CDC (2016): Methods of applying the 1994 case definition of chronic fatigue syndrome

[Dolphin]

A lot of the people didn't have memory or concentration problems which is concerning.

Memory or concentration problems lasting for six months or longer were less frequent in individuals in the only M2 group (25.93 %), compared to those in M1/M2 (56.82 %) and only M1 (46.67 %) groups.

Saying that, simply having the symptom some of the time wouldn't have qualified:

Case defining symptoms
We asked all participants about their experience during the past month with each of the eight symptoms specified in the 1994 case definition, e.g., “during the past month how often have you had a sore throat?” with response choices “all of the time,” “most of the time”, “some of the time”, “rarely”, or “never”. Those responding “all” or “most of the time” for any symptom were asked if the symptom was bothering them 6 months or longer (response choices: “yes”, “no”, “don’t know”, “not applicable”, or “refused”). A symptom that was present “all” or “most of the time” and “yes” ≥6 months duration was considered to be endorsed. Participants endorsing ≥4 symptoms were considered to meet the symptom criterion.

 

[Kati]

I have been one of the biggest critics of the empiric criteria (Reeves et al 2005). One of the big problems is could qualify as having CFS even if one had no physical functioning impairments e.g. scored 100 out of 100 on the SF 36 physical functioning subscale. One could qualify as being disabled if one was impaired due to emotional reasons.


Interestingly in this study, such a scenario arose in no cases:

Meets SF-36 criterion based on Role Emotional Alone 0 0 0


This means one can be more confident that the patients are genuine CFS patients.

Thank you so much @Dolphin for submitting such a rapid response at PubMed Commons. i hope you get an answer.

 

[Kati]

A lot of the people didn't have memory or concentration problems which is concerning.

Speaking for myself, memory troubles came or compounded over time, not early on in the course of my disease. It's amazing what you miss when you are unaware.

 

[Dolphin]

Minor point:

I think there is a good chance there are errors in Table 4 in terms of listing which groups are different statistically on some criteria. For example, for Role Physical and Social Functioning, it says the only differences are between M1 only and M2 only but it looks very likely that M1 only would also be different from M1/M2 given that compared to M2, the scores for M1/M2 are worse again, the SEMs are smaller and the sample size is bigger.

 

[duncan]

What could possibly motivate Unger to lend her name to an effort that resurrects the Wichita study - knowing as she must what the ME/CFS community thought/thinks of it?

Science?

Interesting timing, too.

 

[Kati]

What could possibly motivate Unger to lend her name to an effort that resurrects the Wichita study - knowing as she must what the ME/CFS community thought/thinks of it?

Science?

Interesting timing, too.

She is an author on the Wichita paper
http://www.ncbi.nlm.nih.gov/pubmed/12860574

And the CDC has the intense need to be credible and useful. If they drop older criteria and cohort they loose both.

 

[duncan]

Good grief.

 

[Scarecrow]

A lot of the people didn't have memory or concentration problems which is concerning.

It isn't low for M2 alone considering the way the question is asked in the Symptom Inventory:

Memory Problems
C.12 During the past month, have you had forgetfulness or memory problems that caused you to
substantially cut back on your activities?
q1 Yes
q2 No (Skip to C.12f)

I have unremitting problems with my memory but if I interpreted the question literally, I would have to answer 'No' because it isn't really an activity limiting issue. It affects how much I get out of an activity or well I can do it but, on the whole, it doesn't prevent me from participating in day to day activities. So I'd be judged to have no current problems with memory even though it's been a real life changer for over thirty years.

 

[Dolphin]

It isn't low for M2 alone considering the way the question is asked in the Symptom Inventory:

Memory Problems
C.12 During the past month, have you had forgetfulness or memory problems that caused you to
substantially cut back on your activities? q1 Yes
q2 No (Skip to C.12f)

I have unremitting problems with my memory but if I interpreted the question literally, I would have to answer 'No' because it isn't really an activity limiting issue. It affects how much I get out of an activity or well I can do it but, on the whole, it doesn't prevent me from participating in day to day activities. So I'd be judged to have no current problems with memory even though it's been a real life changer for over thirty years.

But would you not be limited by your concentration?

During the past month, have you had difficulty with thinking or concentrating that caused you to substantially cut back on your activities?

It is memory or concentration problems.

 

[Scarecrow]

But would you not be limited by your concentration?
.
It is memory or concentration problems.

Similar response to memory. As a stand alone symptom, it doesn't cause me to cut back. Try and fail, yes, but not cut back. I may be being a little picky over the wording but I do tend to be quite literal. I think the questionnaire is poor.

Edited to add: strangely, the questions about memory and concentration are the only ones that are tied to cutting back on activities. Pain isn't. Fatigue isn't.

 

[Dolphin]

Edited to add: strangely, the questions about memory and concentration are the only ones that are tied to cutting back on activities. Pain isn't. Fatigue isn't.

It is somewhat strange. I don't think I've seen it described in this way before.

But in my case I would still qualify as being affected by it but then I am quite severely affected.

 

[Justin30]

I know this off topic a bit.

Im just throwing this out their....but I am not sure if the NIH Study has taken this into account.

- Have all patients had a diagnosis based on the fact that they do not have any other medical codition validated through testing?

- The NIH is using the CCC Criteria which outlines diseases to look at and test for to determine if this is ME/CFS patients included in the NIH study may require additional testing to rule this out, if it has not be done therefore If they have not had the exclusion testing then immediately they shoulf be excluded from the study.

- I know patients are being referred by ME/CFS Clinics. Can someone please carify if this is only half of the patients in the study? They all referals should come from designated ME/CFS Clinics and if not should be a major area where we should contest.

- Can someone please calrify @duncan response based on the 3 step proecess for inclusion in the study and a link?

My last point is with IAN LIPKINS close ties to Dr Daniel Petterson and Simmaron Research that his biobank samples are being used by the NIH and a specific subset will be defined likely the subset that responds to ampligen.

 

[Simon]

I've responding to a point made by @Dolphin on the PACE thread, because it seems more relevant here

there is a CFS group with a mean SF-36 physical functioning score of 78.67. (This is taken from the table 4 data)

This is not with a unusual definition for CFS but the CFS (Fukuda et al., 1994) group that does not also satisfy the empiric criteria (Reeves et al 2005). In some ways one can't get any more mainstream.

Though it's hard to see how such a high average score (some will be higher) fits with Fukuda's requirement for "substantial reduction in previous levels of occupational, educational, social, or personal activities". I guess there's a lot of ambiguity in that phrase. The new paper looks really weird.

By contrast, a UK general-practice based study found a SF36 PF score of 30 using Fukuda (Table 2), though that does look on the low side. In theory, a GP based survey in the UK, where there is universal healthcare coverage, should apporximate to a population study, though there are bound to be some biases.

Note PACE required a SF-36 physical function of 65 or less to qualify for entry into the trial

That SF36 PF score alone (79/100) looks odd to me - maybe there was such a high overlap of 'Fukuda' patients with Reeves because the Fukuda patients included many with mild symptoms who other researchers would not diagnose as mecfs.

 

[anciendaze]

Comparing one defective set of diagnostic criteria with another and finding substantial concordance is scarcely the way to guide effective research. The truth about the Fukuda definition is that it has been used by groups with diametrically opposed views on etiology, who have then assembled cohorts based on their own prejudices by a process of emphasizing some factors and excluding others.

Based on what happened in the cohort used in Lipkin's study on XMRV we should assume that they would not include, e.g., any patient who had a measurable decrease in thyroid function. ("That's Hashimoto's thyroiditis, which we already understand." "Really? What causes the autoimmune response to thyroid tissue?") We have since seen that some patients who came here have Ehlers-Danlos Syndrome, which would almost certainly lead to exclusion. That patient responded to Rituximab. We just had a patient test positive for paraneoplastic autoantibodies. We've had a patient with the pathognomonic sign of Wilson's disease make a brief appearance on the forum -- after being examined by MDs. This would not show up on questionnaires. The criteria in use scarcely have anything to do with anything physically measurable.

If the goal was to do some relatively cheap research on lots of people, and produce cohorts that would make further research as difficult as possible, this approach would serve admirably.

I'm afraid this reinforces my prejudice that the CDC is mainly competent in dealing with infectious diseases with rapid progression and transmission, and has no special skills appropriate for chronic disease of any kind. The organization has shown itself to be irrelevant to solving such a problem.

 

[jimells]

I'm afraid this reinforces my prejudice that the CDC is mainly competent in dealing with infectious diseases with rapid progression and transmission, and has no special skills appropriate for chronic disease of any kind. The organization has shown itself to be irrelevant to solving such a problem.

Amen to that. The CDC decades-long obsession with measuring "fatigue" reminds me of past efforts to identify criminals by measuring their skulls - and is just as useful.

And the CDC has the intense need to be credible and useful. If they drop older criteria and cohort they loose both.

If this is true then we will never see anything remotely helpful from CDC. But it's not surprising, since the first instinct of any bureaucracy is it's *own* survival - not ours.

 

[anciendaze]

I'd like to point out that the funding which allowed Montoya's research at Stanford came from a private source, the OMI initiative was also privately funded to the tune of 10 million dollars, Lipkin's microbiome study was crowdfunded. You might compare these results with the sum total of CFS research funding channeled through CDC over several decades.

What does this tell you about funding channels and ability to produce change?

 

[medfeb]

A few observations but I may be misunderstanding something so don't hesitate to correct me if I am

1) On the SF-36 - the paper said that there were no patients who satisfied just the Role Emotional subscale criteria. However, I don't think the paper said how many patients satisfied only the Role Emotional and Social criteria but did not satisfy one of the physical scale criteria. As Jason pointed out in the 2008 paper, patients could have technically satisfied just the Role Emotional and Social criteria without having physical impairment.

2) Regarding the CDC symptom inventory - The CDC symptom inventory is a list of 19 symptoms scored for frequency and severity. The cutoff score is >25, calculated as the sum of the scores for each of the eight CFS individual symptoms, where those scores are calculated as the frequency score times the severity score. But as Jason noted in his 2008 paper, the threshold of 25 could be reached by just two symptoms and those did not need to be core symptoms of the disease. From his paper:

"the criterion would be met if an individual rated only two symptoms as occurring all the time, and one was of moderate and the other of severe severity... Similarly, a person with MDD could endorse symptoms that would easily meet criteria for this scale, such as unrefreshing sleep, impaired memory, and headaches, and muscle pain at a moderate to severe level. However, the most important factor is that the Symptom Inventory does not distinguish critical symptoms for CFS such as postexertional malaise, unrefreshing sleep, and cognitive difficulties. Each symptom is given the same value, which means that a participant reporting severe and frequent headaches is given the same value as a participant reporting severe and frequent postexertional malaise.
​

The original protocol published by the NIH for the intramural study indicated that they were using the CDC symptom inventory with a cutoff of > 25. Its not clear how that symptom assessment method (tool plus cutoff) can be used to assess CCC for the reasons stated above and because some key symptoms like orthostatic intolerance are not included in that instrument. I do not know if NIH intends to still use that instrument.

3) This paper states "substantial concordance" between the two methods. But my understanding is that the Reeves 2005 paper also compared these two methods (referred to there as surveillance versus empirical) and stated "There was minimal association between the empirical classification and classification by the surveillance criteria." (e.g. Table 5 - Of the 43 patients classified by CFS by the Georgia method, only 10 had been diagnosed as CFS by the Wichita method.) So how did Reeves 2005 "minimal association" become "substantial concordance"?

4) Maybe just being thick but I don't understand the clinical validity of the M1/M2 group? It seems meaningless to me as it does not represent a particular diagnostic method but rather throwing two different groups of patients together. This seems particularly problematic when according to their own 2005 paper, the Wichita method showed "scant stability of CFS over time."

 

[Snow Leopard]

At what point do we accept that criteria based purely on questionnaires or clinical judgement are always going to lack both specificity and or sensitivity?

 

[Dolphin]

I've responding to a point made by @Dolphin on the PACE thread, because it seems more relevant here

there is a CFS group with a mean SF-36 physical functioning score of 78.67. (This is taken from the table 4 data)

This is not with a unusual definition for CFS but the CFS (Fukuda et al., 1994) group that does not also satisfy the empiric criteria (Reeves et al 2005). In some ways one can't get any more mainstream.

Though it's hard to see how such a high average score (some will be higher) fits with Fukuda's requirement for "substantial reduction in previous levels of occupational, educational, social, or personal activities". I guess there's a lot of ambiguity in that phrase. The new paper looks really weird.

By contrast, a UK general-practice based study found a SF36 PF score of 30 using Fukuda (Table 2), though that does look on the low side. In theory, a GP based survey in the UK, where there is universal healthcare coverage, should apporximate to a population study, though there are bound to be some biases.

Note PACE required a SF-36 physical function of 65 or less to qualify for entry into the trial

That SF36 PF score alone (79/100) looks odd to me - maybe there was such a high overlap of 'Fukuda' patients with Reeves because the Fukuda patients included many with mild symptoms who other researchers would not diagnose as mecfs.

Medical Outcomes Study: 36-Item Short Form Survey Instrument (SF-36)
https://www.rand.org/health/surveys_tools/mos/mos_core_36item_survey.html
this is an automated version of the form:
http://www.sf-36.org/demos/SF-36.html



When I was mildly affected, the only one I might have said I was limited a lot for would be "Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports?". I might have scored 80 or even more.

Though I probably wouldn't have been a good candidate for many research studies as there might be some doubt about my diagnosis.

 

[Scarecrow]

But in my case I would still qualify as being affected by it but then I am quite severely affected.

I'm not sure that this has much to do with severity. More to do with duration of illness, how you've adapted to it and, perhaps, stability of symptoms. If the question was posed in terms of "Compared to your pre-illness activity, have you had forgetfulness or memory [or concentration] problems that have caused you to cut back on activities?", it might prompt a different - and correct - response. Perhaps it's implicit in the question that it's in comparison to pre-illness but it would certainly have caught me out. And a question shouldn't be phrased in such a way that it requires this level of analysis.