Stroke, with the team from NIH, and we're
excited to once again let folks know
about what's been going on on our end
in ME/CFS research and this is our third
telebriefing of 2019. In today's
teleconference, which we're going to do
on WebEx, so folks should be able to see
the slides, Dr. Andrew Breeden will
briefly introduce the council working
group that presented their findings to
the NINDS Council just a month or so
ago on ME/CFS research. And in that vein
we're delighted to be joined by Steve
Roberds. Dr. Steve Roberds is the chief
scientific officer at the Tuberous
Sclerosis Alliance. He's a member of our
Council and he worked very hard with a
great team of folks to chair the council
working group on ME/CFS research.
We've invited Dr. Roberds to give us an
overview of the working group and
discuss the working group's report which
is really the focus of today's
teleconference. Afterwards we'll hear
from Dr. Vicky Whittemore who works very
closely with Dr. Joe Breen from the
NIAID Institute here at NIH and they'll
discuss how Trans-NIH ME/CFS Working
Group will work to implement the report.
As always we're very eager to hear from
folks and take questions, so we'll keep
our remarks as brief as possible before
opening the phone lines for your
questions. With that I'd like to turn the
call over to Dr. Breeden. Thank you Dr.
Koroshetz. So as Dr. Koroshetz mentioned
today we'll hear from two speakers about
the recent efforts of a working group of
the NINDS Advisory Council that was
formed to identify gaps and
opportunities in ME/CFS research, as well
as strategies to move the field forward.
First Dr. Steve Roberds who chaired the
Working Group will describe how the
Working Group produced its final report
and summarize the report's findings.
Next Dr. Vicky Whittemore will describe
plans for implementing the strategies
outlined in the report. Before we hear
from Drs. Roberds and Whittemore with more
details, I first want to briefly
give some background about the Working
Group. Each NIH Institute or Center has a
National Advisory Council that's made up
of scientific and medical experts who
can advise the Institute director, in
this case Dr. Koroshetz, on important
policies and procedures. In the summer of
2018 NINDS formed the Working Group
that we've been discussing of our
Advisory Council that was focused on how
to best advance ME/CFS research. The
Working Group was composed of scientists,
clinicians,
representatives from advocacy
organizations and individuals with ME/CFS.
The working group was charged with three
main things. The first was to identify
gaps in current knowledge, opportunities
for future action, and a series of
potential strategies to move forward in
each gap and opportunity. The second was
to examine how to attract and train a
pipeline of new and early career ME/CFS
investigators. And finally moving forward
to examine how to enhance ongoing
research collaboration and communication.
Dr. Roberds will soon describe the
many productive meetings held by the
working group that culminated in a
report that was presented to the NINDS
Advisory Council in September. The report
is publicly available online and we will
soon include a link on the slides that
you'll be able to see where to access
the report. And the report was approved,
was accepted, by the NINDS Council and
so the 23 NIH institutes offices and
centers that compose the Trans-NIH ME/CFS
Working group have been holding
discussions on how to prioritize and
implement the strategies outlined in the
report. Dr. Whittemore will describe
these efforts. With that I will turn it
over to Dr. Steve Roberds who chaired
the working group. Dr. Roberds is the
chief scientific officer of the Tuberous
Sclerosis Alliance and has played a key
role in leading the development and
execution of research strategies in a
variety of contexts. We are very grateful
to Dr. Roberds for leading that
ME/CFS Working Group. Dr. Roberds. Thanks
Dr. Breeden, I really appreciate the kind
introduction and setting the stage and
thanks to Dr. Koroshetz for asking me to take
on this responsibility. I was really
truly honored to be a part of this. It
was a great opportunity to come from
outside the ME/CFS field, to learn a lot about it
and what's going on, but you know and
really really bring perspectives
together with you know what I think was
an open mind right unbiased view because
I wasn't in the field. So you know I
really appreciate the trust that was
placed in me and the other members of
the working group. So if you could go to
the next slide please,
I wanted to just start by stating what
might be obvious, that the burden of
the illness is not only substantial but
severe and high and because the burden
of the illness is so impactful and we
don't know anything about the etiology
and pathogenesis of the disease there's
no diagnostic tests there are no
approved therapies all of this as all of
you on this on the call know really set
the stage for an urgent need to expand
research in ME/CFS and, next slide please. So as Dr.
Breeden outlined the working group of
Council had three charges and I
reiterate those because I'm going to
address each of those as in the next few
minutes. So the first was to identify
gaps and opportunities in ME/CFS
research and then the second was to
consider strategies for NIH to support
ME/CFS research to attract and train a
pipeline of new and young investigators
and then the third was to identify
potential ways to really
enhance the ongoing collaboration and
communication and research in ME/CFS
as I'm sure you're all aware we can
do a lot more together than we can give
you separately and individually. And
speaking of working together, on the next
slide, is the working group. So I'd like
to acknowledge all of these individuals
for their time and effort. I like to
think of the way this slide is organized
that the people on the lower right are
actually the ones who put in huge
amounts of time and kind of as you work
backwards to the upper left you know we
were privileged to be a part of it
and to provide that you know that
insight and guidance with the NIH
staff. Really I want to express my
appreciation for all the work that they
did in the background to you know get
data together and help answer questions
that members of the working group had
over the last year, year and a half, so
next slide. Just a brief overview of the
process.
So as Dr. Breeden said we started over a
year ago and we started having monthly
calls in September of 2018. We organized
a time in December when all of us could
get together face to face to you know
really hash through some of the key
questions that we needed to address over the
next several months before making the
presentation to council and so with
these weekly calls and laid the
groundwork and we divided into
subcommittees so that we could divide
and conquer right all the different that
needed to be done and so some of
the folks work just how do we gather
stakeholder input and some worked on
thinking about what might this structure
for ongoing collaboration look like
and then others dug into what are our
real gaps in knowledge both around
pathobiology of ME/CFS and what we know
about it clinically and we had a group
that thought about, you know, what's going
on in research elsewhere and how do we
loop
them in to this research going forward. So I hope you
can see from this that the working group
was trying to tackle this from a lot of
different perspectives with the goal of
bringing together lots of ideas but also
lots of people who could be committed to
this in the long term, so next slide. I'll
start addressing each of the
charges of the working group and I start
with this one first because I think it's
it's really critical for the long-term
success of increasing the focus on and
the productivity of ME/CFS research and
so that's how do we get enhanced
cooperation and collaboration among
federal agencies and of course other
stakeholders in ME/CFS research and we
talked about some various models and
there's one actually that is very active
and very successful in the epilepsy
field that we really ended up using as
kind of a model of how this could work.
That involves representatives from
across NIH, involves representatives from
other federal agencies like CDC, the
Department of Defense, et cetera who are doing
research, and then it also involves
national organizations and patient
advocacy organizations. So this, it was
really a way to bring all the folks
together at the table and so we started
with that as a concept, developed
this concept of an ME/CFS
collaborative group that includes the
types of organizations that I just
mentioned really having the goals of
sharing information but not for the
purpose of just sharing it but for
highlighting what's actually advancing
and for discussing and digging into the
gaps that still exist and the
opportunities to fill the fill those
gaps. The idea is and we've seen it work
in the epilepsy space, is that it really
drives collaboration among
both the government and the
non-governmental organizations that are
a part of this and it allows, because
everybody's at this table, it allows them
to monitor the progress of the research
field as a whole one. So we think this
can serve as a good model for ME/CFS as
well and the working group emphasized
that the patient advocacy involvement is
really critical for at least a few areas,
and probably many more, but one is
identifying the priorities of research
because the patients who are living with
this are the ones who need and know the
priorities best and keep an eye on the
progress and make sure it's it's moving
in the right direction. And then the
other, another, way that they can be involved
is to address those barriers to
participation in clinical research and
clinical trials so you know the last
thing that we want is for you know for
researchers to undertake a  large and
expensive and long term clinical trial
and you have it fail because it didn't
meet the needs of the patients that they
needed to be enrolled in this to have it be
successful. So there are a number of reasons the
patient advocates should be at that
table. On the next slide,
another of the charges to the working
group was to develop some possibilities
of ways that NIH can help attract and
train a pipeline of new and young
investigators and I wanted to make sure
we understood why so I haven't put the
data here again NIH staff helped us by
by pulling out some data and that's in
the report and the presentation that
was made to Council but it turns out
that there are a really a low number of
ME/CFS related applications funded
because there are a low number submitted
and it turns out that the grants that
have been funded over the last few years
are primarily going to the same subset
of investigators. So this really speaks
to a need to increase the number of
people who
are aware of and interested in research
related to priorities for ME/CFS and so
that that increases the number of
applications so NIH can increase the
amount of funding and really broaden
that you know broaden the experts that
are being groomed for the next
generation. So next slide please. So the
approaches that the working group
suggested for this is first of all the
the low-hanging fruit if you will is to
increase the awareness of what already
exists, increasing the awareness of the
disease. Setting up folks with, so new or
or young investigators setting them
up with mentors who know the
ME/CFS field and then promoting the
importance and the value of research on
ME/CFS and the willingness of NIH to
fund research proposals that that
come to them also promoting a more
collaborative or a multidisciplinary
approach and encouraging the sharing of
resources. Sometimes barriers to getting
new investigators in a field as it can
be that they don't have access to the
same samples or they don't have access
to the patients because those are with
the people who have always been in the
field, so we felt that it was really
important to emphasize that NIH take a
you know take actions to ensure that
there are wide access to biosamples
collected from people with ME/CFS so that
researchers across the country
and across the world can do novel and
innovative research, that data are
collected in consistent ways so that you
can compare data from one study to another and
really even on the you know the fourth
bullet here helping to define
certain case, you know cases, of ME/CFS
and I don't mean individuals, but I mean
you know, phenotypes. And again as you know
ME/CFS is very different from person to
person and so there are these different
sorts of cases for lack of a better word
that studies might might use or
definitions of ME/CFS different studies
may use and so really having these more
standardized and very well defined, it
could help standardize research and
therefore learn from you know for more
studies learn more from more
studies around the world. And then of
course strategic planning which comes up
next is probably best informed how do
you get new investigators involved. Well
one way is to bring them into the
strategic planning process, bring some
investigators who maybe haven't worked
on ME/CFS directly but are perhaps in
related fields, and bring them into the
strategic planning process of the a they
bring their sort of outside viewpoint
into ME/CFS but they also might then get
hooked into the challenges and the
importance and the need in ME/CFS
research. And so finally on on the next
slide and i want to stop talking so
we can move on and hear about you
know what next, but the third charge of
the working group was to devise an
overarching research strategy and of
course we don't the working group was
relatively small you saw the the names
on the slide so really qualified to
develop a detailed strategic plan for
ME/CFS but we know that one is needed and
that and so we recommended to NIH that
that be an undertaking because there are
such large gaps in our understanding of
ME/CFS. What are the underlying mechanisms,
what are the triggers, how do you define
the different stages, how do you
distinguish ME/CFS from other syndromes
that may
look and how do we you know with that
knowledge how do we come up with markers
and medical models, whether cellular
models and/or animal models and really
stimulate the development of new
treatments, particularly drugs that
might be effective so I hope this
overview has been somewhat helpful and
just summarizing in five or ten
minutes what are the highlights that were
presented through the council on behalf
of the ME/CFS Working Group. And so next up
on our agenda is Dr. Vicky Whittemore
who will tell us some about how the
implementation of working group's
recommendations is expected to
proceed and in some ways is already
beginning. Thank you very much Steve that
was an excellent overview of the work of
the Working Group and so we really
appreciate you being on and thank you
once again for your chairing of the
Working Group. It was really a fantastic
experience I think for everyone who was
involved. What I want to do today is to
tell you all about our initial
discussions and how we're thinking about
implementation of the report from the
Working Group of council and just by
way of explaining how and who will be
working on this. So the implementation of
the strategies and recommendations in
the report will be coordinated by the
Trans-NIH ME/CFS Working Group and we are
working with our NINDS Office of
Science Policy and Planning as well as
the Office of Communications to really
help us with this effort going forward.
So we had the initial meeting of the
Working Group to discuss the
implementation of the report in
September and we really took a careful look at what was in the
report and if you've looked at the
report you know that there are many
different strategies that were outlined
in the report itself and so taking a
look at those strategic research
objectives we identified that really a
lot of them are for a strategic planning
process are already outlined
in the report and what we need to do is
identify areas that will need additional
research and discussion so just to go
back to the report for a minute these
are all of the strategic areas that were
outlined in the report and the way we've
grouped the strategies that were
detailed. And first encouragement of
research topics, and approaches,
instruments and Common Data Elements,
data sharing and biobanking, increasing
collaboration and cooperation, outreach
to scientific investigators, general
outreach, conferences and workshops,
research training, scientific review and
then strategic planning. So the way we've
begun to look at all of the strategies
in the report is that is to put them
into three different buckets. And the
first bucket is are those strategies
that we actually are already
implementing things that we're already
doing and taking a look at, are we doing
as much as we can for each of those
strategies and/or are there additional
things that we should be doing. The
second is short term strategy, so
low-hanging fruit, things that we think
are easy or easier to implement will are
things that we can implement in a fairly
short period of time and then the
longer-term strategies that are a little more
difficult or will require a lot more
time to implement across the board. So
what I'm going to do today is
just to tell you about some of the
things that are already in progress, some
of our short-term objectives, and then
the longer term which is clearly the
strategic research planning process
and I'll come to that last. So first of
all under encouragement of research
topics and approaches, there were many
strategies outlined in the report and
all of those are going to be included in
the funding opportunity announcements or
FOAs for abbreviation that will be
be released as PARs, or program
announcements with special review. So
we've incorporated all of those
strategies into those funding
announcements and we'll do that for any
additional funding announcements
down the road. Under instruments and
Common Data Elements as many of you know
we have Common Data Elements that were
developed for ME/CFS and so we're going
to certainly encourage their use and
include that language in the funding
announcements as they're released. We
also have just formed an ME/CFS Common
Data Element Oversight Committee that
will be looking at any new additions, any
revisions that need to be made to the
Common Data Elements going forward and
we're working with all of the
individuals that were part of the Common
Data Elements group that helped to put
those Common Data Elements in place to
submit a publication it's currently
under review at the CDC and here at NIH
and will be submitted for publication
very soon. In terms of outreach to
scientific investigators, we are going to
provide information on ME/CFS to the
NINDS exhibit materials at professional
conferences. This is something that we've
not done in the past but will be added
to our exhibit materials and will
encourage discussion with investigators
about research and research
opportunities within ME/CFS. And then
general outreach. We are continuing to
respond to requests for information and
interviews from the media, from other
nonprofit organizations, and this is
something that Joe Breen and I and
Barbara McMakin from our Office of
Communications do on
ongoing basis as those requests come in.
So under data sharing and biobanking we
have an ME/CFS biorepository in place at
our contract site which we call BioSEND.
It's a biorepository that is located at
Indiana University and we have specimens
there from the CFI funded study and
we're just in the process of adding the
clinical data and will very soon make
those biospecimens available to the
research community and we also have a
proposed pilot to add additional
biospecimens that we're working on right
now that will greatly expand the number
of biospecimens that are in BioSEND and
will be available to investigators. The
neuro-related Institutes at NIH came
together and have what they call
NeuroBioBank, which is actually several
different brain
banks and banking facilities that are
funded through contracts where
individuals can donate tissues at the
time of surgery or at the time of death
and so this is a resource to that we're
working with the nonprofit organizations
to get the word out about the
availability of this NeuroBioBank and
we currently do have two brains from
individuals with ME/CFS who were
donated at the time of their deaths that
are available for research and hope to
expand that as well. We're partnering
with Solve ME/CFS Initiative to support
the development of their registry,
patient registry, and a research app
that's being developed by Columbia
University through their funded Center,
ME/CFS Center, and we're also implementing
what are called GUIDs which is a way to
identify an individual who may be
participating in multiple studies,
because what you don't want in research
is to think that you're using say 100
samples from a hundred different people
when in fact half of those
individuals were participating in two
different studies so you really are only
using say 50 samples from 50 individuals.
So it's a way that we're going to
implement this through the network
initially and then hopefully on a
broader scale for ME/CFS research. And
then last in this category we're working
with RTI, which is the Data Management
Coordinating Center for the ME/CFS
research network, to develop what we're
calling MapME/CFS,
which is a really awesome database that
they're developing as a way for
investigators to share data and datasets.
So initially this will be piloted and
used within the network and then
eventually opened up for greater use by
the research community. In terms of
outreach to scientific investigators, we
have ongoing support to investigators
who contact us all the time about
interest in submitting grants on ME/CFS,
they submitted a grant that was in
review that was not funded, we work with
them to improve and help them to revise
their applications. We also are doing
outreach as I said at professional
society conferences and as soon as the
funding announcements, the PARs, are ready
to be released or are released we'll do an
email blast to the ME/CFS research community
and beyond. In terms of conferences and
workshops one of the recommendations
from the Working Group was that NIH hold
regular conferences such as the one that
we organized here at NIH on the NIH
campus in April of this year and we are
still considering how to implement that
request or that strategy, but in the
meantime we are supporting, NINDS will
be supporting a conference grant to Dr.
Fred Friedberg for the IACFS conference
that will take place in June 2020. And we
will also have plans for participation in
the Invest in ME conference that will
take place in London in May 2020,
including
the Young Investigator workshop that
they hold just prior to their actual
conference every year. So some short term
strategies that we're working on is
to increase collaboration and
cooperation. Steve very nicely explained
our plans for the Interagency Working
Group so we're now looking at how to
actually put that in place. And we
will be doing that hopefully within the
very near future because we see the
great need for better communication and
collaboration across the federal
agencies as well as with other patient
advocacy groups. And we're looking at
ways in which we can coordinate research
on overlapping conditions, for example
with the Pain Consortium here at NIH and
other groups as well. Under research
training, we're continuing to work with
Invest in ME to implement early
career tools and activities and as I
said we are going to continue to
do and increase our outreach to other
scientific investigators. So in terms of
strategic planning as I said many of the
research strategies were outlined in the
report so we're pulling those together
into the beginning of a strategic
planning process and we're looking at
ways to strengthen our ongoing
activities as well as to identify gaps.
We're looking for, to identify areas that
require additional discussion and what
we'll be doing for those likely will be
to develop and have organized and hold
workshops or think tanks to bring
individuals together to really focus on
those specific areas. As part of our
strategic plan we're doing an overall
planning for the process for the
research strategic planning and how we
will actually roll this out, who will be
involved, that's all currently under
discussion and hopefully we'll be able
to report on that in the very near
future as well. So with that I will end
and this is the link to the report from
the working group of Council
it's kind of a very long URL but it's
also on the NINDS website under the
council information, Advisory Council
information, but I'll leave this up here
for a while if you want to write it down.
In addition these slides will also be
posted on ME/CFS website NIH website
together with the transcript from this
call so you'll be able to find the link
there as well. So with that I will okay
sorry I'm just getting my instructions
here. So at this point we'll go to
questions and so please use the raise hand
feature on WebEx if you would like to
ask a question and we will unmute you so
that you can ask a question and one of
us here in the room will attempt to
answer your questions. So please raise
your hand if you have a question to ask.
So first we'd like to call on Claudia
Carrera. Claudia your line is open.
I am wondering about the timeline here
for all of these issues because at the
September NANDS Council meeting
we heard that the council had approved
program announcements for ME/CFS all the
way back in May and so I'm really glad
to see that those are you know that the
implementation is in progress, but I'm
wondering when exactly they're going to
come out and can can you commit to
having them come out before the end of
November which will be six months in
advance of when we're funded. And I also
am interested in knowing how much money
would be included, if there would be
guaranteed funding included, and how much
it would be. So first of all they're
program announcements with special
review, which means there is not
set-aside funding so there's not
specific funding associated with those
PARs. It was a way to stimulate research
as well as to direct grants to the ME/CFS
Special Emphasis Panel because we're
finding
that ME/CFS grants were being reviewed in
other study sections that really did not
have the specific expertise. So they are
in process. You can imagine it takes a
lot to coordinate input from 24
different Institutes, Centers and
Offices to put one of these PARs in
place. So the concept was approved in May
and we're close to submitting them for
review here at NIH and I can't guarantee
when they will come out because that
really is dependent on the review
process in the Office of Extramural
Research, so we are working to feverishly
to get them out and we hope they'll
hopefully come out as soon as possible.
So the next question is from DL. I'm not
sure who that is, but you're unmuted.
Thank you. The NIH clinical study uses
experts to adjudicate patients in order
to ensure that only appropriately
characterized patients are studied. This
is done in part to avoid the polluted
cohorts that have been studied in the
past and that make up such a distorted
base of literature that gets conflated
with ME. While the NINDS report talks
about the need for a strategic plan,
research case definition, et cetera there are
no ongoing or scheduled efforts
currently underway regarding development
for these. The absence of an appropriate
and a research case definition, please
detail for us how NIH will ensure that
all ME studies have the same rigorous
adjudication criteria as a NIH clinical
study thank you.
So I'll respond and see if Dr. Koroshetz
also wants to respond. So one of the
things that came up in discussion in our
Trans-NIH Working Group meeting in
September was the need to really bring
together the experts to identify the
case definition or diagnostic criteria
that we will be using going forward and
to really address clinical outcome
measures that can be utilized in studies
that are validated and specific for this
community. So those are areas that we
identified really do need for the
research and discussion and are really
were beyond sort of the tasks of the
working group itself and as beyond the
really what the Trans-NIH Working Group
can do, so we will likely be pulling
together workshops to really address
those specific issues. Dr. Koroshetz?
Yeah I just add that you know that the
study at NIH is looking at patients who
fit previously established criteria for
ME/CFS and we feel quite secure that
the patients coming in do fit all those
criteria, but I would say that they're
also only studying a subset of those
patients so I think we need to get at is
a way of subdividing the multiple
different types of ME/CFS that we may be
dealing with. And so for instance the
protocol at the NIH Clinical Center is
just honing down on one subpopulation,
which is those folks who are within a
certain period of time of the onset and
when the onset appeared to be related to
an infectious-like illness, so it's an
example of how when one studies ME/CFS,
one not only has to be observant to the
criteria that've already been
established
but also to indicate what subgroups of
ME/CFS patients one might be studying. So
we don't see any other questions. So if
you have a question at this time would
you use the raise hand feature so that
you can identify yourself as
wanting to ask a question? I see a
question from Charmain. Charmain your line is
unmuted. My question is will pediatric studies be specifically included in the PAR announcements or mentioned specifically in outreach to investigators?
So Joe and I are looking at each other. They're not
excluded but whether we specifically
call them out I would have to go back
and look at them. I'll turn the question
back to you. Do you think that's a
critical piece that needs to be included?
Yeah we certainly can do that if we
didn't I don't think
we specified adult or pediatric but I
think we can specifically call that out.
Any other questions, use the raise hand
feature. So I see a question from SS, your
line is unmuted. SS are you there?
No okay I see question from Liz
Burlingame, Liz your line is unmuted. Yes
during the announcement after you
released this report sounded like Dr.
Roberds said that ME is actually a
disease of exclusion. I'm really worried
about that characteristic. According to
the 2015 IOM Institute of Medicine
report we are our own disease. We're
talking about the post-exertional
malaise. Can you please speak to that?
I think that was, if I
recollected, that was an acknowledgement
of the inadequacy of our diagnostic
criteria but not in any way reflecting
on that it was not a disease. So we think
that I guess two points, one is that we
need to develop positive diagnostic
criteria that have, you know, biological
markers with them, a blood test, an
imaging test, a physiological test. Really
important if you're going to screen
patients, if you're going to subdivide
different patient groups. And then I
think also I'm not sure if Dr. Roberds
was hinting at this but we know say from
the clinical study at NIH, it's
incredibly important to identify other
disorders
that have a known pathophysiology but
can present with symptoms of ME/CFS. So
some of the discoveries the Clinical
Center we're finding underlying diseases
in people who had ME/CFS and were unknown
to have these other disorders, oftentimes
the autoimmune or chronic infections.
Thanks Dr. Koroshetz. I remember
saying that and was really thinking of, I
think the first situation, where it shouldn't
be a disease of exclusion, we don't want it to be that, and that's I think one of the
reasons that a clear research strategy
and a lot more research in the area is
needed to identify what we can use as a
marker to definitively give a diagnosis rather
than not being able to find any other
diagnosis and then labeling it as ME/CFS and we don't think that's
appropriate. We want to move research so we can get away from that. Thanks Steve. Okay I see a
question from Courtney Alexander.
Courtney your line is unmuted.
Hi I'm hoping this works through the
phone. I want to thank you all for your
presentation and the detailed work
you're doing on this disease and I
wanted to particularly echo Dr. Koroshetz,
your comments and I appreciate them, on the
need to carefully subset patient groups
for studies and in particular for
movement toward treatment trials and I
just want to raise
the bar on moving this research toward
the ability to try treatments, run
treatment trials, run rigorous trials
that will get us to approved
treatments and urge this whole
process to move as quickly as possible
to helping lay out the foundation for
ultimately approvable treatments for the
disease. And I think the subsetting is
essential but I also think NIH and
NINDS can play a leadership role in
starting to fund some trials that will
bring us some of the response, you know
the criteria, the characteristics the you
know, that characterize response in
subsets of patients that we're going to
learn more on the road to subsetting
very specifically if we start studying
that worked for some and not for others
and identify those the
markers that can separate those groups
and reiterate the need to move that
on a parallel track with the research
where you all have laid out and are
pursuing and moving through the
different Institutes and investigators
but the parallel track is essential for
the changing the dynamic that there are
zero treatments for patients that are
that even approved
under the FDA. Thank you again for
your work, it's well needed. Thank You
Courtney I couldn't agree with you more
and you know that is really what
everyone's working for and you know I
would just say that you know in a
rational drug design one is looking for
a biological target that a particular
treatment will hit that is then thought
to be beneficial and so there may be
many multiple different targets
depending on the subset of ME/CFS
patients we're talking about or there
could be you know for
instance something that is symptomatic, a
circuit that would improve you know
say fatigue or post-exertional malaise
that symptomatic treatment might work
for many different forms of ME/CFS so
that's kind of the goal of the
work is to identify these targets and
and go after them. Either things that
will be what we call disease modifying
and potentially cure the disease but
also things that are going to be a
symptomatic benefit without a
cure but can still really improve
functional level for folks who are
suffering. Well thanks for that.
Yeah, thank you Courtney.
So next we'll take a question for Winston
Christy-Blick your line is unmuted. Hi there, thanks
so much for your work to help us get our
lives back,
we so appreciate it. I'm wondering in
particular how are the efforts of the
working group will help us get around
this catch-22 of being unable to secure
funding because research being proposed
wasn't sufficiently hypothesis-driven
and getting kind of the background
research we need to just get our footing
in this space.
So I'd have to say that in the five
years that I've been really focused on
ME/CFS the research grants are becoming
more and more hypothesis-driven. There is
still the need for discovery science as
well and I think that's the interesting
thing about the Special Emphasis Panel
and the reviewers really I think
understand that we're at a phase in this
research where we really do need to do a
lot of research to understand the
underlying mechanisms and just lay the
groundwork for research. In terms of
securing funding, typically the way
things function at NIH, short of a
congressional appropriation for specific
funding for things like, for example, the
BRAIN Initiative or the opioid addiction
now or autism or Alzheimer's research, we
go through a process which is what we're
in the middle of now in terms of doing a
strategic research planning process
looking at where the research gaps are
and then issuing, if needed, the request
for applications, the RFAs, where there
would be set-aside funding. So I think
that we're driving that process and
hopefully as quickly and efficiently as
we can. Like I said I think it's very,
it's not all that common to have
set-aside funding other than through
specific requests for applications here
at NIH. Dr. Koroshetz do you want to
comment? Well I just say that so the
issue of I think I understand what the
question is so the chicken and egg
question, that you need to have hypotheses to
get the grant then on the other hand you
need data to somehow support the grant
that collecting the data is going to
give you
the answer. But I don't
see them as this data collection and
hypotheses as mutually exclusive at all.
Basically what the investigator has to
put forward to the reviewers is that
collecting the data is going to answer
some questions that are important for
ME/CFS and I think that you know there
are really smart people out there thinking
about it that certainly can
put in grants you know in that space and
and certainly if you look at what's
going on now in the consortium, it's
primarily data collection to get answers
for particular areas, it's not focused on
one mechanism or another mechanism.
We're just not there yet. But all
those grants are definitely collecting
data trying to see if it's pointing in a
direction but some of them are you know,
there are hypotheses that you know are
there potentially infectious agents that
can be found in the bloodstream by
different types of analyses that might
have indicated that there was a trigger
so those those kind of hypotheses are
really still you know fundable
hypotheses that will allow data
collection and you know it's when
we give grants out particularly these
R01 grants, one can move
with the data you're not forced to do
exactly what you propose but you can go
in the direction the data takes you.
Okay thank you Dr. Koroshetz. The next
question is from Emily Chablet I'm sorry
if I mispronounced your last name. Emily.
Hello can you hear me all right? We
can thank you.
Great, I'm Emily Chablet. I'm the patient
administrator for the Stanford
in-patient groups and for Kaiser's ME/CFS
patient groups.
So I'm in sort of a unique position in
that I hear the stories of 450 and more
patients every day and what works for
them. What I am most concerned with is
what's working now, what are the best
working protocols now, and we and part of,
I understand the importance of the
research and identifying the specific
biochemical processes that are that
underpin ME/CFS but I am most interested
in a boots-on-the-ground approach. What
are the best treatment protocols out
there now and I look at the disease maybe
a little bit different from you folks
in that I see component illnesses that
already have treatment protocols and so
what are the best protocols for those
component illnesses and how do they
inform an overall treatment protocol. And
so my approach I would like to ask is
there a way to put together what are the
things that are really working right now
that can really help patients right now?
I have heard so many things from
patients or let's put it another way
I've had many patients tell me this
really works for me and that has come up
for a lot this so that I've seen
patients regain functionality from say
40% to 70%, from 10% to 40%, and it seems
like every little tweak that could be
put into the best working protocol
increases functionality by say a
percentage of 5% something like that. Is
there any effort being made to put
together the best working protocol at
this time and of course that would be
updated as we get better research. I'm
the most interested in how do we apply
the best research we know now that's
corroborated scientific research and
apply to a working protocol.
So thank you for that question and I
actually had the privilege of visiting
Cindy Bateman's clinic, the Bateman Horne
Center in Salt Lake City last week and
had lengthy discussions with her about
this.
She has been heading up a clinical
consortium that really has two goals and
one is to do exactly that-
to compare notes across clinicians and
input in terms of what is working for
these patients or what absolutely
doesn't work in this
population
and sort of getting a better sense of
what treatments work specifically for
components of the disease. For example
her specific interest is orthostatic
intolerance and so that clinical
consortium is in process and is
working together. Clinical care really
in that vein falls outside the mission,
the research mission of NIH but not to
say that new information coming from the
research can't inform and won't inform
in the future those kinds of clinical
protocols but we have, I think, great
interest in the Trans-NIH Working Group
representatives are very interested in
in absolutely translating what we can
from research and from those clinicians
who are out there caring for individuals
with ME/CFS to provide information for
the best care for individuals with ME/CFS.
I would just add that the role of NIH in
this space is to provide the evidence that
will inform the doctors and patients on
what to try and so we do that through what's
called comparative effectiveness
research. So these are clinical trials in
which patients are randomized to one
treatment or the other to see which one
is best and that that is
generally how NIH has developed the
evidence and informs doctors on what to
try I mean would you come up what you're
presenting is actually even more
innovative than that and something we
haven't done as much of but as important
is to actually develop algorithms for
treatment so when you see a patient for
instance with epilepsy you may try drug
A because the evidence says drug A is
the best for a population of patients
that was studied but your patient may
not respond to drug A and then you would
move to drug B, so that kind of stepwise
treatment algorithm is also something
that could be studied in comparative
effectiveness testing, say one algorithm
versus another one as we've done that in
some senses with the treatment of status
epilepticus in the emergency setting
looking at one algorithm versus another,
changing drugs to see which one is best.
So those type of research questions
are certainly the kind of things we'd
like to see. That requires a consortium
of investigators to kind of come
together and you know put away their own
personal favorites to test
things in a kind of organized manner but
that that is certainly something we'd be
interested in. Okay at this time we have
time for one more question on today's
call and I know that there might be
other people that we weren't able to
respond to so if you can send any of
your unanswered questions to
braininfo@ninds.nih.gov or simply go to
the NIH ME/CFS website and click on the
contact us link to submit those
questions. Now the last question for
today. So we're coming back to SS your
line is is unmuted if you have a question.
Thank you.
First of all just wanted to let you know
most of us could not hear Dr. Roberds at
all. We tried to get in touch
through this format and of course there
was no response. So just wanted you to
know that was a complete waste for us.
It's very unfortunate. Moving on in the
previous meeting on September 4th Dr.
Roberds announced that ME/CFS is a
diagnosis of exclusion. We were horrified
to hear this misinformation. The IOM
report stated that ME/CFS is not a
clinical diagnosis of exclusion.
Could somebody brief Dr. Roberds so that
NIH is not spreading misinformation? We
were shocked at this sloppiness. Please
do better. So I think we addressed that
question earlier that the comment
was that is a testament to the
inadequacy of our diagnostic test is not
to mean that it's a diagnosis of
exclusion is to mean that it should not
be a diagnosis of exclusion, but in many
clinics around the country that's
kind of a so, that was a
comment indicating that we really do
need better diagnostic criteria to nail
down this diagnosis so apologize for
that. And for Dr. Roberds yes I'm
sorry, we could hear him well here in
our room so and we're on yeah, not sure
what the problem was. Were you on a
telephone or on the computer? A telephone.
And also I understand what
what you were saying in your response
but what I'm saying and I want you to
understand this so please tell me you
know  I've had ME for forty one years
so I may not be explaining this
accurately but what I'm
asking
really what I'm saying here today about
Dr. Roberds announcing that it's a
diagnosis of exclusion. No he did not say, that is not what he meant. Let me
finish. Let me finish. That the
issue is for people who are listening in
on this call who may not know the
backstory
or the other 85% of the iceberg they're
hearing misinformation
so when NIH speaks you need to be
accurate and that's what we're asking
for we can't rely on you to have to come
in and clean up misinformation
afterwards. We're asking you to be
accurate in what you say and that was
inaccurate. Do you understand what I'm
saying?
Yes, yes I do but it was certainly
not intended to be that way. But it was
misleading and that's the issue and
I don't want to fight or argue with you
because I'm sick. I understand.
Okay so
at this time we're going to end
the call and we thank all of you for
being on and participating and for
all of your questions and Alissa if you
want to wrap up? In closing
today's call I just want to remind all
of you about our listserv for updates
from NIH. To be added to the listserv
please visit the NIH ME/CFS website at
www.nih.gov/mecfs and click on Join our Listserv at the bottom
of the left sidebar. Thanks again for all of your informative and thoughtful discussion and
we wish all of you a good afternoon.
Thanks very much everyone. 
Thank you.
