs i.e. not a very high threshold of proof.

 

Member RLC has done a great analysis of how messed up the CFS ME defintions are in another thread if anybody is interested. It might be a good starting point of what Dr Unger should think about trying to untangle now she has taken over the CDC.

See post #22 in thread below for excellent break down of just how muddied the science is in defining CFS/ME.

http://forums.phoenixrising.me/show...e-difference-between-ME-and-CFS-to-the-public

 

Indeed Dr. Unger is impressive in all ways. However, after thirty plus years of the CDC doing everything possible to damage and discredit ME/CFS and label us as severe mental patients, I have NO faith whatsoever that the CDC and Dr. Unger will do much of anything of value for us. I hope I am very wrong but 30 years of a continued unethical and illegal pattern is pretty telling. Unger also went along with Reeve's and showed that she did NOT have the balls to stand up against unethical behavior. Her tune may have changed a bit after being put into the lead position for CDC/CFS but I am still not seeing changes to the CDC/CFS page or other major turn arounds in ME/CFS research, etc.

In my opinion, I would vastly prefer that the CDC remove itself from any and all research on ME/CFS. The funding for CDC/CFS is so very little as to not be an issue. But the damage that they have done and can continue to do with that tiny amount was/is immense. I do NOT trust the CDC to deal with us in an ethical manner. So, for me: Get the CDC out of ME/CFS research. Period.

 

I want some proof of change before anything is done towards more research also.

Even if all she does is continue with a small amount of innocuous research using "Empirical" inclusion, that would still hurt us because it doesn't tell anyone a thing about the disease we actually have, but it would produce paper with the disease title assigned to us on them (and it spends money and gives Congress the impression something is being done for us).