UNITED STATES OF
AMERICA
FOOD AND DRUG
ADMINISTRATION
CENTER FOR DEVICES AND
RADIOLOGICAL HEALTH
MEDICAL DEVICES ADVISORY
COMMITTEE
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CIRCULATORY SYSTEM
DEVICES PANEL
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MEETING
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THURSDAY,
JANUARY 13, 2005
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The
Panel met at 9:00 a.m. in Salons A, B and C of the Hilton Washington, D.C.,
North/ Gaithersburg, 620 Perry Parkway, Gaithersburg, Maryland, Dr. William H.
Maisel, Acting Chairperson, presiding.
PRESENT:
WILLIAM H. MAISEL, M.D. Acting Chairperson
CHARLES R. BRIDGES, M.D. Consultant
THOMAS B. FERGUSON, M.D. Consultant
KENNETH W. JOHNSTON, M.D. Consultant
JOANNE LINDENFELD, M.D. Consultant
NORMAN S. KATO, M.D. Consultant
MITCHELL W. KRUCOFF, M.D. Member
MICHAEL C. MORTON Industry Rep.
LINDA A. MOTTLE, M.S.M.R.N.,CCRP Consumer Rep.
GARY G. NICHOLAS, M.D. Consultant
SHARON-LISE T. NORMAND, Ph.D. Member
JOHN C. SOMBERG, M.D. Consultant
CLYDE YANCY, M.D. Consultant
JUDAH Z. WEINBERGER, M.D., Ph.D. Consultant
CHRISTOPHER J. WHITE, M.D. Member
GERETTA WOOD Exec. Secretary
FDA REPRESENTATIVES:
BRAM ZUCKERMAN, M.D.
DOROTHY ABEL
BINITA ASHAR, M.D., MBA
DAVID BUCKLES, Ph.D.
ANDREW FARB, M.D.
GARY L. KAMER
MEGAN MOYNAHAN
SPONSOR REPRESENTATIVES:
MICHEL S. MAKAROUN, M.D., F.A.C.S.
R. SCOTT MITCHELL, M.D., F.A.C.S.
MICHAEL C. NILSON
AGENDA ITEM PAGE
WELCOME/OPENING REMARKS:
William Maisel.................................. 5
CONFLICT OF INTEREST:
Geretta Wood.................................... 5
INTRODUCTIONS:.................................. 8
VOTING STATUS STATEMENT:....................... 10
CRITICAL PATH INITIATIVE:
Binita Ashar................................... 11
GUIDANT COMPANION UPDATE and
PHILIPS MEDICAL HEARTSTART HOME OVER-THE-COUNTER
AED:
Megan Moynahan.............................. 23/26
LIFELINE REGISTRY:
Rodney White................................... 31
SOCIETY FOR VASCULAR SURGERY:
Greg Sicard.................................... 38
AUDIENCE MEMBER COMMENT:
Bill Tinker.................................... 40
HARVARD MEDICAL SCHOOL:
Richard Cambria................................ 43
LOYOLA UNIVERSITY:
Michael Tuchek................................. 47
HARBORVIEW MEDICAL CENTER:
Riyad Karmy-Jones.............................. 51
QUESTIONS:..................................... 53
SPONSOR PRESENTATION:
GORE TAG THORACIC ENDOPROSTHESIS:
Mike Nilson.................................... 57
ETIOLOGY AND CURRENT THERAPY:
Scott Mitchell................................. 59
TAG DEVICE, HISTORY AND DESIGN:
Mike Nilson.................................... 65
CLINICAL TRIAL PROGRAM RESULTS/DATA:
Michel Makaroun................................ 73
CLOSING REMARKS:
Scott Mitchell................................. 99
Mike Nilson................................... 102
Q&A SESSION:.................................. 103
FDA PRESENTATION:
Dorothy Abel.................................. 121
Andrew Farb................................... 133
Gary Kamer.................................... 146
AGENDA CONTINUED PAGE
PANEL QUESTIONS:.............................. 156
PANEL REVIEWS AND SPONSOR QUESTIONS:
Henry Edmunds............................. 182/303
Clyde Yancy............................... 183/299
Judah Weinberger.............................. 194
Ken Johnston.................................. 198
Sharon-Lise Normand........................... 212
Norm Kato..................................... 232
John Somberg.................................. 239
Charles Bridges............................... 245
Gary Nicholas................................. 254
Mitch Krucoff................................. 260
Joanne Lindenfeld............................. 281
Tom Ferguson.................................. 294
William Maisel................................ 301
QUESTIONS TO PANEL:
Question 1 - Assurance of Safety.............. 307
Question 2 - Assurance of Effectiveness....... 313
Question 3 - Control Group Differences........ 320
Question 4 - Indication For Use............... 320
Question 5 - Additional Warnings.............. 326
Question 6 - Labeling Comments................ 328
Question 7 - Physician Training Plan.......... 330
Question 8 - Post-Approval Study/Follow-Up.... 336
Question 9 - Post-Approval Study Plan Adequacy 345
PUBLIC HEARING SESSION:
Riyad Karmy-Jones............................. 346
Gregorio Sicard............................... 350
Rodney White.................................. 352
J. Michael Tuchek............................. 353
ADDITIONAL FDA COMMENTS:
Dave Buckles.................................. 356
MOTION TO APPROVE WITH CONDITIONS:............ 363
CONDITION 1 - POST-APPROVAL STUDY............. 363
VOTE TO APPROVE CONDITION 1:.................. 368
CONDITION 2 - APPROPRIATE TRAINING:........... 371
VOTE TO APPROVE CONDITION 2:.................. 372
CONDITION 3 - INCLUSION/EXCLUSION CRITERIA:... 372
VOTE TO APPROVE CONDITION 3:.................. 373
VOTE TO APPROVE WITH CONDITIONS:.............. 375
ADJOURN:
William Maisel................................ 384
P-R-O-C-E-E-D-I-N-G-S
9:01
a.m.
ACTING
CHAIR MAISEL: Good morning. I would like to call to order this meeting
of the Circulatory System Devices Panel.
Today's topic is discussion of a pre-market application for the W.L.
Gore and Associates GORE TAG Thoracic Endoprosthesis, P040043. I would like to ask Geretta Wood to read the
Conflict of Interest statement.
EXEC.
SEC. WOOD: The following announcement
addresses Conflict of Interest issues associated with this meeting and is made
a part of the record to prevent even the appearance of an impropriety. To determine if any conflict existed, the
Agency reviewed the submitted agenda and all financial interest reported by the
Committee participants. The Conflict of
Interest statutes prohibit special Government employees from participating in
matters that could affect their or their employer's financial interest.
However,
the Agency has determined that participation of certain members and
consultants, the need for whose services outweighs the potential conflict of
interest involved is in the best interest of the Government. Therefore, waivers have been granted for
Drs. Charles Bridges, L. Henry Edmunds, Thomas Ferguson, William Maisel, Clyde
Yancy and a waiver was previously granted for Dr. Judah Weinberger for their
interest in firms that could potentially be affected by the Panel's
recommendation.
The
waivers for Drs. Bridges, Edmunds, Ferguson and Maisel involve a grant to their
institution for the sponsor's study.
The panelists had no knowledge of the funding and had no involvement in
the generation or analysis. Dr.
Ferguson's waiver also involves his affiliation with a nonprofit organization
that is the recipient of an unrelated educational grant from a competitor.
Funding
to the organization is between $100,001 and $300,000 per year. Dr. Yancy's waiver involves unrelated
consulting services with a competitor for which his fees have not yet been
determined. Dr. Weinberger's waiver
includes a stockholding in a competitor in which the value is between $50,001
and $100,000. The waivers allow these
individuals to participate fully in today's deliberations.
Copies
of these waivers may be obtained from the Agency's Freedom of Information
Office, Room 112A-15 of the Parklawn Building.
We would like to note for the record that the Agency took into
consideration other matters involving Drs. Mitchell Krucoff, Joanne Lindenfeld
and Clyde Yancy. These panelists
reported past or current interest involving firms at issue, but in matters that
are not related to today's agenda. The
Agency has determined therefore that these individuals may participate fully in
the Panel's deliberations.
The
Agency also would like to note that in the event that the discussion involves
any other products or firms not already on the agenda for which an FDA
participant has a financial interest, the participant should excuse him or
herself from such involvement and the exclusion will be noted for the record. With respect to all other participants, we
ask in the interest of fairness that all persons making statements or
presentations disclose any current or previous financial involvement with any
firm whose products they may wish to comment on.
ACTING
CHAIR MAISEL: Thank you, Geretta. My name is Dr. William Maisel. I'm a cardiologist at Brigham and Women's
Hospital and I would like to invite the Panel Members to introduce themselves
starting on my left with Dr. Zuckerman.
DR.
ZUCKERMAN: Bram Zuckerman, Director,
FDA Division of Cardiovascular Devices.
DR.
FERGUSON: Tom Ferguson, Professor
Emeritus, Washington University, Saint Louis.
DR.
LINDENFELD: Joanne Lindenfeld. I'm a Cardiologist at the University of
Colorado.
DR.
KRUCOFF: Mitch Krucoff. I'm a Cardiologist at Duke University
Medical Center and the Director of the Cardiovascular Devices Unit at the Duke
Clinical Research Institute.
DR.
NICHOLAS: Gary Nicholas, a vascular
surgeon, Professor of Surgery, Penn State University, Lehigh Valley Hospital.
DR.
BRIDGES: Charles Bridges,
Cardiothoracic Surgeon, University of Pennsylvania.
EXEC.
SEC. WOOD: Geretta Wood, Executive
Secretary for the Advisory Panel.
DR.
SOMBERG: I'm John Somberg. I'm a Professor of Medicine and Pharmacology
at Rush University in Chicago, Illinois.
DR.
KATO: Norman Kato, Cardiothoracic
Surgery, private practice, Encino, California.
DR.
NORMAND: Sharon-Lise Norman, Professor
of Health Care Policy and Biostatistics at Harvard Medical School and Harvard
School of Public Health.
DR.
JOHNSTON: Wayne Johnston, Vascular
Surgeon, Professor of Surgery at University of Toronto.
DR.
WEINBERGER: Judah Weinberger,
Interventional Cardiologist at Columbia University.
MR.
MORTON: Michael Morton. I'm the industry representative. I'm employed by Medtronics.
MS.
MOTTLE: Linda Mottle, Director and
Faculty of the Clinical Research Program at Gateway Community College.
ACTING
CHAIR MAISEL: Thank you. Geretta, if you would read the voting status
statement, please?
EXEC.
SEC. WOOD: Pursuant to the authority
granted under the Medical Devices Advisory Committee Charter dated October 27,
1990 and as amended August 18, 1999, I appoint the following individuals as
voting members of the Circulatory System Devices Panel for this meeting on
January 13, 2005: Charles R. Bridges,
M.D., L. Henry Edmunds, Jr., M.D., Thomas B. Ferguson, M.D., Kenneth W.
Johnston, M.D., Joanne Lindenfeld, M.D., Norman S. Kato, M.D., Gary G. Nicholas,
M.D., John C. Somberg, M.D., Clyde Yancy, M.D., Judah Z. Weinberger, M.D.,
Ph.D.
For
the record, these individuals are special Government employees and are
consultants to this Panel under the Medical Devices Advisory Committee. They have undergone the customary Conflict
of Interest review and have reviewed the material to be considered at this
meeting. The Agency would also like to
note that Dr. William Maisel has consented to serve as Chair for the duration
of this meeting. This is signed by
Daniel G. Schultz, M.D., Director, Center for Devices and Radiological Health
and signed January 11, 2005.
ACTING
CHAIR MAISEL: Thank you. Before we begin this morning's discussion on
this application, the FDA has two brief presentations. I would like to invite Dr. Binita Ashar,
Acting Clinical Director, of the CDRH to talk about the Critical Path
Initiative.
DR.
ASHAR: Great. Thank you and good morning.
I appreciate this opportunity to discuss with you the Agency's Critical
Path Initiative from the CDRH perspective.
Basically, what I'm going to do this morning is I'm going to identify
some of the challenges in medical product development. Then I will define for you what the Critical
Path Initiative is and then describe what our future efforts are for bringing
this initiative further.
Basically,
the present state of affairs is that there is a scientific challenge that we
have a number of disease processes, Alzheimer's, AIDS, cardiovascular diseases
that need better treatments and we not only need better treatments, but we need
better preventative therapies. At the
same time, we're faced with a societal challenge and that is the urgency for
timely development of treatments for these diseases. And not only do we need these treatments to be timely, but we
also need these treatments to be affordable.
In
the present state of affairs, there is great optimism based on new biomedical
discovery. We have sequenced the human
genome. We have new genomic and
proteomic technologies. There are
advances in medical imaging. We have
nanotechnology advances that potentially can offer the right treatment to the
right patient in the right location with far fewer side effects than ever
before. And at the same time, we have
been investing to produce these basic biomedical advances.
There
has been an increase in NIH funding of double over the past five years. And pharmaceutical research and development
has also increased at the same rate.
Overall, our society has provided major investments in basic biomedical
technology research and this is a graphical representation demonstrating the
increase in research spending, both from the pharmaceutical RND side as well as
in the NIH budget.
Now,
you would expect that this acceleration in development, this would have
translated into increased medical product development. However, from the drugs and biologic side,
in fact, there has been a decline in the number of FDA new products that have
been submitted. Now, this necessarily
hasn't been the case for medical devices, but the fact of the matter is we
could be doing better. And this is a
graphical representation demonstrating the 10-year trend in pre-market device
application showing the number of original PMAs that have been submitted.
Now,
at the same time, we are noticing that, at least on the drug and biologic side,
the cost of bringing a new drug to market is estimated to be about $1.7
billion, and the reason for this is largely because there is a high failure
rate of new drug candidates late in the clinical development process. Now, what is the cause of this problem? Well, some of these new technologies aren't
at their full potential.
And
what has been occurring or what we have noticed to occur is that industries
have been focusing on easier targets and because of various business
arrangements have focused on potentially the cash cows and not necessarily
treatments that might affect smaller populations. They have found that the development process has become
uncertain. Some of the additional
challenges that I have mentioned already are that there is a failure late in
the clinical development process, at least for drugs and biologics.
Now,
I want to mention that the Critical Path is different for devices. Device development is different because of
the device regulation process. We have
a least burdensome provision of FDAMA, which is different than drugs and
biologics. We are committed to finding
a least burdensome path to market. We
have quality systems and design controls that are not prescriptive, but are
focused on what the end result is and has the product, indeed, met the
expectations that we have requested.
The
innovation process is different for devices.
The small molecule issue is biocompatibility, not necessarily
biometabolism. The process is an
iterative process whereby sometimes during the clinical development phase,
there might be minor changes in the device.
There is a user learning curve that we face with the use of medical
devices and performance and durability are also engineering issues. Different pharmaceuticals in the device
industry is represented by small manufacturers that may not have the resources
to put forth all of the time and effort and expenditures that they might need
to to bring a product forward.
Other
additional causative factors that have been shown as a hurdle in the medical
product development is that some of the basic science investment and progress
has surpassed what we are able to actually translate into new medical
products. Essentially, we are using the
evaluation tools and infrastructure of the last century to bring forth new
medical products of this century. We
are doing randomized controlled clinical trials like we have always done them.
We
are not necessarily using our cumulative knowledge of the society to overcome
some of the development hurdles, so that we can bring medical products to
market faster without compromising our safety and effectiveness
evaluations. And this has resulted in a
bottleneck at the Critical Path for delivering new medical products to
patients.
So
the central Critical Path thesis is that there has been a great societal
investment in research and development to improve medical product
development. However, there has not
been an investment in the tools necessary to translate this basic biomedical
research into new medical products. So
what do I mean by this? Well, tools
that might be computer simulation tools or registries or new surrogate markers
that have been validated or biomarkers that might be able to identify patient
populations that might be most amenable to these treatments that would
potentially cut down the size of these various clinical trials.
There
has been a great investment in the basic research, but not investment and
attention to the tools to bring this research to translate into medical
products. And some of the problem is
that academia is not adequately funded to perform the scientific investigations
to develop new tools. This has
generally not been conceptualized up until this point, at least, as being FDA's
role. And any efforts to develop
valuative tools in the private sector are proprietary and they are, therefore,
not generalizable and available for use for the population at large.
So
the FDA's Critical Path Initiative is an attempt to bring attention and focus
to the need for targeted scientific efforts to modernize the techniques and
methods used to evaluate the safety, effectiveness and quality of medical
products as they move from product selection to design and mass
manufacture. And this diagram demonstrates
how Critical Path research differs from what is generally considered
translational research.
You
notice that basic scientific research is the type of research that is largely
conducted by academic organizations and by our sister agencies like NIH. NIH is also quite interested in translational
research of bringing this new basic research into the clinical arena. However, Critical Path research is really
FDA's arena where this translational research is looked at from the perspective
of mass manufacture and mass marketing.
Can
these clinical trial results formed in a small population translate into the
generalized patient populations that we are approving a device for? And in evaluating any sort of medical
products, you look at three dimensions of Critical Path. You look at safety. Can this device adequately perform in a safe
manner? Can this device demonstrate
efficacy in the population? And can
this device be mass produced to the point that it is generalizable to not only
the premiere centers in the United States, but also to all of the community
hospitals? And can these results that
we see in these early clinical trials be ones that can be replicated over and over
again in smaller areas?
And
so if we had tools that might be able to help us in our assessment in deciding
whether a product is safe or effective or can be industrialized, wouldn't it be
great to be able to bring these products to development faster without
compromising our safety and effectiveness evaluation? So basically, the Critical Path science basis is to be able to
understand what types of tools we might be able to invest in.
And
FDA potentially could take an organizational role in bringing groups together,
consumer groups, patient groups, academia and industry groups to develop some
of these scientific tools that might be then available in the public arena for
use by all industry groups. And this is
something that NIH and academia have generally not focused on and Critical Path
is intended to be something that is supplementing what we already have learned
in our translational research basis.
So
the work ahead, basically, this is for scientific improvement. It is not to be confused with regulatory
evolution or streamlining or making the paper pushing faster or easier. It is, essentially, using the science that
we already know to develop tools that help in our evaluations. The regulatory process is a related effort
and can assist with this, but it is not the focus of this initiative.
So
what have we done so far with Critical Path?
Well, basically, there was a Federal Register docket open
describing a Critical Path that was open through the summer and we received a
number of responses from industry groups, patient groups, professional
organizations, individual industries.
This initiative was also presented to the FDA Advisory Board, the
Science Board, to receive some of their feedback. And we have had individual meetings with various scientists,
companies, patient groups and many, many others just to get the word out, just
to get feedback out.
This
has also been presented at the FDA Science Forum and at many speeches and panel
presentations. And, basically, we have
received overwhelming support. In fact,
they have asked FDA to embark on doing things that is well outside of FDA's
resources. And we have heard this
really from all of our patient groups and all of our industry groups.
Submitters
actually, again, ask for us to work on a number of things intent actually
outside of some of our range. And some
of the things that they suggested is, you know, streamlining clinical trials if
we had better biomarkers, if we had a process by which we knew that we could
validate a surrogate endpoint and promote effective product development. What they wanted repeatedly was FDA feedback
on particular endpoints and particular surrogate endpoints. And how we can harmonize internationally so
that we could better do this so that a clinical trial in one area of the world
would be applicable to the United States, how we could focus on cancer trials,
combination products.
Some
industry groups actually have commented on the use of proprietary data. You know, very tentatively, they mentioned
that perhaps FDA might find a way to use some of this information with the
consent of all involved parties to further medical product development. And so, basically, the bottom line is this
is an initiative that is intended to use science to integrate into the
regulatory process, so that we can make our safety and effectiveness
evaluations faster and more cost effectively.
This
is not just an FDA effort. We can't do
this alone. We need to work with our
stakeholders to make this a reality.
And we need to focus on particular scientific areas that first and
perhaps expand at a later date. So the
next step on a Critical Path is from the docket we received a number of
comments. We are identifying all of the
possible proposals and prioritizing various opportunities for developing
valuative tools. We will be putting
forth a national Critical Path opportunities list that reflects all of the
comments that we have received.
We
need to find a mechanism by which we can continue to obtain such feedback and
update this list so that not only FDA, but other interested parties, might
embark on Critical Path research. Thank
you very much for your attention.
ACTING
CHAIR MAISEL: Thank you very much. Next, I would like to invite Megan Moynahan,
who is the Branch Chief for Pacing, Defibrillator and Leads, to update the
Panel on some recent decisions.
DR.
MOYNAHAN: Good morning. Thank you very much. I would like to take a few minutes this
morning to update you on the Panel meeting that occurred in July this past year
in which the panelists discussed the Guidant Companion application, a labeling
review, and the Philips Medical HeartStart Home Over-the-Counter AED.
Beginning
with companion, the FDA raised a number of concerns to the Panel and I'm not
going to represent them all here, but the primary one related to whether the
Panel felt that the data were sufficient to support an expanded patient
population for the Guidant CRT-D Device to include patients who did not have to
have a requirement for an ICD. There
was a lot of discussion about the change in definition of hospitalization and
the FDA has some concern about how to interpret both the primary and secondary
endpoints based on that.
We
asked the Panel to comment on how the indication should be worded and we asked
for some broad labeling recommendations on that application. The Panel recommended that the data supports
expanding the indicated patient population, but they had some concerns about
how that would be worded in the indication statement. They specifically asked us to avoid using the term
"all-cause hospitalization" in the indication statement. And they wanted a special separate section
of the labeling to call out the benefit with respect to the primary endpoint.
The
approved indications appears as follows, and as you see, it only indicates the
intended patient population, so it is indicated for patients with moderate to
severe heart failure who remain symptomatic despite stable optimal heart
failure drug therapy and have an LVEF of less than 35 percent and a QRS no
greater than 120. And now, there is a
new clinical outcome section that appears in the labeling just after the
indication statement in which we go into more detail as to the clinical benefit
to patients.
Here
is where we identify the reduction in risk of all-cause mortality or first
hospitalization, is how it is presented, and then we go onto define how
hospitalization was used in that trial, including noting that the
hospitalizations did not include the device implant attempt or any
reattempts. We also identified the
reduction and risk of all-cause mortality and we mentioned the reduction of
heart failure symptoms.
The
Panel also made a number of other recommendations with respect to the labeling
and, in particular, they were interested to see how we were going to be
presenting hospitalizations. While they
agreed that the representation of the primary endpoint should not include the
index or implant hospitalization, they felt that it would be important to
present in clinically meaningful information to physicians and patients that
describe hospitalizations in general.
And
so this is an example of the approved labeling that we've worked with the
company to develop. This is the
original Kaplan-Meier curve for the primary endpoint of all-cause mortality or
first heart failure hospitalization and this is the same as what you would see
in the published literature. But the
labeling also represents a number of hospitalizations per patient year and that
was done to account for the difference in follow-up for the two different
groups.
It
presents this information comparing the OPT or the control group to the CRT-D group
and it also gives you an idea of the relative contribution of the implant
hospitalization in both cases. There is
also a graph in the labeling that depicts the number of hospitalization days
per patient year, again distinguishing between the OPT group and the CRT-D
group and also indicating a relative contribution of the implant
hospitalizations that occurred in both groups.
And
finally, there is a representation of the number of heart failure
hospitalization days per patient year comparing the OPT group to the CRT-D
group. Based on their Panel
recommendations, the FDA approved the companion submission on September 14,
2004.
Now,
moving on to the Philips Medical Over-the-Counter AED, the FDA raised a number
of concerns to the Panel that day including asking whether the data was
sufficient to support over-the-counter availability of the device and, in
particular, we wanted them to comment on the adequacy of the user testing and
whether the sponsor had appropriately integrated CPR prompts and notifications
to dial 911 or to notify the Emergency Medical Services.
We
asked the Panel to comment on whether the data were sufficient to support
over-the-counter availability of the pediatric pads. We asked broadly for labeling recommendations and to comment on
the sponsor's methods for tracking devices in the event of a recall or adverse
event reporting and whether they believe that a post-market study would be
required. Because this was a 510(k)
application, there was no vote.
However, the Panel was felt to be generally in favor of over-the-counter
availability of the device. They felt
that the usability testing was adequate and that the voice prompts for CPR and
the visual prompts for calling 911 were felt to be adequate.
There
was no consensus, however, on whether the pediatric pads should be available
over-the-counter. There were quite a
number of specific labeling recommendations that were given to us and the Panel
recommended a post-market study, but asked FDA to review the tracking and
adverse event reporting methods. FDA
ultimately concurred with the Panel that there was sufficient usability testing
and we did not require additional testing on the part of the sponsor. We felt that the prompts for CPR were
appropriate and with minor modifications to the 911 reminders we felt that they
were appropriate as well.
Importantly,
the pediatric pads were not included in our over-the-counter decision and they
still remain available as a prescription accessory. And that was done for a number of reasons. We felt that ultimately this would simplify
a very complex purchasing decision by not offering too many options or
accessory products to the user. We felt
that it sent an important message that underscores that sudden cardiac arrest
is an adult public health concern, one that's not shared equally by the
pediatric population.
We
feel that this decision ensures safe and effective use on both adults and
children. And we felt that this was not
going to impact availability too detrimentally of families who have higher risk
children, because those families should be well-integrated into the medical
system and would easily be able to get a prescription for the products.
We
made substantial labeling modifications based on Panel recommendations. I'm not going to go through all of them, but
I'll give you one example. The Panel
felt that the outer box should be designed to help customers make an informed
purchase decision and these are some of the things that appear now on the
outside of the box and also appear on websites that are offering this product
for over-the-counter sale.
For
example, it mentions that you should speak to your doctor and that a
defibrillator does not take the place of seeking medical help, that you can't
use the device on yourself, that users may need to perform CPR, that responding
to cardiac arrest may require you to kneel, that voice instructions and
materials are in English and that the HeartStart provides audible and visible
indicators for maintenance.
FDA's
clearance decision included acceptance of the sponsor's methods for post-market
tracking and adverse event reporting and we're continuing to work with the
sponsor on developing the Post-Market Study Plan. Ultimately, FDA cleared this product for over-the-counter use on
September 16, 2004. Thank you very
much.
ACTING
CHAIR MAISEL: Thank you, Megan, for
those updates. At this point, we will
begin the open public session of this morning's meeting, both the Food and Drug
Administration and the public believe in a transparent process for information
gathering and decision making to ensure such transparency at the open public
hearing session of the Advisory Committee meeting, FDA believes that it is
important to understand the context of an individual's presentation.
For
this reason, FDA encourages you, the open public hearing speaker, at the
beginning of your written or oral statement to advise the Committee of any
financial relationship that you may have with the sponsor, its product, and if
known, its direct competitors. For
example, this financial information may include the sponsor's payment of your
travel, lodging or other expenses in connection with your attendance at this
meeting.
Likewise,
FDA encourages you at the beginning of your statement to advise the Committee
if you do not have any such financial relationships. If you choose not to address this issue of financial
relationships at the beginning of your statement, it will not preclude you from
speaking. At this point, I would like
to invite Dr. Rodney White to approach and address the Panel.
DR.
WHITE: Thank you very much. It's a pleasure to be here today. I'm representing the Society for Vascular
Surgery and a project that you have heard about before, I think, that we would
like to update you on. The Lifeline
Registry, which now is the SVS/American Vascular Association Outcomes Registry
has been an effort that we have updated Panels on serially related endoluminal
grafts.
At
the beginning of this, I would like to tell you that my Conflicts of Interest are
that I have no commercial interest in Gore.
I'm not a Gore investigator. I
am here representing the Society for Vascular Surgery as the Secretary and
Chairman of the SVS/AVA Lifeline Registry Committee. I'm an academic surgeon.
I make my living treating these kinds of patients and get promoted based
on publishing papers, so I think my major conflict is I make a living doing
this sort of stuff.
The
Lifeline Registry was established in 1997 to look prospectively at
post-approval of abdominal aortic aneurysms.
The SVS has now recently, in association with the American Vascular
Association, an expansion of our nonprofit foundation efforts, extended the SVS
capability to look at outcomes analysis, not only to the endoluminal grafts,
but to the technologies we're talking about today, thoracic grafts or in a
concurrent effort to carotid stents and endarterectomy.
A
unique aspect we offer is that we can look at both of these technologies
concurrently and in that regard, we would like to emphasize from the beginning
that the SVS is going to make a specific effort to make available operative
data related to these technologies, so as we move into these other areas, it
will be relevant.
Registry
is unique in that the initial attempt was to do something that hadn't been done
successfully previously and that was to look prospectively to establish a
registry that would take scientific data, put it together over time and
actually look at a number of stakeholders involved in this, including the
societies and clinicians, the foundation that I mentioned, federal agencies,
and we have been very fortunate to have both FDA and CMS active in these
efforts with their input.
An
industrial advisory committee made of, in this case, the following companies
which have supported that effort, I will emphasize that of the group today W.L.
Gore was a founding member of the registry, has been very proactive in
supporting this effort and that this has been an important part in how we
progress. The registry goals were to
evaluate long-term and prospectively endoluminal graft function.
Because
of the requirement for post-market surveillance, I think this is a topic that
will come up later, we were able to establish with a central registry committee
working beneath the foundation and again with the ex officio input of the FDA,
NIH, CMS and this industrial advisory committee and our data center, New
England Research Institute, a way to be able to collect this data, put it
together and report it.
The
funding mechanisms are by the foundation itself and industrial partners feeding
this data and collecting it. The
registry then initially was to look at the post-market IDE data, collect that
and look at it over the five-year surveillance interval that was
available. Now, if you think about
that, that makes it a very high compliance audited data set. There are then two parts to this registry
I'll tell you about briefly, because we've got now six-year results to look at,
was to take this five- year PMA model, look at these patients over time and
because of the post-approval market, we're able to look at the requirement of
the Agency to have the manufacturers submit this data and work out a
collaborative effort to collect this.
The
long-term results of the FDA devices have then been evaluated and in a
collective fashion you will see. Now,
these are just some numbers to give you an idea of how these can be powered
over time, but with four approved devices and some commercial site entries, you
will see we're now nearly at 3,000 patients.
A very important part of this is we also have a concurrent surgical
control group of patients that can be compared for outcomes analysis. And in the kinds of considerations we're
doing today, these are particularly important.
Primary
and secondary endpoints that I won't list in detail were looked at and were
able to, in almost all cases now, start to look at very important outcome
issues and patient selection parameters and have reached statistical
significance in many of these related to the outcome comparing endoluminal
grafts to the conventional stent graft technologies. The same for hospital parameters, ICU stays, things that are
routinely looked at and again we can compare these two groups.
What
we have come up with then, now, these are six-year curves, are comparisons of
morbidity, mortality, aneurysm-related mortality, freedom from rupture, gender
analysis, this has been highlighted in other examples, freedom from surgical
conversion. And again, just to
highlight this very briefly, there is a data set that was presented at the SVS
this year in a publication submitted to the Journal of Vascular Surgery
that will summarize these six-year data outcomes and forward. But in general, it gives us a very good
standard to be able to apply this to and have a surgical cohort group.