NIH post-infectious CFS study

[Scarecrow]

I cannot shake the sense that some internal NIH politics were at play here.

Me, too!

I hoping that someone can come up with a reasonable explanation for including the FMD group.

 

[Bob]

why include the FMD group?

I don't understand the thinking behind the inclusion of a FMD control group either. I'm not sure if I should be pleased or concerned. At the moment I'm mainly concerned, seeing as how some clinicians like to give ME patients a functional diagnosis.

 

[jimells]

I cannot shake the sense that some internal NIH politics were at play here.

Yes, I was thinking how their apparent protocol and our reaction to it compares to, say, the current Fluge & Mella studies. The difference is the NIH project reads like it was created by a committee, and well, some compromises had to be accepted in order to get everyone on board.

 

[Bob]

I'm also perplexed by this exclusion criterion:
"History of head injury with loss of consciousness, or history of head injury with amnesia lasting greater than a few seconds".

As a schoolboy I used to play rugby at county level and was knocked unconscious several times. The last time it happened (thirty years ago now) I had amnesiac episodes for up to a year. I had several brain scans, which were "normal". My current ME/CFS symptoms started abruptly after an URT infection. Why on earth should my historic episodes of unconsciousness be an exclusion factor? Are they saying all my current flu-like symptoms etc. may be a result of some delayed and hitherto undetected neurological damage?

That's just good practice. If there's any chance that the symptoms in some patients may be caused by historic head injury, then it makes sense not to include those patients, as it will confuse the overall results. They need as tight a cohort of patients as possible. It doesn't say anything about your personal situation.

 

[jimells]

It does seem a bit arbitrary to include ex-Lyme patients as a control, but I think it's a useful control.

I don't think so. Any kind of Lyme related group is going to be a huge unknown, given the huge unknowns and controversies around that illness too. What can possibly be learned by comparing one unknown group to another?

 

[Bob]

I've just realised that the information on that webpage doesn't exclude using the CCC as part of the study. It simply lists the minimum enrolment criteria. They can carry out sub-diagnosis using CCC after recruitment. But it would be better to use CCC and/or Reeves/Fukuda for recruitment.

 

[Scarecrow]

My bolding:

Exclusion criteria for all participants:
- -
- -
-Current DSM-5-defined major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
- -
- -

Is this a concern from a research perspective?

 

[Denise]

Definitely not looking at severely ill people...

"--Functional impairment as determined using the Short-Form 36 (SF-36): score of greater than or equal to 70 physical function subscale, or greater than or equal to 50 on role physical subscale, or greater than or equal to 75 on social function subscale, or greater than or equal to 66 on emotional subscale. " (emphasis added)

 

[Bob]

Any kind of Lyme related group is going to be a huge unknown, given the huge unknowns and controversies around that illness too. What can possibly be learned by comparing one unknown group to another?

They are including patients who had a definite Lyme bacteria infection, and who were successfully treated. I'm not sure that I agree that there are many unknowns involved in that. It seems quite clear cut.

 

[Bob]

Definitely not looking at severely ill people...

"--Functional impairment as determined using the Short-Form 36 (SF-36): score of greater than or equal to 70 physical function subscale, or greater than or equal to 50 on role physical subscale, or greater than or equal to 75 on social function subscale, or greater than or equal to 66 on emotional subscale. " (emphasis added)

If I remember correctly, Reeves 2005 uses an SF-36 PF score of 70 as a cut-off point for a diagnosis, so I think the above quote should be an exclusion criteria, not an inclusion criteria. I think it's been placed in the wrong section by error. Edit: or it should say "less than" rather that "greater than".

 

[Scarecrow]

Definitely not looking at severely ill people...

"--Functional impairment as determined using the Short-Form 36 (SF-36): score of greater than or equal to 70 physical function subscale, or greater than or equal to 50 on role physical subscale, or greater than or equal to 75 on social function subscale, or greater than or equal to 66 on emotional subscale. " (emphasis added)

They surely mean less than in each case?
A physical function score of 70 is still well below normal.

 

[Bob]

Exclusion criteria for all participants:
- -
- -
-Current DSM-5-defined major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
- -
- -

Is this a concern from a research perspective?

Just my opinion, but I think this is sensible to exclude those patients. Some ME patients have secondary psychiatric symptoms, but we don't want primary psychiatric patients included in the study. But I'm not sure about including same patients if they have a stable treatment regimen.

 

[Denise]

If I remember correctly, Reeves 2005 uses an SF-36 PF score of 70 as a cut-off point for a diagnosis, so I think the above quote should be an exclusion criteria, not an inclusion criteria. I think it's been placed in the wrong section by error. Edit: or it should say "less than" rather that "greater than".

I think you are right @Bob. Thanks for correcting me.
It looks as though it should read "less than or equal to"...


"Illness classification by standardized clinically empirical criteria
We used information from the SF-36, MFI and Symptom Inventory to classify subjects empirically according to the 3 main dimensions of CFS: functional impairment (SF-36), fatigue (MFI) and accompanying symptoms (Symptom Inventory). We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (≤ 70), or role physical (≤ 50), or social function (≤ 75), or role emotional (≤ 66.7) subscales of the SF-36."

https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-3-19

 

[Scarecrow]

Just my opinion, but I think this is sensible to exclude those patients. Some ME patients have secondary psychiatric symptoms, but we don't want primary psychiatric patients included in the study. But I'm not sure about including same patients if they have a stable treatment regimen.

It was the exclusion to the exclusion that I was thinking about:

unless managed for more than six months with a stable treatment regimen

(I'll bold it in the original post.)

 

[jimells]

I'm not sure that I agree that there are many unknowns involved in that. It seems quite clear cut.

Well I keep hearing about "chronic Lyme" and "post treatment Lyme" and "no those things don't exist" and "the diagnostic tests are unreliable" and "the tests are fine". That seems like a lot of controversy to me, but I don't follow the Lyme discussions very often, so maybe I'm misunderstanding the issues.

 

[duncan]

I wonder how many recovered Lyme patients - who satisfied the CDC 2T requirements - they will attract.

There is potential for a study within a study here. Bets the NIH Lyme peeps are monitoring this?

 

[Denise]

I'd like to know how many patients they are enrolling and how many participants they want for their control groups.

I believe when we were first told this study would happen they said it would be small (and yet we get admonished right, left and center because our studies are "too small").

 

[medfeb]

Definitely not looking at severely ill people...

"--Functional impairment as determined using the Short-Form 36 (SF-36): score of greater than or equal to 70 physical function subscale, or greater than or equal to 50 on role physical subscale, or greater than or equal to 75 on social function subscale, or greater than or equal to 66 on emotional subscale. " (emphasis added)

As Jason pointed out in a 2007 study, the functional impairment criteria (using "or") means that a patient can have impairment on just the emotional subscale - no physical impairment - and still meet the criteria.

Regarding the Reeves/Empirical definition, the IOM stated “A study suggesting a role for childhood trauma in ME/CFS used the broad empirical definition of ME/CFS, which resulted in a biased sample with overrepresentation of individuals with depression and posttraumatic stress disorder (PTSD)" and said that the "unusually high proportion of subjects with serious psychiatric problems" explains the study finding of an association between ME/CFS and adverse childhood experiences.

Regarding the exercise bicycle test - they don't specify CPET, just bicycle exercise so its not clear that they will be including gas exchange measurements during the exercise. If not, can't quantify level of effort, PEM as onset of anaerobic energy production at low levels of effort with a second day decline.

 

[Nielk]

Is this the intramural study that Collins recently promised?

 

[medfeb]

yes