[Senate Hearing 113-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2014
----------
WEDNESDAY, APRIL 2, 2014
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10 a.m., in room SD-192, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Durbin, Mikulski, Moran, Cochran,
Shelby, and Kirk.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR
ACCOMPANIED BY:
ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
HAROLD E. VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
GARY H. GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG AND BLOOD
INSTITUTE
STORY C. LANDIS, PH.D., DIRECTOR, NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
CHRISTOPHER P. AUSTIN, M.D., DIRECTOR, NATIONAL CENTER FOR
ADVANCING TRANSLATIONAL SCIENCES
opening statement of senator tom harkin
Senator Harkin. The Appropriations Subcommittee on Labor,
Health and Human Services, and Education, and Related Agencies
will come to order. Good morning, everyone, and welcome. Sorry
we are a little late. We had a vote at 10--that is all.
Well, today will be my final Appropriations budget hearing
for the NIH (National Institutes of Health) as the chair of
this subcommittee. I took over this subcommittee from Senator
Lawton Chiles in 1989. That is a long time ago it seems, a
quarter century. I am so proud of all that we have done--all of
us here--often on a bipartisan basis, to transform the National
Institutes of Health into truly the jewel and the crown of
biomedical research not only in the United States, but
globally.
On Tuesday, as many of you know, I was on the NIH campus to
help dedicate the new John Porter Neurosciences building. I was
struck as I drove around the campus by the growth and
modernization that has taken place there in the last 25 years.
But that physical transformation has been more than matched by
the transformational science and discovery that has sprung from
that campus.
If you do not mind, a little bit of reminiscences. My first
year as chair was the first year that we invested NIH dollars
in an exciting new project to map the human genome, 1989. I
will never forget. I had taken over this subcommittee and I was
visited by Dr. James Watson, whom I had never met before, but
of course I had read about him--the famous Nobel Prize winner--
Watson and Crick, discoverers of the double helix. And so, I
was quite full of myself when as a freshman Senator I was
visited by this great scientist who wanted to talk to me about
investing in mapping and sequencing the human gene. I had no
idea what he was even talking about at that time, but he
brought me along a little bit, and so we were able to put a
little bit of money into that.
Thanks again to all that initial work. And thanks to the
work of Dr. Collins and his colleagues at NIH. We can now
sequence the human genome at a fraction of the cost that it
required, and in a shorter timeframe. I might just add, there
was a study done by the Battelle Institute. It came out last
year and said that the U.S. Federal Government's $3.8 billion
funding of the Human Genome Project between 1988--actually it's
1989, but that is okay--between 1988 and 2003 drove $796
billion in U.S. economic impact due to the growth of the
genomics technology industry and the use of genomics in
healthcare, energy, agriculture, and other sectors--quite a
rate of return on investment.
And consider this: In 1989--I remember it well in the
1980s--HIV (human immunodeficiency virus) was a death sentence.
Today, thanks in large part to the leadership of Dr. Anthony
Fauci, HIV is a manageable chronic disease, and we know how to
prevent it. Since 1989, the proportion of older people with
chronic disabilities has dropped by nearly one-third. Cancer
death rates in the U.S. are now falling at a rate of nearly 1
percent each year. And each 1-percent decline saves our Nation
nearly $500 billion. There has been near miraculous progress in
the fight against childhood cancers with the 5-year survival
rate for the most common type, acute lymphocytic leukemia, now
rising to a 90-percent cure rate. That is fantastic.
Two of our witnesses here today direct centers that did not
exist, that were not part of NIH in 1989. The National
Institute of Mental Health moved from SAMHSA (Substance Abuse
and Mental Health Services Administration) to NIH in 1992, and
this subcommittee created the National Center for Advancing
Translational Sciences (NCATS) in 2011. And although the
directors are not here today, I am particularly proud to have
authored the bill that created the National Institute on
Deafness and Communication Disorders in 1988. Again, as I said,
we worked to elevate the Genome Research Office at that time to
a center in 1989, and we created the National Center for
Complementary and Alternative Medicine in fiscal year 1992.
Looking back to 1989, my notes tell me that in 1989 a Yale
scientist named Francis Collins led a research team to discover
the gene for cystic fibrosis.
How far the NIH has come in 25 years. So many Nobel Prizes.
So many life-saving discoveries. This subcommittee has had no
higher priority than to support NIH and the scientists all
across America dedicated to reducing suffering and improving
public health. So this is a bittersweet moment for me and for
all of us who revere the work of NIH because these great
achievements are in the past. The future leadership of NIH is
threatened by penny wise, pound foolish thinking by too many
here in the Congress. Most in Congress are obsessed by budget
deficits. I am more concerned by our deficits of vision and
ambition and leadership.
I am proud to say that since 1989, I have either chaired or
been the ranking member of this subcommittee. Most of that time
with Senator Arlen Specter. We kept changing back and forth as
the leadership of the Senate would change, more recently with
both Senator Shelby and now Senator Moran on this committee. So
it has been, for me, an enlightening experience, through all
these years. I do not have a science background, a bit of an
engineering background, but not much of science. So for me it
has just been eye opening to see what has happened with NIH
through all these years.
As our Government charts a course of stagnation and
disinvestment in biomedical research, other countries are
surging ahead. China's government pledged to increase its basic
research investment by a staggering 26 percent just in the last
year and will invest more than $300 billion in biotechnology
over the next 5 years, twice what we are planning on doing.
So this is the context in which we consider the proposed
funding levels for fiscal year 2015. The Murray-Ryan budget
deal partially replaced the sequester for the coming year, and
while I am pleased that the subcommittee has a solid top line
figure to work with, these austere budget caps are wreaking
havoc on NIH and other national priorities.
With a non-defense cap that increases by $583 million this
year, it is mathematically impossible to fully replace the
remaining NIH sequester and provide just an inflationary
increase to NIH without forcing additional cuts to education,
and job training, and other priorities.
By not replacing the sequester this year, we are foregoing
$56 billion that could be invested in programs to grow our
economy, programs like NIH. The President proposed a fully
offset opportunity growth and security initiative that
represents the $56 billion in lost--that was lost to sequester.
That initiative would allow for investing an additional $900
million in NIH, enough to bring NIH back to the pre-sequester
level and then provide a small increase. That is what we are
losing by clinging to this devastating policy of sequester.
Make no mistake: Keeping the sequester in place will mean a
steady, destructive erosion in our NIH investment. It is no
longer a question of politics; it is just a question of math.
So I look forward to the discussion today about the
exciting work that NIH is doing in the face of these budget
problems, and in the hopes that we can all work together to
support this vital institution, and to maintain America's
leadership in our biomedical sciences. With that, I will yield
to Senator Moran for his opening statement.
statement of senator jerry moran
Senator Moran. Mr. Chairman, thank you. I look forward to
continuing to work with you during the remainder of your term
as chairman of this subcommittee along with Senator Shelby, the
ranking member, and Chairwoman Mikulski to see that we
accomplish some of the goals that you outlined in your
statement.
And I do appreciate Dr. Collins and his colleagues being
with us today to discuss the National Institutes of Health. In
my view, NIH represents hope for millions of patients suffering
from conditions from Alzheimer's disease to cancer. NIH-funded
research has raised life expectancy, improved the quality of
life, and is an economic engine helping to sustain America's
competitiveness.
Over the past year, cutting-edge NIH-supported research
discovered a blood test to predict if a healthy person will
develop dementia or Alzheimer's disease, uncovered a set of
rare mutations to a gene that provides protection against type
2 diabetes, and used targeted immunotherapy to induce remission
in leukemia. What wonderful developments. A continued
commitment to NIH is essential to address our Nation's growing
health concerns, spur medical innovation, sustain American
competitiveness, and reduce healthcare costs.
I think NIH is at a critical juncture. We have spent years
focusing on doubling the NIH budget, and now a decade later the
NIH budget is falling victim to an Administration's budget that
does not prioritize biomedical research. The fiscal year 2015
budget touts an increase of $200 million, or 0.7 percent,
seven-tenths of a percent. However, with the use of, really, a
budget gimmick, the increase is all but eliminated with the
President's proposal to increase the evaluation set-aside.
Under the President's proposal, $142 million of the $200
million increase would be transferred to other programs within
the Department of Health and Human Services, leaving NIH with
only a $58 million increase.
Without a consistent commitment to funding our premiere
medical research agency, the future of biomedical research in
the United States is in jeopardy. Grant success rates are at an
all-time low. The average age of a first-time R01 grantee is 42
years old, up from 38 years old in 1980. I looked out across
the list of the panel of witnesses and discovered that you all
remain very young, so perhaps that is defeating the point I am
trying to make. But our researchers are becoming older as we
continue this process. In fact, our principal investigators who
are 65 or older receive more than twice as many R01 grants than
those 36 and under. Young scientists, which we desperately
need, will be discouraged by these statistics, and many have
fled research fields or left for opportunities in other
countries, putting our Nation at a serious risk for losing our
global competitiveness in the biomedical research field and
reducing the chances that we find cures and treatments.
Dr. Collins has consistently raised this concern about what
he calls ``deep long-term damage'' to biomedical research, and
we should all pay attention to his warnings. We cannot let
these research opportunities slip away. We cannot lose the
brilliant scientists, the scientific minds that will make
future ground-breaking discoveries in biomedical research to
alternative careers or other countries. And we must not
squander the scientific capacity that we have developed.
I believe funding decisions represent more than just
dollars. They reflect our Nation's priorities. And this
Congress faces unprecedented challenges to reduce Government
spending. Now is the time to reevaluate our funding priorities
and invest after evaluating those priorities in biomedical
research. This is the time of promise in research, and the
United States should be at the forefront in this area. To do
so, we must commit to pay for the research. We must accomplish
this. And I thank you, Mr. Chairman.
Senator Harkin. Thank you, Senator Moran. Well, again, Dr.
Collins and colleagues, welcome again to our subcommittee. I
got your statement. I read it. It will be a part of the record
in its entirety. And, Dr. Collins, we will recognize you. Just
proceed as you so desire for 10 minutes or so, or whatever it
takes you to get it done. Welcome back, Dr. Collins.
summary statement of dr. francis s. collins
Dr. Collins. Well, thank you, and good morning, Chairman
Harkin, Ranking Member Moran, and members of the subcommittee.
Let me introduce the folks at the table who are here with me:
Over to your right, my left, Dr. Harold Varmus, the Director of
the National Cancer Institute (NCI), formerly the director of
the NIH; next to him, Dr. Gary Gibbons, Director of the
National Heart, Lung, and Blood Institute; and immediately to
my left, Dr. Christopher Austin, Director of the new National
Center for Advancing Translational Sciences, NCATS; to my
right, Dr. Story Landis, the Director of the National Institute
of Neurological Disorders and Stroke; and finally as already
mentioned, Dr. Anthony Fauci, Director of the National
Institute of Allergy and Infectious Diseases. And they are here
to answer your questions, as am I.
Well, it is a great honor for us to be here to appear
before you and present the Administration's fiscal year 2015
budget request, and to provide an overview of our Agency's
critical role in enhancing the Nation's health through
scientific discovery. But before I begin today, I would be
remiss if I did not take a moment to thank you, Mr. Chairman,
for your extraordinary leadership on this subcommittee over
these 25 years. You have been a remarkable--I would say even
historic--advocate for biomedical research and for the NIH. We
are all very grateful for your service, and will truly miss you
on this subcommittee in the years to come.
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national institutes of health mission
Dr. Collins. NIH has been advancing our understanding of
health and disease for more than a century. Scientific and
technological breakthroughs generated by NIH-supported research
are behind many of the gains that you can see in this image of
how our country has enjoyed gains in longevity and in health.
For example, over the last 60 years, deaths from heart disease
have fallen by more than 70 percent. Meanwhile, cancer death
rates, as you have already cited, have been dropping about 1
percent annually for the last 15 years, life expectancy gains
that have saved our Nation trillions of dollars. Likewise, HIV/
AIDS treatments have greatly extended lives, and prevention
strategies are enabling us to envision the first AIDS-free
generation since this virus emerged more than 30 years ago.
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Dr. Collins. But none of these advances could have happened
without the strong support of the Administration and the U.S.
Congress, and specifically of this subcommittee. This
subcommittee came together in a bipartisan way, and I want to
thank you for that, to make it possible in the fiscal year 2014
omnibus appropriation to turn a corner.
budget challenges
To be honest, the previous year was quite challenging for
us. Sequestration applied damaging cuts to ground-breaking
medical research and affected the morale of the scientific
community. That impact was further exacerbated by the
Government shutdown, which forced me to send 12,000 scientists
home for 16 long days, and required us to turn patients away
from the NIH Clinical Center.
With the fiscal year 2014 omnibus, we are optimistic that a
corner has been turned after a difficult decade during which
NIH has lost more than 20 percent of its purchasing power for
medical research, 20 percent down from where we were in 2003.
The Administration now proposes a fiscal year 2015 budget
request that is $211 million, or .7 percent, above the fiscal
year 2014 level. This budget request reflects the President's
and the Secretary's commitment to improving the health of the
Nation and to maintaining our leadership in the life sciences
while remaining within the constraints of the Murray-Ryan
budget envelope. It allocates resources to areas with the most
extraordinary promise for medical research, while maintaining
the flexibility to pursue unexpected scientific opportunities,
and to address unforeseen public health needs.
Within the Administration's fiscal year 2015 budget, NIH
will increase our primary funding mechanism for investigator-
initiated research, the research project grants, or RPGs. And
this is a critical priority. In fiscal year 2013, our grant
success rate, as you can see in this graph, reached an all-time
low of 16.8 percent, a number that desperately needs to rise
again.
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Dr. Collins. By careful stewardship of resources, we expect
to support 9,326 new and competing RPGs next fiscal year, which
will be an increase of 329 over fiscal year 2014 levels,
although the total number of grants we support will remain
approximately the same.
But now, let me turn to some of the exciting scientific
opportunities that NIH is pursuing today.
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future of biomedical research
Dr. Collins. I can assure you the future of biomedical
research has never been brighter. Basic science, for which the
Federal Government serves as the main source of support in the
U.S., had led the way. Advances in genomics, proteomics, stem
cells, imagine, the microbiome, and other technologies have led
to phenomenal advances in our understanding of how life works,
and also the discovery of more than a thousand new risk factors
for disease.
NIH will continue to spend a little more than half of our
budget on these basic science advances. But as you know, we are
also deeply committed to catalyzing the translation of these
discoveries into clinical advances. And this can be quite
challenging to the dismay of researchers, drug companies, and
especially patients. We face a situation today where the vast
majority of drugs entering the development pipeline fall by the
wayside.
The most distressing failures, as you see here, occur when
a drug is found to be ineffective in the later stages of
development, in phase two or phase three clinical trials, after
years of work and millions of dollars have already been spent.
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accelerating medicines partnership
Dr. Collins. A major reason for such failures is that
scientists often have not had enough information to choose the
right biological targets, and if a drug is aimed at the wrong
target, it will not be effective against the disease it was
intended to treat, and a failure will occur.
So to this end, we were particularly thrilled to announce
the launch of the Accelerating Medicines Partnership, AMP, just
6 weeks ago.
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Dr. Collins. This pre-competitive partnership, which will
share all data openly, will initially focus on three disease
areas that are ripe for drug discovery: Alzheimer's disease,
type 2 diabetes, and the autoimmune disorders lupus and
rheumatoid arthritis.
Besides NIH, the partners in AMP include the FDA and 10
biopharmaceutical firms, listed here, and a number of non-
profits, including patient advocacy groups.
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universal flu vaccine
Dr. Collins. This unprecedented public/private
collaboration will use cutting-edge scientific approaches to
sift through a long list of potential therapeutic targets and
choose those most likely to lead to success, with the cost
being shared evenly by NIH and industry.
But we are not stopping there. Influenza is another area
where we are poised for rapid progress. In fact, NIH-funded
scientists are well on their way to developing a universal
vaccine. The outside of the flu virus, shown here, is coated
with tiny mushroom-shaped proteins, and each of these proteins
has a head and a stem.
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Dr. Collins. Current vaccines target the head of that
mushroom, but this mutates over time. Here you can see in
yellow the changes that occurred in three different flu
viruses.
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Dr. Collins. These changes, primarily in the head, are
happening all the time. To keep up, a new vaccine must be
produced every year.
On the other hand, you can see here the stem of the viral
protein remains almost entirely unaltered over time. A
universal flu vaccine that targets the relatively stable stem
would not only eliminate the need for an annual flu shot, but
would also provide protection against outbreaks like the H5N1
and H7N9 events in Southeast Asia that are causing considerable
worldwide concern right now.
brain initiative
Another major challenge is exploring what has been called
the most complex structure in the known universe, the human
brain. As you know, NIH is leading the new Brain Research
through Advancing Innovative Neurotechnologies, B-R-A-I-N,
BRAIN Initiative, and we are grateful for your support.
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Dr. Collins. This initiative will provide a foundational
platform for major advances in Alzheimer's disease, autism,
schizophrenia, traumatic brain injury, epilepsy, and many other
brain disorders.
But a final area of scientific opportunity that I want to
highlight today involves one of our Nation's biggest and most
feared killers, cancer. Until recently, our weapons for
attacking cancer have been surgery, radiation, and
chemotherapy, all of which can be effective, but carry risks.
Recent advances have given us insights into the intricate
workings of the cancer cell, and a whole new generation of
targeted therapeutics is emerging, ushering in an era of
individualized precision medicine.
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opportunities in cancer research
Dr. Collins. This image on the left shows a dramatic
example of just how effective such targeted therapies can be
because on the left is a scan of a melanoma patient who carries
a mutation and a gene that codes a protein called B-Raf. Now,
B-Raf is implicated when mutated in the development of cancer.
The hot spots that you see all over this individual's body
indicate dividing cancer cells that have spread throughout.
After treatment with a new drug targeted to block the effects
of mutant RAF, those hot spots almost vanish. The promise of
targeted therapy is apparent.
But now, there is a new powerful weapon in the arsenal,
cancer immunotherapy, a revolutionary new approach that Science
magazine named its 2013 breakthrough of the year.
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Dr. Collins. This involves harnessing the body's own immune
system to fight this dreaded disease. In one of those new
approaches, certain types of immune cells called T-cells--you
can see them here--are collected from cancer patients and
engineered to produce special proteins on their surface. When
these engineered T-cells are infused back into patients, they
have the power to seek and destroy cancer cells.
And in this video, you can see one of those modified T-
cells doing just that, actually obliterating the cancer cell.
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Dr. Collins. Knowing how to turn T-cells into little Ninja
warriors required big investments in basic biomedical research
over more than a decade, but the consequences are starting to
be amazing.
I would like to share this story, in closing, of Emily
Whitehead.
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Dr. Collins. Nearly 2 years ago, this brave little girl
became the first pediatric patient to be treated with a new
kind of cancer immunotherapy. Emily was suffering from acute
lymphoblastic leukemia, a disease that, as was pointed out by
Senator Moran, now we cure 90 percent of the time with
chemotherapy. But distressingly, Emily was in the 10 percent
where that fails.
Her parents decided to enroll her in a pioneering cancer
immunotherapy trial at the Children's Hospital of Philadelphia.
Emily's T-cells were collected from her blood and re-engineered
in the lab to recognize a protein found only on the surface of
her leukemia cells. Those T-cells were then infused back into
Emily's blood where they circulated throughout her body on a
mission to seek and destroy leukemia. Just 28 days after
treatment, she was cancer free, and she remains so to this day.
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Dr. Collins. Here is Emily today, a happy, healthy third
grader who is looking forward to celebrating her ninth birthday
next month. As her mom, Kerry, puts it, ``If you didn't know
what happened to her and you saw her now, you would have no
idea what she has been through.'' A wonderful story of success.
prepared statements
And, Senators, I believe there are a great many more Emilys
on the horizon. Our Nation has never witnessed a time of
greater promise for advances in medicine. With your support, we
can realize our vision of accelerating discovery across the
vast landscape of biomedical research. From basic scientific
inquiry to human clinical trials, the National Institutes of
Hope is ready to move forward.
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Dr. Collins. Thank you, Mr. Chairman, for your support of
NIH. My colleagues and I welcome your questions.
[The statements follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good morning, Mr. Chairman and distinguished members of the
subcommittee. I am Francis S. Collins, M.D., Ph.D., Director of the
National Institutes of Health (NIH). It is an honor to appear before
you today to present the Administration's fiscal year 2015 budget
request for the NIH and provide an overview of our critical role in
enhancing our Nation's health through scientific discovery.
As the Nation's biomedical research agency, NIH's mission is to
seek fundamental knowledge about the nature and behavior of living
systems and to apply that knowledge to enhance human health, lengthen
life, and reduce illness and disability. I can report to you that NIH
leadership, employees, and grantees continue to believe passionately in
this mission.
Before I discuss the tremendous strides we have made and the
exciting scientific opportunities on the horizon, I want to thank you,
Mr. Chairman, and Ranking Member Moran, as well as your colleagues, for
the recent fiscal year 2014 Omnibus Appropriation bill. The
subcommittee came together in a bipartisan way to increase funding for
NIH and we are truly grateful for your action. The past year has been
challenging for us: The sequester reduced funding for groundbreaking
medical research and affected the morale of the scientific community.
This impact was further exacerbated by the shutdown.
There is much good news to report about the science that we
support. NIH has been advancing our understanding of health and disease
for more than a century; scientific and technological breakthroughs
generated by NIH-supported research are behind much of the gains our
country has enjoyed in health and longevity. For example, deaths from
heart disease have been reduced by more than 70 percent from 1950 to
2008. Cancer death rates have been dropping about 1 percent annually
for the past 15 years--life expectancy gains that save the Nation
billions of dollars. HIV/AIDS treatment and prevention now enable us to
envision the first AIDS-free generation since this virus emerged more
than 30 years ago. NIH research also has given us vaccines to protect
against an array of life-threatening diseases, including cervical
cancer, influenza, and meningitis. We can look forward to a future in
which advanced prevention and treatment strategies such as these allow
everyone to have a significantly better chance of living a long and
healthy life.
These statistics tell you how far we have come--but our aim is to
go even further, faster. To this end, the Administration's fiscal year
2015 budget request for the NIH is $30.362 billion, $211 million, or
0.7 percent, above the fiscal year 2014 level. This budget request
reflects the President's and the Secretary's commitment to improving
the health of the Nation and to maintaining our Nation's leadership in
the life sciences. The request highlights investments in innovative
research that will advance fundamental knowledge and speed the
development of new therapies, diagnostics, and preventive measures to
improve public health.
The fiscal year 2015 budget request will enhance NIH's ability to
support cutting-edge research and training of the scientific workforce.
Within the Administration's fiscal year 2015 budget, we will continue
to increase Research Project Grants (RPGs), NIH's funding mechanism for
investigator-initiated research. NIH expects to support 9,326 new and
competing RPGs in fiscal year 2015, an increase of 329 over fiscal year
2014 levels. For fiscal year 2015, NIH anticipates funding a total of
34,197 RPGs. The budget request allocates resources to areas of the
most extraordinary promise for biomedical research, while maintaining
the flexibility to pursue unplanned scientific opportunities and
address unforeseen health needs.
While we are very grateful for any budget increase, the fully paid
$56 billion Opportunity, Growth, and Security Initiative (OGSI), a
program included in the President's budget, would provide an additional
$970 million investment in NIH programs that would allow NIH to fund or
expand a host of other cutting-edge initiatives, speeding the
development of vaccines and cures, and restoring sequestration cuts to
the number of research project grants.
Let me describe a few of the many areas in which NIH-supported
research is opening up extraordinary opportunities to improve the
health of the American public.
A major program that began this year is the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative, for which
thanks are due to this subcommittee for its fiscal year 2014 support.
NIH is a major player in this pioneering multiagency venture that will
enable the creation of new tools capable of examining the activity of
billions of nerve cells, networks, and pathways in real time. By
measuring activity at the scale of circuits and networks in living
organisms, we can begin to decode sensory experience and, potentially,
even memory, emotion, and thought. Successful pursuit of the BRAIN
Initiative will revolutionize neuroscience, providing a foundational
platform for major advances in Alzheimer's disease, autism,
schizophrenia, epilepsy, traumatic brain injury, and many other brain
disorders.
As technology allows us to tackle mind-boggling tasks like
recording the activity of billions of nerve cells in the brain or
determining the DNA sequence of tens of thousands of human genomes,
researchers are generating enormous quantities of data at an
unprecedented pace. The challenge posed by this revolution is how to
store, retrieve, integrate, and analyze this mountain of complex data--
and transform it into knowledge that can improve human health. To
address this challenge that affects virtually all areas of biomedical
research, we have just launched the Big Data to Knowledge (BD2K)
initiative. The goals of BD2K are to develop and disseminate new
analytical methods and software, enhance training of data scientists,
and facilitate broad use and sharing of complex biomedical datasets.
With sustained investment and effort, we will overcome the challenges
associated with Big Data to accelerate real-world applications of basic
science discoveries.
We are also excited about another area of intense interest: the
development of therapeutics. Recent advances in genomics, proteomics,
imaging, and other technologies have led to the recent discovery of
more than a thousand risk factors for disease--biological insights that
ought to hold promise as targets for drugs. But drug development is a
terribly difficult and failure-prone business. To the dismay of
researchers, drug companies, and patients, the vast majority of drugs
entering the development pipeline fall by the wayside. The most
distressing failures occur when a drug is found to be ineffective in
the later stages of development--in Phase II or Phase III clinical
studies--after years of work and millions of dollars have already been
spent. A major reason for such failures is that scientists often have
not had enough information to choose the right biological targets. If a
drug is aimed at the wrong target, it won't work against the disease it
was intended to treat.
With that challenge in mind, we were thrilled last month to launch
the Accelerating Medicines Partnership (AMP). This unprecedented
public-private effort will use cutting-edge scientific approaches to
sift through a very long list of potential therapeutic targets, and
choose those most likely to lead to success. Besides NIH, the AMP
partners include the FDA, 10 biopharmaceutical firms and a number of
nonprofits, including patient advocacy groups. This precompetitive
partnership, which will share all data openly, will initially focus on
three disease areas that are ripe for discovery: Alzheimer's disease,
type 2 diabetes, and the autoimmune disorders, lupus and rheumatoid
arthritis. Through this team effort, we believe we can reach our shared
goals of treating and curing disease faster.
Preventing disease is another top priority, and influenza is one
area of prevention in which we are poised for rapid progress.
Currently, to provide protection against the rapidly evolving influenza
virus, a new vaccine must be produced each year and we all need to get
an annual flu shot. Also, despite best efforts, the vaccine isn't
always ideal. In an average year, the flu claims up to 49,000 American
lives and costs the U.S. economy about $87 billion. But it does not
have to be that way. NIH-funded researchers are now working on a
universal flu vaccine--designed to protect people against virtually all
strains of the flu for extended periods of time and, thus, potentially
reduce the need for annual flu shots. Of critical importance, such a
vaccine could also protect against a future global flu pandemic.
While we are several years away from having a universal flu vaccine
available to the public, our researchers have already demonstrated
proof of concept and are testing a number of approaches, including two-
stage ``prime boost'' vaccines and ferritin nanoparticles. Clearly, the
prospect of a universal flu vaccine is not science fiction. Early
clinical studies are already underway. With sustained investment, the
United States may be a few years away from realizing its potential to
benefit our health and our economy.
As impressive as a universal flu vaccine would be, it is not the
only trick we are teaching our immune systems. We are also aiming to
harness the body's own immune system to fight cancer. Until recently,
our weapons for attacking cancer have been largely limited to surgery,
radiation, and chemotherapy--treatments that carry risks and cause
adverse side effects. Now, after years of intense basic and
translational research, we have an exciting new possibility: Cancer
immunotherapy.
Researchers have long been puzzled by the uncanny ability of cancer
cells to evade the immune response. What stops the body from waging its
own ``war on cancer?'' As it turns out, our bodies have built-in
checkpoints to prevent our immune systems from going into overdrive and
killing healthy cells. Now, NIH-funded researchers have discovered a
way to genetically modify certain white blood cells called T-cells--the
soldiers of the immune system--to attack tumor cells. In this new
approach, T-cells are collected from cancer patients and engineered in
the lab to produce special proteins on their surface, called chimeric
antigen receptors (CARs). When the modified cells are infused back into
patients, they multiply and, with guidance from their newly engineered
receptors, seek and destroy tumor cells. Promising results in patients
with leukemia prompted Science magazine to name this its 2013
Breakthrough of the Year.
Today, I have provided a very brief overview of NIH's past
successes and continuing commitment to basic, translational, and
clinical research. Our Nation has never witnessed a time of greater
promise for advances in medicine. With your support, we can anticipate
a future of accelerating discovery across NIH's broad research
landscape, from fundamental scientific inquiry to human clinical
trials. The ``National Institutes of Hope'' is ready to move forward.
This concludes my testimony, Mr. Chairman. I look forward to your
questions.
______
Prepared Statement of Anthony S. Fauci, M.D.
Mr. Chairman and Members of the Committee: I am pleased to discuss
current and future plans for biomedical research at the National
Institute of Allergy and Infectious Diseases (NIAID) of the National
Institutes of Health (NIH). The President's fiscal year 2015 NIAID
budget request of $4,423,357,000 billion is approximately $31 million
more than the fiscal year 2014 funding level ($4,392,670,000).
NIAID conducts, supports, and translates basic and clinical
research into the development of diagnostics, therapeutics, and
vaccines to detect, treat, and prevent infectious and immune-mediated
diseases. NIAID has a dual mandate that balances research addressing
current biomedical challenges with the capacity to rapidly respond to
new threats from emerging and re-emerging infectious diseases and
bioterrorism.
infectious diseases research
HIV/AIDS.--NIAID is leading transformational progress in basic and
clinical research on HIV/AIDS. The decades-long NIAID investment in
HIV/AIDS research has made the goal of an AIDS-free generation a
possibility with sustained effort. NIAID continues to improve and
refine HIV prevention and treatment tools, including antiretroviral
therapies to effectively manage disease and reduce HIV transmission,
and pre-exposure prophylaxis to protect against HIV. NIAID also is
advancing research toward the development of an effective HIV vaccine
to complement existing prevention strategies. HIV vaccine development
will be informed by NIAID efforts to identify immunological markers in
the subset of people protected against HIV infection in the RV144
trial, the first HIV vaccine trial to show modest efficacy. The NIAID
Vaccine Research Center together with several NIAID grantees are making
rapid progress on ways to generate broadly neutralizing antibodies to
protect against multiple strains of HIV, research that may translate to
vaccines and therapeutics of global public health significance.
Years of NIAID-supported research on HIV pathogenesis and the role
of HIV reservoirs have suggested the feasibility of curing some HIV-
infected individuals. NIAID will investigate promising reports of a
handful of infants who were born HIV-positive but now test negative for
the virus following aggressive antiretroviral treatment initiated
shortly after birth by supporting a clinical trial to determine if this
strategy is safe and effective for other infants. NIAID also will play
a major role in implementing the President's $100 million HIV/AIDS cure
research initiative. As part of this effort, NIAID will support
additional research on HIV latency and persistence. Understanding these
processes may reveal new strategies toward a cure.
NIAID recently restructured its HIV/AIDS Clinical Trials Networks
to capitalize on the growing body of promising HIV research findings
and to better address current research questions. The Networks will
focus on improved ways to prevent and treat HIV, tuberculosis and
hepatitis C co-infections, and on research toward development of a
vaccine, microbicides, and a cure.
Tuberculosis.--Tuberculosis (TB) remains a significant cause of
illness and death throughout the world, especially among those also
infected with HIV. NIAID recently launched a genome sequencing project
that will examine the genetic diversity of TB bacteria and patterns of
drug resistance to understand TB pathogenesis and to identify new drug
targets and molecular mechanisms of resistance. This research will be
particularly important to address the emergence of multi- and
extensively drug-resistant TB. NIAID-supported scientists also are
working to modify the existing antibiotic spectinomycin to bypass
mechanisms of resistance to this drug. These efforts have shown promise
in TB animal models.
Malaria.--NIAID continues to progress toward its goal to control,
eliminate, and ultimately eradicate malaria worldwide. The development
of vaccines is a critical part of this endeavor. NIAID researchers and
grantees recently completed an early-stage clinical trial that showed a
novel vaccine composed of weakened malaria sporozoites was safe and
protected against malaria. NIAID has developed two new tests to rapidly
and inexpensively detect resistance to artemisinin, a first-line
antimalarial drug. NIAID also is exploring innovative methods to
control the spread of malaria. For example, NIAID-funded researchers
have established a bacterial infection that passes from female
mosquitoes to their offspring and kills malaria parasites within the
mosquitoes before they can infect humans.
Other Infectious Diseases of Domestic and Global Health
Importance.--NIAID is committed to research on infectious diseases
affecting global health. Influenza is among the most important
infectious diseases of domestic and global concern. NIAID research
addresses the challenge of seasonal influenza and prepares for the
threat of an emerging pandemic. NIAID is developing and evaluating
vaccines against the avian influenza strains H5N1 and H7N9 to deploy if
needed to prevent further spread among humans. NIAID also is examining
these vaccines paired with adjuvants--components that enhance the
immune response--to provide the greatest protection with the smallest
dose possible. NIAID investigators and grantees are making significant
progress toward the development of a universal influenza vaccine that
could generate durable protection over a period of years against a wide
range of seasonal and pandemic influenza strains. Studies conducted by
NIAID scientists at the NIAID Special Clinical Studies Unit in the NIH
Clinical Center are providing important clues into the susceptibility
and immune response of patients to influenza infection. Future studies
will examine the effectiveness of new vaccines and therapeutics.
Respiratory syncytial virus (RSV) is a serious respiratory
infection primarily of young children that causes significant illness
and hospitalizations in the U.S. and thousands of deaths worldwide.
There is no vaccine to protect infants and children against RSV.
Researchers at the NIAID Vaccine Research Center recently determined
the structure of a key RSV protein bound to a broadly neutralizing
human RSV antibody and used it to design an experimental RSV vaccine
that is effective in animal models. NIAID has advanced this
groundbreaking RSV vaccine into early-stage clinical trials in humans.
Science magazine highlighted this discovery among the top 10 scientific
breakthroughs in 2013.
Hepatitis C virus (HCV) is a significant cause of chronic liver
disease and cancer, and often co-infects people with HIV. Traditional
HCV therapies frequently have severe side effects and may not be
successful in many patients. NIAID and NIH Clinical Center
investigators recently led a Phase II trial of a new HCV drug,
sofosbuvir. The trial demonstrated that sofosbuvir, combined with the
antiviral drug ribavirin, was highly effective and well tolerated even
in patients predicted to have poor outcomes with traditional HCV
treatments. Sofosbuvir and similar therapies for the treatment of HCV
have recently been approved, potentially revolutionizing treatment
outcomes.
Antimicrobial resistance is a significant public health challenge
and an NIAID priority. NIAID recently reassessed research needs for
this important issue and established a Leadership Group to design,
implement, and manage the clinical research agenda for a new
antibacterial resistance research network. NIAID provides resources to
lower the investment risk for industry, academia, and non-profit
organizations to facilitate a robust pipeline of diagnostics, vaccines,
and therapeutics for resistant microbes.
research on immunology and immune-mediated disorders
NIAID's commitment to research on basic and clinical immunology
continues to foster important insights that ultimately will help to
better treat and prevent immune-mediated disorders, including food
allergy. NIAID-funded investigators recently demonstrated that female
sex hormones affect the gut microbiome and promote development of
autoimmunity in an animal model, providing clues into why women are
more likely to be affected by autoimmune diseases. NIAID-supported
researchers have made progress in understanding how exposure to certain
microbes in early life, especially those found in homes with dogs, may
protect against the development of asthma and other allergies. NIAID
grantees also developed two urine tests to diagnose and predict
rejection of a transplanted kidney. These simple tests could one day
replace the invasive procedure currently used to detect organ rejection
and particularly would benefit African Americans, who are
disproportionately affected by organ transplant rejection.
conclusion
For more than 60 years, basic and clinical research conducted and
supported by NIAID on infectious and immune-mediated diseases has
spurred the development of vaccines, therapeutics, and diagnostics to
improve the health of millions around the world. NIAID will continue to
perform the basic, clinical, and translational research critical to
advancing the health of our Nation and the world.
______
Prepared Statement of Harold E. Varmus, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Cancer Institute (NCI)
of the National Institutes of Health (NIH). The fiscal year 2015 NCI
budget of $4,930,715,000 includes an increase of $7,944,000, or 0.2
percent, compared to the fiscal year 2014 level of $4,922,771,000.
overview of nci research priorities
This is an era of remarkable opportunity in cancer research. Armed
with broad knowledge about how various cancers arise and with powerful
new research tools, the NCI is well equipped to accelerate progress
towards preventing, diagnosing, and treating cancer more effectively.
This era of opportunity is due in significant part to the
subcommittee's consistent support for biomedical research at NCI and
NIH.
The resources that you provide allow NCI to address an ambitious
challenge: reducing the incidence, morbidity, and mortality for all of
the many types of cancer, with tangible benefits for all Americans. The
fiscal year 2015 budget will allow the NCI to build on the tremendous
progress in many areas of cancer research, with the aim of improving
outcomes for patients with all types of cancer.
I will summarize some recent accomplishments and highlight new
opportunities in five areas of NCI-supported research--genomics, cancer
immunology, targeted therapeutics, bioinformatics, and prevention--to
illustrate the breadth and pace of NCI's progress.
The Cancer Genomics research that NCI supports has dramatically
altered our understanding of how cancer develops, identified the
molecular signatures that can be used to diagnose and categorize cancer
more precisely, and provided new targets for therapeutic intervention.
For example, two major initiatives--TCGA (The Cancer Genome Atlas) and
TARGET (Therapeutically Applicable Research to Generate Effective
Treatments)--have addressed nearly twenty common adult cancers and
several less common cancers that occur in adults and children,
revealing both tissue-specific patterns of genetic changes and changes
that are common to several types of cancers. TCGA is a joint initiative
of the NCI and the Human Genome Research Institute. During the past
year, TCGA published comprehensive characterizations of acute myeloid
leukemia, endometrial cancer, and clear cell renal carcinoma, among
others. While every cancer is distinct genetically, many changes in the
genome are shared among a wide array of cancer types, and each type of
cancer has distinct patterns that often reflect exposure to
carcinogenic agents, such as tobacco smoke and ultraviolet radiation.
As these massive surveys come to conclusion, the NCI's Center for
Cancer Genomics is leading efforts to make full use of the TCGA
results, including the best ways to incorporate genomic findings into
the design of clinical trials.
Some of the surprising findings from the TCGA and TARGET projects--
such as the involvement of genes that govern the chemistry of
chromosomal proteins, that influence cell metabolism, and that guide
the processing of RNAs and proteins--are influencing the study of
cancer biology throughout the NCI's programs. TCGA and TARGET will
certainly enlarge our understanding of carcinogenesis and will likely
open new frontiers for preventing, diagnosing, and treating cancers.
Cancer immunology is a rapidly advancing field that, in just the
past few years, has dramatically altered our understanding of host
defenses in response to cancers. It has also produced new and well-
validated methods for treating cancer using antibodies that attach to
proteins on cancer cell surfaces and using methods that modulate the
complex behavior of the immune system to attack cancer cells.
For several years, monoclonal antibodies against cancer cell
proteins have been used to treat blood cancers, such as certain
lymphomas and leukemias, and subsets of several types of solid tumors,
such as breast and colorectal cancer. More recently, immunotoxins have
been created by genetic engineering to fuse antibodies with parts of
bacterial toxins to selectively kill cancer cells. For example, such
immunotoxins developed in the NCI intramural program have induced
remissions in late stage cases of mesothelioma, ovarian cancer, triple-
negative breast cancer, drug-resistant hairy cell leukemia, and
childhood acute lymphoblastic leukemia.
There is also great optimism within the science community about
modulating the immune system by introducing novel antigen receptors
into cancer-killing T cells and especially by infusing antibodies that
interfere with a system that impedes the immune response to cancer
cells. These ``immune-modulating'' antibodies have recently received
FDA approval, and other antibodies that bond other immune cell
regulators may soon follow. In 2011, FDA approved a monoclonal
antibody, called ipilimumab, to treat advanced melanoma. Some patients
with metastatic melanoma being treated with ipilimumab are still alive
several years after completing treatment. In 2013, another promising
antibody to treat melanoma--lambrolizumab--received ``breakthrough''
designation by the FDA, helping expedite its development and further
use in clinical trials, with the possibility of an expedited FDA
review. In recognition of these and other recent achievements in the
field of immunology, and the promise of further developments, ``cancer
immunotherapy'' was named this year's Breakthrough of the Year by
Science magazine.
Targeted therapies, based on the use of drugs that inhibit specific
proteins implicated in the behavior of cancer cells, are now being
developed and tested for their effects in patients with many types of
cancer. Over the past decade, FDA has approved several drugs that rely
on this therapeutic approach to treat cancers of blood cells, lung
cancer, melanoma, and other cancers, and many more are in development.
This activity has accelerated because of discoveries in genomics, cell
signaling pathways, chemistry, and structural biology, and with the
identification of new ways to inhibit proteins that are required for
the integrity of cancer cells.
Mutant RAS proteins are perhaps the most prominent potential
targets for new therapies that the academic and commercial research
sectors have thus far failed to target with inhibitory drugs. The
importance of the RAS gene family in cancer has been clear for over 30
years; one family member, K-RAS, is mutated in more than 90 percent of
pancreatic adenocarcinomas, about 40 percent of colorectal cancers, and
about 25 percent of lung adenocarcinomas. For this reason, the NCI
recently launched the RAS Project, a large-scale collaboration between
investigators at the NCI's Frederick National Laboratory for Cancer
Research and those in NCI's intramural and extramural communities. The
RAS Project is motivated in part by new developments in the study of
RAS proteins, including new information about their structural
properties, binding of mutant RAS proteins to mutant-specific
inhibitors, interactions with other cellular proteins required for
function, and new tests for genes required to allow RAS mutants to
exert their effects.
Still, while pursuing a path that leads to ``precision medicine,''
the NCI must also maintain its capacity to test new ways to deploy the
currently dominant means of therapy. For instance, a recent study of
patients with metastatic prostate cancer showed markedly increased
survival in men who received chemotherapy when starting anti-androgenic
hormone therapy, a result that is likely to change clinical practice
for a cancer that continues to kill about 30,000 American men annually.
Drug resistance commonly emerges in cancers being treated with
either traditional chemotherapies or novel targeted therapies, allowing
disease to progress. Over the past decade, NCI-supported studies have
revealed several mechanisms by which resistance occurs, including
additional mutations affecting the target molecules, mutations in
related genes, and changes in gene expression. In some cases,
especially chronic myeloid leukemias, drugs that overcome resistance
have been identified, developed and FDA-approved. But in other
situations, resistance to targeted drugs remains a major impediment to
success, and the NCI is making major investments to study this problem.
Bioinformatics, the management of enormous sets of molecular and
clinical data is a critical component of NCI's toolkit to study cancer
in all of its manifestations. In work that ranges from cancer genomics,
to cell signaling, and to clinical trials, the proper collection,
analysis, storage, retrieval, and distribution of ``big data'' are
critical elements of the Institute's charge. The NCI's Center for
Bioinformatics and Information Technology (CBIIT) is addressing these
responsibilities, in conjunction with NCI divisions. Part of the
current effort requires the costly development of ``cloud computing''
to work with the vast (petabyte) amounts of genomic data generated by
TCGA, TARGET, and other projects, and to assemble and ultimately
integrate clinical data with genomic data in manageable forms to
promote further discovery and improve cancer care.
Prevention of cancer remains NCI's most desired goal. While
complete avoidance of cancer may be impossible, since cancers often
arise through spontaneous mutations, the control of tobacco use,
vaccination against cancer-causing viruses (human hepatitis B virus and
human papillomaviruses), sunlight avoidance, and regulation of dietary
and carcinogenic substances (such as asbestos) have already reduced the
incidence and the mortality rates of many cancers. For instance,
between 2001 and 2010, largely due to the earlier reductions in tobacco
use, there was a 25 percent decrease in male death rates and an 8
percent decrease in female death rates due to lung cancer, the major
cause of death from cancer in the United States. Likewise, vaccination
with current HPV vaccines can drastically reduce the incidence and
mortality of several types of cancer, including cervical, anal, and
oropharyngeal cancers that are caused by infection with certain strains
of HPV.
Still, NCI recognizes that these successes are incomplete, and
therefore invests heavily in efforts to address several pertinent
behavioral and biological questions. For instance, despite dramatic
declines in the use of tobacco, about 18 percent of Americans continue
to smoke. New approaches are needed to convince young people not to use
tobacco and to convince current smokers to quit. Use of HPV vaccines
remains far from the desired levels among adolescent girls and boys in
the United States, as the February 2014 report from the President's
Cancer Panel emphasized. Better methods to promote the use of these
potentially lifesaving vaccines are needed, at the same time as the
dosing schedules and the protective breadth of the vaccines are
improved.
conclusion
An important measure of the overall success of NCI's work is the
annual ``Report to the Nation,'' which describes trends in the
incidence and death rates in the United States for many types of
cancer. As has now been true for over a decade, the most reliable
indicator--death rates from all cancers combined for men, women, and
children--continues to decline by about one and a half percent per
year. This reduction represents the savings of an enormous number of
years of life and can be ascribed in large measure to the work of the
NCI to prevent and treat cancers more effectively.
Still, although mortality rates have been decreasing for most
cancers, progress has not occurred as rapidly as desired, and for some
cancers the numbers have not improved--or have worsened. Thus, much
work remains. But the overall success apparent from both the public
health data and recent achievements in the laboratory and clinical
sciences inspires the NCI's conviction that expanded efforts on all
frontiers of cancer research will produce better health in the United
States and around the globe.
______
Prepared Statement of Gary H. Gibbons, M.D.
Mr. Chairman and distinguished members of the subcommittee: I am
pleased to present the President's budget request for the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health (NIH). The fiscal year 2015 budget of $2,987,685,000 includes an
increase of $4,948,000 over the fiscal year 2014 enacted level of
$2,982,737,000.
NHLBI's highest priorities for research investment are conditions
that contribute substantially to the global burden of disease. Heart
and lung diseases are the leading causes of death, disability, and
rising healthcare costs from non-communicable diseases in the United
States and worldwide. Research supported by the NHLBI has contributed
to dramatic improvements in longevity, quality of life, and the wealth
of the Nation. Deaths from cardiovascular disease, for example, have
dropped by 70 percent in the past 40 years. This success reflects a
balanced approach to supporting discovery science that spans basic,
clinical, and population research. As accountable stewards seeking to
maximize the public's return-on-investment, we are committed to
continually improving our approach to strategic priority-setting and
systematic evaluation of our portfolio to ensure the highest possible
impact on science and health.
Reflecting upon the NHLBI's legacy of success, many of the previous
advances involved interventions at the latter stages of chronic
disease. The fiscal year 2015 budget envisions a research agenda that
elucidates the underlying mechanisms of disease such that clinicians
can more accurately predict at-risk individuals and tailor preventive
interventions for disease long before symptoms and irreversible damage
occur. Our strategic vision is guided by the breathtaking scientific
opportunities at hand and public health needs, in consultation with
domain-experts at the leading edge of discovery science. The fiscal
year 2015 budget continues a journey toward predictive, preventive
precision medicine that holds promise for turning research-to-results,
continuing the dramatic decline in the burden of chronic disease in our
Nation.
unprecedented scientific opportunities
Sustained investments in fundamental discovery science have led to
new tools and technologies that stand to revolutionize medical research
and clinical practice. Biomedical advances in congenital heart disease
(CHD), the most common structural birth defect, have led to dramatic
improvements in infant survival over the past 50 years, now with more
adults living with CHD than children. However, current palliative
approaches that repair birth defects have limitations that compromise
the length and quality of life. Recent NHLBI-supported research,
applying the latest genomic technologies, has identified spontaneous
genetic mutations that increase the risk of CHD. This breakthrough
finding is beginning to unlock the mysteries of CHD, helping to define
what goes awry during the formation of the heart and lay the foundation
for preventing or fixing defects in the womb. To that end, NHLBI is
investing in regenerative medicine research to enhance the capacity of
the heart to repair itself. The 2012 Nobel Laureate, Shinya Yamanaka,
is part of a large inter-institutional team of NHLBI-funded
investigators studying how to use a child's own cells to repair a
congenital defect or create a tissue graft that could grow as a child
ages.
NHLBI investments in reparative biology and tissue bioengineering
may also hold promise for accelerating new drug development platforms
in partnership with the private sector. For example, NHLBI-funded
investigators at Stanford University are using stem cells derived from
adult tissue in a laboratory to create heart cells and model diseases
such as those that perturb the electrical system of the heart in atrial
fibrillation. These models are being used to more efficiently screen
many novel drugs to determine efficacy as well as potential toxicities,
augmenting the discovery pipeline.
preempting and preventing chronic disease
New scientific discoveries hold promise for making public health
inroads to halt chronic diseases before they become debilitating. In
sickle cell disease (SCD), for example, we have made great strides in
reducing complications from the disease, such as penicillin to prevent
fatal infections in infants, transfusions to reduce stroke risk, and
hydroxyurea to reduce pain and hospital admissions. While these
advances have extended lifespans from childhood into the sixth decade
of life, they target complications not the disease itself--a disease
that disproportionately affects African Americans (about 1 in 500
births). We recently funded a new program that we hope will lead to the
next generation of SCD treatments. Particularly exciting are studies
that are attempting to raise fetal hemoglobin levels (the most powerful
known modifier of SCD severity) through modulation of a gene called
Bcl11A that is involved in the switch from fetal to adult hemoglobin
during development. These studies open the door to potential treatments
that can reactivate the fetal hemoglobin gene to inhibit the sickle
cell shape change of red blood cells, which could preempt disease
progression.
Chronic obstructive pulmonary disease (COPD), the third leading
cause of death, is a prime example of a chronic disease in which
biomedical research advances have ameliorated symptoms; yet most
interventions fail to dramatically alter the natural course of the
disease. There is a critical need to identify at-risk individuals
earlier in the disease process to prevent disease progression. NHLBI's
COPDgene study is integrating genetics and imaging studies to
characterize pre-clinical subtypes of COPD. Such characterization can
enable clinicians to detect subtle changes in lung function and
structure long before symptoms develop, conventional clinical tests
show abnormalities, or progressive lung damage occurs. This leading-
edge research points to a horizon of individualized, precision medicine
to preempt chronic lung disease.
translating discoveries into public health impact
While basic science is the cornerstone of scientific discovery, it
is the beginning of a long path to public health impact. NHLBI has been
a leader in traversing this road. Noted research initiatives like the
Framingham Heart Study first identified the cardiovascular disease risk
factors now addressed in routine physicals, which led to basic research
that won Brown and Goldstein the Nobel Prize for their research on
cholesterol metabolism--setting the stage for the development of statin
drugs.
We are currently amidst the unfolding of a similar story. The
recent discovery of a mutation in the gene PCSK9 among a family with
very low LDL cholesterol levels and reduced risk of heart attack has
led to basic science discoveries and the rapid development of PCSK9
inhibitors. This public-private partnership is moving toward potential
widespread clinical use as the next generation of cholesterol lowering
drugs.
We now know, however, that we must look beyond one-size-fits-all
treatments. Population science and genetics research have clearly
demonstrated individual differences not only in predisposition to
disease but also in treatment response. For example, 26 million
Americans currently suffer from asthma--the leading cause of missed
school days for children and a driver of preventable hospitalizations
and emergency room visits. Asthma disproportionately affects African
Americans; African American children are twice as likely to have asthma
as white children and, as adults, are two to three times more likely to
die of asthma than any other racial or ethnic group. While effective
treatments exist, they do not reach all of those in need. NHLBI will be
seeking applications focused on identifying barriers and testing
strategies to enhance the implementation of evidence-based practices in
diverse communities across the Nation. Beyond the current treatments,
next generation therapies should target these differences to achieve
maximal benefit. NHLBI's multi-center clinical trial network,
AsthmaNet, is beginning the Best African American Response to Asthma
Drugs (BARD) study to compare the effectiveness of different treatments
on the management of asthma in African Americans. BARD will also assess
how genetics may influence an individual's response to the treatments,
which could be a paradigm shift in addressing challenges like
disparities in asthma care.
conclusion
We are in the midst of a very exciting period in science in which
the capacity to enhance human health has never been greater. New tools
and technologies are daring us to envision a future that is unburdened
by chronic heart, lung, and blood diseases--not only ensuring wellness
but also increasing economic productivity and reducing healthcare
costs. For example, research shows that treating patients at moderate
risk for cardiovascular disease with statin drugs to lower cholesterol
can reduce annual medical spending by up to $430 million. Imagine how
much can be saved by preventive interventions earlier in the disease
course before symptoms begin and the costs of treatment rise
dramatically. By achieving that goal, the return-on-investment of
biomedical research will strengthen both the health and the wealth of
the Nation.
______
Prepared Statement of Story C. Landis, Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of
Neurological Disorders and Stroke (NINDS) of the National Institutes of
Health (NIH). The fiscal year 2015 NINDS budget of $1,608,461,000
includes an increase of $22,664,000 over the comparable fiscal year
2014 level of $1,585,797,000. NINDS supports research to reduce the
burden of neurological disorders, from basic studies of the normal
brain through clinical trials of prevention and treatment
interventions. Today, I will make four points: (1) the burden of
neurological disorders is enormous; (2) past NINDS research has paid
off; (3) opportunities for future progress are extraordinary; and (4)
we have well informed plans to exploit these opportunities.
burden of neurological disorders
Nearly 800,000 Americans experience a stroke each year, and 15 to
30 percent of the 6.8 million stroke survivors alive today suffer
permanent disability.\1\ Traumatic brain injury (TBI) is the leading
cause of death and disability in children and young adults, common
among the elderly, and a major concern for the military and veterans.
In the United States, 2.5 million people receive emergency care for a
TBI each year, and millions more suffer mild TBI (concussions).
Epilepsy affects 2.3 million Americans, including 1 in 26 people at
some time in their lives. Alzheimer's disease is receiving increasing
attention, but most people are less aware that frontotemporal dementia
(FTD) is the most common dementia in people under age 60, and vascular
dementia, which affects blood vessels in the brain, is the second most
common dementia overall and is so closely intertwined with Alzheimer's
disease that most dementia patients have a combination of the two.
Parkinson's disease, spinal cord injury, cerebral palsy, multiple
sclerosis, and hundreds of rare diseases that affect children and
adults add to the immeasurable human and economic burden.
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\1\ Statistics for stroke, TBI, and epilepsy from U.S. Centers from
Disease Control and Prevention www.cdc.gov
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progress for patients and families
NINDS research drives progress directly, and indirectly catalyzes
private sector advances. NINDS studies on risk factors and prevention
contributed to a decline in the age-adjusted stroke death rate by 35.8
percent from 2000 to 2010; the actual number of stroke deaths fell 22.8
percent.\2\ NINDS research developed the only approved emergency drug
therapy that restores blood flow to the brain following stroke,
increasing likelihood of recovery with little or no disability by 30
percent. Research has also demonstrated, defying conventional wisdom, a
wider window of opportunity for stroke rehabilitation--even patients
who start rehabilitation as late as 6 months after a stroke can
improve, and patients can continue to improve 1 year after a stroke.
For people with epilepsy, an implantable device approved this year
senses impending seizures and delivers electrical pulses to stop them.
Long-term NINDS research provided the essential foundation for private
sector development of this device. Similarly, NINDS research directly
and indirectly contributed to deep brain stimulation (DBS) therapies
now in use for Parkinson's, essential tremor, and dystonia and under
clinical testing for many other disorders, as well as to development of
drugs for multiple sclerosis--10 are now on the market, including the
first oral drugs. Overall, the private sector has nearly 450 medicines
in development for neurological disorders, which would not be possible
without the foundation of NIH research.\3\
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\2\ Circulation 2014; 129:e28-e292
\3\ 2013 Report: Medicines in Development for Neurological
Disorders, Pharmaceutical Researchers and Manufacturers of America
http://www.phrma.org/innovation/meds-in-development
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extraordinary opportunities
Science and technology are opening unprecedented opportunities for
progress against neurological disorders. Studies on the normal brain
build the foundation. Notable recent advances, for example, revealed
how the brain clears out debris during sleep, how molecular structures
called ion channels control electrical activity, and the first human
``connectome'' maps, providing astonishing views of the basic wiring
diagram of living, thinking human brains. Advances in stem cell biology
now enable researchers to reproduce in cell culture key steps in
amyotrophic lateral sclerosis (ALS) and other disorders using brain
cells derived from patients' own skin cells. Basic science has led to
new insights that explain how chronic pain is wired in the brain, what
happens in the brain following a concussion, and how cell-to-cell
propagation of abnormally folded proteins could drive progression of
Parkinson's, Alzheimer's, and other neurodegenerative disorders. New
gene sequencing methods and high throughput gene silencing technologies
have accelerated the discovery of genes that cause epilepsy and
revealed potential new drug targets for Parkinson's disease. In a few
dramatic cases, gene discoveries have led directly to treatments that
help patients with rare disorders, including subtypes of dystonia and
childhood neurodegenerative disease, but more often painstaking
translational research is required to advance genetic and other
discoveries toward therapies. Among the many examples, promising
reports in laboratory animals this year demonstrated a drug therapy
that prevented the development of epilepsy, cell transplants that
controlled seizures, natural growth factor rescue of neonatal brain
injury, therapies that improved cognition in Down syndrome, and a hand
neuroprosthesis that restored touch sensation as well as movement.
programs and priorities
NINDS relies heavily upon the wisdom and ingenuity of researchers
throughout the United States to propose and evaluate the best
scientific opportunities. Complementing investigator-initiated
programs, NINDS initiatives target unmet opportunities or public health
needs. Institute priorities reflect strategic and disease-specific
planning that engages the scientific community and the public, and
rigorous evaluation of programs, closing those that have met their
goals or are no longer appropriate for today's science. Recent plans
focused on stroke, epilepsy, Parkinson's disease, and Alzheimer's
Disease-Related Dementias. Among recent initiatives:
--the Stroke Trials Network will determine more quickly and at less
cost what treatment, prevention, and rehabilitation strategies
work best.
--new Epilepsy Centers without Walls will target Sudden Unexplained
Death in Epilepsy (SUDEP) and disease modification or
prevention.
--the Parkinson's Disease Biomarkers Program is developing assessment
tools that will overcome roadblocks to more effective clinical
trials.
--the International TBI Research Initiative, coordinated with the
European Union and the Canadian Institute of Health Research,
will answer questions on care and classification of TBI that
have confounded development of interventions.
--two major cooperative studies are investigating the long-term
changes in the brain years after a single TBI or multiple
concussions, coordinated via the Foundation for NIH's Sports
and Health Research Program, which was established with a
donation from the National Football League.
--the NeuroBioBank, NINDS Human Genetics Repository, Federal
Interagency TBI Research database, Common Data Elements
Program, and an epilepsy clinical genetics data repository are
examples of new and continuing resource initiatives that
empower individual investigators and promote data sharing.
Finally, and most ambitiously, the President's Brain Research
through Advancing Innovative Neurotechnologies (BRAIN) Initiative will
dramatically improve tools to understand heretofore unapproachable
questions about how networks, or circuits, of brain cells enable us to
perceive, think, and act. There are many reasons for confidence that
this basic research initiative will ultimately advance progress against
disease. Autism, dystonia, and epilepsy, for example, are fundamentally
disorders of brain circuitry, and stroke, Parkinson's, and Alzheimer's
disease disrupt brain circuits as nerve cells die. Even with our
limited understanding of brain circuits and imprecise technologies for
altering them, interventions that compensate for malfunctioning brain
circuits already produce remarkable results. For example, DBS reverses
symptoms for many people with Parkinson's disease and dystonia, and
paralyzed people have controlled a robotic arm by signals directly
monitored from their brains' movement control circuits. It is perhaps
obvious that better understanding of brain circuits and tools to
influence their activity would greatly improve these interventions, but
history teaches that the most important payoffs of the BRAIN
Initiative, as for basic research generally, may be entirely
unforeseen.
______
Prepared Statement of Christopher P. Austin, M.D.
Mr. Chairman, Ranking Member, and Members of the Committee: Thank
you for the opportunity to present to you the President's budget
request for the National Center for Advancing Translational Sciences
(NCATS) for fiscal year 2015. The fiscal year 2015 budget for NCATS is
$657,471,000, which represents an increase of $25,075,000 over the
fiscal year 2014 level of $632,396,000. The request includes
$471,719,000 for the Clinical and Translational Science Awards (CTSA)
program and $29,810,000 for the Cures Acceleration Network (CAN).
translational research
In recent years, biomedical research has led to significant
advances in our understanding of human biology. We have sequenced the
human genome, explored the potential of stem cells, and discovered RNA
interference. All of these advances have been celebrated as holding
enormous promise for improving human health, but the road from promise
to tangible improvements in public health has been long, complex and
full of obstacles. NCATS aims to turn these game-changing discoveries
into treatments for patients by addressing the ``translational
sciences'' needed to close the gap. Translational sciences comprise the
process of turning observations in the laboratory and clinic into
effective interventions that improve the health of individuals and the
public--from diagnostics and therapeutics to medical procedures and
behavioral changes.
NCATS takes a system-wide approach to diseases and the
translational science process. It serves as an ``adaptor'' to connect
basic, clinical and public health research and as a ``convener'' for
disparate organizations that play roles in the process of turning
discoveries into health improvements. Every NCATS initiative is a
collaboration with partners in the public, private, government or
nonprofit sector. The Center is committed to developing technologies
and paradigms that improve the efficiency and effectiveness of one or
more steps in the translational process, demonstrating that these
innovations work in specific use cases, and disseminating the
translational advances widely to catalyze improvements in all
translational efforts with the ultimate and critically important goal
of improving health.
mission into action
One NCATS initiative that exemplifies these goals is the
Discovering New Therapeutic Uses for Existing Molecules program. This
program matches academic research groups with pharmaceutical companies
to explore new disease indications for investigational compounds that
are no longer being pursued by the pharmaceutical companies. The aim is
to address several challenges in the translation process: the need for
treatments for the several thousand diseases that have no effective
therapy, the complicated process of negotiating agreements between
parties who want to work together, and the largely ad hoc process by
which academic and pharmaceutical researchers develop collaborative
projects. In fiscal year 2013, NCATS funded nine projects covering
eight disease areas, including Alzheimer's disease, Duchenne muscular
dystrophy and schizophrenia. The program already has resulted in
positive outcomes. Within 3 months of the grantees receiving funds,
three compounds were being tested in humans for new uses--two to treat
schizophrenia and one to treat Alzheimer's disease. In addition, the
time to establish collaborations between industry and academics has
been shortened to only 13 weeks from the more typical 9 months to a
year. NCATS will solicit a second group of projects in fiscal year
2014.
The NCATS emphasis on innovation is central to its collaboration
with the National Eye Institute and Organovo (which makes 3-D tissue
printers) to develop 3-D, architecturally accurate eye tissue. Such
tissues have the potential to accelerate the drug discovery process--
enabling treatments to be developed faster and at a lower cost--by
giving researchers a more accurate view of how drugs will behave in
human cells before those drugs ever enter clinical trials.
NCATS serves as a catalyst to increase the efficiency of the
translational ecosystem, as illustrated by the formation of a research
team that included scientists from the Johns Hopkins School of Medicine
and the NCATS Assay Development and Screening Technology Laboratory.
This team developed new methods to overcome several translational
roadblocks and was able to demonstrate their effectiveness by
identifying a promising new compound that prevents the death of cells
in the eye from glaucoma, a disease that can lead to blindness. Working
together, the collaborators were able to solve a problem that none of
them could address alone.
translational research spectrum
Strengthening and supporting the entire spectrum of translational
research with the ultimate aim of improved public health is a top
priority for NCATS, and the CTSA program is crucial for these efforts.
The CTSA program develops new technologies, methods, resources and
operational paradigms that catalyze clinical research progress, and
supports the training and career development of translational
researchers. In June 2013, the Institute of Medicine (IOM) issued a
report following a review of the CTSA program. The report recommended
that NCATS take a more active role in the program's governance and
direction, formalize the evaluation processes of the program, advance
innovation in education and training programs, and ensure that the
patient community participates in all phases of research. Since the
publication of the report, the Center has increased programmatic and
fiscal management of the grants that support the CTSA program and has
streamlined the governance of the consortium, consulting closely with
the CTSA Principal Investigators. A Working Group of the NCATS Advisory
Council was established in December 2013 to provide input on measurable
objectives for the program. The Working Group will submit its report to
the NCATS Advisory Council in May 2014.
focus on rare diseases
NCATS is deeply committed to developing treatments for rare
diseases, which are defined in the U.S. as affecting fewer than 200,000
individuals. There are approximately 6,500 rare diseases, but only 250
have treatments. The NCATS Therapeutics for Rare and Neglected Diseases
(TRND) program advances potential treatments for rare and neglected
diseases to first-in-human trials, an approach known as ``de-risking.''
This strategy makes new drugs more commercially attractive to
biopharmaceutical companies, despite the small patient population that
is characteristic of these diseases. For example, in 2013, a clinical
trial was started to evaluate a drug candidate called cyclodextrin as a
possible treatment for Niemann-Pick disease type C1 (NPC1), a rare and
fatal genetic brain disease affecting children. A TRND-led team of more
than 20 investigators from NIH, academia, a pharmaceutical company, and
patient groups developed cyclodextrin as a treatment as well as an NPC
biomarker to guide its clinical development. An Investigational New
Drug application for cyclodextrin was approved by the FDA, and a Phase
I clinical trial currently is ongoing.
cures acceleration network
CAN was authorized to advance the development of high-need cures
and reduce significant barriers between research discovery and clinical
trials. At NCATS, CAN is intended to advance initiatives designed to
address scientific and technical challenges that impede translational
research.
Currently, CAN supports the Tissue Chip for Drug Screening Program,
which is a partnership with the Defense Advanced Research Projects
Agency (DARPA) and the FDA to develop 3-D human tissue chips that
accurately model the structure and function of human organs, such as
the lung, liver and heart. These devices will enable researchers to
predict harmful health effects of new drugs more accurately, thus
addressing one of the main reasons that drug studies often fail.
NCATS has had success moving projects forward with its rare disease
therapeutics program, but there are significantly fewer groups working
on developing medical devices, for which there is a great need. NCATS
could launch a comprehensive collaborative effort to accelerate device
development as part of the next phase in the CAN program.
conclusion
These projects are just a few examples of the exciting and
innovative activities underway at NCATS. Though the Center is still
relatively new, early successes demonstrate how its distinctive
approaches can help solve some of the most challenging problems in
translational science. We will build on our accomplishments over the
past 2 years to accelerate our programs further in fiscal year 2015. I
look forward to sharing more of our achievements with you as NCATS
continues to evolve.
[Clerk's note.--The following Institutes of the National
Institutes of Health did not appear before the subcommittee
this year. Chairman Harkin requested these Institutes to submit
testimony in support of their fiscal year 2015 budget request.
Those statements follow:]
Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S.
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's budget request for the National Institute of
Environmental Health Sciences (NIEHS) of the National Institutes of
Health (NIH). The fiscal year 2015 NIEHS budget of $665,080,000
includes an increase of $556,000 from the comparable fiscal year 2014
level of $664,524,000. The NIEHS Strategic Plan, Advancing Science,
Improving Health continues to guide efforts toward fulfilling our
mission to discover how the environment affects people in order to
prevent both acute and chronic illness.
breast cancer
NIEHS continues its robust investment into environmental factors
affecting breast cancer, with the goal of learning how we can prevent
this widespread disease. NIEHS and the National Cancer Institute (NCI)
collaborated to support the Interagency Breast Cancer and Environmental
Research Coordinating Committee, whose report, Prioritizing Prevention,
recommends strategies to mitigate the environmental causes of breast
cancer. NIEHS supports several major epidemiological and translational
breast cancer initiatives. The Breast Cancer and the Environment
Research Program is a transdisciplinary initiative cosponsored by NCI
and NIEHS, in which basic scientists, epidemiologists, clinicians, and
community partners work together to examine the effects of
environmental exposures that may predispose a woman to breast cancer
throughout her life, including exposures during puberty, menopause,
pregnancy, and other ``windows of susceptibility.'' The NIEHS Sister
Study has recruited a cohort of 50,884 U.S. and Puerto Rican women with
a sister diagnosed with breast cancer, to prospectively study
environmental and genetic factors that influence breast cancer risk and
survival. More than 1,500 incident breast cancers have been diagnosed
to date. A May 2013 publication from these researchers showed that DNA
methylation profiling in blood samples may hold promise for breast
cancer detection and disease risk prediction. The Agricultural Health
Study, a collaborative effort by NCI, NIEHS, the National Institute for
Occupational Safety and Health (NIOSH), and the Environmental
Protection Agency (EPA), includes a comprehensive evaluation of many
commonly used herbicides and pesticides and their potential impact on
risk of breast cancer among 32,000 women who are married to pesticide
applicators (primarily farmers).
environment and autoimmunity
NIEHS supports scientists who are exploring how environmental
exposures can cause immune system dysfunction. There is evidence that
autoimmune diseases likely involve an environmental component.
Therefore, the Environmental Autoimmunity Group in the Clinical
Research Program at NIEHS is looking at the relationship between
environmental factors and autoimmune disease. Autoimmune diseases
result from an immune response directed against the body's own tissues
and they collectively afflict approximately 24.5 million Americans,
with women disproportionately affected. The cause(s) of autoimmune
disorders remain largely unknown and are likely multifactorial
involving both genetic and environmental influences. In 2013, NIEHS
released a Funding Opportunity Announcement (FOA) to enable a better
understanding of the links between exposures and autoimmune disease.
NIEHS continues to support autoimmune disease research in the
underserved community of Libby, Montana where the population has been
exposed to asbestos minerals as a byproduct of vermiculite ore mining.
Of particular concern is early childhood exposure, since susceptibility
may be increased during this life stage. Recent efforts to characterize
children's exposure in Libby estimated up to 15 times higher levels of
airborne asbestos concentrations during outdoor activities and 73
percent of the study participants indicated these activities occurred
in the presence of children.\1\ NIEHS grantees are investigating
whether childhood asbestos exposures in Libby are associated with
pulmonary disease later in life.
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\1\ Ryan PH et al. Childhood exposure to Libby amphibole during
outdoor activities. May 22, 2013. J. Expo. Sci. Environ. Epidemiol.
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/
?term=PMID%3A+23695492
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environment and neurological disorders
Evidence indicates there is both an environmental and genetic
component in neurological disorders. NIEHS funds research to advance
the understanding of environmental factors and gene-environment
interactions related to neurodegenerative diseases and to help create
new prevention and treatment approaches. At the NIEHS Centers for
Neurodegeneration Science (CNS) and in partnerships with the National
Institute of Neurological Disorders and Stroke (NINDS) and National
Institute on Aging (NIA), teams of top scientists from different
disciplines collaborate to examine the root causes of neurodegenerative
diseases. CNS researchers study how exposure to pesticides, metals
(e.g. arsenic, lead), and other chemicals affect the development of
neurodegenerative diseases such as Parkinson's and Alzheimer's disease.
NIEHS recently published two Funding Opportunity Announcements to
expand neurological research: one on environmental exposures and
Alzheimer's disease, and the other on environmental exposures and
neurodegenerative disease.
Autism is a highly variable neurodevelopmental disorder, which is
likely influenced by environmental exposures. NIEHS-funded researchers
have published work indicating prenatal vitamins might reduce the risk
of having children with autism.\2\ Exposure to air pollution during
pregnancy and during the first year of life was also associated with
autism.\3\ \4\ \5\ NIEHS funds two key autism studies: the Childhood
Autism Risks from Genetics and the Environment (CHARGE) study, and the
Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) study.
In April 2014, NIEHS hosted a community virtual forum on autism and the
environment that was webcast live and featured a panel of autism
research experts.
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\2\ Int J Epidemiol. 2014 Feb 11. [Epub ahead of print] Maternal
lifestyle and environmental risk factors for autism spectrum disorders.
Lyall K1, Schmidt RJ, Hertz-Picciotto I.
\3\ Epidemiology. 2014 Jan;25(1):44-7. Autism spectrum disorder:
interaction of air pollution with the MET receptor tyrosine kinase
gene. Volk HE1, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R,
Campbell DB.
\4\ JAMA Psychiatry. 2013 Jan;70(1):71-7. doi: 10.1001/
jamapsychiatry.2013.266. Traffic-related air pollution, particulate
matter, and autism. Volk HE1, Lurmann F, Penfold B, Hertz-Picciotto I,
McConnell R.
\5\ Autism Res. 2013 Aug;6(4):248-57. doi: 10.1002/aur.1287. Epub
2013 Mar 11. Prenatal and early-life exposure to high-level diesel
exhaust particles leads to increased locomotor activity and repetitive
behaviors in mice. Thirtamara Rajamani K1, Doherty-Lyons S, Bolden C,
Willis D, Hoffman C, Zelikoff J, Chen LC, Gu H.
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research update on endocrine disruptors
NIEHS is the leading government agency funding research on the
human health effects of exposure to endocrine disrupting chemicals
(EDCs). EDCs have the potential to interfere with a host of
physiological functions, contributing to the development of costly and
devastating illnesses such as obesity, diabetes, attention deficit
hyperactivity disorder (ADHD) and behavioral disorders, asthma,
endometriosis and uterine fibroids, reproductive disorders and
infertility, and breast, uterine, and prostate cancers. Exposures to
EDCs have been documented across the population, with fetuses and young
children at greater risk due to their stages of rapid development.
NIEHS is currently funding over 100 grants examining effects of EDCs
including bisphenol A (BPA), arsenic, pesticides, flame retardants, and
others.
NIEHS has focused particular efforts on BPA, in part due to its
ubiquity, that results in daily exposures for most people, mainly
through diet. The Consortium Linking Academic and Regulatory Insights
on BPA Toxicity (CLARITY--BPA) research program is a collaborative
effort of the NIEHS, the National Toxicology Program (NTP), the Food
and Drug Administration's National Center for Toxicological Research,
and academic researchers studying a range of health endpoints, while
also establishing new testing standards and methodologies. A recent
study of another EDC, phthalates, shows that levels of some
plasticizers have fallen since a Federal ban on their use in children's
products and voluntary removal from many consumer goods.\6\ However,
research at Brown University suggests that replacement chemicals may be
just as damaging to the reproductive development of boys.\7\
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\6\ Zota AR, Calafat AM, Woodruff TJ. 2014. Temporal trends in
phthalate exposures: findings from the National Health and Nutrition
Examination Survey, 2001-2010. Environ Health Perspect; http://
www.ncbi.nlm.nih.gov/pubmed/24425099.
\7\ Saffarini CM, Heger NE, Yamasaki H; Liu T, Hall SJ, Boekelheide
K. 2012. Induction and persistence of abnormal testicular germ cells
following gestational exposure to di-(n-butyl) phthalate in p53-null
mice. J Andrology; 33(3):505-513. http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3607946
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research update on gulf oil spill
The release of millions of gallons of crude oil following the 2010
Deepwater Horizon (DWH) disaster posed unpredictable risk to over
130,000 workers trained and potentially involved in various remediation
activities and to the people living along the Gulf Coast. To date,
there have been limited studies on the human health effects of oil
spills, especially long-term effects. The NIEHS Gulf Long-term Follow-
up Study (GuLF STUDY), funded in part by the NIH Common Fund, is
investigating potential short- and long-term health effects associated
with oil spill cleanup activities. The GuLF STUDY has enrolled 32,786
individuals and has completed home visits for 11,200 participants,
during which clinical measurements were taken and biospecimens were
collected for future research.
NIEHS leads the DWH Research Consortia that funds a network of
academic and community partners to study health effects in people
residing in regions affected by the disaster. These studies are
examining resilience at the individual and community levels,
perceptions of risk among women and children, and the potential
contamination of seafood in the Gulf (Strategic Plan Goals 4-6). While
NTP is conducting research to increase our understanding of the
toxicology of crude oil, NIEHS grantees have preliminary results that
suggest increased depression and anxiety among Gulf Coast residents,
but also suggest strong community networks promote resilience.
______
Prepared Statement of Josephine P. Briggs, M.D.
Mr. Chairman and Members of the Committee: As the Director of the
National Center for Complementary and Alternative Medicine (NCCAM) of
the National Institutes of Health (NIH), I am pleased to present the
President's fiscal year 2015 budget request for NCCAM. The fiscal year
2015 budget includes $124,509,000, which is $384,000 more than the
comparable fiscal year 2014 appropriation of $124,125,000.
The National Center for Complementary and Alternative Medicine
(NCCAM) is the Federal Government's lead agency for supporting
scientific research on complementary practices and integrative health
interventions. NCCAM's mission is to define, through rigorous
scientific investigation, the usefulness and safety of such practices
and their roles in improving health and healthcare.
complementary and integrative health care
Complementary and integrative health practices are defined as
having origins outside of mainstream conventional medicine and include
both self-care practices like meditation, yoga, and dietary
supplements, as well as healthcare provider administered care such as
acupuncture, chiropractic, osteopathic and naturopathic medicine. As
these modalities are increasingly integrated into mainstream
healthcare, NCCAM is committed to developing the scientific evidence
needed by the public, healthcare professionals and health policymakers
to make informed decisions about the use and integration of these
various practices.
use of complementary and integrative health care
For the past decade, some 30 to 40 percent of Americans have used
complementary and integrative health practices, according to data from
the National Health Interview Survey (NHIS) conducted by the Centers
for Disease Control and Prevention (CDC). The NHIS data shows that
Americans are willing to pay for these services, spending some $34
billion in 2007, which represented 1.5 percent of total health
expenditures and 11 percent of out-of-pocket costs. NCCAM has worked
with the CDC since 2002, to develop the questions on complementary
healthcare that are included in the NHIS every 5 years (2002, 2007, and
2012). Results from the latest survey are currently being analyzed for
publication later this spring. Analysis will include, for the first
time, a comparison of regional variations in use of complementary
health practices by adults in the United States. We also look forward
to the first detailed look at integration of complementary
interventions into private medical practice when the results of the
2012 National Ambulatory Medical Care Survey, which involved interviews
of 30,000 physicians, are analyzed. NCCAM worked closely with the CDC
to develop the questions used in this survey, as well.
impact on public health
NCCAM's approach to setting priorities and investment in research
is guided by the need for rigorous evidence that ultimately may have a
significant impact on public health. One example of this approach
involves a major clinical trial supported jointly by NCCAM and the
National Heart, Lung, and Blood Institute examining the efficacy of
using EDTA-based chelation therapy to reduce cardiovascular disease and
prevent heart attacks. The trial, which involved 1,700 patients, showed
a modest reduction in cardiovascular events for adults aged 50 and
older who had suffered a prior heart attack. However, the results from
a secondary analysis of the trial data suggest that the chelation
treatments produced a marked reduction in cardiovascular events and
death in patients with diabetes but not in those without diabetes.
Addressing cardiovascular disease in diabetics is an important public
health challenge, and better treatment options are required. As this
study was not designed to discover how or why chelation might benefit
patients with diabetes, further investigation is needed. Thus, NCCAM is
exploring the possibility of a follow-up study in collaboration with
several other NIH Institutes.
reducing pain and improving symptom management
According to the Institute of Medicine, pain is a major public
health problem affecting more than 100 million Americans and costing
the Nation over $600 billion in medical costs and lost productivity.
Pain is also the most common reason Americans turn to complementary and
integrative health practices, as conventional medicine often provides
incomplete relief. Therefore, pain research is a top priority for
NCCAM. As such, we continue to invest in research on several promising
approaches for treating pain, such as spinal manipulation, massage,
yoga, meditation, and acupuncture. We are particularly interested in
understanding how these interventions work, for what type of pain
condition, and for determining the optimal method of practice and
delivery. Toward this end, NCCAM partners with others in supporting
research initiatives, participates in the NIH Pain Consortium, and
leads an NIH Task Force to improve standards for research on chronic
low back pain (cLBP). The cLBP Task Force has developed common
standards, measures, and other tools for clinical research on cLBP, and
a report is expected to be published in The Journal of Pain later this
year.
Another important collaborative effort is our partnership with the
National Institute on Drug Abuse and the Department of Veterans Affairs
to foster research on complementary and integrative approaches to
managing pain and other symptoms experienced by military personnel and
veterans. A number of grant applications were submitted in response to
our joint solicitation, and we anticipate funding multiple studies
later this fall.
One area of particular interest is the means by which complementary
health practices affect the perception of pain by the brain.
Specifically, we seek to understand the mechanisms by which emotions,
attention, and context modulate pain. Using neuroimaging and cutting-
edge technologies, our intramural research program (IRP) is exploring
the central mechanisms of pain and its modulation, with the long-term
goal of improving clinical management of chronic pain through the
integration of pharmacological and non-pharmacological complementary
health approaches. NCCAM's IRP engages and leverages the exceptional
basic and clinical neuroscience efforts across NIH.
advancing research on natural products
Another important area of emphasis for NCCAM is research on natural
products. In addition to exploring the underlying biological effects
and mechanisms of natural products, such as dietary supplements, herbs,
botanicals, and probiotics, we are concerned about their safety. While
there is widespread use of these products by the public, there is
limited scientific evidence about their effectiveness and safety. In
addition to gaining greater understanding of whether natural products
are effective or safe when used alone, there is a need to study how
they interact with prescription medications. This is very important
because many patients taking prescription medications also use natural
products, such as dietary supplements, herbs and probiotics. To
investigate these issues, NCCAM will launch an initiative to develop
rigorous methods to evaluate potential interactions between natural
products and medications. The ultimate goal is to ensure that
consumers, healthcare providers, and health policymakers are better
informed of the potential risks and/or benefits associated with the use
of natural products in combination with medications.
To propel needed innovations in technology and methodology for
research on natural products, NCCAM and the NIH Office of Dietary
Supplements are supporting the establishment of a Center for Advancing
Natural Products Technology and Innovation. The Center is expected to
better support the needs of the natural products community while
reducing resource redundancies.
providing useful information to the public
NCCAM provides objective, evidence-based information to scientists,
healthcare providers, and the general public through a variety of
approaches, including emerging technology and platforms (i.e., video,
social media, and mobile applications) and an information-rich Web site
(www.nccam.nih.gov). Through these approaches, science-based
information on the safety and efficacy of complementary and integrative
health practices--already in wide public use--is made available to a
broad audience.
conclusion
NCCAM continues to support research, collaborate with others, and
leverage partnerships to build the scientific evidence needed by
consumers, healthcare professionals, and health policymakers regarding
the safety and value of complementary and integrative health practices.
______
Prepared Statement of Roger I. Glass, M.D., Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the Fogarty International Center
(FIC) of the National Institutes of Health (NIH). The fiscal year 2015
FIC budget of $67.776 million includes an increase of $0.292 million
more than the fiscal year 2014 enacted level of $67.484 million.
The United States and the NIH have historically been at the
forefront of major scientific discoveries that have improved health
here at home and around the world. Building on these successes,
ambitious health targets for the future now seem possible--such as a
decrease in the overall mortality rate of children under the age of 5,
to 20 deaths per 1,000 over the next two decades and an AIDS-free
generation. Reductions in morbidity and mortality from non-communicable
diseases have also begun to affect populations worldwide. At this
critical juncture, the Fogarty International Center mission and
investments will continue to accelerate the pace and progress of
research, engage the best and brightest minds by building capacity at
research institutions across the globe, and develop the evidence needed
to confront health challenges wherever they occur. By continuing to
invest in training outstanding early-career investigators and
developing future global health research leaders, Fogarty will advance
the goals and sustain the leadership of the NIH and the U.S. Government
in biomedical research, while improving the health of Americans and
populations worldwide.
today's basic science for tomorrow's breakthroughs
Non-communicable diseases and disorders (NCDs) are rapidly becoming
the dominant causes of poor health in all low and middle-income country
(LMIC) regions \1\ except sub-Saharan Africa, where they are second
only to HIV/AIDS. For example, World Health Organization data suggest
that one billion people worldwide suffer from some type of mental,
neurological or substance abuse disorder.
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\1\ LMIC is a World Bank designation for the classification of
economies, based on Gross National Income (GNI) per capita. Low income
countries have a GNI per capita of $1,035 or less, and middle income
countries have a GNI per capita of $1,036-$12,615.
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In collaboration with eight NIH Institutes and Centers (ICs),
Fogarty's Brain Disorders in the Developing World: Research Across the
Lifespan program supports cutting-edge basic science research in LMICs
on the nervous system. This research could lead to important new
diagnostics, prevention and treatment strategies, and interventions of
direct relevance to both LMIC and U.S. populations. For example,
Argentinian scientists, in collaboration with Northwestern University,
are studying neuroprotective gene therapy in a preclinical trial. This
team demonstrated that a unique vector gene delivery system using two
powerful neuroprotective molecules could be effectively injected over
time restoring neuronal function. Future studies will use magnetic
nanoparticles to perform targeted gene therapy with the goal of
treating neurodegenerative disease such as Parkinson's, the second-most
common neurological disease in the United States, affecting
approximately 1 million Americans (National Parkinson Foundation).
nurturing talent and innovation
Fogarty programs have supported long-term research training for
more than 4,500 scientists worldwide, in collaboration with more than
230 U.S. and LMIC research institutions. These investments provide
unique training opportunities for early-career global health
researchers, enabling them to effectively collaborate with foreign
partners in diverse, low-resource international settings to confront
global health challenges. Fogarty supports these hands-on, clinical
research training experiences in LMICs in close partnership with a
number of NIH ICs, providing experiences that encourage U.S.
investigators to creatively approach problems under constraints that
may not exist in high-income settings. Scientists trained with Fogarty
support have conducted research on cardiovascular disease in Kenya,
surgical capacity in Rwanda, mental health impacts of slum-dwelling in
India, and the link between breast cancer and osteoporosis in China.
Solving many of today's complex public health problems requires the
engagement of investigators from a wide variety of fields. Fogarty's
Framework Programs for Global Health Innovation awards support efforts
to bring biomedical scientists together with students from various
disciplines-- such as engineering, nutrition, business, law,
environmental science, social sciences, agriculture and public health--
to develop research training initiatives that encourage innovative,
health-related products, processes and policies. This program supports:
scientists at Michigan State University studying interactions between
agriculture, water resource utilization and malaria in Malawi; grantees
at Northwestern University, Chicago, and the University of Cape Town,
South Africa training researchers in developing healthcare technologies
in Nigeria; and scientists at Tufts University School of Medicine,
Boston, and Christian Medical College, Vellore, India developing a
training program in translational research related to non-communicable
and infectious diseases. These international teams are identifying
critical health needs and conducting the research needed to develop and
test novel solutions.
the path forward: addressing dual burdens of disease and harnessing the
information and communication technology revolution for global health
research
For over 25 years, Fogarty has contributed to the U.S. Government
fight against HIV, training and supporting some of the world's foremost
vaccine and biomedical researchers. As the global burden of disease
shifts to a greater level of NCDs, Fogarty programs will continue
critical work in HIV research training while also responding to both
the NCD epidemic through research and training programs and the nexus
between the HIV and NCD epidemics, represented by NCD co-morbidities of
HIV infection and treatment. As scientific priorities evolve to match
the changing burden of disease, Fogarty research and research training
programs will train the best and brightest researchers around the world
and facilitate scientific collaboration that meets new priorities while
building on existing capacity and infrastructure.
The information and communication technology (ICT) revolution
presents exceptional opportunities and new tools for global health
research and research education. ICT is a broad term that encompasses
communication devices, applications, and services, such as cell phones,
computers, radios, videoconferencing and distance learning. Fogarty
will expand its support of innovation in the use of ICT to generate
knowledge, scientific exchange, and research education in the hope of
stimulating the capacity to develop and evaluate different models of
distance learning and other ICT strategies, as well as adapt various
ICT platforms for the needs of research and research educational
communities. This will enable professionals in LMIC institutions to
determine what works best for their particular settings as they develop
novel education tools. Students and faculty will access, teach, and
share information in creative and transformative ways, enabling new
approaches to collaborative learning and problem solving in partnership
with colleagues next door and across continents.
The enormous potential for mobile technology to impact healthcare
and research has led to the rapid development of new health-related
phone applications. Rigorous evaluation of health outcomes after
implementation of these interventions are often lacking. New emphases
are being pursued to develop mobile technologies tailored to LMIC
settings, assess their impact on health and determine how they can be
effectively scaled up in diverse, low-resource settings. Significantly,
this evidence base is not only critical for LMIC populations, but can
also be applied to healthcare in the U.S.
These are indeed exciting times for global health with new
opportunities for partnership within and outside the NIH, the
introduction of transformative technologies and mutual scientific
priorities based on a shared burden of disease across high-income and
LMIC. Capitalizing on these developments demands a multidisciplinary
research workforce that can function across cultures and borders to
solve common health problems. Fogarty will continue to invest in
training the next generation of leaders in global health research at
home and abroad to ensure that the U.S. will continue to play a key
role in confronting the global health challenges of today.
______
Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2015 budget request for the National
Institute of Nursing Research (NINR) of the National Institutes of
Health (NIH). The fiscal year 2015 NINR budget is $140,452,000 which is
$128,000 more than the comparable fiscal year 2014 appropriation of
$140,324,000.
I appreciate the opportunity to share with you a brief summary of
some of the exciting areas of research and future scientific directions
of NINR. The mission of NINR is to promote and improve the health of
individuals, families, and communities. We fulfill this mission by
supporting clinical and basic research to build the scientific
foundation for clinical practice, prevent disease and disability,
manage and eliminate symptoms caused by illness, enhance end-of-life
and palliative care, and train the next generation of nurse scientists.
Today, I offer an overview of NINR's efforts and accomplishments in
five key scientific areas and provide examples of how the research we
support improves quality of life, health, and wellness across the
lifespan.
symptom science: promoting personalized health strategies
NINR is committed to finding new and better ways to treat the
symptoms of chronic and acute illnesses which can cause significant
suffering for individuals and families. While we still have much to
learn about the unique ways people experience symptoms and respond to
treatments, recent advances in genomics are providing new opportunities
to develop improved, personalized strategies to address adverse
symptoms of illness, such as pain, fatigue, and disordered sleep. By
providing a better understanding of the basic underlying biological and
genetic mechanisms of symptoms, NINR-supported researchers are making
important contributions to improving health and quality of life. For
example, one NINR-supported project found that, for pregnant women with
depression, poor sleep was associated with higher levels of
inflammatory chemicals in the body known as cytokines, as well as
adverse pregnancy outcomes such as preterm birth. Other NINR-supported
scientists identified pro- and anti-inflammatory biomarkers that
predict how patients experience pain at different stages of breast
cancer treatment, drawing a new link between pain and inflammation.
Discoveries such as these pave the way for the development of
personalized and effective treatments for adverse symptoms of illness.
self-management of chronic illness
According to the Centers for Disease Control (CDC), chronic illness
accounts for more than 75 percent of healthcare costs in the U.S., and
often requires long-term management of illness among individuals,
families, and healthcare providers. Learning how to manage chronic
illness presents challenges to individuals of any age as well as their
family members, from children remembering to bring their asthma
medication with them to school to older adults maintaining daily
activities as they face multiple chronic conditions, such as arthritis
and heart disease. To address such challenges, NINR supports research
that enables individuals with chronic illness and their caregivers to
take an active role in understanding and managing their condition, and
improving their quality of life. One current NINR-led initiative aims
to equip families with effective strategies for improving self-
management of chronic illness in children and adolescents, enabling
them to follow treatment regimens and make healthy lifestyle choices
while still allowing ``kids to be kids.'' Another initiative emphasizes
family-centered self-management that integrates family members as
partners in care while promoting self-management for individuals of any
age; this initiative has the potential to strengthen the ability of
family members to work together to make treatment decisions, manage
symptoms, and navigate the healthcare system. Through efforts like
these, NINR's investment in self-management research contributes to
helping people live active and healthy lives in the face of chronic
illness.
wellness: promoting health and preventing illness
Another area of emphasis at NINR is on wellness research, which
seeks to understand the physical, social, behavioral, and environmental
causes of illness, identify healthy lifestyle behaviors, and develop
interventions to promote health and prevent illness across the lifespan
and in diverse communities. One study supported by NINR is refining and
examining the effectiveness of a home-based sensor system for older
adults, which monitors pulse, breathing, and restlessness while
sleeping, and alerts healthcare providers to potential illness so that
they can intervene early. Such warning systems may allow older adults
to stay active and remain in their homes longer. In another project,
researchers developed a teacher-delivered healthy lifestyles
intervention that improved health behaviors and academic outcomes in
high school adolescents. NINR also maintains its commitment to
promoting wellness in vulnerable groups who are disproportionately
affected by chronic illness. We currently lead an initiative to reduce
health disparities in minority and underserved children through the
development of culturally-appropriate, multifaceted interventions.
enhancing end-of-life and palliative care
Addressing the needs of patients with life-limiting illness through
high-quality, effective end-of-life and palliative care continues to be
a critical focus of NINR. As the lead NIH Institute for end-of-life
research, NINR supports research to ease symptoms and support patients
and their caregivers in coping with advanced illness, while also
addressing the challenges of planning for end-of-life decisions. As an
example, NINR-supported scientists recently found that pain continues
to be underdiagnosed and undertreated for hospitalized patients at the
end of life, suggesting that more work is needed to better understand
the needs of individuals facing life-threatening illnesses. Recognizing
that palliative care is a critical component of maintaining quality of
life at any age and at any stage of illness, not just at the end of
life, NINR supports initiatives to enhance palliative care. Given that
a diagnosis of serious illness in a child is particularly difficult for
families, NINR launched the Palliative Care: Conversations
MatterTM campaign to raise awareness of pediatric palliative
care and to provide evidence-based materials to help healthcare
providers initiate often difficult conversations with pediatric
patients and their families. NINR also continues to support a
palliative care research cooperative to enhance the evidence base for
palliative care interventions. A new NINR initiative to promote use of
and long-term sustainability of the cooperative will encourage
researchers across the country to capitalize on the existing resources
and expertise and streamline the research process.
looking toward the future: nurse scientists
A primary goal of NINR is to prepare the next generation of nurse
scientists to address health challenges and to contribute to an
innovative, multidisciplinary, and diverse scientific workforce. NINR
funds training and career development grants and programs to prepare
nurse scientists to conduct research to build the scientific foundation
for clinical practice. NINR's Summer Genetics Institute is an intensive
training program on molecular genetics designed to improve research and
clinical practice among graduate students and faculty. This year, our
week-long Methodologies Boot Camp focuses on using Big Data in symptom
research, and provides a research intensive program for participants to
learn new state-of-the-art methodologies from nationally and
internationally known scientists. By training nurse scientists to use
new, innovative scientific methodologies, NINR advances nursing science
to improve health.
In closing, thank you for the opportunity to share with the
Committee some of the ways the science we support impacts the health of
the Nation. In fiscal year 2015, NINR will continue our mission to
improve quality of life by advancing nursing science and by supporting
research to inform high-quality and effective clinical care.
______
Prepared Statement of Eric Green, M.D., Ph.D
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2015 President's budget request for the National Human
Genome Research Institute (NHGRI). The fiscal year 2015 budget of
$498,451,000 reflects an increase of $1,323,000 above the enacted
fiscal year 2014 level of $497,128,000.
The research funded and conducted by NHGRI in fiscal year 2015 will
continue to unlock the secrets of life's DNA code. We still have much
to discover with regard to how the three billion DNA bases of the human
genome influence our physical and biochemical characteristics--and, in
turn, our health. While we continue to reveal all the information
encoded by DNA, we have started pursuing clinical applications of
genomic knowledge and implementing genomic medicine.
Understanding how the structure and function of the human genome
relates to health and disease will be essential for the implementation
of genomic medicine. Among the knowledge to be gained is how the
:20,000 genes in the human genome are turned on and off at the
appropriate times and in the appropriate places; this is largely the
role of regulatory elements within the genome that act like ``dimmer
switches'' controlling lights. Through the Institute's Encyclopedia of
DNA Elements (ENCODE) Project, a more detailed inventory of these
regulatory elements is emerging. In fiscal year 2015, the Genomics of
Gene Regulation (GGR) initiative will begin to investigate the
choreography of these different elements in different cells and
tissues. Many of the elements that ENCODE has identified and GGR will
characterize play a role in human diseases and traits, underscoring the
foundational value of these projects.
More than 25 million Americans suffer from rare diseases,
cumulatively more than those afflicted with cancer. While the genomic
bases for just over 5,000 rare diseases have been established--the
majority of those established since the end of the Human Genome
Project--the causal genes for an estimated 2,000-4,000 additional rare
diseases remain to be identified. To investigate the latter, NHGRI's
Centers for Mendelian Genomics Program is harnessing powerful DNA-
sequencing technologies to analyze patients' genomes on an
unprecedented scale en route to establishing the genomic underpinnings
of these remaining rare disorders. The resulting discoveries offer the
promise of ending the diagnostic odyssey of afflicted patients as well
as insights about the diseases that may lead to new therapeutic
approaches.
In fiscal year 2015, NHGRI will also focus on more common, but more
genomically complex, diseases--those diseases that reflect great public
health burdens. One such disease, cancer, is fundamentally a disease of
the genome. Hence, NHGRI has been collaborating with the National
Cancer Institute in developing The Cancer Genome Atlas (TCGA) since
2006, studying the genomes of different types of tumors and cataloging
the discovered genomic aberrations. In fiscal year 2015, TCGA will
reach the milestone of analyzing 10,000 tumor samples, revealing many
new insights about cancer.
Similarly, NHGRI has partnered with the National Institute on Aging
to pursue the largest genomics study of Alzheimer's disease to date.
The Alzheimer's Disease Sequencing Project (ADSP) is sequencing and
analyzing the genomes of several hundred Alzheimer's patients to help
identify the genomic factors contributing to this complex disease,
which affects as many as 5 million Americans aged 65 and older.
Investigators throughout the biomedical research enterprise--well
beyond the study of genetic diseases--are now incorporating genomic
analyses into their research. A major catalyst for this dissemination
has been NHGRI's unparalleled Advanced DNA Sequencing Technology
Program, the successes of which have led to a phenomenal drop in the
cost of DNA sequencing,\1\ enabling many more investigators to
incorporate genomic analyses into their research. However, these
researchers have a widespread and urgent need for improved analytical
tools for analyzing DNA sequence data. To address this, NHGRI has
created the Genome Sequencing Informatics Tools (GS-IT) program. Like
the Institute's development of cutting-edge innovations in DNA
sequencing, GS-IT is creating pioneering robust data-analysis tools for
studying genomes.
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\1\ Nature 507, 294-295 (20 March 2014) http://www.nature.com/news/
technology-the-1-000-genome-1.14901
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To become a reality, genomic medicine needs refined approaches for
using genomic information to improve health outcomes. For instance, in
fiscal year 2015, the Implementing Genomics Into Clinical Practice
(IGNITE) Network will test methods for disseminating genomic medicine
strategies more widely. IGNITE investigators will be initially studying
the use of genomic risk information for treating kidney disease, the
utility of family health history, and the use of genomic information
for selecting appropriate medications. In another effort, NHGRI is
partnering with the Eunice Kennedy Shriver National Institute of Child
Health and Human Development to support the Newborn Sequencing in
Genomic Medicine and Public Health (NSIGHT) Program, which is examining
the potential for genome sequencing to improve the care of newborns.
Pilot programs such as IGNITE and NSIGHT, in addition to other
large genomics projects, are only valuable if the generated knowledge
diffuses through the medical establishment. To help healthcare
professionals become competent with genomic information in delivering
patient care, NHGRI is working with the National Center for
Biotechnology Information to develop the Clinical Genome Resource
(ClinGen), which will provide a curated knowledgebase of clinically
relevant genomic variants. ClinGen will be freely available to
clinicians, researchers, and professional organizations developing
clinical practice guidelines, helping to usher in larger-scale
implementation of genomic medicine.
To capitalize on the genomics research funded by NHGRI and other
NIH institutes for medicine, the next generation of scientists and
clinicians must be equipped with the skills to lead their fields during
the 21st century. In fiscal year 2015, new institutional training
programs and individual career awards in genomics research and in
genomic medicine will develop leaders in those respective fields,
including the provision of cross-training in associated disciplines
such as bioethics and data science.
Another of NHGRI's educational efforts targets the general public.
The Institute collaborated with the Smithsonian Institution's National
Museum of Natural History to create the exhibition Genome: Unlocking
Life's Code. Privately funded, this widely acclaimed exhibition is
expected to be visited by more than 3.5 million people before the end
of fiscal year 2015. In addition, a series of nine public engagement
programs are being produced; these events will remain accessible via
the web to complement the exhibition as it travels North America over
the next 5 years.
As described above, NHGRI's genome sciences portfolio will continue
to explain the role of the genome in human traits and disease, while
its genomic medicine portfolio will apply that knowledge to improve
human health. The Institute will ensure that information about genomic
advances is disseminated to scientists and healthcare professionals as
well as the general public, and that the technologies and generated
knowledgebase will continue to be a growth engine for our economy.\2\
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\2\ http://www.unitedformedicalresearch.com/advocacy_reports/the-
impact-of-genomics-on-the-u-s-economy/
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______
Prepared Statement of Alan E. Guttmacher, M.D.
Mr. Chairman and Members of the Committee, I am pleased to present
the fiscal year 2015 President's budget request for the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD) of $1,283,487,000. This reflects an increase of $2,657,000 over
the fiscal year 2014 level of $1,280,830,000.
Understanding human development, both normative and atypical,
comprises the core of NICHD's mission. The Institute supports a broad
range of research, conducted largely at academic institutions across
the country, ranging from efforts to increase understanding of basic
biological mechanisms to testing health interventions aimed at
improving the lives of children, women, families, and those with
disabilities. NICHD-supported research contributes to knowledge about
our health, from the earliest stages through maturity.
pregnancy and birth outcomes
Based on NICHD-supported research showing less than optimal health
outcomes for infants born at 37 and 38 weeks of pregnancy (previously
considered full-term), leading professional societies announced in the
past year a new policy that pregnancy would now be considered full-term
only after 39 weeks. This change should lead to improved standards of
care and better health outcomes for mothers and infants.
While previous studies had found that alcohol and illegal drug use
during pregnancy frequently produce poorer infant health outcomes, a
NICHD-funded network study has now provided evidence that smoking
(including secondhand smoke), prescription painkillers, and illegal
drugs used during pregnancy can double or triple the risk of
stillbirth. These findings provide women and their clinicians important
information about healthy behaviors in pregnancy.
Through our Hunter Kelly Newborn Screening Research Program, NICHD
has long provided the evidence base for determining whether a health
condition can be detected in newborns, and whether it can be cured or
treated. Currently, most states screen newborns for a panel of 29
conditions, thus preventing extensive disease and disability. Now NICHD
is partnering with the National Human Genome Research Institute on a
major study to explore the possibilities for early diagnosis of a much
larger number of disorders by sequencing newborns' genomes, while also
exploring technical, clinical, and ethical questions raised by this new
technology. Researchers also plan to develop a tool to help parents
understand sequencing results, placing special emphasis on the needs of
families from diverse cultures and their clinicians.
pediatric and adolescent development
For many conditions, the earlier they are identified and treatment
begun, the better the outcome. One of the goals of the NICHD-led
National Children's Study is to amass an unprecedented amount of
information about children's health, development, and environment to
understand and improve health. Recently, researchers supported by NICHD
have developed an updated screening tool, administered to parents, to
help determine if a child between 18 months and 2 years old has autism,
much earlier than the current average age of diagnosis of 4 years.
Previous research has shown that earlier interventions can help improve
developmental outcomes for children with autism. This tool is now
widely available online, in 45 different languages.
Since variations in nutrition and environment so heavily influence
children's growth and development, NICHD engages in international
studies to increase knowledge about optimal health in childhood. In
some nutrient-deficient areas, children receive iron supplements to
enhance development and prevent anemia; yet, recently, public health
officials have become concerned that these supplements may increase
children's risk for malaria. To test this theory, NICHD-supported
researchers conducted a randomized clinical trial combining iron
supplementation with prevention efforts (such as sleeping nets) in a
malaria-prone area of Ghana, finding that the incidence of malaria was
no higher for children who received the supplements than for those who
did not, and assuring that beneficial iron supplementation could
continue.
Understanding human development in adolescence, with that period's
substantial physical, mental, and behavioral changes, poses a
particular challenge for researchers. While there is increased emphasis
on encouraging young people to be physically active to reduce
overweight and increase health, engaging in some physical activities
may pose risks. Concerns have been raised about the potential long-term
effects of repeated concussions in children, especially young athletes.
Recently, NICHD partnered with other NIH ICs and the National Football
League on eight research projects to help understand the effects of
head injuries and improve the diagnosis of concussions. Although
awareness is increasing that young people who may have had a concussion
should not immediately return to play, these studies will help us
understand the brain's healing process and what is required to prevent
permanent damage to this vital organ, leading to such advances as more
precise return to play policies.
Parents of teenagers will not be surprised that adolescents often
engage in risk-taking behaviors. They may, however, be surprised that
informed parental supervision can have an impact on adolescent
behaviors and even on potential injury or death. An intramural NICHD
study on teen driving behaviors collected data from a nationally
representative sample of 10th graders, finding that adolescents who
reported being exposed to riding with an intoxicated driver in the 10th
grade were considerably more likely to report driving while intoxicated
in the 12th grade. The study indicates the importance of parents' not
only monitoring their own children's driving behaviors, but also that
of other young drivers with whom their children may be riding.
women's health
One result of NICHD's 2012 ``Scientific Visioning'' process, which
took a fresh look at what the Institute might accomplish across its
broad mission over the next decade, was the establishment of the new
extramural Gynecologic Health and Disease Branch. Researchers supported
by the branch recently shed light on the relative success and safety of
two surgical treatments for pelvic organ prolapse (a form of pelvic
hernia). Previous research supported by NICHD suggested about 3 percent
of U.S. women experience prolapse in a given year, most commonly older
women and those who have given birth several times. The study found no
statistically significant difference between the two types of surgery,
providing critical information for surgeons and the 300,000 U.S. women
who have this surgery each year.
individuals with special needs
NICHD has long supported research on the causes and effects of
intellectual and developmental disabilities, and on identifying
effective therapies for these conditions. By working closely with
leading researchers, clinicians, self-advocates, and families,
Institute scientists identify the scientific resources most critical to
ongoing progress on these conditions. In September 2013, NICHD, with
the support of the NIH Down Syndrome Working Group and the Down
Syndrome Consortium, launched DS-ConnectTM: The Down
Syndrome Registry. DS-ConnectTM, which already includes over
1,500 registrants, is a web-based, voluntary, secure health registry
serving the Down syndrome community, providing anonymized information
to families and clinicians, and facilitating connections between
researchers and potential clinical research participants. In addition,
the Down syndrome community recently provided extensive input on a
revised NIH Research Plan on Down Syndrome, which will be available
mid-2014.
Another pressing need for scientists conducting research on
cognition and brain disorders is the availability of sufficient brain
tissue specimens. While NIH historically has funded investigator-
initiated, disease-specific brain banks, it is now taking a new
approach to providing these scarce research resources by supporting a
tissue-sharing collaboration among five brain banks. This new
``NeuroBioBank'' will increase availability of biospecimens and
establish a standardized resource for the research community.
embracing research opportunities
Increasingly, biomedical and biobehavioral researchers need to work
in transdisciplinary teams, manage massive amounts of data, and acquire
new and diverse skill sets. For example, the medical rehabilitation
needs of those with physical disabilities require a wide range of
research, from improving our understanding of neurological repair to
developing new generations of prostheses and assistive devices. In
2012, a Blue Ribbon Panel made a series of recommendations to NICHD to
bolster rehabilitation research at NICHD's National Center for Medical
Rehabilitation Research (NCMRR) and across NIH. NICHD is implementing
an innovative new operating model for NCMRR that is intended to greatly
increase coordination of rehabilitation research among the many ICs
that support it.
NICHD is excited to launch the Human Placenta Project, a
coordinated international initiative to understand in real time the
structure and function of the human placenta, arguably the least
understood human organ. The placenta is not only critical for both
maternal and fetal health, but also has substantial implications for
conditions that arise later in life in both the mother and child, such
as cardiovascular disease. The Project's goals include understanding
placental development in normal and abnormal pregnancies, developing
biomarkers to help predict adverse pregnancy outcomes, and developing
interventions to prevent abnormal placental and fetal development. The
currently projected span of the project is a decade, beginning with a
workshop in May 2014 to develop a research plan.
Thank you for the opportunity to submit some of NICHD's
accomplishments over the last year and a few of its many exciting plans
for the immediate future.
______
Prepared Statement of Richard J. Hodes, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2015 budget request for the National
Institute on Aging (NIA) of the National Institutes of Health (NIH).
The fiscal year 2015 budget includes $1,170,880,000, which is
$1,453,000 more than the comparable fiscal year 2014 level of
$1,169,427,000.
More than 40 million people age 65 and older live in the United
States, and data from the Federal Interagency Forum on Aging-Related
Statistics indicate that their numbers will double by 2040. In less
than 50 years, the number of ``oldest old''--people ages 85 and older--
may quadruple. As record numbers of Americans reach retirement age and
beyond, profound changes will occur in our economic, healthcare, and
social systems.
The NIA leads the national effort to understand aging and to
develop interventions that will help older adults enjoy robust health
and independence, and continue to make positive contributions to their
families and communities. We support genetic, biological, clinical,
behavioral, and social research related to the aging process, healthy
aging, and diseases and conditions that often increase with age. We
also support training of the next generation of researchers.
understanding aging at its most basic level
NIA-supported studies in the emerging field of geroscience, which
explores the basic mechanisms underlying age-related changes, including
those which could lead to increased disease susceptibility, will
provide needed insight into ways to address aging-related diseases and
disorders. The NIA-led NIH GeroScience Interest Group (GSIG) involves
active participation by 20 NIH Institutes and is leading the effort to
accelerate and coordinate efforts to promote further discoveries on the
common risks and mechanisms behind age-related diseases and conditions.
In October 2013, the GSIG and private-sector partners convened a
national Summit, ``Advances in Geroscience: Impact on Healthspan and
Chronic Disease,'' which drew more than 500 expert participants from
around the world. We expect its outcomes to further energize this
field.
An increasingly important research area is the identification of
genes and gene variants related to aging and age-related disease. Such
research will be accelerated by the addition of data on more than
78,000 older individuals from one of the Nation's largest and most
diverse genomics projects, Genetic Epidemiology Research on Aging, to
the NIH database of Genotypes and Phenotypes (dbGAP). These data will
be widely available to qualified investigators.
improving the health and well-being of older americans
NIH-supported investigators are testing a variety of interventions
for health conditions common to old age. Ongoing studies include: the
ASPirin in Reducing Events in the Elderly (ASPREE) trial, designed to
determine whether the benefits of aspirin outweigh the risks in people
over 70; testosterone supplementation to delay or prevent frailty in
older men; exercise for mood, health, and cognition; and an array of
interventions for menopausal symptoms.
NIA also supports research aimed at development of interventions
that will enable older adults to remain independent for as long as
possible. For example, researchers used data from nine large NIA-funded
studies to develop diagnostic criteria for low muscle mass and
weakness. These conditions lead to disability in older people, but are
rarely recognized as clinical problems by healthcare providers. This
work is a milestone toward the development of new diagnostic and
treatment strategies for this common and disabling condition. In
addition, the recent NIA-supported finding that training to improve
cognitive abilities in healthy older people lasts to some degree for 10
years after the training program was completed provides an important
piece of evidence that cognitive health can be improved and maintained
into older age.
Serious injuries from falls, such as broken bones or traumatic
brain injury, are a major reason for the loss of independence among
older people. In 2013, NIA and the Patient-Centered Outcomes Research
Initiative (PCORI) solicited applications for funding to conduct a
randomized clinical trial of a multifactorial strategy for preventing
serious fall-related injuries among non-institutionalized older people.
The trial will begin in 2014.
NIA is also a leader in the trans-NIH Science of Behavior Change
initiative. We are hoping that the long-term outcome of this initiative
will be to enhance the efficacy of interventions to help individuals
make and maintain positive changes in their health behaviors. As an
example, one NIA-managed study in this initiative has shed light on how
stress can reduce or eliminate the ability of individuals to benefit
from training designed to help them regulate their emotions and better
control their behavior, suggesting possible changes to our behavioral
intervention strategies.
Because investigators often, for a variety of reasons, have
difficulty recruiting older people into clinical research studies, NIA
is collaborating with the Administration for Community Living, the
Centers for Disease Control and Prevention, state and community-based
health and social service providers, researchers, and private
organizations on the Recruiting Older Adults into Research (ROAR)
project.
building momentum against alzheimer's disease
NIA is the lead Federal agency supporting research on Alzheimer's
disease (AD), which despite our best efforts continues to be a serious
public health issue that directly affects as many as 5 million
Americans. In fiscal year 2014, NIA received approximately $100 million
in additional appropriated funds. We plan to use these additional funds
to support Alzheimer's research in areas of strategic priority, funding
additional awards to applications received from Funding Opportunity
Announcements issued in fiscal year 2013-fiscal year 2014. We will
continue to be guided by the strategic goals outlined in the National
Action Plan on Alzheimer's Disease and the results from the 2012
Alzheimer's Disease Summit. A second Summit is planned for February
2015 to update milestones and stimulate further research.
Recent findings have expanded our understanding of AD and provided
insights into prevention and treatment of the disease. For example,
NIA-funded researchers recently identified a molecule called REST,
which is lost in the brains of patients with Alzheimer's disease, and
whose deletion in mice leads to neurodegeneration. REST represents a
novel potential target for intervention into the disease. Investigators
have also found that conjugated equine estrogens, the most common type
of postmenopausal hormone therapy in the United States, has no long-
term risk or benefit to cognitive function in younger postmenopausal
women, aged 50-55. The earlier Women's Health Initiative Memory Study
linked the same type of hormone therapy to cognitive decline and
dementia in older postmenopausal women, but this finding suggests that
women taking certain estrogen-based hormone therapies in their early
postmenopausal years may not be at increased risk for eventual
cognitive decline.
empowering the next generation of researchers in aging
As the number of older Americans continues to grow, we must not
only increase the number of practicing physicians trained in geriatrics
and relevant subspecialties but also foster the development of the next
generation of physician-scientists whose clinical research will lead to
improved care and more effective treatment options for older patients
with complex medical conditions. Two ongoing programs--Grants for Early
Medical/Surgical Subspecialists' Transition to Aging Research
(GEMSSTAR), supporting physicians who seek to become clinician-
scientists in geriatric aspects of their subspecialty, and Medical
Students Training in Aging Research (MSTAR), targeting first-year
medical students in order to stimulate early interest in an aging
research career--remain highly successful. Building on new technologies
that enable us to reach a wide audience efficiently and inexpensively,
we have initiated a series of Technical Assistance webinars to provide
participants, particularly those with an interest in health disparities
research, with guidance on navigating the NIA grants application
process. Finally, the Butler-Williams Scholars Program (formerly the
NIA Summer Institute) remains a vibrant and vital institution at NIA,
drawing a record number of applications for the 2014 session.
______
Prepared Statement of Stephen I. Katz, M.D., Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS) of the National
Institutes of Health (NIH). The fiscal year 2015 NIAMS budget of
$520.189 million includes an increase of $0.851 million over the
comparable fiscal year 2014 level of $519.338 million.
The NIAMS supports a broad range of research, training, and
information dissemination activities. Many of the conditions within the
NIAMS mission are very common while some are rare, affecting only a few
thousand people world-wide. All have a major impact on the quality of
people's lives. Diseases addressed by NIAMS affect individuals of all
ages and of all racial and ethnic backgrounds; many disproportionately
affect women and minorities. Over the years, NIAMS-funded research
teams have made significant progress in uncovering the causes of and
improving the treatments for many disorders of the bones, muscles,
joints, and skin.
While many treatments for arthritis and musculoskeletal and skin
conditions have their origins in NIH-supported basic research, the
timeframes for translating fundamental knowledge into therapies remain
unacceptably long, and too many potential therapies fail late in
development. To improve the drug development process, NIAMS has
partnered with industry, non-profit groups, and other government
agencies for the NIH Accelerating Medicines Partnership program in
lupus and rheumatoid arthritis (RA). Through the program, a network of
investigators will use advanced tools and techniques to analyze blood
and tissue samples from patients. The overall goals are to gain
insights into lupus and RA biology, improve the selection of biological
targets for drug development, and ultimately produce new therapies.
The advent of technologies for collecting and analyzing large
amounts of data corresponds with an increasing appreciation of the
interactions that occur among different tissues and organ systems, and
with the microorganisms inside our body or on our skin. When
researchers compared the gut microbes of people who had newly
diagnosed, untreated RA with those found in the digestive tracts of
healthy people, patients with RA who were receiving treatment, and
psoriatic arthritis patients, they found that the bacterium Prevotella
copri (P. copri) was more abundant in patients with new-onset RA than
in the other groups. If additional studies determine that altered
levels of P. copri contribute to RA, therapies that target the
bacterium could help to prevent the disease or delay its onset.
Similarly, another group of researchers recently demonstrated that
Staphylococcus aureus colonies on the skin of people who have atopic
dermatitis, or eczema, release a toxin that causes skin inflammation.
This finding provides an impetus for further studies into whether
blocking the toxin could help people who are susceptible to atopic
dermatitis.
Other research is uncovering complex connections between the immune
system and skeletal health, and the role of hormones produced by bone
on the development and function of the nervous system. Recent findings
have linked the misfolding of a protein that helps immune cells
recognize and destroy invading bacteria or viruses to the bone erosion
that characterizes spondyloarthritis of the spine. Other research has
revealed that the bone-derived hormone osteocalcin is capable of
interacting with neurons in the brain and influencing brain structure
and behavior, at least in mice.
Many people think of broken bones as a normal part of an active,
healthy childhood. Although any bone will break if enough force is
applied to it, researchers are learning that the bones of some children
and teens have structural deficits that can be readily identified based
on what the patient was doing when the bone was broken. Children who
broke an arm because of moderate impact, as would occur when falling
off a bicycle, had bones that resembled their uninjured peers; but,
those whose forearm bones broke upon mild impact (e.g., a fall during a
minor playground scuffle) showed signs of compromised bone strength and
bone quality. While we do not know the extent to which bone weakness
during childhood predisposes people to osteoporosis and fragility
fractures later in life, this study is the first to suggest that a
simple screening question could identify the young people who might
benefit most from dietary changes and activities to improve bone
health.
NIAMS also is involved in efforts to identify laboratory-based or
imaging biomarkers that will guide treatment development or will
improve patient care. Activities include the Foundation for the NIH
(FNIH) Biomarkers Consortium project to evaluate biochemical and
imaging biomarkers for more precise ways of measuring osteoarthritis
progression during clinical trials; this project builds on resources
created by the Osteoarthritis Initiative (OAI), a public-private
partnership spearheaded by NIAMS and the National Institute on Aging
with support from other NIH components, the U.S. Food and Drug
Administration, the FNIH, and private sponsors. A separate research
team, focused on molecular changes associated with scleroderma,
recently reported that blood levels of a protein appeared to
distinguish between patients who were likely to develop life-
threatening lung complications that require aggressive treatments and
those whose disease would not warrant risky therapies. Investigators
are confirming their observations as a next step before the findings
are applied clinically.
Additional research into disease-associated genetic defects and
molecular pathways is pointing to new uses for drugs that have been
approved for other conditions. Work by investigators studying a group
of muscle diseases called the disferlinopathies--which includes limb-
girdle muscular dystrophy type 2B--suggests that calcium channel
blocking drugs might reduce some of the tissue damage that accumulates
as the diseases progress. Another example comes from a team that
identified 42 areas in the human genome that are associated with RA;
many of the gene products are already targeted by existing drugs. These
potential drug repurposing opportunities will be explored more
thoroughly before clinical trials can begin in patients.
Once results from clinical studies are available, many healthcare
providers insist that findings be validated before changing how they
practice medicine. The ability to verify conclusions is equally
important at the basic and preclinical levels of research, particularly
when results become the basis for clinical trials. In fiscal year 2015,
NIAMS plans to refocus the Pilot and Feasibility Clinical Research
Grants in Arthritis and Musculoskeletal and Skin Diseases program--a
grant mechanism to foster early-stage clinical trials on which larger,
more robust studies will be based--to emphasize the need for a strong
scientific premise on which a proposed project is based.
NIAMS is committed to ensuring that well-trained basic scientists
and clinical researchers are prepared to conduct cutting-edge studies
related to rheumatic, musculoskeletal, and skin diseases. The Institute
awards a combination of institutional training grants and individual
fellowships for this purpose. NIAMS has expanded its participation in
NIH training programs for fiscal year 2015 to include the Ruth L.
Kirschstein National Research Service Awards for Individual Predoctoral
MD/PhD and Other Dual Doctoral Degree Fellows (F30) program. The
Institute also has begun meeting with clinical or patient-oriented
research career development awardees--both early in their award and as
they are about to transition to independent careers--to identify
challenges that they face and ways to better support them and future
awardees.
As part of a commitment to communicating about NIAMS programs and
research results, NIAMS has enhanced its outreach to patients,
healthcare and research professionals, and the general public via
social media and other activities. Building on a successful 2013 effort
to ensure that the results of NIH research investments and health
messages reach all Americans, NIAMS again partnered with other
components of the Department of Health and Human Services and with
patient advocacy groups to create a new set of health planners, titled
A Year of Health, A Guide to a Healthy 2014 for You and Your Family. In
the past 2 years, NIAMS received requests for these health planners
from all 50 states and five U.S. territories, demonstrating a robust
need for credible, research-based health information in African
American, American Indian/Alaska Native/Native Hawaiian, Asian
American/Pacific Islander, and Hispanic/Latino communities.
Looking to the future, we are updating the Institute's Long-Range
Plan. As with the fiscal year 2010-2014 plan, the new document will
inform the Institute's priority setting process while enabling the
NIAMS to adapt to the rapidly changing biomedical and behavioral
science landscapes. When complete, the plan will outline the
Institute's perspective on research needs and opportunities within the
NIAMS mission, and will serve as a resource for all who are interested
in our activities.
______
Prepared Statement of George Koob, Ph.D.
Mr. Chairman and Members of the Committee: As the new Director of
the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the
National Institutes of Health (NIH), I am pleased to present the
President's budget request for the Institute. The fiscal year 2015
NIAAA budget request of $446,017,000 reflects an increase of $606,000
over the comparable fiscal year 2014 enacted level of $445,411,000.
scope of the problem
Excessive alcohol use has profound effects on individuals, families
and communities; and the Centers for Disease Control and Prevention
(CDC) estimates that excessive alcohol consumption cost the U.S. $224
billion in 2006. In 2012, nearly one quarter of the U.S. population
aged 21 and older and over 15 percent of young people ages 12-20
reported binge drinking (i.e. consuming five or more drinks on a single
occasion) at least once in the past month, according to the Substance
Abuse and Mental Health Services Administration (SAMHSA). Binge
drinking has serious acute and long term consequences--both for youth
and adults. NIAAA estimates that 18 million Americans have an alcohol
use disorder (AUD) and NIAAA research has established an important
connection between early alcohol use and the development and severity
of AUD. Of those who meet the criteria for an AUD, only about 15
percent ever seek treatment.
niaaa research
To reduce the considerable burden of illness and the societal costs
associated with alcohol misuse, NIAAA is working to advance evidence-
based prevention and treatment for alcohol problems for individuals at
all stages of life, including those with co-occurring disorders.
NIAAA's research portfolio is broad, ranging from studies on the
underlying biological mechanisms that drive excessive drinking and the
development of medications for AUD targeting these mechanisms, to
studies on policies and interventions designed to reduce harm both to
drinkers and those around them. NIAAA's portfolio also includes both
research on the health benefits associated with moderate drinking and
on the consequences of alcohol misuse, including fetal alcohol spectrum
disorders (FASD), alcohol effects on the developing adolescent brain,
and alcohol effects on tissue and organ damage.
NIAAA's cutting edge work in the neuroscience of alcohol effects on
the brain provides not only a firm foundation for development of novel
treatments for AUD but also a framework for prevention. The NIAAA
portfolio focuses on the neurocircuitry changes that promote the
development of AUD as well as those that convey resilience.
Particularly critical are the studies of the adolescent brain and how
excessive alcohol intake can delay, or permanently compromise normal
development of the brain's executive and self-regulatory functions.
A key goal of NIAAA is to work with other NIH Institutes and
Centers and Federal agencies to enhance integration of research on the
abuse of alcohol and other substances. Notably, NIAAA co-leads the
Collaborative Research on Addictions at NIH (CRAN) with the National
Institute on Drug Abuse (NIDA) and the National Cancer Institute (NCI);
co-chairs the Alcohol Policy and Underage Drinking Subcommittee of the
HHS Behavioral Health Coordinating Council with the CDC; and
collaborates with the National Institute of Mental Health (NIMH), NIDA,
Department of Defense (DOD) and the Veterans Administration (VA) on the
implementation of the National Research Action Plan for Improving
Access to Mental Health Services for Veterans, Service Members, and
Military Families.
Recognizing that medications currently available to treat AUD can
be highly effective but do not work for everyone, NIAAA continues to
make significant progress towards developing additional evidence based
pharmacotherapies. NIAAA's Clinical Investigations Group (NCIG),
established to rapidly test candidate compounds (within 12-18 months),
is streamlining the medications development process for AUD. NCIG
recently completed a multisite clinical trial that showed the anti-
smoking medication varenicline (Chantix) significantly reduced alcohol
consumption and craving in both smokers and non-smokers with AUD. Going
forward, NCIG will test both repurposed and novel compounds often
working in collaboration with extramural scientists and the
pharmaceutical industry. NIAAA also supports promising pharmacotherapy
research outside of NCIG. In an independent study, the widely
prescribed anti-seizure medication gabapentin, used to treat pain and
used off-label for migraines, reduced heavy drinking and other related
symptoms in alcohol dependent patients. A study to replicate the
gabapentin finding within NCIG is anticipated. It is important to note
that currently available medications are very effective for many, and
that NIAAA is working to make clinicians and the public aware of the
range of available treatment options for AUD, as well as promoting
research into more effective implementation of treatment.
Given that AUD often co-occurs with other substance use and/or
mental health disorders, major priorities of the Institute are to
understand the complex relationships between and develop effective
treatments for alcohol misuse and co-occurring disorders. For example,
AUD frequently co-occurs with post-traumatic stress disorder (PTSD),
thereby complicating treatment for both conditions. PTSD is prevalent
among military personnel and veterans, and also among individuals who
have experienced sexual assault--a far too common occurrence on college
campuses, and one often associated with excessive drinking by both
perpetrators and victims. PTSD increases risk for AUD; conversely,
chronic alcohol use may increase the risk for PTSD by altering the
brain's ability to recover from a traumatic experience. Using an animal
model of PTSD, NIAAA intramural researchers discovered that chronic
alcohol exposure altered neurons in the medial prefrontal cortex region
of the brain, making the animals slower to suppress a conditioned fear
response. Differences in the ability to handle fear responses could
help explain differences in vulnerability to PTSD among humans, and
lead to new therapeutic approaches and diagnostic risk biomarkers.
NIAAA also supports other promising studies on co-occurring PTSD and
AUD.
The consequences of binge drinking for all ages range from acute,
e.g. injuries and blackouts, to long term, e.g. severe AUD and organ
damage. Recent results of NIAAA-supported research have revealed that
binge drinking may be harmful in more ways than previously thought. For
example, in results published this year, a single episode of binge
drinking (which in the study raised the blood alcohol concentration to
0.08 g/dL, the legal limit for driving while intoxicated, within 60
minutes) increased leakage of bacterial endotoxins from the gut into
the bloodstream and elicited an immune response, demonstrating that
binge drinking produces acute damage in the body, even in healthy
people. Notably, women had higher blood alcohol levels and circulating
endotoxin levels than men. Often viewed as a rite of passage, binge
drinking is pervasive among our Nations' youth with 1.7 million young
people ages 12-20 engaging in this behavior five or more times per
month according to SAMHSA. NIAAA's current studies on the effects of
alcohol on the developing brain will inform a more extensive study
under CRAN to assess the effects of drugs and alcohol, alone and in
combination, on the adolescent brain. College and University Presidents
are especially concerned about the rampant heavy use of alcohol among
their students resulting in an estimated 1,825 deaths, 696,000
assaults, and 97,000 sexual assaults annually. NIAAA will soon release
a decision tool to help college administrators select effective
evidence-based interventions appropriate for their campuses. NIAAA also
promotes screening and brief intervention (SBI) for youth, and launched
an online course with Medscape to provide continuing medical education
for healthcare professionals to help them conduct fast, evidence-based
alcohol SBI with youth. To date, over 14,000 healthcare providers have
been Medscape certified.
Preventing, diagnosing, and treating alcoholic liver disease (ALD)
is also a major priority. NIAAA funds four research consortia to pursue
new clinical approaches to treat alcoholic hepatitis, a severe form of
ALD. NIAAA will also continue to pursue biomarkers of liver injury to
facilitate earlier diagnosis.
NIAAA has significantly advanced our understanding of the health
and social impacts of alcohol use and misuse. NIAAA will continue to
pursue opportunities leading to better outcomes for alcohol-related
problems, and support a diverse biomedical research workforce that is
equipped to tackle these public health challenges.
______
Prepared Statement of Donald A.B. Lindberg, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Library of Medicine
(NLM) of the National Institutes of Health (NIH). The fiscal year 2015
budget of $372,851,000 includes an increase of $5,628,000 over the
comparable fiscal year 2014 level of $367,223,000.
The National Library of Medicine, the world's largest biomedical
library, builds and provides electronic information resources used
billions of times each year by millions of scientists, health
professionals and members of the public. Many health information
searches that are initiated on the Internet actually retrieve
information from an NLM Web site. NLM is crucial in the dissemination
of biomedical research results--DNA sequences, clinical trials data,
toxicology and environmental health data, research publications, and
consumer health information to scientists, health professionals, and
the public. A leader in biomedical informatics and information
technology, NLM also supports and conducts research, development, and
training in biomedical informatics, data science, and health
information technology; and coordinates the 6,100-member National
Network of Libraries of Medicine that promotes and provides access to
health information in communities across the United States.
NLM's programs and services directly support NIH's key initiatives
in basic research, precision medicine, research training, as well as in
data science and Big Data. NLM's National Center for Biotechnology
Information (NCBI) is a focal point for ``Big Data'' in biomedicine and
a leader in organizing and providing rapid access to massive amounts of
genetic sequence data generated from evolving high-throughput
sequencing technologies. NCBI serves more than 30 terabytes of
biomedical data to more than 3.3 million users daily. Some of the
largest datasets, such as those from NIH's 1000 Genomes Project, are
also available in the Amazon cloud. This allows faster access and
analysis by researchers who may be otherwise hampered by insufficient
bandwidth or computing power. Additionally, the Library organizes and
provides access to the published medical literature; assembles data
about small molecules to support research and therapeutic discovery;
provides the world's largest clinical trials registry and results
database; and is the definitive source of published evidence for
healthcare decisions. NLM's PubMed Central (PMC) provides essential
infrastructure for the NIH Public Access Policy, making published NIH-
funded research freely and permanently available to the public. NLM/
NCBI databases are cited in laws and Congressional legislation (e.g.,
Public Law 110-161,Consolidated Appropriations Act and HR 4186, the
Frontiers in Innovation, Research, Science, and Technology) as a model
for facilitating public access to federally funded data and
publications.
Research supported or conducted by NLM underpins today's electronic
health record systems. The Library has been the principal funder of
university-based informatics research training for 40 years, supporting
the development of today's leaders in informatics research and health
information technology. NLM's databases and its partnership with the
Nation's health sciences libraries deliver research results wherever
they can fuel discovery and support health decisionmaking.
biomedical and health information services
NLM's PubMed/MEDLINE database is the world's gateway to research
results published in the biomedical literature. It links to full-text
articles in PubMed Central, including those deposited under the NIH
Public Access Policy, and on publishers' Web sites, as well as
connecting to vast collections of scientific data. PubMed contains more
than 23 million references to articles in the biomedical and life
sciences journals providing high quality information to about 2.3
million users per day. NLM is a primary source for results of patient-
centered outcomes research, providing access to evidence on best
practices to improve patient safety and healthcare quality. NLM is also
a hub for the international exchange and use of data utilized in
molecular biology, genomics, and clinical and translational research.
Many NCBI databases, including dbGaP, the Genetic Testing Registry
(GTR), and ClinVar are fundamental to the identification of important
associations between genes and disease, and to the translation of new
knowledge into better diagnoses and treatments.
NLM's Lister Hill National Center for Biomedical Communications
operates ClinicalTrials.gov, the world's most comprehensive clinical
trials database. It contains registration data for more than 160,000
clinical studies with sites in 185 countries and summary results for
more than 11,000 trials, including many results that are not available
elsewhere.
standards for electronic health records
For 40 years, NLM has supported seminal research on electronic
patient records, clinical decision support, and health information
exchange, including concepts and methods now reflected in electronic
health record (EHR) products and personal health record tools. EHRs
with advanced decision-support capabilities and connections to relevant
health information are essential to improving healthcare and helping
Americans manage their own health. As the Department of Health and
Human Services (HHS) coordinating body for clinical terminology
standards, NLM works closely with the Office of the National
Coordinator for Health Information Technology and the Centers for
Medicare and Medicaid Services to facilitate adoption and ``meaningful
use'' of EHRs. NLM supports, develops, and distributes key terminology
standards now required for U.S. health information exchange. To help
EHR developers implement standard terminologies, NLM produces related
software tools, frequently used subsets, and mappings to administrative
code sets, and provides the authoritative versions of terminology value
sets for required clinical quality measures. NLM's MedlinePlus Connect
also supports meaningful use by providing a way for EHR products to
link patients to high quality health information relevant to a specific
health conditions, medications, and tests, directly from their EHRs.
health information for the public
The NLM has a wide range of outreach programs to enhance awareness
of NLM's diverse information services among biomedical researchers,
health professionals, librarians, patients, and the public. To improve
access to high quality health information, NLM works with the 6,100
institutions of the National Network of Libraries of Medicine, a
network of academic health sciences libraries, hospital libraries,
public libraries, and community-based organizations and has formal
partnerships with tribal colleges and other minority serving
institutions. In fiscal year 2013, dozens of community-based projects
were funded across the country to enhance awareness and access to
health information, including in disaster and emergency situations, and
to address health literacy issues.
The Library's MedlinePlus Web site provides integrated access to
high quality consumer health information produced by all NIH components
and HHS agencies, other Federal departments, and authoritative private
organizations. It serves as a gateway to specialized NLM information
sources for consumers, such as the Genetic Home Reference and the
Household Products Database. Available in English and Spanish, with
selected information in 40 other languages, MedlinePlus averages well
over 750,000 visits per day. Mobile MedlinePlus, also in both English
and Spanish, reaches the large and rapidly growing mobile Internet
audience.
The NIH MedlinePlus print and online magazine, in English and
Spanish, is an outreach effort made possible with support from many
parts of NIH and the Friends of the NLM. Distributed free to the public
via physician offices, community health centers, libraries and other
locations, the print magazine reaches a readership of up to 5 million
nationwide and the online version reaches millions more. Each issue
focuses on the latest research results, clinical trials and guidelines
from the 27 NIH Institutes and Centers.
The Library diversifies access to all its information resources,
through mobile devices and ``apps.'' NLM continues to be a leading
player in social media amongst HHS agencies with active Facebook,
Twitter, and You Tube accounts, including the very popular @medlineplus
Twitter feed and a Spanish-language counterpart, several online
newsletters, and its National Network of Libraries of Medicine, which
covers the United States and hosts eight Facebook pages, 10 Twitter
feeds and 12 blogs. NLM is consistently ranked among the most liked,
most followed, and most mentioned organizations amongst small
government agencies with social media accounts.
In conclusion, the Library is a trustworthy source of health
information for the public and vital to the practice of 21st century
medicine and the progress of science. NLM's information services and
research programs serve the Nation and the world by supporting
scientific discovery, clinical research, education, healthcare
delivery, public health response, and the empowerment of people to
improve personal health. The Library is committed to the innovative use
of computing and communications to enhance public access to the results
of biomedical research.
______
Prepared Statement of Jon R. Lorsch, PH.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget for the National Institute of General Medical
Sciences (NIGMS) of the National Institutes of Health (NIH). The fiscal
year 2015 budget of $2,368,877,000 includes an increase of $6,983,000
above the comparable fiscal year 2014 level of $2,361,894,000. NIGMS
considers its public funds a precious resource and focuses on
efficiency and effectiveness in making investments in research and
training. The Institute spends 97 percent of its budget outside of the
NIH, funding biomedical research and training at universities and other
institutions across the country--where creative minds are at work every
day producing new knowledge about health and disease.
Scientific discovery is the engine for advances in medicine, as
research results lead to new treatments and refine current standards of
care. Biomedical research relies on attracting and retaining a creative
and well-trained workforce. NIGMS remains committed to enabling
researchers throughout the United States to answer important scientific
questions in fields such as cell biology, biophysics, genetics,
developmental biology, pharmacology, physiology, biological chemistry,
biomedical technology, bioinformatics, computational biology, selected
aspects of the behavioral sciences and specific cross-cutting clinical
areas that affect multiple organ systems. To assure the vitality and
continued productivity of the research enterprise, NIGMS also provides
leadership in training the next generation of scientists as well as in
developing and increasing the diversity of the scientific workforce.
back to basics
The high value of investigator-initiated research has stood the
test of time. This approach, in which scientists decide what questions
are important to study, ultimately leads to major advances in medicine
and technology. Examples include:
--Studies of virus-resistant bacteria led to the discovery of
restriction enzymes, which act like highly specific scissors
for cutting DNA. This discovery launched the multi-billion-
dollar biotechnology industry, starting with the laboratory-
based production of life-saving medicines like insulin and now
extending even beyond biomedicine into agriculture and
biofuels.
--Seemingly esoteric studies of how electric fields affect DNA
replication in bacteria lead directly to the discovery of the
anti-cancer drug cisplatin, which has saved thousands of human
lives.
--Studies of enzymes that copy DNA and RNA and that cut proteins
enabled the development of drugs to treat HIV infection.
To ensure a continued pipeline of fundamental scientific advances
that will lead to future medical and technological breakthroughs, NIGMS
is rebalancing its portfolio to renew and reinvigorate its support for
question-driven, investigator-initiated research. This rebalancing has
received strong support from stakeholder organizations, including the
Federation of American Societies for Experimental Biology, an umbrella
group representing 26 scientific societies and over 115, 000
researchers.
planning carefully for the future
NIGMS has begun a new strategic planning process that is focusing
on enhancing the efficacy, efficiency, and adaptability of the
Institute's internal processes and the mechanisms through which we
support biomedical research. In particular, we are exploring the
development of new grant mechanisms that would increase stability and
flexibility for researchers and maximize the scientific return on
taxpayers' investment. These mechanisms will focus on the efficient use
of funds, encouraging scientists to undertake ambitious and creative
projects that may be the breakthroughs of tomorrow.
NIGMS is also developing new strategies to strengthen and maintain
the pipeline of talented, creative, diverse and highly skilled young
investigators. This segment of the biomedical workforce is essential
for the future of scientific research in the United States, which is in
turn essential for the future health and economic competitiveness of
our Nation. Specific strategies we are considering to address the
challenges facing young investigators include outcomes-based
enhancements of our training programs and efforts to improve the
competitiveness of young investigators in obtaining and keeping
research grants.
supporting a diversity of ideas
NIGMS is proud to be the home of the IDeA program, which ensures
that cutting-edge research is conducted in every region of the country.
This strategy is critical to the strength of our biomedical research
enterprise, as it meets the need to involve the most diverse set of
minds, experiences and approaches for solving difficult health-related
problems. Last year, NIGMS funded or co-funded 58 competing grants to
IDeA researchers, this included 25 competing Centers of Biomedical
Research Excellence awards. Particularly exciting research developments
funded by the IDeA program include the demonstration by Kentucky
researchers that electrical stimulation of the spinal cord can restore
some motor function in individuals with paraplegia; a study by
scientists in South Carolina showing that nanoparticles coated with
antioxidant proteins can protect against stroke-related damage; and a
neonatal telemedicine center in Arkansas that has contributed to a
significant decrease in statewide infant mortality.
As requested by both the House and Senate and required by the
Consolidated Appropriations Act of 2014, NIH has submitted a response
to the National Academies' Report on EPSCoR and related programs. As
part of the NIGMS strategic planning process, we are developing plans
for enhancing access to resources for moving discoveries and innovative
ideas from laboratories in IDeA states into commercial products. In
particular, we are exploring support for regional biotechnology
incubators that would give faculty in IDeA states access to laboratory
space, equipment, expertise, and advice required to make their work
competitive for SBIR/STTR and venture capital funding.
advancing health through discovery
This past year, NIGMS-funded scientists broke new ground in a range
of areas relevant to health, including chemistry, microbe-host
interactions, computer modeling, and metabolism. Selected examples
include:
--A Tennessee researcher developed a chemical method to shave the
cost of manufacturing expensive drugs, including those used to
treat HIV/AIDS. The method is also environmentally friendly in
that it employs natural molecules called enzymes instead of
synthetic chemicals that are often hazardous.
--A scientist from Vermont created the first-ever interaction map of
human proteins that attach to proteins from arenavirus and
hantavirus, providing potential new targets for therapies to
treat the often deadly illnesses caused by these classes of
viruses.
--A Pennsylvania researcher found compounds that block a recently
discovered pathway for preventing production of damaged
proteins. These chemicals have antibiotic activity, suggesting
they might eventually be developed into a new class of
antibacterial drugs.
--A scientist from California learned from mouse studies that a high-
fat diet influences the internal body clock controlling liver
metabolism. The team also discovered that the effect was
reversible by returning to a balanced, low-fat diet.
These discoveries are a small subset of the productivity of the
nearly 4,000 scientists NIGMS supports throughout the United States.
Our public investment to fuel their curiosity-driven exploration of
biomedicine is growing knowledge, and local economies, as well as
improving the health of all Americans.
Thank you, Mr. Chairman. I would be pleased to answer any questions
that the Committee may have.
______
Prepared Statement of Yvonne T. Maddox, Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget for the National Institute on Minority Health
and Health Disparities (NIMHD) of the National Institutes of Health
(NIH). The fiscal year 2015 budget of $267,953,000 is the same as the
fiscal year 2014 enacted level of $267,953,000.
introduction
As the primary Federal agency for leading, coordinating and
facilitating research to improve minority health and eliminate health
disparities, NIMHD impacts the lives of millions of Americans burdened
by disparities in health status and healthcare delivery, including
racial and ethnic minority groups as well as rural and low-income
populations. A population is a health disparity population if it is
determined that there is a significant disparity in the overall rate of
disease incidence, prevalence, morbidity, mortality, or survival rates
in the population as compared to the health status of the general
population. The elimination of health disparities requires a
multidisciplinary approach, with collaboration, coordination, and
integration across NIH Institutes and Centers (ICs), other Federal
agencies and private-sector organizations to fully understand and solve
the underlying biological and non-biological causes of health
disparities.
fundamentals of health disparities
In order to understand the social, behavioral, biological, and
environmental factors influencing health disparities, NIMHD is studying
the fundamental causes of diseases and conditions that
disproportionately affect individuals from health disparity
backgrounds. For example, one project studies the higher incidence and
mortality of breast cancer in African American women through research
that examines the role genetic differences in the tumor suppressor
protein, p53, plays in the disparity. Researchers hypothesize that some
racial/ethnic groups have disproportionate p53 variants that may
contribute to breast cancer health disparities in the age of onset,
incidence, and lack of pregnancy protection in African American women.
Another study takes knowledge about causal pathways learned at the
bench and extends the findings to social, behavioral, health services
and/or policy approaches to test ways to improve minority health and
eliminate health disparities. This project examined unconscious
stereotyping of Hispanic patients among medical and nursing students.
The study found that students endorsed stereotypes that Hispanic
patients would be non-compliant or likely to engage in high-risk health
behaviors, even if the students reported trying consciously to avoid
biased thinking. This unconscious bias of medical providers can be one
factor in the disparity in healthcare delivery faced by minority
patients.
collaborative research framework
Comprehensively addressing health disparities requires a
transdisciplinary framework that fosters an integrated approach
involving biology, behavioral and social sciences, environmental
science, public health, healthcare delivery, economics, public policy,
and many other disciplines. It also requires strong collaborations
between researchers and community organizations, service providers and
systems, government agencies, and other stakeholders to ensure that
contextually appropriate and relevant research is conducted, and that
findings can translate into sustainable individual, community, and
systems level changes that improve the health of the U.S. population.
The NIMHD supports two programs that focus on transdisciplinary and
translational research: the Centers of Excellence (COE) and the
Transdisciplinary Collaborative Centers for Health Disparities Research
(TCC). The COEs, which were established as partnerships between
academic institutions and community organizations, have been in place
for over a decade and have reached more than 102 sites, across 31
States, the District of Columbia, Puerto Rico, and the U.S. Virgin
Islands. The COEs are addressing health disparities research along the
translational spectrum from basic science to clinical research, with
information dissemination a required component.
The TCC Program, established in fiscal year 2012, supports
research, implementation, and dissemination of activities that
transcend customary discipline-specific approaches conducted at the
local level. Transdisciplinary research collaboration at the regional
level provides opportunities for academic institutions, community-based
organizations, and other partners to conduct targeted research to
respond to specific population-based, environmental, sociocultural, and
political factors that influence health within a particular region.
The Collaborative Research Center for American Indian Health is
bringing together tribal communities and health researchers from a
variety of disciplines to work together to address the significant
health disparities experienced by American Indians in South Dakota,
North Dakota and Minnesota, particularly the social determinants of
health and its application to programming public health interventions.
The National Transdisciplinary Collaborative Center for African
American Men's Health is addressing unintentional and violence-related
injuries as well as chronic diseases that affect African American men
across the life course, as part of a national initiative.
community engagement
Active community involvement in biomedical and behavioral research
is essential to improving the health of the public. The NIMHD
Community-Based Participatory Research (CBPR) Initiative supports the
development, implementation, and evaluation of intervention research
that utilizes the principles of community engagement as partners in the
full spectrum of research. A number of CBPR planning phase and
dissemination phase projects are under way. The Partnerships to Improve
Lifestyle Interventions and Partners in Care programs tested the
effectiveness of a culturally adapted diabetes self-management
intervention among Native Hawaiians and Pacific Islanders. The study
found improvements in weight loss, physical capacity, and diabetes
self-management.
Another CBPR project focused on a culturally appropriate, church-
based Hepatitis B screening and vaccination intervention program for
Korean Americans which found increased screening and immunization rates
in the intervention group compared with the control group. Academic-
community partnerships were essential in balancing science and
community needs in the design and conduct of the needs assessment,
pilot and full-scale clinical trial.
research training and infrastructure
In order to advance the science and speed translation of
discoveries into better health outcomes for all Americans, it is
critical to expand and diversify the Nation's workforce of well-trained
scientists who are dedicated to improving minority health and
eliminating health disparities. A diverse biomedical workforce will
improve the quality of the educational and training environment,
balance and broaden the perspective in setting research priorities,
improve the ability to recruit subjects from diverse backgrounds into
clinical research protocols, and improve the Nation's capacity to
address and eliminate health disparities. NIMHD-supported programs to
train researchers to conduct minority health and health disparities
research are focusing on providing educational, mentoring, and/or
career development programs for individuals from health disparity
populations that are underrepresented in the biomedical, clinical,
behavioral, and social sciences. NIMHD continues to support research
training and infrastructure through its Research Endowment Program,
Building Research Infrastructure and Capacity Program, and Research
Centers in Minority Institutions Program.
conclusion
NIMHD has a unique and critical role at the NIH as the focal point
for conducting and coordinating research on minority health and health
disparities, raising national awareness about the prevalence and impact
of health disparities, and the dissemination of effective individual,
community, and population-level interventions to reduce and ultimately
eliminate health disparities. NIMHD is looking forward to identifying
new opportunities to accelerate the pace of research and to advance its
mission through strengthening partnerships and enhancing its role in
the community.
______
Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) of the National Institutes of Health
(NIH). The fiscal year 2015 NIBIB budget request of $328,532,000 is
$2,173,000 more than the fiscal year 2014 enacted level of
$326,359,000.
NIBIB is dedicated to improving human health through the
integration of the physical and biological sciences. NIBIB's mission
spans the entire health spectrum and is not limited to a single
disease, group of illnesses, or population. Working with doctors from
every field of medicine and bringing together teams of scientists and
engineers from many different backgrounds, NIBIB aims to develop
innovative approaches to healthcare. Our research focus is to improve
the understanding, detection, treatment and ultimately, the prevention
of disease.
innovation in treating spinal cord injury: new hope for those with
paralysis
Building on a long history of research on restoring function in
spinal cord injury, researchers have discovered a fundamentally new
intervention that led to voluntary movement in individuals with
complete paralysis. This outcome, initially seen in a single
individual, has now been reported in three successive patients, all of
whom had been paralyzed for more than 2 years. This achievement is a
significant milestone in spinal cord injury research. In the approach,
electrical stimulation is applied to the surface of the spinal cord
through a surgically implanted device that is normally used for the
suppression of back pain. After just a week of stimulation, on average,
the patients were able to voluntarily move their legs and flex their
feet and toes when the stimulator was turned on. With continued daily
stimulation and extensive physical training, the patients saw
improvements in their movements and could initiate them with decreased
stimulation. With their stimulators turned on, the patients are now
able to stand for about an hour. Restored function was accompanied by
increased muscle mass. In addition, these individuals have regained
bladder and bowel function and experienced improvements in autonomic
responses such as sweating and return of sexual function in some cases.
immunoengineering to modifiscal year immune system responses
The immune system is the body's defense against an array of
infectious agents. However, the immune system can also trigger many
diseases such as diabetes, rheumatoid arthritis, lupus or multiple
sclerosis; this occurs when immune cells are directed against an
individual's own cells and is referred to as autoimmunity. As our
understanding of the immune system increases, we are approaching a
point where the immune response can be engineered to enhance or reduce
specific responses. Two recent examples highlight this
``immunoengineering'' approach. In the first case, the problem being
addressed is improving targeted delivery of chemotherapeutic drugs to
tumors. Nanoparticles can be used to ferry chemotherapy directly to
tumors, minimizing exposure of these toxic medications to healthy
tissues in the body. Researchers have found a way to ferry
nanoparticles carrying chemotherapy drugs past cells of the immune
system, which would normally engulf the particles, preventing them from
reaching their target. The technique takes advantage of the fact that
all cells in the human body display a protein on their membranes that
functions as a specific ``passport'' in instructing immune cells not to
attack them. By attaching a small piece of this protein to
nanoparticles, scientists were able to get immune cells in mice to
recognize the particles as ``self'' rather than foreign particles, and
thereby not attack them. The nanoparticles also have other labels that
can concentrate the drugs in the tumors, so higher doses of
chemotherapy are delivered to the tumor.
In a second example, researchers have developed a strategy to
modulate the immune system to halt the progress of a disease model of
multiple sclerosis in mice. In multiple sclerosis, the immune system
attacks the myelin sheaths that surround nerve cells. To stop this
attack, engineered nanoparticles are coated with myelin antigens, and
these nanoparticles are presented to another set of cells in the immune
system that re-identifies myelin as `self' rather than `foreign'. The
result is that the immune system stops attacking myelin as a foreign
body, and the disease progression is halted. This approach begins to
take advantage of the complex control of immune response which contains
multiple positive and negative feedback loops in order to selectively
turn off one specific inflammatory response. It holds promise for
treating multiple sclerosis and other autoimmune diseases that
previously have escaped effective therapies.
cancer detection from a routine blood sample
Most cancers spread by way of the circulatory system. As a result,
there are cancer cells present in blood samples. The number of cells,
however, is so low that they have been difficult or impossible to find.
The problem is to find and isolate the few cancer cells from the
billions of other cells that are present in the blood. Researchers over
the past several years have developed new techniques to find these
cells, but those techniques have generally been destructive to the
cancer cells. Now, with a new sorting technology, researchers have
demonstrated the ability to sort the cancer cells and, of equal
importance, to collect them for further analysis. After collection, the
circulating tumor cells can be subjected to the full array of analysis
techniques available to normal tissue biopsies of a tumor. This
technology also permits sorting, using a variety of markers that allow,
for example, the identification of triple negative breast cancer cells.
Successful isolation has been demonstrated in several other cancers
including lung, prostate, pancreas, breast, and melanoma. This new tool
has the potential to improve both the early diagnosis and effective
treatment of cancer.
an implantable artificial kidney holds promise for patients on dialysis
Expenditures in the United States for end stage renal disease
exceed $40 billion annually. Treatment of end stage renal disease
includes renal transplant and thrice-weekly, in-center hemodialysis.
Renal transplant is limited to a small fraction of potential recipients
by a shortage of donor organs. As a result, more than 400,000 Americans
are on dialysis, which is expensive, inconvenient, and over time
associated with significant morbidity and mortality. Researchers are
developing an implantable bioartificial kidney called the Implantable
Renal Assist Device (iRAD), in which a patient's blood will be filtered
through an artificial kidney consisting of silicon nanopore membranes
and a bioreactor of cells to mimic the functions of a healthy kidney.
Such a device could offer numerous advantages for patients including:
freedom of mobility, decreased infection risk due to a permanent
vascular connection, and continuous treatment, which avoids the build-
up of toxins that occurs between in-center hemodialysis visits. In
addition, incorporation of the patient's own cells could provide normal
renal metabolic function that would be more physiologic than dialysis
and not require anti-rejection drugs used for transplant. This combined
filtration and metabolic treatment has been shown to work using a room-
sized external model. Multi-day animal model testing to demonstrate
hemofilter biocompatiblity has been conducted. Although human studies
have not been initiated with the iRAD, these researchers are working
with the Food and Drug Administration (FDA) on an initiative that
facilitates new ways for FDA staff and innovators to jointly bring
breakthrough medical device technologies to patients faster and more
efficiently.
smart homes for healthy independent living at all ages
The population is aging and, increasingly, medical treatment
involves the management of chronic and/or degenerative diseases.
Management of such conditions requires monitoring and early
intervention to prevent more severe complications. The rapid
development and ever expanding capabilities of smart phones, advanced
sensors, point-of-care diagnostics, and integrated Internet
connectivity provides a framework on which new healthcare models can be
developed to provide this monitoring and intervention. Investigators
are testing real-time home observation of high-risk patients for early
signs of illness, using a built-in camera, computer tablet and a smart
phone for simultaneous monitoring of daily activities by family members
and health professionals. This includes analysis of daily habits,
mobility patterns, and gait rate and rhythm as indicators of change in
health status. Developing automated technologies to help identify early
indicators of changes in health status will extend the amount of time
individuals can live independently in their own homes.
______
Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2015 budget request for the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the
National Institutes of Health (NIH). The fiscal year 2015 budget
includes $1,743,336,000, which is $1,462,000 above the comparable
fiscal year 2014 appropriation of $1,741,874,000. Complementing these
funds is an additional $150,000,000 authorized in fiscal year 2015 from
the Special Statutory Funding Program for Type 1 Diabetes Research.
NIDDK supports research on a wide range of common, chronic, costly, and
consequential diseases and health problems that affect millions of
Americans. These include diabetes and other endocrine and metabolic
diseases; digestive and liver diseases; kidney and urologic diseases;
blood diseases; obesity; and nutrition disorders.
today's basic science for tomorrow's breakthroughs
NIDDK-supported basic research is achieving remarkable progress and
building the foundation for previously unimaginable strategies to
improve health and quality of life. For example, recent research has
better defined human brown adipose (fat) tissue in the neck, and has
further elucidated the role of a family of proteins as molecular
signals regulating brown fat physiology--findings that could help
inform new approaches for altering metabolism to clinical advantage.
The microorganisms that inhabit the gastrointestinal tract are
important factors in maintaining or tipping the balance between health
and disease. A recent study of young twin pairs in Malawi revealed that
gut microbes may play an important role in causing severe malnutrition
in children that persists in spite of nutritional interventions.
Gaining new insight into gastric bypass surgery, scientists studying a
mouse model found that restructuring of the digestive tract leads to
weight loss and metabolic benefits in part by altering the communities
of bacteria that normally live in the intestines. Another study has
shown that deletion of the protein olfactomedin-4 in white blood cells
improves their ability to eradicate infections with the harmful
bacteria Staphylococcus aureus in an animal model of the immune
disorder chronic granulomatous disease. Scientists supported by our
Institute have used a series of genetically engineered mice to identify
the contribution of different kidney cell subtypes to the process of
fibrosis that follows kidney injury, confirming myofibroblasts'
contribution to fibrosis and tracking their developmental origins--
results that could inform future treatment strategies. Scientists have
discovered a link between two proteins known to contribute to the most
common form of polycystic kidney disease and a cell-surface structure
in a subset of kidney cells in mice. NIDDK-supported researchers
conducted a study in mice showing that chemotherapy damages nerves that
regulate bone marrow niches responsible for making new blood cells;
future research in humans could explore ways to reduce nerve damage and
improve blood cell regeneration after chemotherapy. A new study has
shown that it may one day be possible to treat people with cystic
fibrosis (CF) using a combination of medicines that work cooperatively
to stabilize an aberrant form of CFTR, the protein that is defective in
CF.
NIDDK will continue support for basic research across the
Institute's mission, to gain further insights into health and disease
and propel new ideas for interventions. Areas of emerging opportunity
include research on generating or repairing nephrons that can function
within the kidney; diet-host microbiome interactions in autoimmune and
metabolic diseases; and a collaborative research network on disease
modeling and tissue repair and regeneration.
clinical science and precision medicine
Through innovative design and rigorous testing of interventions--
whether in the operating room, doctor's office, or home or community
settings--NIDDK-supported researchers are improving lives with new
approaches to prevent, treat, and reverse diseases and disorders. For
example, researchers studying type 1 diabetes have used smartphone
technology to move a step closer toward developing an artificial,
bionic, pancreas. Scientists reported data on insulin resistance and
secretion that suggest early and rapid deterioration of pancreatic beta
cell function in youth with type 2 diabetes, underscoring the need to
intervene early and aggressively. Researchers have found that patients
with irritable bowel syndrome show an improvement in symptoms following
a short course of group therapy involving psychological and educational
approaches. Recent research has shown that in dialysis patients with
diabetes, measuring another set of modified blood proteins may better
predict the risk of death and cardiovascular disease than the current
standard test to assess blood glucose control.
The NIDDK supports research aimed at tailoring treatments for
disease to the individual characteristics of each patient. For example,
a detailed genetic study has now identified rare mutations of the
SLC30A8 gene that sharply reduce risk for type 2 diabetes in several
different racial/ethnic populations, suggesting that inhibitors of the
Slc30A8 protein may one day be therapeutically valuable. New research
has greatly expanded knowledge of the specific genetic mutations
capable of causing CF, leading to much more comprehensive CF genetic
testing. A recently discovered set of mutations in the DGKE gene may be
behind some cases of the serious blood disorder hemolytic uremic
syndrome. Scientists participating in NIDDK's Childhood Liver Disease
Research and Education Network have utilized patient samples and an
animal model to identify a genetic deletion in the GPC1 gene that may
play a role in the development of biliary atresia. NIDDK researchers
have created and confirmed the accuracy of a mathematical model that
predicts how weight and body fat in children respond to adjustment in
diet and physical activity.
nurturing talent and innovation
NIDDK will continue programs to train and support researchers at
all stages of their careers, and to ensure that we benefit from the
best scientific minds. One major objective of the Network of Minority
Health Research Investigators is to encourage and facilitate
participation of members of underrepresented population groups and
others interested in minority health in the conduct of biomedical
research. In addition, several NIDDK-sponsored programs provide
opportunities for minority students to obtain research experience. The
NIDDK's Short-Term Education Program for Underrepresented Persons, or
STEP-UP, provides research education grants to seven institutions to
coordinate high school and undergraduate STEP-UP programs that enable
students to gain summer research experience and training.
integrating science-based information into practice
NIDDK also will continue to support education, outreach, and
awareness programs. Research clearly shows that communications alone
about the seriousness of diabetes will not reverse the diabetes
epidemic. The NIDDK is committed to focusing more efforts to promote
the theme of moving from awareness to action, by providing behavior
change tools and other resources to help people with diabetes and those
at risk make and sustain lifestyle changes. For example, the NIDDK-CDC
National Diabetes Education Program has developed the Diabetes
HealthSense Web site, an online library of tools and resources
developed by partners from around the country to address a wide array
of psychosocial and lifestyle challenges. The NIDDK's National Kidney
Disease Education Program (NKDEP) works to identify people with chronic
kidney disease (CKD) and promote the implementation of evidence-based
interventions, focusing on populations at highest risk for CKD and the
providers who serve them. In addition, through collaborative community
partnerships with organizations such as the Chi Eta Phi Nursing
Sorority and the American Diabetes Association, NKDEP brings NIH
science-based information to the grassroots.
In closing, NIDDK's future research investments will be guided by
five principles: maintain a vigorous investigator-initiated research
portfolio; support pivotal clinical studies and trials; preserve a
stable pool of new investigators; foster research training and
mentoring; and disseminate science-based knowledge through education
and outreach programs.
______
Prepared Statement of Paul A. Sieving, M.D., Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Eye Institute (NEI) of
the National Institutes of Health (NIH). The fiscal year 2015 budget
proposal is $675,168,000, which is $0.9 million more than the fiscal
year 2014 enacted level of $674,249,000. As the director of the NEI, it
is my privilege to report on the many research opportunities that exist
to reduce the burden of eye disease.
nei audacious goal initiative
Vision research is often on the cutting edge of biomedical
research, from the first successful gene therapy clinical trials that
restored some visual function in patients with an inherited form of
blindness, to clinical trials for macular degeneration using tissue
derived from embryonic stem cells, to a retinal electrical prosthesis,
approved this past year by the FDA, after years of development by
Second Site, a small business that received research support from both
NEI and the Department of Energy. NEI is now starting a new chapter in
its ambitious research agenda. I have launched a new initiative--The
NEI Audacious Goal Initiative in Vision Research and Blindness
Rehabilitation--to identify a groundbreaking long-term research goal
that will markedly improve prevention and treatment of common eye
diseases.
We started this effort over a year ago by soliciting audacious
ideas from scientists, stakeholders, patients, clinicians, and the
public through a Challenge Competition. After a thorough scientific
review of more than 500 submissions, we chose 10 winning entries, which
were presented and intensively discussed at the NEI Audacious Goals
Development Meeting last year. In May, I announced that the NEI
Audacious Goal will be to Regenerate Neurons and Neural Connections in
the Eye and Visual System. To kick start this initiative, we will soon
release funding opportunities focusing on different components of this
goal. Implementation of work toward the goal will include oversight,
guidance, and direction from non-governmental consultant experts.
This goal will focus on two types of retinal neuronal cells that
underpin many of the leading causes of visual impairment. One such
target is photoreceptor cells, the specialized neurons in the retina
that detect light and initiate the neural response. Blindness in some
diseases, such as retinitis pigmentosa, is a direct result of
photoreceptor cell death, whereas in other diseases such as diabetic
retinopathy or macular degeneration, damage elsewhere in the retina
indirectly causes photoreceptor cells to die.
Retinal ganglion cells (RGCs) are the second cell type targeted in
this program. These neurons reside in the retina but send long
projections (axons in the optic nerve) that connect to the brain. When
RGCs degenerate and die in diseases such as glaucoma and multiple
sclerosis, vision signals from the eye can't get to the brain. Two of
the primary scientific challenges of this initiative include protecting
newly regenerated cells from dying, and inducing them to form
appropriate neural connections in the brain. Success in achieving this
goal will not just revolutionize how we approach diseases in vision,
but all of neuroscience.
NEI is also a key contributor and participant in the President's
BRAIN initiative, which seeks to decode the brain, just as the Human
Genome Initiative decoded DNA. While NEI's Audacious Goal is
independent from the BRAIN initiative, the eye is the gateway to the
brain--it is the most accessible part of the central nervous system.
There is good opportunity for synergy between these exciting
initiatives.
new areas of emphasis
In the process of identifying our Audacious Goal, we also
identified two high-priority, complementary areas of emphasis, for
which we have released two funding opportunities and are currently
reviewing grant applications: Molecular Therapy for Eye Disease; and
the Intersection of Aging and Biological Mechanisms of Eye Disease.
With recent advances in genomics, we now have a good understanding of
genes and molecules that are altered in many diseases. The National
Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE), is a
critical resource created by NEI for identifying the mutated genes in
patients with inherited eye disorders and giving researchers access to
DNA samples (over 4,000 collected since 2006), clinical information,
and patients looking to participate in research studies. But the
current tools at our disposal to treat genetic diseases are limited.
Building on our recent successes in gene therapy, the exciting
potential of designing personalized therapies to correct mutant genes
lies in the research ahead of us over the next decade.
Many eye diseases are associated with aging: from cataracts and
presbyopia, which are common in all adults as they age, to some of the
leading vision impairment diseases, age-related macular degeneration
(AMD) and glaucoma. Understanding what aspects of the aging process
contribute to eye disease has the potential to delay the onset of
vision loss or even avert the disease.
nei regenerative medicine program
Also contributing to the Audacious Goal Initiative are researchers
at NEI, working with the NIH Center for Regenerative Medicine to create
retinal tissues from induced pluripotent stem (iPS) cells for several
basic and translational research applications. iPS cells can be
generated from any adult cell, and then converted into virtually any
other type of cells. A major thrust of this program is to derive iPS
cells from patients with retinal diseases. Then, the iPS cells are
differentiated to form retinal pigment epithelial (RPE) cells or
photoreceptors and studied to identify disease-causing molecular
pathways. Diseases of interest currently include AMD, Best disease,
late-onset retinal degeneration, Stargardt's disease, and retinitis
pigmentosa. This program is exploiting these techniques to develop
high-throughput drug screens to identify potential therapeutic
compounds for treating retinal degenerative diseases.
Another potentially powerful application of iPS cell technology is
to generate iPS cells from normal tissue and then differentiate those
cells into monolayer sheets of RPE for tissue transplants. NEI
intramural investigators are engineering a bio-degradable scaffold in
order to grow the RPE tissue and transfer it to patients with RPE-
associated retinal degenerative diseases. In fiscal year 2015, the stem
cell program will also use stem cell technologies to evaluate synaptic
connections in 3-D retinas derived from iPS cells.
As I reflect on the remarkable progress the vision community has
made in these past few years, I can hardly anticipate the exciting
opportunities that lay ahead.
______
Prepared Statement of Martha Somerman D.D.S., Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Dental and
Craniofacial Research (NIDCR) of the National Institutes of Health
(NIH). The fiscal year 2015 NIDCR budget of $397,131,000 includes an
increase of $29,000 over the enacted fiscal year 2014 level of
$397,102,000.
In keeping with its mission to improve the Nation's oral health,
the breadth of NIDCR's research touches the lives of nearly all
Americans. Our research spans multiple disciplines, scientific
approaches, and research directions, all focused on the goal of
improving people's lives. Today, I will highlight selected areas of
particular promise in our efforts to understand the development of
tissues of the face and head, conquer oral infectious diseases through
better understanding of the body's own defenses, help people facing
chronic orofacial pain conditions, and develop new approaches to
improve oral cancer survival.
development and regeneration
The human face is among the body's most distinctive structures.
NIDCR is the leading supporter of research on the development of the
human face and skull, collectively known as the craniofacial region. By
defining the complex web of environmental and genetic instructions that
drive craniofacial development, the hope is that scientists one day
will learn to repair damaged or malformed facial structures such as
cleft lip and palate by harnessing the body's ability to heal itself.
Five years ago, NIDCR began assembling information on the genetic
code that instructs facial development with the launch of its FaceBase
Consortium. Through this endeavor, scientists have assembled nearly 500
publicly available datasets involving the biological instructions for
the middle region of the human face, which includes the nose, upper
lip, and palate, or roof of the mouth. FaceBase begins a second phase
this year, as it expands its focus to include studies on additional
regions of the face. This new phase will add to our knowledge about the
genetics that underlie craniosynostosis, a birth skull defect that may
result in severe and permanent problems if not corrected.
NIDCR is also translating knowledge about craniofacial development
into tools to re-grow bone and cartilage damaged by disease or injury.
Ongoing studies are using the power of stem cells to regenerate
tissues, improve wound healing, and help control inflammatory-
associated diseases of the mouth. Related research uses specially
designed stable small molecules modified from naturally occurring
molecules called resolvins that control inflammation in a wide range of
conditions to target oral inflammatory diseases such as periodontitis.
We envision a future where natural tool kits are used to regenerate and
repair damaged teeth, diseased gums, and broken or defective bones by
utilizing stem cells and adapting natural molecules and processes.
oral infections, immunity and the microbiome
The NIH's human microbiome project has reinforced that no man is an
island. Although human beings coexist with a plethora of
microorganisms, microbial cells outnumber human cells by 10 to 1,
living on surfaces of our body in sticky layers of polymicrobial
communities called biofilms. Under normal circumstances, these
microbial guests coexist with us and even contribute to sustaining
human health. But, if conditions in some part of the body are altered,
the balance is disrupted, and the disease-causing organisms that live
on our gums and teeth can overwhelm our natural immune defense systems
causing oral infectious diseases such as tooth decay and periodontal
diseases. NIDCR-supported scientists are beginning to assemble the
precise molecular details of how select oral pathogens destabilize the
immune system to cause oral diseases. For example, individuals with
leukocyte adhesion deficiency (a rare genetic disorder affecting the
body's immune system) suffer from frequent bacterial infections,
including severe periodontitis. New research has demonstrated that
blocking certain molecules that are part of the individual's own immune
system can reverse this inflammation and resulting bone loss.
In combination with these discoveries, we have made great strides
in understanding how an individual's own microbiome affects his or her
health and disease. NIDCR continues to invest in microbiome research,
supporting a database of information on oral microbes that will one day
allow dentists to visualize the microbes within a patient's oral
biofilm in real time--offering new tools to diagnose and treat oral
disease. For example, a dentist might observe an overgrowth of a
particular type of bacteria that uniquely predisposes a patient to
tooth decay, and could treat that bacterial imbalance to prevent the
individual from developing cavities. These emerging leads will not only
guide future personalized dental treatment for millions of Americans;
they will help scientists throughout biomedical research to inform
better treatment approaches for other microbe-host diseases such as
colitis.
temporomandibular joint disorders
Thousands of Americans this year will be diagnosed with a painful
and debilitating disorder of the jaw called temporomandibular joint and
muscle disorder (TMD). Some of these individuals will recover after a
single bout of TMD, while others will go on to develop chronic
disease--and their healthcare providers, currently, are unable to
predict the likely outcome for any individual patient. NIDCR-supported
research is providing key insights that could identify people at risk
for developing TMD, and predict the likelihood of progression to
chronic disease. In 2006, NIDCR launched the Orofacial Pain:
Prospective Evaluation and Risk Assessment (OPPERA) study. The study's
latest findings present the most in-depth picture to date of the
factors that may contribute to a person's developing an initial bout of
painful TMD. Among the many interesting findings is that there is
almost no difference in the rate at which men and women develop TMD for
the first time. And yet, females are far more likely to progress to
chronic TMD than males. Researchers will continue to examine potential
causes of this difference, such as hormonal regulatory factors, leading
to more targeted strategies for detecting and managing TMD in the
future.
Although TMD specifically afflicts the jaw, OPPERA researchers
found only about 15 percent of OPPERA participants diagnosed with
chronic TMD have orofacial pain only. The other 85 percent have
additional ailments, many of which are painful in nature, including
chronic fatigue syndrome, fibromyalgia headache, and low back pain.
This finding demonstrates that first-onset and chronic TMD are complex
disorders that must be understood within a biological, psychological,
and social model of illness. NIDCR will continue to help lead the way
for all those battling these chronic conditions to find relief through
a more accurate diagnosis and more personalized care.
oral cancer and human papillomavirus (hpv)
When many people hear the acronym HPV, they think of its
association with cervical cancer. But over the last decade, various
types of this virus also have been shown to contribute to head and neck
cancers. In fact, the incidence of HPV-related head and neck cancer has
risen steadily over the last decade and if the pace continues, it will
soon surpass the incidence of cervical cancer. This trend is
particularly alarming because no effective diagnostic test currently
exists to detect early HPV-related head and neck cancer. Tools are
needed to screen those at increased risk of the condition and to test
for possible persistence of the condition following therapy.
NIDCR will help to fill this public health need by launching an
initiative to develop a viable diagnostic test. The initiative will
identify DNA markers associated with HPV-related head and neck cancer,
develop and validate saliva and plasma-based diagnostic tests, and
evaluate and test the biomarkers in humans. Clinical studies are also
ongoing to establish the safety and feasibility of administration of a
DNA vaccine in certain HPV-associated head and neck cancer patients.
NIDCR scientists recognize the urgency of developing innovative
approaches to detect oral cancer early, when personalized treatment can
be more successful, leading to better patient outcomes.
There has never been a better time to take advantage of the
remarkable opportunities in science and technology waiting at our
doorstep. Seizing this moment brings us closer to preventing and
treating dental, oral, and craniofacial conditions as well as other
diseases that share risk factors and therapeutic strategies.
______
Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the Office of the Director (OD) of
the National Institutes of Health (NIH). The fiscal year 2015 OD budget
of $1,451,786,000 includes an increase of $51,033,000 above the
comparable fiscal year 2014 level of $1,399,753,000.
The OD promotes and fosters NIH research and research training
efforts in the prevention and treatment of disease through the policy
oversight of both the extramural grant and contract award functions and
the Intramural Research program. The OD stimulates specific areas of
research to complement the ongoing efforts of the Institutes and
Centers through the activities of several cross-cutting program
offices. The OD also develops policies in response to emerging
scientific opportunities employing ethical and legal considerations;
provides oversight and management of peer review policies; coordinates
information technology across the Agency; and, coordinates the
communication of health information to the public and scientific
communities. Moreover, the OD provides the core management and
administrative services, such as budget and financial management,
personnel, property, and procurement services, ethics oversight, and
the administration of equal employment policies and practices.
The fiscal year 2015 request will also support activities managed
by the OD's operational offices. OD Operations is comprised of several
OD Offices that provide advice to the NIH Director, policy direction
and oversight to the NIH research community and administer centralized
support services essential to the NIH mission.
The functions and initiatives of the OD's research offices are
described in detail as follows:
division of program coordination, planning, and strategic initiatives
(dpcpsi)
DPCPSI provides leadership for identifying, reporting, and funding
trans-NIH research that represents important areas of emerging
scientific opportunities, rising public health challenges, or knowledge
gaps that merit further research and would benefit from collaboration
between two or more Institutes or Centers (ICs), or from strategic
coordination and planning.
The Division includes major programmatic offices that coordinate
and support research and activities related to HIV/AIDS, women's
health, behavioral and social sciences, disease prevention, dietary
supplements, research infrastructure, and science education. DPCPSI
serves as a resource for the ICs and the NIH Office of the Director for
portfolio analysis by developing, using, and disseminating data-driven
approaches and computational tools.
The fiscal year 2015 budget for DPCPSI, including the immediate
Office of the DPCPSI Director, the Offices of Portfolio Analysis and
Program Evaluation and Performance, and the Office of Strategic
Coordination is $11,138,000.
office of research infrastructure programs (orip)
ORIP provides support for a variety of research infrastructure
needs, including animal models and facilities; research models, human
biospecimens, and biological materials; training and career development
for veterinarians engaged in research; the acquisition of state-of-the-
art and shared and high-end instrumentation; and research resources
grants to expand, re-model, renovate, or alter existing research
facilities. The ORIP budget for fiscal year 2015 is $275,654,000.
science education partnership awards (sepa)
The goal of the Science Education Partnership Awards (SEPA) program
is to invest in educational activities that enhance the training of a
workforce to meet the Nation's biomedical, behavioral and clinical
research needs. The SEPA program encourages the development of
innovative educational activities for pre-kindergarten to grade 12 (P-
12), teachers and students from underserved communities with a focus on
Courses for Skills Development, Research Experiences, Mentoring
Activities, Curriculum or Methods Development or Informal Science
Education (ISE) exhibits, and Outreach activities. In fiscal year 2015,
the SEPA Program will be coordinated with the Department of Education
to ensure that program activities are aligned with ongoing P-12 reform
efforts included in the President's budget request. In fiscal year
2015, the budget for SEPAs is $18,541,000.
the office of aids research (oar)
OAR plays a unique role at NIH by serving as a model of trans-NIH
planning and management, vested with primary responsibility for
overseeing all NIH AIDS-related research. OAR coordinates the
scientific, budgetary, legislative, and policy elements of the NIH AIDS
research program. OAR's response to the AIDS epidemic requires a unique
and complex multi-institute, multi-disciplinary, global research
program. This diverse research portfolio demands an unprecedented level
of scientific coordination and management of research funds to identify
the highest priority areas of scientific opportunity, enhance
collaboration, minimize duplication, and ensure that precious research
dollars are invested effectively and efficiently, allowing NIH to
pursue a united research front against the global AIDS epidemic. The
fiscal year 2015 budget for OAR is $61,923,000.
the office of behavioral and social sciences research (obssr)
OBSSR furthers the mission of the NIH by emphasizing the critical
role that behavioral and social factors play in health, healthcare and
well-being. OBSSR serves as a liaison between NIH and the extramural
research communities, other Federal agencies, academic and scientific
societies, national voluntary health agencies, the media, and the
general public on matters pertaining to behavioral and social sciences
research. OBSSR's vision is to bring together the biomedical,
behavioral, and social science communities to work more collaboratively
to solve the pressing health challenges facing our Nation. OBSSR also
coordinates and helps support the NIH Basic Behavioral and Social
Science Opportunity Network, a trans-NIH initiative to expand the
agency's funding of basic behavioral and social sciences research. The
fiscal year 2015 budget for OBSSR is $26,094,000.
the office of research on women's health (orwh)
Since its creation in 1990, ORWH has worked to ensure the inclusion
of women in NIH clinical research, to advance and expand women's health
research, and to promote advancement of women in biomedical careers.
ORWH is the focal point for NIH women's health research and works in
partnership with the NIH ICs to incorporate a women's health and sex
differences research perspective into the NIH scientific framework.
ORWH activities are guided by the 2010 NIH Strategic Plan for Women's
Health Research. This strategic plan outlines six goals to maximize
impact of NIH research effort. The NIH strategic plan for women's
health and sex differences research serves as a framework for
interdisciplinary scientific approaches. The fiscal year 2015 budget
for ORWH is $40,903,000.
the office of disease prevention (odp)
The ODP is responsible for assessing, facilitating, and stimulating
research in disease prevention and health promotion, and disseminating
the results of this research to improve public health. Research on
disease prevention is an important part of the NIH mission because the
knowledge gained from this research leads to stronger clinical
practice, health policy, and community health programs. In early fiscal
year 2014, ODP released its first strategic plan. This plan outlines
the priorities that the Office will focus on over the next 5 years and
highlights the ODP's role in advancing prevention research at the NIH.
The fiscal year 2013 budget for ODP is $5,861,000. The Office of
Dietary Supplements (ODS) is within the ODP organizational structure.
The mission of the ODS is to strengthen knowledge and understanding of
dietary supplements by evaluating scientific information, stimulating
and supporting research, disseminating research results, and educating
the public to foster an enhanced quality of life and health for the
U.S. population. The fiscal year 2015 budget for ODS is $26,786,000.
the office of strategic coordination (osc) and the common fund
OSC oversees the management of the Common Fund (CF), working with
trans-NIH teams for each of the more than 30 Common Fund programs.
These teams ensure that each program meets the criteria of Common Fund
programs to synergize with IC funded research. The NIH CF was created
by the 2006 NIH Reform Act which codified the approach of the NIH
Roadmap for Medical Research to support cross-cutting, trans-NIH
programs that require participation by at least two NIH ICs or would
otherwise benefit from strategic planning and coordination. CF programs
tackle major challenges in biomedical research that affect many
diseases or conditions or that broadly relate to human health. The CF
provides limited-term funding for goal-driven, coordinated research
networks to generate data, solve technological problems, and/or pilot
resources and tools that will stimulate the broader research community.
The fiscal year 2015 budget for the Common Fund is $583,039,000.
loan repayment and scholarship programs
The mission of the NIH Intramural Loan Repayment Programs is to
seek to recruit and retain highly qualified physicians, dentists, and
other health professionals with doctoral-level degrees. These programs
offer financial incentives and other benefits to attract highly
qualified physicians, nurses, and scientists into careers in
biomedical, behavioral, and clinical research as employees of the NIH.
The Undergraduate Scholarship Programs (UGSP) offers competitive
scholarships to exceptional college students from disadvantaged
backgrounds that are committed to biomedical, behavioral, and social
science health-related research careers at the NIH. The fiscal year
2015 budget for ILRSP is $7,145,000.
I am happy to answer any questions you may have about the OD's
programs and activities as well as our plans for the upcoming year.
______
Prepared Statement of Nora D. Volkow, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2015 President's budget request for the National
Institute on Drug Abuse (NIDA). The fiscal year 2015 budget request for
NIDA is $1,023,268,000, which reflects an increase of $7,514,000 over
the fiscal year 2014 level of $1,015,754,000.
The impact of substance abuse in this country is daunting; the
economic toll alone exceeds $700 billion \1\ a year in healthcare,
crime-related, and productivity losses. NIDA strives to translate the
returns of its investments in genetics, neuroscience, pharmacotherapy,
and behavioral and health services research into new strategies for
preventing and treating substance abuse and addiction. This scientific
investment is crucial if we are to tackle rapidly evolving public
health threats such as the increase in marijuana use among young people
and the growing prevalence of opioid addiction and overdose deaths.
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\1\ U.S.DHHS. The Health Consequences of Smoking--50 Years of
Progress: A Report of the Surgeon General. Atlanta, GA, CDCP, National
Center for Chronic Disease Prevention and Health Promotion, Office on
Smoking and Health, 2014; Rehm J, Mathers C, Popova S,
Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of
disease and injury and economic cost attributable to alcohol use and
alcohol-use disorders. Lancet. 2009 Jun 27;373(9682):2223-33; National
Drug Intelligence Center (2010). National Threat Assessment: The
Economic Impact of Illicit Drug Use on American Society. Washington,
DC: United States Department of Justice.
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today's basic science for tomorrow's breakthroughs
There is a fundamental need to understand the complex steps of how
body chemistry influences behavior and how their disruption can lead to
addiction. A more detailed and personalized account of these steps will
lead to a more effective and precise medicine to prevent and treat this
complex brain disorder.
In this context, and thanks to recent technological developments,
we've made important advances in linking genes with behavior. As a
result, we now have an unprecedented capacity to screen for thousands
of genetic variations and catalogue how they modulate abuse/addiction
risk by influencing brain maturation, its neural architecture, and
behavioral patterns. NIDA researchers are also pursuing genome and
whole individual sequence analysis to identify genes that modulate
addiction risk (e.g., genes that regulate drug metabolism), advancing
their understanding of how environmental factors (e.g., parental style,
drug exposure) can affect the expression of those genes to either
strengthen or weaken behavioral patterns through epigenetic changes.
The systematic identification of genetic, environmental, and
neurocircuitry variations that modulate abuse/addiction risk will
revolutionize our prevention and treatment capacities.
big opportunities in big data
Big data sets are essential platforms for the analysis of complex
systems in genetics and epigenetics, proteomics, brain imaging and
clinical science. Vast amounts of data are being produced by the
overlaying of structural and functional brain imaging information that
links the molecular and cellular data with the expression of higher
level brain function. A prime example is the new fMRI-based approach to
generating images of the functional connectivity (FC) among brain
regions in the absence of any specific task, so called resting state
(rs) FC. This technique offers a powerful window into circuit-level
functions that may generate behavioral responses underlying
vulnerability or a diseased state. Open access to such massive
databases could lead to the identification of biomarkers of psychiatric
illness risk including addiction, their trajectories, and treatment
responses that could be translated for clinical use and the optimal
management of patients.
Similarly, NIDA is funding the development of an open source, open
framework, free National Pain Registry that collects patient
demographic and treatment information from around the Nation. This
information can be used to identify which pain management interventions
are most effective for specific chronic pain patients and predict which
patients might be at higher risk for opioid addiction. Combined with
concerted efforts in the pharmacogenomics of prescription opioids, pain
registries are poised to help us maximize the effectiveness of pain
treatments while minimizing the likelihood of prescription opioid abuse
and addiction.
nurturing talent and innovation
NIDA currently supports a great deal of innovative research on drug
addiction and related health problems such as pain and HIV/AIDS and
will continue to be at the forefront of training the next generation of
innovative researchers. The 6-year old Avant-Garde award is a good
example of a program that stimulates high--impact research that could
lead to groundbreaking opportunities for the prevention and treatment
of HIV/AIDS in substance users. NIDA is now crafting a new kind of
award, which blends NIH's Pioneer and New Innovator award mechanisms.
This new opportunity, called the ``AVENIR'' award, is designed to
attract creative young investigators to genetic research on substance
use disorders and HIV/drug abuse research. Another example is NIDA's
Cutting-Edge Basic Research Awards (CEBRA), designed to foster highly
innovative or conceptually creative research that advances our
understanding of drug abuse and addiction. The latest results of this
effort include three independent studies exploring the potential
benefits of neurofeedback training, transcranial magnetic stimulation,
and meditation on facilitating smoking cessation.
better pain management: a major goal of addiction research
Pain management is an important component of high-quality,
compassionate medical care. Opioid analgesics are among the most
effective medications for the management of severe pain and frequently
used for pain treatment. Unfortunately, the benefits of long term
opioid analgesic treatment are accompanied by significant risk of
developing drug tolerance (and the need for escalating doses) and
hyperalgesia (increased pain sensitivity). Exposure to potentially
rewarding substances, like opioid analgesics, may reinforce drug taking
behavior for persons with risk factors for addiction and trigger
relapse in those that are in recovery. These are intrinsic liabilities
of opioid analgesics that clearly increase the risk for diversion,
abuse, addiction and overdose.
NIDA recognizes it has a critical role in ensuring the availability
of safe and efficacious chronic pain management options while
minimizing risk of abuse. This is why we are committed to supporting
research to better predict who is at risk of addiction and to develop
new classes of effective, non-addicting pain medications. Parallel to
these efforts, NIDA is proactively pursuing methods to minimize the
risk of overdose with existing medications. For example, NIDA and
Lightlake Therapeutics Inc. have partnered to develop an intranasal
delivery system of naloxone (an opioid receptor blocker that can
rapidly reverse the overdose of prescription and illicit opioids),
which could greatly expand its availability and use in preventing
opioid-related deaths, a public health problem of epidemic proportion
in the U.S.
health consequences of marijuana use
There is a dangerous and growing misperception that marijuana use
is harmless, resulting in its status as the most commonly used illicit
drug in the United States with about 12 percent of people aged 12 and
over reporting use in the past year.\2\ Marijuana use has been
associated with significant adverse effects, including addiction,
cognitive impairment and car accidents. The key to minimizing negative
outcomes lies with the intensification of our efforts to educate the
public about the dangers of marijuana use and, with the deployment of
multipronged, evidence-based strategies to prevent and treat the abuse
of and addiction to marijuana and other drugs. To meet this challenge,
NIDA has released several funding announcements to encourage research
on the impact of changing marijuana policies; and, in partnership with
other NIH institutes, is planning a large-scale, prospective study that
follows children prior to drug use into early adulthood to determine
whether and how marijuana and other commonly used substances (e.g.,
alcohol, tobacco) affect the developing brain.
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\2\ Substance Abuse and Mental Health Services Administration,
Results from the 2012 National Survey on Drug Use and Health: Summary
of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-
4795. Rockville, MD: Substance Abuse and Mental Health Services
Administration, 2013.
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medications development
Our current approaches to develop next-generation pharmaceuticals
take advantage of new technologies using immunotherapeutic or biologic
(e.g., bioengineered enzymes) approaches for treating addiction. The
goal is to develop safe and effective vaccines or antibodies that
target specific drugs, like nicotine, cocaine, and heroin, or drug
combinations. If successful, immunotherapies--alone or in combination
with other medications, behavioral treatments, or enzymatic
approaches--stand to revolutionize how we treat, and maybe even someday
prevent addiction.
conclusion
The field of addiction research continues to benefit from the
explosion in genetic knowledge, the advent of precise technologies to
probe neuronal circuits, and the emergence of openly accessible big
data platforms. NIDA's research is strategically poised to take full
advantage of these and other emerging opportunities to develop the
knowledge base that can be used to reduce drug use in this country.
______
Prepared Statement of Jack Whitescarver, Ph.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for fiscal year 2015 for the trans-NIH
AIDS research program, which is $3,004,973,000. This amount is
$19,882,000 above the fiscal year 2014 enacted level of $2,985,091,000.
The authorizing law requires that the Office of AIDS Research (OAR)
function as ``an institute without walls'' and allocate all dollars
associated with this area of research across the NIH. Therefore, the
total for AIDS research includes both extramural and intramural
research (including research management support, management fund, and
service and supply fund), buildings and facilities, training, and
evaluation, as well as research on the many HIV-associated co-
infections and co-morbidities, including TB, hepatitis C, and HIV-
associated cancers. It also includes all of the basic science
underlying this research. Other disease areas are not reported this
way. Therefore the total for AIDS-related research is not comparable to
spending reported for other individual diseases.
nih aids research accomplishments
In the three decades since AIDS was first reported, NIH continues
to be the global leader in research on HIV and its many related
conditions. New avenues for discovery have been identified, providing
possibilities for the development of new strategies to prevent, treat,
and potentially cure HIV. Recent accomplishments include:
--Development of new treatments for many HIV-associated co-
infections, co-morbidities, malignancies, and clinical
manifestations;
--Development of new strategies for the prevention of mother-to-child
transmission;
--Demonstration of the first proof of concept that a vaccine can
prevent HIV infection and identification of potential immune
markers for protection;
--Discovery of more than 20 potent human antibodies that can stop up
to 95 percent of known global HIV strains from infecting human
cells in the laboratory;
--Demonstration that the use of antiretroviral therapy by infected
individuals can dramatically reduce HIV transmission to an
uninfected partner; and that the use of antiretroviral drugs by
uninfected individuals can reduce their risk of HIV
acquisition;
--Discovery that genetic variants may play a role in enabling some
individuals, known as ``elite controllers,'' to control HIV
infection without therapy; and
--Advances in basic and treatment research aimed at eliminating viral
reservoirs in the body that for the first time are leading
scientists to design and conduct research aimed at a cure for
HIV/AIDS.
In just the past several months, NIH intramural and extramural
researchers have produced a number of exciting new advances. NIH
researchers published the results of studies utilizing potent human
neutralizing antibodies that successfully suppressed a form of HIV in
primates. This important research could potentially result in a new
form of treatment for HIV that could be used as an adjunct to
antiretroviral therapy and could lead to opportunities for novel
research to treat and potentially cure HIV. NIH-sponsored researchers
also have made tremendous strides in producing and analyzing proteins
that may provide an important new pathway in AIDS vaccine design.
A team of NIH-funded investigators recently reported the first case
of a newborn in Mississippi who was ``functionally cured'' of HIV
infection. The infant received antiretroviral therapy immediately after
being diagnosed at birth but was then lost to follow-up and treatment.
The now nearly three year-old child has re-entered care with no
indication of HIV disease and no detectable virus in the absence of
therapy. Additional studies are under way to better understand this
case and may lead to clinical trials to see whether a similar approach
could be used to achieve a ``functional cure'' for other HIV-infected
newborns. NIH is leading global research efforts to capitalize on all
of these advances, move science forward, and begin to turn the tide
against this pandemic.
the aids pandemic
Despite this progress, the HIV/AIDS pandemic will remain the most
serious global public health crisis of our time until better, more
effective, and affordable prevention and treatment regimens--and
eventually a cure--are developed and available around the world. UNAIDS
reports that in 2012, more than 35 million people were estimated to be
living with HIV/AIDS; 2.3 million were newly infected (half of them
women); and 1.6 million people died of AIDS-related illnesses.
In the United States, HIV/AIDS continues to be an unrelenting
public health crisis, disproportionately affecting racial and ethnic
populations, women of color, young adults, and men who have sex with
men. The Centers for Disease Control and Prevention estimates that
approximately 1.1 million people are HIV-infected; approximately 50,300
new infections occur each year; and one in four people living with HIV
infection in the U.S. is female.
coordinated trans-nih aids research program
The NIH AIDS research program is coordinated and managed by the
OAR, and carried out by nearly every NIH Institute and Center (IC).
Through its unique trans-NIH planning, budget, and portfolio review
processes, OAR identifies the highest priority areas of scientific
opportunity and ensures that precious research dollars are invested
effectively. Scientific priorities for AIDS research are constantly
reassessed and reflected in the budget. The annual trans-NIH AIDS
strategic plan, developed by OAR in collaboration with both government
and non-government experts, guides the development of the trans-NIH
AIDS research budget. Each year, the state of the science is reviewed,
newly emerged and critical public health needs are assessed, and
scientific opportunities are identified. This annual process culminates
with the identification of the highest strategic priorities and
critical research needs. OAR develops each IC's AIDS research
allocation based on the Plan, scientific opportunities, and the IC's
capacity to absorb and expend resources for the most meritorious
science----not on a formula. This process reduces redundancy and
ensures cross-Institute collaboration. The fiscal year 2015 budget
request reflects the priorities of the fiscal year 2015 strategic
planning process.
aids research priorities and opportunities
The advances made by NIH investigators have opened doors for new
and exciting research opportunities to answer key scientific questions
that remain in the search for strategies to prevent and treat HIV
infection both in the United States and around the world. The fiscal
year 2015 budget priorities are:
--Basic research that will underpin further development of critically
needed prevention methodologies, including vaccines;
--Innovative multi-disciplinary research and international
collaborations to develop novel approaches and strategies to
eliminate viral reservoirs that could lead toward a cure for
HIV;
--Research to develop better, less toxic treatments and to
investigate how genetic determinants, sex, gender, race, age,
nutritional status, treatment during pregnancy, and other
factors interact to affect treatment success or failure and/or
disease progression; and
--Studies to address the increased incidence of co-morbidities,
including AIDS-associated malignancies; cardiovascular,
neurological and metabolic complications; and premature aging
associated with long-term HIV disease and antiretroviral
treatment.
summary
The NIH investment in AIDS research has produced groundbreaking
scientific advances that have benefited not only patients with HIV, but
those with other diseases as well. For example, the development of
protease inhibitors to treat HIV has led to development of a new drug
combination that can cure hepatitis C, which affects about 150 million
people globally. That advance in hepatitis C research may, in turn,
provide important knowledge toward an HIV cure. Drugs developed to
treat HIV-associated opportunistic infections are benefiting the more
than 28,000 Americans who receive an organ transplant each year.
Research on HIV-associated neurologic and cognitive manifestations
ultimately will benefit millions of patients with Alzheimer's disease
and other aging and dementia issues.
Despite these advances, however, AIDS is not over, and it is far
too soon to declare victory. Serious challenges lie ahead. The HIV/AIDS
pandemic will remain the most critical public health crisis of our time
until improved and affordable prevention and treatment regimens are
developed and universally available. NIH will continue to search for
critical solutions to prevent, treat, and eventually cure AIDS.
Thank you for your continued support for these efforts.
Senator Harkin. Thank you very much, Dr. Collins. We will
start a round now of 5-minute questions. As I said at the NIH,
I have never come away from a conversation or listening to you,
Dr. Collins, without being more enlightened and more hopeful
about the future. I like that ``National Institutes of Hope.''
Let me just ask you a question about the BRAIN Initiative,
if I can start with that. I have got two or three questions on
the BRAIN Initiative. Paint for me a picture of how you see the
research going ahead in the BRAIN Initiative. And we have some
partners, four outside partners, right now that are also
putting money into this, and you have an advisory group from
DARPA (Defense Advanced Research Projects Agency) and NSF
(National Science Foundation). Paint for me the picture of how
you see this developing in the next 2, 3, 4, 5 years. And sort
of what do we hope to get from this?
BRAIN INITIATIVE
Dr. Collins. Well, we are enormously excited about this,
and I am going to ask my colleague, Story Landis, who is a
major leader at NIH in the BRAIN Initiative, to say a word. But
just very briefly from my perspective, this is one of those
moments that comes along once in a long time where the
technology to be able to tackle a truly important problem,
understanding how the circuits in the human brain work, has
arrived at the point where we have this kind of push, bringing
disciplines together that have not necessarily found each
other, and making this a priority. We believe we can transform
our understanding of this incredible organ with its 86 billion
neurons, each of which has maybe a thousand connections. But,
Story, say where we are and where we are going.
Dr. Landis. So we are very excited about the opportunity to
really understand how neural circuits in the human brain work--
86 billion neurons, each of which are connected in complicated
circuits and pathways that process information, that allow us
to see an image and interpret it, to hear words and understand
what they mean, to remember, to reason.
We have some understanding now of how those 86 billion
neurons are organized into circuits, but we do not nearly have
enough detail, and we do not know enough about how information
is processed. And the goal of the BRAIN Initiative in the first
five or so years is to really develop the tools that will allow
us to probe those questions. There will be early on potential
opportunities to translate to disease, and I could give you
some examples if you would like.
Senator Harkin. Let me ask you this, Dr. Landis. Are you
working with the National Institute on Aging? Is there any
connectivity between the BRAIN Initiative and Alzheimer's
research?
Dr. Landis. Absolutely, although the understanding that we
will gain from the BRAIN Initiative will then be applied to
understanding how circuits are perturbed in Alzheimer's.
Alzheimer's disease nerve cells die. We would like to prevent
that death, but in the absence of tools yet to do that, the
circuits reorganize when cells are lost. And the BRAIN
Initiative will give us a better understanding of why that
reorganization occurs and how we can potentially use the
neurons that remain to have much more function.
Senator Harkin. Well, I asked that because, you know, we
have a lot of things confronting us in the future. I will get
to Dr. Varmus and cancer. But if we do not do something about
Alzheimer's, that is a tsunami that is going to hit us big
time. And so I just really wanted to get that on the record
that the money that we are putting into the BRAIN program,
BRAIN research program, also has a connectivity to Alzheimer's
research.
Dr. Landis. Absolutely.
Senator Harkin. Okay.
Dr. Collins. Think of the BRAIN Project as a foundation for
all neurological diseases, just like the Genome Project was a
foundation for all genetic diseases. It lifts all of those
boats of research to go higher and faster.
Senator Harkin. Sure.
Dr. Landis. And psychiatric diseases and drug abuse, all
the brain disorders.
FUTURE OF CANCER RESEARCH
Senator Harkin. Exactly. Dr. Varmus, again, I would be
remiss if I did not thank you for a lifetime of devotion and
dedication to biomedical research, stewardship of the NIH for a
lot of the time I was either chairman or ranking member. And it
is good to have you back as the head of the National Cancer
Institute.
Here is my question: What excites you the most right now?
In all of cancer research and stuff, what is it that gets you
up in the morning right now that you are looking ahead to do?
Dr. Varmus. Thank you. And before I give you a brief answer
to that question, let me first of all compliment you on your
service. You and I have been facing each other across the dais
like this for 20 years off and on, and I have always admired
your passion, your commitment to the NIH, your honesty. And
even on those rare occasions when we disagreed on a few issues,
we have had a collegial and constructive relationship. And your
departure from this Congress is a heavy blow to the NIH and to
its supporters.
Senator Harkin. I appreciate that.
Dr. Varmus. What most excites me at the moment is the deep
intellectual understanding we have about how cancer arises and
how the body tries to respond to it. And the connection between
basic science and its very near apposition to what we can do
practically is thrilling.
Over 40 years ago, I have to confess when I began doing
cancer research, the application of what we were trying to
learn with chicken viruses and mouse viruses was very far away.
Today we use tools of genomics and immunology and biochemistry
in a way that is very closely connected to what we are doing in
the clinic. So when we discover a new gene that is involved in
cancer, it is not long before we find some drug, perhaps an
existing drug, that can be applied to patients whose tumors are
being analyzed with the instruments of genomics to identify
exactly what is wrong with that cancer, and to carry out in a
precise fashion a clinical trial that is designed in entirely
new ways.
Similarly, we have learned from basic immunology the kind
of thing that Dr. Collins just illustrated is also being
applied in immediate ways to try to interfere with the breaks
on the immune system that have kept the immune system from
attacking cancer cells.
Senator Harkin. My time has run out, but I will have a
follow-up on that on immunotherapy and Dr. Rosenberg and what
he is doing out there. Okay.
Senator Moran.
ALZHEIMER'S DISEASE
Senator Moran. Mr. Chairman, thank you very much. Dr.
Collins, Dr. Landis, and others, thank you very much for
attending the recent hearing we had in regard to Alzheimer's in
particular. Several members asked that day if we would reach
the goal of a cure for Alzheimer's by 2025 and how much money
it would take to do so.
I understand how difficult it must be to quantify such an
answer, but I think it is important for us to know if our
Alzheimer's research funding is on track. Therefore, I am
looking for your professional opinion or opinions as to how
much money does NIH need in fiscal year 2015 to keep pace with
the goal of a cure for Alzheimer's by 2025.
Dr. Collins. Well, thanks for the question, Senator, and
that was an excellent hearing that was held by this
subcommittee. And we had a great opportunity there to look at
the challenge and also the scientific opportunities, which are
really coming forward in very exciting ways, recognizing that
the challenge here in terms of both the economic and human cost
of this disease can hardly be overstated.
As you have pointed out, we have an action plan for
Alzheimer's disease, part of the legislation that put in place
this project--plan. And the National Institute on Aging,
directed by Dr. Hodes, has been deeply engaged in that, running
a research summit at NIH, and polling the entire community
about where the research opportunities would be. It is
wonderful that in fiscal year 2014, largely due to this
subcommittee's efforts, $100 million has been appropriated for
the National Institute on Aging, the bulk of which will be put
into promising Alzheimer's research.
I have looked carefully at the way in which the Alzheimer's
plan maps across the various years. As you know, science tends
not to operate in 1 year intervals. Many of the components of
the plan are more in a 3-year kind of timetable. I could show
you a Gantt chart that goes on for many pages about how each of
these components might start and hopefully reach a milestone.
It is very difficult, though, with all the multiyear aspect
of this to say, well, what do we need exactly in fiscal year
2015? And I have sort of tried with Dr. Hodes to come up with
that kind of estimate, and I am afraid it would not be a
reliable one. Part of that is, of course, we do not have the
ability in science to know exactly what is going to happen next
month or the month after that. And a lot of the research in
Alzheimer's is being developed by investigators out there in
our wonderful brain trust, the universities that are doing this
research. And we might wake up tomorrow and find that something
has happened that completely changes the direction we want to
go. So while this plan is a good one to work with, it will
undoubtedly evolve over time.
So I know I am sounding like I am not giving you an answer,
and I guess I am trying to say I think to put a dollar figure
right now on fiscal year 2015 would be to overstate what I
really can predict to be necessary for this purpose. Again, we
are thrilled with $100 million in 2014. We were delighted to
see in the President's Opportunity, Growth, and Security
Initiative another $100 million would come to Alzheimer's
disease should that become possible.
Senator Moran. You have the capability, Dr. Collins, I
assume, of telling us or telling me that the $100 million in
fiscal year 2014 was not too much.
Dr. Collins. It was not too much. You are quite right about
that. And, you know, you are asking about Alzheimer's. You
could be asking about many other areas of NIH research as well,
and I would tell you we do not have too much money to work on
anything that we are working on. We are not limited by ideas.
We are limited by resources, whether it is cancer, infectious
disease, heart disease, whatever. That is our current state.
Senator Moran. Doctor, let me take this question in a
broader step. But first let me say that my expectation would be
as those scientific developments occur, a reason that we should
have the kind of hearings that we have on an ongoing basis is
so that you can then come to us and say this development has
happened in some university in the country or here at NIH. And,
therefore, if you would invest additional dollars in this area,
we believe we can advance the outcomes more quickly.
And so, my continued effort, I think, will be to try to get
you to help us prioritize spending based upon science, based
upon success in research where we ought to put the dollars that
we have to allocate within the 27 Institutes and Centers that
you and NIH engage in.
Dr. Collins. Senator, I would welcome those kinds of
conversations at any time, and appreciate your leadership in
that kind of planning process.
DISEASE SPECIFIC FUNDING
Senator Moran. I have 28 seconds left for a follow-up
question, which is this: You have--you, NIH--has historically
opposed disease-specific funding. You want the allocations to
occur based upon science, not on politics, and I certainly
share that goal. If we are underfunding in an area of
research--if we start with low funding in a particular area of
research, it is harder to have the developments that then allow
you to come to us and say we have had a breakthrough, we need
more. We need to accelerate the funding of that research.
How are you--I mean, can you give me examples--I do not
have the history that Senator Harkin has, but does it happen
from time to time in which you come to Congress and say we need
to prioritize the research in this area, and are you willing
then to tell us that we reduced the priority someplace else?
How do we ever get into the circumstance in which any of us are
willing to say our money should go into this basket, knowing
that it is not infinite? The money has to come out of some
other basket.
Dr. Collins. Well, again, I appreciate the question. And
this is the kind of conversation we have around the table at
NIH all the time with the 27 Institute and Center directors,
each of whom has a strategic plan that they are constantly
refreshing and revising.
The good news is that the boundaries between those
institutes are very porous. And if we collectively identify an
opportunity that demands additional investments in a particular
direction, we often can figure out how to do that without
having to go through a long lead time to try to adjust a future
year's budget. And we are quite capable of doing so.
And increasingly, that is a good thing because the next
breakthrough in cancer might come from the Diabetes Institute,
and the next breakthrough in infectious disease might come from
the Center that is looking at translational sciences. So we are
really, more than we ever have been, a unit, a whole here that
thinks about biomedical research collectively, not in a series
of buckets.
Senator Moran. Thank you very much.
Senator Harkin. Thank you, Senator Moran. And our
distinguished Chair of the entire Appropriations Committee, who
happens to have a real interest in NIH, I can tell you that.
Senator Mikulski.
Senator Mikulski. Thank you very much, Senator Harkin, and
we are so glad that you are holding this hearing. And I think
it shows the significance of the way we think about the
National Institutes of Health, which we all affectionately and
with great admiration do call the National Institutes of Hope.
The fact that Senator Shelby is here, the vice chairman of the
Appropriations, and myself shows our commitment to really
trying to make sure that NIH has the resources it needs to
continue to be the premiere global agency for biomedical
research, and to do it on a bipartisan basis.
I know you spoke earlier, if I could. You were kind of
emotional about this hearing, and I am emotional about this
hearing for you. I recall coming to the United States Senate. I
was sworn in 1987, working with then the beloved Nancy
Kassebaum, you, and Ted Kennedy, when women were not even
included in the protocols, many of the research things, at NIH.
There were many reasons. Many were just flawed sociology rather
than good biology.
Imagine in those years when we were not even included, and
then we advocated for the Office of Women's Health. The funding
then for breast cancer was quite spartan and skimpy. Again, we
turned to you. And then as we made steady advances, George
Herbert Walker Bush appointed Bernadine Healy to be the head of
NIH. Dr. Healy also reached out again to us to ask us to look
for a famous longitudinal study on hormone therapy. That
hormone therapy study resulted in the change in the way
hormones are treated in terms of hormone therapy for women, and
it resulted in breast cancer coming down by 15 percent.
I recall with great emotion my last call with Bernadine
Healy, and this is what she said. I called her, and there was
an article in the New York Times, Dr. Varmus, that said breast
cancer rates have come down 15 percent. And I said, ``My god,
Bernadine, can you believe that?'' She said, ``Yes, Barbara.
Can you believe because we worked together we are saving lives
a million at a time?''
That is what we are trying to do here with this hearing. We
are trying to look at these issues. And I am going to say to
you, Senator Harkin, the Catholic nuns had a phrase when they
taught people like me. They had a phrase in Latin called
``exegi monumentum aere perennius aedificabo.'' It means we
will build a monument more lasting than bronze. I feel our
monument to you, to both you, to Senator Specter, to Bill
Frist, Ted Kennedy, is the way we walked across the aisle is to
build a monument more lasting than bronze, and that is to make
a significant public investment this year in the National
Institutes of Health to get it right back on track to where it
was, and to have a steady growth plan of action so that at the
end of the day, at the end of the year, at the end of our
terms, we know that we have been working together to save lives
a million at a time. So I want to just shake your hand and
thank you. And, Moran, you are from Kansas.
Senator Moran. Yes.
Senator Mikulski. You know what Nancy did shoulder to
shoulder here. Senator Shelby has been a great advocate.
I have many questions that I am going to ask. We could hold
a hearing on each and every one of those people--distinguished
people here. We are lucky to have them. Their combined years of
service are stunning. Many of them at this table could be in
such lucrative careers in the private sector.
I remember working with Dr. Fauci when there was this
unknown disease in which men were dying all over the country.
It was called AIDS. A little boy named Ryan White came here
with his mother when he had been targeted by his classmates for
taunts and isolation. Now look at where we are. We could take
item after item, issue after issue, and it really shows what we
need to do.
So we need to not only fund the research, we need to
support the people who do the research. And to those young
people out there right now thinking about careers that there is
hope in trying to find cures to give people hope. And so, this
is where we really need to work on a bipartisan basis, hands
across the aisle, hands across the dome. And I think we can
make a significant difference. So we want to help build a
monument more lasting than bronze.
I yield back my time.
Senator Harkin. Thank you very much. That was a very
poignant statement, and I thank you for that. The only thing I
would add is we have to come to grips with the funding, and I
am open for any and all suggestions.
Senator Mikulski. I know we are all going to get into this.
Senator Harkin. I just met yesterday with a couple of
people who had an interesting idea on funding for translational
science. Gordon Gund and Karen Petrou from the Foundation for
Fighting Blindness have come up with--I do not need to go into
that now, but there are ideas being spawned out there on how we
might raise more money for NIH. So anybody that has got
suggestions, we need to keep looking.
PREFERRED METHOD OF FUNDING
Senator Mikulski. And, Mr. Chairman, if I could, if Dr.
Collins could comment. We had a great hearing on Alzheimer's,
and also that is an epidemic in our country, as is autism,
quite frankly. And again, many here could comment on it. And
then there are those things that seem benign and not too scary,
but then along comes flu. But when we look at the ``A'' words--
autism--there was talk of, like, do we need, like, a Manhattan
Project.
And I wonder to Dr. Collins and the esteemed panel, what is
it that is the best thing for NIH, sustained, steady growth
with kind of an agreement across the aisle and across the dome
of steady increases to the way we had the concept of--I
understand if we added--kept pace with inflation at 3 percent,
and then another 5 percent, we could get to almost doubling
NIH--we do not want to use that phrase anymore--to $40 billion.
Is that better rather than a concentrated big buck expenditure
on one particular area for----
Dr. Collins. I really appreciate the question. And I wanted
to show you a graph----
[The graph follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Senator Mikulski. In other words, does the idea of a
Manhattan like project really have efficacy, or does it sound
good, but----
Dr. Collins. What you see on the screen here is the
projection over the past years since 1990 of the NIH support
corrected for inflation because we have to deal with that. That
is the yellow line. You see the blue bar is there for the
Recovery Act, those 2 years of an increment which helped with
sort of pent-up need.
But notice the doubling, which happened there between 1998
and 2003, then encountered essentially flat budgets, which
inflation has eroded ever since. And you can see interestingly,
the dotted line is the trajectory we were on before the
doubling, which if you go back to 1970, we were on a period of
about 3.7-percent annual growth. If we had stayed on that
steady trajectory, we would now be $10 billion almost higher
than we are. Very interesting to sort of contemplate this.
Now, the doubling was wonderful. The doubling did huge
things for biomedical research. But what came after has been
really quite painful. And to answer Senator Mikulski's
question, the worst thing you can do, I think, to biomedical
research is to create an area of uncertainty, of ups and down,
of a roller coaster. Science operates not as a spring, but a
marathon. You need confidence that there is going to be support
there so that young scientists can tackle really innovative
risky projects. And this up and down circumstance now hitting
historic lows in terms of opportunities to get support is
really quite damaging.
And what would be vastly better, Senator, would be for us
to be able to count on a more or less stable trajectory of
inflation plus some percentage that you could be fairly
confident was going to be maintained. I understand how hard
that is in the current fiscal situation, but if you are asking
my judgment about what NIH needs in order to flourish and in
order to contribute to this Nation what we think we can
contribute and to the world, that would be it, that kind of
steady trajectory that you could be confident in.
Senator Harkin. Thank you, Dr. Collins. Senator Shelby, our
ranking member of the entire committee. Used to be the ranking
member of this subcommittee.
Senator Shelby. Thank you. Thank you, Chairman Harkin, and
thank you for all your service here and advocacy for NIH. I
believe as a veteran member of the Appropriations Committee
looking at all the aspects of the various requests for money
that the NIH, I think, by far is the best investment we have
made. And we should make sure that it is properly funded and
not let it be eaten up with inflation.
ECONOMIC IMPACT OF BIOMEDICAL RESEARCH
Dr. Collins, tell us the economic impact of biomedical
research, including pharmaceutical research--NIH is the leader,
but going on elsewhere, too, in the private sector--in this
country, and how important is it not to just our health, but to
our economy and our leadership in the world. You have some
numbers there?
Dr. Collins. I have some numbers. I could go on all day
with numbers because----
Senator Shelby. How about taking a few minutes?
Because the chairman will gavel----
Dr. Collins. I will try to rein it in here.
Senator Shelby. Thank you.
Dr. Collins. I will tell you when I came to this job to be
Director of NIH, I did not realize how important it was going
to be to have this kind of case in front of the public and in
front of the Congress in order to justify what we are doing
because the main reason I am excited about being at NIH is the
advances in research that are going to help people. But there
is another great story here, which is that every $1 that we
give out in grants to all 50 States, by most estimates, returns
more than two-fold in terms of economic----
Senator Shelby. It is a huge multiplier, is it not?
Dr. Collins. It is about $2.21 per $1 according to one----
Senator Shelby. In GDP (gross domestic product) and jobs,
right?
Dr. Collins. And in jobs. We directly support about 432,000
jobs through our grants. But if you figure out how NIH is sort
of part of the ecosystem that creates jobs in biotech and in
pharma, the estimate is something like 7 million jobs are
dependent upon the progress that NIH makes, and are somewhat
jeopardized by our current circumstance.
And when you look at the competition issue, which is
another one that people raise, certainly America has led the
world in biomedical research for the last 20 or 30 years, but
that is gradually eroding, and, in fact, eroding more quickly
these days, especially after sequester. And if we are
interested in seeing those kinds of returns like were talked
about with the Genome Project, a 141 to 1 return on those
dollars, do we really want those returns to go somewhere else,
or do we want them to happen right here?
AUTOIMMUNE DISEASES
Senator Shelby. Absolutely not. We want to keep it here.
Let me ask you a question. I am limited in time. We have a
chairman with a good gavel here. In the autoimmune area that I
have worked with you before, rheumatoid arthritis and lupus,
are you cutting back on the money there? It seems like you are.
And if so, why?
Dr. Collins. We are only cutting back because we have to
cut back everywhere.
Senator Shelby. Because of lack of money.
Dr. Collins. Even with the wonderful things you all did
with the fiscal year 2014 omnibus, we did not recover
everything we lost in the sequester. I will say one bit of good
news about lupus is the development of this partnership with
industry called the Accelerating Medicines Partnership, AMP,
because lupus is one of the targets that we are going after.
Senator Shelby. They are kind of matching you on money,
right?
Dr. Collins. They are, $230 million over 5 years, half of
it from us, half from them, and bringing scientists around the
same table who would not normally be talking to each other, and
having this all done in an open access fashion. This is an
interesting experiment, but it may very well get us that next
generation of drug targets for lupus.
Senator Shelby. Doctor, how important is not just for
lupus, but all the autoimmune diseases--the whole spectrum
affects so many of the areas of research that you are working
on, does it not?
Dr. Collins. Absolutely, and maybe Dr. Fauci would want to
say a word about this since he is the most distinguished
immunologist in the room.
Senator Shelby. We know.
Dr. Fauci. Thank you for the question, Senator. Indeed, I
think the issue with autoimmunity is really an example of how
fundamental basic research and understanding how the immune
system is regulated over the last several years have provided
extraordinary insight into how we can better manage, diagnose,
and ultimately treat, and in some cases even prevent,
autoimmune diseases.
Whenever you think about autoimmunity, the terminology
itself is descriptive, namely an immune response against
oneself that is inappropriate, and that is what is studied at
the very basic level. At the NIH, we now are developing
consortia where, as you hinted, multiple institutes are
involved in immunology--the Cancer Institute, the Heart, Lung,
and Blood Institute, our institute, the Arthritis
Musculoskeletal and Skin Diseases Institute, et cetera. They
all are, and we have a consortium now----
Senator Shelby. Immunology kind of transcends it all, does
it not?
Dr. Fauci. It is one of those disciplines that essentially
touches to a greater or lesser degree virtually everything we
do.
CYSTIC FIBROSIS
Senator Shelby. Dr. Collins, in another area--my time is
limited, just a few seconds--but cystic fibrosis. We have come
a long way there. We are a long way from a cure, but we have
extended a lot of the children's lives, you know, beyond, gosh,
what we thought. Where are we today, and what are some of the
hopes there?
Dr. Collins. Well, cystic fibrosis is a wonderful example
of how knowing the molecular basis of a disease can get you to
a point with a great deal of hard work to a targeted
therapeutic that is not just hoping something will work, but
designing it to work.
So cystic fibrosis, where my lab had the privilege of being
involved in that and found the gene in 1989. Just a year ago,
the first really effective therapeutic for about 5 percent of
cystic fibrosis patients that have a particular mutation in
that gene was approved by the FDA, infact. And it is truly
dramatic the stories you hear from those individuals. I have
heard stories of kids who were on the lung transplant list who
are now not on it anymore.
The main challenge now is to find an equivalent therapy for
the majority of cystic fibrosis patients that have a different
mutation, the so-called Delta F508, and there is a clinical
trial very actively underway by Vertex. The drug is called VX-
809. We are all holding our breath to see what the results of
that will look like. The initial glimpse with a smaller phase
two study looked pretty promising.
So you have gone--it took a long time. And one of the
things that NCATS, and my colleague here, Dr. Austin, is
charged to do is to try to shorten what would be a 20-year
timetable into something much faster. But the pathway here that
was charted by cystic fibrosis in a collaboration with the CF
Foundation that was a major partner here is truly exciting. It
is a paradigm. We could do this again.
Senator Shelby. Thank you very much for the work you do.
Thank you, Mr. Chairman.
Senator Harkin. Thank you, Senator Shelby.
Senator Kirk.
REHABILITATION STANDARDS
Senator Kirk. I want to ask Story a question as a stroke
survivor. We have two members--senators on this committee who
are stroke survivors. I would like to take you into the world
of our rehab standards, which Senator Johnson and I have both
introduced legislation, S. 1027, to speak on behalf of the
900,000 Americans who will survive stroke we expect this year.
We know that roughly one-third of them will never return to
work. And Tim Johnson and I have a belief that we could set a
national standard of returning those stroke survivors to work.
That would unlock a hell of a lot of Americans to pay taxes and
be productive.
Let me just burrow in for rehabilitation standards. My
understanding is out of the $3 billion NIH, about $66 million
is spent. I think the country would do well to have NIH
establish a rehabilitation standard.
Dr. Landis. So, NINDS (National Institute of Neurological
Disorders and Stroke) recently established a stroke network of
clinical centers that will undertake stroke trials. And one of
the major reasons we did this was to have a balance in our
investment in prevention, acute treatment, and stroke
rehabilitation. We have recently finished one trial, which has
shown that it is not--never too late to start rehabilitation
for stroke, that significant gains can be made even after 6
months. We have another trial underway. But this has clearly
been an area where there has not been sufficient investment,
and this clinical trials network will enable us to do more
trials better and faster, which will create the kind of
standards that you are asking for.
Dr. Collins. Could I add one thing, that the number you
mentioned is the funding for the National Center for Medical
Rehabilitation Research, NCMRR, which is actually within the
National Institute of Child Health and Human Development. But
that is not the sum total of all that we spend on
rehabilitation research. Much of what Dr. Landis was just
talking about is in a different part of the budget. So the
total expenditures on rehabilitation research are several times
that number, just to clarify.
JOHN PORTER MEMORIAL
Senator Kirk. Thank you, Mr. Chairman. I just wanted to--
could I follow up and thank you for honoring my political
mentor, Congressman John Porter, the other day, the man who on
a bipartisan level led to the doubling of funding for this
institution. You guys honored a great man who really put
together an awesome team with Speaker Gingrich on that.
Dr. Collins. And, Senator, let me thank you for sending a
wonderful video that the 400-some people who were there for
that dedication watched and were touched by. And I appreciate
very much your contributing to our event. This was a grand
moment for NIH.
Let me say one other thing about rehabilitation research.
We are very much in the process now of seeking a new director
for this National Center for Medical Rehabilitation Research,
someone who will be particularly forward looking in identifying
opportunities, how to work with the institutes, how to build
the case here for rehabilitation research to be even more
vigorous than it has been. And we are looking for the very best
person on the planet to do that.
Senator Harkin. Thank you very much. We will start another
round.
FUNDING HISTORY AND SUCCESS RATES
Dr. Collins, do you still have that chart that showed where
that doubling was? You showed that line for the constant
inflationary increase of, I think it was $3.7 or something.
That one right there.
[The graphic follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Senator Harkin. Again, just for the record--there may be
people who were not here at that time. Here is how we came
about that doubling. In the 1990s, we saw the rate of approval
of grants percentage going down and down and down from what it
had been in the 1980s.
And so, meeting with people at the Institute then--it was
Dr. Varmus at that time, if I remember right, others. We were
talking about what would it take to sort of get back up to that
level where we were in the 1980s for the percentage of--what is
the phrase I am looking for--grant approvals, right?
Dr. Collins. Success rate. Success rate.
Senator Harkin. Yes, success rate. And so, we got that. And
what that would take would be--what it meant was to double the
funding over a period of 5 years. Our thought was that once we
did that and got up there, that blue would then start up there
where the top was, and we would go on----
Dr. Collins. That is what we were hoping for, too, believe
me.
Voice. The soft landing.
Senator Harkin. This was never meant as some transitory
type of a funding bump. Now, maybe the Recovery Act was. That
was sort of a transitory bump, but the doubling was to get us
back up to that level and then continue on.
Dr. Collins. Yes.
Senator Harkin. And so, we sat here through the 2000s and
saw what happened. Again, I do not mean to speak politically,
but just factually. We had two wars going on. 9/11 had
happened. More and more money was being siphoned off for that.
I am not making a judgment call on that. That is just what
happened. And we were in a situation where we were not raising
revenues, but more and more money was going for the War on
Terrorism, and that is what happened. We just did not have the
resources, and we came back down, and that is where we are
today.
It pains me, and it pains a lot of people to think that
that happened. We deliberately did that to get that line back
up there and to keep it going. And, well, other things
happened, and so we are back in this situation now, and we are
scrambling to find the resources that we need to do this. We
need more revenues. That is just my own thing. We need revenue.
I think the taxpayers of this country would not mind paying a
little bit more in their taxes or the wealthy or the
corporations, everybody, to know that this was going to help
NIH and that is where the money was going.
And so, somehow we have just got to get the revenues in for
this, and like I said, I am open for any other thoughts and
suggestions on how to do it. Senator Hatfield at one time had
an ingenious idea of doing that. I joined him in that. That did
not get very far, but it was a proposal that we would take, I
think it was 1 cent out of every $1 that went for healthcare
premiums. See, a lot of people do not know that when you go to
a drugstore and you buy a prescription, and when you get a
prescription drug or something like that, some of that money
goes for research. But we do not do that in our healthcare
policies. When you buy a healthcare policy, none of that goes
for research.
So the idea that Hatfield came up with was that 1 cent out
of every $1 that would be--go into a fund that would come to
this committee. That would go to NIH as long as we funded NIH
at last year--at the previous----
Senator Mikulski. Maintenance of effort.
Senator Harkin. Maintenance of effort, thank you. That
phrase, ``maintenance of effort,'' then that money would be
available to NIH. That would have been a great deal to have,
but we did not get it. And I am still thinking that there is
something out there in that realm of healthcare policies where
people who are buying healthcare policies would say, ``Yes, I
would like to have a half a penny or something go to biomedical
research and come into a fund.'' I think people would support
that if they knew that is where it was going. It was going to
NIH. They would support that. So I have not quite totally given
up on that idea, but there may be others.
RETIREMENT OF CHIMPANZEES
Dr. Collins, I have one other question I want to ask sort
of off of what we have been talking about here, but it is one
that I hear a lot of about, people keep asking me about. There
is a great interest in this country about what is happening to
our chimpanzees. As you know, we have had a great partnership
with you, with the Humane Society, on retiring these
chimpanzees from research.
I know Senator Landrieu has been kind of in the forefront
of this, and I know she wants me to also ask this question. I
was one of three Senators who requested the IOM (Institute of
Medicine) report that revealed that chimpanzee research could
not be justified except for a very few conditions. Again, Dr.
Collins, you are to be commended for adopting the IOM
recommendations so promptly, the very day the report was
released. Your decision to retire approximately 310 of the 360
Government-owned chimpanzees currently in laboratories was a
bold maneuver, and I thank you for that.
As a long-time appropriator, however, I know that the work
takes far longer than the issuing of a policy or the signing of
a bill. I am keenly aware of the complexity of creating
sanctuary space, grouping, transporting chimpanzees, arranging
for their care. Many of these chimpanzees suffer from illnesses
and conditions we gave them for the sake of research. So could
you please update the subcommittee on the plan for retiring
these chimpanzees? Can you highlight the challenges and
considerations involved, including any funding challenges that
we need to be cognizant of?
Dr. Collins. Well, thank you, Mr. Chairman, and thank you
for your leadership on this issue in many steps along the way,
including asking the IOM to conduct that study, which concluded
that the need for chimpanzees in research had now been greatly
reduced and that we could, in fact, get by just fine by keeping
a small group of 50 available for emergency needs or special
things where only chimpanzees could be used for research.
And you also helped us with a fix on what had been a
legislative problem about a cap on the amount of funds that NIH
was allowed to spend on chimps in sanctuaries, and that made it
possible for the retirements that we very much wanted to go
forward. But you are quite right, we have a long way to go here
in terms of the number of chimps that need to be moved into
sanctuaries. And at the present time, that space does not
exist.
We have moved many already into Chimp Haven, which is
already now pretty close to capacity. We are looking vigorously
at other----
Senator Harkin. Is that the one in Louisiana?
Dr. Collins. Yes, and we are vigorously looking at other
alternatives because there are other chimp sanctuaries to make
sure that they meet the standards that you would want to see so
these chimps are well cared for. And there is much interest in
philanthropy in helping out with this, and the Humane Society
has been a wonderful partner as well. My dear friend, Jane
Goodall, who will turn 80 years tomorrow, has been very helpful
in raising the consciousness of everyone about what an
important issue this is.
I would not tell you that we have this solved. I think it
is going to be several years before the space can be
identified, the funds can be found, and the completion of the
retirements can be achieved so that we are left with just those
50 chimps for research. And we will be re-evaluating that
regularly as well to see whether those are even needed at that
level. But I appreciate your interest and this committee's
interest in this, and we are going to keep you regularly
briefed on what the needs might be.
Senator Harkin. This started back in the late 1990s, and
that is when Jane Goodall came to see us. And Senator Bingaman
I know was involved. The Senator on the Senate side that
introduced the bill on saving the chimps was Senator Bob Smith
from New Hampshire. I remember that. I forget who the other one
was, but there was a strong bipartisan effort. And so, it has
taken a long time. I know we got that cap removed. It was a $30
million cap if I am not mistaken. We got that removed.
Dr. Collins. Yes. Yes.
Senator Harkin. But there is a great deal of interest in
moving ahead on this. And maybe if you cannot today, could you
get to the committee sort of the timelines you see and what
more do we need to do to kind of expedite this?
Dr. Collins. I am glad to do that.
[Clerk's Note: The information requested can be found in the
``Additional Committee Questions'' for Senator Harkin.]
Dr. Collins. And, Mr. Chairman, again, when I came to this
job as NIH Director, I did not imagine that this issue would
become so prominent. And yet it has turned out to be, I think,
one of the more gratifying opportunities to work across many
different constituencies and do the right thing for these
special animals, who are our closest relatives.
Senator Harkin. Our closest cousins.
Dr. Collins. Absolutely.
Senator Harkin. Thank you very much.
Senator Moran.
DISEASE FUNDING PRIORITIZATION
Senator Moran. Chairman, again, thank you. Dr. Collins, I
am going to ask one more question about prioritization, and
then a couple of questions for a couple of your directors.
What are the criteria--when you say this is an ongoing
conversation about how to prioritize funding within NIH among
the various diseases--that you look at? Is it the likelihood of
success, the next opportunity for a breakthrough? What role
does it play about the cost of the disease? How many people are
afflicted, what the cost of care and treatment are? Is it a
more scientific exercise in trying to prioritize how to spend
money correctly, or is it a broader concept that you pursue?
Dr. Collins. That is a great question, and it is something
that we work on every day. It is a mix of all those things.
Certainly the public health impact has to be a concern for us,
the number of people affected, and the severity of the illness,
and what it does in terms of quality of life or premature
death. Those are all factored in. But if we only thought about
those things, then rare diseases would get neglected, and we
have learned so much from studying rare diseases. And if it is
your family, it does not matter so much to you that it is a
rare disease than if it is your child who is suffering from it.
We also think about scientific opportunity because that has
got to be a major reason to decide to make a push in a
particular direction, that something is emerging that is
possible and maybe it was not a year or two previously, and you
do not want to lose the opportunity to push forward on that.
On top of that, of course, a lot of our portfolio is not
top down managed, and it should not be. It comes from the
insights, the ingenuity, the creativity, the bold vision of
those investigators out there and the universities across this
country who are remarkable in their abilities to think of
things that we could not have thought of. And, we, therefore,
have a very substantial fraction of our portfolio that is not
targeted or directed based on anybody's idea about public
health need or about scientific opportunities other than the
fact that they are proposing something scientific. Those then
go through a peer review process. If the idea does not measure
up, it does not make it into the next tier.
I would tell you, though, that peer review, while it is
critical, it is not the only part of what we do. And all of the
Institute directors you see here, once we have had the peer
review, look across that, and the things that are somewhere
near the pay line, decide what is the highest program priority
based upon the issues that I just talked about--public health
need, scientific opportunity--and also is our portfolio well
balanced, or do we have a big pile up of things in one area and
neglect in other areas. All of that calculus folds into this
every day that these institute directors and I are struggling
with. And I think we do a reasonable job of it, but we are
always trying to do better.
NATIONAL CANCER INSTITUTE COMMUNITY PROGRAMS
Senator Moran. Thank you for your answer. Dr. Varmus, NCI's
budget request includes information on expanding access to
clinical trials for patients treated in community settings and
expanding access to trials by minority and underserved
populations. One of those underserved populations is rural
Americans, and I was interested in knowing if you could talk
about the goals of that program and how many new NCI community
oncology research programs, projects you might expect to find.
Dr. Varmus. Well, Senator, I cannot give you an exact
number for that, but as you were rattling off the names
suggested, you are aware that we have just amalgamated two of
our community-based programs into one called NCORP for
Community Oncology Research Program, in which we are paying
special attention to minority populations and rural populations
and trying to bring hospitals that are not in our NCI
designated cancer centers into the network of organizations
that organize our clinical trials and provide more patients.
And indeed, many of these centers that compete particularly
effectively for money to support clinical trials have been in
these areas--have been producing large numbers of patients to
accrue them into our trials over the last several years. That
is an important factor in making a decision about who will get
support.
As you know, we have constraints across the board because
our fiscal levels are not what they used to be, so I cannot
promise you any specific number until we have fully competed
and awarded those grants. But our intention is to recruit as
many patients as we need to carry out a new style of clinical
trial that we are encouraging; that is, trials that are based
as much on the genetic damage that has driven the cancer as in
the organ on which the cancer has arisen. So, there is a new
style of doing trials that is more costly because it requires
more preliminary testing.
And we are also under the direction from a report from the
Institute of Medicine to pay our investigators a higher fee for
each patient accrued to those trials, so our trials have become
more costly. So our interest in expanding our trials,
especially with all the new therapeutics, not just drugs, but
also antibodies and immune strategies, and radiotherapy that
have come our way, is difficult to meet under current
conditions because we cannot simply do trials. We also have to
be investing, and this is part of the prioritization question
in the basic research that fuels new therapeutic approaches.
And indeed, I would just make a footnote to your question
about making priority judgments about what we spend our money
on by pointing to a new initiative at the NCI, despite our
declining budget, that targets one particular mutant gene
called RAS that is mutated in over a quarter of all cancers. So
here is a major target against which, despite knowing about
this target for 30 years, we have made very little progress.
So we have started what is called a hub and spoke project
centered in Senator Mikulski's favorite location, Frederick,
Maryland, where we have a contract program called the Frederick
National Laboratory for Cancer Research. We have recruited
somebody from the University of California at San Francisco to
come and lead this effort, which involves grantees around the
country working shoulder to shoulder with a hub of people at
Frederick who are leading the charge on six specific new
opportunities for advancing our understanding of cancers that
are driven by RAS mutations. And this is a way to lead to new
kinds of compounds that can then be tested nationwide in trials
that are specifically directed to cancers that have mutations
in that specific gene.
CLINICAL AND TRANSLATIONAL SCIENCE AWARDS
Senator Moran. Doctor, thank you. My time has expired. Dr.
Austin, I will submit a question in writing to you. I am
interested in the recommendations by the Institute of Medicine
in June of 2013 on the Clinical and Translational Science
Awards, and I am interested in hearing how things are going to
develop. So I look forward to having a conversation with you.
Thank you.
Senator Harkin. Thank you.
Senator Mikulski.
IMPACT OF FUNDING ON U.S. INNOVATION
Senator Mikulski. Thank you very much, Mr. Chairman. And I
just want to say to you and to all the Institute directors and
everyone who works at NIH, we are fortunate to have you. But
again, I want to come back to your longevity, which shows
really your dedication, and we view it as a blessing.
I also want to just comment that we--many of us here are
worried about the innovation deficit both at NIH and in others.
There is an effort that is being led by Senator Durbin in this
area, and to that end, we on the Appropriations Committee are
going to hold a full committee hearing on innovation to make
sure that budget cuts and possibilities of future sequester
does not dampen our standing as a world innovation leader. Yes,
we worry about the deficit, but we also worry about the
innovation deficit. So, we are going to be holding that hearing
on April 29. Dr. Collins will be testifying, the science
advisor. We are going to be listening to NSF, DARPA, and also
the Energy Secretary. So we will be doing that.
WOMEN'S HEALTH
In the short time I have because others are now here, I
want to raise the issue of the Office of Women's Health, that
which I referenced earlier. It has been flat funded for 3 years
at $40 million. Now, what I would like to get a picture of is:
What do you need to have the Office of Women's Health, number
two, kind of the way we are thinking about running it because
each and every one of those institutes does important work with
women. So when we embarked upon our initial endeavor that I
referenced with Dr. Healy, breast cancer was our preoccupation.
Those rates are coming down, but lung cancer in women is high.
Dr. Gibbons could tell me that women with heart disease are
now escalating, and our symptoms are different, but are early
diagnoses there? We could go to Dr. Landis and we think about
something like atrial fib that is there, but if you do not take
your blood thinner, you could end up with a stroke and
wondering where are you, et cetera. And then, of course,
autoimmune is several things, one of which is lupus for which
only recently the first drug--therapeutic drug in 50 years, of
course, came out of Human Genome in a Maryland company. So it
is across all the institutes, which was the idea why we never
wanted an institute on women; we wanted an office that would
work. So could you tell us really with the $40 million, how is
it going, do you need more, and then how do you see this
working across the institutes?
Dr. Collins. Thanks for the question. I very much resonate
with what you are saying, and we have made a lot of progress,
Senator, thanks to you and others for raising this issue to the
attention of NIH 20 years ago. We have been fortunate in the
Office of Research on Women's Health (ORWH) to have remarkable
leaders in Vivian Pinn, who recently retired, and now Janine
Clayton, who is a terrific leader for that effort who I just
met with day before yesterday to go over the status of her
portfolio. And she has been, as Vivian was, very effective in
building partnerships across NIH to support special efforts
that focus on women's health.
There are particular programs in ORWH, particularly the
Specialized Centers of Research on Sex Differences, the SCORE
Programs, as well as training programs that have done a good
job, I think, in increasing both research on women's health and
also increasing the proportion of researchers who are women.
And I would say if you look at the statistics, it looks
reasonably good, but there are obviously things that we need to
do better.
In fiscal year 2013, 57 percent of those enrolled in NIH
clinical research trials were women--57 percent. And you know
what that was 20 years ago, in phase III trials, 73 percent.
So, we have really come a long way. Many of those trials are,
of course, disease specific and may, therefore, be sex
specific, for instance in breast cancer. But many of them as in
heart disease are balanced.
What we are currently particularly concerned about is
actually that this same idea has not trickled down in animal
models, and there is clearly a problem in that many of the
investigators who are studying models of disease are studying
only males--male rats, male mice--for reasons that are not
defensible. And Dr. Clayton and I are about to publish an
exhortation to the community about this, and we are going to
start looking very closely at grants to see whether this can be
corrected because if you did not learn about those sex
differences in your complete clinical, you are going to miss
out on an inference that might be really important.
How much money do we need? Well, we need more money as you
have heard from all of us in every area of what we are doing. I
would say Dr. Clayton has been quite effective in brokering the
dollars that her office has to build relationships and get a
lot done, but there is a lot more we could be doing.
Senator Mikulski. Well, as you know, the health data on
women are changing, and the recent IOM report over the last 2
years shows that mortality and morbidity among women is on the
rise. Anyway, a longer topic.
Dr. Collins. I would love to converse further with you
about this at any time. It is a passion of mine as well.
Senator Mikulski. Thank you.
Senator Harkin. I just want to publicly again thank Senator
Mikulski. When she first came to the Senate opened our eyes and
got the NIH to do internal studies to show that women were not
being included in clinical trials. So it was Senator Mikulski
who really moved the ball forward on that. That has been over
20 years ago.
Senator Mikulski. It has been a long time.
Senator Harkin. A long time ago. And so, we thank you for
moving in the right direction.
Senator Shelby.
ANIMAL RESEARCH
Senator Shelby. Just for the record, I want to touch on
something Senator Harkin brought up, and that is the research
on chimpanzees, animals, and so forth. As a kid growing up in
the Birmingham area in Alabama, I tried to rescue every dog in
the neighborhood. I still love dogs. I still rescue them. But
my parents could only feed so many.
And I was brought to reality, but that did not change my
caring about animals as all of us do. On the other hand, we are
all used in research, you know. I have been used by permission
in research because you gather information that helps
everything. But is there a real substitute--none of us want to
be cruel and inhumane to animals. You have used animals in
biomedical research as you have used us, you know, in different
aspects. But is there a real substitute for that? Dr. Collins,
do you want to pick up on that?
Dr. Collins. I will, and I appreciate your making the point
that research----
Senator Shelby. Because we all love--I love dogs still.
Dr. Collins. So do I.
Senator Shelby. But I do not collect them anymore, you
know.
Dr. Collins. And we have learned enormous amounts from the
study of animals in research, and we will continue to depend
heavily on those insights for advances in human medicine, no
doubt about it. With the chimpanzees, the IOM basically felt
that there was nothing unique that would justify the continued
maintenance of hundreds of chimpanzees.
Senator Shelby. Oh, I totally agree.
Dr. Collins. We could shrink this back to a small group.
But your question about a substitution, I am going to ask Dr.
Austin to say something about an approach to studying toxicity
of drugs, which traditionally has used animals, and maybe now
we have got a better way to do this.
Dr. Austin. Yes, thank you for the question. So this is
common saw in the translational world that the best animal
model is the human. And so, what we are trying to do is move
more of this work to human models, and one of them I actually
have sitting right in front of me. This is a kidney, but it is
a kidney on a chip, and it is populated by human kidney cells,
which is a wonderful model and a much better model of testing
drugs than in a rat or a chimpanzee and predicting which
drugs----
Senator Shelby. Because it is a human being which you are
working on ultimately to help save, right?
Dr. Austin. Right. And so, this is part of a tissue chip
program, that you have probably heard about, that is developing
so-called organoids. They are three-dimensional micro organs on
a little micro fluidic platform, a human on a chip. To be able
to represent human organs in this sort of format that will
dramatically change, but we believe, both the accuracy and the
speed with which this testing is done and will make animal
models irrelevant, obsolete. We are not there yet. We have got
a lot of work to do. And actually----
Senator Shelby. But you are going down the right road, are
you not, Dr. Austin?
Dr. Austin. Yes.
Senator Shelby. You are going down the road.
Dr. Austin. Yes, absolutely.
Senator Shelby. Well, a lot of my lawyer friends are
probably glad to hear this because, you know, people have said
tongue-in-cheek, ``Gosh, if we run out of basic research, we
could use lawyers as a surplus.'' I said, ``Do not do that.''
Thank you.
Dr. Collins. Well, fortunately induced pluripotent stem
cells came along to save the lawyers because we have this
amazing new technology, which this committee has heard about,
but I just got to say it gets better every day. A skin biopsy
or a blood sample from any one of you could be used to make
those kidney cells on that chip by doing all of this clever
manipulation that has only come to light in the last 5 years of
turning genes on or off. And that means that we could generate
not just any old kidney chip, but your kidney chip, and find
out whether that drug that you are going to get is going to be
good for you or it is going to make your kidneys not so good.
BIG DATA TO KNOWLEDGE
Senator Shelby. Dr. Austin referred to something that I
just want to pick up on with you, Dr. Collins. The data that is
collected from all of us in biomedical research willfully and
knowingly will help to cure diseases and so forth. How
important is that in the research field, whatever it might be,
immunization, or neurological, cancer, you name it.
Dr. Collins. It is critical, and of course we have this
challenge to both keep track of increasingly enormous
databases, but also to be sure we are protecting the privacy of
the individuals' data so that it is not exposed in a way that
they would not have given consent for.
I am glad you raised this because NIH has just this year
initiated a new program we are calling BD2K, Big Data to
Knowledge. We have enormous opportunities from genomics, from
imaging, from electronic health records, from everything you
can think of to make insights about health and disease. Unless
we focus on the problem of data itself, the sort of new science
called data science, we are going to get all drowning in the
data that we have produced instead of making inferences from
it.
So we are putting an unprecedented amount of effort into
it, and this omnibus for fiscal year 2014 has given us a nice
push in that regard. We aim to ramp that up to $100 million on
the big data initiatives over the next couple of years, and I
hired a remarkable scientist from San Diego to lead that
effort, Dr. Philip Bourne.
Senator Shelby. Mr. Chairman, one last observation and
question to Dr. Collins. You mentioned earlier about how
important it was for scientific investigators to go down the
right road. Sometimes you do not know you are on the right
road, and sometimes you are on the wrong road and discover
something else, though, do you not--that is worthwhile to
mankind.
Is that a question of supervision of more investigators, or
is it a question of better education correlation with what
people are doing? There may be no answer to it because a lot of
scientific breakthroughs have come from finding something or
they did something backwards. Hey, you all know it better than
I do. Do you want to comment on that?
Dr. Collins. Absolutely. I think you are quite right that
many of the most dramatic observations that have led us to
insights about life and life sciences have come in directions
that nobody would have predicted were going to be the case, you
know, from Pasteur on. And serendipity does sort of favor the
prepared mind. But I worry that at the present time with our
young scientists feeling so constrained by anxieties about
support that they may be less inclined when faced with an
unexpected result to think of that as an opportunity to go down
a new path because of the necessary kind of need to keep
pursuing something that they think is in the mainstream and
more likely to get supported.
This is one of those secondary effects of a difficult
budget situation that worries all of us, that creativity, that
innovation, that risk taking, that sort of seeking a different
pathway than you had planned to is more difficult. We are
funding a certain set of grants that aim to try to make that
possible. The Pioneer Awards are perhaps the best known where
investigators basically get 5 years of support. And if they
encounter something they did not expect, they can go after it.
But many of the other grant systems are not quite so favorable
for that.
Senator Shelby. Thank you, Mr. Chairman.
Senator Harkin. Senator Durbin.
NATIONAL INSTITUTES OF HEALTH FUNDING
Senator Durbin. Thank you very much. Thank you for
dedicating a major part of your professional life to medical
research at the premiere biomedical research agency in the
world. And we are proud of it, and thank you for that. I also
want to acknowledge--he will have plenty of tributes paid, but
when the history is written of the NIH, there will be a chapter
that is entitled ``The Porter-Harkin-Specter'' chapter when
they made a decision to move forward in a dramatic way and
double the appropriation for the National Institutes of Health
over a 10-year period. Tom, of all of your accomplishments, you
probably created more good for the world with that undertaking,
although there are lot more that would compete. So I thank you
for your leadership.
Dr. Collins, when I met with many of you just a few months
ago, I sat down and said where do we go next. I am not sure I
can come with a straight face to Congress and say double it
again. I am not sure they will do it. And we had a conversation
about what it takes each year to increase an investment in
research in NIH and CDC, Department of Defense, healthcare, VA
health research.
And you first noted that when we fall behind the cost of
living, it really ties your hands in the long term to award
grants. The failure to provide a regular cost of living
adjustment (COLA) to NIH, as I understand it, has cost you 22
percent in terms of your ability to award grants for research
over the last 10 years.
The President's budget proposed for your agency for the
next fiscal year gives you, I believe, 0.7 percent COLA. We
know that the actual cost of living increase will be 1.7
percent. So built into the President's budget is a further
decline, falling behind more when it comes to the actual cost
of living.
And at that time, I said, ``Give me an idea of what it
would take in real growth to build this agency forward.'' And
you said--for the record I am going to ask you to comment on
this--``Give us 5 percent real growth per year for 10 years
over the cost of living and we will show you the kind of growth
in research that America and the world needs.''
So here you are on the record, and I am going to remind you
of that conversation since I took it to heart and introduced a
bill. So please tell me if you still believe that.
Dr. Collins. Senator, thank you for the question and for
introducing that bill, and it was a wonderful opportunity to
talk with you when you came to NIH. And your taking on this
leadership is deeply appreciated.
I am showing you here this graph that I think we talked
about when you came to visit, and, yes, it is exactly as you
have said.
[The graphic follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Dr. Collins. The blue bars there are the appropriations for
NIH, but the yellow reflects the effect of the biomedical
research and development price index (BRDPI). It is sort of
like a cost of living, but it is our cost of living for doing
research, the ``BRDPI'' as we call it. And you can see what has
happened since 2003. At the end of the doubling, those yellow
bars have been dipping down steadily ever since.
Earlier when you were at another hearing, I showed another
version of this graph that basically says if we had stayed on
the same pathway we were back in sort of 1970 to 1995, which
was sort of steady growth of inflation plus about 4 percent, we
would now be at about $40 billion as far as the total NIH
budget, $10 billion more than what we currently have.
To get back on that pathway, which would be a wonderful way
to encourage research to really move forward at the pace that
it could because we are not limited by talent or by ideas.
Putting this NIH trajectory on a steady path where you could
count from year to year on inflation plus a percentage--and
five would be wonderful--would get us back to where perhaps we
really need to be in a few years, and would give such a jolt of
confidence and excitement to frankly a fairly demoralized
biomedical research community.
Senator Durbin. And you have told me about it, and we know
the young investigators are disappearing. Three percent are
under the age of 36 today. Back 30 years ago it was 19 percent.
And the other thing that struck me when we talked about AMP was
you were asking for--asked for and received a commitment of
$150 million, if I remember correctly, from the top 10
pharmaceutical companies to be matched by NIH to pursue cures
and whatever in the areas of Alzheimer's, type 1 diabetes, if I
am not mistaken, and rheumatoid arthritis.
To put that in perspective, what I have called for in the
American Cures Act is $140 billion over a 10-year period of
time for the four agencies to get real 5-percent growth--$140
billion. Last year alone we spent over $200 billion in Medicare
and Medicaid on Alzheimer's--$200 billion. If we could delay
the onset of that disease, it would more than pay for all of
the increased investment in research.
We have got to step back and take stock of what we are
doing here. As we short change you, we add to the cost of our
healthcare programs instead of reducing that cost. And just to
put it in a global perspective, other countries are not
waiting. Europe is moving forward. The United Kingdom is moving
forward. In 8 years China will pass us in real dollars spent on
research. And that ought to be sobering, and I hope it will
awaken us.
I know the chairman has a meeting to go in a few minutes as
I do, too, so I will not dwell on this other than to say I am
going to keep pursuing this. I really believe that what you are
doing is really a great credit to this country and will
alleviate suffering and pain around the world. Thank you, Mr.
Chairman.
Dr. Collins. Thank you, Senator.
Senator Harkin. Thank you, Senator Durbin. Thanks for your
kind words. I appreciate that.
Senator Cochran.
Senator Cochran. Mr. Chairman, I am pleased to join you and
other members of the committee at this hearing. We appreciate
your attention to the appropriations request for NIH, and we
congratulate Dr. Collins and his team for the excellent work
they continue to do in biomedical research, and the benefits
that flow from that to our great country.
POTENTIAL CARE FOR AIDS
Last year it came to my attention that at the University of
Mississippi Medical Center, a pediatrician, Dr. Hannah Gay,
reported that a patient of hers who is now more than 3 years
old remained HIV-free after receiving anti-retroviral therapy
within hours of her birth. We have recently heard about a
similar case in California. I am impressed with the research
being done in my State and am hopeful that this could be good
news for continued research efforts, not only in Jackson,
Mississippi, but throughout the country.
What do we know or what do you know about these cases that
you can share with us in terms of their impact? And what does
this mean for research and treatment as far as a potential cure
is concerned?
Dr. Collins. Well, we have the world's expert in the room,
Dr. Fauci.
Dr. Fauci. Thank you, Francis. Thank you for the question,
Senator Cochran. This is truly a very important case because,
as you described accurately, this was a mother who came into a
clinic in Mississippi who was HIV-infected, who had no prenatal
treatment for her HIV, which put the child at very high risk.
The astute physicians, pediatricians in Mississippi, instead of
treating the baby in a prophylactic way to prevent infection,
they immediately aggressively treated the baby as if the baby
were infected. After that very rapid application of full-blown
aggressive therapy as opposed to waiting for a few weeks for
the diagnosis, the baby turned out actually to be infected.
By a series of circumstances after several months on
therapy, there was a discontinuance in care. The mother dropped
out of the healthcare system, came back several months later,
and the baby had not been on therapy for several months. The
physicians watched because they could not find any virus in the
baby, and now 3 years out the baby is well, growing well, and
has no evidence of infection, which is likely the first real
cure of HIV infection.
That has now triggered an NIH-funded study in which a large
number of babies who are born of high-risk mothers, namely
mothers who have not been treated, will be put on aggressive
therapy to see if, in fact, you can cure babies. Now, the
reason that is important is that the risk to benefit ratio of
treating babies aggressively very early on has weighed on the
side of waiting because you are not sure if you are ever going
to have the opportunity of curing someone, so you say let us
not expose the baby to aggressive therapy because you might
actually hurt the baby if the baby is not infected. And all you
are doing is going to be saving a few weeks of treatment.
Now that you know you can actually cure a baby if you are
aggressive, then the risk benefit ratio switches all the way
over to the possible benefits. So it was a very important case,
and it has triggered a study which will begin in the middle or
end of May, a multicenter study to see if we can verify that
and apply it to a larger number of babies.
Senator Cochran. Thank you. That is very exciting, Mr.
Chairman. And I hope we learn from that that we need to listen
to these witnesses when they come before our committee. We are
all going to learn something, and it may be reflected in direct
appropriations that really do improve not only the lives of
American citizens, but actually saves their lives. Thank you
very much.
CONCLUSION
Senator Harkin. Thank you, Senator Cochran. Well, listen,
thank you all very much again. It is always enlightening.
Always a pleasure to hear about the National Institutes of Hope
and what you are doing. I hope that our subcommittee can meet
the obligations of funding that you have talked about here that
is in the President's budget, maybe even go beyond that in some
cases I hope in terms of funding for NIH. We just have to
recommit ourselves to breaking this logjam of the funding for
NIH. We have got to get back to the success rate that is less
than 20 percent across the board. We have got to get down to
that 15 percent level some time. I think that is what we did
after we doubled it. It was down around that area, if I am not
mistaken.
And so, as I said before, I think the American people
support that. I do support it. And we just have to meet our
obligations to do all we can to fund it and, as I said earlier,
to find any ideas on ways of funding and getting more money for
NIH. We just cannot give up on this. We just cannot. Too much
is at stake.
I often think there are so many young people out there with
keen minds, want to get into science, biotechnology. We need to
give them the hope that if they want to pursue that as a life
career like so many of you have had, that they are going to
have the opportunity to succeed. They are going to have the
opportunity to put those keen minds to work and investigating
and asking those questions of how and why and what happens.
Basic research to me has always been the most stimulating.
I often put it in the past in terms of if you have--let us say
you have 10 doors to a potential cure. Well, if you open one
door, the odds are, what, 10 to 1, 9 to 1--I am not too good at
math--that you are not going to find the right door. If you
open five doors, the odds become even better, or eight or nine.
That is what basic research is, is opening those doors. A lot
of times it may not lead to where you think it is going to
lead, but sometimes that basic research leads to something
else. I always remember John--Dr. Enders and the kidney cells,
and the Salk polio vaccine. That is not where he was headed,
but that is what happened later on.
And so, to me basic research needs to be--we just have to
fund it. It always pains me when people say, ``Oh, we put all
that money into basic research, but, you know, when are we
going to have an end date? When are we going to find this cure
and stuff?'' I say, ``Well, that is not a legitimate question
to ask of basic research. The legitimate question to ask of
basic research is do you have a question. Does something
stimulate your curiosity that you are willing to spend some
time to investigate it and take it as far as you can without
knowing exactly what the end result is going to be?'' That is
what basic research is.
And we need to stimulate that kind of thinking in America,
that kind of excitement about basic research. And if we do not
fund NIH, we are telling young people and these keen minds do
something else maybe. Maybe there is something else for you to
do. So to me, the funding for NIH is not only the here and the
now, but it is the next generation, the generation after that
we encourage to take this up and to devote their lives to
science and to basic research. We will do whatever we can to
make sure that that happens.
ADDITIONAL COMMITTEE QUESTIONS
And I thank you all for all of your dedication--your
lifetime dedication to exploring the frontiers of science and
health, finding so many cures and therapies. It has been
amazing, amazing thing to see what has happened in the last 25,
30 years that I have been here. There next 30 years can be even
better. Let us make it so. Thank you very much.
I am supposed to--we will keep the record open--the record
will remain open until April 9 for Senators to submit other
questions and for responses to questions.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted by Senator Tom Harkin
chimpanzee retirement
Question. Dr. Collins, I want to thank you for the partnership you
have had with this subcommittee and the Humane Society on the process
of retiring chimpanzees from research. As you know, I was one of three
Senators who requested the Institute of Medicine (IOM) report that
revealed that chimpanzee research could not be justified except for a
very few conditions. You are to be commended for adopting the IOM
recommendations so promptly--the very day the report was released. Your
decision to retire approximately 310 of the 360 government-owned
chimpanzees currently in laboratories was suitably bold.
As a long-time appropriator, however, I know that the work takes
far longer than the issuing of a policy or the signing of a bill. I am
keenly aware of the complexity of creating sanctuary space, grouping
and transporting chimpanzees, and arranging for their care. Many of
these chimpanzees suffer from illnesses and conditions we gave them for
the sake of research goals.
Can you update the subcommittee on the plan for retiring these
chimpanzees? Can you highlight the challenges and considerations
involved, including any funding challenges?
Answer. Thank you for your leadership in working with the National
Institutes of Health (NIH) and the Institute of Medicine (IOM) to
resolve issues related to NIH-owned or supported chimpanzees in
research. An update on the NIH plan for chimpanzee retirement follows.
Many factors must be considered to ensure a successful chimpanzee
retirement process: Availability and complexity of creating the
physical sanctuary space, grouping of animals based on individual and
group behavioral characteristics, transporting chimpanzees (which
requires healthy animals and temperate weather), and arranging for the
care of an aging population. NIH has retired approximately 270
chimpanzees. At the present time, there is insufficient space in the
Federal chimpanzee sanctuary system to accommodate all of the
chimpanzees that will eventually be transferred. Sufficient and
appropriate sanctuary space is one of the major hurdles to retiring
more animals. Another is the need to select carefully the 50 most
suitable research animals prior to retiring the remainder.
Since 2005, NIH has moved nearly 270 chimpanzees into the Federal
Sanctuary System. Our plan to transfer all remaining NIH-owned
chimpanzees from the New Iberia Research Center has been completed. The
last group of nine chimpanzees was moved to the Federal Sanctuary
System on June 12th. Currently, Chimp Haven, Inc. is the only facility
in the Federal Sanctuary System, and it is nearing capacity. As a
result of natural attrition and careful planning of group composition,
we anticipate retiring approximately 30 more chimpanzees by the end of
2014. We are actively looking for alternate sites that meet, or can be
modified to meet, the high standards required to ensure that these
chimpanzees are well cared for. These requirements include adherence to
PHS Policy on Humane Care and Use of Laboratory Animals, the CHIMP Act
of 2000 (Public Law 106-551); Chimp Haven is Home Act (Public Law 110-
170); the CHIMP Act Amendments of 2013 (Public Law 113-55); and the
sanctuary specific regulations at 42 CFR Part 9. Chimp Haven, Inc.
meets these requirements.
A Request for Information NOT-OD-14-067 (April 7, 2014) was issued
to solicit information from facilities potentially qualified to join
the Federal Chimpanzee Sanctuary System. Responses identified three
potential options for additional sanctuary space, but all would require
additional and potentially costly construction. NIH is looking at all
options to develop sufficient sanctuary space but cannot yet estimate
the time required.
Second, a major hurdle is the determination of the 50 chimpanzees
most suitable for critical research. This selection must occur prior to
retirement because the Chimp Act, as modified by the Chimp Haven is
Home Act, mandates that retired chimpanzees cannot be returned to
invasive research. These research chimpanzees will be chosen after an
extensive NIH review of experimental protocols to ensure that all IOM
criteria are met. These protocols, and the final selection of research
animals, may require a period of several years. No chimpanzees will be
used for NIH-supported invasive biomedical research unless chosen as
part of the group of 50. Chimpanzees will stay at their current
facilities, receiving high-quality medical and dental care, in their
social groups, and under the care of familiar staff. Once the 50 have
been chosen, remaining animals will be transferred to the Federal
Sanctuary System as space permits. NIH will regularly reevaluate
research needs and reduce the number of research animals as warranted.
Some chimpanzees at the research or reserve facilities will be
available to move to the Federal Sanctuary System almost immediately
because they will not be suitable for research protocols. The
professional staff at each facility is currently identifying these
animals based on many criteria. We are making progress, but it is not
yet possible to specify a timeline for the disposition of all
chimpanzees. It is likely to be several years before the completion of
all chimpanzee retirements.
disease prevention
Question. I don't have to tell anyone here about my passion for
disease prevention. NIH has an important role to play in conducting
research on disease prevention--after all, it is the National
Institutes of Health, not the National Institutes of Treatment.
I was very pleased to see that NIH recently released its first 5-
year strategic plan for the Office of Disease Prevention, within the
Office of the Director. How will this new plan help advance disease
prevention research? I'm particularly interested in how the plan will
address gaps in research that are identified by the U.S. Preventive
Services Task Force.
As you know, the ACA included a provision that requires insurance
companies to cover any preventive service recommended by the US
Preventive Services Task Force (USPSTF) with no deductible, no co-pay.
When the USPSTF review interventions, they often find that there is not
enough research to make a recommendation. In those cases, they publish
a number of questions that need to be answered before a recommendation
could be made. NIH does not currently use these questions in their
research agenda planning process.
The Office of Disease Prevention (ODP) was created in 1986 in
response to the Health Research Extension Act of 1985 which required
the creation of an Associate Director for Prevention. ODP includes the
Office of Dietary Supplements, the Tobacco Regulatory Science Program,
and supports NIH's Prevention Research Coordinating Committee.
On January 3, 2014, NIH adopted its first-ever strategic plan for
disease prevention research, which had the following priorities:
--Systematically monitor NIH investments in prevention research and
assess the progress and results of that research.
--Identify prevention research areas for investment or expanded
effort by the NIH.
--Promote the use of the best available methods in prevention
research and support the development of better methods.
--Promote collaborative prevention research projects and facilitate
coordination of such projects across the NIH and with other
public and private entities.
--Identify and promote the use of evidence-based interventions and
promote the conduct of implementation and dissemination
research in prevention.
--Increase the visibility of prevention research at the NIH and
across the country.
Some examples of grants funded by ODP in 2013 are:
--Transforming Cancer Health Messaging: Engaging Alaska Native People
Through Digital Storytelling
--Cyber Partners: Harnessing Group Dynamics to Boost Motivation to
Exercise
--Uganda Working Group on Non-communicable Disease Risk Factors
--Psoriasis and the Risk of Diabetes
--Financial Incentives for Smoking Cessation Among Disadvantaged
Pregnant Women
--Mood and Insulin Resistance in Adolescents at Risk for Diabetes
--Natural Disaster Effects on Aggressive Children and Their
Caregivers
--Biomarkers in HPA Axis and Inflammatory Pathways for Suicidal
Behavior in Youth
--Collaborating to Measure the Effects of Stroke Preventive
Interventions
Answer. In February 2014, the NIH Office of Disease Prevention
(ODP) released its first Strategic Plan which outlines the priorities
that the Office will focus on over the next 5 years. The goal of this
effort is to increase the scope, quality, dissemination, and impact of
prevention research supported by NIH. The ODP will achieve this goal by
providing leadership for the development, coordination, and
implementation of prevention research in collaboration with NIH
Institutes and Centers and with other partners. While the priorities
and objectives outlined in the plan are designed to benefit the broader
NIH prevention research community, the plan itself was developed as a
tool for the ODP and does not represent a trans-NIH plan for prevention
research.
The ODP strategic plan includes six strategic priorities that will
allow the Office to expand its influence by, for example, providing
training in prevention methodology and developing new strategies for
identifying research needs--activities that may not otherwise be
addressed by a single NIH Institute or Center but are important for
advancing disease prevention research more broadly. Interest in disease
prevention has grown, and NIH has a responsibility to ensure that the
best prevention science is supported to inform clinical and public
health initiatives at the individual, organizational, community, and
policy levels. The strategic priorities included in the plan will allow
the ODP to play an important role in that process while giving NIH
Institutes and Centers the flexibility to support prevention research
within its extramural and intramural programs that best reflects its
mission and state of the science of their programs.
Strategic Priority II supports the identification of prevention
research areas that may benefit from investment or expanded effort by
NIH. In addition to utilizing results of new portfolio analysis tools
that are under development (Strategic Priority I), the ODP will achieve
this goal by working closely with the NIH Institutes and Centers, as
well as other Federal and non-Federal partners such as the U.S.
Preventive Services Task Force (USPSTF) to identify and prioritize gaps
in prevention science and promote research in these areas to broaden
the knowledge base. The USPSTF conducts scientific evidence reviews of
a broad range of clinical preventive healthcare services (such as
screening, counseling, and preventive medications) and develops
recommendations for primary care clinicians and health systems. As part
of its clinical recommendation process, the USPSTF identifies
significant gaps in key areas of knowledge that may limit the full
realization of the benefits of evidence-based preventive services
recommendations. Of particular concern to the research community are
areas that receive an Insufficient or ``I'' recommendation by the
USPSTF, which indicates that current evidence is insufficient to assess
the balance of benefits and harms of the service under consideration.
As the NIH liaison to the USPSTF, the ODP refers Insufficient or ``I''
recommendations made by the USPSTF to NIH scientific program staff. The
NIH Institutes and Centers can use this information to help them make
decisions during the post peer-review process to further expand
knowledge within a given research area.
To further advance Strategic Priority II, the ODP is also
developing a systematic process that can be used by NIH Institutes and
Centers to report recent advances or on ongoing research that addresses
the research gaps identified by the USPSTF and other partners. This
information, along with identified gaps, will help to highlight
research areas that are in need of additional support. In addition to
disseminating this information to our colleagues, the ODP will
incorporate this information into its own efforts to promote
collaborative prevention research projects and facilitate coordination
of such projects across NIH and with other public and private entities
(Strategic Priority IV).
rehabilitation research
Question. I was pleased to hear that NIH is implementing many of
the recommendations of the 2012 Blue Ribbon panel on rehabilitation
research. This is a critical area of research to improve the functions
and abilities of people with severe injuries, illnesses or conditions
so that they can live independently.
This research is done across many Institutes and Centers, but there
is no consistent definition of rehabilitation research. Without a
common definition, it is difficult to ensure that core priorities are
being addressed and to accurately track the science across all of the
Institutes and Centers. In the fiscal year 2012 Labor-HHS bill, this
subcommittee asked that NIH adopt an NIH-wide definition. A year later,
the Blue Ribbon panel went a step further to recommend that NIH adopt
the WHO definition. What steps is NIH taking to address this issue?
Rehabilitation research is cross-cutting and focuses on improving
the ability of people with severe injuries, illnesses, disabilities and
chronic conditions to improve skills and functions and live as
independently as possible.
Medical rehabilitation research is conducted at NIH through
numerous Institutes and Centers. The research is intended to be
coordinated by the National Center for Medical Rehabilitation Research
(NCMRR) within the National Institute for Child Health and Human
Development (NICHD). One of the main difficulties in coordinating the
work being done at the various Centers and Institutes is that NIH does
not have a consistent definition of ``rehabilitation research''.
The fiscal year 2012 Senate LHHS report language:
Rehabilitation Research.--The Committee commends NIH for
appointing a blue-ribbon panel to evaluate rehabilitation
research at the National Center for Medical Rehabilitation
Research [NCMRR] and across all of NIH. The Committee requests
a copy of the panel's report when it is available. The panel is
urged to identify gaps in the field of rehabilitation research
and recommend which ICs or other Federal agencies should be
responsible for addressing them. In addition, the Committee
recognizes the improvements that have been made in delineating
rehabilitation research as part of NIH reporting mechanisms
established since the passage of the NIH Reform Act. However,
the Committee encourages NIH, through the leadership of NCMRR,
to further clarify a consistent definition of rehabilitation
across all institutes and centers and to seek ways to delineate
between physical, cognitive, mental and substance abuse
rehabilitation when characterizing NIH-supported research.
Finally, the Committee encourages NCMRR to explore the broader
social, emotional and behavioral context of rehabilitation,
including effective interventions to increase social
participation and reintegrate individuals with disabilities
into their communities.
The December 2012 report from the Blue Ribbon Panel on Medicare
Rehabilitation Research further emphasized the importance of taking
action to clarify the definition of ``rehabilitation research'' by
recommending the following:
``The study of mechanisms and interventions that prevent, improve,
restore or replace lost, underdeveloped or deteriorating function,
where function is defined at the level of impairment, activity and
participation according to the WHO-ICF model (World Health
Organization's International Classification of Function, Disability and
Health).''
Answer. Since enactment of the 1990 law authorizing the
establishment of the National Center for Medical Rehabilitation
Research (NCMRR) under the auspices of the National Institutes of
Health (NIH), NIH has been using the definition of medical
rehabilitation research included in the statement of purpose for the
Center (Sec. 452 of the Public Health Service Act, 42 U.S.C. 285g-4),
which states that the purpose of the Center is to support research,
training, and health information dissemination ``with respect to the
rehabilitation of individuals with physical disabilities resulting from
diseases or disorders of the neurological, musculoskeletal,
cardiovascular, pulmonary, or any other physiological system (hereafter
in this section referred to as ``medical rehabilitation''). This
definition, which is used consistently across NIH, has allowed medical
rehabilitation research to be distinguished from other rehabilitation
research efforts, such as those that involve mental health or addictive
disorders. The World Health Organization (WHO) definition was adopted
since that time; while NIH has no objections to using the WHO
definition, the law would need to be amended to replace current
language.
If the definition were changed, it would need to be translated into
an operational definition to allow appropriate characterization of the
more than 11,000 competing grants that NIH currently funds each year.
NIH uses its ``Research, Condition, and Disease Categorization (RCDC)''
system--a sophisticated text-data mining software--to categorize and
cluster words and phrases that reflect agreed-upon definitions. See
http://report.nih.gov/rcdc/. NIH has already started to develop an RCDC
``fingerprint'' for medical rehabilitation research, which will allow
NIH to track the research portfolio as it changes over time, and to
understand the breadth and depth of the portfolio as part of the
upcoming effort to develop a strategic research plan.
medication in pregnancy
Question. Each year more than four million women give birth in the
United States and more than 3 million breastfeed their infants. Nearly
all of these women will take a medication regularly or receive a
vaccine, but little is known about the effect of most drugs on the
woman or her child. For most drugs, we don't know the impact on child
development and we don't know the impact on the effect of the
medication. A study in the American Journal of Medicine illustrated
that fewer than 10 percent of medications approved by the FDA since
1980 have enough information to determine their risk for birth defects.
Women and doctors are forced to guess whether to continue their
treatment.
This gap in understanding has become increasingly problematic as
more women delay childbearing and rates of chronic disease rise. More
expectant mothers than ever before are requiring medications to manage
conditions such as diabetes, hypertension, depression, and asthma.
What types of research activities is NIH engaged in to fill these
research gaps? What is the state of our understanding of the effect of
drugs during pregnancy and breastfeeding?
Answer. Primarily through its Obstetric and Pediatric Pharmacology
and Therapeutics Branch (OPPTB), the Eunice Kennedy Shriver National
Institute of Child Health and Human Development takes a range of
approaches to support research activities on medication use in
pregnancy and during breastfeeding, collaborating with other NIH
Institutes and Centers as appropriate for their areas of expertise.
The Obstetric-fetal Pharmacology Research Units (OPRU) Network was
established in 2004 with four academic research institutions to improve
the safety and effectiveness of the medications commonly used (but
often never having been tested) in women during pregnancy and
postpartum. The OPRU Network has provided critical research
infrastructure for a multidisciplinary collaboration of researchers to
perform basic/translational studies and phase I/II clinical trials
aimed at characterizing and evaluating the impact of medications on
metabolism and physiological, cellular, and molecular changes during
pregnancy. The OPRU Network also conducted opportunistic studies of
medications in women who were already taking these medications during
pregnancy. More than 100 research articles from these studies have been
published in peer-reviewed scientific journals.
Some study results have directly informed clinical practice. For
example, a study of the anti-diabetes drug glyburide use during
pregnancy showed that glyburide can cross the placenta and that the
drug's concentrations are about 50 percent lower in pregnant women with
type 2 diabetes than in non-pregnant women with type 2 diabetes,
suggesting that a higher dose may be needed to achieve optimal
therapeutic effects. A study of oseltamivir, a medication for treating
and preventing influenza, indicated that the drug plasma concentrations
are much lower and apparent clearance significantly higher in pregnant
women compared with non-pregnant women, suggesting an increased dose
may be necessary to achieve comparable effects.
The OPRU Network currently supports a randomized clinical trial to
determine the pharmacologic effects of anti-diabetic drugs (glyburide
and metformin) separately, and in combination for management of
gestational diabetes, a phase I clinical trial to evaluate the effect
of early treatment with pravastatin for prevention of preeclampsia, and
an exploratory study to identify vaginal biomarkers of response to
progestin treatment of preterm birth. The Network also is funding
several investigator-initiated grants on nicotine replacement therapy
for smoking cessation during pregnancy and safety and effectiveness
studies on anti-hypertensive medications in pregnancy. In addition, to
encourage young investigators working in this area of research, the
OPPTB supports several postdoctoral training programs.
cancer and distress
Question. I know first-hand that a cancer diagnosis can be
devastating for patients and families. Studies show that half of all
cancer patients experience psychological and social distress as a
result of their cancer diagnosis. But there is good news: a study
conducted by Dr. Barbara Andersen and published in the Journal of
Oncology showed that patients with breast cancer who receive distress
screening and social and emotional follow-up care have a 45 percent
reduced risk of cancer recurrence, a 56 percent reduced risk of death;
and a 59 percent reduction in breast cancer death even WITH recurrence.
These are remarkable outcomes. Yet the Institute of Medicine has
consistently concluded that cancer care provides state of the art
biomedical treatment but does little address the psychological and
social needs of cancer patients.
What requirements, if any, does NCI have on its intramural and
extramural research programs to screen patients for distress and ensure
follow up care? What kind of research is being done, either at NCI or
at the Mental Health Institute, to further this promising area of
research?
Answer. As the Federal agency that supports the Nation's cancer
research enterprise, the National Cancer Institute (NCI) conducts and
facilitates research and the development of valid tools that can inform
standard clinical practice and medical decisionmaking. However, NCI
does not establish standards of care or place requirements on care-
givers. Other Federal agencies and private-sector organizations (such
as specialty societies and cancer-specific groups) develop medical
recommendations for cancer, building upon NCI's research and the work
of these other agencies in the Department of Health and Human Services
(HHS) to develop guidelines or recommendations about all aspects of
medical practice related to cancer care.
Still, it is important to emphasize that both NCI and the National
Institute of Mental Health (NIMH) support research related to screening
for emotional distress experienced by patients who receive a cancer
diagnosis and subsequent treatment. In this area, NCI's role is to fund
and support research that shows the efficacy and impact of systematic
screening for emotional distress on cancer survivors' subsequent health
and function. Historically, we have funded--and we continue to
support--randomized controlled trials that test the ability of
psychosocial and behavioral interventions to reduce psychological
distress and promote adaptation to illness. This research has shown
that a wide variety of interventions (both at the individual and group
levels and varying in content) are effective in improving understanding
of illness and adherence to treatment, reducing depression, fatigue,
and stress, and adopting healthy behaviors.
A key response by NCI to the Institute of Medicine (IOM) report,
Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs,
was to include attention to survivorship and palliative care in the
funding of NCI's Community Cancer Centers pilot program (NCCCP). One of
the deliverables for funded NCCCP sites was to develop the capacity to
screen for distress and refer individuals to appropriate psychosocial
care as needed. NCCCP sites also had to expand their psychosocial
programs, as well as training of staff to identify and manage these
issues in patients being treated at each institution. In addition, NCI
solicited information from the clinical-investigator community about
the tools they are using to screen for distress, as part of the Grid
Enabled Measures (or GEM) initiative. The GEM database collects
questions that measure unmet needs, depression, and anxiety. These are
available for clinicians and researchers to access, evaluate, and (with
the exception of copyrighted instruments) be used to care for patients
under active treatment and other cancer survivors. NCI is initiating
collaborations with the American Society of Clinical Oncology (ASCO)
and the Commission on Cancer. In 2012, the Commission gave member sites
until 2015 to implement psychosocial distress screening in their
centers.
NIMH has funded several studies in recent years investigating
psychological distress and depression associated with cancer diagnosis
and treatment. For example, NIMH has supported the development of the
Mental Health Assessment and Dynamic Referral for Oncology software,
which enables oncology treatment providers to screen for and monitor
several patient care domains, including: (1) mental health functioning;
(2) cancer-related symptoms and side effects; (3) the patient-provider
partnership; (4) barriers to treatment; and (5) adherence with medical
regimen and lifestyle change recommendations. Another team of NIMH-
funded researchers has studied whether depression can be prevented in
patients with head and neck cancer during treatment (with relevance to
other cancers), as well as whether initiating prophylactic
antidepressant treatment can improve timely completion of the cancer
therapy and preserve quality of life. Other NIMH-funded researchers
have studied the impact of cancer treatment, as opposed to diagnosis,
on mental health--for example, whether antidepressants can prevent the
impact of melanoma treatment on the brain, endocrine, and immune
systems.
In addition to these extramural efforts, the NIMH Division of
Intramural Research Programs conducted a multiyear study investigating
biological, psychological, and social factors that affect living with a
chronic life-threatening illness such as cancer, HIV, or other rare
diseases, as well as suicide risk and palliative care decisionmaking
procedures for treating children and adolescents with life-threatening
conditions.
______
Questions Submitted by Senator Richard J. Durbin
american cures act
Question. In 1965, the U.S. spent more than 25 percent of our non-
defense discretionary budget on research and development--last year
that number was 10 percent. Between 2003 and 2012, the NIH budget has
not even kept up with inflation, resulting instead in a 22 percent
decline in real purchasing power. The number of research grants at NIH
has declined every year for the past 10 years.
Dr. Collins, you have warned that continuing this trend of funding
will cause some of America's best young researchers to take their
talents to other industries--or other countries.
What promising breakthroughs or developments do you think are at
risk of delay due to the U.S. Federal Government failing to keep pace
with inflation in funding the NIH?
Answer. NIH-supported researchers make scientific discoveries every
day, advancing research related to countless health and disease issues.
While it is impossible to predict exactly when breakthroughs will occur
in a particular scientific field, the pace of discovery will be delayed
if funding fails to keep pace with inflation. For example, this could
cause delays in the significant progress that researchers are making in
developing a universal flu vaccine that could offer protection against
any flu virus strain, including those that may cause pandemics.
Similarly, NIH efforts to develop a vaccine for HIV or even a cure for
AIDS may be hampered.
In cancer research, recent results indicate that immunotherapy may
be a new and effective form of treatment. However, opportunities to
expand this research to include additional patients and other types of
cancer may not be possible if NIH funding remains stagnant. NIH also is
engaged in extensive efforts to respond to the emerging public health
threat from antimicrobial resistance (AMR), including support for basic
research, development of new and faster diagnostics, and creating a
national database of genomic sequence data. These efforts could be
hampered if NIH funding does not keep pace with inflation. NIH efforts
to leverage its resources in partnerships with the private sector also
could be disrupted, such as the new Accelerating Medicines Partnership
(AMP) that brings biopharmaceutical companies and several nonprofit
organizations together with NIH to identify and validate biological
targets of disease for future drug development.
Please describe the biomedical discoveries, training of junior
scientists, and economic benefits that could result if NIH was provided
with a steady source of funding that increased year after year to keep
up with inflation?
Answer. A steady source of funding helps support biomedical
scientists. Having a budget that keeps pace with inflation would help
to reassure scientists that they will have the necessary support for
the duration of their projects. Steady investment in the National
Institutes of Health (NIH) helps enable our researchers to achieve
their full scientific potential in all research areas, fueling
biomedical discoveries from autism to Alzheimer's disease to cancer to
diabetes. Inflation-adjusted budgets also may enable NIH to award more
grants to fund investigator-initiated research, thereby allowing the
country's most innovative scientific thinkers to chart the best path
forward in their research areas.
Promising young scientists who have chosen career paths outside of
biomedical research in recent years due to uncertain funding also would
be encouraged by a stable funding model and may reconsider pursuing
research careers. Coupled with NIH's commitment to fund new
investigators at success rates equal to those of established
investigators, this scenario would enable NIH to attract and sustain a
talented biomedical research workforce.
NIH investments reap substantial economic benefits; the agency
directly supports about 300,000 researchers at more than 2,500
institutions in every state, and these investments spur additional job
creation in those communities as well. In 2012, United for Medical
Research estimated that NIH investments supported more than 402,000
jobs and resulted in $57.8 billion in economic output nationwide. A
report from the Milken Institute indicates that a $1 increase in NIH
funding can increase the bioscience industry output by $1.70 in a given
year, and the long-term effects could be even greater. Given these
short-term economic effects, an inflation-adjusted budget for NIH could
spur job growth across the country, increase economic output, and
reduce health spending by producing better, more cost-effective
treatments and prevention strategies. Over the long term, increased
support for NIH will lead to reductions in disease, longer lifespans,
and improved quality of life for all Americans.
sequestration and government shutdown
Question. The National Institutes of Health is the Nation's medical
research agency and the leading supporter of biomedical research in the
world. More than 80 percent of the NIH's budget goes to over 300,000
research personnel at more than 2,500 universities and research
institutions through the United States. Last year, sequestration cut
the NIH's $30.7 billion budget by almost $1.6 billion. The deleterious
effects of sequestration were compounded by the government shutdown
which took place October 1 to October 16 of 2013 and temporarily
curtailed most of NIH's operations.
Please summarize the impact that sequestration and the government
shutdown had on NIH's ability to award grants and support the training
and education of scientists. Please describe the impact that
sequestration and the government shutdown had on biomedical innovation
and how the cuts in funding impacted patients currently enrolled in
clinical trials.
Impact of Sequestration
Answer. Sequestration dampened NIH's ability to support biomedical
research. The overall award rate for NIH research project grant
applications in fiscal year 2013 fell to approximately 15 percent, a
historic low.\1\ \2\ Compared to fiscal year 2012, in fiscal year 2013,
NIH funded approximately 750 fewer competitive research project grants
(e.g., new or renewal applications) that were determined to be highly
meritorious in grant review, including over 200 fewer competing renewal
applications. Competing renewal applications represent promising
follow-on research stemming from previously funded grants. Lack of
continued funding diminishes the NIH's ability to leverage previous
investments and capitalize on recent scientific progress.
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\1\ http://nexus.od.nih.gov/all/2014/03/05/comparing-success-award-
funding-rates/#sthash.aM0tN2GL.dpuf
\2\ NIH's definition of ``award rate'' is the number of awards made
in a fiscal year divided by the absolute number of applications.
---------------------------------------------------------------------------
NIH Institutes and Centers (ICs) were also forced to reduce funding
for noncompeting, ongoing research grants. Reductions varied by IC, but
the NIH-wide average was -4.7 percent. Further, at least ten new
funding initiatives (``request for applications'' or ``request for
proposals'' concepts) were planned but not published, including cancer
studies that could have improved our ability to distinguish accurately
non-lethal tumors from life-threatening ones, and autism studies to
investigate genetic and environmental factors that affect the risk of
autism in preterm infants.
Many of the NIH ICs also reduced their funding for training grants
and fellowships. For example NIGMS, which sponsors the majority of NIH-
supported pre-doctoral trainees, funded 186 fewer trainees than it
would have without sequestration. Trainees who were already funded also
were affected, as there was no increase in stipend levels for National
Research Service Award recipients in fiscal year 2013.
Sequestration also diminished NIH's ability to conduct research at
the Clinical Center. Approximately 750 fewer new patients were admitted
to the NIH Clinical Center, a decrease from 10,695 new patients in 2012
to approximately 9,945 new patients in 2013. This reduced the number of
patients who could have benefitted from enrollment in clinical
protocols, as well as slowed the pace of important clinical research.
Note that while much of the decrease in enrollment numbers is due to
funding, patient recruitment is dependent on multiple factors.
Funding cuts driven by sequestration have had ripple effects
throughout the biomedical research community. One recent survey
examined sequestration's impact on research conducted by universities
across the country.\3\ The most commonly cited impacts of the sequester
among survey respondents were a reduction in the number of new Federal
research grants (70 percent of responding universities), delayed
research projects (also 70 percent), personnel reductions (58 percent),
reduced research activity (81 percent), admission of fewer graduate
students (23 percent), as well as tuition reductions and reduced
stipend levels for students (14 percent).
---------------------------------------------------------------------------
\3\ Association of American Universities, Association of Public and
Land-grant Universities, and The Science Coalition. Survey on
Sequestration Effects: Selected Results from Private and Public
Research Universities. November 2013.
---------------------------------------------------------------------------
Impact of Government Shutdown
The Government shutdown impacted NIH and the biomedical research
community. Approximately 75 percent of the NIH workforce was furloughed
during shutdown. For the community of NIH's extramural investigators,
shutdown caused delays in grant review and funding processes.
Typically, NIH receives the largest number of grant applications in
October. Because of the prolonged shutdown, all of the October receipt
dates were rescheduled for November, including those for NIH's largest
grant activities, such as the investigator initiated R01 applications,
Small Grants (R03), Exploratory Development Grants (R21), AREA awards
(R15), and Career Development (K) activities. Reviews of more than
11,000 grant applications were delayed by the shutdown.
October is also one of the 3 months with the largest volume of NIH
Scientific Review Group meetings, the first step of peer review. Over
200 Scientific Review Group meetings had to be rescheduled due to the
shutdown; most of the October meetings involved reviewers travelling to
meetings scheduled to be convened ``in-person''. These ``in-person''
meetings had to be rescheduled, and travel arrangements had to be
cancelled and re-arranged.
The NIH Intramural Research Program (IRP) was also profoundly
affected and lost progress during the shutdown. The Clinical Center did
not enroll any new patients in clinical trials or to start new trials.
Therefore, approximately 200 new patients were not admitted to the
Clinical Center. Of those denied access, 30 were children, including 10
with cancer. Only 15 to 20 percent of IRP staff were ``excepted'' from
furlough, so that they could protect life (mostly in the Clinical
Center, where 75 percent of the staff were required to work), guarantee
safety (infrastructure support including security and the power plant),
and protect large investments in materials and property (animals, cell
cultures, and expensive equipment).
The shutdown took a toll on NIH intramural training programs and
trainees, too. In addition to being a biomedical research enterprise,
NIH is the largest training facility in the world for biomedical
researchers. During the shutdown, there were approximately 4,000
postdoctoral fellows, 800 post baccalaureate students, 500 graduate
students, and 45 medical students who were unable to conduct their
research. For many of these trainees, time is of the essence. Their
appointments are time-limited (less than 1 year for the medical
students, up to 2 years for the post baccalaureate students, and
usually three to 4 years for the postdoctoral fellows and graduate
students). Loss of a few weeks of research and mentoring as well as the
additional work time needed to regain momentum--while cell lines are
started up again, animals are bred, and experiments that may have
suffered in the shutdown are repeated--represent a significant
proportion of their NIH training experience that could affect their
future careers.
congenital heart disease
Question. Congenital Heart Disease (CHD) is one of the most
prevalent birth defects in the United States and a leading cause of
birth defect-associated infant mortality. Due to medical advancements,
more people with congenital heart defects are living into adulthood.
The healthcare reform law includes a provision that authorizes the
Centers for Disease Control and Prevention (CDC) to expand surveillance
and track the epidemiology of CHD across the life-course, with an
emphasis on adults. The Consolidated Appropriations Act of 2014
provided the CDC with $2.9 million in new funding for enhanced CHD
surveillance. Recent data suggest that the number of infant deaths
related to CHD is decreasing. Successful interventions in infancy and
childhood are resulting in an aging population of congenital heart
disease survivors.
How is the NIH systematically responding to this new population of
survivors reaching adolescence, adulthood, and advanced age?
How is NIH utilizing adult congenital heart disease research
experts in these efforts?
How is NIH supporting adult CHD professionals so the field can
grow? Is the NIH offering training grants to grow the field? Is the
Pediatric Heart Network inclusive to adult CHD experts? Is your agency
formally engaging adult populations in CHD research?
Answer. Advances in diagnosis and care have led to significant
improvement in survival rates for Congenital Heart Disease (CHD) such
that more adults than children are now living with CHD. The National
Heart, Lung and Blood Institute (NHLBI) supports research on the causes
of CHD and the evolving natural history and co-morbidities in adults
with CHD across the lifespan. For example, the Bench to Bassinet
Program (B2B) is identifying genetic and epigenetic causes of CHD to
help risk-stratify and personalize treatment for children and adults
with CHD. The Pediatric Heart Network (PHN) was launched in 2001 to
conduct studies to improve outcomes and quality of life in children
with heart disease and includes experts in adult congenital heart
disease (ACHD). The PHN is following the largest assembled cohort of
individuals with single ventricle physiology into adulthood to
determine barriers to transitioning to adult care and to evaluate their
health status and co-morbid conditions at specific intervals. The PHN
is also in the process of launching a trial in adolescents and young
adults with single ventricle physiology to assess whether use of a
phosphodiesterase-5-inhibitor medication will prevent functional
deterioration and delay the onset of heart failure.
NHLBI also partners with ACHD-themed organizations to advance the
field of ACHD research, such as The Health, Education and Access
Research Trial (HEART-ACHD) and The Research Empowerment for Adult
Congenital Hearts (REACH) project, both funded by NHLBI and conducted
in partnership with the Adult Congenital Heart Association (ACHA) and
the Alliance of Adult Research in Congenital Cardiology (AARCC). In
June 2014, NHLBI and the ACHA will host a working group, ``Adult
Congenital Heart Disease: Emerging Research Questions,'' to identify
critical research gaps in the care of adults with CHD. This group will
build partnerships between ACHD experts and experts in the
complementary fields of adult cardiovascular care and pediatric
cardiology. Participants will develop methodological approaches that
leverage recent progress in multicenter ACHD research and existing
congenital heart disease data infrastructure, and will develop
strategies to engage patients in the development and execution of
research studies.
To ensure a robust community of ACHD investigators spanning basic
and clinical research, NHLBI supports institutional training grants for
CHD, the PHN Scholars award, to fund small pilot studies, and
individual career development awards for ACHD investigators For
example, an NHLBI-supported career development awardee is developing,
testing, and validating a Quality Assessment Tool for Adults with
Congenital Heart Disease (QAT-ACHD) for the outpatient management of
selected ACHD conditions to help standardize high-quality ACHD care.
Another NHLBI career development awardee is studying the role of
myocardial fibrosis in three ACHD conditions. The same investigator has
also secured funding from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) for a pilot study on
enlarged thoracic aortas in patients with bicuspid aortic valve.
Mechanisms such as these are designed to ensure growing expertise in
the field of ACHD research, with a strong focus on the long-term
implications of CHD and its treatment for the increasing number of
persons who survive for many decades after diagnosis.
______
Questions Submitted by Senator Jeanne Shaheen
oppnet
Question. Can you provide an update about OppNet, the 5-year
initiative to support basic behavioral and social sciences research
that began in 2010? What can you tell us about the findings of that
initiative? When will a report be available?
Answer. Between October 2010 and May 2014, the Basic Behavioral and
Social Science Opportunity Network (OppNet) provided $64.2 million to
fund 152 extramural research projects. OppNet lists all its grants by
original year of funding at http://oppnet.nih.gov/resources-
initiatives.asp. Among the OppNet grants is early investigator Dr.
Santosh Kumar's Predicting Smoking Abstinence via Mobile Monitoring of
Stress and Social Context. This study demonstrates that modern sensor
technology can obtain a much more detailed and accurate representation
of personal and environmental influences on smoking than previously
possible. Based partially on this work, Popular Science magazine named
Dr. Kumar one of the 10 most brilliant young scientists. Another
project, Neural Mechanisms of Habit Formation and Maintenance, analyzes
cellular, molecular, and circuit mechanisms to understand how behaviors
become ``automatic'' regardless of outside influences. Dr. Henry Yin
found that stimulating mouse neurons to generate dopamine can foster
the adoption of healthy behaviors and reduce unhealthy behaviors--all
without providing incentives (e.g., food rewards). These findings,
already appearing in at least five peer-reviewed publications, suggest
exciting possibilities for future studies with important clinical
implications.
OppNet has expanded both the perspective of researchers and NIH
program directors. Nineteen of OppNet's 28 new investigators (68
percent) received non-Federal funding prior to applying, compared with
21 percent of basic behavioral and social sciences research (basic-
BSSR) and 39 percent of applied behavioral and social sciences research
(applied-BSSR)--an example of the initiative's success at expanding
NIH's scope of basic-BSSR. NIH program directors report that OppNet has
increased their knowledge of other NIH Institutes and Centers (ICs)'
missions and research interests and that OppNet has allowed them to
solicit and fund projects that likely could not have occurred without
OppNet's infrastructure. Perhaps the best examples to date are the
grants funded through the funding opportunity, Basic Behavioral
Research on Multisensory Processing http://oppnet.nih.gov/resources-
2013fundedapp.asp. These projects explain how a combination of visual,
auditory, olfactory, gustatory, non-pain somatosensory, and/or
vestibular input influences basic perceptual and behavioral processes.
This initiative stimulated new collaborations between ICs that were
supporting research on sensory processing, but from the perspective of
single sensory systems, such as vision or audition.
ICs are organized somatically or by disease. OppNet's
infrastructure facilitates the trans-sensory and transdisciplinary
research projects that likely would lack a clear ``home.'' Moreover,
OppNet has been so successful at coordinating basic and applied BSSR
across the NIH that some ICs decided to fund all or part of 23
additional projects beyond what was planned for in the OppNet budget.
As the grants funded under OppNet have not gone through a full five-
year funding cycle, a formal and comprehensive program evaluation would
be premature at this time. However, OppNet makes its activities and
accomplishments available to the public through its Web site at http://
oppnet.nih.gov/.
diabetes
Question. I understand that, as a result of previous studies, there
is evidence of a link between poor blood glucose control and
development of diabetes complications, and the tremendous long-term
benefits of early, effective blood glucose control, particularly in
recent onset diabetes. Can you tell me what the agency is doing to
better understand the underpinnings of complications like kidney
disease?
Answer. Controlling and preventing diabetes are the best approaches
to preventing or minimizing its many health complications, including
kidney disease. Diabetes--both type 1 and type 2--is the major cause of
end-stage kidney failure. The landmark NIH-supported Diabetes Control
and Complications Trial (DCCT) and its follow-up study, the
Epidemiology of Diabetes Interventions and Complications (EDIC),
demonstrated how critically important it is to control blood glucose
levels early in the course of type 1 diabetes in order to reduce the
likelihood of subsequent complications. DCCT participants who
intensively controlled their blood glucose levels had significantly
lower rates of eye, nerve, kidney, and cardiovascular complications
than those who received standard care. This effect extended for many
years after the study ended.
A second landmark NIH-supported clinical trial, the Diabetes
Prevention Program (DPP), showed that an intensive lifestyle
intervention designed to achieve modest weight loss through a
combination of diet and exercise lowered type 2 diabetes rates by 58
percent, and that the generic diabetes medication metformin reduced
diabetes rates by 31 percent, relative to placebo. A follow-up study to
the DPP, the DPP Outcomes Study (DPPOS), is assessing the long-term
effects of interventions used in the DPP on the development of type 2
diabetes and its complications. After 10 years of follow-up, DPPOS
found that the lifestyle intervention continued to dramatically reduce
the development of type 2 diabetes--and consequently its
complications--and also reduced cardiovascular risk factors.
Diabetes is the leading cause of kidney disease, followed by high
blood pressure. Abnormally high blood glucose levels damage the
kidney's filtering units, which progressively and irreversibly impairs
kidney function. Thanks to NIH-supported research, scientists have made
great progress in developing methods, in addition to controlling blood
glucose levels, which slow the onset and progression of kidney disease
in people with diabetes. Two types of drugs used to lower blood
pressure, angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs), have proven effective in slowing
the progression of kidney disease in people with diabetes or high blood
pressure.
Because there is no way, at present, to restore kidney function
once it is lost, NIH research focuses on early detection of kidney
disease and strategies to slow or prevent the progression of disease.
The Chronic Renal Insufficiency Cohort (CRIC) Study, one of the largest
and longest ongoing studies of chronic kidney disease epidemiology in
the United States, is examining the natural history of kidney disease
as well as the broad range of illnesses experienced by people with
kidney disease. NIH is supporting a study that aims to identify
biomarkers that indicate a risk of progression of kidney disease.
Research supported by NIH has enhanced our understanding of the origin
of scar tissue that is common in many forms of kidney disease, how it
can impair kidney function, and how it might be prevented or treated. A
new initiative, currently in development, will address challenges
associated with growing nephrons, the kidneys' basic filtering unit.
NIH supports several studies that the private sector most likely would
not undertake, including pilot studies of novel therapies for kidney
disease.
emergency care
Question. The NIH recently created a new division, the Office of
Emergency Care Research. Considering that in New Hampshire, and
throughout the United States, there is an epidemic of narcotic
prescription abuse and overdose deaths, what can the this new office do
to help emergency providers curtail excess narcotic prescribing? How
can we increase awareness among providers to decrease medically
unnecessary narcotic prescriptions?
Answer. The Office of Emergency Care Research (OECR) was
established in 2012 to coordinate and develop emergency care research
across the National Institutes of Health. Emergency departments (EDs)
are unique treatment settings in that they serve some patient
populations that have little or no access to medical care, and who have
few available resources. For example, EDs may be the only facilities at
which poor and underserved populations receive care. For substance-
using populations, they provide a unique opportunity to assess the
overall health needs of the patient and link them to the care and the
support required to meet all of their health needs. OECR and the
National Institute on Drug Abuse (NIDA) are concerned about the
epidemic of narcotic abuse and are aware of the role of the emergency
care system in reducing this abuse.
NIDA is investing in research to develop clinical interventions
tailored to the ED setting. The goals of these interventions are to
facilitate accurate diagnoses and linkage to long-term care programs to
protect the overall health of the individual. Halting accidental or
unnecessary opioid prescriptions is a key component to thwarting the
devastating rise in opioid overdoses. For this reason, NIDA is
supporting research that will increase ED physician knowledge when
treating opioid patients by:
--identifying ways to effectively implement the use of prescription
drug monitoring programs (PDMPs) within the ED to decrease
prescription opioid prescribing, overdoses, and deaths.
Widespread use of PDMPs will provide ED physicians with the
information they need to prescribe opioids to those patients
who would benefit most from these essential medications, while
preventing these medications from reaching populations for
which they are not intended. (For more details see NIH grant
1R01DA036522-01.)
--developing improved, non-invasive devices that can detect traces of
narcotics and alcohol. This will help ED physicians to diagnose
and treat patients with substance abuse issues, because an
accurate diagnosis of substance abuse is the first step to its
treatment. (For more details see NIH grant 5R44DA031530-03.)
Since assuming the position of Director of OECR, Dr. Jeremy Brown
has met with program officers and senior staff at NIDA to discuss
strategies to increase research on drug abuse in the emergency care
setting. In addition, in October 2013, OECR, CDC, and NIDA staff were
scheduled to attend a special day training session on effective
approaches to addressing substance abuse disorders in the Emergency
Department. This conference was held as part of the annual meeting of
the American College of Emergency Physicians. Although the Government
shutdown prevented NIH staff from attending in person, this meeting
emphasizes the way in which NIDA, OECR and professional organizations
are cooperating to address the substance abuse epidemic.
Funding for research on the narcotic epidemic is provided by NIDA,
and the Office of Emergency Care Research will continue to work with
staff from NIDA to support and grow initiatives in this area.
asthma
Question. In November Congresswoman DeLauro and I wrote to
Secretary Sebelius to inquire about a provision in the National Heart,
Lung, and Blood Institute's (NHLBI) 2007 Expert Panel Guidelines for
the Diagnosis and Management of Asthma that recommends that physicians
who treat the majority of children with asthma ``determine exposures,
history of symptoms in presence of exposures, and sensitivities.'' They
make this recommendation so that ``physicians can advise patients on
ways to reduce exposure to allergens.'' While it has been many years
since release of the guidelines, we are concerned that we are failing
to meet this objective. I'd like your assurance that this work will
remain a high priority for the NIH and that you will continue to work
with all stakeholders to accelerate implementation of this laudable
objective.
Answer. NHLBI's National Asthma Education and Prevention Program's
(NAEPP) Guidelines Implementation Panel Report offers suggested
strategies to enhance dissemination and adoption of key recommendations
in the Guidelines. These strategies were offered as a list of possible
activities for NAEPP member organizations and other professional,
private sector, state and local government, and patient groups to
consider undertaking within their respective organizations in order to
improve asthma care, which many organizations have done. All programs
address exposures to environmental allergens and irritants as part of
the comprehensive approach to asthma necessary to achieve and maintain
asthma control.
National professional societies and patient groups and local
healthcare and community groups have made considerable progress in
engaging primary care providers, allergists, and representatives of
health plans to identify and overcome local barriers and accelerate
implementation of recommendations in the Guidelines, including those
relating to control of allergens. For example, the Centers for Medicare
and Medicaid Services Health Care Innovation Awards Program included
five awardees that address asthma; all of these programs incorporate
attention to environmental allergens. The Environmental Protection
Agency's (EPA) vibrant Community Network (http://
www.asthmacommunitynetwork.org/) and annual EPA leadership Awards
program offer outstanding examples of community organizations,
clinicians, and healthcare administrators, including Medicaid service
providers, across the country working together on programs that
incorporate measures to control environmental asthma triggers,
including allergens, into comprehensive asthma management. The Centers
for Disease Control and Prevention's National Asthma Program and the
NHLBI's National Asthma Control Initiative showcase tools and programs
developed by state public health and local community clinics that can
be adapted by other stakeholders. These tools include home-visit
guides, environmental assessment checklists, and clinical pathways for
assessing, treating, and monitoring all aspects of asthma care.
______
Questions Submitted by Senator Jerry Moran
accelerating medicines partnership
Question. The Accelerating Medicines Partnership (AMP) is expected
to address the ``valley of death'' in drug development. How much with
the Partnership shorten the current drug development timeline and how
much money will be saved?
If the Accelerating Medicines Partnership is successful, how will
you determine what future disease and conditions will be added to the
program?
Answer. The Accelerating Medicines Partnership (AMP) is a unique
type of public-private partnership of the National Institutes of Health
(NIH), the Food and Drug Administration (FDA), nonprofit organizations,
and biopharmaceutical companies. AMP is supporting research focused on
identifying and validating biological targets for new therapeutics, a
process called target validation. AMP was just launched in February and
is beginning with three specific pilot projects, in Alzheimer's
disease, type 2 diabetes, and rheumatoid arthritis/lupus.
Over half of drugs fail in phase II and phase III clinical trials
due to lack of efficacy, and improvements in the target validation
process should reduce that failure rate. So while AMP may not affect
the development timeline for a particular drug, it should increase the
success rates of trials by increasing the chances that a particular
drug will be effective. If AMP succeeds in validating a drug target for
a particular disease, that could reduce drug development costs in that
area, since companies should be less likely to conduct costly clinical
trials with compounds that will fail in phase II or III because the
targets of those compounds don't have the desired effect on the
particular disease.
The AMP partners intend to consider other project ideas later this
year. As in the selection of the pilot projects, the AMP partners would
need to agree that there is a scientific opportunity in target
validation in a particular disease area with these characteristics: the
research project would be amenable to a public-private partnership with
joint scientific planning and governance; data would be shared broadly
and not be patented; and industry or research foundations would be
willing to commit substantial financial and other support. The
Foundation for the NIH has a project proposal form on its Web site at
http://fnih.org/work/key-initiatives-0/accelerating-medicines-
partnership to guide interested parties in developing project proposals
for the AMP members to consider, and the AMP partners will also
continue identifying and exploring their own areas of mutual scientific
interest.
darpa-like program
Question. I am concerned that researchers are now reluctant to take
risks because of their concern that their research efforts will not be
supported. How will NIH's new DARPA-like program address this concern?
The new DARPA-like Program is funded at $30 million and would
support high risk, goal-driven activities aimed to achieve rapid
technology development. While I support this type of research, I am
concerned that the funding for the new program is coming from another
program that supports exceptionally creative scientists proposing
innovative and transformative research--High-Risk High-Reward Research.
The High-Risk High-Reward Research program's funding is reduced by
$21.8 million. If funding ``maverick'' science is a priority for NIH,
why does the budget cut one high risk research program's funding to
start a new one?
The Guardian ran a letter in March from a group of prominent
researchers promoting additional funding to support scientific
mavericks. The letter stated, ``Agencies claiming to support blue-skies
research use peer review, of course, discouraging open-ended inquiries
and serious challenges to prevailing orthodoxies.'' In a time when
budget resources are constrained, how do you balance funding for high-
risk research projects with peer-reviewed science?
Answer. Scientific progress often advances by building
incrementally upon a strong foundation of previous research and
preliminary data. However, rapid advances in progress may require
approaches that foster innovation and risk taking. For certain
objectives, where research teams need to be actively managed to achieve
defined, high-risk goals so that new expertise can be added as initial
high-risk attempts fail or as new discoveries are made, the DARPA-like
Other Transaction Authority (OTA) provided to the Common Fund can be
very helpful. The NIH Common Fund's Stimulating Peripheral Activity to
Relieve Conditions (SPARC) program will use the OTA to support a high-
risk, goal-driven endeavor to develop proof of concept for an entirely
new class of neural control devices that have the potential to
precisely treat a wide variety of diseases and conditions.
Neuromodulation to control end-organ system function has been
recognized as a potentially powerful way to treat many diseases and
conditions, such as hypertension and heart failure, gastrointestinal
disorders, diabetes, and inflammatory disorders. However, the
mechanisms of action for neuromodulation therapies are poorly
understood. The SPARC program will support interdisciplinary teams of
investigators to deliver neural circuit maps of several organ systems,
novel electrode designs, minimally invasive surgical procedures, and
stimulation protocols, driven by an end goal to develop new
neuromodulation therapies. The program is expected to be iterative and
dynamic, with the novel technologies informing mapping efforts, and
mapping results defining new technology requirements. Rapid progress in
this nascent field requires high levels of innovation and risk taking
as well as aggressive project management to achieve these ambitious
goals and capitalize on the therapeutic promise of this emerging
research area.
In addition to the SPARC program, several other initiatives within
the Common Fund specifically support high-risk research. The High-Risk
High-Reward program, which includes the Pioneer, New Innovator,
Transformative Research, and Early Independence Awards, supports
exceptionally creative scientists to undertake bold and innovative
research projects in any scientific area relevant to the NIH mission.
For these projects, NIH has no pre-defined objective other than to
foster innovative, exceptionally high-impact research through
investigator-initiated projects. Therefore, for these projects, a grant
mechanism, rather than the OTA mechanism, is most useful. Although
Common Fund support for the High-Risk High-Reward program decreases in
fiscal year 2015, the successful track record of the High-Risk High-
Reward program has moved NIH's Institutes and Centers to increase their
support of these awards, providing additional funding beyond the Common
Fund investment.
All NIH-supported research, including programs designed to support
high-risk research, undergoes a rigorous peer-review process to
identify the most scientifically meritorious projects. Programs
designed to support high-risk research may emphasize different criteria
during peer review compared to more traditional grant mechanisms,
weighting innovation and potential impact more heavily than feasibility
and preliminary data. Highly innovative ``blue skies'' research and
peer review are not mutually exclusive. Although the specific review
processes for SPARC and other OTA programs may be different from grant
or contract reviews, external input will still be sought to help guide
the decisionmaking process.
The question of how to balance funding for high-risk research with
research that is more grounded by preliminary data is perennial, and
the answer varies across the NIH as scientific opportunities and
challenges vary between fields of research. However, risk tolerance is
a founding principle of the NIH Common Fund so that innovative
solutions to the most pressing challenges may be reached.
clinical and translational science awards
Question. How has NCATS implemented the Institute of Medicine's
Clinical and Translational Science Awards (CTSA) recommendations and
how do you see the program growing over the next several years?
Answer. In June 2013, the Institute of Medicine (IOM) issued a
report following a review of the Clinical and Translational Science
Awards (CTSA) Program. The report recommended that the National Center
for Advancing Translational Sciences (NCATS) take a more active role in
the program's governance and direction, formalize the evaluation
processes of the program, advance innovation in education and training
programs, and ensure community engagement in all phases of research.
NCATS leadership is committed to implementing the recommendations
of the IOM report. As a first step, NCATS has increased the
programmatic and fiscal management of the grants that support this
program and streamlined the way the consortium is governed, consulting
closely with the CTSA Principal Investigators (PIs). For example, we
have appointed a new steering committee that includes 12 CTSA PIs with
staggered terms to replace the previous 90-member group.
In parallel, NCATS assembled a Working Group of its Advisory
Council to provide advice on measurable objectives for the CTSA
program. The group was tasked with developing clear, measurable goals
and objectives for the program that address critical issues across the
full spectrum of clinical and translational research (i.e. ``what does
success look like?''). The Working Group presented its report (http://
www.ncats.nih.gov/files/CTSA-IOM-WG-Draft-Report.pdf) at the NCATS
Advisory Council meeting in May. Its report addressed four of the seven
recommendations in the IOM report and focused on: (1) translational
workforce development, (2) engagement and collaboration with patients
and communities, (3) integration of translational science across its
multiple phases and disciplines within complex populations and across
the individual lifespan, and (4) systemic improvements in methods and
processes of translation. The measurable goals and outcomes in this
report are serving as a guide for NCATS as it moves forward in
developing and implementing strategies to strengthen the CTSA program
and for measuring progress.
NCATS recently announced the selection of Petra Kaufmann, M.D.,
M.Sc., to head the NCATS Division of Clinical Innovation, which
includes the CTSA program. Dr. Kaufmann served as Director of the
Office of Clinical Research at NIH's National Institute of Neurological
Disorders and Stroke (NINDS) and brings a wealth of expertise across
the translational sciences spectrum.
With the appointment of a permanent Director for the program, the
recommendations of the IOM report, and the results of deliberations by
the Advisory Council and its working group, NCATS is poised to work
closely with the CTSA community to improve the effectiveness and
efficiency of the process of translation from scientific discovery
through clinical research to improved health outcomes.
brain research through application of innovative neurotechnologies
Question. We discussed the Brain Research through Application of
Innovative Neurotechnologies (BRAIN) Initiative at last year's budget
hearing. This is an exciting proposal that could revolutionize the
field of neuroscience and advance therapies for numerous diseases,
including Alzheimer's. The subcommittee provided funding for this
initiative in fiscal year 2014 and requested a report on the goals,
objectives, budget, and timeline for the BRAIN Initiative. Could you
elaborate on the commitment we are undertaking and provide specific
details on what the 10 year budget picture may entail?
Answer. NIH charged a high-level working group of the Advisory
Committee to the Director (ACD) to develop a rigorous plan for the
Initiative that includes scientific milestones and budgetary
projections (roster at http://www.nih.gov/science/brain/acd-
roster.pdf). This working group comprised visionary leaders across
neuroscience disciplines that were expertly positioned to delineate
bold, yet achievable, multi-year timetables, milestones, and cost
estimates. Over the last year, the working group met with the
scientific community, patient advocates, and the general public to
ensure its plan would be sufficiently informed by stakeholder input.
The working group delivered its final report for consideration by
the ACD at its June 5-6 meeting. The scientific vision outlined in this
report was unanimously supported by the Committee and subsequently
endorsed by the NIH Director. In its findings, the group emphasized
that the NIH efforts on the BRAIN Initiative should seek to map the
circuits of the brain, measure the fluctuating patterns of electrical
and chemical activity flowing within those circuits, and understand how
their interplay creates our unique cognitive and behavioral
capabilities. The following seven scientific goals were identified as
high priorities for achieving this vision:
1. Identify and provide experimental access to the different
brain cell types to determine their roles in health and
disease.
2. Generate circuit diagrams that vary in resolution from
synapses to the whole brain.
3. Produce a dynamic picture of the functioning brain by
developing and applying improved methods for large-scale
monitoring of neural activity.
4. Link brain activity to behavior with precise interventional
tools that change neural circuit dynamics.
5. Produce conceptual foundations for understanding the
biological basis of mental process through development of new
theoretical and data analysis tools.
6. Develop innovative technologies to understand the human brain
and treat its disorders; create and support integrated brain
research networks.
7. Integrate new technological and conceptual approaches produces
in Goals 1-6 to discover how dynamic patters of neural activity
are transformed into cognition, emotion, perception, and action
in health and disease.
These scientific goals will be maximized through seven core
principles:
1. Pursue human studies and non-human models in parallel.
2. Cross boundaries in interdisciplinary collaborations.
3. Integrate spatial and temporal scales.
4. Establish platforms for preserving and sharing data.
5. Validate and disseminate technology.
6. Consider ethical implications of neuroscience research.
7. Create mechanisms to ensure accountability to NIH, the
taxpayer, and the community of basic, translational, and
clinical neuroscientists.
The first year of the BRAIN Initiative, fiscal year 2014, was
seeded by a $40 million commitment from NIH. The President has
requested $100 million in his fiscal year 2015 budget for the second
year of the Initiative. For the remaining years, the working group
suggests an investment ramping up to $400 million a year for fiscal
years 2016-2020 to focus on technology development and validation. They
called for $500 million a year for years 2021-2025 to focus
increasingly on the application of those technologies in an integrated
fashion to make fundamental new discoveries about the brain. The
working group emphasized that its cost estimates, which are
provisional, assume that the budget for the BRAIN Initiative will
supplement--not supplant--NIH's existing investment in the broader
spectrum of basic, translational, and clinical neuroscience research.
A full copy of the report can be found at http://www.nih.gov/
science/brain/2025/index.htm.
alzheimer's funding
Question. Historically, NIH has opposed disease specific funding to
allow research, not politics, to drive scientific funding decisions.
However, this appears to cause a chicken and egg scenario. It is
difficult for scientists to propose Alzheimer's research when there is
not a robust funding stream to support their work, yet there is not a
robust funding stream because scientists may not be proposing
Alzheimer's research projects. So which comes first? The dedicated
funding stream or the research ideas?
Answer. NIH develops targeted funding initiatives to address areas
of scientific need and opportunity as identified by program staff in
consultation with experts in the scientific community. The resulting
initiatives are strategically deployed to make every dollar count by
establishing priorities, setting goals that are both ambitious and
realistic, and identifying the most promising opportunities for
progress through careful planning, coordination, and resource
allocation.
Although these targeted initiatives have enabled us to support a
number of groundbreaking projects, it is important to note that the
bulk of NIH's funding, in Alzheimer's disease and elsewhere, goes to
investigator-initiated proposals--that is, proposals that are not
developed in response to a specific funding initiative. For example, in
fiscal year 2013, fewer than 10 percent of NIH's Alzheimer's-related
research project grants were awarded under an Alzheimer's-specific
funding opportunity announcement (FOA). The majority of Alzheimer's-
related studies were either awarded under a more general neuroscience-
focused FOA or an FOA in a related area, or were truly investigator-
initiated studies reflecting the creativity and innovation of
researchers seeking to build on scientific advances or offering new
ways of thinking about the disease.
The importance of Alzheimer's disease research within the overall
NIH research portfolio continues to be reflected in our strategic
planning process and scientific funding initiatives. Our Alzheimer's-
related funding opportunity announcements (FOAs) are carefully
developed to advance the field consistent with the priorities
established under the National Action Plan for Alzheimer's Disease and
the 2012 Alzheimer's Disease Research Summit. In addition, in the past
5 years NIH has released over 40 FOAs directly relevant to Alzheimer's,
and the response to each of these has been robust. In fact, each year
we receive many more applications for meritorious research in
Alzheimer's disease than we are able to fund.
Question. How do you prioritize funding for a disease when you
know, as in the case of Alzheimer's disease, that the disease burden is
only going to increase over the next 20 years?
Answer. Priority-setting processes at both the NIH and individual
Institute levels are designed to maintain a balance among a wide array
of diverse and compelling priorities, based on close monitoring of the
scientific and medical landscapes by expert program staff and outside
advisors. This enables us to use our funds efficiently and effectively
in order to have the optimal impact both on the scientific field and on
the public health. Alzheimer's disease is one such high-priority
research area. Our planning, priority-setting, and funding initiatives
fully take into account the projected increase in disease burden in
this area.
The NIH Director is responsible for program coordination across the
NIH Institutes and Centers (ICs) and for ensuring a balanced overall
research portfolio. In turn, each IC has a process for establishing
research and funding priorities based on its specific mission and the
long-term research goals articulated within relevant strategic plans.
These priorities are reflected in the ICs' plans to distribute
resources.
To ensure that these priorities are harmonized with the wider NIH
mission, the NIH Director provides centralized coordination and
communication across NIH. During biweekly meetings with the IC
Directors, the NIH Director considers the entire biomedical research
landscape and discusses with his colleagues ways that NIH can be most
effective with its investments. They hear from innovative scientists
about cutting-edge results and deliberate potential new initiatives
that could significantly advance the science in a particular field.
NIH receives input from many sources when setting research and
funding priorities for Alzheimer's. In addition to scientific
workshops, international conferences, and other interactions with the
scientific community, these sources include the National Advisory
Council on Aging and the Advisory Council on Alzheimer's Research,
Care, and Services, established under the 2011 National Alzheimer's
Project Act. In addition, input from the 2012 Alzheimer's Disease
Research Summit and the 2013 workshop on Alzheimer's Disease-Related
Dementias has been instrumental in facilitating the development of our
Alzheimer's research agenda.
______
Question Submitted by Senator Thad Cochran
jackson heart study
Question. Dr. Collins, the Jackson Heart Study, located in Jackson,
Mississippi, is the largest-ever investigation of cardiovascular
disease in African Americans. In the National Heart, Lung and Blood
Institute's congressional budget justification for this year, one of
your focuses is on preventing and pre-empting chronic heart, lung,
blood and sleep disorders. Can you tell me how the Jackson Heart
Study's recent collaboration with the Framingham Heart Study can be
leveraged to specifically address this particular theme?
Answer. Since it began in 1998, the Jackson Heart Study (JHS) has
provided extensive information on the causes of cardiovascular disease
in African Americans. JHS is also one of the largest studies of the
genetic factors that affect high blood pressure, heart disease, stroke,
diabetes, and other diseases that disproportionately affect African
Americans. A recent JHS-related paper, for example, showed that the
gene APOL1, which is known to contribute to chronic kidney disease, was
found to also increase risk of cardiovascular disease in African
Americans. Genetic analyses such as this provide promise for targeted
therapies that can pre-empt disease. In August 2013, NHLBI contracts
supporting the JHS were renewed for another 5 years.
A new collaborative research relationship has been established
between the American Heart Association (AHA) and the University of
Mississippi and Boston University, the academic coordinating center
homes of the JHS and Framingham Heart study (FHS), respectively. The
AHA-led study, called the Cardiovascular Genome Phenome Study (CVGPS),
will expand upon the research taking place within the Framingham and
Jackson Heart studies by investing in parallel genomic and genetic
analyses among other research subjects, expanding diversity and
enhancing new approaches to find more ``personalized'' treatment and
prevention interventions that could pre-empt chronic cardiovascular
disease and other conditions. The CVGPS will also seek to make new data
available for analysis by qualified investigators.
More generally, NHLBI is taking the necessary steps to transform
its epidemiology research efforts in a way that builds on emerging
scientific tools and data platforms. NHLBI has established an Advisory
Council Working Group on Epidemiology Research to strategically examine
how to maximize the potential of our epidemiological studies by joining
complementary data across cohorts such as the FHS and the JHS for new
scientific investigations. Leveraging our available resources, through
strategic partnerships and collaborations, offers the best hope to
address critical needs that will not only improve treatment but also
change the course of disease before irreversible consequences occur.
______
Questions Submitted by Senator Richard C. Shelby
science, technology, engineering, and mathematics
Question. The fiscal year 2015 budget request, once again, proposes
a reorganization of science, technology, engineering, and mathematics
(STEM) education. While the STEM proposal kept the Science Education
Partnership Awards program at NIH, the budget proposes to eliminate
four other STEM initiatives throughout the agency. What metrics were
used to decide these programs should be eliminated?
Answer. The President's budget for fiscal year 2015 proposes a
reorganization of all Federal Science, Technology, Engineering, and
Mathematics (STEM) education programs. Consistent with the Government-
wide STEM reorganization, NIH decided to phase out four of its smaller
STEM programs and notified grantees of the discontinuation of future
new STEM programs supported by the National Institute on Drug Abuse
(NIDA), the National Institute of Environmental Health Science (NIEHS),
the National Institute of Neurological Disorders and Stroke (NINDS),
and the National Institute of Allergies and Infectious Diseases
(NIAID). This decision to discontinue or eliminate these programs
follows the recommendations of the Federal STEM Education 5-Year
Strategic Plan (Appendix Table A6: STEM Education Funding in Millions
by Agency, page 98). Consistent with the report language accompanying
the Consolidated Appropriations Act, 2014 (Public Law 113-76), NIH is
continuing support of the Science Education Partnership Award program
and the Office of Science Education.
clinical and translational science awards
Question. Dr. Austin, can you tell me how the Clinical and
Translational Science Awards (CTSA) program is helping underserved
populations, for example in my home state of Alabama, and in other
underserved states in the Deep South?
Answer. The University of Alabama at Birmingham (UAB) CTSA began a
new program in 2010 called, ``The Deep South Network for Translational
Research (DSNTR).'' It involves the UAB CTSA as the organizing hub,
with participation of other institutions in the Deep South that do not
have a CTSA including, Louisiana State University, Tulane University,
Tuskegee University, University of Alabama-Tuscaloosa, University of
South Alabama, and University of Mississippi Medical Center. It makes
the sophisticated research capabilities of UAB available to
investigators at these other institutions for use in multi-
institutional collaborative research projects, especially those that
focus on underserved populations. Further, in collaboration with
Alabama's Historically Black Colleges and Universities, the UAB CTSA
has built an extensive network for training the next generation of
health disparities researchers.
The University of Arkansas Translational Research Institute (TRI)
aims to translate successful healthcare research projects directly to
patient care delivery regardless of where they live. The TRI partners
with key community organizations across the state to facilitate
research contacts and clinical care connections among rural and
medically underserved populations. The TRI has leveraged and built upon
Arkansas' statewide telemedicine program, in particular the Antenatal
and Neonatal Guidelines, Education, and Learning System (ANGELS)
program, which links obstetricians across the state to UAMS maternal-
fetal medicine specialists. Its partnership with the Tri-County Rural
Health Network has connected elderly and adult disabled citizens with
home and community-based services as alternatives to nursing homes.
Finally, a nascent partnership with the Philips County Faith Task Force
has enabled development of a community-based program for rural veterans
in Jefferson County to build capacity to conduct participatory
research. The project's overarching goal is to establish a community-
linked infrastructure that will increase minority participation in
translational research intended to reduce racial and ethnic health
disparities.
At the Atlanta CTSA, experts in community engagement seek out
community healthcaregivers that can articulate the heath needs of the
local population, especially those who face disproportionately higher
health risks. The Atlanta CTSA includes Emory University, the Georgia
Institute of Technology, and the Morehouse School of Medicine, which is
dedicated to improving the health and well-being of individuals and
communities with emphasis on the underserved urban and rural
populations in Georgia. Morehouse provides leadership in developing
programs that specifically address healthcare needs in the Atlanta
region. Examples include ``e-Healthy Strides,'' which partnered with
Big Bethel AME Church to collect health data and transmit it to the
parishioners' physicians; ``i-Adapt,'' a program designed to provide
instruction and motivation to people with diabetes to facilitate self-
care; and EPICS (Educational Program to Increase Colorectal Cancer
Screening), a program aimed at teaching primary healthcare teams about
screening more effectively for colorectal cancer.
accelerating medicines partnership
Question. Under the new Accelerating Medicines Partnership program,
rheumatoid arthritis and lupus will receive $41.6 million in research
funding over 5 years, with about half of this funding coming from the
NIH and half from pharmaceutical companies. I am concerned that the
funding for lupus is not new NIH funds, but redirected funding from
current research projects. Are you concerned that AMP is taking away
from current lupus research resources as opposed to allocating
additional resources towards lupus?
Will data generated as a result of the Accelerated Medicines
Partnership be available to other scientists studying these diseases?
What other diseases and conditions will this program be supporting
in the future?
Answer. The Accelerating Medicines Partnership (AMP) is a unique
type of public-private partnership of the National Institutes of Health
(NIH), the Food and Drug Administration (FDA), nonprofit organizations,
and biopharmaceutical companies. AMP is supporting research focused on
identifying and validating biological targets for new therapeutics, a
process called target validation. AMP was just launched in February,
and as noted, is beginning with three specific pilot projects,
including a rheumatoid arthritis and lupus project.
The AMP program offers an exceptional opportunity to leverage NIH
investments in lupus research with substantial funds and intellectual
support from industry and non-profit organizations. Recognizing the
need and opportunity, NIH, after consulting with the research
community, released two Requests for Applications (RFAs) to implement
the AMP program in lupus and rheumatoid arthritis. The RFAs will not
take money away from existing lupus projects. We expect that a number
of researchers studying lupus will apply and be funded through the AMP.
Because a major goal of the AMP is to generate pre-competitive,
disease-specific data that will be accessible to the broad biomedical
community, the program will also facilitate research by lupus
investigators not funded through the AMP. AMP partners have also agreed
that the research findings should not be patented.
The AMP partners intend to consider other project ideas later this
year. As in the selection of the pilot projects, the AMP partners would
need to agree that there is a scientific opportunity in target
validation in a particular disease area with these characteristics: the
research project would be amenable to a public-private partnership with
joint scientific planning and governance; data would be shared broadly
and not be patented; and industry or research foundations would be
willing to commit substantial financial and other support. The
Foundation for the NIH has a project proposal form on its Web site at
http://fnih.org/work/key-initiatives-0/accelerating-medicines-
partnership to guide interested parties in developing project proposals
for the AMP members to consider, and the AMP partners will also
continue identifying and exploring their own areas of mutual scientific
interest.
______
Question Submitted by Senator Lindsey Graham
breast cancer screening
Question. From 1990 to 2010, deaths from breast cancer decreased by
34 percent. However, in 2013, 230,000 new cases of breast cancer were
diagnosed in the United States and almost 40,000 women died from breast
cancer.
Recent news coverage has focused on studies that called into
question the value of screening for breast cancers. Although the
majority of scientific studies have corroborated the value of early
detection of breast cancers through screening, these recent articles
have created a less clear picture of the benefits of screening and may
lead women to avoid periodic mammography, an experience some women
already view as uncomfortable.
Given these current controversies, do you think the NCI should
undertake a new study to clarify the benefits of screening so that
women and their doctors will have a better idea of how breast cancer
screening should fit into a woman's overall preventative health
program?
Answer. We are aware of the growing concerns about the balance of
benefits and harms associated with screening mammography. Some of these
concerns have recently been outlined by the Swiss Medical Board in its
recommendation to end the national Swiss breast cancer screening
program (Reference: Biller-Andorno N and Juni P: N Engl J Med
2014;3760:1965-1967). The concerns fall into two categories. First, the
reduction in cancer mortality by early detection of breast cancer using
mammography may decline as more effective adjuvant chemotherapy has
been developed for treatment of early- and mid-stages of breast cancer.
(Much of this unequivocal progress in treatment came from NCI-sponsored
randomized trials of adjuvant therapy.) Nearly all of the randomized
trials testing the efficacy of mammography were conducted decades ago,
in the pre-adjuvant therapy era. A recently reported and widely
publicized Canadian trial started early in the era of adjuvant therapy
and showed no reduction in breast cancer mortality associated with
mammography screening as opposed to screening by physical examination
(Reference: Miller AB, et al.: BMJ 2014; doi: 10.1136/bmj.g366).
Second, new evidence of harms associated with mammography has emerged
in recent years, particularly one known as overdiagnosis--the detection
of non-life threatening tumors that caused anxiety and were treated
with measures that carry risks, such as surgery, radiation, and
chemotherapy (Reviewed in: Pace LE and Keating NL: JAMA 2014;311:1327-
1335).
The emerging evidence has led to calls for additional studies in
the current modern era of breast cancer therapy that would clarify the
balance of benefits and harms of breast cancer screening. The ideal or
``gold standard'' test would be a large randomized trial comparing
screening mammography to a control group that does not receive
screening mammography, but such a study would not be feasible in the
United States. National surveys show that a large proportion of
American women continue to get routine screening mammography, with no
change in usage after the U.S. Preventive Services Task Force issued
its recommendations against routine screening for women ages 40-49 and
for spacing mammography for women age 50-74 from annually to every 2
years (Reference: Pace LE, et al.: Cancer 2013;119:2518-2523). Given
current practice, a true control group for an optimally informative
``gold standard'' trial appears to be impossible.
Therefore, NCI is actively funding and planning other types of
studies to learn more about the benefits and harms of breast cancer
screening, and to try to maximize any benefits while limiting the
harms. First, NCI is taking several approaches to improve on the
benefits of mammography as currently practiced. NCI funds a multi-
institutional Breast Cancer Screening Consortium, a collaborative
network of seven research registries designed to track outcomes of
screening mammography in the community, including recall and biopsy
rates, and tumor stages at diagnosis. A goal is to explore ways to
achieve optimal and reproducible mammography reading in the community.
A recently developed inter-divisional NCI request for applications
(RFA) will focus on studying the process of screening and subsequent
therapy, with a focus on overdiagnosis, which, as noted above, often
leads to inappropriate and potentially harmful treatment. This project
will compare tumor biology and clinical aggressiveness with the method
of detection, including breast imaging, and with the criteria used for
diagnosis. The research aims to identify ways to ensure timely follow-
up of abnormal findings and institution of effective therapy when
necessary.
Additionally, in an effort to minimize the harms of overdiagnosis,
several other methods for screening are under investigation. The Early
Detection Research Network (EDRN) is studying new methods to identify
the molecular ``fingerprints'' of screen-detected tumors with little
lethal potential, so that more patients can be followed without
institution of unnecessary aggressive treatments. A funding opportunity
announcement (FOA) for a consortium of multidisciplinary scientists
specifically focused on identification of early screen-detected ``non-
progressor'' lesions that can be safely followed is under
consideration, with breast cancer as one of the four primary areas of
emphasis of the proposed consortium.
A related research area involves the study of other imaging
modalities to detect breast cancer. The balance of benefits and harms
of breast MRI in the general population is not known, so it is not
usually considered to be suited to general screening. However, some
experts have recommended it as an adjunct screening tool for women at
extremely high risk of breast cancer, such as women who have high-risk
inherited mutations of their BRCA 1 or 2 genes, a history of ionizing
radiation treatments to the chest (administered to treat other
malignancies), or a family history of breast cancer. The screening
recommendations for these women include both an annual mammogram and
MRI for the BRCA mutation carriers and an optional MRI or ultrasound
for the rest. (An update on breast cancer screening and prevention.
Cruz MS, Sarfaty M and Wender RC; Primary Care: Clinics in Office
Practice Vol. 41, Issue 2, June 2014, Pages 283-306.).
FDA has approved digital breast tomosynthesis or 3-D mammography
devices, which use low dose x-rays for breast cancer screening but
experts do not agree on its clinical use. A few small studies have
shown that adding digital breast tomosynthesis to standard mammography
screening may result in a significant reduction in patients being
recalled for additional testing compared to routine screening
mammography alone, but more research is needed. NCI is considering
potential studies to see if breast tomosynthesis can improve
sensitivity and lower recall rates.
SUBCOMMITTEE RECESS
Senator Harkin. Thank you very much.
[Whereupon, at 11:55 a.m., Wednesday, April 2, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]