[House Hearing, 108 Congress]
[From the U.S. Government Publishing Office]
NIH: RE-ENGINEERING CLINICAL RESEARCH
=======================================================================
HEARING
before the
SUBCOMMITTEE ON HEALTH
of the
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED EIGHTH CONGRESS
SECOND SESSION
__________
MARCH 25, 2004
__________
Serial No. 108-69
__________
Printed for the use of the Committee on Energy and Commerce
Available via the World Wide Web: http://www.access.gpo.gov/congress/
house
__________
93-301 U.S. GOVERNMENT PRINTING OFFICE
WASHINGTON : 2003
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COMMITTEE ON ENERGY AND COMMERCE
JOE BARTON, Texas, Chairman
W.J. ``BILLY'' TAUZIN, Louisiana JOHN D. DINGELL, Michigan
RALPH M. HALL, Texas Ranking Member
MICHAEL BILIRAKIS, Florida HENRY A. WAXMAN, California
FRED UPTON, Michigan EDWARD J. MARKEY, Massachusetts
CLIFF STEARNS, Florida RICK BOUCHER, Virginia
PAUL E. GILLMOR, Ohio EDOLPHUS TOWNS, New York
JAMES C. GREENWOOD, Pennsylvania FRANK PALLONE, Jr., New Jersey
CHRISTOPHER COX, California SHERROD BROWN, Ohio
NATHAN DEAL, Georgia BART GORDON, Tennessee
RICHARD BURR, North Carolina PETER DEUTSCH, Florida
ED WHITFIELD, Kentucky BOBBY L. RUSH, Illinois
CHARLIE NORWOOD, Georgia ANNA G. ESHOO, California
BARBARA CUBIN, Wyoming BART STUPAK, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
HEATHER WILSON, New Mexico ALBERT R. WYNN, Maryland
JOHN B. SHADEGG, Arizona GENE GREEN, Texas
CHARLES W. ``CHIP'' PICKERING, KAREN McCARTHY, Missouri
Mississippi, Vice Chairman TED STRICKLAND, Ohio
VITO FOSSELLA, New York DIANA DeGETTE, Colorado
STEVE BUYER, Indiana LOIS CAPPS, California
GEORGE RADANOVICH, California MICHAEL F. DOYLE, Pennsylvania
CHARLES F. BASS, New Hampshire CHRISTOPHER JOHN, Louisiana
JOSEPH R. PITTS, Pennsylvania TOM ALLEN, Maine
MARY BONO, California JIM DAVIS, Florida
GREG WALDEN, Oregon JANICE D. SCHAKOWSKY, Illinois
LEE TERRY, Nebraska HILDA L. SOLIS, California
MIKE FERGUSON, New Jersey CHARLES A. GONZALEZ, Texas
MIKE ROGERS, Michigan
DARRELL E. ISSA, California
C.L. ``BUTCH'' OTTER, Idaho
JOHN SULLIVAN, Oklahoma
Bud Albright, Staff Director
James D. Barnette, General Counsel
Reid P.F. Stuntz, Minority Staff Director and Chief Counsel
______
Subcommittee on Health
MICHAEL BILIRAKIS, Florida, Chairman
RALPH M. HALL, Texas SHERROD BROWN, Ohio
FRED UPTON, Michigan Ranking Member
JAMES C. GREENWOOD, Pennsylvania HENRY A. WAXMAN, California
NATHAN DEAL, Georgia EDOLPHUS TOWNS, New York
RICHARD BURR, North Carolina FRANK PALLONE, Jr., New Jersey
ED WHITFIELD, Kentucky BART GORDON, Tennessee
CHARLIE NORWOOD, Georgia ANNA G. ESHOO, California
Vice Chairman BART STUPAK, Michigan
BARBARA CUBIN, Wyoming ELIOT L. ENGEL, New York
JOHN SHIMKUS, Illinois GENE GREEN, Texas
HEATHER WILSON, New Mexico TED STRICKLAND, Ohio
JOHN B. SHADEGG, Arizona DIANA DeGETTE, Colorado
CHARLES W. ``CHIP'' PICKERING, LOIS CAPPS, California
Mississippi CHRIS JOHN, Louisiana
STEVE BUYER, Indiana BOBBY L. RUSH, Illinois
JOSEPH R. PITTS, Pennsylvania JOHN D. DINGELL, Michigan,
MIKE FERGUSON, New Jersey (Ex Officio)
MIKE ROGERS, Michigan
JOE BARTON, Texas,
(Ex Officio)
(ii)
?
C O N T E N T S
__________
Page
Testimony of:
Barron, Hal, Chief Medical Officer, Genentech................ 28
Beall, Robert J., President and CEO, Cystic Fibrosis
Foundation................................................. 34
Braunwald, Eugene, Harvard Medical School, on behalf of the
Association of American Medical Colleges................... 41
Zerhouni, Elias A., Director, National Institutes of Health.. 7
Additional material submitted for the record:
Barron, Hal, Chief Medical Officer, Genentech, response for
the record................................................. 50
Beall, Robert J., President and CEO, Cystic Fibrosis
Foundation, response for the record........................ 51
Braunwald, Eugene, Harvard Medical School, on behalf of the
Association of American Medical Colleges, response for the
record..................................................... 52
Smolonsky, Marc, Associate Director for Legislative Policy
and Analysis, National Institutes of Health, response for
the record................................................. 52
(iii)
NIH: RE-ENGINEERING CLINICAL RESEARCH
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THURSDAY, MARCH 25, 2004
House of Representatives,
Committee on Energy and Commerce,
Subcommittee on Health,
Washington, DC.
The subcommittee met, pursuant to notice, at 10 a.m., in
room 2322, Rayburn House Office Building, Hon. Michael
Bilirakis (chairman) presiding.
Members present: Representatives Bilirakis, Upton,
Greenwood, Norwood, Wilson, Buyer, Pitts, Brown, Green,
DeGette, and Capps.
Staff present: Jeremy Allen, health policy coordinator;
Cheryl Jaeger, majority professional staff; Eugenia Edwards,
legislative clerk; John Ford, minority counsel; Jeff Donofrio,
minority staff assistant; and Kamilah Pickett, minority
congressional fellow.
Mr. Bilirakis. The hearing will come to order.
Good morning.
First, I would announce that we apply the sort of unwritten
new rules of the Committee to the point where someone waives
their opening statement, they would have as much as 8 minutes
to question, to inquiry of our witnesses. So, hopefully we
would all maybe go or bend that way rather than have our
witness like yesterday's hearing. We had a hearing yesterday
downstairs and we had one witness, Secretary Evans, Secretary
of Commerce. He sat around for almost 1\1/2\ hours while
members gave their opening statements. And that's sort of an
unfair thing to the person testifying.
But in any case, today's Health Subcommittee hearing is the
fifth that I've held or we've held over the past two
Congresses. It is part of an effort to examine a number of
issues related to the National Institutes of Health.
The NIH is an enormous agency with an appropriation in
fiscal year 2004 of approximately $27.68 billion. While NIH has
not been reauthorized in over 10 years, I firmly believe that
our investment in biomedical research--they have received their
funding by the way even though they have not been authorized. I
firmly believe that our investment in biomedical research
through NIH is probably one of the wisest uses of our limited
resources. However, it does remain incumbent upon us here in
Congress to ensure the taxpayer dollars are used in the most
effective manner possible. To that end, I've been very
impressed with the leadership of our current NIH Director Dr.
Alias Zerhouni. The leadership that he has shown in developing
the NIH Roadmap. I believe that this initiative will help NIH
refocus its priorities and improve its track record. I am glad
that Dr. Zerhouni was able to take time out of his very busy
schedule to join us this morning and to speak to 1 of the 3
primary components of the NIH Roadmap, which is the
reengineering of the clinical research enterprise.
Clinical research is a critical part of our efforts to
ensure the taxpayers research gets translated into new
therapies. We explored another major part of this effort last
year when we examined the technology transfer activities of the
NIH and how laws like the Bayh-Dole Act have helped research
from the bench to the bedside. I'm hopeful that the
subcommittee will learn more today about both clinical research
activities of the NIH and Dr. Zerhouni's vision for
reengineering the clinical enterprise.
I also want to take a moment to thank our second panel of
witnesses for appearing for the subcommittee. I think it's
important that this hearing also focuses on clinical research
activities that occur outside the realm of NIH and how we can
leverage these efforts and speed new medicines to patients. As
our panelists all know, new therapies for patients are more
often than not the result of very productive collaborations
between the Federal Government, the university-based research
community and the private sector. Our system allows each of
these entities to play a role that their best suited for, and I
hope members keep in this mind as a delve further into these
complicated topics today.
Again, I would thank Dr. Zerhouni and all our witnesses
that are joining us. Your perspectives will prove valuable as
the Health Subcommittee continues its review of NIH and
considers strategies to help this agency better meet it's
stated goals.
Thank you. And I now yield to the gentleman from Ohio for
an opening statement.
Mr. Brown. Thank you, Mr. Chairman, for holding today's
very important hearing. Dr. Zerhouni, thank you. We welcome
you. Thank you for being here. We greatly appreciate your
willingness to appear before us.
2002 NIH under Dr. Zerhouni's leadership and with
significant contributions from academia, industry, government
and public laid out its Roadmap as a tool to guide the agency's
medical research into the next decades. By addressing new
scientific challenges, identifying potential roadblocks, the
Roadmap outlines how NIH can continue to lead future scientific
discoveries rather than merely keep pace as science advances.
Today we are taking a closer look at the need for advance
clinical research, the scientific tool used to discover
mechanisms of disease prevention, diagnoses and treatment.
At the heart of Dr. Zerhouni's vision is the need to
improve the research partnership among patient communities,
community-based health care providers and academic researchers.
It also involves improving how clinical research information is
recorded developing new models of cooperation between NIH and
patient advocates in creating new strategies to re-energize our
clinical research workforce.
One question I have about this effort is how the NECTAR
system at NIH, which as I understand will use medical
informatics to coordinate clinical research initiative
intersects with private sector initiated clinical research. I'm
interested in how NIH will coordinate with the private sector
and what efforts are underway in the private sector to
modernize the collection of clinical trial data.
In the interest of time, I will submit this as a question
for your written response, Dr. Zerhouni.
I find myself asking the same question I have raised
before: Does NIH have the resources to maintain support for
existing research to advance new research and to implement the
critical components of the Roadmap? Congress allocated
significant budget increases, bipartisanally agreed to over the
last 5 years to support basic research in the biomedical
sciences at NIH. The research accomplishments achieved
throughout the country, in large part because of public sector
NIH investments, have been nothing short of remarkable. But as
a contemplate improving the smallest budget increase NIH has
received in decade, in large part because of budget
mismanagement by the White House and because of tax cuts that
the President continues to ask for, I wonder which NIH
priorities will be neglected due to inadequate funding. This
Congress today makes a decision on the budget. Do we keep doing
more tax cuts or do we fund health care and education and other
priorities.
What are we going to neglect? Will it be research on
Parkinson's or breast cancer or cystic fibrosis? Will the
research on a yet unknown treatment for HIV/AIDS or for
tuberculosis? Will the advances outlined in the NIH Roadmap
including advancing clinical research be put aside because of
budget mismanagement and lack of resources? Will we in the long
run, and this speaks directly to outsourcing in terms of lost
job internationally kind of outsourcing and our economy
overall, will we in the long run lose our competitive edge in
their field because we are not appropriating money we should
for NIH and CDC?
Dr. Zerhouni, your effort to maintain leadership in NIH is
outstanding. We very much appreciate that. The Roadmap is not
only comprehensive, but obtainable.
I hope the members of this Committee and the Congress will
make good in their promises to the many constituencies who seek
research dollars for the diseases that affect their families
and support a budget that will see the implementation of your
Roadmap.
I want to switch gears for a moment and raise an issue that
involves previous NIH investments. The patent AIDS drug Norvir
was discovered in the early 1990's by Abbott Labs under a
multi-year/multi-million dollar grant from NIH. Despite the
fact that NIH resources, tax dollars, contributed to the
development of Norvir, its price has always been higher,
significantly higher in the U.S. than any western European
country. And that was before in December Abbott Labs increased
the U.S. price by 400 percent.
Hundreds of organizations and physicians have asked the FTC
and HHS to step in and do something about this outrageous price
increase, which cost people's lives and they've requested a
public hearing on this issue, which I understand has been
denied. Again, in the interest of time I would like to discuss
this further during the question period.
I thank the Chairman.
Mr. Bilirakis. I thank the gentleman.
The remainder of opening statements will be limited to 3
minutes. Hopefully, many of you will defer to that 8 minute
period of questioning.
And without objection, all the opening statements of all
members of the panel will be made a part of the record,
including this one by Mr. Dingell.
The Chair now recognize Ms. Buyer for an opening statement.
All right. Let's see, Ms. Capps for an opening statement.
Ms. Capps. Thank you, Mr. Chairman. And thank you also,
Director Zerhouni for making yourself available to us today. We
appreciate your time and your willingness to share your
expertise.
And like, I would venture to say every member, I am a very
proud supporter of the NIH and the work you do there. And
National Institutes of Health are truly the crown jewels of the
Federal Government.
The United States has some of the best medical research in
the world, and much of the most advanced health care is
available to some here. These achievements are directly the
result of the amazing job that the National Institutes of
Health has done and the researches that Congress has provided
them. And I think of this often when we see a lot of bashing of
government. I always think to myself and say to as many people
as I can, if you ever question the use of public funds, look at
the National Institutes of Health.
The Congress has just completed the doubling of the NIH
budget. It shows you the bipartisan support for it. But I hope
that this does mean that we will think our job is done and
shortchange the NIH on funding now.
The budget being considered this week here in the House
asks for just minimal increases for the NIH, increased so small
that many in the scientific community are concerned that the
scientific gains from the doubling could be lost. This is an
incredibly poor way for us to handle previous investments. And
I believe the Congress needs to provide an adequate increase
for NIH funding so that the trajectory that has been
established with the doubling in the past can lead to the
fruition of many of the projects that are just underway. We
need to do this in order to take advantage of the investments
already made.
I also want to address an issue that has come up before
this Committee in the past and may come up again today. Some
members have raised questions about NIH grants on human
sexuality. While I do think it is important for Congress to
conduct oversight, it is also important for us to keep politics
from interfering with science.
Many of my colleagues advocate for the use of so called
sound science which seems more about advancing political goals,
not science. It's become quite a buzz word. But when the
world's best scientific institution makes a decision based on
truly sound science, some of our colleagues object to the
results.
NIH was set up to dramatically improve Americans' lives, in
fact lives around the world by increasing the quality and
amount of biomedical research conducted here. And I believe NIH
does this job admirably. And our job in Congress should not be
to micromanage scientists about how to conduct their research.
Our job should be to make sure that they have the support and
resources they need to advance medical science. We can and
should make sure that NIH is run effectively and that its
procedures meet quality standards. We should make sure that
advisory councils are established with broad, diverse bases,
but we should not engage in witch hunts to discourage research
into particular areas.
There is no question that some Americans engage in self-
destructive behavior. If we want to help them make lives
better, we cannot pretend that the behavior does not exist. We
must come to understand it and its effects on public health so
that it can be addressed more effectively. And that is what
scientific research is for, I believe.
Dr. Zerhouni, I was very impressed by a letter which I have
here that you wrote to Chairman Gregg on this very issue. It
was comprehensive and a very thoughtful response to criticism.
And I, for one, am glad to have you with your background in
professional science in a position to explain and to defend the
NIH. And I look forward to hearing from you today.
Mr. Bilirakis. The Chair thanks the gentlelady.
Mr. Upton, for an opening statement? Waive.
Ms. DeGette?
Ms. DeGette. Thank you, Mr. Chairman. And thank you also,
Dr. Zerhouni, for coming today.
I want to talk about two issues that I have been working
very hard on; stem cell research and human subject protection.
As many people here know I have been working with a bipartisan
group for 2 years now talking about a change in the President's
policy on stem cell research. After working with colleagues on
both sides of the aisle, we now believe that there is broad
bipartisan support for stem cell research expansion.
After more than 2 years, we know that the current policy on
stem cells does not work. Instead of the promised 78 embryonic
stem cell lines, today we have only 15 and there is general
agreement that these lines which have aged and may be
contaminated with mouse feeder cells may be unsuitable for
therapeutic use in humans.
Instead of the promised $100 million in funding for NIH
stem cell research, only $17 million was allocated in 2003.
Last year, Dr. Zerhouni, when you came before this Committee
you said that this policy is based on this President's moral
and ethical considerations. I am concerned that the policy is
not based on science, and I know members of this Committee are
also concerned.
This kind of research can cure diseases that affect
millions of Americans, and we should not be making policies
based on moral and ethical considerations. We should be making
them on scientific considerations. And I hope that the
Administration working with NIH will reexamine its stem cell
policy, because it is thwarting disease prevention into so many
important areas.
I also want to talk very briefly about human subject
protection. Today I was pleased to see Dr. Zerhouni in your
testimony you say the coordination of clinical research
policies is described. This is an essential effort that
Congress and all effected agencies must undertake.
I began working on this issue in 1999 when the FDA shut
down medical research programs at the University of Colorado
Health Sciences Center, which is in my District. The Health
Sciences Center had not adequately addressed its institutional
review board's inability to keep up with the overwhelming
volume of research projects. And Mr. Greenwood and I have been
working assiduously on this issue ever since.
I've introduced legislation right now which shores up
protection for research subjects and researchers. I think that
if we can haver this kind of harmonization, it will be very
effective. It is a part of human research protection. And I
look forward, Dr. Zerhouni, when you talk later in your
testimony to talk to you about that, because that's going to be
essential for protecting subjects of human research.
And with that, I yield back the balance of my time.
Mr. Bilirakis. Mr. Green for an opening statement.
Mr. Green. Thank you, Mr. Chairman. And I always appreciate
you holding these hearings on oversight, because I don't think
there's anything more important than what we do than looking at
the clinical research efforts of the National Institutes of
Health. There are few issues on which more Americans agree that
we need to boost scientific funding at National Institutes of
Health. The groundbreaking research done at NIH is the lifeline
of hope for countless individuals living with AIDS, cancer,
diabetes or many other illness. And I find it amazing every
time I have an opportunity to visit either MD Anderson in
Houston or Texas Children's Hospital or Baylor Medical School
to see some of the research projects being done and the hope
for the future. And a lot of that is with both local funds, but
also with NIH grants because of the strong support Congress has
committed resources to double the NIH's budget from 1999 to
1903 and most recently providing $27.7 billion for 1904, a
dramatic increase to accelerate our progress in many areas and
contributed a breakthrough such as mapping of human genome. Yet
the NIH has not been reorganized in any substantive way in over
120 years. And despite major advancements and changes in our
Nation's health needs, and a result it has grown to more than
27 institutes and centers. With this rapid growth and with the
many changes in the scientific research community there are
legitimate questions about NIH's structure and design help or
hinder our progress. That's why Congress mandated a report from
the Institute of Medicine at IOM to determine whether the
structure changes to the NIH was necessary.
IOM's report was released summer and indicate there are
indeed problems with NIH's current and organizational structure
that inhibit research and make several recommendations to
improve research activities at NIH. One of these, I think, is
today's hearing, the reengineering of clinical research
enterprises is of particular interest because clinical research
translate to scientific knowledge of the laboratory and to the
treatments and procedures to use with patients, just like I see
in Houston. If there are obstacles in our current structure
that slow the path of life saving research from reaching the
patient, then we must overcome them. And I know that the road
map includes a number of initiatives including harmonizing
clinical research requirements, integrating clinical research
networks, enhancing workforce training, improving data sharing
and many other provisions. And I noticed in your testimony you
talk about regional centers to make sure that that happens.
They are all interesting approaches and one I think will
help bridge that gap between the bench and the bedside. And I
look forward to hearing your testimony, Dr. Zerhouni. And,
again, welcome to our Committee.
Thank you, Mr. Chairman.
Mr. Bilirakis. The Chair thanks the gentleman.
Mr. Pitts for an opening statement? Waived. Good.
[Additional statement submitted for the record follows:]
Prepared Statement of Hon. Joe Barton, Chairman, Committee on Energy
and Commerce
Thank you, Chairman Bilirakis, for holding this hearing today.
Two weeks ago, the Committee heard testimony from Department of
Health and Human Services Secretary Tommy Thompson about HHS' fiscal
year 2005 budget request. At that hearing, I raised the point that many
health care programs are currently being funded in the appropriations
process without the requisite authorizations from this Committee. I
don't think this is a responsible practice. The National Institutes of
Health is America's and the world's premier medical research
institution. It is also one of the agencies at HHS with the greatest
number of expired authorizations.
For a variety of reasons, this Committee has not moved legislation
to modernize the National Institutes of Health. It's a shame. The NIH
is one of the best examples of a public-private partnership. Eighty-
five percent of the NIH research budget is dedicated to investigator
driven research. These research grants support more than 50,000
scientists affiliated with approximately 1,700 organizations including
universities, medical schools, hospitals, and small businesses in every
state of the nation. Study after study has shown that partnerships
between universities and the private sector are a powerful local
economic driver. The NIH research infrastructure helps to keep this
engine moving. More importantly, it breeds a research environment that
stresses and promotes innovation so that we can better understand
disease, and develop products that will treat and ultimately cure
disease.
There is no question that advancing medical research should be a
top priority of this Committee. NIH does many things well--that's why
Congress doubled the budget of the agency. But that doesn't mean that
NIH is perfect. For example, the more I learn about NIH, the more
concerned I am about the existing authority of the Director and his
ability to set priorities and manage the research portfolio of the
entire agency. I am also concerned that without greater transparency of
NIH program activities, it will be close to impossible for this agency
to be held accountable for the sizeable taxpayer investments we have
made.
NIH Director Dr. Zerhouni recently announced his strategic plan to
optimize NIH's increased budget and research portfolio. It is a
privilege to have Dr. Zerhouni with us today. Dr. Zerhouni has set an
ambitious agenda, placing considerable emphasis on the clinical
research component of NIH portfolio. Today's hearing will provide
Members an opportunity to focus specifically on the clinical research
activities of NIH.
I look forward to the testimony today.
Mr. Bilirakis. We will now go right to Dr. Zerhouni.
Sir, as you know, your written statement is already a part
of the record. And we would hope that you would sort of
supplement, compliment it, whatever the case might be.
We'll set the clock at 10 minutes and give you whatever
time you might need.
Please proceed.
STATEMENT OF ELIAS A. ZERHOUNI, DIRECTOR, NATIONAL INSTITUTES
OF HEALTH
Mr. Zerhouni. Thank you, Mr. Chairman, minority ranking
members and members of the committee. I'm really pleased to be
here and I thank you for your interest in our efforts in
clinical research, as well as your historical support for the
mission of the NIH over the years.
What I'd like to do is really give you the salient points
of why is it that we think at NIH that we need to reengineer
the clinical research enterprise.
I would like you to direct you to the screens on the side.
I will use slides, if you don't mind.
First and foremost, it is clear that clinical research is
the key to translating discovery into practice. It is the
capstone of all of our efforts. What we discover in the
laboratory, what clinical research tells us to look for in the
laboratory, can only have a reality if we apply it to our
patients.
It is clear that NIH is spending a significant portion of
its budget on clinical research, about a third of our budget is
directly spent on clinical research issues. Three thousand
clinical trials are currently active at NIH recruiting patients
throughout the country. There is not one State in the Union in
which we do not conduct clinical research at this point in
time.
What I would like to tell you is that over the years
clinical research has been very successful. Because we have
been successful we have reduced mortality for coronary heart
disease by 50 percent, mortality to stroke by 50 percent,
mortality from AIDS by a factor of six, transforming many
disease from acute to chronic. We have lengthened life
expectancy by about 1 year every 5 years, which also raises new
issues that we have to tackle.
So the evolving public health challenges that require new
strategies of research are as follows:
First and foremost is the transformation of the diseases we
have researched from acute, lethal short term diseases 30, 35
years ago to more chronic, more long term, more permanent
diseases today.
Second is the aging of our population. We need to tackle
that issue. It would be a huge burden to our society if we are
not able to find better ways of maintaining health throughout
life expectancy.
Third, a remaining priority is health disparities. We
cannot afford to have a research enterprise that does not
address the diversity of our population and the inequities that
come from not having a research strategy that attacks that
specifically.
Last, is emerging disease. Not just from the infectious
diseases that we see from time to time in our country, but also
diseases that are emerging at a rapid rate, like obesity, which
we have to tackle because their consequences are dramatic if we
do not.
And last but not least, over the past 3 years biodefense
has become a new priority for NIH.
I would like to show you here a curve of U.S. health
expenditures as a percentage of GDP as they have evolved until
2002. As you can see, there was a flattening of the cost curve
in the 1990's due primarily to managed care but also to the
fact that the aging of the population flattened in the 1990's
because in the 1990's we were seeing the effects of the
depression and the Second World War, whereas birth rates were
lower than after the war. So we are going now to a period where
again we are going to see an acceleration of health care costs.
We have already seen that in 2001/2002 and 2003 with increases
in the 8 to 10 percent range. If this continues unabated, we
will have a greater percentage of our GDP used for health care.
Therefore, we think at NIH that we have to accelerate the
progress that we make in translating our discoveries in finding
completely new ways, revolutionary ways, of preventing disease
from reaching a cost that would not be sustainable.
So how do we need to transform the medical research
enterprise in the 21st century? On your left hand side is the
paradigm of the 20th century. On your right hand side is the
paradigm of the 21st century.
In the 20th century and for 5,000 years before that the
paradigm of medicine was that we treated disease when symptoms
appeared and normal function was lost. That's how you went to
the doctor. You didn't go to the doctor unless you felt sick.
Why? We didn't understand what happened before you became ill.
We didn't understand at the time that before you developed
cancer, many, many years before that, certain changes occurred
in cells that then led years later to the development of a
cancer.
When you developed diabetes, we didn't realize that years
before that there were dysfunctions in your metabolism that led
to diabetes. Because we didn't understand the molecular and
cellular events that led to disease, we didn't know how to
intervene sooner to prevent the disease. That was very
expensive in financial and disability costs.
What is the paradigm of the 21st century? We will intervene
before symptoms appear and preserve normal function for as long
as possible. This is the strategy that we want NIH to go into--
study the preclinical stages of disease and delay, reduce or
eliminate the onset of disease.
Why do we think that this is possible today? Because we
have better methods. We have decoded the human genome. We
understand basic biology a lot better than we ever did. And we
think we have the tools. If we deploy them well to understand
disease processes, then we think we have the ability to detect
those patients at most risk where interventions will preempt
the development of disease. This has the prospect of creating a
new world of medicine that is orders of magnitude more
effective than the world we know today.
So that's in a nutshell what the NIH Roadmap goal is: How
do we accelerate basic research discovery, what we know today,
with the events that have been remarkable over the past 10
years and speed the translation of those discoveries into
clinical practice?
And the Roadmap was essentially an explicit exercise to
address the roadblocks with the entire community, analyze them
explicitly, transparently and identify those roadblocks that
slow the pace of medical research in improving the health of
our people.
Clinical research became and emerged as a key component of
the Roadmap. There are three components to the Roadmap. One is
called New Pathways to Discovery. It is our effort to
accelerate our understanding of the very complex biological
mechanisms that lead to disease.
We also understand that medical research now is a lot more
complicated than it used to be. It requires disciplines such as
physics, mathematics, computer sciences and we need scientific
teams that are more interdisciplinary than they were in the
past. And last but not least, the topic of our hearing today is
we need to tackle the issue of the effectiveness of our
clinical research enterprise.
How do we do this? I am just going to give you some
examples of where we are and where we want to be.
If you look today at a typical disease network, typically
what you see is an academic health center with sites around the
academic health center or multiple academic health centers
focused on that disease with perhaps data coordinating centers.
There are some best practices out there that you will hear from
my colleagues who are following me, in particular the cystic
fibrosis model which I think is a good model to emulate.
However, when you look at research in cancer for example, we do
not have a common language between cancer centers so that the
data can be commingled and analyzed prospectivly.
I'll give you an example. This year we showed that hormone
therapy on a long term basis is not a good public health
measure. We have reduced the utilization of these approaches by
almost 60 percent because of the research we did. If we had a
system whereby we were able to have networks of centers that
are interoperable, as I show on the graph, where we could have
had if we had good informatics, we could have tracked down
online what the effect of introducing a new therapy was on the
population and found out years sooner than we did that, in
fact, the dogma that this was a good thing was not correct.
So we want to build what I call the integration framework,
the grid for clinical research networks. How do we do this?
We create an interoperable network of networks. There is a
specific initiative called the National Electronic Clinical
Trials and Research Network, called NECTAR. NECTAR extracts, if
you will, the knowledge that we need to make conclusions about
the health of our people. This will develop common data
standards, informatics specifically for research, and software
tools. More importantly, it will be web-enabled so that we can
then deploy that system at the practice sites. Because there is
a fundamental change we have to tackle, and that is that before
we had acute diseases that were seen in academic centers in in-
patients. Today we have chronic diseases that are seen in
communities on an out-patient basis. And we need to really
research the disease before it hits. So those are issues that
can only be tackled at the community level.
So we need to have a system that the country will benefit
from if we could have an implementation where there will be an
information system whereby your doctor will have access to the
most up to date information to do the right thing for the
patient who is suffering from that disease at the time.
So we will use existing networks. We have done a lot of
work that is very effective. But we want to get to the next
step of integration.
The second is how are we going to do this? How are patients
going to interact with the clinical research system of the
future? We need trusted intermediaries. Academic scientists are
in their academic centers. They do very advanced research. Many
of the scientists we have trained, in fact, have left academic
practice. Many of them had had training in clinical research,
and then they went into practice. And then the connection is
severed.
We need to reestablish that connection. The idea that I
think will change the landscape of how research is done is the
idea of creating a national clinical research associates corps.
Essentially this would be a diverse national group of
trained and certified community health care providers linked to
regional academic centers. They will enroll and follow their
own patients. They will be trained in the latest best practices
in the diseases they are interested in such as Alzheimer's or
Parkinson's. Patients will then have access to the information
about clinical trials, but also to the best practices at the
time and access to the NIH NECTAR information system at the
practice site. We are determining feasibility as we speak and
we are developing the core competencies. And we want this
system to dovetail with the department-wide initiative of the
health information infrastructure that the department is
working on.
The other point that Ms. DeGette brought up, is the
clinical research regulatory environment. We want to maximize
human subject protection.
It is not a good idea when you try to perform clinical
research to have duplicative and overlapping Federal
requirements and variability among and within agencies. FDA has
different requirements than NIH in terms of information. But
this creates uncertainty about how to comply. And if you have
uncertainty about how to comply, your safety and your
protection is not as good as they could be. So we want to lead
an effort across the Federal Government and with Congress to
try to find better ways of implementing modern ways of tracking
safety. A good example is a collaboration currently between FDA
and NIH to establish an electronic adverse event reporting
system.
When something happens in a clinical trial, right now you
report it many different ways. We want it reported in one data
base so FDA and NIH can immediately find out what is harmful in
any one trial.
And then we need to engage the public in clinical research.
And this sounds like something that is nice to say anyway, but
this is not just a nice thing to do. It has become a core
requirement for research.
If you do not have public participation, if you don't build
trust and enhance the needed partnerships between patients and
researchers, participation rates fall. We only have the 1
percent participation right now in Parkinson's disease
research; 3, 4 percent in cancer. We need to have a much more
efficient way of testing the thousands of good ideas that are
coming out of our laboratories. And we need to do it quickly.
We need to provide ongoing communication and educate patients
and their doctors about research access. It would add to the
translation and speed it up.
A good example already in place is this website of the
National Library of Medicine called clinicaltrials.gov, whereby
any patient anywhere in the country can go to the web now, and
find any of the 3,000 trials that NIH is supporting. For
example, if they are interested in heart attack research in Los
Angeles. This is something that is a real advance. We want to
build on those advances.
So in the end, the reengineering of the clinical research
enterprise is really a comprehensive, systemic look at how
research needs to be conducted in the 21st century. We need to
integrate clinical research networks and also enhance our
community-based research. It will serve our purpose. It will
link existing networks so clinical studies and trials can be
conducted more effectively. But clearly the solution is
partnerships of research. That means that we need to create
communities of research around specific problems, whether it be
Parkinson's disease or Alzheimer's or any other disease that
links patients, their physicians and the scientists to truly
understand very quickly what the best practices are, what
works, what doesn't work in the translational research that we
need to do.
So we are committed to that. We have developed an approach.
Some of the approaches we have developed may work, some may
not. But the key thing here is what you regret in life is not
what you fail at, but what you don't try to do. So NIH wants to
lead and this is why we are here. And I would be be happy to
answer your questions.
[The prepared statement of Elias A. Zerhouni follows:]
Prepared Statement of Elias A. Zerhouni, Director, National Institute
of Health, U.S. Department of Health and Human Services
Mr. Chairman, Members of the Subcommittee, I am Dr. Elias Zerhouni,
the Director of the National Institutes of Health (NIH). I am delighted
to appear before you today to testify about NIH's role in clinical
research.
With the support of Congress and the White House, NIH has been the
driving force behind perhaps the greatest era of discovery in the
history of biomedical research. We are gaining unprecedented knowledge
about human biology and medical conditions. The human genome has been
sequenced. The scientific community is learning how proteins and
molecules function and about the mechanisms of disease. In general, the
knowledge gap about human biology is shrinking quickly.
Of course, these discoveries have far less meaning if we cannot
translate them into prevention methods and treatments for diseases and
disabilities. This translation, commonly known as the ``bench to
bedside'' process, cannot happen without clinical research. Broadly
defined, clinical research involves the participation of human subjects
in various aspects of research. It is the linchpin of the Nation's
biomedical research enterprise. Clinical research ultimately
establishes the safety, effectiveness and availability of new
diagnostic, preventive and therapeutic approaches.
Approximately one-third--$8.4 billion--of the grants awarded by NIH
support clinical research. We have established integrated clinical
research networks for HIV/AIDS, heart disease, and cancer, among
others, that have significantly enhanced the translation of basic
discoveries. At all times, our primary concern must be the safety of
the people participating in clinical studies and trials. The Federal
Government has a rigorous process for ensuring the well-being of human
subjects participating in Federally conducted, supported, or regulated
research, ranging from the initial reviews by Institutional Review
Boards (IRBs), to ongoing reviews by Data Safety and Monitoring Boards,
to the authority to investigate and discipline researchers and
institutions that do not abide by Federal requirements.
NIH continues to expand its clinical research program and provide
resources for infrastructure and training. We have established new
programs to support the professional development of medical students
and medical school graduates in the conduct and ethics of clinical
research. We are funding young clinical investigators and their
mentors; reorganizing study sections to enhance the evaluation of grant
applications about clinical research; and providing educational loan
repayments for new, including minority, clinical investigators.
Longstanding programs for the support of clinical research, including
the General Clinical Research Centers located in academic health
centers around the country and the NIH Clinical Center, also have
developed new training initiatives designed to advance translational
research. These programs and an array of other infrastructural
activities and training mechanisms are aimed at ensuring that the
``critical mass'' of highly skilled personnel and state-of-the-art
resources necessary for a vigorous clinical research enterprise are
available.
As the Director of the largest biomedical research agency in the
world, I believe it is my responsibility to continually review our
programs to ensure that they are working well, and further, to be
certain we are heading in the right direction. So for all our success
in the clinical research area, the question is: have we done all we can
do to speed the process of translation of results from bench to
bedside? The answer is, we can do more and we can do it better.
When I arrived at NIH two years ago, I implemented an initiative
across all of our Institutes and Centers to explore the key scientific
challenges facing investigators today and to delineate the central
roadblocks to scientific progress. With a focus on those activities
that would require the efforts of the agency as a whole, and through
broad consultations with scientists inside and outside NIH, this
extensive planning effort has led to formulation of a ``Roadmap'' for
medical research in the 21st century. One of the key goals of the
Roadmap is to re-engineer the clinical research enterprise. The purpose
of the re-engineering effort is to overcome obstacles to the conduct
and translation of clinical research by transforming its very
structure. The NIH Roadmap plan on ``Re-engineering the Clinical
Research Enterprise'' has four main parts: Facilitating Translational
Research; Enhancing the Clinical Research Workforce; Integrating
Clinical Research Networks; and Coordinating Clinical Research
Policies.
Facilitating Translational Research
To improve human health, scientific discoveries must be translated
into practical applications. Such discoveries typically begin with
observations of patients with diseases then move to the ``bench'' with
basic research--where scientists study the mechanisms and progression
of a disease at the molecular or cellular level--then progress again
toward the study of these phenomena in patients at their ``bedsides.''.
Scientists have become increasingly aware that this bedside-to-
bench-to-bedside approach to translational research requires a variety
of non-traditional expertise and intense two-way collaborations with
clinicians. Not only do basic scientists complement the expertise of
clinicians in making novel observations, clinical researchers also make
unique observations about the nature and progression of disease that
can, in turn, stimulate basic investigations. Thus, translational
research is a key junction in the process, where new knowledge is both
tested and gained, producing new observations and hypotheses that keep
the system productive and rich with discovery. However, I believe that
by strengthening the infrastructure, this critical process and
component of the clinical research enterprise can be accelerated.
Key to building a strong infrastructure will be the ability to
increase the interactions between basic and clinical scientists, and
cross-training of basic and clinical scientists in each other's
disciplines, thus easing the movement of powerful new tools from the
laboratory into the clinic. In one approach aimed at accomplishing this
interaction, NIH intends to develop regional translational research
centers. These centers would provide sophisticated advice and resources
to better enable scientists to master the many steps involved in
bringing a new product from the bench to clinical use. Such steps
involve laboratory studies to understand the mechanisms of action of a
therapeutic agent, preclinical studies in animals to evaluate how the
agent is absorbed by the body and distributed to target tissues, and
assessing its effectiveness as well as tendency to cause unanticipated
side effects.
Once a potential new drug is developed, sufficient amounts of the
drug have to be produced according to rigorous standards for testing
first in animals and then in people. The clinical research re-
engineering plan also envisions translational research core facilities
to provide clinical researchers access to sophisticated manufacturing
capacity, along with expert advice to ensure that drug-development
regulations are observed. Some of these core facilities will be modeled
on, or may evolve through expansion of, existing programs such as the
National Cancer Institute's Rapid Access to Innovation Development
program, which currently provides support for these types of resources
to members of the cancer research community. Their availability to the
broader research community should expedite discoveries for other
disease research as well.
This re-engineering initiative will also support translational
research by developing new technologies to improve the assessment of
clinical outcomes. Many of the most debilitating, chronic illnesses
gradually erode the quality of life because of the associated fatigue,
pain and emotional challenges. Currently, these critical symptoms
cannot be measured objectively in the same way as, for example, blood
sugar levels or blood cell counts. More sensitive, well-validated tools
need to be developed to improve measurements of these types of
symptoms. Technologies, such as a computerized adaptive health
assessment, could revolutionize how symptoms and treatment outcomes are
assessed. Scientists will be better equipped to understand how patients
perceive changes in their health status resulting from new
interventions, thereby directing research to therapies that would be
most highly valued by patients.
Enhancing the Nation's Clinical Research Workforce
The second component of the re-engineering plan is aimed at
enhancing the Nation's clinical research workforce. To fulfill the
promise of 21st century medicine and to make further progress in
controlling major human diseases, the Nation must cultivate and
properly train a cadre of clinical researchers skilled in translating
the findings from clinical trials and other clinical research studies
to applications on the front lines of care. Clinicians must be trained
to work in multidisciplinary, team-oriented environments. Specific
training in disciplines important to the conduct of clinical studies
(e.g., epidemiology, behavioral medicine, and patient-oriented
research) is needed, and the expert skills of engineers,
mathematicians, physicists, and computer science experts also must be
incorporated. This component of the re-engineering plan will enhance
and empower the clinical research workforce through two programs--the
Multidisciplinary Clinical Research Career Development Program and the
National Clinical Research Associates Program.
The Multidisciplinary Clinical Research Career Development Program
will be an NIH-wide effort to train doctoral-level candidates in
clinical research settings that are multidisciplinary and
collaborative. The emphasis will be on new strategies and curricula
with training opportunities that span a variety of disease areas; a
broad range of clinical disciplines, including medicine, nursing,
dentistry, pharmacy and other allied health professions; and a variety
of research areas, including biostatistics, behavioral medicine,
clinical pharmacology and epidemiology. The new program will be
coordinated with and complement other NIH training programs that
support scholars who wish to become clinical researchers. NIH plans
additional programs to help smooth out the early career development
pathway spanning from college to professional school, thus promoting
the early identification and training of students who will become the
future leaders in clinical research. By exposing students to clinical
research early in their careers, it is hoped that this program will
also enhance the integration of clinical research into both basic
science and clinical medicine.
The clinical research workforce also must be broad enough to
support the testing of ideas in large scale studies at the community
level, as well as the translation of proven concepts into medical
practice at the community level. The National Clinical Research
Associates program will help increase the number of clinical
investigators and diversify the settings in which clinical research is
conducted. Through partnerships with academic investigators, the
Associates will form a corps of community-based physicians trained to
carry out clinical studies in their own health care settings. Together
they will form a robust and versatile infrastructure of researchers
well-trained in the responsible conduct of clinical research and
positioned to bring research opportunities to patients while rapidly
disseminating the best science-based practices.
Several projects will be required to realize the vision of the
Associates. These include a study that will examine the challenges
involving community practitioners in clinical research. Building on the
results of this study, recommendations on ways to reduce barriers to
building a model workforce for conducting clinical research are
expected to evolve. Other efforts will focus on the establishment of
national core competencies and best practices needed to conduct high-
quality clinical research and to translate research into clinical
practice. These efforts will apply to researchers working in both
community and academic settings. Competencies would include relevant
board certification; knowledge of clinical research design and
implementation, and conflict-of-interest policies; and documentation of
training in protecting participants in clinical trials. To train the
Associates, the NIH plans to create several nationally recognized
regional Centers of Excellence in Clinical Research Training that will
be based on the results of the feasibility and pilot studies. These
centers will use an integrated approach to conduct training in ``real-
world'' settings.
Integrating Clinical Research Networks
Another component of the re-engineering plan, Integrating Clinical
Research Networks, is designed to promote synergy among diverse
clinical research activities through the development of linkages among
research institutions, medical centers, and existing research networks.
Because of the vast number of therapies, diagnostics, and preventive
approaches that must be evaluated through clinical trials, many
clinical research networks operate simultaneously, but independently of
each other.
Over time, this initiative aims to link research centers and
existing networks in order to develop a National Electronic Clinical
Trials and Research Network (NECTAR). This network will create a
revolutionary new clinical research infrastructure model, which will
result in greatly enhanced communication, computational capacities,
access to resources, and research and analytical tools. Such a system
will ultimately offer economies of scale by allowing complex research
programs to benefit from a common infrastructure, rather than
recreating infrastructure resources time and time again at multiple
sites. Networking will provide for broad access to data and allow
investigators to learn from, utilize and build upon existing data.
Integration of data will encourage the formulation and study of new
research questions and the cross-fertilization of major fields of
inquiry in the process.
This effort will promote and expand clinical research networks that
can rapidly conduct high-quality clinical studies that address multiple
research questions. An inventory of existing clinical research networks
will be undertaken to explore existing infrastructures for informatics
and training, in order to pinpoint characteristics that promote or
inhibit successful network interactivity and productivity and expand or
broaden research scope. Once identified, ``Best Practices'' can then be
widely disseminated, further enhancing the efficiency of clinical
research networks.
To function effectively, these clinical research networks will need
to harness and help integrate information technology and develop a
national informatics network using standardized data, software tools
and network infrastructure. NECTAR, which will dovetail with current
medical informatics initiatives in the Department of Health and Human
Services, will maximize connectivity among existing and newly created
clinical research networks and help researchers to generate, use and
share data, thereby reducing duplication and unnecessary overlap among
trials.
To accomplish this, NECTAR will create common vocabularies,
research and business tools, and common platforms and architectures.
NECTAR will enable more efficient business practices and processes;
enhanced data sharing and analysis; coordinated oversight and improved
patient protections; and rapid translation of research into clinical
findings and practice. NECTAR ultimately will assist in accelerating
the pace of discovery and development, thereby helping clinical
researchers better serve their patients.
Coordinating Clinical Research Policies
The last critical component of re-engineering the clinical research
enterprise recognizes that other potential impediments to efficient
clinical research are the diverse regulations and policies of the
multiple federal agencies that fund, conduct and oversee clinical
research. For example, researchers face varying requirements that
pertain to reporting adverse events to NIH, the Food and Drug
Administration, the Office for Human Research Protections and IRBs,
among others. Clinical researchers must understand and fulfill these
varying requirements.
NIH is working in concert with regulatory agencies, research
communities, and patient advocacy groups to catalyze Federal-wide
coordination of policies pertaining to clinical research, to develop
better processes, and to standardize requirements for reporting adverse
events, human subjects protections, privacy and conflict-of-interest
policies, and standards for electronic data submission. Coordinating
policies and reporting requirements will help minimize unnecessary
burdens that slow research while enhancing patient protections. Thus,
the goal of NIH's Clinical Research Policy Coordination Initiative
(CRPCI) is to work within the federal system of clinical research
oversight to promote the coordination of policies, requirements, and
procedures concerning clinical research, and, where appropriate, to
help create streamlined approaches. The CRPCI will examine an array of
issues and activities on behalf of the NIH and all its Institutes and
Centers and work with other Departmental components and Federal
agencies to help stimulate the development of coordinated policies,
practices and new tools for compliance that take account of the goals
and points of view of NIH's varied organizational components and
stakeholders. As the most important part of our system of human
subjects protections, IRBs will be a primary audience for our efforts.
Some representative activities will include:
1. Studying existing requirements for the conduct and oversight of
clinical research to assess the extent to which unnecessary or
duplicative rules can be addressed without diminishing
protections;
2. Exploring the expanded use of central Institutional Review Boards to
facilitate and achieve greater efficiency in the review of
multicenter clinical trials, such as the National Cancer
Institute's Central Institutional Review Board program for
adult oncology trials;
3. Developing tools and materials to help ensure and facilitate
compliance with existing rules;
4. Promoting the development of coordinated clinical research policies
by working with other Federal entities (such as FDA, OHRP, and
the Departments of Defense and Veterans Affairs) that fund,
conduct, oversee, and establish policy for clinical research;
5. Soliciting input on various policy goals from key communities, such
as patients, scientists, institutional leadership, IRB members,
and other constituencies with a stake in the conduct of
clinical research; andDeveloping educational and training tools
to assist investigators and IRBs in the interpretation of and
compliance with human subjects and related research
requirements.
While NIH has assumed a leadership role in conceptualizing and
implementing this plan to reconfigure the clinical research enterprise,
many other stakeholders have broader roles and vital responsibilities
in assuring the future of clinical research, including other federal
agencies, academic health centers and biomedical research institutions,
private foundations, the pharmaceutical and biotechnology industries,
the health insurance industry, patient advocacy groups, and the general
public. In implementing the re-engineering plan, NIH recognizes that
success will depend on continuing close collaborations and
consultations with these many partners.
Conclusion
In taking bold steps to re-engineer the clinical research
enterprise, NIH hopes to create a new infrastructure to support
clinical research that will facilitate the rapid translation of
discoveries from the laboratory to the clinic and provide a robust
force of clinical investigators to test new diagnostic, therapeutic and
preventive strategies in patients far sooner than is possible at
present. By enhancing the interoperability of clinical research
networks, and by improving the coordination of the important rules and
regulations that ensure the safety and ethics of these studies, the
system will be more efficient and there will be far fewer impediments
to the conduct of clinical research. Clinical research will advance
more swiftly, more and better therapies and preventive measures will be
developed more quickly, and, ultimately, significant improvements will
be made in human health and the quality of life. We look forward to
keeping Congress apprized of our continuing progress in Re-engineering
the Clinical Research Enterprise.
Mr. Bilirakis. Doctor, thank you. It is about as concise
and informative a statement as I have heard in a long, long
time.
Doctor, do you reflect the views of your colleagues at NIH
and, I might say, other colleagues in other research facilities
in the research area, if you will? Yes, do you feel that you
for the most part would be speaking for them, too, in terms of
what is needed, what the future looks like?
Mr. Zerhouni. Right.
Mr. Bilirakis. The Roadmap, the concept, etcetera?
Mr. Zerhouni. Right. I have to say that this concept is not
my concept. The only thing I did was to create an explicit
process of consultation. And over a 1-year period we had over
300 experts and scientists come together and work very
diligently on analyzing the roadblocks, the opportunities, what
it is that no single institute can do but that NIH as a whole
needs to do. That was the framework. And what came out of it is
this Roadmap.
In fact, a good test is that people put their money where
their mouth is. And for the first time all NIH institutes have
agreed to put shared resources into this common pool of
initiatives called the Roadmap. So every institute is
contributing in fact to implementing this, because everyone
realizes that this framework enhances research across the
board. So I think the answer is yes.
Mr. Bilirakis. The answer is a good solid yes? That is good
to hear.
Are you getting all of the cooperation that you need?
Mr. Zerhouni. So far so good.
Mr. Bilirakis. So far so good. Do you feel you have the
resources?
Mr. Zerhouni. Never enough resources.
Mr. Bilirakis. Never enough. Well, I guess any human being
still alive would make that comment regarding resources.
Mr. Zerhouni. Right. I think that the communication that
needs to occur is a new phenomenon for NIH. We have not
historically engaged in processes that do trans-NIH forward-
looking planning processes. That was never really part of the
mechanisms by which we operated at NIH, but it was something
that really was felt to be necessary by the community.
The IOM report, which was the one that you conducted a
hearing on a few months ago, recommends a more explicit way of
undertaking these processes regularly, every 2 or 3 years, to
inform the public, inform Congress of what analysis is, why do
we think this is important and why do we need to do it across
the agency.
Institutionalizing such a process will be very helpful, Mr.
Chairman.
Mr. Bilirakis. Well, do you feel that the current NIH
organization structure encourages clinical research across
multi institutes, encourages basically the vision of the
Roadmap?
Mr. Zerhouni. Yes, I think so. I think that the
realization--the trends that I have described to you going from
acute to chronic. For example, a realization that people in the
field are coming to understand is that as patients age, they do
not suffer from one disease at a time. There are multiple
diseases that affect you at the same time. You can have heart
disease, diabetes, renal disease, musculoskeletal disease at
the same time. So the approach that every single disease needs
a network and one approach is obviously not the approach of the
future. And the institutes are realizing that we have many
trans-NIH collaborations to combine the strength of various
institutes and various diseases in the context of what we call
co-morbidities.
Mr. Bilirakis. So the institutes are realizing that?
Mr. Zerhouni. They are realizing it.
Mr. Bilirakis. You feel that that's happened?
Mr. Zerhouni. But again----
Mr. Bilirakis. You know, this turf thing that we have here
in Washington, protecting one's turf and whatnot----
Mr. Zerhouni. It is alive.
Mr. Bilirakis. It exists. Live and well up there.
Mr. Zerhouni. It's alive and well, and it's not bad.
Because you have decentralization so that you do not make a top
down decision that could be wrong. But the balance is what is
in question. I think we need to have a good balance between the
two and find explicit ways to do this.
One of the things that the directors have agreed to do is
to find a way to better code and analyze the portfolio across
NIH. Do we have a good way of looking at the entire portfolio
and making decisions? That is a valid question. I do not have
the answer to that. We are working on it.
Mr. Bilirakis. Well, Doctor, we requested at the last
hearing that you give us an idea of what help you might need
from the Congress in terms of additional authorities that might
be legislatively required. Hopefully, not, but it might be. And
I am not sure, really, that we--you have basically said to us
that hey we need this or we need that in terms of legislative
fixes.
So I guess what I am saying, I am not asking for a response
at this point in time, but I am just reminding you that we have
not reauthorized NIH for various reasons for years. Obviously,
it has not interfered with their work. We made sure they got
their resources and we have spent a lot of time with NIH, too.
But, you know, in the process of considering whether we go
through a reauthorization this year or whatnot, what you might
need in terms of this Roadmap would be significant in making
our decision. So, please let us know.
Mr. Zerhouni. I should let you know, we are working on
every single recommendation of the IOM report. We are analyzing
those. We are preparing a response to your request.
Mr. Bilirakis. Good. Thank you very much.
Mr. Brown for 5 minutes.
Mr. Brown. Mr. Chairman, thank you.
Dr. Zerhouni, thank you again.
As I mentioned in my testimony, I want to talk about
Norvir, the patented AIDS drug discovered roughly ten plus
years ago by Abbott Labs under a multi-year/multi-million
dollar grant from all of you, from taxpayers.
By year end 2001, Norvir had generated more than a billion
dollars in sales for Abbott. There is evidence to suggest that
development costs borne by Abbott for the drug were relatively
minimal. Norvir sold $7,800 a year in the United States while
the price is less than $720 in Canada and less elsewhere.
Despite the fact that NIH resources, taxpayers, contributed to
the development of Norvir its price has always been higher in
the U.S., as you know, than any other western European country.
And that was before last December, Abbott increased the price
of Norvir by 400 percent. Now we are talking about AIDS
patients.
Norvir is typically used as a booster for other AIDS drugs.
So the price of those drugs skyrocketed. Abbott insulated its
own Norvir boosting product Coletra from the price increase,
giving Abbott a tremendous price advantage.
Two hundred organizations and physicians have asked both
the FTC and the Department of Health and Human Services to step
in and do something about this price increase. My understanding
is that the HHS petition is currently pending in the Office of
Technology Transfer at NIH, right? Okay.
These groups have requested a public hearing. Again, 200
organizations and physicians have requested a public hearing.
They recently received a letter from NIH saying that
representatives from your agency would be willing to meet with
them after a decision is made on the petition.
I am concerned about the after decision. These groups want
to make the case regarding the viability of using Bayh-Dole the
compulsory licensing patent allowing a generic in, given that
specific patents on this product and other issues that make
this case complex. These groups, I believe, deserve the
opportunity to make their case before the decision is made.
Will you give them that opportunity to make their case in a
public hearing prior to?
Mr. Zerhouni. Right. You know my feeling is always
transparency is better than any other process. However, in this
context our regulatory and legal requirements, that the agency
has to review the petition, the facts and this is what we're
doing right now. And that review under the Bayh-Dole Act has to
be done by the agency on the basis of all the historical data,
and I'm told that this is in process right now.
Mr. Brown. But what is the harm before a decision is made
of doing a public hearing? Why cannot you commit----
Mr. Zerhouni. Our technology transfer office is in charge
of implementing Bayh-Dole and all the march-in rights, and we
need to let them do their analysis. At this point I don't have
their----
Mr. Brown. Well, I do not disagree with letting them gather
the information, letting them do the analyses, but before a
decision is made----
Mr. Zerhouni. Right.
Mr. Brown. Before a decision is made, not just an
announcement that it is public----
Mr. Zerhouni. Right.
Mr. Brown. Can you commit to doing a public hearing before
the actual decision is made? You always have believed in
transparency.
Mr. Zerhouni. Yes, I understand.
Mr. Brown. And you have been open with this Committee, with
me personally.
Mr. Zerhouni. Right.
Mr. Brown. I think with all of us here.
Mr. Zerhouni. Right. I can only tell you that if this is
something that doesn't jeopardize the function and obligations
of the agency, I have no objection to it.
Mr. Brown. How could it jeopardize that? I do not
understand.
Mr. Zerhouni. Because of the legal requirements. You have
certain rules and regulations. For example, the majority of
drugs in this market are not developed with NIH's dollars
directly. And the rules say that if you have a component of
government contributions to basic science which is not really
patented within the subsequent patents, the subsequent patents
rule. So that we have to look at that very carefully before an
agency can say there is merit or there is no merit to a
particular approach. We need to do that work. And that work
needs to be done in the context of the regulations that are
there.
The second issue that you are raising is the issue of
pricing. This is an issue that goes way beyond NIH, as you well
know.
We need to know what authority we have in that context. And
the analyses are being made as we speak. But you have my
commitment that if this is something that we can do, that the
legislation allows us to do and if we have any leeway, I would
tend toward open----
Mr. Brown. Okay. Thank you.
Real quickly, Mr. Chairman, I will ask this quickly. To
switch to another drug, Taxol, a breast cancer drug developed
with NIH funding almost entirely with NIH funding including
much of the clinical trials, is my understanding. 2003 GAO
criticized NIH for not collecting adequate royalties for its
contribution in developing Taxol. Share with us, if you would,
NIH has done to ensure that--again, the taxpayers receive
royalties for the efforts that we all as taxpayers put forth.
Mr. Zerhouni. Yes. Let me tell you, I think the facts as we
hear them are not the facts as I know them. So maybe one of the
things we can do is tell you my version of the facts as I have
learned them. I was not there then.
First of all, Taxol was a drug that was developed initially
in the 1950's as a contraceptive and it failed. It wasn't a
patented drug, No. 1.
No. 2, the specific NIH contribution to that was not the
drug itself, it was a method of delivery of the drug. That's
all that NIH did. At the time, NIH wanted to stimulate a relook
at that drug, which we thought could have cancer potential. It
was out of patent. And the only thing that we contributed was
perhaps it could be delivered this way.
It turns out that the subsequent work, the relative
contribution to say that NIH funded 100 percent of it and gave
away its intellectual property rights, is inaccurate. That is
not what we are told.
Now, could NIH have a different strategy in terms of
licensing when it has a real right? We do that when we have the
majority of the intellectual property. NIH received $50 million
a year in royalties from inventions that we have had a
significant contribution to.
So in the Taxol case, I think you are dealing with a drug
that was not invented at NIH. We are dealing with a drug that
was off-patent. The NIH contribution itself from what I am
told, was not the significant contribution. However, NIH funded
the chemistry research that was needed to avoid using the bark
of the yew tree and funded the University of Florida to invent
a synthetic method to do it. That method was licensed to
Bristol-Myers. That patent from the University of Florida
received $400 million in royalties which has allowed the
University of Florida to do research. It didn't come to NIH,
but it came to an NIH grantee.
So I agree with your concern that we are sort of
undervaluing government property. But Taxol, I don't think is
a----
Mr. Brown. Was GAO wrong? Was GAO wrong?
Mr. Zerhouni. No, no, no. What the GAO was reporting was
the GAO said do we have a system, do we have a system by which
the analysis that we are talking about can be done before
licensing? Do we have a way? For example, some of the
conditions we impose on some of our licensees when we have
solid rights.
Remember, in the Bristol-Myers thing there is nothing in
what they did that is directly related to what we did.
Mr. Bilirakis. I share the concern that Mr. Brown has
raised, and I think he would like the answer that he really
wants. But it is basically--but basically I think he is
interested in how the NIH functions in that regard and what
criteria they use in determining proper royalties forthcoming,
and that sort of thing.
Mr. Brown. Right.
Mr. Bilirakis. And not just that particular drug?
Mr. Brown. Right.
Mr. Zerhouni. And we are following that.
Mr. Bilirakis. Good. Thank you, sir. And we would maybe
request that in writing from you after the hearing, along with
all the other questions.
In that case, Mr. Greenwood?
Mr. Greenwood. Mr. Upton and Mr. Buyer said that if I buy
them lunch I can go next, since I have leave. And I appreciate
that. Lunch is in the mail.
Ms. DeGette I think raised the issue of human subjects, and
she and I, as she mentioned in her opening statement are
working on legislation to try to create the harmonization that
is not there now. Could you be a little bit explicit as to
whether you believe, in fact, that legislation is needed and
what specifically you think needs to be in that legislation?
And to the extent that you are aware of some of the
controversies that have impeded our progress getting unanimity
on this, you might comment on that?
Mr. Zerhouni. We are looking into that. We are actually
analyzing right now what common ground you can find between
NIH, FDA, other Federal agencies. We are actively putting a
work group together. We have already done so in the area of
safety. We have worked extensively within NIH on electronic
submission. Someone was asking me about what are we doing with
the other elements of the health care system. What I think we
are doing, is we are trying to bring in the fully-installed
interface for computers to be able to do it. In terms of the
ranking function, it may be necessary at some point after we do
the analyses to come back to you and----
Ms. DeGette. Will the gentleman yield for just 1 second?
Mr. Greenwood. Yes.
Ms. DeGette. Doctor, what kind of timeframe are you looking
at for the NIH to complete its work?
Mr. Bilirakis. The mike--is the mike working?
Mr. Zerhouni. You are right. It is not on.
I'm going to co-chair the Committee on Science with Dr.
Marburger, so we have already reached across to the OVA and
other agencies. And we are doing this in the effort to improve
human subject protection while at the same time making the
rules clear, coordinated and effective.
Mr. Greenwood. Thank you.
On the issue of the clinical researchers themselves, in the
past we have noted a need to have more better trained, trained
not only in the clinical matters but in the ethical matters and
so forth. And legislation that I helped, I was involved in, to
provide funding to do just that; to educate young researcher in
medical school. Are you able to comment on how we're
progressing in that arena?
Mr. Zerhouni. This is a very important area. And NIH has in
fact funded what we call human subject protection enhancement
grants at all the institutions that applied for it to do two
things. One was training of the scientists and actually we
mandated that every scientist that does clinical research,
performs clinical research, has to be certified. That's one.
The second is the significant investment we have made in
terms of clinical research infrastructure. We have developed,
for example, what we call K30 awards which are institutional
awards to provide formal training on a permanent basis to all
of their scientists, all their clinical researchers.
These two programs alone, you are talking about $30, $35
million a year of investment since 2001, I believe.
We are continuing to look at because we believe that it is
actually important to also look at the structure of how human
subject protection is done relative to data and safety
monitoring boards. That is the goal of this policy coordination
group that I have put together. So we are doing it, but I think
you are right, I think that we need to make sure that it is
effectively done on the ground.
Mr. Greenwood. Thank you, Dr. Zerhouni.
My time is about expended, but I just wanted to say that I
think that the intelligence, the integrity and the ability that
you bring to this job are the best thing that has happened to
NIH in a long time. I commend you. Nice to work with you.
Mr. Zerhouni. Thank you.
Mr. Bilirakis. Thanks to the gentleman.
Ms. Capps for 5 minutes.
Ms. Capps. Thank you.
Mr. Bilirakis. And then we will break. We have a series of
votes. Three or four. We will just get back as quickly as we
can. I am not sure what else I can say.
Ms. Capps. And I will try to be brief and maybe not even
use the whole 5 minutes. But I do have three different topics,
each of which could take a long conversation, and I hope you
appreciate the way we kind of do business here.
But the first topic is genetic nondiscrimination. Mapping
of the human genome has been a remarkable accomplishment and
seems to be opening up so many new doors. A lot of what you
were talking about, I kept think that is all because of the
mapping that has occurred. Obviously, this is a very positive
step. But some are concerned about the downside and genetic
discrimination being one of those concerns. Do you think we
need legal or law to protect people from genetic
discrimination?
Mr. Zerhouni. The answer is yes.
Ms. Capps. Okay.
Mr. Zerhouni. We are very supportive. There is a bill that
has passed the Senate.
Ms. Capps. Do you support it?
Mr. Zerhouni. Which we support.
Ms. Capps. Okay.
Mr. Zerhouni. We would like the House to do the same.
Ms. Capps. All right.
Mr. Zerhouni. If possible. And we have talked actually to
Chairman Barton an we are talking to the members of this
Committee to try to see if we could have an equivalent bill in
the House.
Ms. Capps. Thank you.
Mr. Zerhouni. It is very important to that issue.
Ms. Capps. I agree with you, and that is exactly what I
wanted to hear.
Another area, which I hope you can answer briefly, because
then I want to talk about a third topic and give you more time.
And this is a huge topic, too, which is the seeds of distrust
sewn in racial ethnic minority communities with regard to
clinical research and how will you go about persuading more
minorities of their importance in such trials given you're
operating in 50 States, which is remarkable in itself because
that speaks to a lot of diversity. But within those areas there
is probably--I know there are challenges. If you could address
that, please.
Mr. Zerhouni. This is actually the reason why I put public
interaction and public involvement as a very key component of
the Roadmap for NIH. We know from research that you cannot
conduct research in the community unless you have good, trusted
intermediaries that are in the community. That is why the
clinical research corps will be important to have members of
the community connected to the scientific research system. And
this is the only way we are going to be able to do it is by
having community partnerships, otherwise it is hard for me to
see how you go over that distrust there.
Ms. Capps. I agree with you, and I think that is an
important subset of issues, that the regionalization and also
attracting a variety of peoples into science fields so that
there is that connection to cultural. I know you agree with
that, too.
Mr. Zerhouni. Right.
Ms. Capps. I just want for whatever time remaining to have
you talk a little bit more about one of the slides you put up
which talks about the translation of results from bench to
bedside and back and forth. Anyone who has ever been a part of
cancer treatment knows the treatment of clinical trials in the
treatment, not just the study. And I would like to give you a
chance to explain this more fully and how we could support some
of those efforts here.
Mr. Zerhouni. It's very important. We have two
translational issues: One is when there is a discovery and then
you need to really go in for a very early proof of concept.
This is a difficult step to undertake.
Actually in cancer, cancer is probably more advanced than
any other field.
Ms. Capps. Yes.
Mr. Zerhouni. And we have programs now that accelerate the
development. And we have a program with FDA to try to
accelerate, work together very early so that there will be no
obstacles downstream.
Ms. Capps. And some of us believe the ensuring clinical,
allowing people to use their health insurance for participation
would be a good step, too.
Mr. Zerhouni. Right. That is a difficult issue, obviously.
Ms. Capps. It is very difficult.
Mr. Zerhouni. But clearly what would help us the most is
truly connected and organized communities that partner so that
they can participate in clinical trials--that the doctors know
about trials and participate actively in the research effort.
Ms. Capps. So that, again, is part of your rationale for
decentralizing, if you will, and becoming a part of the people.
Mr. Zerhouni. That is correct. That is what our community
researchers are telling us.
Ms. Capps. What ways could Congress assist you this effort?
I know money, but money where, how?
Mr. Bilirakis. Would the gentlelady defer? Are you coming
back?
Ms. Capps. Yes, I plan to.
Mr. Bilirakis. You are planning to? Why do we not go ahead
and break? I am afraid we are really going to have to really
run to make that vote.
Ms. Capps. Okay.
Mr. Bilirakis. And then you can continue. You will have
another minute when we get back.
Would you mind waiting, Doctor? I know it is going to be a
while.
Mr. Zerhouni. No, I do not mind.
Ms. Capps. It will be. Thank you very much. I am happy to
come back. Leave my things here.
[Recess.]
Mr. Green [presiding]. The Committee will come to order.
Ms. Capps, I think we ended with you in the middle of your
questioning, and so you are now recognized to complete that for
1 minute.
Ms. Capps. I got a few extra seconds out of that deal. I
think that was pretty good.
As I went to the floor to vote, Dr. Zerhouni, I reflected
on a pattern that I think you gave both in your testimony and
in your response to me so far, which is the importance of the,
and I forget the title that you have designated these
scientists to be, no less than full participants in NIH but
dispatched, if you will, into the community within perhaps
academic or treatment centers. And well I guess my final
question to you then is, because I want to be pragmatic about
this, would there be legislation that we could craft in a
bipartisan way that could further help you to articulate that?
Funding always help, but also the articulation of that idea
that we could perhaps help within the Congress?
Mr. Zerhouni. I am not sure we need legislative language.
The NIH National Clinical Research Associates Program is a way
for us to formalize connections between academic centers and
the communities. In particular, in many areas, you see those
doctors who are in the community in fact trained at the
academic centers. The tie has been severed because there was no
connections that we supported. We need to support it
financially, obviously, and we need to support it through
training and an infrastructure.
I am not sure we need legislation, but I am not sure either
that we don't.
Ms. Capps. Right. Well in other words you are making the
connections within the structure of NIH to tie these entities
together?
Mr. Zerhouni. Well, we're going to stimulate--as you know,
NIH 85 percent of our budget goes to about 2800 institutions,
212,000 scientists out there. We want to stimulate them and
challenge them to establish models of collaboration and
cooperation within their own communities. And that's how we
will do this.
We will, however, have common training, common
understanding of human subject protection, common guidelines
and a presence at the practice level.
Ms. Capps. I guess if I could make a final comment. The
place then where we would be interested in this, I would be as
if one these sites is my congressional district. And that is
how members could then connect at the local level, which we
appreciate being able to do anyway.
Thank you for your time.
Mr. Zerhouni. Thank you.
Mr. Green. Thank you, Ms. Capps.
Mr. Buyer, you are now recognized for questions.
Mr. Buyer. Thank you.
I apologize I was not here for all of Mr. Greenwood's
questioning, so I did not get to hear your responses on human
subject research protections.
Mr. Zerhouni. Yes.
Mr. Buyer. I took that issue on with the VA, and we have
institutes, from oversight with that. I remember some testimony
at our hearings relative to perhaps even a need that whatever
we do at NIH we really should do for everyone so we are all on
the same sheet of music. and I would only invite--I suggest
that you invite as you go into this process everyone who is in
government that does these types of clinical researches, that
we all really get on the same sheet of music. Does that sound
like a good idea?
Mr. Zerhouni. It is a terrific idea. We support your idea.
We have actually implemented this harmonalization effort Mr.
Buyer. I just wanted that harmonization to be beyond you.
Mr. Zerhouni. Yes, it is. It is.
Mr. Buyer. Okay.
Mr. Zerhouni. We can give you the details of how we go
about it.
Mr. Buyer. All right.
Mr. Zerhouni. But it involved the VA, it involved the
Department of Defense. And, as I said, I am co-chair of the
Committee in Science under Dr. Marburger, and we have brought
that up.
Mr. Buyer. That is great.
Mr. Zerhouni. We have a trans-agency look at it.
Mr. Buyer. All right. That is wonderful.
The other is you captured my attention because of my work
also with the VA and DoD with regard to information technology
architecture and how costly this is to integrate these systems
not only by hardware and software. So my question goes to what
is your cost assessments to implement your architecture?
Mr. Zerhouni. Right now our cost assessment is about $233
million over 5 years. Our goal, obviously, is not to pay for
all the systems. For example, this year we invested about $8
million to create a single language that all clinical data will
be recorded under, it is called SNOMED. We had seven before. So
we have basically made this software off the shelf available
for free to all clinical investigators who want to use that.
The second is the idea of web-based standards. So what NIH
wants to invest in are the common technologies that are needed,
but we have also worked with the VA because the VA actually has
a very good system called VISTA, and we want to enhance that
system and work with them to make it a platform that everybody
can use. But the number is $233, million if I am correct.
Mr. Buyer. But right now what you have are multiple
stovepipes that really cannot communicate well with each other,
correct?
Mr. Zerhouni. Right. Correct.
Mr. Buyer. Our goal is to be able to have everyone deal
with----
Mr. Zerhouni. Talk.
Mr. Buyer. Communicate, share informations, correct?
Mr. Zerhouni. Right. And doing it while protecting privacy.
You see, one of the reasons why you need a system that is
dedicated to clinical research is this issue of patient
privacy. And right now what you have are multiple systems,
different languages, no firewalls and privacy is very hard to
protect. By doing what we are doing, we think it will enhance
the protection and the privacy protection by having sort of a
security strategy for the data that is common across all
clinical research.
Mr. Buyer. Well, I am surprised you can do this at $200
million. I mean, when I compare what this cost us in the VA to
do this integration for seamless with the DoD, this is well
over a billion.
Mr. Zerhouni. Right. We are not paying for the computers.
We are using what is available today. We have already invested
quite a bit of money on what we call Abilene 2, which is the
high-speed Internet. And we are investing in the infrastructure
for Abilene 3, which will mean that all academic institutions
will have access to a high-band width, high-speed Internet. So
we are not making the investments in terms of the institutions
themselves. The VA has to pay for all of that, we do not. The
institutions already have systems in place. What we need to
populate them with is common software, common standards and
interoperable systems.
Mr. Buyer. Well, I compliment on your goals and for willing
to take something as complicated as this on. I think it will
pay great dividends down the future. I really believe that. So
I compliment you for taking that on.
I switch gears to a subject about sexually transmitted
diseases, because I do not always get a chance to talk with
you. In some reading that I had done, and this really surprised
me so I did a little more research on genital herpes. And what
really surprised me was, and this is of the CDC website,
results of a nationally represented survey shows that genital
herpes infection is very common in the United States.
Nationwide at least 45 million people ages 12 and older, 1 out
of every 5 adolescents and adults have genital HSV infections.
Between the late 1970's and early 1990's the number of
Americans with genital herpes infection increased 30 percent.
To me that was pretty shocking.
And I suppose if I can continue to read on VD and gonorrhea
and other sexually transmitted diseases, I would probably still
be as shocked.
So my question is this, and I notice you do your
decisionmaking processes and a lot of your funding goes to
diseases for that which are life threatening. But I do not know
how you define an epidemic. If we have a population where you
have one out of every women are infected with this type of
disease and men and it is growing at this rate, is it prudent
for us to take a look at investments to go after this virus?
Mr. Zerhouni. I think you have put your finger on something
that we have also said in our response. There are 65 million
Americans suffering from sexually transmitted diseases of one
kind or another, increasing by 4 million a year in teenage age.
We have an issue. We have a public health issue.
Most of our investment, as you guess, is in the HIV/AIDS
prevention area. That is where some of the knowledge comes. HPV
is another sexually transmitted disease that is also related to
cancer of the cervix, so we have connections there.
There is no doubt that we have to have a comprehensive
national strategy. CDC is obviously concerned. We have seen an
increased rate of syphilis across the country. And we are also
seeing increasing sexually transmitted disease in the senior
population. So we do have an issue.
Mr. Buyer. So do we have such a plan? Do we have such
compliments of approach? Are you going to turn to Congress and
ask us to fund such a thing, or where are we in this?
Mr. Zerhouni. There is tremendous amount of research
already done on that.
Mr. Buyer. Is there?
Mr. Zerhouni. Yes.
Mr. Buyer. All right.
Mr. Zerhouni. Both by medical and by behavioral research,
and we need both. Because in many ways these are issues that
relate to the environment of the individual as much as the
physiology or biology of the disease.
Mr. Buyer. When you think of 200 million people in our
country and if 65 million are infected, if that is not an
epidemic, I do not know what is, right?
Mr. Zerhouni. It is.
Mr. Buyer. Would you concur?
Mr. Zerhouni. I concur.
Mr. Buyer. All right. Well, I look forward to going a
little further on this issue with your expertise. Not only
yours, but those for whom you can share with me.
Mr. Zerhouni. Sure.
Mr. Buyer. All right. Thank you, sir.
Mr. Green. Thank you, Mr. Buyer.
I recognize myself just for one question.
Now, it is pretty clear Congress has great interest in NIH.
It is indicative of the fact that almost every year Congress
continues to raise the amount of money appropriated to NIH. My
concern over the years is that we got too interested and tried
to meddle too much inside of how sometimes you use that money.
But we do have some oversight responsibility here. So I hope
that is not construed as meddling, but we do have a
responsibility, too. And with that thought in mind, the
clinical research initiatives that you have going on, how would
you recommend that Congress measure the success that you are
having in these incentives. I mean, how do we--we have to, we
should, we want to know are you doing good, doing bad, where
are we? How should we measure that?
Mr. Zerhouni. That is an excellent question. Basically our
approach is to look at the disability rate in a particular
disease condition. For example, one thing that we track is the
disability rate of seniors over the years. We have done this
for 20 years. You can see from the statistic that because of
drugs that we have developed against osteoporosis, the drugs
that we have now developed against arthritis; that if you look
at the disability rate of our seniors, we should have now in
the country, if nothing had been done since 1982, almost 10
million seniors with a disabled acquired condition. We are at 7
million. So you can tell from tracking the data that that is
what is happening.
Other areas the opposite is true. For example, if you look
at coronary heart disease, we can show you over the years that
if we had not done anything, we would have 1.3 million people
dying this year from coronary artery disease and heart attacks.
We have 500,000. But what has happened also is that you now see
increased prevalence patients who have what we call cardiac
failure from aging or hypertension.
So you have to keep track in a systematic fashion of the
disease burden, and this is something that the CDC is working
on to develop measures of burden rather than how many--because
in the context of chronic disease and like acute diseases, like
in cancer, you can measure mortality. Now in cancer it is not
mortality that is important, it is survival.
So I think we need to have an explicit discussion between
the agency, Congress, the public, everyone to say what measures
can we develop that will track now chronic diseases over the
years?
We have done terrifically well, as you know, in stroke for
example. We have reduced the amount of stroke. Hypertension we
are doing well, but not well enough. Only 58 percent of the
patients who should receive the medications that they should
receive them.
So we have a multi-factorial measure that you need to have
and we need to develop for you so you can tell what the
progress is.
Mr. Green. Well, you imply that you agree and think that we
should do that. How do we convert that into action? I think it
would help Congress greatly to have a measurement like that
sooner rather than later.
Mr. Zerhouni. We have many measures in the main diseases.
We do not have them all across-the-board. But certainly perhaps
one thing we could start doing is to have a more explicit way
of representing them to you.
Mr. Green. Doctor, thank you very much for your testimony.
We appreciate your time and effort into this. And you are
dismissed. Thank you.
And if the other panel will seat itself.
Gentlemen, I know that you do not have time to waste, and I
apologize for the 45 minutes that has gone back by as we cast
some really important votes. But all of us are very impressed
that you are here and appreciative that you are here. And I
think that I am absolutely amazed at who we were able to get
here for this particular hearing. We have got a table full of
good folks out there, and I am anxious personally to hear you
and get your statements into the record.
So, Dr. Barron, let us start with you. And you are now
recognized for your statement.
Does everybody want to work at Genentech?
STATEMENTS OF HAL BARRON, CHIEF MEDICAL OFFICER, GENENTECH;
ROBERT J. BEALL, PRESIDENT AND CEO OF THE CYSTIC FIBROSIS
FOUNDATION; AND EUGENE BRAUNWALD, HARVARD MEDICAL SCHOOL, ON
BEHALF OF THE ASSOCIATION OF AMERICAN MEDICAL COLLEGES
Mr. Barron. That is what I hear.
Good morning, Mr. Chairman, and thank you for the
opportunity to testify here before this subcommittee.
The task that I think I have been asked to perform today is
to talk to you a little bit about the clinical trials in the
drug development process within a different model, that is
within the biotech industry. What I would like to do is go over
three specific ideas, concepts that drive what we do at
Genentech, as I think that it is a model for a lot of different
biotech and some pharmaceutical companies.
Just as introduction, my name is Hal Barron. I am a
cardiologist and the Chief Medical Officer at Genentech
responsible for both the preclinical component of drug
development as well as the clinical piece.
I thought what I could do is describe to you the drug
development process from its beginnings in the research arena
and follow it through the various stages that ultimately
translate into a therapeutic for patients. Tell you a little
bit about the exciting, what we call, pipeline. The molecules
that are in the development phase and have recently been
approved, and show you as an example how that has resulted from
great science from bench to bedside. And finally, just comment
a little bit on the discussions this morning from Dr. Zerhouni
about how we see the great accomplishments of the NIH
complimenting the work that we are doing.
So just to begin, the efforts that we put forth in drug
development really start in the discovery phase. Our scientists
come up with an idea of what we call a hypothesis about how a
drug might work and begin to test it in various animal models
to try, in many respects, to disprove their idea so that we can
actually weed out those bad ideas and find the ones that are
most exciting to move forward.
The Genentech scientists are one of the most prolific in
the biotechnology industry, publishing at a rate of almost a
paper a day in peer review journals. They are considered some
of the best researchers in the world as reflected by the number
of citations that they get in the published literature. They
have secured over 4300 patents to date and have another 5,000
pending.
And our research complex, which is over 500,000 square
feet, is the single largest biotech facility in the world.
The projects, although most do not make it out of the
research setting, once they do, once the data is compelling
enough, move into the clinical development arena where we
perform numerous clinical trials on the molecules to determine
whether they are both safe and effective in the indications
that are being studied. We do this in collaboration with other
industry, with collaboration with academics and many trials are
designed and developed within house.
Currently the process that I just described has resulted in
13 molecules that have been approved and around 30 or 35
projects that are in our development portfolio right now. I
just thought I would highlight three recent approvals, which is
really to your question earlier. Our metric for success is how
many of these ideas ultimately 10 or 15 years down the road get
approved and translate into therapeutics for patients. And in
the last 10 months, we have actually had three which is for us,
and for any biotech, is a remarkable accomplishment.
About 10 months ago we had the approval of a drug called
Xolair, which is a monoclonal antibody, which is one of our
focus areas that it basically blocks the interaction of
molecule with its receptor by binding to it. And these
monoclonal antibodies can be developed to virtually any antigen
that we identify as being in a process that involves a disease.
In asthma, research has defined that the elevations of a
molecule called IGE are central in the disease process. And by
blocking that with an antibody to IGE, we were able to
intervene in patients with asthma and reduce their incidence of
asthma severity. That was approved, as I mentioned in June.
Raptiva is another drug that intervenes on a central
pathway in psoriasis where it has been known for a while from
research that we have done as well as at the NIH and academia,
that the T-cells, immune cells in the body which are in the
blood vessels marginate and move into the skin and cause
placque psoriasis. By blocking that through this antibody that
centrally targets that mechanism, we have been able to make
major advances in psoriasis.
And most recently, just several weeks ago we had approval
of an antibody against one of the most important proteins that
a cancer makes that blocks cancer's ability to form blood
vessels and therefore it starves, if you will, a tumor. And
this molecule called Avastin is approved for the treatment of
Metastatic colon rectal cancer where it was shown in clinical
trials to improve survival.
So these recent studies as well as numerous other studies
treating macular degeneration, the leading cause of blindness,
looking at various other cancer therapeutics to target,
prostrate, ovarian, lung, breast and other typical cancers that
affect patients and a whole slew of immunology products that
are developed to specifically target patients with lupus
erythematosus, rheumatoid arthritis, MS and other diseases.
Just because I am running out of time, I just wanted to
conclude with some final remarks about how we think we can best
with the NIH. There has been quite a bit of clinical research--
I'm sorry.
Mr. Green. Mr. Barron, I am not going to cut you off at 5
minutes. If you need a few more minutes, please not.
Mr. Barron. Okay. Well, then I will make one more comment
before I conclude.
I think there are two things that really drive some of the
same themes that Dr. Zerhouni's sort of described in his talk.
And that is that we really strive to do three things at
Genentech. One is to really develop new chemical entities that
are novel. We are not in the business, nor do I think most
biotech companies are in the business of developing ``me too''
drugs as they are called. These are intended to be novel
therapeutics for major unmet medical needs as he describes and
virtually all of what we do.
The second is to really follow the science. Many people
thought the whole story with Avastin and inhibiting blood
vessel growth was not going to translate into a reality. And,
in fact, we ourselves had a negative clinical trial, a very
large phase three clinical trial. But we really followed the
science and I think like the NIH, that translated into the
success in a different cancer, in the colon cancer. And we knew
that it would not be active in every cancer, but one needs to
really follow the science and strive to improve patient care.
And third, and probably most important from where I sit, is
to always ensure that the drugs that we are developing are for
unmet diseases and that patient safety is No. 1, as we design
these trials.
So I think with that we have had successful drug
development. We, as I say, measure ourselves by the number of
drugs approved. And having three in the last 10 months and 13
over the history of the company is been a rewarding experience
in many different ways.
I think just finally, the success stories that I have just
described I think could not have happened without the excellent
basic science that has emerged from NIH funded programs. The
partnership with the NIH has enabled us to conduct many
successful clinical programs that we could not have conducted
without that collaboration. As Dr. Braunwald reminded me
earlier, even one of our first drugs, Tissue Plasminogen
Activator, TPA, was developed in collaboration with the NIH and
Dr. Braunwald Graham back in the early 1980's.
We have other examples, including Evastin for kidney
cancer, a disease that is a relatively small population but
certainly an unmet need that is being done in collaboration
with the NCI and a very small disease, but very, very
problematic called vasculitis or associated vasculitis that we
are doing with the Immune Tolerance Network. and these are just
three of many examples where collaborations with the NIH have
resulted in fruitful therapeutics for patients.
So in summary, the drug development process at Genentech,
although I only highlighted the research and the development
component, really is much more complicated. There is the
manufacturing, the process sciences, the scale up of small
fermentations from research grade material to patient grade
material. The quality controls, the regulatory controls. There
is a lot of different, in fact thousands of people that work at
Genentech just on these areas to enable the discoveries from
the clinic to actually translate into a vial that doctors can
use to treat patients. And that component is, again, another
expertise of us that enables this, as well as the component
that comes from the commercial arena where it is the education
of the physicians about the data so that it can ultimately be
translated into use. But, as I say, none of this could happen
without the excellent people that work at the company, the
collaborations that we have and importantly and maybe the most
important is all the patients who volunteer for these trials
and really provide us with the opportunity to learn about this.
So, I will end there.
[The prepared statement of Hal Barron follows:]
Prepared Statement of Hal Barron, Chief Medical Officer, Genentech,
Inc.
Good morning, Mr. Chairman, and thank you for the opportunity to
testify before the Subcommittee on the most important issue of clinical
trials. My name is Dr. Hal Barron. I am Chief Medical Officer for
Genentech, one of the nation's leading biotechnology companies
headquartered in South San Francisco, California. As you are no doubt
aware, Genentech was founded in 1976 by Herb Boyer and Bob Swanson, and
has the unique distinction of being the very first biotech company.
Since 1976, a robust and productive industry has grown from the
foresight, innovation and risk-taking of Dr. Boyer and Mr. Swanson.
Genentech alone has discovered, developed and currently manufacture 13
therapies targeted at such unmet medical needs as cardiovascular
disease, Cystic Fibrosis and cancer. Last month, the Food and Drug
Administration (FDA) approved Avastin, a groundbreaking therapy that
reduces blood supply to tumors. This product was approved for the
treatment of colorectal cancer and we are in the process of studying
whether the drug is active in a number of different cancers.
Ours is a terrific--and unusual--success story. We are a soup-to-
nuts company, doing everything from basic research to clinical
development to manufacturing to marketing. My written testimony
describes for you in detail the myriad steps and challenges present in
the discovery, development and manufacturing of breakthrough biologics.
My presentation today will focus on one critical piece of the
development process absolutely essential to our success--the clinical
trials we conduct with our patients. I am delighted to have the chance
to discuss with you Genentech's rich experience in drug discovery and
development, our experience with clinical trials, and our valuable
interactions with the National Institutes of Health (NIH). Also for
your edification, I have attached a presentation that provides
comprehensive review of our development organization.
Genentech has one of the biotechnology industry's most extensive
track record in all phases of bringing new disease treatments to
patients--from discovery research through development,
commercialization and product operations. With 13 protein-based
products on the market for serious or life-threatening medical
conditions, Genentech has experience taking a drug from A to Z,
transforming the seed of an idea in a lab into a novel therapy for a
patient in need. Such a fully integrated approach differentiates
Genentech from many other biotechnology companies. Although I won't be
focusing on how we partner with other biotech/pharmaceutical companies,
Genentech has worked closely with such companies as Xoma, Novartis, OSI
pharmaceutical, Amgen, and Roche
DISCOVERY RESEARCH
Research is the wellspring of potential products, and Genentech's
research organization is among the worlds finest. Genentech scientists
are the most prolific in the biotechnology industry, publishing at a
rate of 250 to 300 scientific papers a year, and are among the top one
percent of researchers in the world in terms of total citations. In
addition, Genentech's scientists have secured more than 4,300 patents
worldwide and have another 5,000 pending.
Discovery research at Genentech focuses primarily on three areas of
medicine where there is a strong need for safer, more efficacious
therapies: oncology, immunology and vascular biology. In addition,
Genentech remains open to other projects where the company has
significant opportunities to fill a therapeutic void in important areas
of medicine. To ensure continued scientific excellence, Genentech
opened the Founders Research center, a 275,000 square-foot, $85 million
research facility devoted solely to biotechnology, in October 1992. It
was dedicated to Bob Swanson and Dr. Herbert Boyer in honor of their
pursuit of the promise of biotechnology when they established Genentech
28 years ago in 1976.
In April 2001, the company celebrated its 25th anniversary by
breaking ground on the 280,000 square foot expansion of the Founders
Research Center. The complex--comprising the existing facility and the
new expansion--is the single largest biotechnology research facility in
the world, with more than 500,000 square feet of research space
containing specialized laboratories and state-of-the-science equipment
in several interconnected buildings.
CLINICAL DEVELOPMENT
Genentech uses a rigorous set of criteria, including scientific
factors, medical need and market potential, to determine which projects
to move from discovery research into development. The physicians,
scientists and medical professionals in Development play the essential
role of translating basic science into patient benefit. They help
Genentech determine which potential new drugs are tested against
specific diseases in the clinic and determine how the chosen drug
candidates should move through the many phases of clinical testing.
Since these therapeutic proteins must be delivered into the body
safely, and their effectiveness must be measured and documented in
order to secure marketing approval. These scientists leverage their
expertise in clinical medicine, clinical study design, epidemiology,
bio-statistics and health care economics to design these trials. They
incorporate some of the newest technologies such as molecular
diagnostics, imaging studies (such as CT and MRI scans) as well as
novel biomarkers into these trials as well.
Genentech's development pipeline has both breadth and depth, with
projects targeting a range of disease areas across all phases of
clinical development. This very broad pipeline requires leadership from
the best experts. Our MDs and PhDs come from many prestigious academic
institutions such as Harvard, Yale, Stanford, University of California,
San Francisco (UCSF) and many other top institutions.
COMMERCIALIZATION
Commercial translates research and development innovations into
changes in medical practice that enhance and extend patients' lives.
The Commercial team introduces multiple products into new and different
markets, directs pre-launch commercial development activities, and
utilizes cutting-edge sales approaches. The Commercial organization is
also involved with development activities that bring forward products
in the pipeline in the most efficient way to meet the demands of the
market and the healthcare community--directing market research,
sponsoring medical education efforts, and developing a leading patient
reimbursement program. The Commercial team's unique consultative
education, sales, marketing, and distribution models have resulted in
13 successfully marketed products to date and have made Genentech a
valuable and sought-after partner.
PRODUCT OPERATIONS
Biotech's rich promise is only truly fulfilled when its scientific
breakthroughs are transformed into safe, effective therapies and made
available in quantities sufficient to treat all those in need. This
extremely complex and demanding task is the responsibility of various
product operations groups in the company, including Process Sciences,
Engineering, Quality and Manufacturing.
PROCESS SCIENCES
At Genentech, the transition from laboratory production to full-
scale manufacturing is the work of the Process Sciences group. This
group is made up of five divisions: Cell Culture & Fermentation R&D,
Recovery Sciences, Analytical Chemistry, Pharmaceutical R&D, and
Manufacturing Sciences. The Cell Culture group grows increasingly
larger and more efficient cultures of cells that produce the desired
protein. Recovery Science extracts and purifies the protein molecules
from the cell cultures, with the goal of both high yield and high
purity. Analytical Chemistry is the function that checks to ensure the
purified protein is the right one, and that it is active and able to be
made into a medicine. And Pharmaceutical R&D determines the
formulation--or recipe--for the final medicine, how it should be
administered and its packaging. Finally, Genentech's Process Sciences
group works closely with the FDA to ensure an approved manufacturing
process is in place and pure product is available to patients upon
approval of new pharmaceuticals.
QUALITY
The Quality group is comprised of two main areas: Quality Control,
which executes the many different procedures for testing Genentech's
products; and Quality Assurance, which evaluates all documentation to
determine whether each procedure was completed correctly. Genentech
strictly adheres to federal requirements for quality and collaborates
with the FDA to ensure its processes are of the highest standards.
Every medicine that leaves Genentech has been subjected to stringent
standards and procedures to ensure its quality and purity.
MANUFACTURING
Genentech was the first biotechnology company to scale up protein
manufacturing successfully from the small quantities used for research
to the much larger quantities needed for clinical trials and marketing.
With state-of-the-art facilities in the United States and Europe, the
company continues to be a world leader in the manufacture of human bio-
therapeutics, processing approximately three million liters of product
annually for clinical research and the marketplace through a variety of
fermentation and proprietary purification processes.
In 1998, Genentech completed its second manufacturing facility in
Vacaville, California. The largest multi-product biotechnology
manufacturing facility in the world, the Vacaville plant occupies
420,000 square feet on 100 acres. It became operational in 1999 and
received FDA licensure in April 2000. Also in April 2000, Genentech
further expanded its manufacturing capacity with the purchase of a cell
culture manufacturing facility in Porrino, Spain. When renovated and
licensed, the facility will supplement Genentech's existing bulk cell
culture production capacity.
THE NIH AND DRUG DISCOVERY AND DEVELOPMENT
It is these many complex and interrelated steps that explain why
the vast majority of drugs approved for patients have been discovered
and developed by companies like Genentech. As a research-intensive
company, we learn a great deal from the basic research conducted by the
NIH. The NIH performs this function extremely well and we support and
appreciate the continued increases in funding you have given the NIH
over the past several years. In addition, we partner with the NIH on
clinical trials particularly in areas outside our area of expertise or
where trials could not be conducted without NIH support. This
collaboration is extremely important as Genentech or any company for
that matter, cannot do everything alone and we greatly benefit from the
expertise of the NIH and academia in general.
The opportunities for industry/government collaboration have been
fruitful and could be even more substantial. One area in which the NIH
is particularly well suited to make important advances is that of
molecular diagnostics and discovery of novel ``bio-markers''-markers
that identify which patients with a given disease have the worst
prognosis. Advances in identifying biomarkers presents a real
opportunity to benefit patients at a much faster pace than today's R&D
efforts, and is an area that could enable industry to be more
successful in their endeavors to bring targeted therapeutics to market.
In addition, there is an opportunity for industry to work with the
NIH in developing drugs for indications that the company decides not to
pursue. It is clear that a company such as Genentech cannot design and
implement all the necessary clinical trials to maximize the benefit of
their new therapeutics. Thus, certain patient populations may not
always be examined. Whether it is because the trials will take too
long, represent too small a population or fall outside a company's
focus area, providing the NIH access to our novel therapeutics can and
has been invaluable. We hope such activities continue to be funded as
they have the opportunity to make a significant difference in patient
care.
I hope that this presentation has given you a better understanding
of the processes and challenges we face in bringing new, breakthrough
biologic to market for patients. I hope you also have a better
understanding of the relationship between the NIH and private industry.
We look forward to exploring these and other partnership opportunities
with Dr. Zerhouni and this Subcommittee. Thank you again, Mr. Chairman,
for this opportunity to testify before you and the Subcommittee. I am
happy to answer any questions you may have.
Mr. Green. Thank you very much, Doctor. And you are the CMO
at Genentech and have all the way from California. And you need
to understand we are grateful for your efforts to be here.
Mr. Barron. Thank you.
Mr. Green. Mr. Beall, Robert Beall, President and CEO of
the Cystic Fibrosis Foundation. I was talking too fast there.
That is hard for a southern, too.
We are delighted you are here and we look forward to your
testimony. And you are now recognized.
STATEMENT OF ROBERT J. BEALL
Mr. Beall. Thank you.
As you said, I am the President and CEO of the Cystic
Fibrosis Foundation. This is a private, nonprofit voluntary
health organization dedicated to find a cure and control for
cystic fibrosis.
It is particularly an honor for me today to be able to have
the opportunity to follow Dr. Zerhouni, because we believe that
he has inspired some great vision for the NIH. And it is a very
critical juncture that at the NIH that we are all looking at
through your efforts and through the NIH, and through the
voluntary health organizations in academia.
I actually spent the very part of my own professional
career at the NIH, and I can tell you that under Dr. Zerhouni's
leadership and vision, I have never been more optimistic about
the future role of the NIH and how it can play a great part
improving the quality of life and length of life for all
Americans.
We believe the changes that are set forth in the Roadmap
are necessary to ensure that the NIH continues to be the
biomedical research leader that we expect of it in the 21st
century.
In the last decade, the Cystic Fibrosis Foundation has
reengineered its own research approach to ensure the success of
our mission to cure this genetic disease, cystic fibrosis. And
as Dr. Zerhouni mentioned in his comments, we have created a
model infrastructure of basic and clinical research to promote
and accelerate the development of new therapies to treat cystic
fibrosis. With the discovery of our CF gene in 1989 and the
increased understanding of the pathogeneses of this disease, we
made a big leap in the 1990's of translating this knowledge
from the lab to the bedside.
As a result of our comprehensive approach, we now have
nearly two dozen drugs that are in clinical trial. This is our
metric for success at this point. Any one of these drugs could
have a major impact on the quality of life and the length of
life of CF patients and more importantly, to provide for the
ultimate cure for cystic fibrosis.
I would like to share with you a few points about the
lessons we have learned in this process that may be appropriate
something that we can think about as the NIH Roadmap moves
forward.
The first thing is that it is mandatory that new cutting-
edge technologies like high-throughput screening, proteomics,
structural genomics be utilized to expedite discovery of new
and novel compounds. During the past 5 years, our organization
has committed more than $100 million to apply these
technologies to cystic fibrosis. It used to take 2 or 3 days
for a single chemist to be able to evaluate one or two
compounds. We can now screen more than 20,000 compounds per day
to see if they might be the drugs of the future for CF. In
fact, we have identified several lead compounds for CF that we
hope will enter clinical trials within the next 18 months. None
of these compounds would have been discovered were it not for
the application of these incredible new technologies for cystic
fibrosis. The Roadmap's focus on new technologies could be just
as fruitful.
Second, creative mechanisms must be put into place to
entice the biopharmaceutical industry to develop drugs for
orphan diseases like cystic fibrosis. With the cost of
development drugs approaching the billion dollar level, many
companies are not willing to make the investment needed for
orphan diseases like cystic fibrosis. As a result, our
foundation has made commitments to companies for up to $25
million to reduce their financial risk and to help them develop
CF drugs. Most of the drugs that I mention in our pipeline are
the efforts of these financial alliances between the foundation
and without biopharmaceutical partners. NIH should join forces
with the private sector nonprofits to facilitate orphan drug
development for diseases like cystic fibrosis and other orphan
diseases.
Third, clinical trial networks are essential for
coordinating the clinical research efforts of industry,
academia and the Federal Government. In 1998, we established
our own clinical trials network that now includes 18 centers,
linked by the web to a coordinating center at Children's
Hospital and Regional Medical Center in Seattle. The CF
Foundation's Therapeutics Development Network has played a
major role in bring biopharmaceutical companies into the area
of cystic fibrosis.
Equally important, the network facilitates access to the CF
patients who are absolutely eager to participate in safe, well-
designed clinical trials.
Since this network was established, nearly 30 clinical
trials have been completed or underway. We are grateful to
Genentech for showing us the need for these networks as we
worked with them very closely in the early 1990's in the
development of Pulmozine, which is now being used by over
18,000 patients with cystic fibrosis.
Our work to bring new drugs to people with CF and the
successful improvements in the health of the CF population
really reaffirms Dr. Zerhouni's vision for the NIH. There comes
a time in any research organization when the accumulation of
knowledge is not an end in itself. Efforts must be made to
translate this knowledge into treatments for people with
disease.
The CF Foundation is very fortunate to have a productive
relationship with several institutes and centers at the NIH.
The future at NIH is critical to all of us.
Certain changes at the NIH would clearly strengthen its
ability to advance clinical research. Clearly the Roadmap
addresses most of these issues, and we endorse its aggressive
implementation. We strongly encourage the Congress to provide
Dr. Zerhouni with the resources and the authorization and the
support to capitalize on the potential of the Roadmap.
Toward that end, the CF Foundation's recommendations for
the NIH include:
An increase in the NIH's role in the discovery and
development of new drugs for orphan disease.
We encourage the improved training of clinical researchers
and the recognition that clinical research is a viable career
in academic medicine.
We encourage the establishment of special emphasis research
panels to improve the peer review process of clinical research
proposals.
We want to see the increased collaboration among the NIH,
amongst academic institutions and private foundations and
industry for the support of NIH supported clinical trials
network.
And finally, we want to see, and it could be one of the
most important, a reduction in the redundancy of bureaucratic
hurdles that impede the efficient conduct of clinical trials
but in no way facilitate patient safety.
We believe that the NIH must embrace the opportunity to
translate knowledge fathered from basic research to assure the
development of new therapies.
We certainly thank you for holding these hearings. Congress
has reason to be proud of its role in supporting the NIH over
the years, and we now feel that you can have a great role in
terms of supporting the shape of the future of the NIH and in
terms of improving the quality of health care for all Americans
during the 21st century.
CF Foundation can serve as a model for clinical research on
other orphan diseases. We stand ready to work with the NIH and
congressional leaders as they consider these important changes
for the future.
Thank you very much.
[The prepared statement of Robert J. Beall follows:]
Prepared Statement of Robert J. Beall, President and CEO, Cystic
Fibrosis Foundation
Good morning, Mr. Chairman and Members of the Committee. I am
Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis
Foundation, a private nonprofit foundation with a mission of finding a
cure for cystic fibrosis (CF). It is a great pleasure to appear before
the Committee today to discuss the research approaches that the CF
Foundation has adopted, and it is certainly an honor to appear at this
hearing with Elias Zerhouni, M.D., who is providing strong and creative
leadership at a critical juncture in the history of the National
Institutes of Health (NIH).
In the last decade, Congress has generously increased funding for
NIH. Between fiscal years 1999 and 2003, Congress accomplished the
impressive goal of doubling the NIH budget. The substantial funding of
NIH contributed to significant advances in basic research, including
the mapping of the human genome, and deepened our understanding of a
number of diseases.
It is now vital to assess our ability to translate the basic
research advances of the last decade into treatment advances. The CF
Foundation has, in the last decade, reformulated its own research
approach to encompass many types of research, from basic research
through Phase III clinical trials, and has created the infrastructure
required to accelerate the development of new CF therapies. As a
result, we now have a pipeline of nearly two dozen potential therapies
that are being examined to treat people with CF. We applaud Dr.
Zerhouni for undertaking a meticulous review of NIH, its structure, and
its methods of funding research, as we believe progressive changes are
necessary to ensure that NIH continues to be the biomedical research
leader of the 21st century.
LIVING WITH CYSTIC FIBROSIS
Before I present the CF Foundation's comprehensive approach to
research, I would like to describe CF and its effects on the
individuals living with the disease. Each year, 1,000 children in the
United States are born with CF, and there are about 30,000 Americans
living with CF. In 1989, CF Foundation-supported researchers discovered
the gene that is altered in CF, and since that time our fundamental
understanding of the disease has improved significantly.
The defective CF gene causes the body to produce abnormally thick,
sticky mucus that clogs the lungs and leads to life-threatening lung
infections. The thick mucus in those with CF also can obstruct the
pancreas, preventing digestive enzymes from reaching the intestines to
break down and aid in the absorption of food.
The common symptoms of CF include chronic cough, wheezing or
shortness of breath, excessive appetite but poor weight gain, and
greasy, bulky stools. CF symptoms vary from patient to patient, due to
the fact that there are more than 1,000 mutations of the CF gene.
CF has been transformed to a chronic disease, but living with CF as
a chronic disease requires a rigorous daily regimen of therapy.
Treatments for individuals with CF include enzymes that aid digestion,
antibiotics administered during bacterial infections and as a
preventive measure, and daily therapy to loosen the mucus in the lungs.
Several new drugs have been approved in the last decade that have
improved the health of people with CF, including Pulmozyme, which thins
the mucus so that it can be coughed up, enabling the individual to
breathe easier and reducing the chance for infections. Strict adherence
to CF treatments improves the health status and quality of life for
individuals with CF, but the stringent regimen can be a physical,
emotional and financial challenge for patients and their families.
When the CF Foundation was founded in 1955, people with CF often
did not live to attend elementary school. Over the past five decades,
the median age of survival has improved significantly and is now in the
early 30s. This improvement in the life expectancy for those with CF
can be attributed to research advances, which I will discuss in some
detail later, and to the teams of CF caregivers who offer specialized
care of the highest quality. The CF Foundation supports a nationwide
network that includes 117 CF care centers at large academic and medical
institutions, and a number of smaller affiliate care centers, as well
as nearly 85 programs that are focused on the care of adult patients
who are 18 years and older. The CF care center network ensures that
information about advances in care can be immediately disseminated to
all CF caregivers who provide cutting edge care to the more than 90
percent of the individuals with CF who receive care at these centers.
The care center network also functions as a training ground for those
who seek careers in CF care or research. Together, Dr. Zerhouni has
referred to this as the CF ``community of research,'' as the CF
community works to bring research to the bedside to improve care.
THE RESEARCH MISSION OF THE CF FOUNDATION
The cornerstone of the CF Foundation's effort has been to quickly
put into place the critical elements necessary to translate basic
research knowledge to new therapies. I'd like to share a few points
with you today about lessons learned by the CF Foundation which may be
appropriate for the NIH as it moves forward in the Roadmap effort.
We believe that the key to finding the cure for CF, and improving
the quality of life of those with the disease, lies in the CF
Foundation's research program. There are several key elements to the CF
research program that are making it successful:
1) An aggressive program to discover potential CF drug candidates.
Although the discovery of the CF gene in 1989 was an important step
forward, there is still much to be learned about the disease. As a
result, the CF Foundation continues to invest in basic research on CF
to deepen our knowledge of the disease and to understand how we may
intervene in the disease course. During the past five years, we have
committed more than $100 million for cutting-edge technologies to aid
in the discovery of new compounds for CF. We have now identified
several lead compounds that we hope will begin clinical trials in CF in
the next 18 months. None of these compounds would have been discovered
without the application of these cutting-edge technologies.
2) Establishing a clinical trials network. The CF Foundation
established a network for clinical trials, called the Therapeutics
Development Network (TDN), in 1998 specifically to work with industry
to pursue new treatments for CF. The network is a critical enticement
for industry to focus on CF, as its leaders provide expert advice on
trial design and its very structure facilitates patient recruitment.
The usefulness and efficiency of such a network were demonstrated
through collaborations in the early 1990s with Genentech, Inc. on the
development of Pulmozyme and with Pathogenesis (now Chiron) on the
development of TOBI. The network links key CF clinical research centers
with a centralized coordinating center at the Children's Hospital and
Regional Medical Center at the University of Washington at Seattle.
Expanded twice, the network now includes 18 centers across the country
to further enhance recruitment, while building on the core features of
centralized data management and analysis, and a coordinated system of
data safety monitoring with disease-specific expertise for protection
of patients. Since the TDN was put into place, nearly thirty clinical
trials--including Phase I, II, and III trials--have been completed or
are underway. Anyone of these drugs in clinical trials could have a
major impact on the disease or provide an ultimate cure.
3) A matching awards program for companies to develop CF therapies.
Because CF is an orphan disease--with fewer than 200,000 persons
affected--it presents companies developing new drugs a smaller possible
financial return than other diseases. To encourage companies to become
engaged in CF drug development, the CF Foundation established the
Therapeutics Development Program, which includes awards to companies to
undertake research and development of promising drug candidates. We
established financial collaborations with biotechnology and
pharmaceutical companies to bring them into the field of CF. These
commitments, ranging up to $25 million, help companies reduce their
financial risks in order to focus on CF. Most of the drugs in our
current pipeline would not be tested in CF patients were it not for
these initiatives.
4) Evaluation of existing drugs to determine their utility in
treatment of CF. While the CF Foundation pursues strategies for the
development of new CF treatments, it simultaneously employs a ``low-
hanging fruit'' approach, investigating new uses of drugs that have
been approved by the Food and Drug Administration (FDA). This strategy
has already proven successful, with the completion in 2002 of a Phase
III trial that tested the use of the oral antibiotic azithromycin in
individuals with CF who had chronic Pseudomonas aeruginosa infections
in their lungs. The results of the trial, coordinated by the TDN,
showed that those who received azithromycin three times a week for 24
weeks experienced improved lung function, gained weight, and spent only
half as many days in the hospital as those who received a placebo.
OVERHAULING CLINICAL RESEARCH AT CF FOUNDATION AND NIH
Our efforts to bring new drugs to people with CF reaffirm Dr.
Zerhouni's vision for the NIH. There comes a time in the history of any
research organization when the accumulation of critical knowledge must
be translated into treatments for people with disease. The NIH Roadmap
provides the opportunity for the NIH to do this. However, unless the
NIH takes an active role in translation, many of the diseases for which
we now have identified the gene and possess a strong understanding of
their pathophysiology will never be researched, as few organizations
have the financial resources to exploit the basic research
opportunities to find new therapies.
When the CF Foundation undertook the establishment of the CF
clinical trials system in 1998, we asked several fundamental questions
about the status of the CF research effort and our ability to translate
basic research findings into new CF treatments. When we read the NIH
Roadmap at the time of its release in September 2003, we found that
NIH, under the leadership of Dr. Zerhouni, had asked the same basic
questions about the NIH. Those questions were: 1) What are today's
scientific challenges? 2) What are the roadblocks to progress? 3) What
do we need to do to overcome those roadblocks? and 4) What can't be
accomplished by any single Institute--but is the responsibility of NIH
(or the CF Foundation)--as a whole?
The answers to those questions--as they applied to CF research--led
us to the determination that we had to form the TDN to streamline CF
clinical trials and accelerate the translation of basic research into
new treatments. We are pleased that the team that worked on development
of the NIH Roadmap reached a parallel conclusion--that the clinical
research enterprise supported by NIH must be re-engineered. The Roadmap
recommends the integration of clinical research networks, improvements
in the training of the clinical research workforce, and the development
of core services for translational research initiatives. The CF
Foundation applauds Dr. Zerhouni for undertaking a thorough evaluation
of NIH and assembling a team to assist in the redesign of key NIH
clinical trial programs.
We believe lessons learned in the CF Foundation's TDN will be
instructive as NIH proceeds with establishing clinical trials networks
and will provide special insights regarding the most efficient means of
conducting clinical trials on orphan diseases. Supporting orphan
disease research must be a central tenet of NIH, as few in the private
sector can undertake this difficult and costly work.
THE PARTNERSHIP BETWEEN CF FOUNDATION AND NIH
The CF Foundation has enjoyed a productive relationship with
several institutes and centers at NIH. The National Center for Research
Resources (NCRR), under the leadership of Judith Vaitukaitis, M.D.,
appreciated the CF Foundation vision for improving its clinical trials
capacity and provided important early financial support for the TDN
coordinating center. The support the coordinating center has received
is in keeping with the NCRR mission of providing CF clinical
researchers the tools they need for the efficient completion of their
studies, and we look forward to a continued strong relationship with
NCRR.
A number of basic and clinical CF research projects have received
support from the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood
Institute (NHLBI), and research on the human genome--of tremendous
importance to CF--has been supported by the National Human Genome
Research Institute (NHGRI). We are very pleased that NIDDK recently
released a Request for Applications for Cystic Fibrosis Research and
Translation Core Centers to support both basic and clinical research on
CF. As envisioned by NIDDK, the Core Centers will provide shared
resources to support research to develop and test new CF therapies and
will foster collaboration among strong CF research centers.
While the CF Foundation is fortunate to have incredibly dedicated
volunteers who are willing to raise significant dollars to support the
mission of finding a cure, this undertaking cannot be successful
without a strong partnership with the NIH. All of these relationships
with NIH institutes and centers are critical to our efforts to advance
CF research.
RECOMMENDATIONS FOR RE-ENGINEERING CLINICAL RESEARCH
We offer several recommendations for reform at NIH. While the CF
Foundation has worked productively with NIH, we believe that certain
changes would strengthen the ability of NIH to advance clinical
research. Most of the issues we identify below are addressed in large
part by the NIH Roadmap, and we endorse its aggressive implementation.
We encourage Congress to provide Dr. Zerhouni and the NIH with the
tools and resources to capitalize on the potential of the Roadmap. In
order to realize the benefits of the substantial investment this
country has made in basic research, we must take this enterprise to the
next level to benefit Americans living with life-threatening diseases
today. Toward that end, the CF Foundation recommends:
Improved training of clinical researchers and acceptance of clinical
research as a viable career in academic medicine. A number of
blue ribbon panels have reported in recent years the various
influences on young physicians that discourage them from
choosing a clinical research career. If steps are not taken
soon to improve training of clinical researchers and ensure
these researchers a means of succeeding in academic
institutions, the nation's clinical research enterprise will be
crippled.
Collaboration among NIH, academic institutions, private foundations,
and industry in NIH-supported clinical trials networks. The CF
Foundation has learned, through direct experience, that
cooperation among all players must be ensured early in the
clinical trials process. The involvement of industry is
critical. Moreover, the traditional roles that the players in
clinical trials have assumed may not be the most appropriate
ones in all circumstances. For example, the CF Foundation chose
to fund biotechnology companies, as that strategy appeared to
be the best way to stimulate development of a new treatment.
Another potential reform is action by academic institutions to
streamline their research review processes to ensure that
multi-institution clinical trials can function smoothly. We
must all work together to facilitate clinical trials so that we
can improve the health of our country.
The improvement of peer review of clinical research proposals through
routine establishment of special emphasis panels. As noted in
the article in JAMA (2004 Feb18;291 (7):836-43), clinical
research proposals submitted to NIH fare poorly when they are
reviewed by basic scientists who may not have appropriate
experience or knowledge to review such proposals. In certain
disciplines, special emphasis panels have been established for
review of clinical research proposals. We recommend that such
panels be established on a more routine basis to encourage
appropriate consideration of clinical research proposals.
Bureaucratic obstacles to the speedy completion of clinical trials
must be eliminated. Efforts must be made to reduce duplication
in the review of trials by institutional review boards (IRBs).
Although patient safety must be a primary concern in any
clinical trial, the current system of review allows duplication
and delay without improving patient protection.
THE FUTURE OF CLINICAL RESEARCH
The CF Foundation is committed to pursuing whatever steps necessary
to bring new treatment options to people with this disease. To date,
those steps have included funding basic and clinical research; in the
future they may encompass other aspects of drug development if public
or private collaborations are not forthcoming. Our vision is
unswerving, as we have shown that we can fill a pipeline with promising
options for patients. We believe the NIH must embrace the opportunity
to translate the knowledge gathered from basic research to securing the
development of new therapies. Just as the CF Foundation does not have
all the answers from CF basic research, we believe it is essential to
move forward and to take risks to find new treatments. No lives can be
saved without taking risks while at the same time assessing patient
safety. And, the risks of not taking such steps are unacceptable to the
CF Foundation.
On behalf of the Cystic Fibrosis Foundation, I would like to
express my appreciation to the Committee for holding this hearing to
discuss the future of NIH. Congress has reason to be proud of its role
in supporting NIH, which is the world's leader in biomedical research.
The NIH has strong leadership to move into the new century, when we
will see the translation of basic research into new treatments for many
diseases. We believe the experience of the CF Foundation in clinical
research can serve as a model for research on other orphan diseases,
and we stand ready to work with NIH and Congressional leaders as they
consider changes for the future.
Mr. Green. Thank you, Dr. Beall.
And our last distinguished witness today is Dr. Eugene
Braunwald, Hersey Distinguished Professor of Medicine and
Faculty Dean for Academic Programs, Partners Healthcare System,
Brigham and Women's Hospital, Harvard Medical School,
Association of Medical Colleges.
And, Doctor, you are here on behalf of the Association of
Medical Colleges today.
And you are recognized for whatever time you might consume.
STATEMENT OF EUGENE BRAUNWALD
Mr. Braunwald. Thank you, sir. Thank you for inviting me to
testify on this important subject.
Clinical research is the bottleneck through which all
scientific developments in biomedicine must flow before they
can be of real-world benefit. And the academic community has an
essential role to play in loosening this bottleneck, and I am
pleased to be here to represent the Association of American
Medical Colleges, which I'll refer to as the AAMC.
The AAMC represents the Nation's 126 medical schools, 400
major teaching hospitals and more than 105,000 faculty in 96
academic and scientific societies.
Now, I have conducted clinical research for more than 50
years, and 12 of these years was at the NIH. And since 1972 I
have been at Harvard and my own work is in cardiovascular
disease.
And the opportunities and the challenges that we face now
are greater than they have been at anytime through my
professional life. Now the opportunities referred to about all
morning, namely that useful life now has the potential of being
prolonged and major chronic illnesses such as stroke, cancer,
Alzheimer's Disease, mental illness which has not been
mentioned can all be ameliorated. And this comes from the
landmark developments of genetics, bioengineering,
neuroscience; the work that the NIH has done and that has been
so wonderfully supported by the Congress.
So that is the tremendous opportunity; to take advantage of
this information.
The challenge is to translate it. And if we are unable to
translate it, then we will have missed the opportunity. Without
a robust national program of clinical research that enjoys the
participation of patient groups, that enjoys the involvement of
academics, of industry, then the effect on the public health
could be quite deleterious, and I am sorry to say that the
national program of clinical research is anything but robust
right now. And there is a lot of work that needs to be done.
So what is the problem? The problem that we see and one
that I encounter in my work everyday, is a lack of coordination
among the different pieces. The pieces are very strong, but
they are not well coordinated. So there is a fragment of
cottage industry which investigators each going in their own
directions. There are tremendous inefficiencies. As teams are
assembled for specific projects and then they are quickly
disbanded when the project is completed and the funding ceases.
And you have lost a tremendous amount in that process of
putting it together and in breaking it apart.
The regulatory burdens are enormous. And they do not really
help and protect patients in the field. I mean, they are well
intentioned, but they slow the process down.
The information systems that are used in clinical research,
they are based on billing records. And there is no good way of
having information systems that ties clinical research together
in the way Dr. Zerhouni showed. And basically what we're using
now in clinical research are pretty much a gerryrigged system
off the clinical record keeping and clinical billing.
Another problem is protecting the integrity of research and
fostering the public trust. So we invite subjects to
participate in clinical research and it's essential that they
have our trust. The AAMC and the member organizations recognize
that there's a very special relationship between investigators
and their subjects. And that safety of the human participants
in trials is of paramount importance. And we need to go beyond
the simple compliance and create a culture of conscience that
we train our young people in.
Clinical researchers need very clear standards of conflict
of interest. And these standards have to be clear and absolute.
and it is my understanding from discussions with colleagues at
the NIH, that some of the rules have been a little ambiguous.
And I think it is important to clarify them, but at the same
time it is equally important that industry should not be
deprived of valuable information and valuable advice and
consultation that can be offered by government scientists and
by academic scientists.
Another problem that's faced by clinical research is a
shrinking pool of clinical investigators. Now it has been my
privilege to train a number of successful clinical researchers
over the years. And the route is not an easy one. You have to
get an advanced doctoral degree, M.D., then serve an
internship, serve a residency, then do a rigorous research
fellowship in a specialty. And the first faculty position where
you can actually conduct research on your own, is usually
obtained until the person is the thirties or the mid, sometimes
in the late thirties. And success depends in large part on
being able to obtain funding, which in turn depends on the
fortunes and sometimes the whims of the sponsoring agency or
the sponsoring company.
So Instability of funding coupled with the need to support
a family is a tremendous deterrent to talented young physicians
who are considering a career in clinical research. And, of
course, they are the future and they are the ones we have to
find a way of bringing them into the system.
So I think that the answer lies with both research sponsors
and academic partners. We have to increase training
opportunities. The NIH has done well in the last 3 or 4 years,
but it is just a drop in the bucket. We have to provide more
mentored programs. We have to expand the Federal loan repayment
programs, and I've served on the NIH committee that has done
that for the National Health Institute. It is just in its
infancy. It is going to have a great impact, but that needs to
be supported.
And most important, it is important to provide longer
commitments of support so that there is a feeling of stability
in a career in clinical research.
So I think that to conclude, I think we need a balance
tripartite system for clinical research.
One partner in this tripartite system, of course, is the
Federal Government, which supports clinical research through a
number of agencies, the VA, DoD, the Agency for Healthcare
Research and Quality and of course the NIH, which is the lead
agency.
And the plan that the NIH has developed and that Dr.
Zerhouni has articulated is a plan that the AAMC, and I can say
that all of us at the academic institutions around the country
support with tremendous enthusiasm. So that is one partner.
The second partner in this trio is academic medicine; the
medical schools, the teaching hospitals where the actual
research is conducted. And the majority of researches are at
these institutions and they are the institutions that train the
future clinical investigators. And so I am here representing
the AAMC which speaks for these institutions.
Now the third partner who is equally important is industry.
And we have the biotechnology industry, the pharmaceutical, the
informatics industry. And they provide ideas, resources and
expertise and without that you cannot really bring a product
and make it available to the public.
And the private foundations, as we have just heard, such as
the Cystic Fibrosis play a vital role.
So each of these partners has a stake in the success of the
other. And they tend to be working in separate directions most
of the time. And if it is good for the Federal Government, it
has got to have a tremendous impact on the academic
institutions which is where the scientists come from that
populate the laboratories at Genentech and vice versa.
So I think that getting to the specific case of clinical
research, I think that the multiple medical schools and
hospitals and clinics have to be tied together in networks and
using modern information systems. And these need to be stable
networks and they should carry out clinical research that has
both industrial, private as well as Federal sponsorships
whenever possible.
Then we have stable networks, then they will attract the
most creative young minds for long term careers in research.
And if we develop a robust clinical research enterprise, then
the ultimate win, of course, is going to be the public who have
the greatest stake of all in this proceed.
Thank you very much for inviting me.
[The prepared statement of Eugene Braunwald follows:]
Prepared Statement of Eugene Braunwald, Hersey Distinguished Professor
of Medicine, Harvard Medical School, Chairman, TIMI Study Group,
Brigham and Women's Hospital
Good morning. Thank you Mr. Chairman and members of the
subcommittee for inviting me to testify today on this important
subject.
I am a Professor of Medicine at Harvard Medical School. I have
conducted clinical research on heart disease for almost 50 years, from
1955 to 1968 at NIH, then at the University of California, and since
1972 at Harvard. I have also served as Chief Academic Officer and
Faculty Dean at Partners HealthCare, an integrated academic health care
system that includes two Harvard affiliated hospitals--Massachusetts
General and Brigham and Women's.
Clinical research is the neck of the scientific bottle through
which all scientific developments in biomedicine must flow before they
can be of real-world benefit to the public. I believe that the academic
community has an essential role to play in loosening this bottleneck
and I am pleased to be representing the Association of American Medical
Colleges (AAMC). The AAMC represents the nation's 126 accredited
allopathic medical schools, some 400 major teaching hospitals and
health systems, and more than 105,000 faculty through 96 academic and
scientific societies. The Association is the most appropriate
representative of the academic community in this policy arena because
the performance of clinical research is a defining characteristic of
medical schools and teaching hospitals. The AAMC membership conducts a
very large share of the biomedical and behavioral research performed in
this country, and has been the source of many of the dramatic
breakthroughs that have revolutionized biology and are transforming
medicine. My testimony today will focus on the role of academia in
clinical research and where there is room for improvement.
The AAMC has been concerned about the clinical research enterprise
for several years and convened a consensus development conference in
1998, out of which came a broadly inclusive definition of clinical
research that led to the conception of a national ``clinical research
enterprise,'' and recommendation of actions to strengthen that
enterprise. That conference led to the establishment of the Clinical
Research Roundtable in the Institute of Medicine (IOM) and an AAMC Task
Force on Clinical Research. The Task Force was charged with assessing
the opportunities and challenges facing clinical research in medical
schools and teaching hospitals, and developing a set of findings and
recommendations to strengthen clinical research in those institutions.
The Task Force report, ``For the Health of the Public: Ensuring the
Future of Clinical Research'' was issued in January 2000. It concluded
that the future of clinical research in medical schools and teaching
hospitals is synonymous with the viability of their defining academic
missions and their commitment to advancing the health of the public.
The conclusions of the Task Force still hold true today and my
testimony will focus on the ideas generated by the Task Force and the
current thinking in this important policy arena.
Too often, clinical research has been considered synonymous with
clinical trials. Clinical research is a component of medical and health
research intended to produce knowledge essential for understanding
human disease, preventing and treating illness, and promoting health.
Clinical research embraces a continuum of studies involving interaction
with patients, diagnostic clinical materials or data, or populations,
in any of these categories: disease mechanisms; translational research;
clinical knowledge, detection, diagnosis, and natural history of
disease; therapeutic interventions including clinical trials;
prevention and health promotion; behavioral research; health services
research; epidemiology; and community-based and managed care-based
research. This broad and inclusive definition is responsive to the
dynamic changes that are taking place within the biomedical and health
sciences and in the organization and financing of health care. The
support and conduct of this research enable advancements across diverse
fields of science to be applied to human health and may well transform
the practice of medicine and the delivery of health care in this
century.
Both the opportunities and challenges that we face in clinical
research today are greater than at any time during my professional
lifetime. The basic research resulting from the doubling of the NIH
budget and the sequencing of the human genome have provided vast
possibilities for improving human health, by improving diagnosis,
treatment and prevention. Opportunities now exist to prolong useful
life by combating the major chronic illnesses such as cancer,
hypertension, stroke, heart attack, arthritis, emphysema, Alzheimer's
disease, and mental illness.
Actually, at no time in human history has the potential been
greater for translating biological knowledge and technological
capability into powerful tools for preventing and treating disease and
caring for our communities' health.
However, the landmark developments in genetics, bioengineering,
neuroscience, and molecular and structural biology that have occurred
during the past twenty years will mean little in practical terms if
clinical researchers are unable to translate this science into new and
effective medical and health practices. Without a robust and coherent
national program of clinical research that enjoys the participation and
harnesses the full strength of all components of the health sector, the
impact of revolutionary advances in the biomedical and health sciences
on the health of the public will be greatly slowed. And the national
program of clinical research that now exists is anything but robust or
coherent.
The major blocks in biomedical science are now at the interface of
basic research and clinical care. The lack of coordination of the
clinical research enterprise has led to a fragmented cottage industry
of investigators each going in their own separate directions. There are
great inefficiencies as teams are assembled for specific projects, then
quickly disbanded when the project is completed and funding ceases.
Regulatory burdens are enormous and growing; they impose delays, costs,
and daunting disincentives on clinical researchers and dissuade many
bright young medical graduates from choosing careers in clinical
research. Information systems available to clinical investigators and
designed to support clinical research are relatively primitive. Most of
these systems are based on the financial and administrative needs of
provider organizations, and virtually all are inadequate for clinical
research.
Advances in information technology will be critical to the future
of clinical research and to improvements in health care in the 21st
century. The creation of federated, inter-operable databases is
essential to help exploit the power provided by the Human Genome
Project to enrich our understanding of human diseases, guide the
development of therapeutics and preventives, identify potential
subjects for clinical trials, and track long-term outcomes through
post-trial and post-marketing surveillance. There is presently a
profound lack of public or private investment in technology development
in the clinical research arena, perhaps due to the lack of financial
incentive; I believe that this is an area of urgent need that should be
an attractive target for novel public-private partnerships. Since
progress in this area is almost certain to increase efficiency in all
aspects of clinical research, it is imperative that academia and the
federal government work together to develop principles for the
standardization, collection and sharing of research data, as well as a
nationally inter-operable clinical research information system that is
designed to meet the needs, and exploit the opportunities, now
presented in clinical research.
Protecting the integrity of research and sustaining the public's
trust is as important a building block for clinical research as other
more tangible items such as informatics, molecular libraries, and
physical facilities. The AAMC and its members recognize that academic
medicine and the American public have forged a special relationship
rooted in trust that is nowhere more evident, or more fragile, than in
clinical research involving human participants. The safety of human
participants in research is of the utmost importance and must continue
to be our highest priority. In this regard, the AAMC is pleased to have
played a leadership role in recently creating the Association for the
Accreditation of Human Research Protection Programs (AAHRPP). AAHRPP is
a non-profit entity that the AAMC believes can help to lead the
nation's clinical research community beyond compliance to a culture of
conscience and responsibility in every investigator, every individual
who participates in clinical research, and every supervisor of the
research.
To accomplish this will require that clinical researchers operate
under a standard policy on conflicts of interest that is clear and
absolute. For example, it is my understanding from discussing this
issue with colleagues at the NIH that some of the rules have been
ambiguous. This ambiguity must be removed, but at the same time
industry should not be deprived of valuable advice and consultation,
nor academic research of the enrichment provided to both governmental
and academic scientists, through appropriate consultative interactions.
The recent reports by an AAMC task force on individual and
institutional financial interests in clinical research provide a
helpful framework for structuring and monitoring such interactions.
In a paper published in the February 18, 2004, issue of the Journal
of the American Medical Association (JAMA), Kotchen, et al., state
``[I]t appears that the greatest threat to clinical research, however,
is the relatively small and shrinking pool of clinical investigators.''
AAMC President Jordan Cohen, M.D., made similar arguments in a November
2003 commentary, stating ``the NIH's grand vision will become reality
only if we can produce a steady supply of well-trained physician-
scientists who are both clinically and scientifically competent, and
offer them attractive, stable career pathways.''
It has been my privilege to train a number of successful clinical
researchers. The route is not an easy one. After obtaining the MD
degree, an internship and residency, and rigorous research training in
a specialty are required, and a first faculty position is not usually
obtained until the persons are in their mid or late thirties. Success
depends in large part on being able to obtain funding, which in turn
depends on the fortunes and sometimes the whims of the sponsoring
agency. Instability of funding coupled with the need to support a
family is the greatest deterrent to talented young physicians
considering a career in clinical research.
The answer to this problem lies with both the research sponsors and
the academic partners. The NIH has been responsive to the
recommendations of the 1997 Nathan Report, and has established a number
of clinical research training mechanisms such as the K awards and the
loan repayment programs authorized by the Congress. We need to continue
to increase training opportunities in all areas of clinical research by
providing additional mentoring programs, expanding the existing federal
loan repayment programs, and most importantly by providing longer
commitments of support to the most creative, energetic and humane
clinical researchers. Just as important, once they finish their
training, clinical investigators must be supported not only with
adequate opportunities for funding for their research but also with
``nurturing environments'' that offer reasonable, long-term career
paths.
There are many important tasks ahead in developing a workable
clinical research enterprise. One of the first challenges is in the
organization of the system. I believe that we need a balanced
tripartite system. One partner must be the federal government, which
supports clinical research through several agencies, including the NIH,
the Department of Veterans Affairs (VA), the Centers for Disease
Control and Prevention (CDC), and the Agency for Healthcare Research
and Quality (AHRQ). The NIH, as the lead agency, has developed a
visionary plan for clinical research in its Roadmap initiative, a plan
that we support with enthusiasm. The second partner is academic
medicine--the medical schools and teaching hospitals where most
innovative, hypothesis-driven clinical research is conducted. A large
majority of clinical researchers in this country are faculty members
and the trainees at these institutions are the future clinical
investigators. These institutions are represented by the AAMC.
The third partner is industry--largely the pharmaceutical,
biotechnology and information technology industries. Industry provides
ideas, resources, and expertise that are essential to bringing a
product to market and actually making it available to the public. Each
of the three partners has a stake in the success of the other. Stable
clinical research networks involving multiple medical schools and
hospitals and their patients should be created and tied together with
modern information systems, and these networks should conduct research
sponsored by both the government and industry. Many projects should
have dual sponsorship. The stability and resources of these networks,
in turn, will attract the most creative young physicians who are eager
to engage in a career of research. After training at our medical
schools they can then conduct clinical research in a variety of sites,
including academic, industrial and federal laboratories, as well as
teaching hospitals and health systems.
The ultimate winner, of course, will be the public, which has the
greatest stake in the outcome of this noble effort.
Once again, thank you for the opportunity to testify before you
today. I would be pleased to respond to any questions you might have.
Mr. Bilirakis. And thank you very much, Doctor.
I am fascinated by your testimony, and I apologize to
Doctors Barron and Beall for not being here. It is just amazing
the life that we lead here running from hearing to hearing and
meeting to meeting, and that sort of thing. You are very
important to us and I apologize for the fact that we do not
have more members here.
I appreciate Mr. Green returning.
All right. So you have already indicated that you certainly
agree with the views, I guess more than anything else, the
vision of Dr. Zerhouni in terms of the Roadmap.
Now, Dr. Braunwald, you mentioned the lack of coordination,
you have gone into it in many different ways. I would imagine
possibly maybe we might have heard the same thing from Drs.
Barron and Beall. I do not know. But do you feel that Dr.
Zerhouni's Roadmap if implemented, once implemented, will
basically satisfy that, will take care of that problem
adequately?
Mr. Braunwald. Yes. I think will go a very, very long way,
sir. I think that what it is implicit in the Roadmap, though it
was not explicitly articulated, is that these networks are
going to have some stability. And that does not mean that they
should be frozen and never change. But people who work in them
have to feel that this is a career; whether the worker is a
physician or a nurse. And I think that it is very important to
provide them with the authority and then ultimately with the
funding so that these are not turned on and off like a water
spigot.
Mr. Bilirakis. Yes. Dr. Beall, you wanted to add to that?
Mr. Beall. Yes, I would like to add. As I mentioned in my
testimony, we have a network and it is in the coordinating
centers in Seattle. We have 39 employees there. We also have 18
sites around the country where we provide core resources so
that when a clinical trial stops from one clinical trial, these
people do not have to get fired. They do not have to leave.
There is a continuity in terms of people. And so we have a
carry over of ideas of how to design the clinical trials. And
that only provides a value added to when the industry comes to
us and it certainly facilitates it.
So I think that these networks, and I think ours has proven
to be an excellent network that is all coordinated by the
Internet. If a patient comes to us today and undergoes a
clinical study today, we add data back. It literally goes back
to our network in Seattle, goes to a data safety monitoring
board tomorrow and we can have the decision whether or not to
move forward for another dose the next day.
So it is a continuity of people and it is taking advantage
of the web and it has taken advantage of the great
opportunities that we have with bioinformatics now to make it
move very efficiently.
Mr. Bilirakis. So you are basically satisfied that you are
on top of or at least knowledgeable of all the cystic fibrosis
clinical research that has taken place at various locations?
Mr. Beall. Absolutely. We have been very fortunate in that
the community has accepted us as the leader. And I think in any
kind of a disease, you obviously have to have somebody take a
leadership role. And fortunately for us, the basic researchers,
the clinical researchers, the caregivers, the parents and so
forth have really looked upon the foundation as that
organization that will develop a new therapy. So I think we are
very blessed.
And fortunately Bill Gates gave us $20 million for our
effort----
Mr. Bilirakis. That helped.
Mr. Beall. [continuing] to move forward in some of these
things. And he liked our innovative approaches. And we have a
great group of volunteers around the country that raise a lot
of money so we can make these investments like $25 million or
$100 million.
Mr. Bilirakis. Well now, and forgive my ignorance, might
there be clinical research taking place regarding, let us say,
another illness in parts of the country whereby possibly some
of the byproducts of that research would be helpful as far as
cystic fibrosis is concerned? And if that is possible or
probable that that could be taking place, are you sort of
cranked into that at all to be knowledgeable of it?
Mr. Beall. Absolutely. Dr. Zerhouni talked about his
clinical trial net that lists all the clinical trials that are
going on in the United States and supported by the NIH. And I
think those things help us. I think there is a lot more
information exchanged than we have ever had before. But as he
said, there are a different systems that are out there. But I
clearly believe that with the integration of this I think we
are all going to be more informed about what is going on. But I
do think that with communication, with the availability of
papers on the web, access to information quicker than we ever
had before, I think we are pretty well informed. But I think we
have to consolidate it and get it under the leadership of the
NIH.
Mr. Bilirakis. Great.
Dr. Barron, the bell just rang again. It is only one vote,
but still we are going to have to break. So hopefully we can
get through and let you all go.
Did you have anything you wanted to sort of add?
Mr. Barron. Maybe just one comment to add. I think Dr.
Braunwald's point about this being a bit of a tripartite is one
to keep in mind.
And while I think the networking theoretically can
facilitate exactly what is being described here, I think that
in designing the network has to be, I think, ensure that the
process does not impede either academia or industry from doing
the kind of trials that are needed for the success of all three
groups.
So I think if it is viewed as an infrastructure to enable
the bottleneck of clinical research to be de-bottlenecked, if
you will, then it will provide a tremendous opportunity. I
think that to some extent maybe the devil could be in the
details when one looks at the issues around how the networks
are set up.
Mr. Bilirakis. Well, all three of you heard Dr. Zerhouni's
testimony and you heard us, basically, pretty well beg for
recommendations. Because if we are going to be helpful in this
regard, I mean the more information we have the better.
And I am going to turn it over to Mr. Green now. But I
would ask you to please, I know you have made some
recommendations and whatnot in your written remarks. But
anything at all that you can furnish us in writing. There will
be questions that we will furnish you and ask for your
responses there, too. But anything above and beyond that, any
recommendations, whatnot, keep in mind.
You know, are we going to reauthorize or reauthorize NIH
this year? I do not know. It is a tough political year. If we
do not do it this year, more likely we will do it next year. If
we don't this year, probably. So we need your input. And you
are the grass--I hate to refer to you as grassroots. But you
know you are at that level where you basically see it happening
on a day-to-day basis; what regulations that you mentioned, Dr.
Braunwald and whatnot. So please feel free to submit any of
that information to us because it can be very helpful.
And I would yield to Mr. Green.
Mr. Green. Thank you, Mr. Chairman.
I have a question for both Dr. Barron and Dr. Beall, but if
I do not get to them before we have to go vote, can we submit
them and ask for a response.
Mr. Bilirakis. By all means.
Mr. Green. Because both, obviously, on the private sector
and from the Cystic Fibrosis as a representative of the
foundations and the efforts is so important to the partnerships
with NIH.
But, Dr. Braunwald, you mentioned in your testimony the
factor that influencing shortages of qualified clinical
research and the instability of funding. Now, I can imagine the
5 year increases in the NIH budget, did that do something to
help with those concerns? And also if it did, then what is the
impact of the last--the recent reductions in the increases in
funding on having clinical researchers into the system?
Mr. Braunwald. Yes. I can tell you that, you know, working
in the trenches, as it were, the growth or lack of growth of
the NIH budget has an enormous impact on decisionmaking on
career decisions that young people make. And I think before the
Congress generously increased the doubling, I think there was a
feeling research is not valued and the opportunities were few
and although the opportunities for research were great, the
career path was not there. So during this period of the
doubling, there has been a tremendous feeling of optimism. I
think people now are scared again because they can do the
arithmetic, and the arithmetic suggests that if we are
flattened at 2 or 2.5 percent, that really represents about a 5
percent decline.
So I think that I can tell you, sir, that this is watched
very, very closely by in particularly the young people who have
other career choices. And what we are so afraid of is that an
entire generation may become lost to this.
Mr. Green. The next question I was concerned about it so
much of our medical research is done at our academic medical
institutions, just like yours. So there are lots of other
Federal programs other than NIH, for example Medicare and
Medicaid programs that are also part of teaching hospitals, for
example. I would imagine that much of the clinical research we
are discussing takes place at these hospitals. And when you see
cuts in direct or indirect medical education programs with caps
on residencies, you also see that as a problem in attracting
your researchers.
Beyond the NIH and the Roadmap, what more can the Federal
Government do to support the academic medical institutions?
Mr. Braunwald. Well, I think that you put your finger on
something very important. If an academic medical institution,
if the indirect and the direct calls for education disappear or
shrivel, then again it breaks a very important link in the
chain, and that is the training opportunity for students and
the training opportunity for residents who then go into
research. And I think that that is an equally important
problem.
Mr. Green. Mr. Chairman, I have one more general question,
though, that I would like to ask and I know we are within the
10 minutes I guess.
Mr. Bilirakis. Why do you not ask it and possibly we can
get some very brief responses.
Mr. Green. Okay. This is for all the panelists. And, gain,
I have specific questions for Dr. Beall and Dr. Barron that I
will submit.
and I understand in the NIH Roadmap with respect
reengineering clinical research it seeks to foster
collaboration among research and emphasize the importance of
training clinicians to work in multiple disciplinary and also
team oriented environments. While this may indeed help future
generations of clinicians, what is being done to foster desired
levels with established clinical researchers? And, again, this
is a cross whether it be at the academic institutes, whether it
be at the non-profits, for example, Cystic Fibrosis, and how
they interface with the profit making in, for example, the
Genentech. And just in a general does that Roadmap foster that
effort to have all of us involved?
Mr. Beall. I will comment first. I think it does, because I
think it does foster the increased relationship between special
industry and academics because these networks that we talk
about there, the development of the clinical researchers, can
only facilitate the entire clinical structure.
It is clearly that the biopharmacuetical industry cannot do
what it needs to do without the academic environment. The
networks that we talked about being created can only facilitate
the ability of Genentech and others to do clinical trials. And
I think that that whole process is really being integrated much
more in the concept of the Roadmap because you are going to
bring technology people, institutions and companies altogether
under a single umbrella.
Mr. Green. Dr. Barron?
Mr. Barron. Yes. I think from the industry standpoint the
training that is needed within the company is actually a little
different than the training that maybe the academic people
need, although the specific training is similar in terms of
what is needed for clinical research. and I think part of the
problem that exists is having the time for the academic folks
to actually take the courses.
I know at the institution I trained, USCF and many other
institutions. There is actually training programs to become
better clinical researchers. The problem is taking the time for
1 or 2 years to actually immerse yourself in this clinical
training requires to be funded for those 2 years. So at
Genentech we actually take the time and put the resources
toward training of the clinicians that join. So we have about
docs and we have specific programs for them. The NIH Roadmap
will facilitate the number and quality of these training
programs that we can send people to. So I think, as Dr.
Braunwald said, it is really just trying to increase the
resources really earmarked for training and then putting
programs in place to facilitate that will be very advantageous.
Mr. Green. Thank you, Mr. Chairman.
Mr. Bilirakis. Thank you, Mr. Green. Again, thanks for
returning.
Gentlemen, we are so very grateful to all three of you, not
only for being here today but for your dedication over the
years. Your work, of course, is the magic that we look forward
to to keep us well or to get us well, or whatever the case may
be. In keeping well, I guess, as Dr. Zerhouni accented is our
biggest problem. Take a look at me and how overweight I am. It
is just ridiculous.
But anyhow, thanks so very much. And, again, please we
would be disappointed if we did not receive--now we are going
to furnish you with questions. But in addition to that, if you
could just furnish us with suggestions. Put yourself in the
shoes of a Member of Congress and see what we can do maybe to
help you.
Thank you so much.
Hearing is adjourned.
[Whereupon, at 12:50 p.m., the subcommittee was adjourned.]
[Additional material submitted for the record follows:]
Responses to Questions for Dr. Hal Barron From Hon. John D. Dingell
Question 1. The mapping of the human genome has been a remarkable
accomplishment and already seems to be opening doors for biomedical
research. Obviously this is a positive step. But some are concerned
about the possibility of generic discrimination. Do you think we need a
law to protect people from genetic discrimination?
Response. Genentech has consistently supported legislation and
regulations that create federal standards to protect the
confidentiality of patient health information, including genetic
information. With the implementation of the Health Insurance
Portability and Accountability Act (HIPAA) medical privacy regulations
in 2003, we believe patients are provided with far greater assurances
that any health information created and used in the health care context
will not be inappropriately disclosed to insurers, employers or other
third parties. As with all law and regulation in this area, it is
critical that Congress balance the important goals of protecting the
privacy of an individual's health information, including genetic
information, while also allowing for appropriate use of certain data
for critical research purposes.
Question. The Senate recently unanimously passed S. 1053, a bill to
prohibit discrimination on the basis of genetic information with
respect to health insurance and employment. Do you support this
legislation?
Response. Genentech certainly supports strong protections against
discrimination of individuals based on genetic information in both the
workplace. It is important for research participants to feel confident
in the protection of this information so as to encourage robust
participation in clinical research. Genentech worked closely with our
trade association, the Biotechnology Industry Organization (BIO), to
make significant improvements to S. 1063 to ensure appropriate access
to health information for research purposes.
______
April 21, 2004
The Honorable Joe Barton, Chairman
The Honorable John D. Dingell, Ranking Member
U.S. House of Representatives
Committee on Energy and Commerce
Washington, D.C. 20515-6115
Dear Representative Barton and Representative Dingell: Thank you
for your letter with additional questions after the hearing about
``NIH: Reengineering Clinical Research.''
Question 1. The mapping of the human genome has been a remarkable
accomplishment and already seems to be opening doors for biomedical
research. Obviously, this is a positive step. Bust some are concerned
about the possibility of genetic discrimination. Do you think we need a
law to protect people from genetic discrimination?
Question 2. The Seante recently unanimously passed S. 1053, a bill
to prohibit discrimination on the basis of genetic information with
respect to health insurance and employment. Do you support this
legislation?]
Response. In response to your questions about genetic
discrimination, we wanted to let you know that we are supportive of
legislation to protect people from genetic discrimination in general,
and we support of the Senate's bill on this issue, S. 1053.
Cystic Fibrosis (CF) is genetic disease; people with this disease
must inherit two copies of the gene to have the disease and individuals
with one copy are non-symptomatic carriers. Individuals with CF
participated in research, which led to the discovery of the CF gene in
1989. Now, more than 1000 mutations of this gene have been identified.
Nearly 80 percent of people with CF have been genotyped; researchers
are using the information about the genetic make-up of the disease to
identify new treatments or a cure. (add genotyped done . . . in
research situation? Or with consent?)
Research to develop gene therapy to treat CF is critical, and the
CF community has been on the forefront of this research for much of the
last decade. In addition to supporting gene therapy, the CF Foundation
has invested in numerous potential therapies based on the genetic
defect and the types of mutations involved.
For example, this week we will announce an investment into a
product that could impact individuals with the main mutation called
DeltaF508. This mutation allows the CF gene to make its protein, but
the protein is not delivered to the spot on the cell membrane where it
can do its job of shuttling ions in and out of the cells. This product
has potential to correct this defect. But it is less clear if it will
impact individuals with other mutations. We will send you a copy of the
press release/a copy is attached. This is just one example of the types
of genetic research we are pursuing to find new treatments based on
genetic information.
The CF Foundation believes this legislation is necessary for many
reasons. Clearly, the public is afraid of the misuse of genetic
information and therefore hesitant to participate in genetic research.
This legislation addresses that public fear by prohibiting the misuse
of genetic information in the most serious situations--denial of health
insurance, and impact on employment. People who are carriers of one
copy of the CF gene, but who do not have CF, are most likely to benefit
from this legislation. This legislation is a step forward to address
inappropriate uses of genetic information about which individuals have
no control and which may not impact their health or employability. We
believe no one should be subjected to discrimination on this basis.
Legislation to prohibit genetic discrimination by health insurance
carriers and by employers can make individuals more secure that their
genetic make-up will not be used to harm them. While this legislation
does not solve all problems related to genetic discrimination, it makes
positive progress to better enable individuals with genetic diseases or
risk factors to obtain and retain health insurance and to be treated
fairly in employment settings.
We encourage you and the House leadership to take up the
legislation banning genetic discrimination. Research holds the key to a
positive future and better health. Genetic research holds great hope
for the future. If people fail to participate in research because of
fear of genetic discrimination or misuse of genetic information to
affect health insurance or employment opportunities, critical, life
saving research will be undermined and future cures will be delayed if
not deterred altogether. This research holds great possibilities to
change the future of many individuals now suffering--and dying--from
genetic diseases.
The CF Foundation appreciates the invitation to testify before this
Committee. We continue to take assertive measures to examine promising
new treatments for people with CF through our clinical trials network,
and to reengineer the clinical trials process. While the lives of
people with CF have improved in the last few decades with the increase
in expected life span from early kindergarten to the early thirties
today, there is still much more to be done. Your efforts to facilitate
oversight of the clinical trials regulatory system and to protect the
public from unintended consequences of genetic research advances are
key.
Please let us know if you have additional questions.
Sincerely,
Robert J. Beall, Ph.D.
President & CEO, Cystic Fibrosis Foundation
cc: The Honorable Michael Bilirakis, Chairman, Subcommittee on Health
The Honorable Sherrod Brown, Ranking Member, Subcommittee on Health
______
Response to Questions for Dr. Eugene Braunwald From Hon. John D.
Dingell
Question 1) The mapping of the human genome has been a remarkable
accomplishment and already seems to be opening doors for biomedical
research. Obviously, this is a positive step. But some are concerned
about the possibility of genetic discrimination. Do you think we need a
law to protect people from genetic discrimination?
Response. The mapping of the human genome is an extraordinary
scientific advance. This achievement is the foundation for research
that is expected to one day reveal every person's genetic
predisposition to a variety of diseases. While this genetic information
will be an important tool to prevent and treat disease, it can also be
misused to discriminate against individuals. The Association of
American Medical Colleges (AAMC) is concerned that many Americans will
be discouraged from participating in vital medical research for fear of
discrimination by employers or health insurance providers who
improperly use genetic information. Accordingly, protections are needed
to prevent this information from being used inappropriately. The AAMC
has encouraged Congress to pass legislation that provides sufficient
protection against job loss, health insurance cancellation or denial of
coverage as a result of genetic discrimination. It is essential that
the American people are reassured that participating in medical
research will not compromise their health insurance or their
livelihoods.
Question 2) The Senate recently unanimously passed S. 1053, a bill
to prohibit discrimination on the basis of genetic information with
respect to health insurance and employment. Do you support this
legislation?
Response. The AAMC supports enactment of S. 1053, and joined over
90 other organizations as part of the Coalition for Genetic Fairness in
a Nov. 4, 2003, letter to House Speaker Dennis Hastert urging him to
schedule a vote on the legislation. The coalition represents patients,
people with disabilities, consumers, women, health and health
professional and civil rights organizations, and many others.
______
Department of Health & Human Services
Public Health Service, National Institutes of Health
April 16, 2004
The Honorable John Dingell, Ranking Minority Member
Committee on Energy and Commerce
United States House of Representatives
Washington, DC 20515
Dear Representative Dingell: I am responding to your April 7, 2004,
letter to Dr. Elias Zerhouni, Director of the National Institutes of
Health (NIH), following up on the March 25, 2004, hearing entitled:
``NIH: Re-engineering Clinical Research.'' Enclosed are responses to
the questions you forwarded from members of the Subcommittee on Health.
We continue to look forward to working with the House Energy and
Commerce Committee as it continues to review NIH.
I have also provided a copy of this response to Chairmen Joe Barton
and Michael Bilirakis.
Sincerely,
Marc Smolonsky
Associate Director for Legislative Policy and Analysis
Enclosures
cc: The Honorable Joe Barton, Chairman, Committee on Energy and
Commerce
The Honorable Michael Bilirakis, Chairman, Subcommittee on Health
Questions for Dr. Zerhouni from the Honorable Sherrod Brown
Question. The NECTAR system at NIH, which uses medical informatics
to coordinate clinical research initiatives, intersects with private
sector-initiated clinical research. How will NIH coordinate with the
private sector, and what efforts are underway in the private sector to
modernize the collection of clinical trial data?
Response. An early step in the development of NECTAR will be an
extensive inventory of ongoing public and private sector initiatives
that have advanced the development of data standards and vocabularies,
applications and tools, and informatics infrastructures and
architectures, which are the critical elements of a nation-wide network
of clinical research information systems. NIH is consulting widely with
the clinical research community, health care providers, and informatics
vendors to gather data on best practices in systems design and
standards development. For example, innovative information systems in
academic institutions such as the Mayo Clinic, Partners HealthCare,
Columbia University College of Physicians and Scientists, and the
Regenstrief Institute, whose systems are designed to fulfill the
specific information needs of clinical research, are being studied.
IBM's Information Based Medicine system, Cerner Corporation's
Integrating the Health Enterprise program, and Kaiser Permanente's
Electronic Health Record are a few of the commercial and non-profit
sector initiatives that are also being reviewed. Through site visits,
workshops, and conferences, NECTAR's development will be informed by
and build upon best practices and state-of-the-art tools that will
enable us to create a clinical research informatics system that will be
fully responsive to evolving technology and the changing needs of the
dynamic clinical research environment.
Questions for Dr. Zerhouni from the Honorable Gene Green
Question 1. In 2001, National Cancer Institute (NCI) researchers
published two articles on breast implant patients, which found that
women with implants were more likely to have cancer compared to other
plastic surgery patients of the same age. In fact, breast implant
patients were twice as likely to die from brain cancer, three times as
likely to die from lung cancer, and four times as likely to commit
suicide, compared to other plastic surgery patients.
Five years have passed since those data were analyzed. Dr. Louise
Brinton and other NCI researchers had hoped to follow-up on the women
who were still alive five years ago, to find out how many are still
alive and how many are healthy. That will provide more conclusive
evidence about a possible link between breast implants and cancer or
suicide. Is that research being done?
Response. Although the NCI study did not find that breast implant
patients were more likely than other plastic surgery patients to
develop any cancer, it is true that there were some excess risks for
certain sites, including brain and lung cancers. These excesses were
difficult to interpret given that they were based on small numbers. The
NCI therefore has plans to continue following the patients from the
study to evaluate future deaths from different causes. Data from the
National Death Index, now available through 2002, will provide an
additional five years of important information. These additional years
will yield considerably more statistical power for evaluating rare
outcomes of interest, including brain cancers.
The timeline for the completion of this work will be similar to
other epidemiology studies of this size and complexity. We anticipate
that data collection and analysis, writing, and initial review will be
completed in Spring of 2005. Draft materials will then be submitted to
a scientific journal for peer review and publishing. We hope,
therefore, that results from this follow-up may be published in early
2006.
Question 2. Another issue of concern for me is the role of NIH's
newest institute, the National Institute of Biomedical Imaging and
Bioengineering (NIBIB). As a proud co-sponsor of legislation to create
this Institute, with my friends Congressman Burr and Congresswoman
Eshoo, I feel that the National Institute of Biomedical Imaging and
Bioengineering should have a prominent role in your effort to re-
engineer the clinical research enterprise at the NIH as well as in the
entire NIH Roadmap.
What is your view of the role of the NIBIB in the NIH Roadmap and
over the long term as the focus for the development of new technologies
at the NIH? Would you work with this Committee and the Appropriations
Committee to develop a long-range plan for the Institute?
Response. The NIH Roadmap for Medical Research focuses on the most
compelling opportunities in three main areas: new pathways to
discovery, research teams of the future, and re-engineering the
clinical research enterprise. These cross-cutting areas span the
missions of the 27 Institutes and Centers (ICs) of the NIH. As such,
all ICs support and actively participate in the development and
implementation of Roadmap initiatives.
The mission of the NIBIB is to improve human health by leading the
development and accelerating the application of biomedical
technologies. The Institute is committed to integrating the physical
and engineering sciences with the life sciences to advance basic
research and medical care. To that end, the NIBIB strongly supports the
NIH Roadmap, since a major Roadmap goal is to facilitate the
development of innovative, novel and multi-disciplinary science and
technology that has the potential to further advances in health care.
For example, the NIBIB is participating in an initiative that will
facilitate the formation of collaborative research teams capable of
generating novel probes for molecular and cellular imaging. The overall
goal is to establish programs to create complete tool sets for the
detection of single molecule events in living cells and to generate new
strategies for dramatically increasing the imaging resolution of
dynamic cellular processes.
Other Roadmap areas of immediate interest to and supported by the
NIBIB include the development of nanomedicine technologies, new tools
for the study of proteomics and metabolic pathways, data and techniques
for computational biology, and advances in bioinformatics. For example,
in the theme area of new pathways to discovery, NIBIB program staff are
participating in the formulation and execution of initiatives relating
to metabolomics and proteomics as well as an initiative for the
National Centers for Biomedical Computing. The NIBIB is also
participating in the planning for the Nanomedicine Development Centers.
In the theme area of re-engineering the clinical research
enterprise, NIBIB Program Staff are active participants in the Trans-
NIH Informatics Committee (TNIC) which is coordinating the informatics
components in all three Roadmap areas. The TNIC is currently focusing
on the National Electronic Clinical Trials and Research System (NECTAR)
which will allow community-based clinicians from the NIH Clinical
Research Associates to participate in national studies, facilitate the
sharing of data and resources, and augment clinical research
performance and analysis.
In the theme area of research teams of the future, several
initiatives have been developed to encourage and enable an
interdisciplinary workforce through the implementation of novel
training programs. Training a new cadre of interdisciplinary
researchers is an important component of the NIBIB mission and the
Institute is actively participating in the development and
implementation of Roadmap initiatives in this area.
Regarding long-range planning, in February 2004, the NIBIB embarked
on a strategic planning process which will culminate in a draft of the
Institute's first strategic plan later this year. The NIBIB has created
a Strategic Planning Working Group, composed of the Senior Staff of the
Institute and has also formed a Strategic Planning Subcommittee within
its' National Advisory Council. The Institute is soliciting broad
public input on their web site (http://www.nibib1.nih.gov/about/SP/
strategicplan.htm) which also serves to update interested individuals
on the ongoing, iterative planning process.