CFSAC Meeting Day 1 – IOM Study Process and Q&A (Aug 2015)


>>Great to be back.
This is nice, I get to add information to the help involve all the conversations needed
around this illness I served as committee chair and I know how hard it is to make the
time on your calendars and get here but it’s a terribly important issue and we appreciate
time you put into help move the field forward and help patient versus the care they need.
To that end the IOM head was commissioned at the behest of HHS from response to committee’s
earlier recommendations to address a number of issues and I have been asked to go over
that process and how it came to be, what the final recommendations were and answer what
questions I may. I am of course representing a committee.
My individual self here. My own opinion, try to be responsive as one
of the committee members and see how that goes.
This is the committee, I think you will see on the committee it’s an interesting mix of
people. Many raise concerns early in the process and
concerns were heard. The committee was expanded or included more
content experts than they have in IOM process. If you would see typically in the IOM you
want committee provided in expert process of review literature making recommendations
not necessarily experts in illness they are reviewing.
They’re expert at literature review critical analysis, and putting these together.
roughly half the committee is that sort. Very experienced our chair was amazing.
Ellen clayton has done this before. She keeps you on task and keeps you — keeps
the ambitious mission. A doable mission and very good.
The content experts as you can see rather the Chronic Fatigue Syndrome experts on the
committee, you will recognize, some of the serve on this committee really choose physician
who is a patient advocate on the committee. Cindy Bateman, you all know very well myself,
Dr. Lerner, Ben NAGLeson, Peter rowe, people well known to the research and clinical community.
You would be surprised to realize people on that list, I won’t reveal who had family members
or personally were touched by this illness and they were the process, if you would, members.
I was pleased when I got to that committee realize we were talking together everyone
was committed to trying to do something meaningful that would help the field.
This is the committee, it met endlessly, it was a lot of work, put a year aside of your
life when you’re on a committee because it takes a lot of work.
Do all that, and you put together as we did this large dock, international experts.
Great to see Dr. NABAWANBY, it’s a lovely thing to tap into our international collegues.
Cathy ROWe, pediatrician extraordinaire from Australia presented to this committee before,
amazing people — amazing people willing to put the time an effort into this report.
This is the outline, we reviewed the background, context of illness, our task and then we had
— went through this long process to approach the task.
Ultimately came up with these four recommendations. And quite a bit of discussion about other
things maybe beyond the scope of the task. Y’all know the background ME/CFS.
I will tell you more about it because you’re the experts but the most important take home
here, I think y’all need to hear me say this, one of the missions this committee took seriously
was the 80 to 85% of undiagnosed cases in this country.
That’s a huge thing an really the thing that pressed this economy the most, how can we
make a difference so that your average primary care doc knows this illness, knows how to
define it, and put people into proper tracks of care.
It’s a horrible hole in our medical knowledge. You know patients that fall deep into that
hole and had to clam more out themselves trying to find experts and get into overburdened
clinics, few expert clinics in this country have weighed this and struggle themselves
to say financially viable to provide care for these patients.
So that is a terribly important piece, and we took it very seriousliful the other issues
multiple case definitions, clinical case definitions and recall that our task, major task was clinical,
not research understand clinical case definition that we can educate providers and the community
at large. A tool that would be useful to help diagnose
know these patients. — diagnose these patients so more background
about the struggle. And misconceptions revolving around the poor
patient populations that seeks care and doesn’t get it.
there’s also an issue around disability and the amount of disability that is results from
this illness an integrate cost to society, subpoena to $24 billion, — 17 to $24 billion,
evidence based CDC. The context is HHS commissioned the IOM to
put these people — IOM asked to put these people together to address case definition.
We had several charges. We were to develop an evidence based diagnostic
criteria for clinical use. Let me keep underscoring clinical because
a lot of the flash back on this has been that it’s not a research case definition, never
supposed to be a research case definition. Supposed to be a clinical case definition.
Supposed to address whether or not there might be a better name than ME/CFS.
We all agreed from the get go at this time’s a terrible name, ME/CFS doesn’t do the patient
community or the clinical community any great service.
And to develop a strategy to disseminate the new knowledge that would come from this report.
This is a process, my eyes aren’t good enough to read the slide, must have gotten lost in
a text there. Let me just run through it.
You can’t see the brown knocked it out in the reformat we lost the color.
It happens. First arrow is the task to the IOM to start
this, then a committee selection process. This is where this committee raised concerns
and context experts were at it so this is a dynamic process and ultimately satisfied
everyone that this committee represented well people who unthe illness as well process of
creating reports such as this. There were a number of meetings, four long
meetings here in D.C. and between every meeting there was a tremendous amount of home work.
I could say as a committee member, while the IOM staff did a literature review and some
27,000 articles an honed down 10 make what could have been 5,000 page readable document
so there was this process. So we had the meetings, we drafted, redrafted,
we voted a lot, redrafted, redrafted some more and then the fall this draft went out
for review, and the viewing committee which also kneed significant time to get through
completed review process in mid December and mid December we have one last go at quickly
reading it the week before Christmas before it was going to be sent to press, then went
to press an released in the early part of the year.
The committee’s approach was deliberative approach, consensus approach that means we
spent a lot of time and discussion, a lot of time.
There were two public sessions, this was important to the committee we called it half the committee,
unfamiliar with the illness and the passion of the patients and their comments greatly
influenced the process. Greatly.
I won’t say that too many times, greatly. They were touched, they were moved. Those of us that live and breathe it were like “Yes, this is the people we take care of.” But the people that were hearing the stories were really touched by how difficult of a road to go this has been.>>The post-exertional piece discriminates
this illness from a lot of other illnesses so it’s required in this case definition.
And then even though there are many elements to this illness and we agree to it, the things
that are evidence-based and discern it from other things, clinical are cognitive impairment
and the dysautonomia. So those two are up there — but we note the
non-restorative sleep because that’s an element that is evidence based and consistently found.
So we have this clinical case definition. But notice it doesn’t have biomarkers attached
to it. There is obvious lay work up that need to
be done, this is where doctors use their brain and does work ups and do the rule outs through
work ups. We’re not saying do it exactly this way, we’re
asking partly because we discovered that when earlier recommendations said do this small
battery, the third party payers weren’t paying for anything else, which is ridiculous.
You have to have a proper workup. The other is the biomarker work in this field,
we all agreed and said clearly in the document that natural killer cells, this function has
strong evidence while it doesn’t discriminate from another disease it discriminates normal
very well. The discussion around that was can the average
doc get a good NK cell study function done or not, that needs to be done.
That’s the CDC right now doing exactly that study and we appreciate that, because there
was not enough evidence in the literature to say the quality of the test done outside
of sophisticated labs like Dr. Fletchers and others is necessarily good enough to put into
recommendations so I hope it be addressed in the next round of discussion which was
also recommendation to take this all back up again in a couple of few years when there’s
more data available. There’s a diagnostic algorithm written down
one thing you see in the algorithm is that this is in the report, also in the clinical
guidelines clinician guidelines report came outside by side, much shorter and quicker
to role through, basically how to make this diagnosis, this algorithm is there.
It’s got some thinking three things obvious way to go through this.
It’s a simpler algorithm than any other case reports.
If I might say as a doc that had to sit through board exams I should be able to know that
one. That case definition is knowable, I can memorize
it think it know it. Whereas the other case definitions that we
have in this field you need ad cheat sheet to get through it.
You couldn’t keep it in your head. I’m doing this for 30 years, we’re not going
to be 30 plus years. Too tight there.
But when I have an attorney in front of me I see the FCUDA criteria so I don’t misit
and I have been doing it 30 years and I have trouble keeping eight symptom criteria the
proper order in my head. The Canadian case definition.
Is even more, remember I’m on these committees, the Canadian, the ICC, and help these case
definitions and each and every day have to sit with algorithms to figure it out.
If you need the back-up page that’s easy, that’s very easy, you don’t have to have a
thinking tree in your head to do it. It’s simple, post exertional malaise, non-restorative
sleep with cognitive or static symptoms and/or. Very simple.
To review further the symptoms be severe enough, the duration long enough, there are other
common manifestations. Here is the list of symptoms if you can pull
this right out of any of these other case definitions, you can see in the report not
to be ignored. But they weren’t discriminating enough to
make diagnosis or common symptoms when there’s inflammation.
Or there are don’t have enough evidence base to tell you where people with these illnesses
have these symptoms so pain is common and in the literature varies quite a bit.
They’re triggering infection, strong evidence for that, very clearly in the chapter that
reviews viral infections that Epstein bar is a trigger for this.
And also it’s said clearly in that chapter that the immune dysfunction was significant
enough to be concerned about viruses reactivating. Didn’t necessarily recommend you had to do
viral serology, et cetera, lay down the ground work for you to say the immune system is broken,
viruses will reactivate in that setting. The gastro GI and GU symptoms were mentioned,
the inflammatory symptoms like sore throat, scratchY throat and painful tender lymph nodes
and the neuroinflammatory symptoms sensitivity to external stimuli, all common manifestations.
The dysautonomia got a solid endorse. Because it made the case definition when we describe
in here what symptoms that might — how that might present.
I won’t review that for this this group. You know it well but drop in blood pressure
racing hearts and that comes with a lot of symptoms.
There is indeed immune dysfunction. I’m going to say I pull off the IOM tag off
the bottom of my slides, if I wrote this slide. I didn’t want to give you — I had thoughts
to include but I didn’t want to have to pass it through the IOM hierarchy so I pulled the
logo off my slides if I threw it in. So this is one of my slides, the immune dysfunction
is present, endorse natural killer cell function is impaired.
And the evidence was sufficient, strong. Sufficient to say that.
More research was necessary to address cytokine abnormalities.
If you would you put in a point in time that literature went through May of last summer,
2014. And there was very important articles that
came out since that probably would have influenced that.
The big thing here, this is the problem with our field is there’s a host of papers that
were unfunded pilot studies out there, and there’s some better funded and larger studies
out there. So Dr. Fletcher’s paper on cytokines was a
strong paper but there weren’t sufficient large studies to validate that.
So they were often the big paper was out there but the validation paper was not.
So now I think what you see is even in the last year since we finished this lit review
the papers are out there. If you revisited this, there might have been
quite a different recommendation even today than there were at the time.
This is what we had at the time and committee consensus.
So the conclusion there was immune dysfunction in MECFS, NK cells are broken, more cells
are needed. Neuroendocrine dysfunction the same way, there’s
evidence of hypothalamic and pituitary dysfunction T adrenal appeared intact.
There’s signaling abnormalities that signal evidence to make our evidence base list.
But it was insufficient evidence to conclude any specific neuroendocrine abnormality in
this illness differentiated people with the illness than people without.
This is another one of my slides thrown in, the role infections play there Doctor learner
on this committee is very passionate and has spent his career and we all love Dr. LERNER
who is ill right now and all of a sudden his good thoughts and much good care.
Dr. LERNER is passionate about this, he was certainly a strong voice but the committee
a very knowledgeable committee did say as I said that EBV triggers are real, that infectious
illness maybe co-morbid and there was sufficient immune dysfunction to suspect that.
Pediatric pieced ME/CFS here, the problem is there’s a public case definition for pediatrics
from the IACFS that required a three month duration instead of a six month duration but
that has yet to be evidence base, that hasn’t been tested so the evidence look at the literature
is on six month so this pediatric case definition said that the same case definition can apply
with the six months lead and that there is an illness in kids that is significant and
serious. And often follows Epstein barR.
What does this mean to clinic? Really important.
You’re not trying to reach clinicians in this room you don’t need convincing we’re trying
to reach clinics not knowledgeable. This is about a tool to get out to the clinicians
that are missing this diagnosis every time it stairs them in the face.
Saying this is real, not psychosematic, it’s medical has elements that are causing it to
be this serious that has a core set of symptoms, it’s diagnoseable, treatable, and you can
avoid hurting your patients further by misdiagnosing and treating for the wrong thing.
— misdiagnosing. It’s the most important message we have got
here, terribly while there is not a lot of evidence based therapy yet, this is not one
of the charges of this committee to find all therapies.
We did do a fair literature review, there is not evidence for evidence based therapies
in this illness, when the — one desperate area that needs more research.
But you still can’t walk away, there’s co-morbid conditions that are treatable, treat them.
If one person looses a December ability because we as committee created a new case definition
that through out of their financial safety network, that was not our intention, the intention
was to draw the broad, broad net. It was absolutely important that it not be
a narrow subgroup case definition or research case definition that was trying to reduce
the heterogeneity, this was supposed to be Test test
>>By the medical community and by the public, it has already.
You have already seen it, it’s been a very effective set of tools.
Partly because the IOM not only has a process to create this lovely report, but they have
a dissemination process that was part of the charge to disseminate so they have had very
aggressively disseminated this report. It’s still in the top ten dementia ten downloads
and have been whatever eight months since it came out, seven months, it’s top ten downloads,
it has had a tremendous play. And the patients come to me now with saying
I have had my own patients say I go to my primary care doctor now and they say I’m sorry
for not having taken this more seriously, I want to hear that.
That’s exactly what I was hoping to hear. So one of the recommendations then was that
the HHS develop a tool kit appropriate for screening and diagnosing patients and use
broadly across medical specialties. So there was a clinician guide that came out
with this side by side, that was shorter easier to read zip through it kind of guide, the
CDC posted that on their website as has the many other sites.
It’s very helpful guide to get through diagnostic. It obviously needs the next step which is
the therapeutic guide. Which we would have to have another whole
meeting to try to figure out. It may get this to the point of diagnosis
and symptom management and recommendations down that path.
Third recommendation, the whole thing should be reexamined.
Rather important thing. We recognize this field was moving, there
were large studies not published yes, the fact we have the unpublished CFE data and
the CFI papers have come out since and CDC is publishing papers.
There’s more literature that would have come to bear on this discussion.
We strongly recommend it happen certainly within five years, be more appropriate in
two to three years, it would make a difference. Then again, this is your committee to advise
HHS what could be the tasks you will assign to IOM report at that point or some other
mechanism at that point. The fourth reasons is to rename it.
if I up to this point said here is the case definition love it, hate it, here is the case
definition, here is a name, love, hate but here is a name.
Two separate things so don’t throw them together and trash the whole thing.
It’s important that clinical case definition is long an hard and a lot went into it.
When I say a lot went into it we saw those names we saw the different committees.
A lot went into it so we were still at the close to tend of our process and it was no
consensus on the name. None.
What would be better, recommending there be a meeting to create a new name?
With that meeting, you brought the expert in the planet together to a meeting for a
day and said let’s come out of this with a name, is that a more informed group than our
group that spent a whole year living breathing doing this, why don’t we give the best effort?
I said, this is me I will take responsibility but so did other people.
Maybe a chicken way out to say punt it because we thought about it a lot.
So we did what you do consensus billing. We had we voted, we voted more, rearranged
the letter, looked up the acronyms online and made sure they were in use.
There was a lot of names that were great that would have meant something different when
you Google it. So this is what we came up with.
Again, it was — we may recall we asked an evidence based group to come up with name.
So we’re looking for evidence. Is it systemic?
Yes, it is. Is there exertion induced relapse?
That’s part of the case definition now, it’s a really important part that was one of the
into your head when you study for the boards. And is it a disease?
Yeah, it’s a disease. So this is what we came up with.
And you can love it, hate it but we came up with this and I will stand by it because I
think it’s better than the chronic fatigue syndrome.
The patient community put forward loads of names, all published in the report.
You can see there’s a great big list of names. There’s not one that’s saying to your — singing
to your soul. Just like ours.
Honestly, if there have been a better name the last 30 years don’t you think we would
have been all over? It we talked about it over and over an over
and over and over and over again, all sick of saying this is a lousy name let’s have
a new one, give me a new one. This is a name.
I’m happy to strap it if you guys come up with another name, in the process fine, isle
get behind whatever name but let’s not let it be chronic fatigue syndrome.
Please. There you have it that’s my take.
One of the IOM speaking of Nancy again. The pediatric impact of this report is terribly
important, another important to address, it is important with this committee heard excellent
testimony from impacted families, school systems, how awful this illness is to the poor kids
afflicted, to the point where they have been misdiagnosed and removed from their families.
It is a terribly important piece. There’s a strong evidence that was reviewed,
a lengthy chapter, probably the longest chapter in pediatrics and reviews literature very
well. The conclusion was that there is an illness,
it’s serious, it involves dysautonomia and neurocognitive abnormalities, and profound
fatigue and acute mononucleosis. That was a pretty good thing.
Based on all this the criteria revisited for the kids, discuss the six month criteria being
listed but Ellen Clayton, our chair is a pediatrician. She was passionate about this, she said for
heaven sake don’t let kids swim for six months while you’re waiting for them to hit the mark.
You are responsible for caring for these children from the moment they’re ill.
And just because you put a six month time line does not give you a six month punt.
We also discussed comorbidities associated with the illness, here is a shopping lift
of co-morbid conditions, all approachable and treatable.
Definitely need to be addressed. Then they’re very common.
Literature varies. There is another CFI paper came out, it was
in April. That addressed this, there’s other papers,
CDC has papers coming out of their various cohorts studies as well, published many of
this as well so there’s quite a bit of evidence onco morbidity, there’s debate whether or
not there’s sufficient evidence, there’s sufficient evidence and comorbidities are common and
here they are. areas these are further study, these really
important for hearing, this is their slide, not mine.
Remarkably little research funding has been made available.
So as we have these discussions, please address very creatively how to inspire more people
coming into this field that had the honor of chairing the last NIH review panel.
There were four new groups listed in that group, I was excitedded to see people that
weren’t in the field that had applied, that made me happy.
But also remind you histotorcal things when office of — women’s health and NIH put a
set aside pot, one round ever, once, there were 38 applications that round.
So it does help to come up with innovative strategies.
At the NIH level, office of congressionally drifted research is another opportunity, there’s
a lot of opportunities but remarkably little research funding is made available was one
of the key phrases that was said. We wanted more to review, where is the big
punchY literature? Where are the high enstudies?
So these — high end studies so the bias biorepositories in Carol’s group an CFI and CDC is doing,
they’re terribly important. And the — people can do large end studies.
I can’t tell you the number with six, seven, eight
A. We were trying to — subjects we were trying to use as evidence that were poor because
you can’t say much, couldn’t get that published, couldn’t get that funded.
Amaidsing you can — amazing. If I wint in with a proposal that says I’ll
do ten, forget it. Peer review.
That’s important. Dissemination diagnostic criteria. this is
the dissemination plan, that’s well underway, where is it going, where has it been, the
IOM patient is a big deal and the fact that it’s a free download that, helps a lot.
There’s a price attached to that, maybe didn’t get quite so much.
As I said in the JAMA article with 48,000 downloads that’s a lot of downloads for one
JAMA article. Certainly wasn’t the highest impact article
in years. But the IOM report itself is being downloaded
in those numbers and links are there and there are other ways to access this.
So I get rolling out, they engage the press aggressively to get this out and you saw there’s
a med escap that’s another way to get a lot of docs on board or clinicians on board.
And there’s a very good medSCAPE article on there.
And it was in lay press and there’s New York Times articles and Washington post articles
and so forth. So the next step is how do you get — audiences
that influence primary care providers such as school based professionals, the independent
organizations and professional societies and there’s been an effort to roll that out as
well. There’s been a lot of activities dissemination
activities, another shopping list of activities. IOM has a very long reach, one of the reasons
why you chose to use the IOM as the your vehicle, not just do the report but guess it out so
— but get it out so it’s out and continues to be a very active process.
Basically the process, we want to thank everybody, we on the committee thank everyone that influenced
an helped and assisted and shared their data. Reviewers and members of the processful — process.
We thank particularly the IOM staff, CC was the study director, she’s extraordinary professional,
this is her list of people who assisted and Rick ERDman director of the board on health
of selective populations attended many meetings and was very involved in the entire process.
So we thank everyone there at the IOM. That is pretty much what I have to say.
So thank you very much.>>Thank you very much, Nancy.
Terrific presentation. Thank you for your efforts as well.
We have time for a brief break, if members want or do you want to ask questions?
Go ahead, Lisa.>>Thank you very much, that was a great presentation
and I really appreciate all the work that the committee did.
This maybe a very specific question but speaking as primary care doctor who does see patients
with CFS but still wears my primary care hat most of the time the part about getting information
out is important to me and close to home. So this maybe too specific a question but
I’m thinking the push pull strategy so there’s the push the media putting out in front of
us all the time and that’s been successful because I know my colleagues with some to
me saying we heard about it and they want a little conversation hallway is that is telling.
The pull strategy is when a colleague is in the room with a patient, you go I wonder if
this is that newly named chronic fatigue syndrome, where do you go for information and up to
date is the thing people want to run to, I have not looked to see if there are any changes
but is that one of the places the IOM recommended or the strategy has been changed to get information
on up to date, for example.>>Interesting.
So the focus of this committee is on diagnostics not therapeutics.
I wish we had a therapeutics run just like this.
That would help a lot if we have the next step of this out there for clinicians.
From the diagnostics perspective, this is listed — you can easily fine it in medSCAPE,
I haven’t looked up to date to see if it’s there.
But one of the plans to go through those types of things.
Anyone looked? I didn’t look to see.>>Donna PEARSO NCI.
That is in the list of IOM recommendations. It has changed but it’s — we think it can
be improved.>>The biggest improvement is the doctor like
you people come to all thesyme thyme and say, other — all the time and say what do I do.
You want to send them to a place, so the places I send them to, I send to the IOM report,
it’s good and I send them to CDC website that has parts of it some could be upgraded but
because we haven’t given direction how to do it I don’t want the trash the CDC when
we haven’t given a therapeutics document that’s to update that would be useful.
Then — but the IACFS website is great. The IECFS website has the conferences and
lots of discussions. Our — I mean, there are individual web sites
and mine has every conference given with all the speakers and that.
So I will send them there because we have a lot of 101, 201 lectures on our site.
So people like quick carts, they don’t want to sit through a two hour lecture.>>I want to add one thing, Donna PEARson,
there’s guideline.gov has the IECFS primer on there at this point pretty much still applies
in terms of treatment.>>The primer is the best thing you can hand
them, it’s free downloads of that though they prefer a little donation. But the —
>>Before I recognize Carol, I want to see a general show of hands to see how many of
you will have questions for Dr. KLYMAS. I have a few myself.
Go ahead Carol.>>Thank you, Nancy, that was great.
As we continue to build and grow our biobank and patient registry, it is the base which
many researchers use to gather patients for their studies, in fact we are providing a
foundational level for lots of research, I understand the difference between the clinical
criteria an regional diagnostic criteria. I have not seen a research criteria so maybe
you can help. As we bring patients into this registry, we
tend to look for Canadian as baseline defining who is included, who is not.
So there’s complexities about a research, I welcome comments you have on appropriate
way to define the research criteria for database like ours that is used for many research studies.>>That’s the crux, research studies so the
CFI we debated this long, hard and we have a portion of the biorepository that meets
this — the Canadian as well as FAKUDA. One thing you want to know if you develop
a biomarker for the illness, and you’re trying to discern if it’s capturing the type group
or broader group, you need the broader group in the biorepository.
So biorepository questions are different. A third of study by study thing.>>We do gulf war illness research, if you
want a great debate about case definitions jury into gulf war, there are 12 case definitions.
12 case definitions, which about five are broadly used.
And you have to define your population an justify the definition you selected as you
go forward for funding or project underway so messier.
Yet we’re making tremendous progress down that line so what I will say is, I have sat
in these rooms listening to everyone say if we don’t have a case definition, we’ll make
no progress. Wrong.
You need to have co-use and you don’t go beyond it when you publish a patient.
If you want CCC for research case definition fine do it for your repository, people publish
that, they will say within the confines of this case definition we found this.
Moving the field. Don’t get hung up that you stop.
That’s what I’m saying. We have done that as a community.
And we need to stop doing that. We need to just okay.
We got what we got, let’s move. If we can improve, improve on it but keep
the ball rolling. Too important to let it slow down.
If I were designing a big biorepository I use a broad one but capture all the elements
of that — and let me define anyone in it under any case definition.>>Thank you.
That’s what we have been doing, generally broad but we have enough data that we can
specify the needs for researchers.>>And have a big enough subgrouping portion
that you can say something, I have enough men here, enough long duration, enough short
duration, so on. That’s what you do with a biorepository, enhance,
the need to enhance on these elements because they really do matter.>>Go ahead.>>I’m sorry.
Want me to wait?>>Donna PEARson.
The concern of Fukuda is you do not have to have IOM.
IOM is saying that’s a requirement of the disease so when you suggest Fukuda, are you
suggesting patients that don’t have PEM? Or are you saying they should have that?>>In a biorepository.>>That depends because in Fukuda, you have
to be careful, chronic depression with Fukuda. So you have to at least know that.
And measure to know if you did that. So one of the issues in the biorepository
shouldn’t be limited to disease you study, you need to grab rheumatoid arthritis and
MS and depression and this and that and the other thing and say does this biomarker discriminate
between these different types of illnesses? Biorepository, don’t misunderstand what I’m
saying. Research purposes, you need the case definition
for research you have in minds. That’s whey I’m saying.
Our group is very immunologic group, doing — so we use a titer, we use Canadian and
if need be we’ll have elements of biomarker requirements and the case — in our entry
criteria depending on the study we’re doing and don’t publish —
>>What I would like is draw discussion back towards — to IOM.
Clinical case definition. Because as you stated so well, your goal is
to develop the document useful for clinicians. Obviously you have done a fantastic overreaching
job reviewing the literature. Working with Donna’s group, though the algorithm
is neat and easy to memorize, et cetera, I would say playing devil’s advocate, there’s
— you brought out Lenny’s paper some concerns about the net cast too widely with this short
case definition. Want to hear some of the arguments your group
discussed suggesting that maybe we shouldn’t limit to four criteria.
Secondly, argument for keeping exclusions in, if there were any.
People would argue –>>Separate that out.
And if I could just take the case definition question.
Biomarker talk about clinical symptoms. The literature review, defined only those
elements in the final case definition is evidence based.
That is the most important part. While there is a shopping list, take CCC a
moment and neurology thing. Please recall I was in that room.
There was part of that process. Clinicians were drawing symptoms that we thought
would be reasonably considered neurologic or reasonably considered neuroendocrine or
immune in the CCC. They were reasonably considered that.
Have anyone since this taken that ten neurologic symptoms and actually put them into a platform
where they can be tested? Even the depaul symptom survey which is extensive,
doesn’t have all ten. Other symptoms if you would, if you narrow
CTC to what’s in the depaul instrument, you’re going to see more evidence in the literature
because the instrument is used broadly to test large populations for various and sundry
symptoms an severity. It’s a great instrument but it doesn’t capture
everything in the CCC, it doesn’t capture everything, it was designed before the ICC.
So it’s not every element of CCC is not evidence based, not the literature, not there to support
it. That literature that is there across the huge
symptoms, and space, during duration an severity, these elements were the ones that have the
strongest evidence. In terms of the discerning from other populations,
post exertional malaise was felt strongly to be the core, the Lynch pen, if you would,
to discriminate this population of profoundly fatigued people from other profoundly fatigued
people. Clinics which was nice because we had so many
chronic fatigue contempt experts in the room, — content experts in the room was well enterhe
want accepted by the clinicians the piece was critical and it became the focus of everything
and and everything else had to fall under that PEM, all the other cases, other symptoms
in their evidence base. So if you read the IOM report you see comprehensive
evaluations of the literature on cognition. Comprehensive on sleep and other elements
that made the list. The other list, other things commonly seen,
those folks all had significant evidence will the literature that they existed, didn’t discern
well from inflammatory or fatiguing illnesses or the literature wasn’t quite as robust.
So I’m comfortable saying that that case definition wasn’t making it short, that wasn’t the point
though glad it came out short because easier to remember, it is what is evidence based.
That’s what’s in that case definition. Okay?
Your other question was –>>I know you mention argument, do away with
exclusionary criteria. what are arguments to keep it in, the fact — to have exclusionary
criteria?>>I think —
>>Everybody is in agreement?>>Pretty close to it.
Not that we skipped over it or anything, there was a lot of discussion but it wasn’t very
— my recommendation, I’m not supposed to go through all the discussions but my recollection
is that it was a quick to embrace this. The real reason why, from the non-content
expert as well as context experts is where else do you do that
Q. What other illness do you put exclusion crew tieria that lists that shopping list
of other illnesses? There’s really no good example.>>If you were to disseminate this document,
devil’s advocate here, I understand the amount of work and analysis you put in.
But let’s say with a new newly minted resident primary care doctor, despite what you say
they’re all good doctors should go through their list and other diseases may not have
this, it seems to me that you might want to explicitly state what other disorders should
be considered and really go one by one excluding them to make sure you’re not also capturing
people with a malignancy or TB.>>You and I talked about this a long time
so again personal rather than committee discussion. Part has to do the changing way we do medicine
in the last 30 years. In my early career people came with extensive
evaluations sometimes 18 doctors three MRIs CAT scans, whatever but the huge work ups
and there was a period of time they came with nothing.
Absolutely nothing. I was shocked, picking up anemia and hypothyroidism
and specialty clinic freaking me out someone show up in my place and I pick up iron deficiency
anemia. That seems silly.
And that’s when I thought whole of medicine moving to triage doctor and there was no such
thing as primary care, just triage people. I think partly thank you for the new Medicare
guidelines being able to be paid better for complex illnesses is going to make a difference.
And people spending more time per patient when complex is going to make difference but
the pressure to get someone out of your office was that you only had seven minutes and they
had to get out of your office before the next patient walked in.
So back in the day, when I was on these other committees discussing case definitions it
was that. And that — it was about that.
You had to make people do a CBC. How stupid.
But I had to make people do a CBC or thyroid test or chem 23.
That minimal panel, super minimal if you might recall it was a CBC chem 23, thyroid test,
ANA rheumatoid factor, fed rate, they found people only doing that so that was crazy.
We were missing all kinds of easy to diagnose things by making them stop thinking but what
would you recommend? I throw it back at you, I want people to think.
When they see it. I don’t want them themselve to pigeon hole
them and move them to another task. So —
>>I guess as you say this is a work in progress, substantial baseline place you got us to,
that the IOM committee put out something as you say do we have anything better to offer?
Not yet but definitely a work in progress. One other point, if any of you committee people
want to chime in, I’m going to spend my two cents part of Donna’s working group later.
How did you deliberate how the clinician measures PM in clinical set something there’s some
things in the appendix.>>Supporting slides on that.
>>you don’t want a two day cardiopulmonary, we don’t have any New York City but what are
some of the questions that a primary care person or someone else may ask to elicit a
response because it’s not having to do a marathon, we get post exertional malaise,ing up, doing
the dishes or putting your underwear on, all these things lead to PEM in MECFS patients
how do we ask the right questions?>>In the physician guide there’s a nice section
on this. This is in part from this first what is post
exertional malaise, then specific questions to ask.
This I think is there’s a very nice section, what happens when you do this.
Or how much activity does it take before you experience a crash?>>Keeping the diary part is an important
thing.>>Diary is nice.
And we have that for various symptoms but I think that other thing about the process.
I will show you this quick because I thought it was cool.
This is what we did. This is voting.
If you had a symptom, or something you thought was important to address in this case definition,
we had a grid. We each of us would go through these votings
an votings and votings and votings trying to come up with consensus across any contentious
issue. If we were all — just raise our hand together
if we all agree but lots of things we didn’t agree on but we went through this iterative
process over and over and over again until we came up with consensus.
So there was — it was a — IOM is good at this.
They do this all the time. And I say Alan Clayton in particular is good
at herding cats and sometimes we were a whole room full of cats.
But the — but I thought overall the process was a good one.
I digress from your question but what we did is try to give language, there are tools like
ortho static intolerance we had a suggestion, a straight up suggestion take the blood pressure
flat and stand them up ten minute and then do it again blood pressure and pulse.
I want sounds like you’re teach — it sounds like you’re teaching something they should
have learned in medical school. You learned three minutes in medical school,
not ten and in this feel it takes ten minutes to start seeing the ortho static changes so
we gave practical tips how to do physical exam, how to do history.
I think then you would be surprised I think, go through that physicians guide.
Describe the patient that comes in historical descriptions to you, what are the phrases
they use to make you think this. ?
And questions you might do to try to quantify and to better get hand on that.>>Dr. Lee.>>This is Nancy.
Quick question. Do you know for example for this post exertional
malaise, is this validated or –>>Very evidence based.
Validated.>>This questionnaire.>>This questionnaire.>>Yeah.>>There are elements of — (overlapping speakers)
>>One of the recommendations was to develop more tools, et cetera.>>These are questions polled from evidence
basted questionnaires. Most coming from the depaul instrument but
not all.>>Is it validated against the two day test?>>Oh gosh no.
The two day test only has a couple of papers. The two day test I can talk about as a person
but not the IOM committee but the IOM committee didn’t think there was sufficient evidence
in the literature validating the two day common tool.>>Mary Ann did you have a question?
Go ahead.>>As a laboratory person I’m a little bit
disappointed that the committee saw fit to include no biomarkers at all.
In making — what it leads I believe what it leads to is that the probability most of
the people who come in and get diagnosed will be no way for them to go for treatment.
Because the — institute of medicine trashed all the biomarkers except for one.
And I have had really puzzling and unfortunate. I will say more this afternoon.>>Okay.>>My action is that NK cells almost made
it to the top. NK cells are very close.
And the issue was not they weren’t good-bye markers, it fits strongly in the report NK
cells are best biomarkers in the literature now and the issue was —
>>Access right?>>The feeling with a clinicians that the
common laboratories that we have access to, in private practice don’t do it well.
Fit has to be done within 24 hours, you send a patient to go to, we won’t mention names
but a common laboratory, that blood will be drawn and sent to regional dispersing site
as an overnight and the next day be sent again overnight to the specialty labs so the blood
is 48 hours ole before it arrives to be tested. And as you
have published, Mary Ann, as you have published,
it’s no good after 24. So the issue wasn’t it shouldn’t be there,
the issue was the method commonly accessible to your primary care doc not a specialty clinic
like mine where I happily have your laboratory to back me up in a assay or certainly 24 hour
assay, not everyone has overnight access to that laboratory or at least not aware of it.
Nonetheless the laboratories most people’s insurance covers offer the bad test the 48
hour test an charge for it but give you back a result you can’t interpret.
So that was state-of-the-art. That’s my problem in terms of final recommendation.
I’m thrilled NK cell function in particular made the list.
I would have personally been even more thrilled if some of the other biomarkers got to the
top. But I can see the point of meeting large end
studies to validate your very good work and the field is already large in studies but
needs validation but other large end studies.>>I agree about natural killer cell function
as we currently do, looking at the CDC right now to maybe find other way that are not so
dependent on time from draw. We have probably been remiss going for many
years using this assay, this only really good for the first eight hours.
Soon after that begins to fall off precipitously. I think there are ways to look at it but other
things just completely trashed by the institute of medicine report, particularly plasma cytokines
and other biomarkers. And that –ly talk about that this afternoon.>>I look forward to that discussion.
>>Okay.>>Any other questions for Dr. KLYMAS?
Go ahead, Steve.>>I want to commend the IOM.
I know when it started, I was skeptical as a member of the community but having had the
benefit of hearing other member on the IACFS and looking at the report, it’s a wonderful
job. And I made sure I want to make sure I said
that today.>>Thank you, Steve.
I appreciate that. It was a lot of work and amazing process.>>I thought the pediatric chapter was well
done, nice to see information from about school because that
is very important to our parents who have
sick kids.>>Two questions, in the massive literature
review, did
you — long face question, interest, were there study following pediatric MECFS patients
to adulthood that you came across?>>I was on the pediatric — I wasn’t on the
subcommittee but we have heard Cathy ROWE at this meeting present that.
It was probably the only person I know that has that quality of
data. So back when to Cathy spoke here about three,
four years ago, maybe five years ago, getting old.
She did — I don’t remember exact numbers but she had very reassuring data that as a
children get older through college and beyond the recovery rate was good.
On the other hand what the kids considered recovered was lower function than what you
or I consider normal function. But they were happy.
I can no longer consider themselves ill. So I don’t remember the exact percent so don’t
quote me but Cathy presented that also at the IACFS and has paper on that.>>Thank you.
Now will you be here the rest of the day? Most of the rest of the day.
I’m here for the one o’clock adventures of the review of
the IOM report.>>So if
we
have further questions for Nancy she will
be here. Why don’t we take an 8 or 10 minute break and
be back here at 11:15 sharp for public comment.>>I had to make people do a CBC. How stupid! But I had to make people do a CBC, or a thyroid test or a chem 23. I mean, at the minimum that panel was very minimal, as you’ll recall. It was a CBC, a chem 23, a thyroid test, an ANA, a rheumatoid factor, a sed rate, that was it. Well then we found people only doing that. Well that was crazy. We were missing all kinds of easy-to-diagnose things by making them stop thinking. So what would you recommend, you know, I would throw it right back at you because I want people to think when they see a sick patient. I don’t want them to just pigeon-hole them and move them on out to another path, so…>>Well, you know. I guess as you say, this is a work in progress. This is, I think, a very substantial baseline place that you got us to, that the IOM committee put out, as you say. Do we have anything better to offer? No, not yet. But I think it’s definitely a work in progress, and I think one of the other points and if any of you other committee people wanna chime in, and I’m gonna present my two cents as part of Donna’s working group thing later. How did you guys deliberate about how a clinician might measure PEM in the clinical setting? And I know there’s some things in the back, in the appendix about the questions.>>Yea, and I have some supporting slides on that.>>You know, aside from, we don’t wanna do a two-day coronary pulmonary because it’s bad on the patient, etc. and it’s too expensive and we can’t – we don’t have any in New York City – but what are some of the questions that a primary care person or someone else may ask to elicit a response because it’s not having to do a marathon that we get post-exertia malaise. It’s sitting up and doing the dishes or putting your underwear on, you know all these things may lead to PEM in a CFS patient. How do we ask the right questions to assess the symptom?>>Right, so actually in the patient guide In the physician guide there’s a nice section on this. This is in part from this first what is post exertional malaise, then specific questions to ask. This I think is there’s a very nice section, what happens when you do this?
Or how much activity does it take before you experience a crash?>>Keeping the diary part is an important thing. Diary is nice. And we have that for various symptoms but I think that other thing about the process. I will show you this quick because I thought it was cool.
This is what we did. This is voting. If you had a symptom, or something you thought was important to address in this case definition, we had a grid. We each of us would go through these votings an votings and votings and votings trying to come up with consensus across any contentious issue. If we were all — just raise our hand together if we all agree but lots of things we didn’t agree on but we went through this iterative process over and over and over again until we came up with consensus. So there was — it was a — IOM is good at this.They do this all the time. And I say Alan Clayton in particular is good at herding cats and sometimes we were a whole room full of cats. But the — but I thought overall the process was a good one. I digress from your question but what we did is try to give language, there are tools like ortho static intolerance we had a suggestion, a straight up suggestion take the blood pressure flat and stand them up ten minute and then do it again blood pressure and pulse. I want sounds like you’re teach — it sounds like you’re teaching something they should have learned in medical school. You learned three minutes in medical school, not ten and in this feel it takes ten minutes to start seeing the ortho static changes so we gave practical tips how to do physical exam, how to do history. I think then you would be surprised I think, go through that physicians guide. Describe the patient that comes in historical descriptions to you, what are the phrases they use to make you think this? And questions you might do to try to quantify and to better get hand on that.>>Dr. Lee, go ahead.>>This is Nancy. Quick question. Do you know for example for this post-exertional malaise, is this validated?
>>That was validated. That was very evidence based.>>What I mean is, this questionnaire.
>>Oh, this questionnaire.
>>Yeah. One of the recommendations was to develop more tools, etc.>>These are questions polled from evidence-based questionnaires, most coming from the depaul instrument but not all.
>>Is it validated against the two day test?>>Oh gosh no.The two day test only has a couple of papers.The two day test I can talk about as a person but not the IOM committee but the IOM committee didn’t think there was sufficient evidence in the literature validating the two day common tool.>>Mary Ann did you have a question?
Go ahead.>>As a laboratory person I’m a little bit disappointed that the committee saw fit to include no biomarkers at all in making — what it leads I believe what it leads to is that the probability most of the people who come in and get diagnosed will be no way for them to go for treatment. Because the — institute of medicine trashed all the biomarkers except for one. And I have had really puzzling and unfortunate. I will say more this afternoon.>>Ok. My reaction is that NK cells almost made it to the top. NK cells are very close. And the issue was not they weren’t good-bye markers, it fits strongly in the report NK cells are best biomarkers in the literature now and the issue was –>>Laboratory access, right?>>The feeling with a clinicians that the common laboratories that we have access to, in private practice don’t do it well. So if it has to be done within 24 hours, you send a patient to go to, we won’t mention names but a common laboratory, that blood will be drawn and sent to regional dispersing site as an overnight and the next day be sent again overnight to the specialty labs so the blood is 48 hours old before it arrives to be tested. And as you have published, Mary Ann, as you have published, it’s no good after 24. So the issue wasn’t it shouldn’t be there… the issue was the method commonly accessible to your primary care doc not a specialty clinic like mine where I happily have your laboratory to back me up in a assay or certainly 24 hour assay, not everyone has overnight access to that laboratory or at least not aware of it. Nonetheless the laboratories most people’s insurance covers offer the bad test the 48 hour test an charge for it but give you back a result you can’t interpret. So that was state-of-the-art. And that’s my problem in terms of final recommendation. I’m thrilled NK cell function in particular made the list. I would have personally been even more thrilled if some of the other biomarkers got to the top. But I can see the point of meeting large end studies to validate your very good work and the field is already large in studies but needs validation but other large end studies.>>I agree about natural killer cell function as we currently do, looking at the CDC right now to maybe find other way that are not so dependent on time from draw. We have probably been remiss going for many years using this assay, this only really good for the first eight hours. Soon after that begins to fall off precipitously. I think there are ways to look at it but other things just completely trashed by the institute of medicine report, particularly plasma cytokines and other biomarkers. And that –ly talk about that this afternoon.>>I look forward to that discussion.
>>Okay.
>>Any other questions for Dr. KLYMAS?
Go ahead, Steve.>>I want to commend the IOM. I know when it started, I was skeptical as a member of the committee, but having had the benefit of hearing other member on the IACFS and looking at the report, it’s a wonderful job. And I made sure I want to make sure I said that today.>>Thank you, Steve. I appreciate that.
It was a lot of work and amazing process.>>I thought the pediatric chapter was well done, nice to see information from about school because that is very important to our parents who have sick kids.>>Two questions, in the massive literature review, did you — long face question, interest, were there study following pediatric MECFS patients to adulthood that you came across?>>I was on the pediatric — I wasn’t on the subcommittee but we have heard Cathy ROWE at this meeting present that. It was probably the only person I know that has that quality of data. So back when to Cathy spoke here about three, four years ago, maybe five years ago, getting old. She did — I don’t remember exact numbers but she had very reassuring data that as a children get older through college and beyond the recovery rate was good. On the other hand what the kids considered recovered was lower function than what you or I consider normal function. But they were happy. I can no longer consider themselves ill.
So I don’t remember the exact percent so don’t quote me but Cathy presented that also at the IACFS and has paper on that.>>Thank you. Now will you be here the rest of the day? Most of the rest of the day. I’m here for the one o’clock adventures of the review of the IOM report.>>So if we have further questions for Nancy she will be here. Why don’t we take an 8 or 10 minute break and be back here at 11:15 sharp for public comment.
>>Thank you very much.

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