Excerpted from Transcript provided by

**NEAL R. GROSS**

COURT REPORTERS AND TRANSCRIBERS

1323 RHODE ISLAND AVE., N.W.

\(202\) 234-4433 WASHINGTON, D.C. 20005-3701 www.nealrgross.com

# Introductory Remarks

## By James Dillard, Hugh Beebe, Dorothy Abel, Megan Moynahan

DIRECTOR DILLARD: Good morning. My name is Jim Dillard, and I am the
Director of the Division of Cardiovascular Respiratory Devices, in the
Office of Device Evaluation, at the Center for Devices in Radiological
Health.

And so we have put up only one of those little bit of acronyms because I
think really from my perspective certainly in the Office of Device
Evaluation, we rely very heavily on the other components within the
center.

Certainly our Office of Science and Technology, and a number of the
other offices, that really pull together in combination with all of what
we do \-- pre-market, post-market, pre-clinical testing, and clinical
testing, to try to come up with the best sort of test methodologies to
bring products to the market.

And I am very pleased to be here today, and I certainly wanted to
welcome everybody. I know that this has been a large effort. Hopefully
this will be the first annual Endovascular Graft Worksheet.

It has been a large effort certainly not only on FDA\'s part, but I
think from everybody\'s perspective here in the audience, and we really
appreciate you making the time to come to today to talk about a very
important issue, and a very important new technology.

And I think one that is probably very revolutionary in everybody\'s
minds here, or you probably wouldn\'t be here. But also is in its
infancy, I think, in its development stages. And from the FDA\'s
perspective, it is a technology that we need great help with.

We have got a couple of very early designs that are on the market, and
we have a number of other types of technologies for endovascular
grafting that are under investigation.

And when we look at that from the agency\'s perspective, and the types
of test methods that we need to evaluate the technology, it is very
crucial for us to understand pre-clinically how to do the right types of
testing and what sort of test methodologies are the most appropriate.

And I think that with that, what I would like to do is thank certainly
Megan and Dorothy. They are two of the best and brightest on my staff,
and they had this great idea about 6 or 8 months ago to try to put
together a workshop funded not exclusively, but to a large degree, with
some sort of FDA money that didn\'t exist at the time.

And they came and talked to me and said that this is really a great
idea, and we think we can put the best and brightest around the world in
a room, and talk about pre-clinical testing.

And being the person that I am, I sort of shrugged my shoulders a little
bit, and they beat up on me a little bit more and said, no, we can
really do this, and we can do this fairly cheaply, and I think that was
really the genesis of this, and moved on to get a lot of variable people
to put this program together.

And in the next couple of days, I am very excited that we are going to
be focusing at least in the next couple of days on pre-clinical testing,
although I have seen on the agenda that the clinical relevance and the
clinical significance of the pre-clinical testing is going to be a large
focus.

And I think with that that we will really have the right sort of
approach, and we will take a look at what is going to be very important.
And I will just sort of end with one more comment.

And that is that we are really moving in the direction to try to pull
together all components, pre-clinical testing, clinical testing,
post-market evaluation, and the best possible way to take a look at
technology.

This technology I think is going to be a great example, because we have
the opportunity in the next couple of days to look at what we have
learned, and certainly in the early phases, and take a look at how to
evaluate the technology, and then even most importantly, how do we take
pre-clinical information, feed that back into the development of product
so that we as a regulatory authority, and you as industry and
clinicians, can get the most out of the technology at the earliest
possible time so that it is available to patients in a very timely way.

And I think that moving from exclusively a clinical kind of evaluation
to something that might have great ties in the pre-clinical testing
arena is something that we are very excited about, and very
enthusiastic.

And I have very high hopes that at the end of this conference, if we
haven\'t at a bare minimum brought up the most important questions that
need to be addressed, and hopefully also thought about the next steps
about how do we really focus on addressing those issues, and what sort
of tests can we utilize, and how do we get the most out of the
pre-clinical testing environment, which I think is perhaps the most
challenging in the next couple of days, is going to be very important.

And so with that, again, I would say welcome. Hopefully the hotel here
is reasonable accommodations. I don\'t know. Many of you have probably
come to panel members here, and the last 2 or 3 that we have had there
has been a lot of construction going on, and I think they are getting
pretty close to being complete.

And hopefully you will find the accommodations and everything else
reasonable. If you have any questions, Anne Marie Williams is one of our
greatest, too, of putting together these types of meetings. Her and her
staff will be available if you need anything.

So please don\'t hesitate. And Anne Marie, if you want to maybe wave.
Many of you may know Anne Marie. Please don\'t hesitate to get her, and
Megan and Dorothy can certainly help out, too.

And with that, I think I will turn it over to the much more important
people who are going to focus on in the next couple of days. Dorothy,
are you next? Oh, Dr. Beebe.

DR. BEEBE: Thanks, Jim. I guess I am going to make a few remarks on
behalf of the steering committee. We want to add our welcome to Jim\'s.

Change in clinical practice is usually incremental, and taken in
conservative steps, and validated by empirical evidence. And there is
safety in this process, quite analogous to driving pitons in direct aid
mountain climbing, but it is slow, and it is expensive, and it kind of
inhibits true innovation.

The advent of endovascular grafts can be considered a big leap, kind of
like a lateral pendulum traverse, to continue the mountaineering
analogy. But it probably should still be considered incremental because
it was based on the concepts of conventional open surgery.

And these concepts did not prepare us for what was observed in practice.
Examples that prove this point abound. Consider only that we didn\'t
even know what the dimensions of aortic aneurysms were, or that Dr. Juan
Parodi began without using a distal stent, or that we were all surprised
to see that excluded aneurysms were shrinking, and we didn\'t know why.

It is also important to acknowledge that endograft development has been
seriously burdened by the lack of an appropriate and practical
experimental model.

So here we were trying to do something completely new, and no relevant
laboratory experienced, and somewhat inappropriate concepts, and
certainly a situation that would predict a steep learning curve to
climb.

Well, what have we learned? Well, one thing that we have learned is that
the value of pre-clinical testing would be immense if we only knew how
to do it.

In the beginning of endografting, preclinical testing standards didn\'t
exist, and to have invented some would have been arbitrary, and
certainly unsuccessful.

But today we have the accumulated experience of a decade of clinical
application of endografts, and it is time to take a fresh look at
preclinical testing.

There are two ultimate questions to ask. Do we know enough to set
uniform preclinical testing standards, and if we do, what should they
be. This workshop on preclinical testing begins the process of answering
these questions.

But along the way, we are going to discover a lot of other questions
that need answers before approaching the two ultimate ones. This
workshop brings together a diverse group.

We have people here from different clinical disciplines who are
investigators of endograft technology, with different perspectives and
insight. We have manufacturing industry, each with their own
perspectives, and with their own proprietary interests.

And we encourage you to take the risk of contributing to the
commonwealth need of making all endografts better, and perhaps we can
get into that a little bit outside the sessions, and talk about how we
all stand or fall together at this point.

And we have regulatory evaluators, and isn\'t it cool that we are all
here in the same room, so that we can belay each other on the climb. We
should be capable of accomplishing a practical result at this
conference, because there is a lot of talent in this room, and a lot of
motivation to use it.

And I think we should have as a goal to come out of this with a
practical concrete result. Progress to the summit of patient safety and
endograft effectiveness, however, will take a lot of effort because we
have a long way to go. Thank you.

(Applause.)

DR. BEEBE: Now here is the deal. Some of you people who are giving
introductory kind of talks have got stuff on CD. Does anybody have
slides? Technology-challenged people from California can use a slide
projector.

And if you don\'t have Cds and you have not already discovered it, you
can plug your laptop in over here, and that is kind of cool, too. I have
been \-- for some reason Dr. Parodi has a really neat advertisement for
Air France on his as a screen saver. If any of you want to see that, you
can come over and look at it.

And so that is the A/V thing, and now I think \-- Dorothy, are you going
to say some things about how the conference is going to work? Megan is
the only one who is out of uniform. Dorothy is dressed in pink, and I
wore my pink shirt, and I somehow forgot to tell Megan.

MS. ABEL: Sorry about that, Megan. I am actually going to tell you about
how this conference came to me, as opposed to how the next couple of
days are going to run, and that is going to be Megan\'s job.

But I don\'t want to take up too much time, and I think that Jim already
set the stage, in terms of how we found out that there was funding, and
we took advantage of it.

I just wanted to let you know that we thought that this workshop would
be possible because of the dedication of all the different interested
parties in this device area.

I think we have got a unique group, and it shows in the standards
development, and in the professional society meetings, where there is a
lot of sharing of information. There is a lot of working together with a
common goal.

We even have clinicians talking to clinicians, and engineers talking to
engineers at our regulatory meetings now, instead of reg affairs people
talking to regulators.

So I think we are really at the point where we can all get together and
try to work on improving the frequent field testing for these devices.

In February, at the ISO meeting, we asked the standards group if there
was an interest in having this type of a workshop, and there was. So we
pushed ahead. We called for volunteers to help us plan the meeting, and
they are going to show up on the screen here any minute now.

And the folks who showed up at the first planning meeting are the
steering committee. So obviously it wasn\'t hand-selected. It was by
volunteers, and they are listed here.

The exception is Dr. Beebe, who was an invited moderator due to his
wonderful skills at that. What we did with the steering committee was
try to figure out how to lay out this workshop, and come up with the
questions that needed to be answered, and worked on the work
assignments.

And we found that since we only had two days to do what we were trying
to do, that it would be beneficial to send out the work assignment in
advance, and try to get the compiled document that you now see before
you.

The asterisks show who actually responded to the work assignment, and we
would like to give them a round of applause because that was a huge
effort that the folks put into doing that.

(Applause.)

MS. ABEL: Those without the asterisks were invited, but did not send in
their work assignments, or they sent them yesterday morning. So not all
of them are reflected in the information that you have.

We received 13 completed assignments in case you didn\'t want to count
the little asterisks. The other thing that I want to mention is that
although we have listed individual goals for the separate sessions of
the workshop, it is important to just acknowledge that what we are
really trying to do is to improve the pre-clinical evaluation of these
devices.

We are hoping that this can be accomplished both through what the
individuals walk away from this workshop with, and through feedback into
the standards committee that is currently in the process of trying to
develop test methods for these devices.

And as a final note, I just wanted to acknowledge that the pre-clinical
testing will never take the place of well-controlled clinical trials to
really find out how well these devices are going to work.

But we certainly want to learn as much as possible about each of these
devices before we move into that ultimate test. Now, Megan is going to
tell you how the next couple of days are going to run.

MS. MOYNAHAN: Good morning. And welcome. Actually, I am very encouraged
by the turnout today. I have to say that we were a little intimidated as
all the responses were coming in that we might not have a big enough
place, but it looks like everyone is comfortably seated.

I would like to explain a little bit about how the next two days are
going to proceed. Basically, the flow of the workshop is going to go
through the entire work assignment that you have in front of you.

If you know Dorothy and me, you know that we are very goal oriented, and
we fully intend to finish all seven questions by the end of two days. We
have structured the workshop to have presentations that kind of kick off
the discussion.

And really the purpose of the presentation is just to set the stage for
the rest of the discussion that follows, and to bring up some clinical
perspective on some of this pre-clinical testing.

After each presentation, Dorothy and I will spend a few minutes
orienting you to the material that is in the binders, because we realize
that a lot of you haven\'t seen this before.

And then that will start the working participants and discussion over
the working compiled assignment. At the end of the working session, we
will have a wrap-up comment by Dr. Beebe, and it will also be an
opportunity for the audience if they want to add in.

Our goal is really to have a version of the work assignment that
reflects the input for the next two days, both from the participants\'
point of view, and also from the audience members\' point of view.

But I want to emphasize that this is really not designed to be a
consensus conference, per se. We are not really trying to get one
consensus statement in one particular area.

If there are points though in agreement that we can all acknowledge,
then that would be fine.

The last thing just as a reminder is that we are having portions of this
transcribed for the record. We will be transcribing the presentations
and the audience comments.

We are not going to be documenting all the back and forth during the
working session. But that means that it is important as audience members
when you do want to comment to use a microphone and to introduce
yourselves for the purpose of the transcriptionist.

MS. ABEL: And the agenda is really just a tentative agenda, and it
certainly is subject to change.

MS. MOYNAHAN: Right. We want to have the most flexibility as possible.
If we feel that there are areas where we need to spend more time, let\'s
go ahead and do that, and then we will try to shuffle things around a
little bit later. So the agenda is really just a tentative agenda. All
right.