[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


                               __________

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                            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

                              ----------                              


                        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.

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