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DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Elizabeth G. Nabel, M.D., Director

National Heart, Lung, and Blood Institute

March 9, 2005

William Beldon, Deputy Assistant Secretary, Budget

Mr. Chairman and Members of the Committee:

I am pleased to present the Fiscal Year (FY) 2006 President's Budget
request for the National Heart, Lung, and Blood Institute (NHLBI). The
FY 2006 budget includes \$2,951,270,000, an increase of \$10,069,000
over the fiscal year 2005 enacted level of \$2,941,201,000 comparable
for transfers proposed in the President's request. I come to you with
pride on behalf of the NIH component that is responsible for much of the
gain in life expectancy that we have enjoyed over the past three decades
in the United States, as shown in this chart. At the same time, however,
I come with deep concern because the diseases under NHLBI responsibility
still comprise three of the four leading causes of death in this country
-- heart disease, stroke, and chronic obstructive pulmonary disease
(COPD). Clearly, we have come a long way, but we have far to go.

A VISION FOR THE FUTURE OF THE NHLBI

As the NHLBI's first new director in 22 years, I would like to take this
opportunity to share with the Committee my vision for the Institute.
This vision is based upon a fundamental set of values -- excellence,
integrity, innovation, respect, and compassion -- that will permeate all
activities in the NHLBI. I believe that scientific discovery provides
the basis for progress and that the NHLBI is uniquely positioned to
catalyze changes that must be made to transform our new scientific
knowledge into tangible benefits for the people of this country. Within
this framework, let me articulate four themes that will guide priority
setting of our research agenda.

THEME ONE: DISCOVERY

The first theme -- stimulating basic discoveries of the causes of
diseases ­-- is vital to developing new, critically needed treatments.
Basic research provides the foundation of the NHLBI portfolio and has
been one of its great strengths. The typical model of investigation --
research conducted by single investigators or small groups of
investigators on projects of their own inspiration -- accounts for most
of the unanticipated and major scientific discoveries in this country. I
believe strongly that we must protect and nurture investigator-initiated
research. The NHLBI will continue to invest in the most talented
scientists conducting the highest caliber research. Innovation and
creativity using the most advanced biomedical technologies will be our
goal.

We have an exciting opportunity to support emerging new scientific
fields. Major strides are being made in computer sciences,
bioengineering, material sciences, chemistry, and other areas of study
that vastly benefit medical research, and the pace of discovery in these
disciplines should be accelerated. One approach is to develop funding
mechanisms (e.g., for support of high-risk research) that encourage
innovative thinkers to turn their attention to the major current
challenges in heart, lung, and blood diseases.

Another objective is to generate large, publicly available sets of
reagents and data that could function as a "tool kit" for NHLBI
investigators. Gene sequences and maps, cell lines, knockouts and
knockdowns of genes in selected animals, reference sets of proteins,
protein affinity reagents, and libraries of small molecules are examples
of resources that will provide our investigators with the technologies
required for innovative discoveries.

THEME TWO: TRANSLATION

Our second task is to speed translation to clinical applications so that
people can benefit as quickly as possible from the basic research
enterprise. Clinical research, and more specifically, translational
research ("bench to bedside") are vital to our mission, so that we can
translate basic discoveries into the reality of better health for our
country.

The NHLBI must further develop the infrastructure for clinical research
so that it serves the evolving field of scientific discovery and
provides a foundation for evidence-based clinical decision-making.
Clinical research is critical to ensuring that new products and
techniques are safe and effective before they are widely applied.
However, clinical research is often time-consuming and inefficient, and
is increasingly burdened by regulatory hurdles. Our challenge is to
expand clinical research to complement the exciting basic science
discoveries, while making it more efficient and cost-effective.

We intend to develop a translational research agenda supported by
clinical trials, clinical networks, and clinical workforce training. Key
components will focus on increasing interactions between basic and
clinical investigators and easing the movement of new tools from
laboratories to clinics. We will build upon our rich experience with
clinical trials and networks to develop new partnerships among organized
patient communities, community-based physicians, and academic
researchers. We will work on improving bioinformatics and clinical
databases, standards for clinical research protocols, measures of
clinical outcomes, and quality assessment. Translational research
requires the expertise of many fields and should include analysis of
health education, outcomes, health-care delivery, and health-care
economics. This focus fits well with the Re-engineering the Clinical
Research Enterprise of the Roadmap.

The NHLBI must cultivate a cadre of clinical researchers who have skills
commensurate with the complexity and needs of our research enterprise.
Clinicians must be trained to work in the interdisciplinary,
team-oriented environments that characterize today's research efforts.
We further anticipate that specific training will be required in an
array of disciplines important to clinical research, including genetics,
epidemiology, biostatistics, and behavioral medicine.

At the core of this vision is the need to develop new partnerships of
research with organized patient communities, community-based health care
providers, and academic researchers. We will rely on our partnerships to
facilitate the conduct of this clinical research, to train our clinical
investigators, and most important, to achieve our common goals of
improved health for the public.

THEME THREE: INTERACTIONS

The third theme is facilitating communication between scientists and
physicians so that new ideas can be generated, shared, and advanced.

Today's science is far more complex than that of yesteryear. Research,
whether basic or clinical, is now commonly done by teams of scientists
wherein each individual brings specific talents and expertise to the
overall effort. We will stimulate and facilitate the conduct of
interdisciplinary research, so that advances can be made more quickly.
Principal-investigator status will be granted not to just one
investigator, as is the norm, but to all key members of the research
team. Integrated reviews of grants will take into account the melding of
various disciplines to address the problem at hand, and
interdisciplinary teams will be encouraged to evolve in both directed
and unexpected ways.

An essential component of our efforts in research collaboration will be
community-based clinical trials, which enhance the conduct of clinical
research at academic medical centers. An outstanding example is our
ALLHAT (Antihypertensive and Lipid-Lowering to Prevent Heart Attack
Trial), in which physicians from many types of medical settings -- a
total of 623 sites in 47 states, Puerto Rico, the U.S. Virgin Islands,
and Canada -- successfully enrolled over 42,000 patients and followed
them for 6 years. The physicians participated because they believed in
the importance of the scientific questions being addressed with regard
to patient care and because of the direct benefits of participation to
their patients, including free medications. These community-based
physicians conducted the trial at very high standards -- follow up was
over 97 percent. As part of our plan to disseminate the ALLHAT results,
participating community physicians are now working with other doctors in
their local communities to treat patients with high blood pressure.

THEME FOUR: COMMUNICATION

Our fourth task is to effectively communicate our research advances to
the public to improve understanding of new, promising science.

The NHLBI has an outstanding history of outreach in the areas of high
blood pressure, cholesterol, asthma, heart attack, obesity, sleep
disorders, and women's cardiovascular health, and new efforts are under
way with respect to COPD and peripheral arterial disease. I
wholeheartedly support these programs that serve the mission of our
Institute and the Nation. Education of our patients and the public
regarding prevention and treatment of heart, lung, blood, and sleep
disorders is one of my highest priorities.

We will continue to work collaboratively with our colleagues in the
DHHS, including the CDC and the FDA, to support prevention and control
programs. We also have an unprecedented opportunity to build upon our
partnerships with professional organizations, who have a large stake in
developing and implementing practice guidelines and monitoring their
effectiveness, and with patient advocacy groups. One of our most
gratifying partnership programs has been The Heart Truth, which is
successfully raising awareness nationwide that heart disease is the
leading cause of death among American women. The "reach" of this
campaign continues to expand as we forge additional fruitful
partnerships with entities in the public and private sectors.

Disparities in health status constitute a significant global issue.
Research is essential to understand the diverse contributions of
genetics, health behavior, diet, socioeconomic status, culture, and
environmental exposures in the genesis of health disparities in heart,
lung, and blood diseases and to formulate, evaluate, and disseminate
well-conceived, focused intervention programs. This work will
necessarily entail a vigorous effort to increase the representation of
minorities in the ranks of NHLBI researchers. We are also cognizant of
the need to improve and expand programs to prevent, manage, and treat
diseases and conditions that disproportionately affect U.S. minority and
underserved populations, such as cardiovascular disease and asthma, and
to evaluate the effectiveness of our research, treatment, and education
programs. A full resolution of the health disparities problem will occur
only through committed and sustained efforts by many in our government,
health centers, and society.

SUMMMARY

The realization of this vision will require the efforts of many. We are
engaged in a special form of public service, that is, the promotion of
patient and public health. I will work diligently to preserve public
trust in the Institute, the NIH, and the biomedical research enterprise,
and to ensure that the NHLBI serves the public with the highest level of
integrity. This trust is essential for meeting our common goals of
making important new scientific discoveries and translating them to
improve health in this country.

Thank you, Mr. Chairman. I would be pleased to answer any questions that
the Committee may have.

ELIZABETH G. NABEL, M.D.

Director

National Heart, Lung, and Blood Institute

National Institutes of Health

Elizabeth G. Nabel, Director of the National Heart, Lung, and Blood
Institute (NHLBI) of the National Institutes of Health, joined the NHLBI
in September 1999 as the Institute's Scientific Director of Clinical
Research. Previously she had been Chief, Division of Cardiology,
Director, Cardiovascular Research Center, and Professor of Internal
Medicine and Physiology at the University of Michigan.

Dr. Nabel is a board-certified cardiologist who has taken care of many
patients with cardiovascular disease, including women with heart
disease.

A native of Minneapolis, Minnesota, Dr. Nabel received her medical
education at Cornell University Medical College before moving to Brigham
and Women's Hospital and Harvard University where she completed an
internship and residency in internal medicine and a clinical and
research fellowship in cardiovascular medicine. She joined the faculty
at the University of Michigan in 1987 as an Assistant Professor of
Medicine and rose through the ranks, becoming Director of the
Cardiovascular Research Center in 1992, Professor of Internal Medicine
and Physiology in 1994, and Director of the Division of Cardiology in
1997. While at the University of Michigan, she became known for her
research in the field of vascular biology and molecular cardiology and
for her gene transfer studies of the cardiovascular system.

Dr. Nabel has had a longstanding interest in genetic and cellular
therapies for cardiovascular disease, having developed techniques for
the introduction and expression of recombinant genes into blood vessels
in vivo. Her group has conducted a number of basic studies,
investigating the expression and function of growth factor, cytokine,
and cell cycle genes in the vasculature. These basic studies led to
several clinical gene therapy trials of cardiovascular diseases in the
United States and Europe.

Dr. Nabel's career has intertwined basic research and translation to
clinical medicine and practice. She has been a champion of the concept
"from bench to bedside." Her current research interests are focused on
the regulation of vascular growth and the molecular genetics of vascular
diseases. Dr. Nabel has investigated the regulation of smooth muscle
cell growth by cell cycle regulatory proteins, a process important for
the development of atherosclerosis and restenosis. Her Vascular Biology
Lab at NHLBI has characterized the role of the cyclin-dependent kinase
inhibitors on vascular proliferation, inflammation and progenitor cells
using a variety of genetic tools. These proteins are important negative
regulators of vascular smooth muscle cell growth and vascular
inflammation, and work from her lab has opened up new avenues for
therapeutic targets in the vasculature. She is also conducting clinical
studies examining genomics and proteomics in vascular diseases, such as
one study of in-stent restenosis. The Vascular Biology Lab has published
more than 200 papers and Dr. Nabel has mentored 42 students and fellows
associated with her lab.

Dr. Nabel has received numerous awards, including the Distinguished
Achievement Award from the Basic Cardiovascular Sciences Council of the
American Heart Association and the Amgen-Scientific Achievement Award
from the American Society for Biochemistry and Molecular Biology. She is
an elected member of the American Society of Clinical Investigation, the
Association of American Physicians, and the Institute of Medicine of the
National Academy of Sciences. In 2001, Dr. Nabel received an honorary
doctoral degree from the University of Leuven, Leuven, Belgium.

Dr. Nabel is an editorial board member of *The New England Journal of
Medicine.* She has been a reviewing editor for *Science* and an
editorial board member of the *Journal of Clinical Investigation*. She
also served as a consulting editor for *Circulation*, *Circulation
Research*, and *Arteriosclerosis, Thrombosis, and Vascular Biology*.

Dr. Nabel has served on American Heart Association committees, including
the Board of Directors; the Scientific Publishing Committee (Chair); the
Atherosclerosis, Thrombosis and Vascular Biology Council (Chair); the
executive committee of the Basic Cardiovascular Sciences Council and the
Science Advisory and Coordinating Committee. Other national and
international leadership roles include President of the North American
Vascular Biology Organization, Councilor of the American Society of
Clinical Investigation, member of the Board of Directors for the
Keystone Symposium, member of the Scientific Advisory Board of The
Stanley J. Sarnoff Endowment for Cardiovascular Science, and as a member
of the membership committee of the Institutes of Medicine. She has also
served on international advisory committees including the Center for
Transgene Technology and Gene Therapy and the Center for Molecular and
Vascular Biology at the University of Leuven, and the International
Vascular Biology Organization.

Number range CHAPTERDepartment of Health and Human Services

Office of Budget

William R. Beldon

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor's
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.