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Scientific progress stumbles without a valid [CFS] case definition - Leonard Jason

Commentary from Lenny Jason.
Current estimates from the Centers for Disease Control and Prevention (CDC) of the number of people in the United States with chronic fatigue syndrome (CFS) increased from about 20,000 to as many as four million within a ten-year period. If this were true, we would be amidst an epidemic of unprecedented proportions. I believe that these increases in prevalence rates can be explained by unreliable case definitions.

For example, in 1994, the CDC’s case definition did not require patients to have core symptoms of the CFS. Making matters worse, in 2005, in an effort to operationalize their inadequate case definition, the CDC broadened the case definition so that ten times as many patients would be identified. Even though these estimates were challenged as bringing into the CFS case definition many who did not have this illness such as Major Depressive Disorder, as late as 2016, the CDC re-affirmed the merit in this broader case definition.

Another misguided effort occurred in 2015, when the Institute of Medicine (IOM) developed a revised clinical case definition that at least did specify core symptoms, but unfortunately also eliminated almost all exclusionary conditions, so those who had had previously been diagnosed with other illnesses such as Melancholic Depressive Disorders, could now be classified as meeting the new IOM criteria.

This case definition has the unfortunate consequence of again broadening the types of patients that will now be identified, thus their effort also will inappropriately select many patients with other diseases as meeting the new IOM criteria. Making matters even worse, the clinical case definition was not designed to be used for research purposes, but it is clearly being used in this way, and one group of researchers has already inaccurately reported that the new clinical case definition is as effective at selecting patients as research case definitions.
Extra spacing mine for ease of readability.

Read more at https://blog.oup.com/2017/08/scientific-progress-without-valid-case-definition/
 

A.B.

Senior Member
Messages
3,780
There seems to be an ongoing disagreement between the Jason and the Montoya group on the SEID definition. This article seems to be a response to this

Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox
http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1362750

I thought the Montoya group made some interesting arguments, such as (paraphrasing)

"a more restrictive definition does not mean that it identifies the illness better than less restrictive definitions"

"orthostatic intollerance seems to be present in nearly all patients in some form and in varying degrees of severity"

"existing case definitions were based on patients that have been ill for a long time and may not accurately reflect the initial stages of the illness"

"lack of exclusionary criteria in the SEID definition is important because patients can easily have multiple medical conditions, whereas with exclusionary criteria they would not be able to have all their illnesses diagnosed and treated"
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
ALL the definitions are flawed, though perhaps the worst is the Oxford definition of CFS, especially when its presumed to cover ME.

Jason is right in this much ... we need a valid diagnostic category or categories. For that we need biomarkers. The history of definitions is that consensus definitions or one expert definitions tend to be varyingly inaccurate, and hard to verify, and this is not just the case with ME or CFS. Reliable biomarkers will change that.

I do not see this debate being definitively resolved until provably reliable diagnostic biomarkers are clinically available. When that happens we might find all the definitions and names are abandoned or modified.

Most of our researchers are very aware of the biomarker dilemma. Its no coincidence that many are moving to try to identify one or many diagnostic biomarkers. However this might require we first figure out the specific disease process/es at least in outline.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
What about the 'pooped out serum' test that Ron Davis has devised? It'd be good to see it tested out on a large sample.
You need a lot of things to create a validated diagnostic biomarker. If it finds something, that is only step one. Along the way you have to determine specificity and sensitivity. If you do not have a good grasp of the disease to start with this can be very difficult. Specificity is a real bear because you have to demonstrate this finding is not in other diseases. So it requires much more than a regular biobank. Sensitivity is about finding valid ME or CFS cases, and a biobank will help a lot there. I am omitting a lot of stuff here, and there is probably a lot I do not know about.

You can determine if something shows a regular pathophysiological biomarker much easier than a diagnostic one. Its also a step along the way. I would be surprised if the impedance chip were not tested to this standard by late next year. It might be much sooner of course. We already have this in the two day CPET, which also shows high sensitivity and some specificity.

Its specificity testing that is going to be the big challenge.
 
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62milestogojoe

What's a forum then?
Messages
221
Location
UK
You need a lot of things to create a validated diagnostic biomarker. If it finds something, that is only step one. Along the way you have to determine specificity and sensitivity. If you do not have a good grasp of the disease to start with this can be very difficult. Specificity is a real bear because you have to demonstrate this finding is not in other diseases
You are right about that. I work as a biomed in the NHS and am currently 'lobbying' for a repeat of the Osaka PET scan study (in neurological symptoms forum) and trying to gather information from PR members regarding AAB positive results (immunology symptoms forum).

Could be an impossible ask but the former might show extent of neuroinflammation and the latter might confirm AAB. (If indeed, these relate to pathogenesis/pathophysiology).

ME/CFS is a very slippery disease to pin down diagnostically-but once that technique/s is validated we may finally see resources being aimed at treatment. This will not happen until we have a viable method/s of diagnosis.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
You are right about that. I work as a biomed in the NHS and am currently 'lobbying' for a repeat of the Osaka PET scan study (in neurological symptoms forum) and trying to gather information from PR members regarding AAB positive results (immunology symptoms forum).

Could be an impossible ask but the former might show extent of neuroinflammation and the latter might confirm AAB. (If indeed, these relate to pathogenesis/pathophysiology).
Could you remind me what AAB is, please?