Keith Burkhart: Keith Burkhart with the FDA.
One class of drugs in that that we’ve -- thanks.
One class of drugs is -- are some of the tyrosine kinase inhibitors in oncology, which there’s
been some recent labeling of SJS within that group, and there’s a lot more new ones in
that coming on board as far as active surveillance, with the cancer patients often having a lot
of genomics work done as well, so be curious to her from Howard and other experiences,
you know, from within those kind of networks as far as a patient population to try to maybe
be a little more active in some surveillance within.
Carolyn Hutter: Howard, do you have a follow-up to that comment?
Howard McLeod: We’re seeing a lot of dermatological disorders
but not -- I haven’t seen the SJS signal at our institution, so I was actually just
emailing some folks to go and look harder --
[laughter]
-- because I know it does occur, but I’m wondering, you know, are we seeing it and
its being shipped out the back door to Tampa General’s burn unit or are we -- you know,
basically, what we’re doing, so I guess I don’t know the answer.
But certainly, the TK -- tyrosine kinase inhibitors are bringing a lot of additional dermatologic
problems.
Well, a lot of its hand-foot syndrome-type work.
Carolyn Hutter: Lars.
Lars French: Yeah, I can confirm with the TKIs we haven’t
seen any Stephens-Johnson/TEN.
We’ve had one interesting cases -- or case, and were going to report that.
We had an SJS-like clinical picture occur in a melanoma patient receiving NTPD1 [unintelligible],
and that’s -- also underscores that being on the list.
And we worked it up, and we’ve been running microarrays on skin biopsies of patients with
maculopapular rash, TEN, AGEP, and graft-versus-host disease and could see that really TEN and
graft-versus-host disease segregate completely differently.
So although there may be some similarities, they are molecularly different.
And then we ran the same set of genes on this case because we we’re wondering if the NTDP1
was lifting the tolerance and inducing a sort of graft-versus-host, and the genes that came
up were those that you see in TEN, so it really seems to classify on that side.
So it’s only one case.
I don’t know if you’ve seen any.
Howard McLeod: Yeah, we have.
Lars French: You have seen, too?
So that’s really interesting.
Howard McLeod: Well, we didn’t call it Stevens-Johnson
Syndrome, but we’re definitely seeing what you described in -- we did a lot of the early
phase I and II and then two of our -- we lead the melanoma and lung cancer big phase IIIs,
and so we ended up with a disproportionate number of patients there, but we definitely
have it.
Lars French: Is the histology there?
You also have a histology with Necrolysis developing?
Howard McLeod: I don’t know.
Lars French: You don’t know.
Carolyn Hutter: So Bob is the other co-chair.
Do you have any specific points you’d like to raise?
Robert Davis: No.
[laughter]
Carolyn Hutter: I heard you say you were struck by some fact,
so what was it?
[laughter]
Robert Davis: I was struck by the desire to say no.
Teri Manolio: So I’m wondering -- you know, one of the
things we probably didn’t do in our -- in our office on working group three -- and thanks,
Simone, for going through that so carefully.
Did we identify sort of our top-priority research need?
Did we kind of pick out one or a few that we felt were really sort of the most important.
I mean, I remember discussing race-ethnic breakdown of data in the FDA databases and
then some difficulties that they have in collecting that information.
But what were sort of the -- kind of the highest-priority ones?
Carolyn Hutter: And I’m going to let the chairs answer,
and then, Marc, you can --
Marc Williams: I was just…
Robert Davis: I thought -- at risk of sort of showing my
biases, I thought there were three take-home suggestions that seemed to resonate with people
or with the group.
One was the need to -- if to develop pharmacosurveillance to really begin to address the race/ethic
breakdown of SJS/TEN in the United States.
I think, you know, the unsaid thing here is that there’s -- I’m not aware of any data,
honestly, in the United States that’s been published over the last 20 years that can
actually speak to that, and it’s critically important given what we now know about sort
of the very specific risks in other countries.
So that’s one thing.
The second one was the point I think Mark may make in a more articulate manner but just
the real idea to begin to focus in on a standardized case definition, and I guess I interpreted
the discussion a little bit differently.
I thought that the discussion was really saying let’s focus on a minimum set of criteria
that can be useful for both retrospective and prospective studies so that we’re not
constantly comparing apples to oranges because that’s just -- but there’s always this
tradeoff in the sensitivity and specificity, and I’m not sure that we’re going to have
a whole lot of success solving that issue, because this comes up in every sort of large
-- big epidemiological question I’ve been involved in.
And the third, I think, was an idea of to really look at the utility of burn units.
That seemed to really resonate with people, and I didn’t have access to The New England
Journal, so I went to Wikipedia instead today and found out that there are less than -- there
are about 5 dozen burn units that cover the United States.
And, you know, that’s actually a tractable number to begin to think about.
So -- and we didn’t really explore that in any great detail, but it seemed to really
strike people’s ideas as -- in terms of being able to do active case validation and
accrual of specimens in a relatively pragmatic fashion.
Carolyn Hutter: Simone, anything you want to add?
Simone Pinheiro: No.
[laughter]
Carolyn Hutter: Marc?
Marc Williams: What I was going to say is I think the first
action item, which is less about research and more about infrastructure, was the recognition
that there are a number of case definition forms that are currently in use.
And so the first step was to aggregate all of those, compare them, and then see what
the commonalities are and so we don’t start with a tabula rasa, but we actually take what’s
being used, as we’ve heard about from Munir and from Maja and others, and began there.
Male Speaker: So I think that that’s exactly what we should
do, and we should do it in an Adelphi exercise where you take all the different statements
and then everybody get together and they agree on how appropriate the statements are, and
then you just do the math and if there’s agreement at the end.
And then you just publish your little consensus statement saying these are the things that
should be collected when a patient comes in with TEN.
Marc Williams.
And I did not pay Emanuel to say that.
[laughter]
Carolyn Hutter: Howard.
Howard McLeod: I just wanted to mention that I think NIGMS
still has a burn research program that interacts with a lot of these burn units and -- maybe
not all of them but some of them, so it might be worthwhile reaching out.
I didn’t see Dick Okita or any of the GMS folks in the room at the moment, but you might
be able to have a short reach to them through some existing relationships at GMS.
Carolyn Hutter: Yeah, and we have members from GMS on the
NIH working group that’s been formed to be talking about SJS/TEN, so we can also follow
up.
Other questions or points?
Okay, well, I think I’m going to turn it over to the next session.
Santa Tumminia: Hi, everybody.
My name is Santa Tumminia, and I work here at the NIH at the National Eye Institute,
and I just wanted to thank everybody for a very, very informative and educational two
days’ worth.
I really learned a lot from all of you, so thank you.
So now I have the pleasure of re-welcoming Teri Manolio to the podium.
Teri is director of the Division of Genomic Medicine at the National Human Genome Research
Institute, and she’s going to lead us through a discussion of next steps and where we go
from here.
So Teri?
Teri Manolio: Thanks.
And actually, it may take me a minute to get booted up here, so if y’all want to, like,
talk or check your email or whatever.
Yeah, so -- because it’s not coming up.
Carolyn Hutter: So the thumb drive’s not…
Teri Manolio: Yeah, it’s not -- it’s not reading it.
Male Speaker: This isn’t --
Teri Manolio: -- because Marc told a story.
Say what?
Male Speaker: This is not working.
Teri Manolio: Oh, fine.
[laughter]
Okay, it was working this morning.
Surakameth Mahasirimongko: What the IT guy did was unplug this and plug
it back here.
Teri Manolio: Oh, right, he did.
Carolyn Hutter: Oh, right.
Teri Manolio: I saw him do that.
But --
Surakameth Mahasirimongko: It seemed to work for mine.
Teri Manolio: Oh, really?
Yeah, I saw him do that, and I thought it was just -- look at that.
All right, so Surakameth has figured out a way to overcome the security thing here, so
he’s a -- he’s a man to watch out for; that’s for sure.
Male Speaker: It should be the CIA website.
Teri Manolio: Yeah, that’s right.
I don’t see it, though, and I know it was here.
So I’m sorry; which drive would this be?
Is it removable disks, Surakameth?
Surakameth Mahasirimongko: Yes.
Teri Manolio: Because it’s not…
Male Speaker: Look over here.
Teri Manolio: No, we put it -- no, we put it down here because
we couldn’t get this to work.
Male Speaker: Is it one of these?
Teri Manolio: No, it’s not there, and I know I just saved
it.
So I’ll have to save it again.
Can I just pull it out?
Male Speaker: Checked it.
Teri Manolio: Damn.
Male Speaker: Sorry about that.
Santa Tumminia: No, no problem.
So I will say I can’t remember if yesterday it was Marc, but somebody else but somebody
was talking about how ophthalmologists take terrible, terrible notes, and I want you to
know that -- okay, well, there were a couple of ophthalmologists in the audience, and I
was watching their body language, so they did hear you.
I’m sure I’m going to hear about it when I go back, but I just wanted to let you know
they heard you.
Carolyn Hutter: But I think -- I think that the comment was
that their notes are very difficult to draw from in an electronic form because they’re
pictures, so they’re not something that’s in a form or even that you do natural language
processing on because they’re hand drawn pictures.
Santa Tumminia: So I don’t disagree with you.
We actually have a network where we have clinicians from around the United States send us documentation
for their patients, and the drawings range from quite artistic and beautiful so we can
actually tell it’s an eye and then some where even, you know, the eye would be a challenged
stick figure, so we did appreciate the commentary.
[end of transcript]