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 DR
SAXMAN: My name is Scott Saxman, and I am in the Clinical Investigations
Branch of CTEP. One of my responsibilities is the lung cancer portfolio.
The first thing I would like to do this morning is introduce you
to the meeting, give you a better sense of why you are here, I think,
how this meeting came into being and what we hope to accomplish
during this meeting.
I would like
to start this off by introducing Dr. Bob Wittes. Dr. Wittes is the
Director of the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute.
DR. WITTES:
Thank you, Scott, for putting this meeting together so ably with
your colleagues in CTEP. I just wanted to spend a few minutes putting
the meeting in context actually and telling you a little bit about
what our hopes and expectations are for this process.
Probably all
of you are totally familiar with the fact that the Cancer Institute
and many of the investigators who work with us have been engaged
over the last two to three yeaps in an intense process of reconsideration,
the thought being that important aspects of the clinical trials
program need to be restructured to meet the challenges and the opportunities
afforded by scientific and technological advances in the discovery
of new approaches to the development of interventions.
The process
that we have been through has been very participatory. Many of our
other constituencies on the outside of the Institute that we work
with, in fact, all of the ones that we could identify, have worked
with us on this. It is consistent with a staged process with several
components, the two most important of which were a group chaired
by Jim Armitage producing a series of general recommendations—I
think there were about 45 or 46 of them— followed then by a
set of implementation considerations that came from a group co-chaired
by Michaele Christian and John Glick.
We are at the
moment busy implementing, either in a definitive way or in a pilot
way, the vast majority of the recommendations that came from this
implementation process, and probably many of you have seen the report.
If you haven't, and you are interested in looking at it, I would
commend it to you. It is available on the cancer Trials website.
I think it is the second or the third item on the left that you
click on in order to get actually a sort of a user friendly translation
of the full report. The items that we are concerned with addressing
cover what we think is really the full range of issues in imagining
how we get from where we are now to an efficient, effective clinical
trials program that addresses the needs of cancer patients in the
most expeditious ways possible. If you take a look at this report,
what you will see is a pretty wide range of issues— we think
everything from the generation of ideas all the way through to how
trials are carried out, and some of the many and fearsome societal
obstacles in clinical research today in the United States.
So, for example,
the process identified access to a full menu of studies as one of
the prime issues that we ought to deal with, access not only on
the part of would-be participating physicians but also on the part
of patients around the country who sometimes are denied access for
one of a number of reasons. So what we are in the process of constructing
now is a system in which the cooperative groups, which have always
been important and will continue to be pivotal in any clinical trials
program that we envisage, are integrated into a national system
supported by a support unit. We imagine the support unit as functioning
as a sort of a user friendly interface, presenting a common interface
between the clinical trials program on the one hand and participating
physicians and health care professionals on the other. That is just
one of probably two dozen examples of the kinds of changes that
we imagine will facilitate the participation of physicians and patients
in clinical trials.
We are in the
process of building an informatics system that is adequate to the
charge. This is a hugely ambitious project, and many of you are
familiar at least in outline with what it is that is needed and
what it is that we are trying to do.
Now, the issue
of access is more than simply "I want to participate in a trial;
how do I do it?" The issue of access, also, applies to ideas. In
fact, in some ways it applies more importantly than anything else
to the matter of getting the best ideas into clinical tests as soon
as the idea or the therapeutic reagent or combination of reagents
are ready for it. To address some of the preclinical barriers to
getting new reagents into trial and to address the problem of how
early clinical trials that focus on proof of principle of new therapeutic
approaches should be supported, we have got a bunch of other initiatives
either in the drafting stage or already in operation.
Several of
you, I know, are familiar with the RAID (Rapid Access to Intervention
Development) program. Most of you, I would hope, are familiar with
the fact that we have now a Clinical Oncology Study Section that
when it has finished its shakedown cruise—and maybe even already—will
be fully adequate, we hope, to the task of evaluating clinical proposals,
clinical grants. Clinical grants, as we all know, have long been,
I think it is fair to say, stepchildren in the way that scientific
review has handled them, at least compared to basic science grants.
Okay, but we
are still left at the end of the day with this matter of ideas,
how we discuss them as a community, how we decide which ones should
be pushed with the aid of public funds. In order to address that
aspect of the problem, of the challenge really, we thought that
a series of national forums should begin in which experts in the
field are gotten together with the express purpose of trying to
figure this out together. The focus of these meetings actually will
be predominantly, perhaps not exclusively but predominantly, on
the clinical translation of ideas and reagents, either actual or
potential reagents from laboratory to clinic and the interplay that
occurs across that barrier, across that divide. Sometimes it is
a divide.
We have imagined
for the most part that these State of the Science meetings will
be open meetings of relatively small size, such as this. We actually
talked about this a lot at the beginning of thinking about how to
do this, and I, personally, vacillated all the way from very small
meetings to meetings that would fill the better part of a sizeable
hotel ballroom, because if the issue is access then part of the
atmospherics of doing a meeting like this correctly is the notion
that anyone is welcome who thinks that he or she is working on a
potentially exploitable issue for translational research.
We decided
on this kind of a forum as an initial foray into this, but as Scott
implied in his opening comments, nothing about this meeting or other
meetings that will follow this one is written in stone. Above all,
we want these meetings to be useful to the people doing the work.
We also want them to be useful to us as planners, as we figure out
how best to deploy public funds toward improving the lot of cancer
patients.
So the issue
of openness affects these meetings in the following way. We purposely
would like these meetings to have access on the part of people who
are outside what one might call the system. By the system, I guess
what I mean is the orbit of the Cancer Institute, the familiar orbit.
When one comes to small cell meetings over the years, one sometimes
has the feeling just the way you do when you go to a Hodgkin's disease
meeting or any other kind of meeting that you are seeing the same
old friends year after year, and that is great. Sometimes small
cell meetings, John, all credit to you and your colleagues, seem
like a reunion of the old Navy Branch, which they are in an important
way, but the idea is to add to that of course and to bring in folks
from outside the familiar orbits who have something to contribute.
It becomes more challenging and more fun to identify such people
as the science spreads and as things become relevant to translational
research that haven't been, that one couldn't even imagine five
or ten years ago.
The SPORE (Specialized
Program of Research Excellence) meetings, for example, are full
of such science. That is an important link, or could be an important
link, as a resource to the rest of the country, to the rest of clinical
investigation.
So we imagine
that the benefits of this meeting will come from a full discussion
of the issues and from some sort of—I don't exactly want to
use the word "consensus" because this is not a consensus meeting
in the sense in which the term is used—but it would be satisfying,
shall we say, if some sort of general notions emerged from this
meeting about what the best things are for us to do. That is the
sense in which this meeting and these meetings might differ a bit
from some of the other ones.
Our community
these days is full of meetings that are devoted to translational
research, either in general or focused on specific diseases. One
of the things we are going to have to decide in planning future
meetings is how many we should sponsor independent of those because
you can only get the people that you want to come to meetings like
this so many times a year. It is just not reasonable to have meeting
after meeting with largely overlapping agendas.
So if there
is a prostate cancer meeting for example at Memorial, and there
is another prostate cancer meeting at the University of Iowa, how
many prostate cancer meetings focused on molecular targets are reasonable?
The answer is a limited number, but this not just a group therapy
session or another meeting on targets or another meeting on something
else.
What we really
would like to come out with is a sense of what the clinical trialists
who are planning the translational interface should be paying most
of their attention to as we try to feed this new spiffy system that
so many of us are running around trying to create right now.
You could have
the most wonderful system in the world, and it is only going to
be as good as the questions that it feeds itself. What we plan on
doing is countering to some extent the small size and compass of
this meeting by making its deliberations available on the web for
public enjoyment and edification. It is actually going to be rather
hard to measure how meetings like this affect what we do in clinical
trials in the future, but if we play our cards right at meetings
like this, I have no doubt, none, that there will be an important
effect on trials planning in the future. We are going to need ideas,
and potential reagents are coming from so many different sources
and are of so many different types, it is only going to accelerate
in the future. We need some way of bringing all of this together
and making aggregate decisions about the best thing to do.
Are there any
questions or comments of a general sort about anything that I have
said or any other thoughts that folks have about perhaps what we
ought to pay attention to? I don't think we have actually planned
a discussion here, but it might be good just to take a deep breath
and see whether there are any additional ideas that people wish
to raise.
DR. BRAUN:
One quick comment: much of what you said has been created at an
embryonic level in the private sector. Have you given thought to
making this fully interactive with the development of preclinical
and translational research in the private sector?
DR. WITTES:
By the private sector, do you mean the drug industry?
DR. BRAUN:
Exactly.
DR. WITTES:
I don't know exactly what you mean. The interest in targets, in
molecular targets in the drug industry and in the biotech sector
is, of course, very high.
DR. BRAUN:
Maybe I could amplify. Specifically, private sector companies always
have problems going through the preclinical proof of concept and
early clinical trials phase without interacting heavily with academic
centers who do that. It is just that it seems to be catch as catch
can. There doesn't seem to be, at least in my experience, an easy
way in which the private sector can come to some sort of a clearinghouse
and say, "We have got a molecule or a therapeutic or a diagnostic
that we want to get some very quick information on in a preclinical
proof of concept setting and an early clinical trials setting. Can
you facilitate that process for us?"
DR. WITTES:
Right. We like to think we have been doing that for decades. Many
people don't know that we do it. Many people in industry don't know
that we do it, and there are probably better ways to do it than
the ones that we have been using. We have many approaches to that,
but I mean the general answer to your question is yes, we are giving
a tremendous amount of thought actually to industry interactions
and the creation of new kinds of consortia with companies, not only
over the development of individual products, which is very important
and which is what you are addressing, but over some of the grander
issues that we could all do together. For example, let me just tell
you that I think it was last week we cosponsored a meeting with
NEMA, the National Electrical Manufacturers Association and, also,
with the FDA and the Health Care Financing Administration over an
attempt—and we had been thinking about this for two years now,
and we did it—an attempt to work with the imaging device industry
as a whole, with HCFA and with the FDA, in trying to realize molecular
in vivo imaging in a kind of a national effort, and this is at the
very beginning of thinking.
We had a tremendous
amount of enthusiasm on the part not only of company scientists
but, also business people and the FDA, and it is sort of an example
of grander ways of thinking about industrial involvement in what
we do.
We are beginning
now to think about approaching the drug and biotech industry with
a similar kind of set of ideas. We have already talked to many industry
representatives, for example, about setting up a system by which
we might broker the availability of combinatorial libraries between
sources of chemical diversity on the one hand and screeners on the
other.
So he short
answer is yes, we are doing a lot of thinking about stuff like that.
Anything else?
Okay, thank
you all very much for coming.
DR. SAXMAN:
What I would like to do in the next ten minutes or so is introduce
you to the State of the Science meeting, not so much the big picture
as Dr. Wittes has so eloquently done, but the practical matter of
today.
Why are we
here today, and what are the expectations for today?
TOP
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In
the Internet age, we talk about FAQs, frequently asked questions,
and this is the most frequently asked question I have gotten as
I have put this meeting together, as I have sent e-mails, as I have
talked to people over the phone. Quite honestly it has been somewhat
of a difficult question to answer because the answer has evolved
over the time that we have put this meeting together. Different
people, both within and outside of the NCI, have had slightly different
takes on exactly what the answer should be. So I struggled a little
bit to answer this question for you today. A few colleagues of mine
suggested that perhaps the best way to answer the question was to
tell you how we put this meeting together, where we started, and
how we made the decisions that brought you to where you are today
and then to charge you with what we would like to accomplish with
this meeting.
We
started off basically with this very simple but overriding goal,
and that was that we wanted to stimulate and accelerate the development
of new clinical interventions for patients with lung cancer. Significant
advances have been made in the understanding of the biology of lung
cancer over the past several years and so we felt that new interventions
should exploit what we know and what we are learning about the biology
of the disease. We should target the biology and let the biology
lead people toward therapeutic interventions. 
One
of the first questions we asked was, "Should this meeting be about
lung cancer in general, or should we separate out small cell and
non-small cell lung cancer as two separate diseases?" This actually
turned out at least to us to be a relatively easy question.
We
discussed several types of meeting formats. Originally I felt that
perhaps this would be just a series of presentations with panel
discussions. We evolved from that to the current format, which is
a planned presentation with discussion or breakout groups.
I
think there are two ways to begin to cross the bridge between the
basic sciences and the clinic, and one is to look at the problem
from the standpoint of the biology of disease and ask how the biology
of the disease helps us define or to begin to solve clinical problems
that we see in taking care of patients. Another approach is to identify
the clinical problem, i.e., radioresistance. Radioresistance is
a problem, and how do we go back to the biology and use what we
know about the biology to try to solve that particular problem?
And while these two ways of looking at this I think are extremely
complementary and very similar, I don't think that they are identical.
So we structured this meeting to start with the biology and move
towards the clinic, and the questions that are in your packets were
intended to stimulate or begin to get people to think about those
types of issues. 
The
charge to you as participants is to participate openly in a dialogue
that is intended to discuss promising developments or opportunities
in research in small cell lung cancer and their application to clinical
intervention and to discuss and make recommendations or suggestions
regarding the steps that will be necessary to move novel therapeutic
approaches to definitive clinical trials. 
This
was not a solo effort by any means, and I would like to take just
a minute and thank the people who were instrumental in helping put
this meeting together. The cosponsors of this meeting are individuals
in the Division of Cancer Biology, Alan Mufson and Dan Gallahan.
In Cancer Diagnostics, Tracy Lugo and Sheila Taube were extremely
helpful, and their input was very beneficial. We could not have
done it without them or Diane Bronzert, Rick Kaplan and Jeff Abrams,
my colleagues at CTEP. In the cooperative groups, David Johnson
and Mark Green were on the committee and were extremely helpful
in helping us not only format the meeting but decide who the appropriate
individuals were to be here. John Minna and Paul Bunn were also
extremely helpful in helping to identify the appropriate individuals
to participate in this meeting.