David Tuller - Trial By Error: A Q-and-A with Leonard Jason, on Case Definition

[Kalliope]

A Q-and-A with Leonard Jason, on Case Definition

A Brief Update: Berkeley’s crowdfunding period closed on April 30th–Monday night. I ended the campaign with $87,580. After Berkeley’s 7.5% in fees, the funds will cover my salary/benefit from July 1, 2018 to June 30, 2019, and some travel costs. I really, really appreciate the fantastic support. Thanks to everyone! I’ve taken a few days to regroup from my Australia trip and catch up on my time zones.

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Leonard Jason is a professor of psychology at DePaul University in Chicago. He has served as vice president of the International American Association of CFS/ME and as chairperson of the Research Subcommittee of the U.S. Chronic Fatigue Syndrome Advisory Committee. Professor Jason began investigating chronic fatigue syndrome almost 30 years ago. Much of his work has focused on the epidemiology and prevalence of the illness and on the impact of using various case definitions. He has long been concerned that the lack of a uniform set of criteria for identifying study participants has hindered progress in the science.

Dr. Jason recently shared his thoughts about these issues.

 

[Webdog]

the IOM report was correct in requiring several core symptoms, such as PEM. But I believe these authors made a mistake in indicating that a patient could have either cognitive impairment or orthostatic intolerance—one or the other. Cognitive impairment should have been required for all patients to have.

I couldn't agree more. Cognitive impairment should be a core symptom of this disease, and the IOM screwed up badly by making it optional.

 

[Melanie]

Cognitive impairment should be a core symptom of this disease

Measuring cognitive impairment is a WHOLE DEAL but measuring OI is easy. On a clinical level diagnosing someone is easy with SEID and if PEM is used I don't see a doctor getting the diagnosis wrong. I swear Lenny is TRYING to misdiagnose people.

 

[Webdog]

Disagree with Jason's automatic dismissal of patients diagnosed with a primary psychiatric disorder. Many ME/CFS sufferers are misdiagnosed for years with a primary psychiatric disorder, before finally finding a doctor that recognizes ME/CFS.

When it comes to ME/CFS, having a primary psychiatric disorder diagnosis on your medical record does not mean you actually have a primary psychiatric disorder.

 

[Esther12]

There's so much uncertainty around criteria that I find it difficult to have much of an opinion about anything.

 

[Ravn]

Totally agree with the gist of the interview: we need good case definitions to get good research results. No argument.

But there's a very strange statement in this paragraph (bolding mine):

the IOM report was correct in requiring several core symptoms, such as PEM. But I believe these authors made a mistake in indicating that a patient could have either cognitive impairment or orthostatic intolerance—one or the other. Cognitive impairment should have been required for all patients to have. But a more serious problem is that they inadvertently expanded the case definition by having just about no exclusionary illnesses, such as primary psychiatric disorders. My team recently conducted a study where about half the people with a variety of medical and psychiatric illnesses met the IOM criteria.

This is effectively saying that “about half the people with a variety of medical and psychiatric illnesses” actually have PEM. How can this be? Some serious issue with defining PEM here, surely!

 

[Ravn]

Disagree with Jason's automatic dismissal of patients diagnosed with a primary psychiatric disorder. Many ME/CFS sufferers are misdiagnosed for years with a primary psychiatric disorder, before finally finding a doctor that recognizes ME/CFS.

I think what he means is that for research purposes it's important to distinguish between a patient with ME, a patient with a primary psychiatric disorder and a patient with possibly both. Otherwise you end up with muddled data.

Obviously it's also important to distinguish between those in a clinical setting so the patient gets the correct diagnosis and treatment.

 

[Webdog]

I think what he means is that for research purposes it's important to distinguish between a patient with ME, a patient with a primary psychiatric disorder and a patient with possibly both. Otherwise you end up with muddled data.

Obviously it's also important to distinguish between those in a clinical setting so the patient gets the correct diagnosis and treatment.

I hear you. But it can take years for a ME/CFS patient to get a primary psychiatric disorder misdiagnosis removed. Many patients likely don't bother, or aren't aware they still have a psych misdiagnosis on their medical record.

Should these ME/CFS patients be excluded from participating in research? Not a rhetorical question. I honestly don't know the answer and it isn't so clearcut to me.

 

[Barry]

Disagree with Jason's automatic dismissal of patients diagnosed with a primary psychiatric disorder. Many ME/CFS sufferers are misdiagnosed for years with a primary psychiatric disorder, before finally finding a doctor that recognizes ME/CFS.

When it comes to ME/CFS, having a primary psychiatric disorder diagnosis on your medical record does not mean you actually have a primary psychiatric disorder.

I think this misunderstands what Jason is trying to get across. He is not saying that someone with a diagnosis of a primary psychiatric disorder might not in fact be a genuine ME sufferer who has been misdiagnosed. Jason very carefully clarified the distinction between a research case definition versus a clinical case definition, and the need for that distinction. He is saying that in order to avoid confounding factors in the research trials, it is vital to only run those trials with people known to primarily only suffer from ME. It is nothing to do with whether the other people might be PwME but misdiagnosed, it is simply about keeping the research as noise-free as possible.

So if you use a very stringent research case definition, in order to get high quality research trial data, this may then help develop a more meaningful clinical case definition, that might then better avoid misdiagnosis of PwME as having primarily psychiatric disorders.

When trying to analyse complex problems, where there are a lot of unknowns, it is usually good to minimise the number of variables, so you can focus on those variables you are most interested in. This can sometimes mean, for experimental purposes at least, opting for artificially 'ideal' samples. Maybe later on, once you have learnt from these experiments, it may then be possible to work with more complex samples.

Edit: I see @Ravn said this much more concisely than I have.

 

[Barry]

Should these ME/CFS patients be excluded from participating in research? Not a rhetorical question. I honestly don't know the answer and it isn't so clearcut to me.

My feeling is that the purpose of research is to try and get the best quality answers for PwME, and should not in any way be obliged to include participants who would - unwittingly maybe - detract from that. Even though it may not be a person's fault they are not the right person for trial participation, if they are not the right person, then they would just hold back research if they somehow did get in. It may be harsh on the feelings of that individual, but otherwise much harsher on the many many more people who would benefit from having the best, most incisive research trials.

 

[Forbin]

If the problem with the ICC is that it specifies too many symptoms - apparently thus capturing people with a primary psychiatric disorder because they will assert most every symptom in the book - I don't see how the solution to that problem is to use a criteria that lists fewer symptoms (like the CCC). That won't deter primary psychiatric cases from continuing to assert they suffer from almost every symptom available on that smaller list .

If you have a criteria with a large number of symptom options, the solution would seem to be to have both a minimum and a maximum number of symptoms needed for diagnosis. Thus a person could be excluded (from research at least) if they asserted too many symptoms as well as too few.

[Of course, then you have the problem of how do you keep people from knowing that they shouldn't claim too many symptoms?]

 

[Inara]

Physicians see lots of people coming into their practices, where the patients are seeking help for their fatigue, and in fact it is one of the most common reasons for seeing a doctor

Is this true? I read it so often. But myself, I never went to a doctor because of tiredness - I never would have thought about it. Did someone here?

(On the other hand, I couldn't work anymore because I felt like if I went on I would crack due to a heavy exhaustion and pain and feeling worse from day to day...)

 

[chrisb]

The most puzzling aspect of this discussion is that we seem to be reinventing the wheel. I suggest that in the 1980s it was well appreciated that in order to pursue research in this field it was necessary to reduce the variables to a minimum. If abnormalities were then found in that group you look for them on extended groups. Admittedly this was only an impression gained over seven years of consultations.

I do not doubt that those who came up with the Oxford criteria were intelligent men, nor that intelligent men act for reasons. It is just that the reasons which have been proffered for broadening the criteria have never appeared persuasive.

 

[Trish]

I couldn't agree more. Cognitive impairment should be a core symptom of this disease, and the IOM screwed up badly by making it optional.

I don't agree, @Webdog.

Take me as an example - I have had ME for 28 years. I definitely get PEM - delayed 24 hours after exceeding my physical energy envelope, lasting several days or weeks, and my PEM has always involved flu-like crash that puts me to bed with pretty severe multiple symptoms, not just increased pain and fatigue.

My main other symptoms are rapid muscle fatiguability, unrefreshing sleep, muscle pain, orthostatic intolerance, headaches and nausea. I have had all those symptoms for 28 years through mild, moderate and now severe levels of disability. Yet during my mild years I had very little cognitive dysfunction except during PEM, and even now brain fog is my least disabling symptom. Are you saying I should not have been diagnosed with ME?

 

[Forbin]

Yet during my mild years I had very little cognitive dysfunction except during PEM, and even now brain fog is my least disabling symptom.

I wondered about this too, as the only definitive cognitive problem I can recall developing in the immediate aftermath of the onset of ME was "word finding." I noticed this problem quite early in the illness, years before there were any formal definitions of ME/CFS that included it.

But, if you look at the CCC, the range of neurological/cognitive symptoms goes far beyond what one might think (I highlighted ones that have affected me in blue).

Neurological/Cognitive Manifestations: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances e.g., spatial instability and disorientation and inability to focus vision. Ataxia, muscle weakness and fasciculations are common. There may be overload phenomena: cognitive, sensory e.g., photophobia and hypersensitivity to noise and/or emotional overload, which may lead to crash periods and/or anxiety.

Cognitive problems I had not considered until reading this list included "short term memory consolidation" and "difficulty with information processing." It was quite some time after onset before I first noticed that, if I was given a sequence of instructions/tasks to perform, my mind just went "blank" on first hearing them. Somewhat embarrassingly, I would always have to ask for the whole thing to be repeated before it would sink into my memory. This was not a problem I'd had before the onset of ME.

 

[Inara]

Jason very carefully clarified the distinction between a research case definition versus a clinical case definition, and the need for that distinction.

At least in Germany there would be no people left for research if people with psychiatric (mis)diagnoses are excluded. I would say nearly everyone here got a psych diagnosis at some point or the other before getting an ME diagnosis. I think this is what you meant, @Webdog?

 

[Trish]

I tend to assume the idea of research definitions excluding people with psychiatric diagnoses intends to exclude those with concurrent recognised psychiatric disorders such as major depressive disorder, from the cohort being studied, so signs and symptoms resulting from that disorder do not confuse the picture of ME.

I wouldn't want it assumed that it would exclude people who had previously been misdiagnosed with depression when their condition was clearly actually ME, even if depression is still on their medical record. But I can see that could become a problem if past medical records are taken into account.

 

[Arnie Pye]

But myself, I never went to a doctor because of tiredness - I never would have thought about it. Did someone here?

Yes. I've suffered from iron deficiency or iron-deficiency anaemia frequently throughout my life, so I've presented with fatigue/tiredness quite often. I've now discovered that I can get iron tests done privately (Edit : without involving a doctor), and I can buy prescription-strength iron pills without a prescription, so I manage the problem myself.

 

[Mij]

I didn't experience cognitive issues for the first 8 years of illness. No PEM either.

Presently (19 years in) PEM and OI issues are what keep me physically and cognitively disabled.

It was a little challenging answering Dr. Jason's questionnaire because the 6 month window he kept referring to didn't apply to me.

 

[Hoopoe]

This is effectively saying that “about half the people with a variety of medical and psychiatric illnesses” actually have PEM. How can this be? Some serious issue with defining PEM here, surely!

I think he is not applying the IOM criteria correctly. Going from my flawed memory, he used a definition of PEM that would allow a person feeling tired after exertion to count as having PEM. During the NIH common data elements public feedback period it also became apparent that Jason has a view of PEM that is somewhat different from that of the community here. The way the IOM defined PEM was much more in line with patient experience, at least in this community.