[Senate Hearing 114-]
[From the U.S. Government Publishing Office]
NIH: INVESTING IN A HEALTHIER FUTURE
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WEDNESDAY, OCTOBER 7, 2015
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:04 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
Present: Senators Blunt, Moran, Shelby, Cochran, Alexander,
Cassidy, Capito, Murray, Durbin, Mikulski, Shaheen, Merkley,
and Schatz.
opening statement of senator roy blunt
Senator Blunt. The Appropriations Subcommittee on Labor,
Health and Human Services, Education, and Related Agencies will
come to order.
I am certainly pleased we could have this opportunity this
morning, Dr. Collins, to talk to you and the other Institute
directors about the work you are doing and the work you would
like to do.
Every family faces health concerns during their lifetime,
and there are so many things that can be done by NIH that I
think can't be done as well anywhere else. A new drug, a new
device, a new treatment, can take anywhere from a decade to
longer to develop. It can cost billions of dollars on occasion,
with a pretty high failure rate even when you think you are on
the right path.
Certainly, it is necessary for the Federal Government to
invest in biomedical research. It represents the hopes of lots
of people and lots of families, and particularly now as we see
conditions growing as people survive heart problems and stroke
problems. We see more people with Alzheimer's and cancer
challenges. We see the potential for designer medicine largely
because of the great work that was done to figure out how to
define and understand the human genome system in a better way.
This year, this subcommittee and the full Committee have
placed a high priority on this research. We have planned for
and have a bill that includes $2 billion of extra money for
that research, an increase of about 7 percent over the current
year's spending.
Over the past decade, with not much new money going into
NIH, the purchasing power at NIH has decreased by about 22
percent. We hope to see that reversed, if we are successful
with what we are trying to do to provide the increase that we
are looking at here.
These are clearly difficult budgetary times, and I am sure
we could spend a lot of this hearing talking about how there
should be more money for other things in this budget, and there
is a disagreement on that in some cases and an agreement in
some cases, that if we had all the money in the world, the
priorities might be a whole lot easier to achieve.
But I will look forward to hearing from you, Dr. Collins,
and from the team that you have brought. As we talked about
this morning, I specifically said, can you bring some of the
Institute Directors that we haven't seen lately who are very
much focused on the individual areas of research, so we can get
a greater sense of understanding what the potential is, what
the needs are, what is out there that you are seeing and
beginning to see?
Also I'd like to discuss the challenge with young
researchers having a research grant approved. They are
dramatically less than they were a decade ago, and I am sure
that that is a topic that we will want to discuss as well. How
long do young researchers stay in research, if they continue to
have their ideas--not allowed to move forward?
So those are all the things we want to talk about today. We
are glad you are here. I want to turn to Senator Murray, who is
a big supporter of your work as well for her opening statement.
[The statement follows:]
Prepared Statement of Senator Roy Blunt
The Appropriations Subcommittee on Labor, Health & Human Services,
Education, and Related Agencies will come to order.
I'm certainly pleased we could have this opportunity this morning,
Dr. Collins, to talk to you and the other Institute Directors about the
work you're doing and the work you'd like to do.
Certainly every family faces health concerns during their lifetime,
and there are so many things that can be done by NIH that I think can't
be done as well anywhere else.
A new drug, a new device, a new treatment, can take anywhere from a
decade to longer to develop. It can cost billions of dollars on
occasion with a pretty high failure rate even when you think you're on
the right path.
Certainly it's necessary for the Federal Government to invest in
biomedical research. It represents the hopes of lots of people and lots
of families, and particularly now as we see conditions growing as
people survive heart problems and stroke problems. We see more people
with Alzheimer's and cancer challenges. We see the potential for
designer medicine largely because of the great work that was done to
figure out how to define and understand the human genome system in a
better way.
This year, this Subcommittee and the full Committee have placed a
high priority on this research. We have planned for and have a bill
that includes two billion dollars of extra money for that research, an
increase of 7 percent over current year's spending.
Over the past decade, with not much new money going into NIH the
purchasing power at NIH has decreased by about twenty two percent. We
hope to see that reversed if we're successful with what we're trying to
do to provide the increase that we're looking at here.
These are clearly difficult budgetary times and I'm sure we could
spend a lot of this hearing talking about how there should be more
money for other things in this budget, and there's a disagreement on
that in some cases and an agreement in some cases that if we had all
the money in the world, the priorities might be a lot easier to
achieve.
But I'll look forward to hearing from you, Dr. Collins, from your
team that you've brought. And as we talked about this morning I
specifically said can you bring some of the people that we haven't seen
lately who are very much focused on the individual areas of research so
we can get a greater sense of understanding what the potential is, what
the needs are, what is out there that you're seeing and begin to see.
And also, the challenge of young researchers having a research
grant approved are dramatically less than they were a decade ago, and
I'm sure that that's a topic that we'll want to discuss as well. How
long do young researchers stay and research if they continue to have
their ideas not allow them to move forward?
So, those are all things we want to talk about today. We're glad
you're here. I want to turn to Senator Murray who is a big supporter of
your work as well for her opening statement.
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Thank you very much, Mr. Chairman,
especially for your focus on this. I think we all really
appreciate it.
Dr. Collins, thank you for being here. I am grateful, as we
all are, for all you have done to champion the critical work
that NIH does. You have been a great partner, and it is great
to see you here.
And thank you to all of your team that is with us today. We
look forward to hearing from all of you.
All of us here today agree there is a lot more we need to
do to keep our families and our communities healthy, and
continue investing in priorities that strengthen our economy
from the middle out. The work of the National Institutes of
Health is vitally important to that effort. The NIH supports
basic research that makes medical advances possible, gives
hopes to those living with chronic and life-threatening
diseases, and helps drive economic growth and competitiveness.
In my own home State of Washington, we have researchers who
are working on ways to repair heart tissue that has been
damaged by disease and injury. We have people working on
decoding difficult-to-treat forms of breast cancer. We use
precision medicine to tackle eye disease and Alzheimer's. The
list goes on.
Those are just a few examples of the incredible work done
to improve health and well-being for families across the
country and really around the globe.
At the same time, the life sciences are helping to drive
economic growth and job creation. In my State, the life
sciences sector directly employs 34,000 people, making it the
fifth largest employment sector in my State.
The investments that we make in NIH and education and other
programs under this subcommittee's jurisdiction that support
the life sciences indirectly will help our economy create the
jobs of the 21st century and help ensure a workforce that can
take them on.
That is why, like Chairman Blunt, I see maintaining our
country's central role in the life sciences as a top priority,
and Federal investments in medical research could not be more
important to this effort. Supporting medical research starts
with making sure shortsighted budgeting does not get in the
way. For far too long, we have seen inflation erode Federal
investments in R&D, making it harder for researchers to get the
support they need.
In fact, I know that you, Dr. Collins, have said that,
increasingly, the NIH is having to turn promising projects
away. For patients and families who are waiting and hoping for
medical breakthroughs, that is unacceptable.
I am very proud that in late 2013, Democrats and
Republicans were able to reach a budget agreement to roll back
sequestration for fiscal years 2014 and 2015. As we all know,
that deal expired last week, which means Congress is going to
once again have to come together and find a solution.
As I have made clear, I believe that we need an agreement
that builds on the bipartisan foundation set in the budget deal
from last Congress, rolls back the cuts to defense and
nondefense investments equally, and protects priorities that
are essential to promoting a strong and growing middle class,
like research and education and infrastructure.
I have been encouraging my colleagues on the other side of
the aisle to come to the table to work with us so that we can
reach another bipartisan budget deal and avoid those automatic
cuts that impact these and other important investments in our
country's future. I am also currently working with Chairman
Alexander, who is here today, on the HELP Committee on a
bipartisan initiative to advance medical innovation. That is an
effort that is very much related to the conversation today. I
see that initiative as an opportunity to help patients get the
best, most effective cures and treatments as quickly as
possible while upholding the highest standards of consumer and
patient safety.
And to me, a central part of accomplishing this goal and
tackling the tough medical challenges our country faces is
making sure that research and development can thrive.
I am pleased that so far we have seen bipartisan interest
in ramping up investments in the NIH and FDA, and I have made
clear that I will only support a bill that does just that. I am
going to be very focused on finding a path forward on this goal
in the coming weeks because, put simply, stronger investment in
medical research mean a stronger, healthier country.
So I am hopeful that Republicans and Democrats can come
together to build on the bipartisan foundation we set in the
budget deal last Congress and make the investments we need to
seize these and other opportunities in a way that helps our
economy and our country work better for our families.
Thank you, Mr. Chairman.
Senator Blunt. Thank you.
Before I yield to Dr. Collins for his opening statement, I
have received a statement from full committee vice chairman,
Senator Mikulski. Her statement will be inserted into the
record at this point.
[The statement follows:]
Prepared Statement of Senator Barbara A. Mikulski
Thank you, Chairman Blunt and Ranking Member Murray for holding
this important hearing today. I also want to thank our witnesses, Dr.
Francis Collins, our brilliant and tireless NIH Director, as well as
all the NIH Institute Directors before us today, including Dr. Douglas
Lowy, Acting Director of the National Cancer Institute who will likely
one day receive a Nobel Prize for his work on the HPV vaccine.
I am so pleased we're here today to talk about an issue very close
to my heart: the National Institutes of Health. I call it the National
Institutes of Hope. When we invest in NIH, we see better cures and
treatments for diseases and conditions that devastate families and
drive up health costs, from Alzheimer's and autism to diabetes, heart
disease, and cancer.
The NIH is a world-class institution responsible for turning
scientific discoveries into better health for us all. Because of the
work at NIH, we have cut the cancer death rate by 11 percent in women
and 19 percent in men. Deaths from heart attack and stroke have been
reduced by 70 percent in the past 60 years. A child born today will
likely live to be 78 years old--nearly three decades longer than a baby
born in 1900.
That's just the start of NIH breakthroughs. In 2013 alone, NIH was
a major source of support for eight of the 10 most highly touted
scientific discoveries of the year. Not a bad year's work! But I know
and I hope that more is to come.
As Chair of the Appropriations Committee, I've been pleased to
secure funding increases for NIH in recent years, including a $1
billion increase in fiscal year 2014 and a $200 million increase in
fiscal year 2015. But it's not enough. Over the past 10 years, NIH
funding has not kept pace with inflation leading to a 20 percent
reduction in purchasing power for NIH. Adjusted for inflation, NIH
actually receives nearly 25 percent less funding today than it did in
2003.
This is quite simply unacceptable. At a time when so many other
countries are ramping up their investments in biomedical research, the
U.S. is scaling back. We must find a way to provide NIH with stable and
reliable funding increases in order to advance life-saving medical
research for patients worldwide.
Lifting budget caps is the most appropriate solution. By doing so,
we lift all boats. We cannot just life caps for defense spending. That
doesn't help NIH. We must also lift caps for non-defense spending--for
NIH, FDA and CDC. Because defense of this country doesn't just mean
troops on the ground or drones in the air. Defense of this country also
means helping defend families in their fights against the very real
diseases that touch their lives every day, like cancer, Parkinson's,
ALS and Alzheimer's. The only way to help those families is to lift the
caps. These current budget caps are caps on innovation, caps on
progress, caps on cures, caps on new treatments and caps on how far NIH
can go.
That's why I've been fighting for a 2-year budget deal that lifts
the caps equally for non-defense spending. Now that we have a CR in
place through December 11, it is time for Leaders across the aisle and
across the dome to come together. It's time to get a budget deal worked
out. One that ends sequester and lifts the caps. A budget deal would
pave the way for this Appropriations Committee to put together a
government spending bill that makes sense.
Without a budget deal, we are stuck. There is simple no way for
this Committee to respond to the needs of American families under the
current caps. Case in point is the fiscal year 2016 Labor-HHS bill
reported out of this committee.
Chairman Blunt did his best considering the limited funding he was
given. But he had to rob Peter to pay Paul. Yes, he was able to give
NIH a $2 billion increase. But in order to do so he had to cut funding
form the Social Security Administration, which would have to close down
field offices and processing centers, making it harder for people to
get their Social Security checks. He had to gut the Corporation for
National and Community Service, which helps improve education from pre-
school up, recover and rebuild communities from natural disasters, and
supports veterans and military families during deployment. He also had
to cut the Centers for Medicare and Medicaid Services, making it harder
for seniors, children and those of modest means access needed
healthcare services.
But I also know that NIH cannot be expected to accomplish our
shared goals if they are operating paycheck to paycheck, crisis to
crisis, shutdown to shutdown. They need stable and reliable funding.
They need to know that their budget can support multi-year grants. They
need to be able to tell young researchers that the United States
Government values them and will support their work in years to come.
A budget deal is the only way to get this done.
Thank you.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Senator Blunt. Dr. Collins, if you want to make an opening
statement and a brief review of the team you brought with you,
we won't count that against your opening time.
STATEMENT OF FRANCIS COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
GRIFFIN P. RODGERS, M.D., M.A.C.P., DIRECTOR, NATIONAL
INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
WALTER J. KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
JON R. LORSCH, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF GENERAL
MEDICAL SCIENCES
NORA D. VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG
ABUSE
Dr. Collins. Thank you, Mr. Chairman. Yes, I would be glad
to introduce the folks at the table with me. We are happy at
NIH that we have a deep bench of really remarkable scientist
leaders. Of the 27 institutes and centers, you will see in
front of you here five of those leaders.
INTRODUCTION OF NIH INSTITUTE DIRECTORS
Starting to my left, your right, Dr. Jon R. Lorsch, the
Director of the National Institute of General Medical Sciences
(NIGMS), an Institute which is, by the way, having a pretty big
day today because the Nobel Prizes in chemistry were given to,
2 out of 3 scientists NIGMS supported for 30 or 35 years, a
nice moment for NIGMS.
Next to Dr. Lorsch, Dr. Walter Koroshetz, who is the
Director of the National Institute of Neurological Disorders
and Stroke, a distinguished neurologist and basic scientist as
well as a clinician.
Over here on my right, Dr. Douglas Lowy, who is the acting
Director of the National Cancer Institute, much recognized for
his work in the development of a vaccine against HPV, which is
saving many lives from cervical cancer and other cancers.
Next to Dr. Lowy, Dr. Griffin P. Rodgers, Director of the
National Institute of Diabetes and Digestive and Kidney
Diseases, and also one of those folks who is being honored this
evening at the Sammies Awards because he is one of the nominees
for this year's awards for public service.
And over on the far end, Dr. Nora D. Volkow, a highly
regarded scientist in the area of addiction science and the
science of the brain, who serves as our able and highly
recognized (by the press), because she often is in front of
them talking about addiction, Director of the National
Institute on Drug Abuse.
That is my team. Now, I will maybe let you start the clock,
and I would like to tell you a few things by way of an opening
statement.
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It is a great honor, for my colleagues and me, to be here
before you to discuss how NIH is investing in a healthier
future for all Americans.
BIOMEDICAL RESEARCH BREAKTHROUGHS
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Longevity, you can see here what has happened.
Breakthroughs generated by NIH-supported research are behind
many of the gains our country has enjoyed in health and
longevity. For example, cardiovascular diseases, death rates
have fallen by more than 70 percent in the last 60 years.
Cancer death rates are now dropping by 1 percent to 2 percent
annually. Likewise, HIV/AIDS originally when first being
written about as a death sentence, now treatments greatly
extend lives, and prevention strategies and the increasing
potential of an effective vaccine are enabling us to envision
in real terms, the first AIDS-free generation.
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So, on behalf of NIH, our employees, our grantees, the
patient community, I want to thank all of you for your
continued support and for holding this hearing today. We see in
front of us, a remarkable landscape of biomedical opportunities
powered by exceptional advances in scientific knowledge and
technological innovation.
This morning's announcement of those Nobel Prizes in
chemistry for studies of DNA repair is a compelling example of
how these investments have been paying off, building upon work
that has gone on over decades.
EMILY WHITEHEAD'S STORY AND HISTORY OF CANCER IMMUNOTHERAPY
I would like to share with you this morning an inspiring
story, another one that has emerged from decades worth of NIH-
funded basic research. This is the story of cancer
immunotherapy, a treatment that involves harnessing the body's
own immune system to fight this dreaded disease.
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So, I would like you to meet Emily. Emily Whitehead, back
in 2010 when this photo was taken, she was struggling with
acute lymphoblastic leukemia, a disease that, thanks to
advances made possible by NIH, chemotherapy can cure 90 percent
of the time.
Unfortunately, Emily was in the other 10 percent. Her
prognosis after failed chemotherapy was grim. But, doctors at
Children's Hospital of Philadelphia approached her parents
about trying something radically different, a clinical trial of
an experimental approach called immunotherapy.
So, I would really like to use this story to make a point
about the long arc of medical research involving many
investigators and many years of work, ultimately leading to
Emily.
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Let's take a brief journey back in time. The history of
cancer immunotherapy can be dated actually back to the 1890s. A
New York surgeon, Dr. William Coley, reported success in
treating a few inoperable cancers by stimulating patients'
immune systems with bacterial toxins.
But, his results were highly variable. The treatment was
very toxic. And this approach largely fell by the wayside until
the mid-1980s.
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Then, at the National Cancer Institute, Dr. Steven
Rosenberg explored the ability of certain immune cells called
cytotoxic T cells to destroy tumor cells. He wondered why the
immune system does not recognize cancer cells all the time and
eliminate them, and whether the immune system could be helped
to do this by taking these T cells out of the body, stimulating
them with an activating factor, and then re-infusing them to
the cancer patient.
It did not always work, but there were some dramatic
responses.
Dr. Steven Rosenberg was and is a true pioneer. In a
wonderful stroke of timing, Steven was named this morning as
the Federal employee of the year by the Partnership for Public
Service and will be recognized in the Sammies Award ceremony
this evening.
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Meanwhile, the recombinant DNA revolution was gathering
momentum. Basic research spearheaded, again in large part by
NIH, led to the discovery of methods to splice fragments of DNA
together, giving birth to the whole field of biotechnology.
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Armed with this powerful set of tools and technologies,
NIH-supported researcher Dr. James Allison pioneered one
particular form of cancer immunotherapy. He discovered that a
particular protein on the surface of those T cells actually
acts as a braking system, preventing the full activation of the
immune system when a cancer is emerging.
By designing and delivering an antibody that blocks that
protein, Dr. Allison showed the brakes could be released.
Dramatic responses to previously untreatable cancers began to
appear.
Again, another award. Dr. Allison just received the Lasker
Award, America's Nobel Prize, for this work last month.
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Building on this growing momentum, other scientists like
Dr. Carl June at the University of Pennsylvania, who is one of
Emily's doctors--and his lab, I know, Chairman Blunt has
recently visited--have been busy designing even more precise
cancer immunotherapies.
In the approach designed by June's group, T cells are
collected from cancer patients and engineered in the lab using
recombinant DNA so that they can produce special proteins on
their surface, called chimeric antigen receptors, or CARs. When
those modified cells are infused back into patients, they
multiply. With guidance from their newly engineered receptors,
they seek and destroy the tumor cells.
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Let me just show you how these killer T cells seek and
destroy cancer cells with a quick video. This is pretty
dynamic, and the results can be dramatic.
So, that is a T cell that you see, there lit up in red. It
is busy migrating around on this Petri dish. It is looking for
foreign invaders.
Now you will see when it finds a cancer cell, it is going
to get really excited. There, you see the cancer cell in blue,
the T cell really going after it.
Now I'm going to change the colors on you in this next
little clip. The T cells are now in green, and the cancer cells
are red. Watch for the red flash. That is where the T cell just
ruptured the membrane of the cancer cell and sent it off to the
cancer cell graveyard. You can watch this happening repeatedly
with different cancer cells being targeted by these T cells
that go after them and figure out how to do away with them.
You can see why one of Dr. Steven Rosenberg's recent
patients refers to those T cells as little ninja warriors. They
do their job.
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This is not just the future of cancer treatment; it is the
present. But again, note that this was built on decades of
work. In fact, going back to Dr. Allison, a recent analysis
shows that the pathway that led to his Lasker Award included
the contributions of 7,000 scientists over more than a century,
with many of those scientists pursuing basic questions that had
no apparent connection to cancer.
So, I tell you this story to emphasize the critical need
for Federal investment in this whole spectrum, from basic to
translational to clinical research. If we do that, we can
realize our vision of accelerating discovery across this vast
landscape of biomedicine, and ultimately save many lives.
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Remember little Emily? Here she is today, a junior
bridesmaid, the picture of health. This happy picture made
possible by her parents' decision to go ahead and enroll her in
that pioneering cancer immunotherapy trial. Twenty-eight days
after that treatment, Emily was cancer-free. And more than 5
years later, she remains cancer-free.
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Emily is just one success story. I can tell you many more,
including all these folks across the entire NIH portfolio,
about how basic scientific inquiry is leading to a healthier
future for all Americans, from the development of
neurotechnologies through the Brain Initiative, to the million
or more cohort person in the Precision Medicine Initiative that
will generate knowledge applicable to an entire range of health
and disease.
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I would say, our future has never been brighter. But to
realize that future, NIH needs your sustained support.
So thank you, Mr. Chairman. My colleagues and I very much
welcome your questions.
[The statement follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good morning, Chairman Blunt, Ranking Member Murray, and
distinguished members of the subcommittee. I am Francis S. Collins,
M.D., Ph.D., and I am the Director of the National Institutes of Health
(NIH). It is an honor to appear before you today to discuss how NIH is
investing in a healthier future for all Americans.
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 improvements
our country has enjoyed in public health. For example, our Nation has
gained about 1 year of longevity every 6 years since 1990.\1\ A child
born today can look forward to an average lifespan of about 78 years--
nearly three decades longer than a baby born in 1900. Deaths from heart
attack and stroke have been reduced by more than 70 percent in the past
60 years. Thanks to NIH-developed anti-viral therapies, HIV-infected
people in their 20s today can expect to live into their 70s. This
compares to a life expectancy measured in months when the disease first
appeared in the 1980s. Cancer death rates have been dropping about 1
percent annually for the past 15 years. These are extraordinary
strides--but we aim to go much further.
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\1\ Http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64 02.pdf.
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On behalf of NIH, our employees, grantees, and patient community, I
want to thank the Members of this Subcommittee for your continued
support, and for holding this hearing today.
This investment could not come at a better time. We are in the
midst of a remarkable stream of scientific advances spurred by dramatic
advances in biotechnology. Today, I want to share with you a few of the
many promising opportunities before us that will lead to a healthier
future for all. I can assure you that the future of scientific research
has never been brighter.
Many recent breakthroughs stem from our Nation's commitment to
investing in basic science research. Basic science lays the foundation
for advances in disease diagnosis, treatment, and prevention by
providing the building blocks for clinical applications. Basic science
is generally not supported in the private sector, and NIH's focus on
understanding fundamental biological processes fosters innovation and
ultimately leads to effective ways to treat complex medical conditions.
But the lead time for medical breakthroughs to arise from basic science
research is often measured in decades, and it is generally not possible
to predict which basic investigations are going to be the most fruitful
in the long run. NIH's successful investment in basic science is
reflected by the awarding of 145 Nobel prizes to NIH-supported
scientists; the vast majority of these individuals were recognized for
basic science advances.
A compelling example of how we are trying to unravel life's
mysteries through basic science is with the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative. With nearly
100 billion neurons and 100 trillion connections, the human brain
remains one of the most daunting frontiers of science and one of the
greatest challenges in medicine. This bold, multi-agency effort to
revolutionize our understanding of the human brain will require the
development of entirely new technologies. Engineers, computer
scientists, nanotechnologists, physicians, and neuroscientists will
need to work together and challenge the limits of their respective
fields of science. By measuring real-time activity at the scale of
complex neural networks in living organisms, we can explore how the
brain enables the human body to record, process, utilize, store, and
retrieve vast quantities of information--all at the speed of thought.
Ultimately, the foundation of understanding developed by the BRAIN
Initiative will help reveal the underlying pathology in a vast array of
brain disorders and provide new therapeutic avenues to treat, cure, and
prevent neurological and psychiatric conditions such as Alzheimer's
disease, autism, schizophrenia, depression, epilepsy, and addiction.
Five years ago, a project like this would have been considered
impossible. But with your support, it is now underway. The first two
rounds of grant awards have been made--and they are tremendously
exciting. In the year since the inaugural round of awards, totaling $46
million, was issued, several exciting new tools and techniques have
been developed for studying brain structure and function. One such
technique, called Drop-Seq, groups neurons based on the genes that they
express, getting us closer to having a complete parts list for the
brain. Another tool, called DREADD (Designer Receptors Exclusively
Activated by Designer Drugs), used designer drugs to turn on and off
genetically engineered neural receptors. While its inventors used
DREADD to precisely control a mouse's motor movements, the tool may
potentially provide a way to restore proper neural function. Among the
second round of awards, totaling $85 million, announced last week are
projects aimed at delivering targeted electrical pulses to the brain to
treat illnesses such as traumatic brain injury and epilepsy, as well as
collaborations with physicists towards building non-invasive tools that
can observe neural activity deep within the brain with unprecedented
spatial detail.
We need to continue to ramp up this effort, and we need your
support for that, as requested in the President's Budget. While the
goals of this initiative are ambitious, the time is right to inspire a
new generation of neuroscientists to undertake this groundbreaking
approach to understanding the human brain.
Another area of exceptional scientific opportunity I want to
highlight today involves one of our Nation's most feared killers:
cancer. Until recently, our weapons for attacking cancer have been
largely limited to surgery, radiation, and chemotherapy--all of which
can be effective, but carry risks and toxicities. Now, after years of
intense basic and translational research, we have two exciting new
possibilities: targeted therapeutics and cancer immunotherapy. I want
to particularly focus on the latter.
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 important
built-in checkpoints to prevent our immune systems from running amok
and killing healthy cells. Certain white blood cells called T-cells--
the armed soldiers of the immune system--are designed to go after
foreign invaders, but they also need a stop signal to prevent going
into overdrive. One way to do this is through a receptor on the T-cell
called CTLA-4 that inhibits its function. Tumor cells have figured out
how to take advantage of this pathway by upregulating CTLA-4; the
result is to put the brakes on the immune system, giving the green
light for the cancer to grow.
NIH-funded researchers have discovered a way to release the brakes
by introducing a monoclonal antibody against CTLA-4, allowing the
normal immune response to be re-activated. Dr. James Allison, who led
the basic science efforts that led to these insights, was just honored
with the receipt of the Lasker Award, the ``American Nobel Prize.''
Promising results in patients with metastatic melanoma and lung cancer
are making this and other immunotherapies the breakthrough treatment of
the future. After President Carter was diagnosed with stage 4
metastatic melanoma, he received immunotherapy as part of his
treatment.
A final area I wish to highlight is precision medicine. As you
know, in his State of the Union address in January of this year,
President Obama announced his intention to launch the Precision
Medicine Initiative (PMI). This is a bold new research effort to
revolutionize the prevention and treatment of disease, and I thank the
Committee for including the requested $200 million for PMI in its
fiscal year 2016 appropriations bill. We believe that the time is right
for this audacious undertaking, and, with your support, the NIH and our
HHS partners, the U.S. Food and Drug Administration (FDA), the Office
of Civil Rights, and the Office of the National Coordinator for Health
Information Technology (ONC), will work with great intensity to achieve
this vision.
Historically, physicians have had to make most recommendations
about disease prevention and treatment based on the expected response
of the average patient. This one-size-fits-all approach works for some
patients and some conditions, but not others. Precision medicine is an
innovative approach that takes into account individual differences in
patients' genes, environments, and lifestyles. This concept is not new;
blood typing, for example, has been used to guide blood transfusions
for a century. Prescription eyeglasses are tailored specifically to the
patient's individual needs. Moreover, the identification of the BRCA1
and BRCA2 genes has made it possible to provide options for women at
high risk for breast and ovarian cancers. And, the gene implicated in
cystic fibrosis has led to widespread availability of screening and
targeted therapeutics.
The prospect of applying this concept broadly to virtually all
diseases, and to disease prevention, has been dramatically improved by
the development of powerful and affordable methods for characterizing
personal biological attributes (such as genomics and metabolomics), the
widespread adoption of electronic health records, the recent revolution
in mobile health technologies, and the emergence of computational tools
for analyzing large biomedical data sets. These advances will help make
possible the dream of personalizing a wide range of health
applications.
With this in mind, we are excited to take a lead in the two key
components of the President's Precision Medicine Initiative that will
be managed by NIH. First is a near-term goal that will focus on cancer,
building on advances in genomics and immunology that make it
increasingly possible for specific therapies to be designed for the
individual, based on the precise molecular characteristics of their
tumor. Second is a longer-term aim to generate knowledge applicable to
the whole range of health and disease. Both components are within
reach, due in large part to recent scientific breakthroughs. Let me
tell you just a little bit more about the longer term project.
In order to achieve the President's ambitious plan, NIH will build
a large national research cohort of one million or more Americans that
will provide the platform for expanding our knowledge of precision
medicine approaches and benefit the Nation for years to come. These
volunteer participants will agree to share health information, provide
biospecimens, and wear sensors that will detect environmental exposures
and body performance--all with appropriate privacy protection. They
will be true partners in this research. Not subjects, not patients--
partners. They will play an active role in how their genetic,
environmental, and medical information is used for the prevention of
illness and management of a wide array of chronic diseases. The goal
will be to expand the benefits of precision medicine into myriad
aspects of health and healthcare. Participants will be at the center of
the project design, and they will have access to their own health data,
as well as research using their data, to help inform their own health
decisions. Through this dynamic community, researchers will be able to
advance the information derived from this cohort into new knowledge,
approaches, and treatments. Researchers from many organizations will,
with proper protection of patient information, have access to the
cohort's data so that the world's brightest scientific and clinical
minds can contribute insights.
In order to help inform the vision for building the national
research cohort of one million or more volunteers, I formed a Precision
Medicine Initiative Working Group, as part of my Advisory Committee, to
develop a specific design plan for creating and managing such a
research cohort. To help carry out its charge, the Working Group
engaged with stakeholders and members of the public through workshops
and requests for information, focusing on issues related to the design
and oversight of the cohort. Public engagement, as well as internal
discussions, led to the vision for the design and utility of the
program, and the Working Group released their report just three weeks
ago. The report includes recommendations in six areas critical to the
development, implementation, and oversight: cohort assembly,
participant engagement, data, biobanking, policy, and governance. We
plan to move swiftly to build the infrastructure so that participants
can begin enrolling in the cohort in 2016, with a goal of at least one
million participants by 2020.
A project of this magnitude will lay the foundation for a myriad of
new prevention strategies and novel therapeutics. Although the
initiative will likely yield its greatest benefits years down the road,
there will be successes in the relatively near future as well. Moving
forward, this pioneering research initiative will require the
involvement of many different sectors of science and society, including
biologists, physicians, technology developers, data scientists,
healthcare organizations, and, most importantly, the American people.
Given related efforts in a few other countries, we will aim to forge
collaborations on a global scale.
With sufficient resources and a strong, sustained commitment of
time, energy, and ingenuity from the scientific, medical, and
participant communities, precision medicine's full potential can be
realized to give everyone the best chance at good health. There's no
better time than now to embark on this ambitious new enterprise to
revolutionize medicine and generate the scientific evidence necessary
to move this individualized approach into everyday clinical practice.
Today, I have outlined for you just a few of the very many
promising scientific opportunities on the horizon. With your support,
the future of medicine can be very bright. This concludes my testimony,
and my colleagues and I look forward to answering your questions.
Senator Blunt. Well, thank you very much, Dr. Collins. I am
certainly glad you are here.
CURE VS. TREATMENT
Let me ask a couple questions. Senator Toomey and I went to
see what Dr. Carl June was doing. That effort, you can correct
me where I am wrong here, very much focused on what the
individual patient needs. Dozens of individual patients at all
age groups have seen success in that particular effort.
But two thoughts about that. One is, is this likely in
cases like this to go beyond treatment to the level of where,
in this particular case, this particular fighting agent is
always there, so you are talking about a cure instead of
treatment? I would be interested in what discussion is going
on, how we look at a world where cure is one of the options as
opposed to a healthcare world that has largely been defined by
treatment up until now.
I will just go ahead and ask my second question at the same
time, which is, on these individual cases, I would assume at
some point one of the challenges is what we do that makes that
most likely to be scalable, so that every patient does not have
all of the expense of a unique treatment, but a scalable effort
made that will come naturally.
But talk to me about those two things, and whoever you
would like to answer those questions.
Dr. Collins. Those are great questions, Mr. Chairman. I
think I will turn to Dr. Lowy as the acting Director of the
National Cancer Institute, who is investing in big ways in
cancer immunotherapy, to address both of those.
Dr. Lowy. Thank you, Senator Blunt.
This is really a critical juncture right now because we
have opportunities for long-term responses. And what you are
asking is, are a subset of those responses going to lead to
cure? And we certainly are optimistic and hopeful that this
will happen, at least in some cases.
We need to understand better, as you point out, what the
mechanisms are that drive the important clinical responses to
immunotherapy. And if we can understand them better, we may be
able to devise even more effective immunotherapies that also
will have fewer side effects.
That is an area that we really are actively supporting
investigations in, because we do hope eventually that we can
get to the area of precision and predictive oncology where
patients, we know what treatment to give to them and we know
what kind of immunotherapy to give to them, in addition to
targeted treatments. Thank you.
Dr. Collins. In terms of the scalability, which is a tough
question for some of the very personalized immunotherapy that
you saw in Carl June's lab, there are certainly strong
interests in companies in figuring out how to do this, where
you can, in fact, make this available to thousands of patients
instead of in small trials. We would think that is a very
appropriate kind of place for public-private partnerships to
spring up, so that this idea of engineering your own T cells to
go after your cancer could be done for more and more
individuals.
Senator Blunt. I would just say, before I turn to Senator
Murray, that this is a topic that I am having some discussions
with people representing health insurance companies. Are you
thinking about a future where traditional treatment may be less
expensive initially but a long-term potential cure more
expensive initially but less expensive over time? What are your
standards going to be? Are you thinking what we can do now?
Really, the whole concept, I am sure we will get to, of
designer medicine, what can happen with the efforts, Dr.
Volkow, on the brain and how that those impacts?
I think we will have time for more than one round of
questions. We have a couple people on a timeframe. We will try
to get to them quickly. We will do this by order of both
appearance and, if you were here on time, seniority on the
committee.
The first person to go to is Senator Murray.
Senator Murray. Thank you very much, Mr. Chairman.
EFFECT OF YEAR-LONG CONTINUING RESOLUTION ON NIH RESEARCH
Dr. Collins, as you know, we are working on a continuing
resolution until December 11. I wanted to ask you, what effect
would a yearlong CR at the current rate have on the NIH
research?
Dr. Collins. Believe me, we are thinking and worrying a lot
about that. We are in a circumstance where, perhaps emboldened
by the enthusiasm, we have seen in both the Senate and House in
fiscal year 2016 budget process, I have a number of very
exciting initiatives that we would like to launch in fiscal
year 2016, the Precision Medicine Initiative, which I am sure
we will talk about in the course of this hearing; the BRAIN
Initiative, which is already underway now for 2 years but is at
a critical point to ramp up and build on what has already been
done; the ability to be able to push our vaccine strategies for
influenza, for HIV/AIDS. All of those are at a critical point
where more investment is needed.
We have been heartened, greatly, by the actions of this
Committee and a similar Committee in the House to believe that
we might have the chance to do these things.
A yearlong CR, unless an anomaly were possible for NIH,
would be simply devastating. The Precision Medicine Initiative,
for instance, would basically have to go into the freezer or on
mothballs or whatever the appropriate discouraging metaphor
would be.
We would just be at the point of starting this effort to
enroll 1 million Americans in this unprecedented study and
carry out exciting new studies in cancer genomics, and those
would basically have to go on hold. That would be enormously
disappointing.
Similarly, imagine the BRAIN Initiative, which is on this
exciting ramp. It would, basically, have to take a pause for a
year just at the point when the momentum is building.
I cannot emphasize enough how much we are worried about
this. We can struggle along with the CR until December 11, but
if it is a yearlong CR without an anomaly, it is going to be a
dark day, indeed, a dark year, indeed.
Senator Murray. Thank you very much.
SHORTAGES IN TREATMENT CENTERS
Dr. Volkow, more than 20 million people in the United
States have a substance abuse problem. We know that only a
small percent of that population will get help and that those
looking for treatment often cannot find it because of long
waiting times for care or because of limited insurance
coverage.
The work that National Institute on Drug Abuse (NIDA) does
to address addiction is critical, but I really worry that
cutting funding for treatment and recovery, as the
Subcommittee's 2016 bill would do, would make it very hard for
addicts to get the help they need, especially at a time when
44,000 more Americans now die annually from overdoses than they
do in car crashes.
The substance abuse block grant that represented 42 percent
of State spending on substance abuse as recently as 2007, that
share would likely drop to below 32 percent under this
subcommittee's bill.
I wanted to ask you, and take advantage of you being here
today, are you seeing shortages in treatment services around
the country for addicts who want help? If so, does that concern
you?
Dr. Volkow. Unfortunately, the answer is yes. Of course, it
concerns us, because the problem of drug addiction is actually
one that has been increasing in our country. We have known all
along that only 15 to 20 percent of those addicted receive
treatment.
Senator Murray. Fifteen percent?
Dr. Volkow. Fifteen percent.
Senator Murray. Only 15 percent of the people who ask for
help?
Dr. Volkow. No, 15 percent of individuals that have
addiction receive it. Not all of them search for treatment, but
one of the reasons they do not search for treatment is they are
discouraged by the lack of infrastructure to support their
needs, as well as the issue of stigma.
So those are two aspects that have made it very, very
difficult to provide treatment.
What NIDA is doing is trying to take advantage of
infrastructure that we have in our country to maximize their
involvement in substance use disorders. That includes the
healthcare system, the criminal justice system. Those two are
structures that we are engaging to provide with evidence-based
treatment that can improve outcomes.
BRAIN INITIATIVE AND CANCER RESEARCH
Senator Murray. Dr. Koroshetz, I wanted to ask you, I know
the BRAIN Initiative recently released its second round of
awards, bringing NIH investment to $85 million for 2015. Can
you tell us about the progress you have already made under the
BRAIN Initiative?
Dr. Koroshetz. Yes, happy to do so. The BRAIN Initiative is
incredibly exciting. It is off to a great start, as Francis
mentioned. The center of the BRAIN Initiative is developing new
technologies to allow us to monitor, interrogate, and also
modulate brain circuit activity. If you think about it, that is
really what patients are suffering from, disorders in brain
circuitry activity.
The problem is that we do not have the technologies to
modulate those circuits except in a very unsophisticated
manner. So some things have already come out that are really,
really exciting.
A couple of examples, there is a new technology, in which
you can put an artificial gene into particular neurons in the
brain, and with a drug that has no other effects you can turn
on or turn off precisely certain neuron types in the brain.
This is really an amazing feat to be able to do that.
Contrast that with treatment for Parkinson's disease, where
a wire is put into the brain and an electric current is sent
in, and it goes willy-nilly. No one knows exactly what it is
doing, but it turned out to be quite effective.
You can just imagine how these new precision technologies
can completely change how we can basically normalize or cause
compensation in brain circuits for patients' neurologic
deficits. So it is really quite exciting.
Senator Murray. Thank you.
Unfortunately, my time is up, so I will wait for the second
round.
Senator Blunt. We are fortunate to have the chairman of the
full committee and the ranking member of the full committee
with us.
Senator Cochran.
COMBATING DIABETES
Senator Cochran. Mr. Chairman, thank you.
In my State of Mississippi, we have one of the highest
rates of type 2 diabetes in the Nation. We are told that over
12.5 percent of our State's adults have the disease, and the
problem is growing rapidly.
Are there any new approaches that you have in mind in
dealing with hotspots, outbreaks, whatever you want to call it,
in areas like our State?
Dr. Collins. That is a great question for Dr. Rodgers,
since his institute oversees diabetes research at NIH.
Dr. Rodgers. Thank you, Senator, for the question.
Type 2 diabetes is increasing at an alarming level. There
are currently about 29 million people in the U.S. with diabetes
and 86 million who have prediabetes. There are two things that
we're doing about that.
Number one, for people who have established diabetes, there
is a common drug that is started on patients called metformin.
But unfortunately, in the great majority of patients, that drug
will no longer be effective.
We've started a trial in which we are characterizing the
combination of metformin with one of four different classes of
drugs to see what the next effective drug would be for given
individuals. This is actually a trial that involves 5,000
individuals in 45 centers around the country to determine the
effectiveness. This really will eventually get to the area of
precision medicine.
The second thing for those people who are sort of
underneath the iceberg, the 86 million Americans who have a
possibility of going on to develop diabetes, we have tried to
translate a very effective Diabetes Prevention Program to scale
this up in a way, to offer this lifestyle, which was quite
effective in these patients, to prevent them or delay them from
becoming a diabetic.
These will have an important financial role in the future,
in terms of cutting costs.
Senator Blunt. Thank you, Mr. Chairman.
Senator Mikulski.
Senator Mikulski. Mr. Chairman, thank you so much for
organizing this hearing.
To our colleagues from NIH, this is the committee and the
members here today are the pragmatists. When you look at us, we
have a chairman who is very much dedicated to NIH, certainly a
vice chairman who is. We have the authorizers here in terms of
Murray and Alexander.
All of us here have a history of support for this, so you
have people who really want to be nonpartisan. So I want you to
know that.
Dr. Collins. Thank you.
NIH WISH LIST
Senator Mikulski. We are stymied by our own processes. When
I first arrived in the Senate, we had a triad that worked.
Authorizing would often create great policy on a bipartisan
basis, Kennedy-Hatch, Kennedy-Kassebaum, et cetera. We had
appropriations that really could move the ball forward. And we
had a budget process that gave us an orderly methodology
process for doing that.
So we have problems here. So we have big problems here. I
know that you live them out every single day.
Colleagues, when I visit the National Institutes of Health,
which has been my great joy to represent for 28 years, I call
it the ``National Institutes of Hope.'' This is what we just
heard here, the National Institutes of Hope, in both what they
do on the campus in Bethesda, but also what they do through the
great extramural research like at the University of Maryland
and Johns Hopkins.
Dr. Lorsch, you are a Hopkins guy. They are going to
dedicate a room the Hopkins Club, the faculty club, 2 weeks
from now. Thirty-eight people associated with Hopkins have won
the Nobel Prize, two-thirds of that have been in life
sciences--38 people, one university--but because of the role
that our government plays in doing that.
But we are an economic engine. When you think about the
jobs that are created because of you in pharmaceuticals,
biomedical, medical devices. You are a turbo engine.
So rather than seeing you as a cost factor, we should see
you as an economic generator. And I hope that we can be able to
do that.
I am deeply concerned about the caps. I do not like budget
caps. Most of all, I don't like the caps on innovation. We
cannot continue to cap innovation. We cannot cap breakthroughs.
We cannot cap the opportunity for young people to dream for
these careers like Dr. Rosenberg and all of you have here.
So here is my question to you. When we look at both the
research to be done and the workforce that needs to do it, I
worry about the young investigator and the debt that they carry
that is a deterrent to pursuing this.
Could you tell me, if we could go down the table, if we
lifted the caps and went to President Obama's budget, nothing
more, President Obama's budget, what would be the three things
each and every one of you could do? And also, how would it
impact young investigators?
Dr. Collins. Okay, folks, there is the challenge. Maybe we
should just quickly go down the table.
Nora, do you want to kick this off?
Dr. Volkow. You want three of them?
Senator Mikulski. If you just have one, one would be
enough.
NIDA
Dr. Volkow. No, no. Number one is we would accelerate the
development of medication for addiction. There are many very
interesting potential targets. But since the pharmaceutical
industry is not investing, that responsibility relies in the
Federal Government money, predominantly through the NIH. So
that would be one.
The second one would be to expand the study to understand
how drugs affect the development of the human brain. We now
have that technology. We should have that information. That
will inform prevention efforts.
The third one will relate to actually making research
careers more accessible to the young investigators so that we
do not lose talent.
NIDDK
Dr. Rodgers. I would just expand upon that. I would say
that the three areas that I would focus on are the young
investigators. We know that there are two critical points in
which an investigator is likely to stay in research or exit.
One is on their first application to get a grant. The second is
getting that renewed. If they get through that second hurdle,
it is likely that they are going to be with us a long time. So
we would like to encourage them by making incentives for both
the first application, as well as the first renewal.
The other point that I would make is that with expanded
funds, we would be able to allow for expansion of some of our
existing clinical studies, which are very expensive, because of
the curtail that we would have to do. One way to amplify the
investment in infrastructure in these clinical trials is by
having ancillary studies to these trials. So I would expand
existing trials, as well as ancillary studies to these trials.
NCI
Dr. Lowy. Thank you, Senator Mikulski. In the question of
young people, we at NCI are in the process of trying to develop
new approaches to enhance their ability to move from being
graduate students and postdoctoral fellows to starting their
own laboratories. The areas where we would invest would be in
cancer prevention, cancer screening, and cancer treatment,
using molecular precision medicine approaches, which have
enormous potential in those areas.
I would highlight the potential of immunotherapy, as was
discussed earlier, because of the issue of its potential for
improved responses, decreased side effects, and scalability, as
Senator Blunt mentioned.
NINDS
Dr. Koroshetz. In terms of research projects, we talked
about the BRAIN Initiative. There is also the National Action
Plan for Alzheimer's Disease Research. Both of those have
milestones. It is all planned out. If we had the funding, we
could really accelerate both of those major projects.
In terms of young people, I think supporting young
investigators is incredibly important. The average age of
becoming independent with an NIH grant is now going to the mid-
40s. We have to move that down. We have a couple of things that
we are considering at NINDS to support somebody who is really
young, who really looks bright, and just give them a chance
much, much earlier in their career.
NIGMS
Dr. Lorsch. My institute mostly funds fundamental basic
research. The great ideas that lead to the discoveries that Dr.
Collins told you about in basic research do not come from me
and, as much as I esteem my colleagues, do not come from them.
They come from the great brilliant minds at the universities,
institutions in your districts across the country. We would
focus on supporting investigator-initiated research to promote
these brilliant scientists to do their work.
As a measure of that, and the success of my Institute, as
Dr. Collins alluded to, has funded a number of Nobel Prizes. I
would have said 81 yesterday, but as of this morning, it is now
83. I think that is an indication of the power of investigator-
initiated research.
We would certainly have a focus on promoting the careers of
the young scientists who will win the Nobel Prizes of the
future.
Senator Blunt. I will point out that only Senator Mikulski
gets 50 percent more time than she is allocated. That is
totally fine with me.
One of the things I did want to do today was get on the
record the kinds of things you would do now. Strictly speaking,
to Senator Mikulski's question, the President asked for half of
the increase that the Committee has proposed that you get. So I
am going to look very carefully at all the things you said you
would do if you had the President's number, and assume I can
multiply that by two, and those will be the things you would do
if you had the number the Committee is proposing that you get
at NIH.
Mr. Shelby.
Senator Shelby. Thank you.
$3 BILLION INCREASE?
Dr. Collins, picking up on what Senator Blunt said, talking
about money, funding, which is important, say you had $3
billion more, above, what could you do with it, as far as
investigating and hoping to turn a lot of the investigative
results into better health and better treatment? What would $3
billion--just use that. I made it up, but I hope we could do
something for you. What would it do for you? What would it do
for us, everybody?
Dr. Collins. Yes, what would it do for America, for the
world? Senator, I appreciate the question. It is a lovely thing
to contemplate. As you have heard, we have lost over the last
12 years, about 22 percent of our purchasing power.
This would be about a 10 percent increase. It would not
quite get us back to where we were in 2003, but, oh my gosh, it
would be an enormous shot in the arm to a community that has
such talent and such energy and is basically being squeezed to
the point that a lot of innovation that we could be doing is
just not happening.
You heard from my colleagues the areas they would pick from
their own particular domains. I am sitting here thinking about
the other institute directors who are not here. I will mention
a couple others that I would want to put on that short list,
that if they were here they might speak to.
Vaccines, I mean, we are on the brink of being able to
develop a vaccine that would work against all influenza
strains. If Dr. Fauci was here, he would tell you all about
that. We have a path toward something that would result in not
needing your yearly flu shot that has to be re-engineered every
year, and sometimes it works and sometimes it does not, but
maybe more importantly protecting against that next worldwide
pandemic, which is overdue. We are not pushing that as hard as
we should because the resources simply are not there.
Vaccine for HIV/AIDS, we really do now see a path to make
that happen after 30 very frustrating years. Yet, we can't go
as fast on that as we would because the resources are
unavailable.
The Precision Medicine Initiative, which we hope to start
in fiscal year 2016, which I think has a lot of bipartisan
support and which the scientific community, after many
workshops and a working group that debated about this, is very
jazzed about. We cannot start that if we have a yearlong CR, as
I said previously, in answer to Senator Murray. But we could
start it, and we could ramp it up much faster if we had this
kind of curve to work with as far as research.
Then there is this whole area that we call high-risk, high-
reward research. We just announced, a couple days ago, the
funding of about 78 of these new awards. These are pioneer
awards, new innovators, early independence, and transformative
awards. These are NIH awards where you cannot apply unless you
have an idea that is really out-of-the-box. And you do not have
to have a lot of preliminary data, if your idea is exciting, we
want to see what you could do. Give the awardee the money and
let them run with it. Many of the institutes are taking that
tack, but we could go faster and could inspire people to be
more risk-taking, if we had that kind of opportunity.
Put all that together and with $3 billion, let's try it.
Let's try the experiment and see how that turns out. I promise
you, it would be amazing.
Senator Shelby. Also, not only health, it would be a good
economic investment in our country.
Dr. Collins. Thank you, Senator. The repeated economic
analyses demonstrate the return on investment for dollars that
go to NIH is about 2.2-fold in the first year to the local
community. And of course, our dollars go out to all 50 States.
UPDATE ON AUTOIMMUNE DISEASES
Senator Shelby. I would like to touch quickly on, where are
we today as far as cutting-edge research on cystic fibrosis and
also a lot of the autoimmune diseases, such as lupus.
Dr. Collins. Well, thank you again. Great questions and
great progress being made in that space. I have a personal,
deep, and longstanding interest in cystic fibrosis, as my own
laboratory found the cause of that back in 1989 when I was at
the University of Michigan.
This is a very exciting time for that disorder because
after all those years of figuring out how that small glitch in
the genome was capable of causing this disease, we now know a
great deal about the protein that is normally made and why it
does not do what it is supposed to in cystic fibrosis.
Just in the last few months, we have now seen the second
drug strategy approved by the FDA for the treatment of more
than half of those with cystic fibrosis based upon a small
molecule, a drug that is based upon molecular understanding of
the disease. Very exciting times, indeed.
I just want to mention one very exciting public-private
partnership, the Accelerating Medicines Partnership, which
several of us have been working very hard to bring together 10
drug companies with NIH to work together. And one of the
targets is, in fact, lupus and rheumatoid arthritis.
Again, I showed that picture about T cells. What is going
on with T cells and lupus? Are they overactive? Are they going
after normal tissue when they should not? What can we do with
the new technologies to understand how single cells are
behaving in order to come up with strategies that work better
than what we currently have?
So all of these areas are just full of potential right now.
Senator Blunt. Thank you, Senator.
Senator Durbin.
Senator Durbin. Thanks, Mr. Chairman. Thank you all for
being here.
Let me just say at the outset, to address this side of the
room for a moment, gathered in this room at this moment in the
United States Senate are the 11 or 12 people who could
literally make a difference for generations in medical
research, as was noted by Senator Mikulski. We have both the
authorizing committee and the appropriating committee in the
Senate. If we took a stand, a bipartisan stand, on medical
research and said, come hell or high water, we are not going to
tolerate a shutdown, a sequestration, a CR. We are going to
increase the funding for NIH and related medical research
agencies. We can make a difference.
We can make it clear, do not try to get through the Senate,
if you are going to touch it.
I want to commend the chairman, because I bothered him,
begged him, challenged him for a long, long time, based on Dr.
Collin's admonition to me: Give me 5 percent real growth for 10
years, and I will light up the scoreboard.
We have done it in this bill. I might add, parenthetically,
at the expense of some other things that are equally important,
I should say, as well.
But I want to commend the chairman for making this
commitment for 7 percent growth at NIH, which includes 5
percent real growth at NIH. And as you said, and was asked by
Senator Shelby, a onetime infusion is a good thing, but
constancy, predictability, is what leads to researcher
commitments and long-term success in what we achieve.
I would like just to throw out as a possibility that we
rally around one particular person who is up here.
For 28 years, Barbara Mikulski has been the strongest voice
for the National Institutes of Health on Capitol Hill. She is
leaving soon, unfortunately, for all of us. But I hope we can
make a Mikulski promise that we are not going to forget the
commitment of this budget and the commitment in years to come.
And I will tell you this, in the time I have been in the
Senate, you do not want to break a promise to Barbara Mikulski.
It is something you will hear about.
Senator Mikulski. Well-said.
UNDERSTANDING ALZHEIMER'S
Senator Durbin. So I hope we can be inspired by that.
Let me try to bring this down to the ground level, if I
can. I have two questions, if I can get to them.
The first is, when we talk about $2 billion in growth, $2
billion in growth in this coming year, I need to ask you, when
it comes to areas like Alzheimer's, we know that we spent $154
billion on Alzheimer's treatment, just Medicare and Medicaid.
We estimate that the private contribution of families is almost
equal to that in value. So we are talking about one-half of 1
percent of what we are spending as a Nation on Alzheimer's as
the delta, the $2 billion that we are looking for here.
When it comes to brain research, we now have reached I
think a point, please confirm if I am right, where we can start
to visualize the development of Alzheimer's in the brain and
know many years before the obvious onset that a person is
moving in that direction.
What do you see, Dr. Collins, or those who are here with
you, in terms of what we could do if we knew 15 years in
advance that Alzheimer's was likely to occur? What could we
look forward to do soon to delay it or, God willing, find a
cure?
Dr. Collins. So, I am showing you a picture that outlines
the statistics. I did not know you were going to ask the
question, but you can see what the relative numbers are here in
terms of what is currently being spent on Alzheimer's disease.
These are 2013 numbers. Obviously, that number is now going up,
and we need it to. But comparing that to what we are spending,
$203 billion in 2013, and an estimated $1.2 trillion in 2050,
if nothing gets done.
So, this is a matter of great urgency, not just because of
the economics, of course, but also because of the enormous
human tragedies that are attached to this disease.
Dr. Koroshetz, as a neurologist, Director of NINDS, can
tell you something about where we are on this and why we are
optimistic that we can actually get to a place that does not
result in that enormous blue arrow.
Dr. Koroshetz. Yes, thanks, Senator. I think you made a
really interesting point, that for the first time, we can
actually see what is going on in the brain in people with
Alzheimer's disease. In the past, we knew what happened when
people died, but we really could not see brain changes
happening in living people. But now, we have brain imaging
markers for amyloid and tau, which are the major culprits in
Alzheimer's disease. We can see that in the brain now of living
people.
As you said, we can see amyloid developing years before the
tau starts to set in. The tau seems to be the thing that kills
the cells. So Alzheimer's is like the gun. Tau is like the
bullet.
So the vision is that we develop a screening tool for
people who are developing the amyloid, determine if they are
going to develop Alzheimer's, and then come in with a drug to
block that process.
In fact, those drugs are currently being tested in clinical
trials. So we could get lucky. I mean, this looks very, very
promising, at this point in time.
Senator Durbin. And let me add, because Secretary Ernest
Moniz would hope that I would add, that this technology, which
allows us to visualize, our Department of Energy and Office of
Science had a lot to do with this.
So when you talk about medical research, the technology
side of this equation relies on other agencies.
Do I have 10 seconds? Darn it. I will try to be here for
the second round.
Dr. Collins. I would like to just quickly say that that is
a very good point. We actually have a joint meeting about the
brain between the Department of Energy and the NIH coming up in
2 weeks in Chicago.
Senator Blunt. Senator Alexander.
Senator Alexander. Thanks, Mr. Chairman.
I am sorry Senator Mikulski left because I would like for
her to know that Dr. Collins played the guitar and sang at a
place that Senator Durbin has been and Senator Mikulski desires
to go, which is the Bluebird Cafe in Nashville. It was quite a
show.
What is that song? Knock Out Disease?
Dr. Collins. That was it. I am surprised that you remember.
I thought you might have suppressed the whole thing.
ADMINISTRATIVE BURDEN
Senator Alexander. It is a great hit.
I mean, we all admire your work, but we also admire the
work of your team. We know they could be making more money some
other place, but the fact that they are here and working to
help other people is something we all respect and appreciate.
I asked you, Dr. Collins, earlier about the bill that
Senator Murray mentioned she and I are working on. We are
trying to create an environment where precision medicine can
succeed, where we get inventions and discoveries through the
process more rapidly.
One of the problems we have is that the National Academies
groups have identified that investigators, the ones that we are
wanting to get more money for, spend 42 percent of their time
on administrative tasks. Now, if we are talking about millions
more for investigators, shouldn't we be spending an equal
amount of time trying to get that 42 percent down, so we create
more dollars there?
There is a new report headed by the former president of the
University of Texas at Austin, which makes a number of serious
specific recommendations about how to deal with that. One of
them includes a research board that would coordinate an
approach towards the regulations and policies that effect
researchers that received the $40 billion we put out, not all
of that through NIH, but to colleges and universities to try to
eliminate duplication and make it more efficient.
My question is, and you do not have to do it today, a lot
of their recommendations have to do with NIH, will you review
that report, and over the next year set up a systematic way to
consider making the changes that it makes? And if you have
impediments either within the administration or the law that
would keep you from doing that, if you could let us know, we
might be able to include them in the legislation Senator Murray
and I are working on.
Dr. Collins. Senator, I appreciate very much the role you
played in bringing this important issue to the attention of the
academic community and other constituents as well, including
the government.
Senator Alexander. Thank you. I am going to ask you to
leave me about 2 minutes, because I have another question I
want to ask.
Dr. Collins. We will take with great seriousness this
report. We have looked at it in a preliminary way. We will look
at it much more deeply. I think we do have a number of ideas
and responses to that. I will be glad to share with you about
how we could do something to reduce that 42 percent.
BEST FUNDING MECHANISMS
Senator Alexander. Thank you. I want to ask you some
questions about funding, but I do not need the answers today.
But I think all of us need the answers in the next few weeks.
The House included something called mandatory funding as
well as discretionary funding. For many of us, mandatory
funding is the villain. The reason you don't have money is
because that part of the budget has gone up like this, and the
discretionary side is like this, and you are on the
discretionary side.
So our visceral reaction is against any new mandatory
funding. But I am convinced that this is a critical time in
science and a critical time of opportunity, so I am willing to
think about that. I have these questions, as I think about
that. These are the questions I would like to talk with you
about some time.
What happens at the end of the 5 years that the House
proposed? There is a cliff, and you lose $2 billion. What
happens then?
What is the purpose of the mandatory funding? If there is a
difference between discretionary funding and mandatory funding,
do you just mix it all up or is there some distinct purpose
that would justify a steadier stream of money toward mandatory
funding? What would that be?
Should there be a focus for the mandatory funding on
preventive medicine, for example? Or on precision medicine, for
example? Or on investigators, for example?
And what about oversight? We had an embarrassing thing
happen in the NIH about its manufacturing of sterile drugs
recently. If you are not accountable to us for what happens
there, then you are not accountable to anybody, really. That is
our job as appropriators.
So as a Republican, when I read Ben Bernanke's column that
says that the Fed cannot create a growth economy, it takes
education, capital formation, infrastructure, and research and
technology, I agree with that. I am all for more research. I
think we should be doubling energy research, rather than
subsidizing windmills and putting money in the pockets of rich
investors somewhere for after 22 or 23 years.
I think we should be setting priorities. My priorities do
include your work and Dr. Moniz's work. But I would like you to
think about the questions I asked about that type of funding
and maybe one of these days we will have a chance to talk about
it.
Dr. Collins. I will certainly do so.
Senator Blunt. Thank you, Senator.
Senator Merkley.
YOUNG INVESTIGATORS
Senator Merkley. Thank you very much, Mr. Chairman.
And thank you, Dr. Collins, and your team, for the vision.
The video of the T cells destroying the cancer cells is
inspiring. I think we're all thinking that we hope that over
the years ahead every possible type of receptor on every
possible type of cancer cell and the ability to program T cells
to attack them will continue to develop. I think that is the
vision that we are anticipating.
One of the concerns that I have heard often, and Oregon
Health Sciences University is a major research partner with
NIH, a lot of grant funding goes there, is the stranding of
young researchers.
Dr. Rodgers, I believe you mentioned the young
investigators, folks who are partway into their career. They
have gone through their postgraduate work. They are in a
laboratory, and then the grants don't come through, and then
they have this incredible specialty about some form of nerve
communication or chemistry deep within the cell that may be the
key, but who knows. But suddenly they are going, ``Well, what
do I do now?''
Does this continue to be a problem? And to what degree
should we be deeply concerned about this loss? We spend a huge
amount of resources to develop that talent and then suddenly
its ability to be applied is cut short.
Dr. Collins. Well, I think we should be deeply concerned.
We do put a great deal of resources into the training of this
generation of young scientists. The talents and skills that
they possess are incredibly impressive.
And yet, if you, as I often do, go and visit universities
across this country and meet with graduate students,
postdoctoral fellows, it used to be when I made those visits,
they wanted to tell me about the science they are doing. Now
they want to tell me about their anxiety about whether there is
a career path for them or not, or whether they ought to think
about doing something else. And some of them have decided to do
other things or have gone to other countries where, in fact,
the support for biomedical research is continuing to grow even
as ours has been shrinking.
Every Institute at NIH thinks about this, worries about
this. We sit around tables together and try to figure out
strategies.
Maybe I will ask Dr. Lorsch, because his Institute is
deeply engaged in our training programs, to say something about
some of the ideas we are pursuing, although I will tell you
there is no magic here without seeing some relief from the
budget squeeze in terms of what we can do. We can try to make
every dollar count.
Senator Merkley. Thank you. I would ask you, Dr. Lorsch, to
be very brief because I have two more questions I want to get
to.
Dr. Lorsch. Sure, I will be very quick. We are starting a
new pilot program to explore a new grant mechanism. There will
be a single grant per researcher that would actually address
some of Senator Alexander's issues about administrative burden,
but it would also be more stable for the investigators because
it would be a single grant. As Dr. Rodgers alluded to, this
would help carry them through that sort of valley of death
after their first grant when the second grant renewal is very
hard. That is something which has our main focuse.
Senator Merkley. Thank you.
SEQUENCING
I want to go back to where it started in terms of the
receptors and the T cells. Earlier in the DNA world that you
were centrally positioned in, it took an enormous amount of
time to do sequencing. Now that is probably, I don't know, 1/
10,000 of the time? I am not sure what the factor is, but it is
just a very tiny fraction.
Do you see a similar curve in terms of the time and effort
it takes to identify T receptors and be able to produce T cells
in a way that can attack specific cancers?
Dr. Collins. Yes. It was 13 years for the first human
genome. You can now get yours sequenced in a day or a little
less, so whatever that factor is.
In terms of looking at proteins, of course they are encoded
by genes, so we have a connection there, where we can take full
advantage of what we have learned all through the last several
decades of recombinant DNA. So we have a pretty good sense of
what in fact are the proteins that are on the surface of
various cells, including cancer cells.
The trick is that every cancer is a little different. This
is where precision medicine part of this fits in. That is very
much, I think, at the cutting edge of trying to bring
immunology, genetics, genomics, and cancer biology together to
figure out how to make that strategy work not in a one-size-
fits-all, because it probably won't work that way, but in a
precision, individualized way.
E-CIGARETTES
Senator Merkley. Shifting topics completely in the last 30
seconds here, e-cigarettes, we have seen a tremendous growth.
There have been studies that NIH has funded about the high
school students tripling their use in a single year, and so
forth.
What do you see as the role of NIH in terms of this new
form of tobacco and tobacco addiction?
Dr. Lowy. Thank you, Senator. The NIH is concerned about
tobacco consumption because it has such an impact on disease.
And in addition, the issue of e-cigarettes where we do not know
what either the short-term or long-term impact is from the
cigarettes themselves, nor do we know what the implications are
for behavior. Therefore, the NIH, in conjunction with the FDA,
is conducting research to investigate these critically
important areas.
Senator Merkley. Thank you very much.
Senator Blunt. Thank you, Senator.
Senator Cassidy.
FUNDING DECISIONS
Senator Cassidy. Hey, doctors, thank you all so much. As a
practicing physician sometimes still, I am so aware of your
good work. I think we should double your budget, because I
understand the impact that would have upon my patients, among
which, when I did my residency in 1983 in Los Angeles, the
epicenter of HIV, at least the Western epicenter, I am very
aware what was formerly a death sentence is now something you
live with.
Let me ask, because, Dr. Collins, you know that I have been
concerned that 20 years ago I think it was GAO or IOM suggested
that NIH rebalance its HIV spending from the 10 percent it had
become to diseases such as Alzheimer's and dementia, which are
more important now.
If you receive the 7 percent increase that the chair and
the ranking member aspire for, we all do, will 10 percent of
that budget continue to go, or roughly 9.5 percent, 10 percent,
of that, will that go to HIV research?
Dr. Collins. Senator, you and I have discussed this on
occasion, and I think you are raising a good point about
whether it makes sense to have a formula-driven way in which we
define how resources are to be spent, or should we focus that
entirely on what the public health needs are and what the
scientific opportunities are, the things that NIH usually does.
No, I do not think that if we had the wonderful good
fortune to receive this kind of increase, that there ought to
be a lockstep 10 percent formula-driven basis upon which we
define the HIV/AIDS research budget. I do think we should not
take our foot off the accelerator at a time when HIV/AIDS is
poised I think for some major advances, including the potential
development of a vaccine. So I think we should step away from
the formula.
Senator Cassidy. And I do not mean to interrupt. I just
have such limited time.
Dr. Collins. Sure.
Senator Cassidy. In your directive, I do not have it in
front of me, but you mentioned among the focal points in terms
of the HIV research would be an emphasis upon comorbidities.
Dr. Collins. Yes.
Senator Cassidy. Now when we hear from Merkley and Blunt
and others about young researchers not having dollars, this is
a concern to me. We pulled the minutes from the 2013 National
Institute of Heart, Lung, Blood. They are speaking about how
the success rate of non-AIDS applications are 18 percent, but
for AIDS applications, they are 42 percent, meaning that it
took a less quality project to be approved. And they hope to
encourage more submissions of AIDS projects and hope to
understand the barriers to submission.
Then I see the project currently being done is looking at
the cardiovascular comorbidities in HIV, along the lines of
that which have proposed. And yet then we find out--I think we
found out that of the 610,000 people who die every year from
heart disease, only roughly 1,800 of them have HIV as a
determinative cause.
But nonetheless the money we're spending on this study is
21 percent of the budget of the National Heart, Lung, Blood
Institute. So we're spending 21 percent of a budget for 0.29
percent of those who die from HIV.
Now if we are going to focus on comorbidities, spending 21
percent of the institute's budget on the 0.29 percent who
happened to be co-infected with HIV, it seems like we're going
in the wrong direction.
Thoughts?
Dr. Collins. So, I am not totally familiar with the
detailed numbers you present, but I will certainly look at
those.
Certainly, we are in the process, Senator, of trying to
right-size the way in which our HIV research budget is being
allocated. The Office of AIDS Research has the potential to
move dollars around between Institutes and between programs.
Senator Cassidy. But can we move it out of HIV? For
example, I have a study here. There has been $1 million that
has gone to study behavior of Chinese men having sex with men
in some city in China, $1 million over the last 4 years. It
would have been great to put that to Alzheimer's or to Oregon,
where Merkley's researcher would find--one of your predecessors
said that we are not the international institute of health, we
are the national institute of health.
Why are we spending 1 million bucks on a behavioral health
study in China?
Dr. Collins. Again, we have now identified I think the four
areas of high priority. Frankly, I do not think that that study
would necessarily fit those priorities.
Senator Cassidy. So I guess my question, you mentioned the
Office of AIDS Research moving dollars between Institutes. But
if this is the kind of study--if at NHLBI, its 42 percent
approval rate for the HIV/AIDS study, frankly, they are getting
too much money for HIV/AIDS. They are having to find people to
apply for something which is 21 percent of their budget.
Can we move money out of that area into neurodegenerative
diseases, Alzheimer's, Parkinson's, ALS?
Dr. Collins. I certainly agree with you that we should be
making decisions across NIH on the basis of public health
needs, scientific priority. I would say there are scientific
priorities emerging in HIV/AIDS that I would not want to see
neglected, particularly the opportunity to end this epidemic,
and particularly the investment in the vaccine, which is likely
to be quite expensive.
So taking your point, I do not think we should in the
process of rethinking this portfolio, which we are doing
actually quite actively right now, we should not neglect the
potential of actually investing in different ways in HIV/AIDS
that will bring an end to this epidemic.
Senator Cassidy. There is something else I have read, and I
will close with this, and I have read so much about this, I
lost this quote. But if you decide to focus exclusively on the
cure of one disease, inevitably, you end up ignoring other more
pressing needs.
We are spending $600 million right now on AIDS vaccine
domestically, and I think $24 million on the international AIDS
vaccine initiative, not that we couldn't spend more, but to
justify 10 percent of the budget on the basis of that seems as
if we will end up neglecting Alzheimer's, dementia, mental
health, addiction, et cetera.
I yield back.
Senator Blunt. Thank you, Senator.
Just for the record, Dr. Collins, you may have mentioned,
but I don't know that I heard it, if you did, the four target
areas in HIV/AIDS research, when did you announce that? That
was a recent reevaluation of where you are headed and a recent
announcement?
Dr. Collins. It was in August, Senator. I can quickly say
those four priorities: reducing the incidence of HIV/AIDS;
research towards a cure for those who are infected who
otherwise are doomed to lifelong treatment; a next-generation
of therapies with better adherence and fewer side effects; and
these HIV-associated comorbidities, recognizing there are many,
many thousands of people already infected who are having some
of those comorbidities. We need to understand them better.
Senator Blunt. Thank you.
Senator Capito.
IDEA PROGRAM
Senator Capito: Thank you, Mr. Chairman.
I thank all of you on the panel.
I would like to thank Dr. Lorsch for coming and spending
time in West Virginia at West Virginia University, talking
about a program that I learned so much about, the IDeA Program,
which is a smart, successful program. So I thank you for that.
There is research with stroke and brain, and also a
collaborative effort with other universities, Marshall
University, West Liberty, and Wheeling Jesuit. So I thank you
for that.
I wanted to give you a chance to say if you had any
takeaways from the visit there that you might be able to
address.
Dr. Lorsch. I want to thank you again, Senator. It was a
fantastic visit that really energized my staff and myself.
One thing we noticed consistently about the IDeA Program is
that it is full of best practices. I think we really saw two
there.
The first, as you mentioned, was sharing resources to
create economies of scale, particularly in access to
technologies, which we saw was very critical, especially for
the young researchers. I think that model of creating economies
of scale through sharing technology resources is something we
should think about moving nationally because it can really get
the taxpayers more science done for their money.
The other area is training young investigators. We saw how
the COBRE program, the Centers of Biomedical Research
Excellence, focuses on training young investigators. There was
recently a paper, just last week, published by a group in
Nevada, showing that investigators who participated in the
COBRE centers were three times more likely to succeed than
investigators who did not participate in the COBRE centers, a
matched set of investigators in terms of getting R01 grants and
publishing papers.
Again, I think given the importance of young investigators,
taking that model from the IDeA Program and thinking about how
we can use it nationally is really important. I certainly give
Senator Cochran a lot of credit for developing the IDeA Program
in the first place.
So thank you again.
DIVERSITY IN CLINICAL TRIALS
Senator Capito. I think the enthusiasm we saw with the
young investigators, the young researchers, is something that
was very inspiring for me. I have heard a lot about the
problems of them moving to the next steps, so hopefully we can
determine that.
Dr. Koroshetz, the National Institute of Aging is partnered
with the Centers for Disease Control and Prevention and the
Administration of Community Living in an initiative to bring
more older Americans into research programs. The program has
specific focus on Alzheimer's patients.
Both my parents recently passed away from Alzheimer's. Can
you talk to somebody like me who is 60 years old? How do you
get into these programs? How expansive are they? What are your
expectations?
And, actually, I went to an Alzheimer's meeting just the
other day, and they were talking about the push for diversity
in your research, where you are researching minorities and
other ethnic groups, women, men, because it manifests itself
differently, possibly in different types of groups, so that is
a big question for a little bit of time.
Dr. Koroshetz. Sure. Well, the National Institute of
Neurological Disorders and Stroke and the National Institute on
Aging, which is the point institute for Alzheimer's disease at
NIH, are really working very hard on Alzheimer's projects.
I think, as you mentioned, one of the stumbling blocks is
the culture of research in this country. So as we develop new
therapies, our barrier is really the number of people that we
can enroll in studies. The National Plan to Address Alzheimer's
Disease has a number of milestones, which are trying to really
expand to increase enrollment.
So in cancer, for instance, a large percentage of patients
with cancer will enroll into a trial. For neurological
disorders, it is much lower. So we really need to push on that.
I think we have some really good plans to do that.
PRESCRIPTION DRUG ABUSE
Senator Capito. I would like to help you with that, because
I think also it goes undiagnosed or it's, ``Well, they are
getting old, and that is just sort of the way it is.'' I am
really excited to hear about what you talked about with the
possibility of a vaccination or vaccine or something.
Quickly, Dr. Volkow, I am from Appalachia, West Virginia.
We have a very high incidence of prescription drug abuse and
now heroin just on an astronomical rise, overdoses and deaths
resulting from the use of heroin.
I am glad to see that you wrote in the Huffington Post,
which is something I don't read very often, I will admit, to
embrace the concept of addiction as a chronic disease. I think
we are all with you there. I do not think one of us probably
has been untouched by this.
Rural America is really suffering from this. Some of the
smaller States, lower socioeconomics, they are going to heroin,
and in other high unemployment areas.
Where do you see your role here?
Dr. Volkow. The urgency and the tragedy of what is going on
around the country, and in the Appalachia region, has made this
one of our priority initiatives. It is also one of the priority
initiatives for HHS.
So we have been working with our sister agencies or brother
agencies to actually integrate our projects to maximize the
likelihood of success. So HHS has three items, one of them is
better prescription practices for the proper management of
pain. NIDA, for example, is very invested in developing
alternative therapy treatments for the management of pain
because we are very restricted by what we currently have, which
has resulted in the overreliance on opiates, item number one.
Item number two, greater access to naloxone, which
basically is a medication that overturns----
Senator Capito. Right, that was just legalized in our
State.
Dr. Volkow. Which is wonderful.
So we are partnering with pharmaceuticals to develop
alternative ways of administering naloxone that do not require
an injection, so anyone can administer it.
The third one is deploying medication-assisted therapies
that actually have been shown to prevent overdoses and prevent
HIV infections. So we are developing alternative medications
that can increase compliance, so we are already doing that.
What we want to do is to partner with CDC in order to
develop a project that can target the Appalachian region. I
visited the place, and I was struck by how minimal the
infrastructure there was in some of these towns. So the issue
is how does one address this? We have tools. How do we deploy
them?
Senator Capito. Right. Thank you.
Thank you very much.
Senator Blunt. Senator Moran.
ALZHEIMER'S RESEARCH FUNDING
Senator Moran. Mr. Chairman, thank you very much.
Dr. Collins and crew, welcome. Thank you for the
opportunity to have a conversation today.
Dr. Collins, NIH recently released its professional
judgment budget for Alzheimer's. Am I correct in assuming that
the President's budget request was the starting point, that you
are going to build upon the President's request? Is that true?
Dr. Collins. That's true. We were building for fiscal year
2017 what a professional judgment would look like, assuming
that the President's budget was the fiscal year 2016 number.
Senator Moran. I want to give you the chance to tell us, if
we are successful in accomplishing what this Committee did in
regard to increases in funding over the President's request,
would it give us a greater opportunity to advance the success,
the research necessary to address the issues of Alzheimer's?
Dr. Collins. Yes, Senator, it would. Because of some of the
things we imagined that we would fund in fiscal year 2017
could, in fact, be started earlier in 2016, so we would want to
revise the number for the fiscal year 2017 professional
judgment budget on that basis.
Senator Moran. So Senator Blunt's subcommittee and the
inclusion of a $2 billion increase at NIH, plus the specific
issues related to brain and Alzheimer's, would have a
significant consequence on the ability to advance the cause,
elimination, cure, treatment?
Dr. Collins. I think we are not limited at the present time
by ideas or talent. We are limited by resources. Certainly, if
it were possible to have more resources in 2016, we could start
projects that would otherwise have to wait longer. So, yes, we
could go faster.
Senator Moran. Of course, Dr. Collins, I think you are a
very bright, intelligent person, but I have discovered that you
also have the ability to say the same thing more than once.
Perhaps you should be a Senator. Dr. Koroshetz.
Dr. Koroshetz. I would just say, to go with what Francis
said, for the Alzheimer's plan and for the BRAIN Initiative as
well, we have serial projects in which one depends on the
other, and we do not know what fiscal year 2016 will do, but we
are ready to go. We have announcements ready but we will not be
able to fund them unless additional money does come.
Senator Moran. So, let me make sure I understand that. You
are prepared to expend the dollars that are included in the
Senate Appropriations Committee recommendations, our
appropriation bill?
Dr. Koroshetz. We are shovel ready.
Senator Moran. Good to hear.
The Alzheimer's Disease Research Summit occurred last
February. NIH is poised to revise the research milestones that
it created in that national plan. When can we expect that?
Dr. Koroshetz. So, the National Plan to Address Alzheimer's
Disease is actually a community plan that was developed with
consultation from the scientific community, advocacy community,
patient community, and the caregiver community. NIH conducts
regular revisits to the search recommendations and milestone
referenced in the plan, so it is revised on a regular timeline.
We alternate between NINDS, which covers Alzheimer's disease-
related dementias (like vascular disease that causes dementia,
Parkinson's disease that causes dementia) and the NIA, which
leads the Alzheimer's focused research milestones.
So, on a regular basis, we are alternating between those
two areas and revising the milestones.
Senator Moran. Thank you very much.
Dr. Collins, in the budget hearing back in April, you and I
had a conversation in which you testified something along these
lines, ``To achieve our mission, we must serve as effective and
efficient stewards of the resources we have been given by the
American public.'' This is continuing to quote you, ``To
support this focus on priority-setting, we are developing an
overarching NIH strategic plan, and will be linking this with
individual Institutes and Centers strategic plans that reflect
the rapid current progress in bioscience.''
My question is, what are the details? Fill in the spaces
about what has transpired since that conversation occurred.
What are you doing that is new and that will mean that we are
going forward, and we have latest opportunities because of that
efficiency to achieve more?
Dr. Collins. Well, we are working very hard on developing
the strategic plan that you mention. We are scheduled to
deliver that to Congress in mid-December. It does try to lay
out in a clear fashion across all of NIH how it is that we set
priorities; how we make decisions about where the dollars are
most efficiently spent; and also how we are being good stewards
in terms of how the process of peer review and council review
and director actions on what we fund is carried out, as well as
a number of other efficiencies that we are concerned about,
including what Senator Alexander was discussing earlier, just
in terms of the burden that is applied to investigators who are
trying to get the research done, as well as human subjects
oversight and so on.
There will be a lot in this document that will lay out, I
think, in greater detail than has been possible before how we
intend to use all the dollars we have for the best benefit.
Senator Moran. Mr. Chairman, Dr. Collins, let me repeat
myself. I have offered this admonition, if that is a safe thing
to say, that we are often told as Members of Congress that we
do not want to be meddling in the ``politics of deciding where
research dollars should be spent.'' I share that view, but it
means it is incumbent on NIH to make the decisions that are
necessary as to where the dollars spent are the most likely to
achieve the quickest, the fastest, the best, the necessary
results.
Dr. Collins. And I welcome that responsibility, as do all
of my colleagues.
Senator Moran. And I apologize if I offended you for
suggesting that you could serve in the United States Senate.
Senator Blunt. There might have been a time when that would
be considered a compliment, but it probably would not be right
now.
We do have time for a second round of questions. We will
start with Senator Murray.
PREVENTING TYPE 2 DIABETES
Senator Murray. Thank you very much.
Dr. Rodgers, I wanted to go back to you. You spoke earlier
about the 29 million Americans who have diabetes, and the 86
million who are prediabetic. That sounds to me like we have a
crisis on our hands, as the number of Americans with that
disease continues to grow.
You mentioned the work your Institute has done on
prevention programs that incorporate regular exercise and
reduce fat intake and the huge difference it makes. The CDC's
chronic disease program, which our bill has regrettably been
forced to cut, helped fund programs like one in my home State
that supported community health efforts through the YMCA and
some other local organizations that promote healthier living.
What might taking that preventative program to scale mean
for this country's diabetic epidemic?
Dr. Rodgers. Thank you, Senator, for that question.
The YMCA that you are referring to, was able to develop
what we did in the clinical trial for the Diabetes Prevention
Program, which is a lifestyle intervention on an individual
basis, scale it up by doing the same lifestyle intervention but
providing it in a group setting. In fact, their results after
the first year or 2 were quite similar to what we achieved in
the individual program, in terms of weight loss, et cetera.
But more interestingly, the costs for patients involved in
this clinical trial with the initial instruction and the
follow-up was about $6,000 per patient. In the group setting in
the YMCA, the cost was cut down to about $400.
In terms of scaling this, for example, if we could expand
this, we have not done any economic analysis on this, but there
is a private group called the Urban Institute that has recently
looked at what happens if you could scale this. They estimate,
given those numbers, about $191 billion could be saved over a
10-year period, with some very conservative assessments or
assumptions, if this could go to scale.
CANCER RESEARCH
Senator Murray. Well, that is impressive.
Dr. Lowy, let me ask you, as Dr. Collins mentioned, we have
seen some significant progress in recent years in the use of
immunotherapy to treat certain forms of melanoma lymphoma and
lung cancer. I believe there is universal support on the
subcommittee for efforts to find similar breakthroughs for
other cancers. I want to ask you, what is NCI doing to make
that happen? And where is the potential for new cures the
greatest?
Dr. Lowy. We are investing in a number of different areas
throughout the cancer spectrum. I think that there are
opportunities in many different areas.
For example, we are investing heavily in pancreatic cancer,
because this is a cancer where we have not had significant
progress despite long-term recognition of how serious this
cancer is.
We also are investing research in pediatric interventions,
and recently NCI supported researchers have develop two new
interventions against pediatric leukemia and lymphoma. And this
was initially developed in the academic sector and has been
picked up by venture capital, and is rapidly going forward for
clinical trials.
We also are interacting with the pharmaceutical industry to
try to identify new and important uses for drugs that are off-
the-shelf, either because they have been approved for one
intervention but not for another. For example, BRAF inhibitors
in melanoma, trying them in other diseases. This is potentially
a very important innovation, because we recognize that a
percentage of patients who have different kinds of cancers may
actually have the same molecular abnormalities and, therefore,
may benefit from targeted treatments initially developed in
other areas.
I could go on but I think that given the time----
Senator Murray. Could you just tell me why immunotherapy is
effective in some patients but not in others who have the same
cancer?
Dr. Lowy. Yes. I think that this is a critically important
issue. I think what we are doing to support research to
understand mechanisms is critically important because if we
could understand why some patients are benefiting, whereas
others are not, that increased understanding should lead to
better interventions for the people who currently are not
responding. Or at the very least, we would not be giving them
treatment for which they are not going to benefit.
Senator Murray. So it is a question we need to answer with
more research.
Dr. Lowy. Yes.
Senator Murray. Okay, thank you very much.
Senator Blunt. I will go last in this second round, so,
Senator Shelby.
REPLICATION OF RESEARCH
Senator Shelby. I will be as fast as I can. Thank you, Mr.
Chairman.
Dr. Collins, there have been several articles regarding
biomedical study results, including those funded by NIH, that
appear in top peer-reviewed journals that cannot be replicated
or reproduced. One of the articles cited a Bayer study
describing how it had halted 64 percent of its early drug
target projects because in-house experiments failed to match
claims made in the publication.
You have done a study on this. What is the problem here?
Why can't they replicate? Is it rushing to print too fast? What
is it? Would you discuss that?
Dr. Collins. Senator, it was you who first brought this
issue to attention in a hearing about 3 years ago as it was
just beginning to appear. I appreciate very much your having
shined a light on a situation that we are taking with great
seriousness.
This is a complicated, multi-factored situation. I am
actually showing up on the screen what NIH has now posted as
far as a summary of all the things we are engaged in to try to
address this, and also to do things to improve the training of
the next generation of scientists about these issues, in terms
of rigor and reproducibility.
I would say, of the factors that are involved, certainly
the hypercompetitive atmosphere that currently exists, much of
it on the basis of the fact that funding is so tight, causes
people to try to get publications out as quickly as possible.
That may, in fact, result in circumstances where the
replication study didn't quite get done. And therefore,
somebody else finds out later it would not have worked.
We have an issue in terms of journals also, in many
instances, not having been as thorough as they should in
evaluating manuscripts.
I am happy to say that through the leadership of Dr.
Lawrence Tabak, the principal deputy, we convened the journals
to talk about this. Now more than 150 journals have signed off
on a checklist that they use when papers come in to be sure
that the experimental details are there, the statistical
methods are described, and so on.
It clearly is something, though, that touches many areas of
science. Dr. Lorsch has been leading an effort where we are
looking at projects on cell lines, because sometimes people
publish a paper about work on a cell line and it turns out that
cell line was not what they thought it was. These things get
passed around.
Training is critical. We actually have some training videos
up on the site, if you want to see what we are now asking
mentors to use in lab meetings and other group meetings, to try
to bring to the attention of trainees these critical issues
about study design, how you set up an experiment where you know
that you have done it rigorously.
So we are all over this, and we are, in fact, pushing
pretty hard to see this problem addressed.
It will always be the case that science gives you results
that, later on, you cannot seem to make sense out of. But if
that happens, we want it to happen in a way that was
unavoidable, not because people were actually cutting corners.
I think we have the whole attention of the community now to
this, and you are going to see the problem get less than it had
been. I hope much less.
Senator Shelby. But this is a very important question,
because it goes right to the essence of the investigation and
replicating what you have found or discovered and what we
benefit from. Is that correct?
Doctor, do you want to comment on that?
Dr. Koroshetz. Yes, I was going to add one other point. We
have looked at this at our Institute, and there is another side
to this, which is that for some of these things, it is not that
you can't reproduce them. It is that given the effort that you
put in, you didn't reproduce them.
So we have, for instance, really interesting technologies.
When you first try to reproduce it, you can't do it. But when
the people who develop the technologies open up their labs,
people can go in and learn how to do it, and then it works.
Senator Shelby. So some of them were on the right road, but
they just did not have the means to finish it?
Dr. Koroshetz. That's right.
Senator Shelby. Thank you, Mr. Chairman.
Senator Blunt. Thank you, Senator.
Let's go to Senator Cassidy and then Senator Moran.
BASIC SCIENCE OF ADDICTION
Senator Cassidy. First, I misspoke last time. $66 million
is not 21 percent of the NHLBI. That was too much. But
nonetheless, the point is taken. The best we can find out, it
is about 1,800 people who die of HIV with cardiovascular
disease. We are spending $66 million on it.
Dr. Volkow, I heard people say that the basic science of
addiction and mental health is a barren field. I am not a
mental health professional nor an addictionologist. But I am
just asking, do you feel as if you had, to take the question
asked earlier, significant more resources, would you be able to
do the clinical and basic science to make significant advances
in the area of addictionology? And could you speak to that for
mental health as well?
Dr. Volkow. Yes. Definitely, we could accelerate a lot of
the discoveries. And I apologize, Senator, but I am going to
disagree, because I would not say the research on mental health
and substance abuse disorders has been barren as it relates to
over the past 10 years, 15 years, a really expanded
understanding about the abnormalities in the brain of people
who suffer from mental illness.
Senator Cassidy. I accept that. Actually, I did not know
enough to disagree, but you would say there is great academic
progress?
Dr. Volkow. There has been great academic progress, and
that has enabled us to identify potential targets for
treatment.
But there is a problem going----
Senator Cassidy. Can I stop you?
Dr. Volkow. Yes.
FUNDING NEURODEGENERATIVE RESEARCH
Senator Cassidy. Dr. Koroshetz, again, the issue on
Alzheimer's dementia and ALS and Parkinson's, I heard people
say the promise is not there as it might be in other fields.
I also have parents with dementia and Alzheimer's. I want
to give you a lot of money. I am hoping to convince my
colleagues who have more sway--that is where they go ahead of
me, they have more sway than me--to do so as well. Would that
be a worthy investment? Is there academic promise in those
fields, that if you got the money, you can do the basic
research, clinical research, et cetera?
Dr. Koroshetz. I think the neurodegeneration field, in
general, is bringing in lots of really smart people to try to
solve these problems. So we have the workforce. I think with
the resources, we could really make hay.
As I said before, there are a couple things that are really
tantalizing now, and that is that all the neurodegenerative
diseases--Parkinson's, Alzheimer's, ALS--all have one common
feature. The cells that die have proteins that aggregate and
get stuck in those cells.
So, people really are on the idea that maybe there is a
unified theory. If we can stop this process for one disease, we
can stop it for all of them.
So, it is a leap of faith right now, but there is evidence
that this is not impossible, that we can make a big
breakthrough.
Senator Cassidy. Dr. Collins.
Dr. Collins. I would just like to add to that----
Senator Cassidy. I have a question for you, Dr. Collins.
Dr. Collins. Okay, this will be quick. Just basically, the
point here is that you are never quite sure where the
breakthroughs are going to come from. We have to be careful not
to overly target research plans in a direction of a specific
disease because the answer might come out of some very
different investigation or some very basic science, as we are
celebrating today with the Nobel Prizes.
Just a quick example, the biggest breakthrough that I have
heard about in the last month for ALS----
DECISION MAKING
Senator Cassidy. No, can I just stop you? I have a minute
and 45 seconds. Can I stop you for a second?
You have a bunch of bright, aggressive people who they
would not be who they are were it not for you being the
pinnacle. Believe me, I am a doc. I know you are the pinnacle
of the docs.
You mentioned earlier the academic promise, the research
promise, of HIV/AIDS as a rationale to somewhat continue there.
I guess what I was trying to figure out is, is it lacking
elsewhere? One of the excuses--or one of the reasons, I should
say, to continue the funding in one area as opposed to others
is the apparent academic promise in the one as opposed to the
others.
How do you balance each of these folks who have such
promise in their field as you make that decision?
Dr. Collins. That is a great question. That is something we
talk about every day around the table.
Certainly, in every one of these Institutes, there are
areas that are up-and-coming and others that perhaps are not
quite as rapidly moving. We are constantly trying to adjust the
decisionmaking, but also not trying to be overly top-down in
making decisions because a lot of the great ideas come from our
wonderful scientific community out there, and we cannot always
anticipate where they are going. So it is a constant revision
day by day, week by week, of where we want to put the emphasis.
Senator Cassidy. Okay.
And if my wish were fulfilled and dollars were redirected
from HIV/AIDS into some of these other areas, it sounds like
there are fertile fields that that money would, indeed,
fertilize and hopefully sow great benefits.
Dr. Collins. There are fertile fields all across our
landscape.
Senator Cassidy. Okay, I yield back. Thank you.
Senator Blunt. Senator Moran.
ALS
Senator Moran. Mr. Chairman, thank you.
Dr. Collins, the most significant development that has
occurred in the last 30 days is? On ALS?
Dr. Collins. Okay, thank you. It sort of fits with the
conversation we are having.
It was an investigator who is actually studying HIV/AIDS
and trying to understand one of the comorbidities, which is a
neurological problem, which resembles ALS in a modest way. This
is an intramural investigator, Avi Nath.
He discovered that there is an activation of an endogenous
retrovirus that we all carry around called HERV and that it
starts making copies of itself and it causes this damage to the
neurological system, particularly those anterior horn cells.
This looks very much like ALS. And in fact, the publication,
which just came out, suggested that this might be one of those
missing clues to what is happening in Lou Gehrig's disease, not
for people who have HIV at all, but who have similar symptoms.
I don't know where that is going to go. Dr. Koroshetz
probably could tell you a lot more about the details.
But it was an interesting example where you are studying
this disease over here, and you learn something about that one
over there, and you didn't expect that to happen.
Senator Moran. Thank you.
UPDATE ON PEDIATRIC MATCH TRIAL
Dr. Lowy, welcome to this panel. I look forward to getting
better acquainted with you. I just want to give you the
opportunity to express, as the relatively new Acting Director,
your vision for the National Cancer Institute. I particularly
wanted to highlight a program that is being launched, a
pediatric clinical trial called Pediatric MATCH trial, and can
you tell me about that and where you see it going and what it
may mean.
Dr. Lowy. The Pediatric MATCH trial, Senator, is a trial
that is currently under development. What it does is
essentially do for pediatric cancer research what the Adult
MATCH trial that started 2 months ago is doing for adults who
have advanced cancer for which there is no standard treatment.
It puts the molecular abnormality of the patient front and
center, rather than the origin in the body of where it occurs.
And it takes drugs that are off-the-shelf, either experimental
drugs or that have been approved for other uses, and it tests
them in these other ways for cancers where they are not yet
approved.
The goal is to improve the outlook for these patients. This
is a trial that, as I said, is under development and one of the
uses for the Precision Medicine Initiative, the oncology
portion, that people have been talking about.
Senator Moran. And your vision for NCI?
Dr. Lowy. The overall vision for NCI is to support basic
research, as we have done historically, to invest in precision
medicine, not just in the areas of cancer treatment, as is
occurring with the Precision Medicine Initiative and the
oncology portion, but also to emphasize precision medicine in
the area of cancer prevention and cancer screening,
understanding better the causes of cancer, understanding better
how cancer comes about, and, in addition, to put a focus on
health disparities in cancer.
Unfortunately, there are many different kinds of cancer
where certain underrepresented minorities have a much higher
incidence of mortality, and we need to treat these populations
as we would any high-risk population to understand the biology,
the lifestyle factors, and the utilization of medical utility,
and, in addition, to try to mitigate these factors just as we
do for any high-risk population.
These are some of the important areas that we are looking
forward to making progress in.
Senator Moran. Thank you very much. I wish you well.
Mr. Chairman, thank you for this hearing. Thanks to you and
Senator Murray for your leadership in this area of medical
research.
SUPPORT FOR INNOVATIVE RESEARCH
Senator Blunt. Well, thank you, Senator Moran.
Dr. Lorsch, when Senator Moran was the ranking member on
this Committee, they started an effort like the Defense
Advanced Research Projects on high-risk. I think it was fiscal
year 2014.
You mentioned high risk, high reward, a couple times. Give
a couple examples of either things that did work out, or things
that did not that we should be thinking about when we think
about going to a high-risk area as opposed to something that is
more likely to produce a result, but maybe not nearly as big of
a result.
Dr. Lorsch. I think the recent developments in gene editing
are an example of something that was an out-of-the-box idea.
Could you use this bacterial system that allows rearrangements
of genes and then use it to edit genes in a mammalian cell to
possibly repair those genes in a diseased state? That is
something, as you may know, that has recently worked and has
taken off and is revolutionizing biotechnology and has the
promise to revolutionize medicine in a variety of ways. I think
that is a great example of that.
Dr. Collins. I might mention that the Common Fund at NIH,
which the Congress made into a permanent part of our budget
back in 2006, is a place that specifically aims to try to
support these high-risk, high-reward projects that no single
Institute would probably be able to invest in, but collectively
we can.
A couple examples there. The microbe biome, this effort to
understand how the microbes that live on us and in us that
actually outnumber us if you start counting up cells, how do
those play a role in our health and in the cause of disease.
This has been an absolutely revolutionary set of insights
coming about because of new technologies that allow us to find
out what is there and how it changes over time. That was one of
those high-risk, high-reward programs that has now changed the
whole landscape of how all the institutes are doing research
because you really do not want to think of the human as an
organism now. You want to think of us as superorganisms. It is
both us and the microbes, and it is the interaction between the
two that makes a big difference. That is an example.
Another one, which is closer to clinical medicine, is to
try to come up with a really standardized, reliable way of
patients reporting outcomes from their perspective. So much of
clinical research is the researchers or doctors saying here is
what we think happened to this patient who was given this
treatment. You want to hear what the patient thought, too.
Sometimes it is not quite the same thing.
But we have not had those majors, so a program called
Promise, which many people thought this was going to be really
hard, has actually transformed that process. It makes it
possible now for us to run more clinical trials where the
patients are not really patients. They are partners. They are
full participants. Their input is guiding our decisionmaking
about what works and what doesn't.
Senator Blunt. I think Washington University is doing some
of the microbial work.
Dr. Collins. They are. Jeff Gordon, your heroic figure
there at Wash. University is one of the main leaders in the
world.
Senator Blunt. And unlike the genetic structure, the
microbial structure is changing all the time and how you impact
that is the question here. Is that right?
Dr. Collins. That is right. And as we are now mounting this
Precision Medicine Initiative, thinking about following 1
million Americans over time, to know what is happening to their
microbe biome would be enormously interesting, as a consequence
of diet, exercise, the presence of illness or not, taking
antibiotics. We could find this out on a scale not previously
imaginable once we get this up and going.
Senator Blunt. Right.
OPIOID AND HERION ABUSE
I am going to come to you, Dr. Volkow. Senator Murray
mentioned earlier the cut to the block grant fund. In fact, we
cut lots of programs in this budget to begin to reorient the
bill towards other priorities. In fact, I think we eliminated
totally funding for 43 programs that this year we are spending
$1.25 billion, all of which had very good titles. There was not
a single title that was not meritorious.
But the process of prioritizing is exactly that. You do not
really prioritize if all you do is get more money and spend it
on something more important than you thought you were spending
on last year. That is not really prioritizing. That is just
adding more money on top for good things.
But what brought me to that when I thought about, well, we
did cut those block grants by about 3 percent. But the majority
of that money, in my view, went into increasing the money to
combat opioid abuse, which, frankly, a handful of years ago I
hadn't heard of at all. But in Committee hearings this year, we
heard about it all the time.
Would you talk a little bit about both opioid abuse and
what research may be going on to come up with pain medicines
that are less easily abused, and less easily converted to other
drugs to be used in other ways? That would be helpful.
Dr. Volkow. Yes, indeed. Unfortunately, you are hearing
about opioids because of their devastating consequences. So on
the one hand, we have basically seen 16,000 people die from
prescription opioid overdoses. Over the past 6 years, we have
seen a fourfold increase in people dying from heroin. So it was
stable for many years, at around 2,000 deaths per year. And in
the past 5 years, it has increased to over 8,000 deaths in
2013. So we are seeing a really steep increase in deaths from
prescription opioids and now from heroin.
That has led us to realize the nature of the problem. So on
the one hand, we have the reality that there are many patients
suffering from chronic pain but we do not have sufficient
alternatives, as I was mentioning before.
So in partnership with the pain consortia at NIH, NIDA is
trying to develop alternative medications that are effective
for severe pain that are not addictive. We are trying to also
partner with the pharmaceutical industry to develop opioid
medications that will not be diverted.
We are partnering, of course, with the funding agencies.
And the FDA recently approved some new indication that an
opioid medication cannot be diverted.
We are also encouraging the better education of the
healthcare providers on how to screen properly for pain and how
to manage opioids, and how to, of course, screen for substance
use disorders.
So there is a multipronged approach, both from the
perspective of NIH with various Institutes working together and
at the same time with our sister agencies.
Senator Blunt. And I would think one of those groups may be
whatever is happening in the Defense Department research on
this topic because, certainly, servicemembers and veterans have
a really high propensity to find themselves in that trap of
becoming addicted to the pain medicines that they are given,
often because of their service-related injuries, and that
cannot be a good thing.
Dr. Volkow. You are pointing at something that,
unfortunately, not many people are aware of. The prevalence of
pain in military people returning is much higher. As a result
of that, they are much more likely to be given prescription
opioids, much higher than the rest of the public.
Therefore, the number of people who are dying from
prescription opioids among the military is higher, just by the
fact of what you are saying. They are suffering from pain, and
we do not have many pain alternatives, so they receive opioid
medications.
Senator Blunt. Well, thank you for your help on that.
Senator Shaheen.
Senator Shaheen. Thank you, Mr. Chairman.
I would like to follow up on the concerns that you are
raising about opioid abuse and also heroin, the fact that it
has led to a heroin epidemic. That is a huge challenge that we
are facing in the Northeast and across this country.
I can tell you that in my little town of Dover with a
population of about 20,000 people, they had two recent deaths
just in 1 day from drug overdoses. I think it should rise to
the level of the kind of cross-agency--it is a crisis, and I
appreciate that you all have a different mission in terms of
research. But this is something that the medical community, the
law enforcement community, the treatment community, all need to
be working on together. Until that happens, we are going to
continue to see this crisis escalate. It is already out of
control, and it is only going to get worse.
So when, in a small town in New Hampshire, you can buy a
bag of heroin for less than you can get your prescription
filled for $7 a bag, then we have a real problem.
So I want to make that point, because I am not sure if
there are other ways in which you all are looking at addressing
this issue, beyond just the challenge of opioids. And the
extent to which that gets people addicted, are there other
things you are looking at with respect to the opioid and heroin
epidemic that is going on in the country right now? I am happy
to direct that to whoever would like to take it.
Dr. Volkow. Yes, indeed. Again, it is a devastating
situation, but one of the reinforcing things to me has been how
integrated the agencies have been in working together to come
up with solutions and how these solutions are actually coming
into very specific action items, like the FDA approving new
indication for deterrent formulations, like the DEA coming up
with let's bring back all those opioid medications that are not
being used.
These actually are resulting in effective interventions. So
there is a very strong, concerted effort.
The good news is that there are medications that we
currently have that are effective for the treatment of people
that become addicted to those opioid prescriptions. The
challenge is that they are not being implemented. So we are
working with agencies to actually develop implementation
strategies to increase it, to provide medications for the
patients that would be easier to take so that they are
compliant.
USE OF NARCAN
Senator Shaheen. Right. Sorry to interrupt.
So does NIH have a view on whether Narcan should be
available over-the-counter to families, not to law enforcement
or other people who actually do interventions, but to families
who are concerned about drug overdoses and their families? Is
that something that you think should be readily available?
Dr. Volkow. I think we are extremely lucky to have Narcan.
We should make it as widely available as possible.
Senator Shaheen. Thank you.
I would just urge NIH to think about all of the ways in
which you can engage on this issue, because it is, as you know,
out of control and getting worse, not better, despite all of
the coordinated efforts. We see those in New Hampshire and
other States that are dealing with this issue, but we still
have not made it, I think, the kind of all-hands-on-deck
priority that it should be.
Dr. Collins. I would just add to that, there is a lot of
interagency work on this. There is interagency pain research
coordinating committee that meets. It is all the Federal
agencies. I think they are doing very good work. We have
education programs.
COORDINATION OF EFFORTS--STATE AND FEDERAL
Senator Shaheen. Can I just interrupt? So how are they
coordinating the work that they are doing at the State level,
with States that are dealing with this issue?
Dr. Collins. I would have to get back to you on the State
level, because that is something that we have not really
approached. But there is a national pain strategy that we are
working on through HHS to be cleared soon that addresses some
of these problems.
There are education programs that NIH funds. One of the
issues is really educating the practitioners on the actual
proper use. So we have centers of excellence for education on
how to manage pain that NIH funds. HHS has a tremendous video
for education of practitioners on the use of narcotics and best
management of pain, trying to reverse this problem.
Senator Shaheen. Well, I do not know how we make sure that
States are aware of the work that is going on, but, certainly,
that seems to be one of the coordinating points that has to
happen in order to better address the crisis. So I would urge
that you all think about that, and if we can be helpful in
thinking about how to make sure that that kind of information
and effort is available.
Dr. Collins. I would just add quickly, Congressman Hal
Rogers, who has been such an effective leader in terms of
bringing attention to this, runs a summit every April and
brings in the States. And Dr. Volkow and I have been at that
summit each time for the last couple years. Tom Frieden, head
of the CDC, comes.
It is an opportunity for States to really hear what the
opportunities are that are being thought about across the
Nation. It is probably not enough because, as you say, we are
still in the thick of a very serious epidemic. But those
connections are trying to be made, and I have to give
Congressman Rogers a lot of credit for being a convener.
Senator Shaheen. Thank you.
Senator Blunt. Thank you, Senator Shaheen.
Dr. Collins, thank you and thank you for the fine
representation of your team. As you suggested, there are even
more on the bench that you could call in at some future time
for a hearing. We might ask you to do that.
ADDITIONAL COMMITTEE QUESTIONS
Over the next week, the record will stay open for
questions. I know Senator Alexander and others have already put
some questions out there, and I am sure you will get some.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted to Dr. Francis S. Collins
Questions Submitted by Senator Roy Blunt
alzheimer's funding
Question. Dr. Collins, the Senate received the NIH's first bypass
budget for funding Alzheimer's disease which requested an increase of
$323 million for fiscal year 2017.
--Given that the Senate Labor/HHS bill for fiscal year 2016 provides
more funding ($350 million) than what NIH requested for fiscal
year 2017, how would the bypass budget be changed for next
year?
--Can we assume all of the requested research projects for fiscal
year 2017 would, instead, be done in fiscal year 2016 if the
Senate funding level for NIH is enacted?
--Dr. Collins, 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?
Dr. Collins, has Alzheimer's research had significant application
to other major disease research efforts? What crossover benefits have
we seen from increasing Alzheimer's research funding?
Answer. NIH recognized that a substantial increase in funding for
Alzheimer's disease (AD) for fiscal year 2016 would have an impact on
the implementation of the milestones linked to the fiscal year 2017
Bypass Budget. To address this possibility, NIH created a separate plan
for accelerating many of the activities outlined in the fiscal year
2017 Bypass Budget milestones to be initiated in fiscal year 2016.
Under this circumstance, the fiscal year 2018 Bypass Budget would
reflect this acceleration and include estimates for targeting new goals
from its overarching list of long-range milestones.\1\
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\1\ Https://www.nia.nih.gov/budget-files/alzheimers-disease-
research-implementation-milestones-2013-2025.pdf.
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Not all of the projects outlined in the fiscal year 2017 milestones
can be accelerated into fiscal year 2016, even if the Senate funding
level for NIH is enacted. For example, the creation of new cohorts to
accelerate the identification of gene variants and other risk and
protective factors is a lengthy, detailed, and labor-intensive process,
as it involves the collection of large amounts of data, including
informed consent from thousands of participants. In addition, some
research areas require further development and will be explored further
in fiscal year 2017. These include aging processes in human cell models
of AD; the planned biorepository for AD biological samples;
translational bioinformatics; and validation of the NIH Toolbox for
Assessment of Neurological and Behavioral Function, among others.
NIH recognizes that the public health burden of AD will only become
larger, if preventative therapies and treatments are not established.
AD is a prominent focus of the Accelerating Medicines Partnership, a
major public-private partnership between NIH, FDA, 10 biopharmaceutical
companies and multiple non-profit organizations to transform the
current model for developing new diagnostics and treatments by jointly
identifying and validating promising biological targets for
therapeutics.
Increased support for Alzheimer's has advanced our knowledge not
only of that disease, but of other diseases and conditions, as well--
most notably other neurodegenerative diseases such as frontotemporal
dementia (FTD). For example:
--The efforts toward discovery and standardization of imaging
biomarkers made in Alzheimer's are being leveraged in other
neurodegenerative diseases, such as FTD and Parkinson's
disease.
--Investments in fluid biomarker discovery using various ``omics''
technologies--metabolomics in particular--are geared toward the
identification of biomarkers that can be used to stratify
patients for clinical trials, and identify participants most
likely to respond to a specific therapy, for both AD and
related dementias.
--NIA has funded research on the development of human induced
pluripotent stem (iPS) cells for AD modeling. Further studies
have shown that such use of ``disease-in-a-dish'' models can be
effectively used to study molecular mechanisms underlying not
only AD, but also other neurodegenerative and
neurodevelopmental diseases.
Systems biology approaches aimed at identifying complex genetic and
molecular networks, such as the Accelerating Medicines Partnership
(AMP), will enable the identification of molecular signatures and
networks underlying the various disease processes that lead to symptoms
associated with AD. These efforts will lay the foundation for precision
medicine for AD and other dementias (i.e., it will enable us to treat
the right disease process with the right drug at the right time). The
AMP-AD systems biology efforts will also enable us to identify
molecular events that are shared between AD and other disorders. This
could facilitate successful repurposing of drugs that prove effective
for AD for their use in other neurodegenerative conditions with similar
underlying pathologies--and vice versa.
Finally, NIH-supported Alzheimer's genetics initiatives have
provided genetic information relevant to several unrelated conditions,
including autism, congenital heart disease, scoliosis, pain, cancer,
and neurologic disease. In 2012, the NIA Genetics of Alzheimer's
Disease Data Storage Site (NIAGADS) and the Database for Genotypes and
Phenotypes (dbGaP) formed a unique partnership in order to efficiently
provide data to the research community. Through this exceptional
arrangement, dbGaP's capacity to work with specific genetics user
communities was augmented. The interface between the two databases now
serves as a prototype for other genetics user communities; similar
designs are being explored or planned by three other NIH Institutes
(NINDS, NHGRI, and NHLBI). Most recently, the Gabrielle Miller Kids
Fund Common Fund initiative has engaged NIAGADS for discussion on
design of a similar interface.
precision medicine
Question. Dr. Collins, at our hearing in April, we discussed the
revolutionary idea of Precision Medicine. Since that time, NIH has made
progress on developing a plan to move this initiative forward and
stakeholders have been able to express their thoughts about the plan. I
have heard several concerns from cancer researchers about the 1 million
person cohort. In particular, researchers have expressed concern about
what scientific question a cohort would be answering and how the NIH
would ensure the cohort includes a proportionate representation of
Americans, particularly individuals from racial and ethnic minorities.
What are your views on these concerns and can you discuss how the
cohort would be setup to take into consideration these concerns and how
a 1 million person cohort will inform the initiative?
Answer. The appropriate size, composition, and research power of
the Precision Medicine Initiative (PMI) cohort were major foci of the
deliberations of the PMI Working Group of the Advisory Committee to the
Director, which delivered its blue print for the PMI Cohort Program on
September 17, 2015. The Working Group included renowned experts from
all sectors: private and public sectors, academic research, clinicians,
and participants. Their deliberations and recommendations were informed
by four major national workshops, two requests for information, and a
public survey. The primary objective of the PMI Cohort Program will be
to enroll one million or more volunteers into a cohort that broadly
reflects the diversity of the U.S. population, and to follow their
health and clinical outcomes over time. The PMI Working Group report
has been widely embraced and applauded by the scientific community
including industry and patient groups.
NIH has now released a number of funding opportunities to solicit
the very best ideas from the scientific community to build the PMI
Cohort (https://www.nih.gov/precision-medicine-initiative-cohort-
program/funding-opportunities). The funding opportunities specifically
request that applicants address past experience with inclusion of
diverse populations and provide specifics plans a capabilities for
doing so as a part of the PMI Cohort Program. The potential of this
diverse cohort of one million or more presents a spectacular variety of
scientific opportunities, including:
--Develop quantitative estimates of risk for a range of diseases by
integrating environmental exposures, genetic factors and gene-
environment interactions
--Identify the causes of individual variation in response to commonly
used therapeutics (pharmacogenomics)
--Discover biological markers that signal increased or decreased risk
of developing common diseases
--Use mobile health (mHealth) technologies to correlate activity,
physiological measures and environmental exposures with health
outcomes
--Develop new disease classifications and relationships
--Empower study participants with data and information to improve
their own health
--Create a platform to enable trials of targeted therapies
pmi and national children's study
Question. Congress appropriated over $1 billion over a decade for a
cohort of children as part of the National Children's Study (NCS). The
NCS was plagued with problems, in particular with composing a cohort
that adequately reflected the diversity of Americans. It eventually was
ended in 2014 with virtually no studies being conducted and $1 billion
being spent. How do we ensure that this will not happen with the
Precision Medicine cohort?
Answer. In order to pre-emptively identify and address challenges
that the Precision Medicine Initiative (PMI) Cohort, a large-scale,
longitudinal cohort, might face, the PMI Working Group consulted on
this issue with research cohort management experts including David
Murray, the NIH Associate Director for Prevention who is tasked with
managing the closure of the NCS, and Sir Rory Collins, the Chief
Executive of the UK Biobank and a member of the PMI Working Group.
These consultations resulted in a number of ``lessons learned'' for
both successful (the UK Biobank was able to bounce back after initial
challenges) and unsuccessful (NCS was unable to find its footing)
large-scale cohort studies. These lessons included the suggestion to
guide the cohort design with a limited set of research questions; to
require partners to provide high degrees of data standardization and
centralize core data; to select a sampling approach that is efficient
and feasible; to design a strong and nimble governance structure that
is aware of and rapidly responsive to changes in the social,
technological, and scientific elements arising in a cohort over time;
to carefully select the right funding mechanisms for the project scope;
to carefully test new procedures in small pilots; and to ensure that
enrollment is convenient.
These ``lessons learned'' were incorporated into the PMI Working
Group recommendations for the PMI Cohort Program. For example, the
Working Group began its work by defining the scientific questions it
expected the cohort to be able to answer. It recommended a core data
set required for partner organizations and volunteers that will be
collected in a centralized data center, with federated inquiries
available for other data. It recommended an approach that favors
diversity over representativeness, and a small and powerful governance
structure, composed primarily of one director and a small executive
committee, that will ensure that the PMI Cohort Program can be
immediately responsive to necessary changes in the program's structure.
The NIH carefully examined the best funding mechanisms for each element
of the program, and proposes early pilots that will allow us to
carefully test and retest the program elements, including proposals to
test the best way to enroll participants directly as well as through
healthcare provider organizations (see Blunt Question: PMI Accuracy and
Quality).
pmi accuracy and quality of data
Question. Dr. Collins, it is challenging to deal with the accuracy
and quality of data when it comes from multiple sources. How will the
Precision Medicine cohort deal with this issue?
Answer. The accuracy and quality of the Precision Medicine
Initiative (PMI) cohort data was another focal point of discussions
for the PMI Working Group of the Advisory Committee to the Director.
The PMI Working Group included multiple experts in the field of
bioinformatics and ``big data'' research, all of whom emphasized that
data standards should be developed before data collection begins, given
that the use of data standards promotes quality science, consistency in
data use and re-use, and meta-analysis. PMI Working Group deliberations
and recommendations were also informed by four major national
workshops, one of which focused specifically on scientific and
methodologic considerations to maximize the quality, accuracy, and
utility of detailed health information for PMI Cohort participants. The
PMI Working Group made a number of recommendations that NIH will
implement in order to ensure accuracy and quality of PMI data coming
from multiple sources, such as recommendation to create a data
coordinating center that will be responsible for the storage,
management, and transmission of a curated and analysis-ready core set
of data; to develop a system whereby the details of data collection and
curation will be agreed upon between data collection sites and the data
coordinating center before data collection begins; to adopt and utilize
existing data standards to the greatest extent possible and require the
use of common data models to develop a structured core data set that
can be distributed to researchers; and to establish a data subcommittee
of the PMI Cohort Program governance structure to oversee ongoing data
collection and ensure that the program maintains high quality,
accuracy, and utility.
______
Questions Submitted by Senator Jerry Moran
alzheimer's disease research
Question. Following the Alzheimer's Disease Research Summit last
February, NIH is poised to revise the research milestones created by
the National Plan. When can we expect to see in the updated milestones?
To what extent do those milestones match the recommendations that were
printed in the journal Alzheimer's & Dementia in October of last year?
Does NIH intend to release program announcements that are tied to the
milestones document?
Answer. NIH released two related sets of research milestones, along
with the fiscal year 2017 Alzheimer's Disease and Related Dementias
Bypass Budget, on July 27, 2015. One was a broad set of Alzheimer's-
specific milestones that included a number of long-range research goals
that extend to 2025: https://www.nia.nih.gov/budget-files/alzheimers-
disease-research-implementation-milestones-2013-2025.pdf. These
milestones reflected recommendations made across the diverse range of
research topics covered at the 2015 Alzheimer's Disease Research
Summit. NIH also released a set of fiscal year 2017-specific milestones
for Alzheimer's and related dementias (https://www.nia.nih.gov/budget-
files/fy-2017-alzheimers-disease-bypass-budget-milestones.pdf). The
latter milestones were used to develop the fiscal year 2017 Alzheimer's
Disease and Related Dementias Bypass Budget: https://www.nia.nih.gov/
budget-files/Reaching-for-a-Cure-Alzheimers-Disease-and-Related-
Dementias-Research-at-NIH.pdf. Thirteen NIH ICs contributed to the
fiscal year 2017 milestones, and they were informed by two scientific
meetings (in addition to the 2012 and 2015 Alzheimer's Disease Research
Summits), the 2013 conference on Alzheimer's Disease-Related Dementias,
and the 2013 meeting on Advancing Treatment for Alzheimer's Disease in
Individuals with Down Syndrome.
With respect to the relationship between the NIH's established
milestones and the recommendations for updating the 2012 milestones
published in the journal Alzheimer's & Dementia, there is considerable
overlap. The recommendations published in the academic journal reflect
input assembled by a non-Federal funding organization, and NIH took
these recommendations into consideration as it produced its latest
published research milestones.
Ten Funding Opportunity Announcements (FOAs) were released by the
NIA in the fall of 2015 to address the updated research milestones and
offer flexibility for funding in a wide range of budgetary
circumstances. The FOAs have set-aside funds associated with them, and
will be supported according to the availability of funds in fiscal year
2016 and fiscal year 2017. They fall into seven broad categories, and
offer opportunities for investigators in virtually every aspect of AD
research--including health disparities, caregiving, epidemiology,
diagnosis and prediction, molecular and cellular mechanisms, brain
aging, and clinical trials. These FOAs incorporate themes and
recommendations from the 2012 and 2015 Alzheimer's Disease Research
Summits. The categories are intentionally wide-ranging and each FOA is
important in its own way.
brain initiative
Question. What would be the biggest impact of a shortfall in the
projected funding for the BRAIN Initiative?
Answer. The biggest impact lies in the inability to fully, and in a
timely manner, realize the bold, ambitious goal of the BRAIN
Initiative: to revolutionize our understanding of the human brain, and
empower researchers seeking new ways to treat, cure, and even prevent
brain disorders.
The gap between NIH's fiscal year 2015 budget request for the BRAIN
Initiative, and the funds actually appropriated, has two direct
consequences. First, it delays the overall pace at which NIH can scale-
up its efforts for the BRAIN Initiative, causing scientific progress to
fall further and further behind the 12-year plan laid out by the
Advisory Committee to the NIH Director (ACD) in their report BRAIN
2025: A Scientific Vision. The BRAIN 2025 plan outlines a step-wise
sequence of research with subsequent steps dependent upon prior
success. Shortfalls in funding slow the stepwise progress. Secondly, it
forces NIH to scale back the scope of research being funded under
current Funding Opportunities which leads to gaps that could undermine
the solid foundation laid out in the BRAIN 2025 plan. As one example, a
major project in the BRAIN Initiative is to assemble research teams to
collect, analyze, and share data from recordings of the human brain.
This project was vetted by the external scientific experts that compose
the BRAIN Multi-Council Working Group and was announced to the
scientific community in fiscal year 2015. However, the grant
solicitation process was halted due to the gap between the budget
request and appropriated funds. This project and the fiscal year 2016
projects described below are ready to launch pending budget
availability. In general, the competition for the fiscal year 2015
BRAIN Initiative awards was extremely competitive and funds were
insufficient to support many otherwise excellent proposals.
The BRAIN Initiative is focused on developing neurotechnologies
that enable scientists to understand the functions of specific brain
circuits, including circuits relevant to neurological disorders such as
Parkinson's disease, epilepsy, recovery from traumatic brain injury and
stroke, mental illness, and addiction. To achieve this goal, NIH is
funding teams of engineers, physicists, chemists, and neuroscientists
to develop devices that can record and modulate activity in the brain
at scales that span from single neurons to entire brain regions. This
work promises to enable accurate early diagnosis of disorders of brain
circuit activity such as depression, autism, and schizophrenia, as well
as to build upon the success of deep brain stimulation for Parkinson's
disease to develop new ways to reduce suffering caused by a variety of
neurological and mental illnesses. Funding shortfalls inevitably lead
to delays in achieving such goals. These delays mean that people
suffering now with devastating brain diseases and disorders may have to
wait longer for the treatment breakthroughs that could transform their
lives and the lives of their families and communities.
alzheimer's disease research
Question. Recent budgets have included money to expand research
efforts related to Alzheimer's disease. Can you tell me about some of
those efforts and things you hope to achieve in the next few years?
Answer. New investments include large-scale research for
identification of new risk and protective genes; development of new
cellular models of the disease to enable rapid screens of potential
therapeutic agents; establishment of translational centers that will
support drug discovery and development; and groundbreaking prevention
trials in people at the highest risk of disease. Joint initiatives are
identifying imaging and fluid biomarkers that enable us to detect and
track the onset and progression of Alzheimer's-related brain changes.
Clinical trials are now underway testing therapies in pre-symptomatic
volunteers at risk for developing Alzheimer's. These ground-breaking
trials may lead to the long-sought interventions that can directly
influence the underlying pathology. Collaborations among NIH, the
biomedical industry and advocacy groups--such as the Accelerating
Medicines Partnership--are overcoming traditional barriers to drug
discovery.
Other new investments include the Alzheimer's Disease Sequencing
Project supporting the analysis of whole exome and genome sequencing
data; testing of anti-amyloid drug interventions through the
Alzheimer's Prevention Initiative APOE4 trial and the Dominantly
Inherited Alzheimer's Network Trials Unit (DIAN-TU); and studies of
exercise and physical activity in preventing, treating, and managing
Alzheimer's disease. Research is also being continued on support
interventions for those caring for individuals with Alzheimer's disease
and other dementias; for example, the NIA-funded REACH II intervention
that is currently being broadly translated in 15 States through the
Department of Veterans Affairs and in 3 States by the Administration on
Aging.
Recently, NIA released 10 Funding Opportunity Announcements (FOAs).
These FOAs incorporate themes and recommendations from the 2012 and
2015 Alzheimer's Disease Research Summits. They fall into seven broad
categories, and offer opportunities for investigators in virtually
every aspect of AD research--including health disparities, caregiving,
epidemiology, diagnosis and prediction, molecular and cellular
mechanisms, brain aging, and clinical trials. The FOAs have set-aside
funds associated with them, and will be supported according to the
availability of funds in fiscal year 2016 and fiscal year 2017.
Finally, while Alzheimer's disease is the most common form of
dementia, related dementias, including vascular, frontotemporal, and
Lewy body dementias, also represent a significant burden of dementia.
Brain vascular disease such as silent stroke, diffuse white matter
disease and arteriosclerosis is exceedingly common in persons with
Alzheimer's dementia. The neurodegenerative processes can be difficult
to distinguish clinically and frequently overlap. Research, too, is
focused on neural processes that are shared among the different
neurodegenerative disease and how aged blood vessels contribute to loss
of brain function. For instance, increased funding for Alzheimer's and
related dementia research allows researchers to begin sequencing DNA
from 1,500 people with frontotemporal dementia and 1,300 people with
Lewy body dementia to identify regions of DNA associated with risk for
these disease and has enabled scientists to better understand the
interactions between blood vessels, neurons, support cells, and
proteins associated with Alzheimer's disease and how these interactions
contribute to dementia.
impact of cr to the precision medicine initiative
Question. I know NIH has kicked off its precision medicine
initiative, which has generated quite a bit of excitement. With the
agency currently under a continuing resolution, what precision medicine
efforts are currently being delayed by limitations on new starts and
new efforts?
Answer. NIH efforts around the Precision Medicine Initiative (PMI)
include both PMI Cohort Program, coordinated through the NIH Office of
the Director (OD), and PMI for Oncology, coordinated through the
National Cancer Institute (NCI). NIH OD is working diligently to
implement the PMI Working Group's recommendations to build the PMI
Cohort Program, developing funding opportunities, governance roles, and
structures, and working to promote policies that are needed for the
success of the PMI Cohort Program. These preparations are critical for
ensuring that the PMI Cohort Program can begin its important work as
soon as possible. Much of this planning can be done under the current
continuing resolution, but a full-year continuing resolution would
require us to put a halt to all of the PMI Cohort Program efforts.
Similarly, NCI's PMI for Oncology has begun foundational work upon
which it will build its PMI effort. By way of example, enrollment was
open and highly successful for the NCI-MATCH trial, which will be
dramatically expanded under the PMI, adding more sites and adding more
therapeutic agents, as well as speeding the development Pediatric
MATCH. These planned expansions are jeopardized under the continuing
resolution, slowing the progress of this critical trial.
funding grants during continuing resolution
Question. The NIH has a set system for operating and dealing with
its grant portfolio during a continuing resolution. Could you please
describe the methodology you must implement when NIH does not have a
full-year appropriation?
Answer. When NIH operates under a continuing resolution (CR) for
part of the year, a Notice in the NIH Guide for Grants and Contracts is
released describing the financial operations planned for grant awards
during the CR (An example notice is NOT-OD-15-050, found at http://
grants.nih.gov/grants/guide/notice-files/NOT-OD-15-050.html).
Generally, NIH's funding policy is to fund non-competing continuation
awards at up to 90 percent of the committed award level, noting that
reductions may be restored after an appropriation is in place. Since
new, competing awards have not yet been committed, they are typically
held until either appropriations legislation has been passed or, as in
fiscal year 2011, a CR is approved to set funding levels through the
end of the fiscal year. As a consequence, funding is delayed for highly
meritorious new awards that are ready to be funded at the start of the
fiscal year.
In fiscal years 2011-2015, more than three-fourths of NIH's new,
competing grants were awarded in the third and fourth quarters when a
final funding resolution or appropriation was in place. Thus, new,
competing awards bear the brunt of funding delays. However, since
yearly continuation award dates are linked to the date of the original,
competing award, the practice of issuing multiple continuing
resolutions affects the NIH funding cycle for the 4-5 year life of new
awards issued in a given fiscal year.
neuronext clinical trials
Question. The University of Kansas Medical Center is a site in the
new NeuroNEXT clinical trials consortium. Can you tell us about the
NeuroNEXT clinical trials program and how it has been a success in
delivering clinical trials to neurology patients faster and more
efficiently?
Answer. The NIH Network of Excellence in Neuroscience Clinical
Trials was established in 2011 to provide shared infrastructure and
centralized resources to expedite the development and execution of
early phase clinical studies across a range of neurological disorders
affecting adult and/or pediatric populations. To date, the network has
initiated five clinical trials in five different neurological
conditions and is streamlining the process of testing new therapies in
patients.
The first study in the network completed enrollment ahead of
schedule, and investigators are currently analyzing the data to
identify early biological markers of spinal muscular atrophy (SMA) in
infants. The raw data from this study will also be shared with the FDA
in order to inform their ongoing evaluations of potential treatments
for SMA. Three other trials are underway and are on target to complete
enrollment on or ahead of schedule: one study is testing the safety and
efficacy of a potential neuroprotective therapy in patients with
progressive multiple sclerosis; another is exploring whether the drug
rituximab can reduce the need for steroid use (which can have
intolerable side effects) in patients with myasthenia gravis; and
another is testing a new agent that has the potential to protect brain
tissue in patients with moderate strokes who have been given the clot-
busting drug tPA. The fifth study in the network was recently approved
and will assess the tolerability of a new drug for treatment of
aggression and irritability in patients with Huntington's Disease (HD),
which are among the most distressing aspects of the disease.
NeuroNEXT has successfully engaged communities and partnered with
private entities. Patient advocacy groups have been involved in all of
the NeuroNEXT studies from early stage protocol development through the
actual conduct of the study. The HD study is being conducted as a Small
Business Innovative Research (SBIR) project, and the other studies have
received contributions from private industry partners. The use of
shared infrastructure and centralized expertise and resources, such as
a single Institutional Review Board, has reduced inefficiencies and
enabled the NeuroNEXT studies to achieve quicker start-up times than
would have been possible in the traditional approach of establishing
separate multi-site processes for each new trial. Further, their
ability to consistently meet recruitment targets on schedule decreases
clinical trial costs and facilitates on-time study completion. The
expertise of the NeuroNEXT team and their ability to effectively
recruit and partner across a broad range of neurology disciplines is
reflected in the diversity of disorders and patient populations being
addressed by the network.
pmi working group
Question. The PMI Working Group that Dr. Collins discussed in his
QFR response has issued a report (which you probably have seen, but
here it is for sake of convenience.\2\ The Working Group recognized
that excluding children would ``limit the scientific validity and
utility of the cohort, deprive PMI cohort participants of opportunities
to benefit from research, and worse, could increase health disparities
for these groups.'' The Working Group also recommended that the PMI--P
include individuals from all life stages.
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\2\ Http://www.nih.gov/precisionmedicine/09172015-pmi-working-
group-report.pdf
---------------------------------------------------------------------------
However, in reference to inclusion of special populations such as
children, the Working Group noted that there are ``scientific, ethical
and policies issues surrounding these populations that warrant further
discussion. Therefore, the Working Group recommends that NIH consider
the safeguards necessary to ensure the appropriate enrollment,
retention, and protection of these groups into the PMI cohort.''
Considering these statements from the Working Group, could we get
an update on NIH's plans for including a pediatric population within
the PMI research cohort now that the Working Group has made
recommendations?
Answer. NIH will include children as participants in the PMI Cohort
Program. As recommended by the PMI Working Group, NIH is currently
considering how to best incorporate pediatric participants into the
cohort while fully addressing the unique scientific approaches and
ethical commitments to this population.
Children present a unique set of legal, ethical and policy issues
in clinical research that warrant careful consideration before actively
recruiting them into the cohort. For example, existing Federal rules
for the protection of research participants provide specific regulatory
requirements for research involving children, including additional
review by the Institutional Review Board and special consent
procedures.\3\ NIH is looking at an early pilot to enroll families as a
way to test the best approaches to pediatric participation.
---------------------------------------------------------------------------
\3\ Please see the HHS Office for Human Research Protections
guidance on subpart D of the HHS regulations at 45 CFR part 46 to learn
more about regulations for research involving children at http://
www.hhs.gov/ohrp/policy/faq/children-research/special-requirements-
children-research.html.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Thad Cochran
cannabidiol (cbd)
Question. At NIH, the Congress traditionally has allowed science to
dictate how research dollars are spent. What is the potential utility
of CBD-rich extracts in refractory childhood epilepsy (and perhaps
other neurological disorders) and is the science there to justify the
expenditure of Federal funds for research in this area?
Answer. There is evidence from small non-controlled (open label)
studies that Cannabidiol-rich extracts may be effective in treating
certain severe forms of childhood epilepsy in some individuals. Other
studies have suggested that medical marijuana in various forms may
relieve some symptoms of other neurological disorders. While these
studies point to the promise of this research, they also highlight the
need for rigorous studies to determine the safety and effectiveness of
these compounds in treating neurological disorders, especially in
children. Investigator-initiated research deemed meritorious through
NIH's peer review process that follows applicable regulations would be
an appropriate mechanism to help answer these important questions. The
National Institute of Neurological Disorders and Stroke (NINDS) is
currently conducting studies to investigate the anti-seizure activity
of some of these compounds through NINDS's Anticonvulsant Screening
Program (ASP), which offers academic and industry-based investigators
the opportunity to screen compounds for anti-seizure activity in a
battery of well-established rodent seizure models. Having obtained
approval for appropriate Schedule 1 licenses, ASP is now collaborating
with NIDA to conduct anti-seizure studies in rodents on Cannabidiol and
tetrahydrocannabidiol (THC), the primary psychotropic compounds found
in marijuana.
Question. If the science is there to justify CBD research, does NIH
have sufficient funding for researchers to conduct these clinical
trials?
Answer. In general, NIH does not set aside funding for research in
a particular area, but rather funds the most meritorious investigator-
initiated research--as determined by the NIH peer review process--
across all the research areas within the NIH mission. Proposals for
clinical trials are carefully reviewed to insure that there is
sufficient pre-clinical research prior to testing potential therapies
in humans. NIH welcomes investigator-initiated research on pre-clinical
and clinical research on the promise of CBD for treating disease.
Question. Does NIDA's current contractor, the University of
Mississippi, have the capacity to cultivate sufficient cannabis to meet
researchers' needs and the ability to produce CBD under Current Good
Manufacturing Practices (cGMP) for clinical research/trials?
Answer. The University of Mississippi has been able to meet the
supply demands of the scientific community for marijuana thus far;
however, interest in marijuana research is rapidly growing and
researchers are interested in many diverse strains of marijuana
including strains with high levels of CBD. While the NIDA contractor
could increase the volume of marijuana grown and available it would be
impractical for NIDA to produce, at this single facility, more than a
few of the varieties of marijuana currently being used in the various
States. This has led some to argue that it is important to license
additional growers of marijuana for research purposes. Federal agencies
including HHS, the Department of Justice (DOJ), the Office of National
Drug Control Policy (ONDCP) and the State Department have been working
together to identify potential solutions to this issue that are in
compliance with U.S. laws and international treaty obligations.
Currently, the NIDA Drug Supply Program does supply CBD for animal
research purposes, and the University of Mississippi has developed a
marijuana extract with a high concentration of CBD under cGMP
procedures. This extract is available for human research studies;
however, the current formulation is not conducive for easy
administration within human clinical trials. Researchers interested in
using this extract for human studies would need to develop a
formulation for easy administration (e.g., oral suspension in sesame
oil). NIDA is currently working with the FDA to develop easy-to-use
formulations and dosages of this extract for human research.
In addition, NIDA recently awarded an SBIR to Aphios to develop a
method for generating cGMP grade CBD for use in clinical trials and
other research projects. The primary goal of this research program is
to develop a process for manufacturing pharmaceutical grade CBD
following current cGMP of the FDA for use in clinical trials for
childhood epilepsy and other indications. The secondary goal is to
develop a standardized, enriched CBD product for use in clinical
trials. Having additional suppliers of both marijuana plant products
and purified CBD would ensure that these products are available to
scientists in a more timely fashion.
Question. If there is both the capacity to cultivate sufficient
amounts of cannabis and the ability to produce CBD under cGMP at the
University of Mississippi, is the barrier to production due to a lack
of funding within NIDA?
Answer. The University of Mississippi has been able to meet the
supply demands of the scientific community for marijuana thus far.
idea program
Question. The Mississippi IDeA Network of Biomedical Research
Excellence links colleges and universities across the State in order to
engage our talented researchers and students in research projects.
NIH's investment in the IDeA program, which benefits almost half the
States in the Nation, is relatively modest compared to the overall NIH
budget. Do you plan to invest more in the IDeA program in the future
and what are your strategies for continuing to ensure the success of
this program?
Answer. NIH appreciates the Committee's support for the
Institutional Development Award (IDeA) program and recognition of the
importance of the goals of providing research infrastructure and
building research capacity in the IDeA institutions. In fiscal year
2016, NIH anticipates making 12 new Center of Biomedical Research
Excellence (COBRE Phase I) awards and supporting up to 8 COBRE
competing continuation (Phase II) awards and 6-7 new COBRE Phase III
awards. Twenty-three IDeA Network of Biomedical Research Excellence
(INBRE) awards have competed successfully for continued support. NIH
anticipates making one additional competing continuation INBRE award
and 4 new IDeA-CTR awards. NIH also anticipates co-funding 25 R01 and
R15 awards across NIH Institutes and Centers. Additionally, support
will be provided for the non-competing COBRE, Institutional Development
Award Program Infrastructure for Clinical and Translational Research
(IDeA-CTR), and INBRE awards that constitute the IDeA base.
To ensure the success of this program, NIH plans to:
--Continue to build active biomedical research environments in IDeA
States and improve access to modern, state-of the-art
biomedical research for students, researchers, and the general
public in IDeA States.
--Ensure that States without medical schools have an opportunity to
develop research capacity for conducting basic, translational
and clinical research.
--Continue to provide opportunities to address health disparities in
medically underserved groups residing in IDeA States.
--Continue promoting the Small Business Innovation Research/Small
Business Technology Transfer programs, technology transfer,
entrepreneurship, and public-private partnerships to create and
enhance vibrant translational research environments within IDeA
supported institutions.
--Encourage collaborations and leveraging among IDeA research
resource centers to capitalize on each other's unique
capabilities to solve complex research queries, and encourage
consolidation of research resources that hold complementary
technologies to improve efficiency and create economies of
scale.
--Enhance the competitiveness of institutions by providing
opportunities for talented undergraduate students to
participate in research training and research careers in the
biomedical sciences.
Develop best practices, training tools, workflows, databases, and
analysis tools that assist clinical and translational researchers to
develop and perform clinical and translational protocols to quickly and
efficiently address important questions in multiple areas of science.
leveraging existing alzheimer's research
Question. The University of Mississippi Medical Center serves as a
study site and conducts research in the Atherosclerosis Risk in
Communities (ARIC) Neurocognitive Study. This study is the most
comprehensive research project currently funded by NIH that examines
risk factors for dementia. How do you plan to maximize the potential of
existing research studies, like ARIC, as NIH moves forward with the
BRAIN initiative?
Answer. The Atherosclerosis Risk in Communities Study (ARIC) is a
prospective study of almost 16,000 participants in four U.S.
communities that is exploring the causes and consequences of
atherosclerosis, and how cardiovascular risk factors, medical care, and
disease vary by race, gender, location, and date. Extensive medical,
social, and demographic information was collected on the participants
through five in-person examinations over 25 years, and their health
status continues to be followed annually by phone. The ARIC
Neurocognitive Study is investigating the role of midlife vascular risk
factors in dementia and cognitive impairment, and how the burden of
these conditions varies by race and sex. Cognitive testing has been
conducted to assess decline in cognitive ability, executive function,
memory, and language skills, and brain MRI has been performed to detect
abnormalities known to be associated with cognitive impairment. These
studies have led to the finding that high blood pressure in midlife was
associated with cognitive decline in later life, results that were
demonstrated in a recent publication (Gottesman et al., 2014. JAMA
Neurol; 71(10): 12181227). An additional ancillary study to ARIC is the
PET-Amyloid Imaging Study, which is conducting specialized brain
imaging on some of the participants to better understand the link
between vascular risk factors and hallmark characteristics of
Alzheimer's disease that can be seen on amyloid imaging, and how their
prevalence associates with development of dementia. The ARIC study
provides an important opportunity to study potentially modifiable risk
factors for dementia over a long period of time and thus could have
important implications for public health.
In addition to large-scale observational studies such as ARIC,
research conducted through the Brain Research through Advancing
Innovative Neurotechnologies (BRAIN) Initiative also holds potential to
advance dementia research. A patient's symptoms are the manifestation
of dysfunction in brain circuit activity, yet currently available tools
for monitoring and modulating brain circuits are inadequate for fully
understanding the basis for neurological and mental disorders. The
BRAIN Initiative promises to deliver new technologies that will amplify
our ability to monitor and therapeutically change brain circuit
activity, leading to a new understanding of how individual cells and
complex neural circuits interact in both normal and disordered
conditions. Advances in neuroimaging technologies in particular will
enhance our ability to study dementia and other brain disorders more
effectively. Unprecedented opportunities will emerge from these
advances to pursue new ways to treat a wide range of brain disorders,
including dementia, and in combination with the wealth of knowledge we
are gaining from studies like ARIC NCS, the research community will be
well poised to translate these discoveries into improved public health.
______
Questions Submitted by Senator Mark Kirk
batten disease
Question. One of the cities I represent has been gripped by the
story of Charlotte and Gwenyth Gray, two beautiful young girls
diagnosed with Batten Disease, a neurodegenerative brain disease that
will leave them blind, immobile, cognitively impaired and eventually
dead between the ages of 6 and 12. A disease for which currently there
is no treatment or cure. This community, that I am proud to represent,
recently came together to raise $350,000 for research to cure Batten,
trying to beat the clock for Charlotte and Gwenyth and believing that
no other parents and children should have to face this horrible disease
and deadly outcomes. However, as you well know, the funds that can be
raised privately pale in comparison to the Federal disease research
infrastructure. What can NIH do to assist researchers racing to help
children with Batten Disease?
Answer. NIH assists researchers racing to help children with Batten
disease directly by supporting their research. NIH also supports the
development of research tools, resources, and basic research that
underpins progress against many diseases, including Batten disease. For
example, researchers studying Batten disease have applied genetic
technologies, online genetics databases, and informatics tools
developed through NIH support to identify specific gene defects that
cause Batten disease. They have used methods from NIH investments in
basic stem cell biology to develop induced pluripotent stem cells
derived from skin cells of patients with Batten disease that enable
them to study crucial aspects of the disease in cell culture and to
screen for potential treatments. And they have capitalized on advances
in genetic engineering to produce transgenic mouse models of Batten
disease to study the disease and test interventions. Likewise,
researchers developing candidate therapeutic interventions for Batten
disease rely on more general progress in gene therapy, stem cells,
biomarkers, imaging technologies, and methods to, among other example,
provide access of therapeutic agents through the blood brain barrier.
For example, studies are underway to advance gene therapy for Batten's
disease using viral vectors to deliver the missing enzyme.
Question. And how can this orphan disease and others like it, get
the Federal grant funding they need to make a difference for children?
Answer. Because of the devastating effects of Batten disease on the
brain, the National Institute of Neurological Disorders and Stroke
(NINDS) leads NIH research against this disease. Other parts of NIH
support research and bring their expertise to bear as appropriate to
their missions; for example, the National Eye Institute (NEI) supports
research on blindness caused by this disease. NINDS, like all of NIH,
places a high priority on supporting research against rare disorders
because the private sector is less likely to invest in rare diseases
and rare disorders provide crucial clues to more common diseases. Most
importantly, rare diseases have an enormous impact on families. NINDS
provides a wide array of different types of grants suitable for all
types of investigator-initiated research on rare diseases, from early
exploratory research to in-depth studies, and from basic research on
disease mechanisms through preclinical therapy development and clinical
trials. The NeuroNext clinical trial network was designed specifically
to serve the needs of clinical research in rare pediatric neurological
diseases, such as Batten disease, as opportunities emerge. Private
advocacy groups play a very important role in encouraging researchers
to take up the challenge of Batten disease and other rare diseases, and
NINDS scientific program directors guide investigators to take
advantage of these funding opportunities. Currently funded grants
related to Batten disease include pilot projects, traditional R01
grants, and multi-investigator projects, and range from basic studies
to understand how gene defects cause harm, though early preclinical
therapy development using a variety of strategies, and clinical studies
in patients to develop advanced MRI and laboratory tests to objectively
measure the progress of the disease and whether patients are responding
to therapies. The NIH RePORT website (https://projectreporter.nih.gov/
reporter.cfm) provides access to summaries and links to published
results from current and past grants on Batten disease.
induced pluripotent stem cells
Question. How are induced pluripotent stem cells being used in
laboratories at NIH to advance biomedical research? To what extent has
this research led to new treatments or cures?
Answer. Recent research has demonstrated that stem cells have the
remarkable potential to develop into many different cell types in the
body. In many bodily tissues, stem cells serve as a kind of internal
repair system, dividing extensively to replenish other cells as long as
the person or animal is alive. When a stem cell divides, each new cell
has the potential either to remain a stem cell or become another type
of cell with a more specialized function, such as a muscle cell, a red
blood cell, or a brain cell. A recently developed research technique,
which garnered the 2012 Nobel Prize in Physiology or Medicine, now
makes it possible to create a new type of stem cell called an induced
pluripotent stem (iPS) cell in the laboratory. iPS cells are derived
from mature cells, typically from a patient's skin or blood, which
researchers can reprogram back to an immature state. These cells can
then be turned into a wide variety of cell types, including liver
cells, neurons, cardiac cells, and blood cells. NIH-funded scientists
are studying iPS cells and other types of stem cells, not only to
understand better cell function and disease pathways, but also to
develop therapies for a variety of diseases and disabilities, including
Parkinson's disease, amyotrophic lateral sclerosis (ALS), spinal cord
injuries, heart disease, diabetes, and arthritis. Since the development
of iPS cells is a relatively new discovery, most NIH funded research is
focused on finding ways to develop different cell types from iPS cells,
refining methods so that the resulting cells would be safe to use in
people, and testing the cells in animal models. Three examples are
given here of promising approaches:
--Macular degeneration: an NIH intramural scientist is pursuing
preclinical efficacy and safety studies with retinal pigment
epithelium tissue, developed from a patient's own skin cells
using iPS technology, to treat age-related macular
degeneration, a leading cause of blindness in the elderly.
--Type 1 diabetes: NIH-funded researchers at Harvard University
developed a multistep process to coax large numbers of both iPS
cells and human embryonic stem cells into a state that closely
resembles naturally-occurring pancreatic beta cells, with the
ability to respond to fluctuating glucose levels by
appropriately increasing or decreasing secretion of insulin.
Two weeks after transplantation into a mouse model of type 1
diabetes, these stem cell-derived beta cells were still able to
produce significant amounts of insulin in response to glucose
and protect against hyperglycemia. Although the process will
need to be adapted for large-scale manufacturing, and further
tests must be conducted to determine if stem cell-derived beta
cells can be a long-term replacement for beta cells in people,
this dramatically improved process for making large amounts of
beta cells is a promising step toward developing therapeutic
stem cell therapies; it may also lead to advances in artificial
organ development.
--Liver failure: NIH-funded researchers at the University of
California, San Francisco and the Gladstone Institutes have
coaxed iPS cells into becoming what appear to be fully
functional liver cells. They have developed a protocol that
transforms human skin cells into mature liver cells that not
only function normally in a lab dish, but proliferate after
they have been transplanted into mice that model human liver
failure. This ability to proliferate is a hallmark of normal
liver cells--and the secret to the liver's astounding capacity
to regenerate after infection or injury.
______
Questions Submitted by Senator Bill Cassidy
hiv funding
Question. As was asked during the Appropriations Hearing on October
7, 2015, in fiscal year 2014, the National Heart, Lung, and Blood
Institute (NHLBI) received $64,044,000 from the Office of AIDS Research
(OAR) (or 2.1 percent of all the AIDS Research funding at NIH) to study
heart, lung, and blood disease co-morbidity with HIV. After much
research, we learned from the American Heart Association that in 2013,
the CDC reported an incidence of 1,815 cardiovascular disease deaths
with HIV as the underlying cause. CDC also reported that about 610,000
Americans die from cardiovascular disease every year. Of those who die
from cardiovascular disease each year, only .29 percent of them have
HIV as underlying cause--that is very low. During the meeting of the
National, Heart, Lung, and Blood Advisory Committee in 2012, it was
reported that the success rates for AIDS application that were much
higher than for non-AIDS applications--42 percent vs 18%--suggesting
that projects with low review scores and low significance are being
funded. Please provide answers to the following related questions:
--What are the success rates for HIV related applications at the
other NIH Institutes that receive OAR funding?
--What are the success rates for non-HIV applications at Institutes?
Answer. NIH Institutes and Centers provide AIDS funding to
unsolicited investigator-initiated grant applications and applications
submitted in response to specific funding opportunity announcements
(FOAs) that are deemed highly meritorious in NIH's dual level peer
review process. Applications awarded under a FOA targeted to a specific
scientific topic or objective may appear to have an unusually high
success rate, but this is not because projects with low review scores
and low significance are being funded; on the converse, targeted FOAs
sometimes attract a small number of applications prepared by applicants
who are exceptionally qualified to address the objectives of the FOA,
and a larger proportion of these applications are deemed to be highly
meritorious in the peer review process.
The success rate indicates the percentage of reviewed grant
applications that were awarded on a fiscal year basis. It is determined
by dividing the number of competing applications funded by the sum of
the total number of competing applications reviewed and the number of
funded carryovers. The success rate calculation is always performed
after the close of the fiscal year. To better reflect the funding of
unique research applications, the number of grant applications is
adjusted by removing the number of revised applications and correcting
for projects where the resubmitted application is submitted in the same
year as the original grant application.
NIH supports a comprehensive program of biomedical, behavioral, and
social science research on HIV/AIDS and its associated comorbidities,
coinfections, and other complications. As therapeutic approaches to
managing patients with HIV/AIDS have improved, so has the longevity of
patients who can tolerate the side effects, toxicities, and other
complications associated with the treatment regimens. As a consequence,
there also is an increasing occurrence of HIV-associated comorbidities,
including cardiovascular, hepatic, metabolic, renal, neurologic, AIDS-
defining, and non-AIDS defining malignancies, and other clinical
complications associated with long-term HIV disease and antiretroviral
therapy. An overarching priority for the NIH HIV/AIDS research program
is the prevention and treatment of HIV-associated comorbidities and
coinfections.
The clinical challenges confronting HIV-infected patients on
optimal antiretroviral therapy is shifting from acute infectious
complications associated with HIV to chronic diseases, such as coronary
artery disease, chronic lung disease, and chronic anemia. By 2030, it
is estimated that 84 percent of the HIV population will have one or
more co-morbidities, and 78 percent will have cardiovascular disease.
Research findings also suggest that HIV-infected individuals are up to
twice as likely as those without HIV to have cardiovascular disease,
yet this important public health issue remains understudied. What we
learn about HIV-related inflammation and other pathophysiological
processes may provide insights into all patients with cardiovascular
disease.
--The success rates for each NIH Institute and Center's HIV-related
research project grant applications in fiscal year 2014 is
provided in the table on the next page. The trans-NIH success
rate for HIV-related research project grants was 22.9 percent
in fiscal year 2014.\4\
---------------------------------------------------------------------------
\4\ Research Project Grants are defined as activity codes R00, R01,
R03, R15, R21, R22, R23, R29, R33, R34, R35, R36, R37, R55, R56, RC1,
RC2, RC3, RC4, RF1, RL1, RL2, RL5, RL9, P01, P42, PN1, PM1, RM1, UA5,
UC1, UC2, UC3, UC4, UC7, UF1, UH2, UH3, UH5, UM1, UM2, U01, U19, U34,
DP1, DP2, DP3, DP4, and DP5. Not all of these activities may be in use
by NIH every year.
---------------------------------------------------------------------------
--The trans-NIH success rate for all applications was 21.0 percent in
fiscal year 2014.
The success rates for each NIH Institute and Center's research
project grant applications in fiscal year 2014 is provided publically
at: http://report.nih.gov/DisplayRePORT.aspx?rid=601.
HIV/AIDS-RELATED SUCCESS RATES FOR RESEARCH PROJECT GRANT APPLICATIONS
BY NIH INSTITUTES AND CENTERS IN FISCAL YEAR 2014 \5\
------------------------------------------------------------------------
Success
Institute/Center Rate
------------------------------------------------------------------------
NCI............................................................ 17.9%
NHLBI.......................................................... 41.2%
NIDCR.......................................................... 28.6%
NIDDK.......................................................... 13.1%
NIGMS.......................................................... 100.%
NICHD.......................................................... 17.1%
NEI............................................................ .......
NIEHS.......................................................... .......
NIAID.......................................................... 13.6%
NIAMS.......................................................... .......
NIDCD.......................................................... 100.%
NIMH........................................................... 11.6%
NIDA........................................................... 23.4%
NIAAA.......................................................... 14.1%
NINR........................................................... 20.%
NHGRI.......................................................... .......
NIBIB.......................................................... 7.1%
NIMHD.......................................................... .......
NCCIH.......................................................... .......
NCATS.......................................................... .......
FIC............................................................ 9.1%
NLM............................................................ .......
ORIP........................................................... 100.%
Total NIH...................................................... 22.9%
------------------------------------------------------------------------
\5\ Research Project Grants are defined as activity codes R00, R01, R03,
R15, R21, R22, R23, R29, R33, R34, R35, R36, R37, R55, R56, RC1, RC2,
RC3, RC4, RF1, RL1, RL2, RL5, RL9, P01, P42, PN1, PM1, RM1, UA5, UC1,
UC2, UC3, UC4, UC7, UF1, UH2, UH3, UH5, UM1, UM2, U01, U19, U34, DP1,
DP2, DP3, DP4, and DP5. Not all of these activities may be in use by
NIH every year.
______
Questions Submitted by Senator Patty Murray
nih centers for accelerated innovations
Question. Please provide an update on the NIH Centers for
Accelerated Innovations (NCAI) program and any progress the initiative
has made in addressing the gap in the commercialization pipeline
between scientific discovery and moving breakthrough innovations. Are
any NIH institutes considering hosting a similar concept with their
funds?
Answer. The National Heart, Lung, and Blood Institute (NHLBI)
established the NIH Centers for Accelerated Innovations (NCAI) as a
pilot program to identify emerging technologies in the academic
laboratory research setting and facilitate their transition into
commercial products that can improve patient care and enhance health.
Launched in September 2013, the three Centers merge the strengths of 15
high-impact research institutions with expertise and resources from
both Federal and private-sector partners. The NHLBI committed $35.5
million over 7 years to the NCAI program, and the Centers have raised
non-Federal matching capital to leverage this Federal investment.
To accomplish their goals, NCAIs support proof-of-concept studies,
educate academics on the technology development process, and provide
early access to the scientific and business expertise needed for
commercialization. NCAIs provide early mentoring to innovators to
develop key business elements (legal, business development, regulatory,
reimbursement, access to partners and capital), which are often not
well understood by academic scientists and are critical for commercial
success of developed technologies. Innovator response to the program
has been robust, and the Centers received a wide range of applications
to develop devices, therapeutics, diagnostics, and tools to address a
broad spectrum of heart, vessel, lung, blood, and sleep disorder and
diseases.
Over the past year, efforts to address the gap in the
commercialization pipeline between scientific discovery and
commercialization were expanded in two ways. First, the National
Institute on Drug Abuse joined the NCAI program and committed $3
million to support innovator education and technologies targeted to
substance abuse at one of the three centers. Second, the NCAI model was
scaled across NIH through a new, 3-year trans-NIH, $9 million dollar
Research Evaluation and Commercialization Hub program (REACH). Working
in concert, the NCAI and REACH programs will enable development of
self-sustaining biomedical technology development ecosystems that
encourage the conversion of laboratory discoveries into products and
services and disseminate best practices for technology development to
other agencies, institutions, and regions across the Nation. NIH will
closely evaluate both of these programs as they are completed. By
moving innovative technologies into the private sector for patient
benefit, this network will enhance the commercial outcomes of
federally-funded research for health, societal, and economic benefit.
brain initiative
Question. What has been the average amount of funding for grants
awarded to date through the BRAIN initiative?
Answer. The average award amount for grants funded by NIH through
the BRAIN Initiative is approximately $650,000 annually per award. Most
are 3-year grants.
Question. Should the additional funding requested for BRAIN be
provided in fiscal year 2016, would NIH expect to use a portion of
these funds to support significantly larger awards to tackle bigger
challenges facing the initiative?
Answer. In short, yes. The BRAIN Initiative is focused on
understanding the functions of specific brain circuits, including
circuits relevant to Parkinson's disease, epilepsy, recovery from
traumatic brain injury and stroke, mental illnesses, and addiction.
Understanding this circuit functionality in the human brain is a
critical goal highlighted by the external scientific advisors that
developed BRAIN 2025, the roadmap for NIH's portion of the BRAIN
Initiative, and one that is echoed by the BRAIN Multi-Council Working
Group, another group of esteemed external neuroscience experts that
provides ongoing oversight of the long-term scientific vision of the
NIH BRAIN Initiative. This goal is also a major challenge facing the
Initiative, and starting in fiscal year 2016, NIH would like to greatly
expand its BRAIN research investments on understanding human brain
circuit function. Such research includes both invasive studies, which
will make use of latest-generation brain stimulating and/or recording
devices, as well as research with noninvasive devices for modulating
brain function, which do not require surgery and do not penetrate the
brain (for example, transcranial magnetic stimulation with a magnetic
coil). These non-invasive devices are rapidly being developed and could
become an alternative or an adjunct to current therapies for various
brain diseases and disorders.
To support this expansion into human brain research, the awards are
likely to be larger than prior NIH-funded BRAIN grants. This is partly
due to the cost of doing research with human subjects, and partly
because NIH has focused much of its current BRAIN investment in smaller
planning grants and other types of preliminary, exploratory awards
aimed at developing new technologies and tools. Nevertheless, it will
be important for NIH to continue supporting a wide range of BRAIN
investigators and while some awards will likely be larger as described,
NIH will still likely continue support of smaller, exploratory, high
risk projects in various areas, under the continued direction of the
BRAIN Multi-Council Working Group.
______
Question Submitted by Senator Jack Reed
idea program
Question. What is NIH doing through IDeA and other initiatives to
help States like Rhode Island become more competitive for Federal
research dollars so that we don't wind up concentrating our investments
in the same institutions and geographic areas?
Answer. The Institutional Development Award (IDeA) program is
designed to enhance the research infrastructure and increase the
research capability and competitiveness of investigators in
institutions located in States with historically low aggregate grant
awards from NIH. Grant awards are made to independent biomedical
research institutions that award doctoral degrees in the health
sciences or sciences related to health within IDeA-eligible States and
to research institutes. The primary objectives of the IDeA program are
to develop research capacity and broaden the geographical distribution
of NIH funding, ensuring that cutting-edge biomedical research is
conducted throughout the Nation.
The IDeA program continues to strive to meet its primary goal of
providing for biomedical research capacity across all of the IDeA-
eligible States and to distribute its resources broadly and
appropriately to support cutting edge biomedical research that serves
the needs of the medically underserved populations in these regions.
The program continues to support competing (new and renewal) and non-
competing Center of Biomedical Research Excellence (COBRE) and IDeA
Network of Biomedical Research Excellence (INBRE) awards that
constitute the IDeA base. Additionally, support is provided for IDeA
Program Infrastructure for Clinical and Translational Research (IDeA-
CTR) awards and continued co-funding of Independent Research Project
(R01 and R15) awards solicited from across the NIH Institutes and
Centers (ICs). In fiscal year 2015, the National Institute of General
Medical Sciences (NIGMS) supported 23 INBRE awards, 54 Phase I/II and
46 Phase III COBRE awards, and 5 IDeA-CTR awards. In fiscal year 2015,
IDeA co-funded 25 R01/R15 awards to 18 NIH ICs.
NIH will continue to support new competing Phase I COBRE awards, as
well as Phase II and Phase III COBRE awards. Funds will be provided to
support competing INBRE applications. Additionally, NIH anticipates
supporting new IDeA-CTR awards.
In terms of collaboration and shared funding from outside NIGMS
sources, NIH ICs are taking increasing interest in and are working with
the IDeA program. For instance, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) is working with
IDeA program staff to develop two funding announcements to support
Pediatric Clinical Research Networks in IDeA States. A proposed Data
Coordinating and Operations Center (DCOC) will support the activities
of the IDeA States Pediatric Clinical Research Network (ISPCRN). The
funded DCOC will cooperate with the IDeA Program Directors/Principal
Investigators to train pediatric clinical trial teams. These teams will
utilize existing infrastructure and networks put in place by the IDeA
program in these States to support new research paradigms to address
pediatric health, particularly in rural and underserved communities.
These initiatives, developed by NICHD in conjunction with NIGMS, will
be supported by funds from the NIH Office of the Director.
IDeA program staff have engaged the Director of the Division of
Extramural Research at NIDCR in exploring ways to inform dental schools
in IDeA States about the funding opportunities for COBRE Phase I
awards. The possibilities discussed were a webinar or having
information available at the NIDCR booth in the dental research
meeting. The NIDCR Director will consult with senior staff at that
institute.
NIGMS and other ICs will continue to support, through co-funding,
meritoriously reviewed research projects that have not made the pay
lines of the other ICs. The IDeA Director sends out solicitations to
all the ICs for meritorious applications for nomination of co-funding
by the IDeA program.
Six IDeA States have Clinical and Translational Science Awards and
institutions in IDeA States continue to be eligible to compete for
these awards. NIGMS is speaking with staff from the National Center for
Advancing Translational Sciences to promote this idea.
Lastly, NIGMS is also considering options to set up biotechnology
accelerators in each of the four IDeA regions to facilitate translating
basic discoveries to marketplace, as directed by the Senate (Senate
LHHS report 2016, page 92).
______
Questions Submitted by Senator Brian Schatz
tobacco to 21
Question. Tobacco prevention and control is one of the most cost-
effective public health interventions we can use as policymakers to
prevent unnecessary tobacco deaths. In March, the Institute of Medicine
concluded that raising the minimum legal age of sale of tobacco
products would result in 223,000 fewer premature deaths, 50,000 fewer
deaths from lung cancer, and 4.2 million fewer years of life lost for
those born between 2000 and 2019. It would also reduce tobacco
initiation, especially among youth 15 to 17 years old. That's why I
introduced S. 2100, the Tobacco to 21 Act with nine of my Senate
colleagues, which would raise the minimum legal age of sale of tobacco
products to 21.
The NIH has a Tobacco Regulatory Science Program that coordinates
the trans-NIH collaborative effort with the FDA's Center for Tobacco
Products to do research and support its tobacco regulatory activities.
I am also aware that the NIH funds numerous studies on tobacco and
nicotine use and their impacts on public health.
I have two questions for Dr. Collins and Dr. Lowy, in particular,
regarding tobacco research:
1. Has NIH studied the relationship between increasing the
minimum legal age of sale of tobacco products and an
improvement in public health? What were the results of that
research? And what would you expect from increasing the minimum
legal age of sale of tobacco products from 18 to 21?
2. What are other demonstrated successes from a research
perspective in the effort to prevent and control tobacco
deaths? Do you have data on deaths averted and lives saved
thanks to these preventive efforts, and/or data on cost-
effectiveness of these efforts?
Answer. The Institute of Medicine (IOM) released the report, Public
Health Implications of Raising the Minimum Age of Legal Access to
Tobacco Products, in March 2015. The report was commissioned by the
Food and Drug Administration (FDA) to specifically address the
questions noted here in part a. That report used statistical modeling
and other methods to determine its findings. Specifically, the report
concluded that, based on modeling, raising the age of legal access to
tobacco products, particularly to age 21 or 25, will likely lead to
substantial reductions in smoking prevalence and smoking related
mortality. The report also concluded that, based on a review of the
literature and on modeling, that an increase in the minimum age of
legal access to tobacco products will likely improve maternal, fetal,
and infant outcomes by reducing the likelihood of maternal and paternal
smoking.
One of the two statistical models that informed the IOM findings is
NCI's Cancer Intervention and Surveillance Modeling Network (CISNET)
smoking population model, which simulates annual age-specific smoking
prevalence and smoking-attributable mortality. NCI also provided
support for the SimSmoke modeling of the potential impact of increasing
the minimum age of sale on birth outcomes. As of this time, NCI has not
funded other research on the potential impact of increasing the minimum
legal age of sale of tobacco products. NCI concurs with the IOM
report's findings that raising the minimum legal age of sale of tobacco
products would likely result in a reduction in the prevalence of
tobacco use and a reduction in disease, including cancers, caused by
tobacco use.
NIH, including NCI and other Institutes and Centers, supports a
broad-based portfolio of tobacco control and prevention research. This
research continues to contribute to the evidence base for understanding
and reducing tobacco use among youth and adults. Successful strategies
to reduce tobacco use include mass media campaigns, raising taxes on
tobacco products, comprehensive smoke-free air laws, efforts to promote
non-smoking norms, and barrier free access to evidence-based smoking
cessation treatment. Over many decades, these and other programs and
policies have contributed to substantially reducing smoking prevalence
and smoking-caused disease. For example, a study conducted by NCI
CISNET investigators estimated that twentieth-century tobacco control
programs and policies averted nearly 800,000 deaths from lung cancer
between 1975 through 2000.\6\ Similarly, NCI supported researchers
determined that the long-running California tobacco control program
reduced smoking prevalence and per capita cigarette consumption; this
research also estimated that between 1989 and 2008, the California
tobacco control program cost $2.4 billion, but led to approximately
$134 billion in healthcare expenditures savings.\7\
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\6\ Http://www.cancer.gov/news-events/press-releases/2012/
TobaccoControlCISNET.
\7\ Http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572143/.
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Despite significant progress in reducing the prevalence of tobacco
use in the United States, and the incidence of tobacco related cancers,
tobacco use continues to represent a major threat to public health. In
addition, decreases in tobacco use have not been consistent across the
population and prevalence remains high among certain groups. For this
reason, NCI supports a broad range of research on the etiology,
prevention, treatment, and control of tobacco use.
Additionally, within the framework of the Family Smoking Prevention
and Tobacco Control Act, signed into law in 2009, the NIH and FDA's
Center for Tobacco Products (CTP) formed an interagency partnership to
foster tobacco regulatory research. NIH biomedical, behavioral and
social sciences research supported in partnership with FDA is providing
the scientific evidence needed to inform FDA's regulatory authorities.
In collaboration with the NIH Tobacco Regulatory Science Program,
NCI is developing an evidence base to inform the FDA CTP regulatory
authority over the manufacture, marketing, and distribution of tobacco
products in order to protect public health. Although a vast and sound
scientific evidence base exists to support the Tobacco Control Act, new
research will provide scientific evidence in several areas. This
includes research to better understand e-cigarettes and other tobacco
products (initiation, use, perceptions, dependence, toxicity), and the
impact of tobacco product characteristics on initiation, especially
among youth and other vulnerable populations.
telehealth and mhealth
Question. As I've talked about before, I am a strong believer in
Telehealth, including mobileHealth or mHealth, and remote patient
monitoring as a way to improve healthcare quality and access, and
decrease costs.
The VA, DOD, and private insurers have well defined protocols and
standards for delivery of Telehealth. However, there are many
restrictions on Medicare reimbursement of Telehealth in the 1834(m)
statute under the Social Security Act which I am working with my
colleagues to address.
Dr. Collins, how is the NIH engaged on research to demonstrate the
efficacy and cost-effectiveness of Telehealth? What initiatives are you
pursuing?
Answer. Listed below are NIH activities related to Telehealth and
mHealth.
NIH's Extramural activities--Telehealth, including mobile health
(mHealth), is well represented in the extramural funding of the various
NIH institutes and centers with over 200 awarded projects in fiscal
year 2015. See selected examples below:
--Randomized Trial of an Innovative Smartphone Intervention for
Smoking Cessation.--With over 400 smoking cessation mobile
applications being downloaded millions of times in the United
States over 2012-2013, there is a need for systematic, rigorous
evaluation of the effectiveness of cessation intervention
trials. This randomized trial will utilize an approach, called
Acceptance & Commitment Therapy (ACT), which has a dual focus
on subjects increasing willingness to experience physical
cravings, emotions, and thoughts that cue smoking while making
values-guided committed behavior changes. If effective, the
smartphone application will provide a cost-effective
intervention with maximal population-level impact.
--Perinatal Nurse Home Visiting Enhanced with mHealth Technology.--
The Institute of Medicine, World Health Organization and
Centers for Disease Control and Prevention recognize that
prenatal home visitation, which improves the well-being of
mother and children, presents an opportunity to provide early
intervention to reduce intimate partner violence (IPV), and the
impact the exposure has on the children. This study will
utilize mHealth technology which aims to increase the
sensitivity of screening instruments and reduce communication
barriers between nurses and clients regarding IPV, as well as
enhance and standardize the implementation of IPV
interventions.
--A personal exposure and response monitoring system for pediatric
asthma study.--This study will develop a button-sized device
that can monitor asthma triggers (chemicals and particulate
matter) and physiological signals of a child 24 hours a day.
This system can potentially impact the epidemiological study of
the pollution exposure-response relationship, and eventually
the prevention of pediatric asthma. The project will bring
together strengths in chemical sensors, particulate matter
detectors, epidemiology, and digital health from different
groups, as well as industry collaborators.
--Dynamic, real-time prediction of alcohol use lapse using mHealth
technologies.--Despite the effectiveness of available
psychosocial and pharmacological treatments to establish
abstinence for patients with alcohol use disorder, the vast
majority of patients relapse within a year and often within the
first few months following treatment. The goals of this project
are to develop, validate, preliminarily optimize, and deliver a
dynamic, real-time lapse risk prediction model for forecasting
alcohol use among abstinent alcoholics. This lapse risk
prediction model will be integrated into an existing validated
mHealth platform to encourage sustained recovery through
adaptive use of continuing care services.
To facilitate rigorous research in mobile health, the Office of
Behavioral and Social Sciences Research (OBSSR) has engaged in a number
of funding opportunity announcements and training activities. For the
past few years, OBSSR has led a number of NIH mHealth training sessions
which bring together biomedical and behavioral researchers and computer
scientists and engineers to learn skills in developing and evaluating
mobile health applications. In fiscal year 2015, OBSSR, NIBIB, and
other partner institutes awarded a mobile health research resource to
the University of California San Francisco (1U2CEB021881) that will
provide researchers with a large test bed of mobile phone users and the
resources to encourage rigorous mobile health research. NIH also
recently released a competitive supplement funding announcement to
encourage current NIH grantees to incorporate and test new mobile and
Telehealth technologies in their research.
NIH Intramural Activities.--NIH's Center for Information Technology
(CIT) is one of the NIH Intramural Research Program leaders in
Telehealth and mHealth. CIT created an extensive Telehealth program for
NCI that connected a number of cancer centers in major hospitals in the
United States and abroad (e.g., Ireland and Jordan) to allow
collaboration on difficult cancer cases. This system, called
TELESYNERGY, provided real time multi-center collaboration and
included high resolution imaging capability. In 2006, CIT adapted for
NIDDK, TELESYNERGY to create a telemedicine clinic that runs in
conjunction with the Indian Health Service's Zuni Indian Hospital. This
clinic meets regularly, and NIH CIT provides technical support as
needed.
More recently, NIH CIT created mHealth iPad application called the
mICU Clinical Information System (CIS) App, which allows the NIH
Critical Care Medicine Department staff to quickly ascertain the status
of patients in their Critical Care Unit. This application has been
approved to be interfaced with the Clinical Center's Clinical Research
Informatics System (CRIS), so that it can go online when connected,
providing a major upgrade in functionality to the CRIS system. Finally,
the Radiation Research Program at NCI is interested in an updated
version of TELESYNERGY that can be deployed via an iPad to physicians
in rural areas or undeveloped countries. These iPads would connect to
servers in the closest major hospitals and provide physicians access to
more specialized diagnosis and treatment options that might not
otherwise be available. NIH CIT also is beginning to develop two new
mHealth applications, an iPad App for the Connectome project in
collaboration NINDS and an iPhone App, to study teen driving habits
with NICHD.
A number of other ICs have started or are planning to start
programs in these areas. On October 22, 2015, NIH had its first mHealth
Interest Group meeting. There is a great deal of enthusiasm in this new
interest group. Roughly 14 NIH ICs have expressed an interest in
participation in this newly formed group.
NIDA Intramural Research Program Treatment Section aims to realize
the full breadth of possibilities for mHealth, seeking results that can
apply not only to substance-use disorders, but to any health condition
with behavioral and environmental-exposure components. Methods for
ambulatory assessment combine real-time self-report, continuous
physiological monitoring, and continuous geospatial tracking; this
combination places individual behavior in the context of the social and
built environment. These efforts have already shown both expected and
unexpected relationships between neighborhood surroundings and
emotional/behavioral States. These findings can inform scientific
theory about addiction and other psychiatric disorders, as well as the
implementation and evaluation of public-health policies. NIDA is now
focusing on methods that can predict the immediate behavioral future
(for example, risk of lapse to drug misuse or HIV-transmitting
behaviors) based on input that poses the least possible burden to the
user (for example, GPS tracks rather than frequent self-reports). These
future-prediction methods could be the basis of treatment interventions
that are automatically triggered by and delivered through smartphones,
exactly when and where they are needed. NIDA has a patent application
submitted for prediction methods. In collaboration with the Biomedical
Informatics Section, NIDA also has developed and tested a program to
deliver HIV-risk reduction education via smartphone.
walkability
Question. Dr. Collins I'd like to ask about NIH's research
regarding the physical and mental health impacts of walkable, livable
communities. Last fall a researcher presented the results of a study
funded by the National Institute on Aging, administered through the
University of Kansas Alzheimer's Disease Center that suggests towns
designed to promote walking can actually blunt cognitive decline in
older adults. In addition to mental health benefits it has been
suggested that cities planned to be ``age-friendly'' can reduce
pedestrian fatalities, increase exercise and increase opportunities for
socialization and community involvement across all age groups. Can you
provide a summary of NIH's body of research on the impact of a person's
built environment on his or her mental and/or physical health? Can you
provide an update about any ongoing studies NIH is funding or
participating in regarding the impact of a person's built environment
on his or her mental and/or physical health? Earlier this year the
Washington Post reported on a trend by physicians to prescribe physical
activity to combat certain mental and physical ailments. Has the NIH
studied the efficacy of this type of treatment compared to prescription
drug interventions?
Answer. Research on the effect of the ``built environment''--the
physical environment in which humans function--on health and well-being
has long been of interest to several NIH Institutes and Centers. For
example, in 2004, the National Institute of Environmental Health
Sciences (NIEHS) hosted the ``Obesity & the Built Environment:
Improving Public Health Through Community Design'' conference that
brought together partner researchers, planners, healthcare providers,
developers, policy makers, and community and business leaders. More
recently, in 2009, NIEHS hosted the third and final meeting of grantees
in the Obesity and Built Environment (OBE) Program. A key aim of the
meeting was how modifiable aspects of the built environment can
influence overweight and obesity among residents and how those factors
may be manipulated to improve public health.
Some NIEHS-supported research has indicated that older individuals
who live in neighborhoods with more ``walkability'' experience a slower
rate of decline in leg strength. Small park areas in neighborhoods seem
to increase physical activity of families with children, and children
who live in neighborhoods with more trees are generally more physically
active.
The National Institute on Aging supports a number of studies on
aging and the built environment, with studies on how physical
surroundings influence mobility, health, and wellbeing. The Eunice
Kennedy Shriver National Institute on Child Health and Human
Development has supported research on potential associations between
aspects of the built environment and childhood obesity, and the
National Heart, Lung, and Blood Institute supports studies on the
influence of the physical environment on exercise behaviors, health,
and function.
A few of the many currently active studies in this area include:
--A study investigating the relationship between physical exercise
and depression risk in older adults, as well as the influence
of the neighborhood environment on both of these factors. The
research team is also evaluating the impact of a program to
improve pedestrian safety for older adults that will be
implemented in 10 neighborhoods within the study area over the
course of the project (R01 MH085132-05).
--A study examining the relationships between neighborhoods built
environment, use of physician services, and preventable
hospitalizations and emergency department visits among elderly,
chronically ill Medicare beneficiaries in an urban environment
(K01 AG039463-05).
--A project to link data on neighborhood characteristics with
longitudinal data on cognitive function assessed in a
nationally representative sample of older adults in the Health
and Retirement Study This study will also examine potential
mediators of this relationship, as well as factors that may
inform pathways by which neighborhoods influence cognitive
outcomes, and will identify subgroups that are most vulnerable
to neighborhood effects based on sociodemographic and genetic
characteristics (R01 AG043960-03).
--A study drawing on data from the Multi-Ethnic Study of
Atherosclerosis and the Study of Women's Health Across the
Nation to improve knowledge about physical and cognitive
functioning and their decline over time in the context of the
neighborhood environment, with special emphasis on social and
physical aspects of neighborhoods, and to elucidate how
neighborhood environments contribute to race/ethnic and
socioeconomic status disparities in function (K01 AG039554-05).
--Studies funded under the Transdisciplinary Research on Energetics
and Cancer initiative that investigate mechanisms by which
built environment features and policies impact physical
activity and obesity and influence carcinogenesis across the
lifespan (U54 CA155626, U54 CA155435, U54 CA155850, U54
CA155496, U01 CA116850).
--The Healthy Communities Study, a national study of community-based
initiates, environment characteristics, and family and child
factors that influence childhood diet, weight, and physical
activity (BAA NHLBI-HB-10-15).
--Studies of the effects of mass transit availability, including bus
and light rail, on physical activity and health outcomes
(Several from NCI and NIDDK)
NIH has studied physical activity and exercise to prevent and treat
a variety of diseases and conditions. One prominent example is the
Diabetes Prevention Program, which found that both lifestyle changes
(diet and exercise) and treatment with the drug metformin reduced the
incidence of diabetes in persons at high risk; however, the lifestyle
intervention was more effective than metformin--particularly among
study participants over age 60. At the 10 year follow-up, the
investigators found that incidences in the former placebo and metformin
groups fell to equal those in the former lifestyle group, but the
cumulative incidence of diabetes remained lowest in the lifestyle
group. Prevention or delay of diabetes with lifestyle intervention or
metformin can persist for at least 10 years.
Other studies comparing physical activity or exercise to
prescription drug interventions include:
--The MS FLASH (Menopause Strategies: Finding Lasting Answers for
Symptoms and Health) suite of studies tested promising
treatments, mostly non-hormonal, for the most common symptoms
of menopause (e.g., hot flashes and night sweats).
Investigators found that yoga did not improve hot flash
frequency or severity; however, participants reported an
improvement in quality of life.
--An ongoing study is comparing changes in bone strength at the hip
and spine in women who take 12 months of either: 1) optimal
calcium and vitamin D alone; 2) bisphosphonate risedronate with
calcium and vitamin D; or 3) a bone-loading exercise program
with calcium and vitamin D.
In addition, exercise is being studied as an adjunct to standard
treatment for a number of conditions, including cognitive decline and
Alzheimer's disease, cardiovascular disease, osteoporosis, and
arthritis.
______
Questions Submitted to Dr. Douglas Lowy
Questions Submitted by Senator Jerry Moran
nci designated cancer centers
Question. As many people know, those of us in Kansas are very proud
of the research conducted at the University of Kansas and felt a sense
of pride when the KU Cancer Center was recognized as a ``National
Cancer Institute-Designated Cancer Center'' in June 2012. I understand
that many NCI-Designated Cancer Centers, including KU, have community
partners to help expand their reach and to ensure that a broader
population has access to clinical research. Can you explain how that
model works, and if this is a standard approach of NCI-designated
cancer centers?
Answer. NCI and NIH share your commitment to ensuring cancer
patients have access to NCI-supported clinical trials. Earlier this
year, NCI's-designated Cancer Centers Program added its 69th
institution, and four other centers were awarded the comprehensive
designation. Much of the work these centers do is collaborative, often
with researchers at other NCI-designated cancer centers as well as with
smaller hospitals and community clinics.
NCI-designated cancer centers and many community hospitals around
the country are part of the network of institutions that comprise NCI's
two major clinical research programs: the National Clinical Trials
Network (NCTN) and the NCI Community Oncology Research Program (NCORP).
NCTN and NCORP form a network of 2,400 clinical sites that covers most
of the United States, ensuring that patients, regardless of where they
live, have access to trials that are testing the latest in cancer
prevention, early detection, treatment, and survivorship care.
The overall goal of NCORP is to bring cancer clinical trials and
cancer care delivery research to individuals in their own communities,
and to contribute to improved patient outcomes and a reduction in
cancer disparities. NCI supports 53 NCORP sites across the country,
including two sites in Kansas--the Wichita NCORP and the Kansas City
NCORP. These 53 community sites and research bases extend their reach
even further through a network of 840 component sites--local cancer
centers, hospitals, and clinics that are affiliated with the NCORP
network and make NCI-supported clinical trials available in a community
setting. For example, in Kansas, the Wichita and Kansas City NCORPs
include 24 component sites across the State.
NCTN was designed to respond rapidly to new and emerging scientific
opportunities. Foremost among these opportunities are precision
medicine clinical trials--a new generation of clinical studies focused
on developing molecularly targeted and immune-based therapies. The
majority of NCTN's lead sites are located within NCI-designated cancer
centers, and many NCORP sites collaborate with NCI-designated cancer
centers through their participation in NCTN. NCORP facilitates patient
and provider access to treatment and imaging trials from the NCTN, and
contributed substantially to patient accrual to NCTN trials. For
example, 240 affiliates of 13 NCORP sites accounted for seventy percent
of all sites preregistered to the NCI Molecular Analysis for Therapy
Choice (MATCH) precision medicine trial launched in August 2015.
Additionally, NCI supports the Partnerships to Advance Cancer
Health Equity (PACHE) program, which enables NCI-designated cancer
centers and institutions serving health disparity populations and
underrepresented students to conduct research in cancer and cancer
health disparities, train scientists from diverse backgrounds, and
effectively deliver cancer advances to underserved communities. NCI
currently funds twenty PACHE partnerships.
The NCI-designated Cancer Centers Program, NCTN, and NCORP form the
foundation of NCI's clinical research efforts and are critical in
brining NCI-supported clinical trials to patients in their own
communities. The continued growth of the Cancer Centers Program, and
the partnerships it fosters, is essential to the success of the
National Cancer Program.
nci precision medicine
Question. Dr. Lowy, what do you envision for how the NCI will
facilitate the NIH's precision medicine initiative? Is there potential
for supplemental Cancer Center Support Grant awards to implement
precision medicine initiatives like the MATCH trial?
Answer. Cancer presents an exceptionally promising opportunity to
refine the principles and practices that will serve as the foundation
for precision medicine. The additional funding associated with the
precision medicine initiative (PMI) will allow NCI to expand the NCI-
MATCH study. This expansion will include the addition of new
genetically targeted therapies to which patients can be matched and an
increase in the number of genetic alterations included in the study.
MATCH is implemented through the NCI Clinical Trials Network (NCTN), a
group that is formally connected to many NCI-designated cancer centers
by their designation as ``lead academic participating sites'' or
``LAPS'' sites. All NCI-designated cancer centers and all NCI's
Community Oncology Research Program (NCORP) sites can enroll patients
into the MATCH study. PMI funding will also accelerate planning for the
Pediatric MATCH study. NCI will continue to provide details and updates
to the committee on established NCI programs in precision oncology and
the status of NCI progress related to the new and expanded activities
under the fiscal year 2016 Precision Medicine Initiative.
The 69 NCI-Designated Cancer Centers form the backbone of NCI's
programs for studying and controlling cancer, and they will be
critically involved in precision medicine initiatives at every stage of
the research continuum. NCI's PMI efforts will be focused on further
developing and expanding research in the following areas:
--Evolution of a new standard for clinical trials in which the
molecular characterization of cancers becomes the clinical
standard for accurate diagnosis and treatment. This requires
identifying or developing an array of treatments that can be
matched to the molecular features of a tumor to successfully
control the disease, overcoming drug resistance in cancer
treatment. The goal is to develop cancer models from tissues
obtained at the time of diagnosis and at relapse to uncover
mechanisms of resistance to treatment. This involves analyzing
tumor DNA and tumor cells circulating in blood samples to
develop methods to predict relapse before this problem is
identified clinically or in radiologic studies. It also
includes testing combinations of targeted agents in clinical
trials.
--Development of new laboratory models for research by greatly
increasing the number of human cancer cell lines available, as
well as the number of patient-derived tumor xenografts--model
systems developed by transplanting a patient's tumor cells into
laboratory mice. Providing these and other tools to researchers
to gain new insights into tumor biology and better predict
patients' responses to cancer treatment.
--Development of a national cancer knowledge system to support
precision medicine by building an information platform. This
would support the integration of genetic information about
tumors with data on how the tumors respond to therapy, and
incorporate genetic, biochemical, environmental and clinical
data from patients to define molecular subtypes and to identify
the approaches to cancer care that will improve patient
outcomes.
NCI will work to achieve these goals by using its existing
infrastructure such as the NCI-Designated Cancer Centers, the NCTN, and
the NCORP, which supports consortia of community hospitals, oncology
practices, and integrated healthcare systems across the country. This
program includes a specific focus on underserved populations, with
twelve NCORP Minority/Underserved Community Sites with patient
populations comprised of at least thirty percent racial/ethnic
minorities or rural residents. NCI also supports a partnership program
between NCI-designated cancer centers and institutions serving
underserved health disparity populations that aims to train scientists
from diverse backgrounds in cancer research and to effectively deliver
cancer advances to underserved communities.
______
Questions Submitted by Senator Mark Kirk
stomach cancer in young people
Question. I am gravely concerned about the rise of stomach cancer
in young people. This recalcitrant cancer hides until it is late stage
and is deadly when metastatic; only 4 percent survive when diagnosed at
late stage. The research investment for this cancer is severely lacking
and the science is not as advanced as it is for other cancers. I hear
from stomach cancer researchers that it is very difficult for them to
get funded in the competitive grants environment and that the lack of
funding is deterring investors from the field of stomach cancer
research altogether.
It is my understanding that promising stomach cancer data is
available from The Cancer Genome Atlas (TCGA). What is the NCI doing to
translate TCGA-generated knowledge to actual advances for stomach
cancer patients, for whom there is a lack of effective treatments?
While I understand the promise of the NCI MATCH Trial, researchers tell
me it will have limited utility for stomach cancer.
Answer. NCI is committed to full exploration of the data from The
Cancer Genome Atlas (TCGA) and similar projects to advance genomic
research and translate findings into the clinic to improve the precise
diagnosis and treatment of cancers such as gastric cancer. NCI supports
a wide range of basic research projects and clinical trials on gastric
cancer, including five Specialized Programs of Research Excellence
(SPORES) focused on gastrointestinal cancers such as stomach,
esophagus, and colon cancers. NCI is currently sponsoring several
clinical trials for gastric and gastro-esophageal (GE) cancers.
Examples include a study of combination chemotherapy for gastric
cancer, a study of a targeted therapy with personalized antibodies for
GE cancer, and a phase II study of a drug that inhibits tumor growth
receptors for advanced esophageal gastric cancer. In addition, NCI's
National Clinical Trials Network (NCTN) is currently supporting several
trials for gastric cancer, including a trial of combination therapy for
gastric cancers with high hepatocyte growth factor receptor (HGFR)
expression, as well evaluating whether the addition of molecularly-
targeted therapies can enhance the survival of patients treated with
combinations of traditional surgical, radiation, and chemotherapeutic
approaches. It is too early to tell what the NCI MATCH Trial will yield
for any particular cancer type, and there are several applicable
targets for gastric cancer, including human epidermal growth factor
receptor 2 (HER2), epidermal growth factor receptor (EGFR), and
Epstein-Barr virus (EBV).
Sequencing data from TCGA has enabled the extensive
characterization of cancer genomes as well as associated analyses
across cancer types that have shown that some cancer subtypes may be
more similar to each other than to others from the same organ-of-
origin. These analyses (called Pan-Can analyses) have also shown that
these cancer types also might share common genetic features that could
be susceptible to some targeted therapies on the market, but not yet
considered for the particular subtype. In other words, seemingly
dissimilar cancer types may share a vulnerability for which a drug is
already available. NCI is supporting new projects to expand on these
analyses and to enable researchers to examine a variety of new research
hypotheses in this area.
NCI is also supporting the development of new cancer models,
including gastric cancer models, sometimes referred to as ``organoid''
cultures and ``conditionally reprogrammed'' cells. NCI has completed a
pilot program in the development of these organoid models and is co-
leading an international consortium effort for broad development of
models for many cancer types. When successful, NCI will distribute
these new cancer models broadly to cancer researchers to help develop
diagnostic and treatment strategies tailored to specific subtypes of
cancer and to specific molecular abnormalities.
Question. Additionally, if stomach cancer researchers have
difficulty competing for research grants because the knowledge base of
stomach cancer is lacking, what can NCI do to help level the playing
field?
Answer. NCI's investment in TCGA and a pilot study specifically to
obtain biospecimens for gastric cancer has enabled more successful
applications focused on gastric cancer research. The success rate for
all gastric cancer grant applications (both new and competing) ranged
from 16 percent and 46 percent between fiscal years 2010-2014, with the
highest gastric cancer success rate to date was in fiscal year 2014,
with 46 percent of gastric cancer applications being funded. The
average success rate for all NCI grant applications during this time
period ranged 12-14 percent.
Results from TCGA analyses to date have led to more than 3,000
articles in research journals. Data from TCGA has not only generated a
large number of publications, it has also stimulated many new research
proposals, many of which have been funded. To date, NIH has received
over 3,000 grant applications utilizing TCGA data, and the success rate
for these applications has been above the NIH average. NCI will
continue to support promising research proposals that address important
scientific questions, and will use the breadth of funding mechanisms
available to support both individual and team science approaches.
Projects like TCGA are providing a new classification framework focused
on the genetic abnormalities of cancer that has the potential to alter
diagnostic categories, enhance treatment strategies, enable early
detection and prevention, and improve outcomes for all patients. NCI is
seeking innovative research proposals to advance these goals through a
variety of funding opportunity announcements.\8\
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\8\ Http://deais.nci.nih.gov/foastatus/RFA-PA.jsp.
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Question. Researchers and patients alike tell me a dedicated
funding stream, such as a through a RFA for stomach cancer, would help
to bridge the research gap and give hope to the many young people who
have or will be diagnosed with stomach cancer. Is this something NCI
could consider to assist these patients?
Answer. NCI is fostering many opportunities to study gastric
(stomach) cancer via several different types of funding opportunity
announcements (FOAs) supporting a wide variety of investigator-
initiated research applications ranging from basic studies of cancer
etiology and structural biology to studies of early detection and
biomarkers and clinical trials. An ``RFA'' (request for applications)
is a specific funding mechanism with set-aside funds that is typically
utilized for defined research areas, and one that may be appropriate in
the future for specific gastric cancer research projects. NCI is also
supporting training opportunities for talented individuals who might
develop an interest in gastric cancer through individual fellowships,
institutional training awards, and career development awards; and NCI
program managers are available to provide guidance to investigators who
seek help in finding the most appropriate funding mechanisms to support
proposed work on gastric cancer and other types of cancers.
______
Question Submitted by Senator Jack Reed
childhood cancer
Question. Director Douglas Lowy, National Cancer Institute--
Childhood Cancer: In July, I introduced the Childhood Cancer
Survivorship, Treatment, Access, and Research (STAR) Act, along with my
colleague on the Subcommittee, Senator Capito. The legislation would
expand opportunities for childhood cancer research, improve efforts to
identify and track childhood cancer incidences, and enhance the quality
of life for childhood cancer survivors. As you know, cancer remains the
leading cause of death by disease among our children--and while
research supported by NIH and NCI is leading to progress, we still have
a long way to go. What do you see as the most promising research
opportunities in this area, and what is NCI doing to support these
efforts?
Answer. NCI is committed to advancing research on all fronts to
benefit children with cancer--from basic science to preclinical
studies, translational research, and clinical trials, as well as
efforts focused on survivorship, quality of life, and psychosocial
care. This work is represented by key investments across our extramural
portfolio, at cancer centers and institutions across the country, as
well as through NCI's Pediatric Oncology Branch at the NIH Clinical
Center.
These priorities include a new 5-year commitment to NCI's Pediatric
Preclinical Testing Consortium and significant investments in NCI's
Children's Oncology Group to support pediatric clinical trials,
including the NCI Pediatric Molecular Analysis for Therapy Choice
(Pediatric MATCH) trial. Pediatric MATCH will provide a tremendous
opportunity to test a range of molecularly targeted therapies in
children with advanced cancers who have few other treatment options.
With the genomic data captured in the trial, it will also produce an
invaluable resource for studying the genetic basis of relapse in
pediatric cancers. Through the Children's Oncology Group, NCI is also
supporting nationwide clinical trials introducing new immunotherapy
agents into evaluation for children with cancer and clinical trials
evaluating precision medicine concepts in children with newly diagnosed
lymphomas and leukemias.
In addition to these efforts, NCI has prioritized the development
of new treatments for pediatric cancer in the NCI Experimental
Therapeutics (NExT) Program.\9\ This program focuses on advancing
breakthrough discoveries in basic and clinical research into new
therapies, and several new inhibitors with potential to treat pediatric
cancer are being studied for this purpose.
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\9\ Http://next.cancer.gov/about/mission.htm.
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NCI's translational research efforts include a recently awarded a
Specialized Program of Research Excellence (SPORE) award focusing on
neurofibromatosis type 1 and related cancers in children and
adolescents and young adults. This award is exciting for a number of
reasons. This is the first SPORE grant that is non-organ specific, and
instead targets a pathway--known as the RAS pathway. SPORE grants are
also typically awarded to a single institution, and this effort is
collaboration across institutions--including the University of
California San Francisco, Indiana University, the University of
Alabama, and the Johns Hopkins University. The effort will also include
a focus on cancer survivorship and understanding how chemotherapy and
radiation promote the development of second cancers--a critical issue
for pediatric and adult cancer survivors.
Childhood cancer survivorship research continues to be a priority
for NCI. The Childhood Cancer Survivor Study, launched by NCI more than
two decades ago, is a critical resource for investigators conducting
survivorship research, as well as for clinicians making treatment
decisions and delivering survivorship care. NCI also supports a
complementary effort, the St. Jude Lifetime study, which will allow for
replication of findings from genomic studies and the development of
collaborative projects to refine risk-based follow-up guidelines and
improve outcomes among childhood cancer survivors.
NCI continues to support new research opportunities and
collaborations in pediatric oncology. In February 2015, NCI brought
together dozens of experts to identify critical gaps in our knowledge
about the genetic changes underlying childhood cancers.\10\ The
Childhood Cancer Genomics Gaps and Opportunities workshop included
researchers and clinicians, members of regulatory agencies, and
advocates for research on childhood cancers. A full summary of the
workshop is available on NCI's website.\11\ Participants continue to
collaborate to pursue opportunities identified at the workshop, and the
workshop discussions also informed NCI's decision to support
Provocative Questions (PQ) meetings focused specifically on pediatric
cancers.\12\ NCI's PQ initiative aims to promote cancer research on
important yet understudied areas or research questions that have proven
difficult to address. NCI launched the PQ effort in 2011 to build on
specific advances in cancer biology and cancer control, and to address
critical questions about cancer biology that were largely unresolved.
The questions are generated from the cancer research community through
NCI-sponsored interactive workshops with researchers. Two of the most
recent PQ workshops took place in November 2015 and focused exclusively
on identifying questions to advance pediatric oncology research.
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\10\ Http://www.cancer.gov/news-events/cancer-currents-blog/2015/
childhood-genomic-workshop.
\11\ Http://www.cancer.gov/types/childhood-cancers/research/
childhood-genomics-workshop-summary.pdf.
\12\ Http://provocativequestions.nci.nih.gov/.
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We agree that the current outlook for children with cancer and
their families is not acceptable--and NCI is committed to doing more to
identify promising new therapies for children, bring these therapies to
the clinic, improve the outlook for childhood cancer survivors, and
support the foundation of basic research needed to achieve all of these
goals.
______
Question Submitted to Dr. Griffin P. Rodgers
Question Submitted by Senator Roy Blunt
kidney disease
Question. Dr. Rodgers, Medicare provides care for every American
with kidney failure, regardless of age. This is an incredibly expensive
endeavor and a good example of how research could slow the progression
of the disease or help develop more cost-effective treatments for those
with kidney disease. Research would have both huge health benefits and
cost savings for the U.S. taxpayer. Could you update the Committee on
your Institute's latest efforts in kidney research?
Answer. Yes, the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) is vigorously supporting research to identify
causes of kidney diseases, slow or stop disease progression, develop
treatments, and prevent kidney diseases and kidney failure in adults
and children. For example, results from the Chronic Renal Insufficiency
Cohort Study, which is evaluating long-term cardiovascular risk and
outcomes of over 3,700 persons with chronic kidney disease (CKD),
showed that systolic blood pressure levels above 130 mmHg -below the
current guideline threshold of 140 mmHg--is associated with worse
kidney outcomes. Building on the importance of blood pressure control,
the NHLBI-led and NIDDK-supported Systolic Blood Pressure Intervention
Trial (SPRINT) is examining the effects of intensive blood pressure
control on the development of kidney disease, and results are expected
to be reported in November 2015.
NIDDK is also studying children with mild to moderately decreased
kidney function in the Chronic Kidney Disease in Children (CKiD) study.
The study is examining risk factors for further kidney decline, as well
as investigating risk factors for heart disease, closely monitoring
brain development, and following long-term effects of poor growth in
this group. The study has already found that growth is relatively
stunted in lower-income youth with kidney disease. In a related effort,
NIDDK is supporting the planning phase of a trial of phosphate binders
to treat children with bone disease as a result of their CKD.
NIDDK established and is recruiting participants for the CKD Pilot
Trials Consortium to help advance possible new CKD therapies. A current
clinical trial is testing whether the generic drug allopurinol could
preserve kidney function in people with type 1 diabetes who are at high
risk of kidney disease; if the result is positive, it could represent a
low cost approach to prevent kidney disease in this population and
potentially in people with type 2 diabetes. NIDDK also renewed a
consortium to promote the discovery and validation of CKD biomarkers.
Biomarkers could allow earlier detection of disease and thus facilitate
earlier treatment, and also enable clinicians and researchers to
measure responses to therapy.
An ongoing effort related to kidney dialysis is a large, pragmatic
clinical trial comparing the effect of adding 30 minutes to the usual
(3.5 hour) duration of dialysis treatments for new dialysis patients.
The trial will determine if the extra dialysis time increases survival,
reduces hospitalizations, and improves health-related quality of life.
NIDDK also is leading Improving Chronic Disease Management with Pieces
(ICD-Pieces), which is a trial in four large healthcare systems that is
testing a novel health information technology (HIT) approach to reduce
hospitalizations in people with CKD, hypertension, and diabetes.
To increase knowledge about nephrotic syndrome, a kidney disorder
that can be caused by a number of diseases, NIDDK recently expanded the
Nephrotic Syndrome Study Network (NEPTUNE) observational study, which
now includes a specific pediatric component. NEPTUNE is investigating
the underlying causes of nephrotic syndrome, toward identifying new
therapeutic targets. Complementing NEPTUNE, the new Cure Glomerulopathy
Network consortium will conduct translational and clinical research to
better understand the causes, treatments, and progression of several
forms of kidney disease. The Network is recruiting 2,400 patients, of
which at least 25 percent will be children. NIDDK also supports the
Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney
Injury (ASSESS-AKI) study, which will provide important information
about the natural history of AKI and recovery.
Recent findings from major NIH trials and studies are providing
novel insights about genetic contributions to the increased risk of
non-diabetic kidney disease in African Americans. For example,
researchers in the SPRINT study found that variants in the APOL1 gene
are associated with increased risk of kidney disease, but not
cardiovascular disease, in African American participants with high
blood pressure. Additionally, results of a study leveraging five NIH-
supported cohort studies suggest that sickle cell trait may be related
to the higher risk of kidney disease in African Americans. These
insights can help identify ways to reduce the burden that kidney
disease places on this population.
To inform future directions for kidney disease research, the NIDDK
spearheaded a Kidney Research National Dialogue, engaging kidney
disease researchers in a discussion to identify research strategies
that would improve understanding of normal kidney function and the
mechanisms underlying kidney disease. The ideas that arose from these
discussions were distilled and published in a series of commentaries--
making them available to the broader community interested in kidney
disease research. Complementing that effort, the Institute has also
sponsored several recent scientific conferences and workshops that are
informing future research directions related to kidney diseases. Topics
of recent meetings included overcoming barriers in AKI, APOL1 and
kidney disease, urinary stones, and the use of health information
technology to identify and manage CKD populations.
______
Questions Submitted by Senator Patty Murray
diabetes prevention research
Question. NIDDK strongly supported the development and testing of
the Diabetes Prevention Program. The Diabetes Prevention Program helps
overweight participants with pre-diabetes to become physically active
and lose weight. In multiple trials, participants have become more
active, lost weight, and reduced the onset of diabetes in at-risk
populations by about 60 percent. The YMCA estimates that 30 percent of
adults could benefit from participation in the Diabetes Prevention
Program, yet real-world participation is disappointingly low. What kind
of research is NIDDK conducting to learn how to increase participation
in the program?
Answer. The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) is pursuing several areas of research that could help
increase participation in the National Diabetes Prevention Program
(NDPP). NDPP is a public health program led by the Centers for Disease
Control and Prevention (CDC) that is based on NIDDK-supported research:
the original NIDDK-led Diabetes Prevention Program (DPP) clinical
trial, as well as a subsequent NIDDK-supported pilot study showing that
local Ys could be used to deliver a lower-cost, group-based adaptation
of the DPP lifestyle intervention. CDC launched the NDPP based on
results of the pilot study, but it was important to have a larger and
longer-term study to provide more definitive evidence for delivery
through local Ys. NIDDK funded that recently published study, which
showed that using the Ys to deliver the DPP lifestyle intervention
achieved meaningful weight loss at 12 months in low-income adults.
Through its Centers for Diabetes Translation Research program, NIDDK
also supported research showing that implementation of a group-based
DPP lifestyle program adapted for American Indian/Alaska Native
communities--populations disproportionately affected by type 2
diabetes--prevented or delayed onset of the disease. This study
demonstrated the feasibility of using a DPP-based lifestyle
intervention in these communities, which can inform future public
health efforts to recruit and retain participants. Additionally, NIDDK
supported a small business grant to Omada Health for online delivery of
the DPP lifestyle intervention; the online program is now NDPP-
certified (https://preventnow.com/). Having an online option could help
reach more people, particularly those who may not live near an in-
person program or have schedules that permit in-person participation.
NIDDK also supports behavioral research that could inform efforts
toward increasing participation in the NDPP, such as a pilot study
specifically seeking to increase NDPP recruitment, group participation,
and retention of men from low resource areas, based on observations
that NDPP participation rates for men, particularly those from minority
populations, are lower than rates for women. NIDDK is also supporting
research examining other ways to deliver the DPP lifestyle intervention
in a variety of community settings to high-risk or underserved
populations through more efficient and scalable means. For example, one
research effort is testing a group-based DPP lifestyle intervention
delivered by community health workers at community centers, and another
is examining the approach of offering a DPP-based lifestyle program to
at-risk retirees during the annual Medicare enrollment process. These
and other efforts can test novel, low-cost, and scalable ways to reach
greater numbers of people who are at risk for type 2 diabetes and
enroll them in DPP-based lifestyle programs.
Screening to identify people with prediabetes who could benefit
from the NDDP is an important component to increasing participation in
the Program. The same simple blood tests identify people with
prediabetes or undiagnosed diabetes; in the United States, there are an
estimated 86 million adults with prediabetes and 8.1 million people
with undiagnosed diabetes. In 2013, NIDDK scientists published a study
showing that following the U.S. Preventative Services Task Force's
(USPSTF's) recommendations for diabetes screening--to recommend
screening only for individuals with high blood pressure--missed about
half of the people with undiagnosed diabetes in the U.S. I am pleased
to report that the USPSTF recently updated its screening guidelines to
recommend that doctors screen for diabetes and prediabetes in all of
their adult patients ages 40 to 70 who are overweight or obese. Because
this is a ``B grade'' recommendation, screening for eligible
individuals will be covered under the Affordable Care Act. This
expanded screening could help identify more people who have prediabetes
and thus could benefit from enrolling in NDPP.
Finally, NIDDK continues to follow the original DPP cohort in the
DPP Outcomes Study (DPPOS) to determine long-term outcomes and
durability of the DPP interventions. DPPOS has found that the lifestyle
intervention continues to be effective for at least 10 years, and that
it is especially effective in people over age 60 and is highly cost
effective. Additionally, the study is examining intervention effects on
other health-related outcomes, including co-morbid conditions such as
depression.
Question. How is NIDDK working with other agencies like the CDC and
HRSA to increase use of the program?
Answer. NIDDK works closely with CDC on the jointly sponsored
National Diabetes Education Program (NDEP). NDEP works with over 200
public and private partners at the Federal, State, and local levels to
improve treatment and outcomes for people with diabetes, promote early
diagnosis, and prevent or delay the onset of type 2 diabetes. One way
that NDEP works to enhance participation in NDPP is by increasing
awareness about the program through its educational materials for
people at risk for type 2 diabetes, their families, and their
healthcare providers. For example, information about NDPP is available
as part of the ``Small Steps. Big Rewards'' educational campaign that,
based on DPP findings, provides tools for people at risk for type 2
diabetes to take steps to reduce their risk of developing the disease.
For healthcare providers, information about NDPP is provided in NDEP's
Guiding Principles document, which is a resource that helps guide
primary care providers and healthcare teams to deliver quality care to
adults with or at risk for diabetes. NDPP also is included in NDEP's
GAMEPLAN toolkit and website for healthcare professionals. These types
of resources can help increase awareness of NDPP, so that people at
risk know about the program and that healthcare providers could refer
their patients to it.
Additionally, NIDDK collaborates with other Federal agencies,
including CDC, the Centers for Medicare & Medicaid Services (CMS), the
Indian Health Service (IHS), the Heath Resources and Services
Administration (HRSA), and the Veterans Health Administration (VHA) on
the statutory Diabetes Mellitus Interagency Coordinating Committee
(DMICC), which NIDDK chairs. DMICC facilitates cooperation,
communication, and collaboration on diabetes among government entities.
NDPP was announced at the November 10, 2009 DMICC meeting, where
initial results of the Y-based DPP adaptation were also presented, and
the Committee expects to follow up on the NDPP in the near future.
DMICC meetings also serve as important venues to share information. For
example, results of the DPP itself and of the research that I described
in response to your first question were shared at DMICC meetings, which
could help inform public health and health delivery efforts by CDC,
CMS, IHS, HRSA, and VHA. Additionally, IHS and VHA efforts to implement
the DPP lifestyle intervention for the populations they serve have been
discussed at DMICC meetings.
______
Questions Submitted to Dr. Walter J. Koroshetz
Questions Submitted by Senator Roy Blunt
department of defense brain bank
Question. The Department of Defense and the NIH are partnering to
create the world's first human brain tissue repository for military
personnel. However, it is my understanding that NIH researchers are
having issues accessing post-mortem tissues from service members
affected by blast injury. Dr. Koroshetz, can you discuss the importance
of having access to brains that have experienced blast injuries?
Answer. We do not know in what ways blasts have similar and
different effects on the brain compared to impact injuries, or rapid
acceleration/deceleration injuries. The behavioral effects of blast TBI
may appear similar to other TBI, but examining brain tissue is key to
understanding both whether blast injury causes distinct pathology in
the brain, and how to prevent it in the future. Although Department of
Defense laboratories are studying the effects of blast injuries on
animals, and scientists are also using computer models to try to model
the physical effects on the brain, it is essential to also study human
brains to understand the effects of blast injury, both in the short and
long term. The human brain is unique in many ways, and the much larger
size of the human brain, especially the cerebral cortex, compared to
animals can substantially change the physical forces on brain tissue
from blast injury. The lack of a systematic evaluation of blast injury
in human brain is a major barrier to advancing research for those
servicemen and women who have experienced blast injury in the past or
may experience it in the future.
Question. What are the hurdles you are facing to gain access to
these resources?
Answer. An April 2015 Report to Congress entitled ``Overcoming the
Challenges of Obtaining Postmortem Brain Specimens from U.S. Service
Members'' addresses research on brain samples and release of
information without a change of DOD policy for consent or interaction
with families of deceased service members. The solutions outlined in
this Report to Congress were considered the most appropriate and
expedient ways to enable brain tissue donations. A neuropathology
laboratory has been set up for the purpose of defining the pathology of
blast injury through the joint
Uniformed Services University of the Health Sciences.''-NIH Center
for Regenerative Medicine (USUHS-CNRM) and the U.S. Army Medical
Research and Materiel Command. Brain tissue in the USUHS-CNRM brain
tissue repository can be accessed by investigators at any institution
that has appropriate regulatory approval. CNRM has a USUHS
Institutional Review Board-approved policy for tissue distribution and
a steering committee that oversees the processes. NIH continues to work
with DOD to improve processes for obtaining brain tissue samples for
research.
alternating hemiplegia of childhood
Question. Dr. Koroshetz, Alternating Hemiplegia of Childhood (AHC)
is a neurodevelopmental disorder characterized by repeated episodes of
weakness or paralysis that may affect one side of the body or the
other. It is rare, estimated to occur in approximately 1 in 1,000,000
births. However, since cases may go unrecognized or misdiagnosed, it is
difficult to determine the true frequency of AHC in the general
population. What research is currently ongoing related to AHC and what
are future research plans likely to focus on, specifically?
Answer. This August I gave the keynote address at the ``4th
Symposium on ATP1A3 in Disease'' in Bethesda. Alternating hemiplegia of
childhood is one of several diseases caused by mutations in the gene
ATP1A3. Others include, for example, types of dystonia-Parkinsonism and
epilepsy. The Bethesda meeting brought together researchers, including
those supported by the NIH, and the disease advocacy community to share
the latest findings, brainstorm about future directions, discuss
collaborations, and highlight funding opportunities.
AHC illustrates how decades of NIH investment can come to bear on a
particular rare disease. ATP1A3 mutations affect the sodium-potassium
ATPase, or ``sodium pump,'' which maintains the balance of ions that is
crucial for electrical activity and other cell functions. This critical
pump utilizes 50 percent of the brain's energy supply. Understanding
how mutations disrupt function was accelerated by many years of basic
studies on the sodium pump, including ongoing research by intramural
and extramural NINDS investigators. Researchers have also capitalized
on new technologies, such as the recent advances in gene sequencing, to
help identify the many different mutations (more than 100), that can
alter the function of this ATPase.
NINDS is currently funding research to understand the full range of
developmental, motor, cognitive, and psychiatric symptoms that
mutations in this gene can cause, which may allow a shared approach to
therapy for the various diseases caused by mutations in this gene based
on the underlying cause. Researchers are also applying advanced brain
imaging to identify the brain areas that are affected. This may enhance
future clinical trials and the ongoing care of patients by providing
objective measures of progress over time, and could point the way to
design of future treatments, including deep brain stimulation. Ongoing
studies of how the mutations affect cells at the molecular level of
analysis will contribute to the design of rational therapies.
As discussed at the symposium, NINDS provides a wide range of
funding opportunities designed to support research across the full
spectrum from basic research of disease mechanisms, through laboratory
development of potential therapies, through clinical trials. One
specific area of focus for future research involves the NeuroNEXT
clinical network, which is designed to facilitate early phase clinical
trials as potential treatments emerge, especially for rare pediatric
disorders. The Institute also works closely with other parts of the
NIH, including the Office of Rare Diseases Research to facilitate
research on diseases like AHC.
______
Questions Submitted to Dr. Nora D. Volkow
Questions Submitted by Senator Roy Blunt
opioid research
Question. Dr. Volkow, there has been a significant increase in
prescription drug abuse over the last several years. What is NIDA's
role in researching new pain medications that may reduce abuse?
Answer. NIDA supports several different areas of research to
develop alternative pain treatments with reduced potential for abuse.
Pain is a symptom of many health problems and disease states, and pain
research is funded by many NIH Institutes and Centers (ICs). The NIH
Pain Consortium was established to enhance and facilitate pain research
and promote collaboration among researchers addressing pain by
coordinating funding opportunities across the 25 participating NIH ICs
(including NIDA) that support pain research.
NIDA specifically supports both clinical and preclinical studies to
develop alternative pain treatments focused on the development of:
--Medications that target the opioid system in new ways to reduce
abuse potential. NIDA is engaging in strategic partnerships
with pharmaceutical and biotechnology companies, private and
public foundations, and small businesses to identify safer and
more effective treatment options. Some examples include:
--A partnership with Signature Therapeutics to develop an abuse
deterrent formulation of OxyContin that uses prodrug
technology--attaching an extension to the opioid molecule
which renders the drug inactive unless it is taken orally.
--New compounds that exhibit novel properties as a result of their
combined activity at different opioid receptors (mu, delta,
and kappa). Compounds with combined activity at the mu and
delta receptors, or at all three receptors can induce
strong analgesia without producing tolerance or dependence
in animal models.
--Medications that target non-opioid neurotransmitter systems,
proteins, and signaling cascades including:
--The cannabinoid system. Research has demonstrated the efficacy of
cannabinoid compounds on central and peripheral neuropathic
pain. A recently announced funding opportunity will support
research to explore the therapeutic potential of the
endocannabinoid system, which modulates pain through
mechanisms distinct from opioids and may have a lower
potential for abuse, as there are little to no mood-
altering effects.\13\
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\13\ Http://grants.nih.gov/grants/guide/pa-files/PA-15-188.html.
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--The transient receptor potential vannilloid (TRPV-1), which moves
to the neuron's surface as nerve cells respond to pain
stimuli. Blocking this TRPV-1 movement to the cell surface
may be a potent means of preventing severe pathological
pain conditions.
--Resiniferatoxin, a novel compound that targets TRPV-1 channels.
It produces robust analgesia in animal models of pain and
FDA has approved its testing for terminal cancer pain (drug
development was also supported by the National Institute of
Dental and Craniofacial Research).
--Other methods of selectively silencing pain fibers, including: 1)
molecules that interrupt pain signals in pain-specific
nerve cells; and 2) optical stimulation using infrared
laser light to inhibit activity in pain neurons (photo-
analgesia).
--Fatty acid binding proteins that regulate inflammatory and pain
responses.
--G-protein receptor 55, which modulates inflammation and pain in
animal models.
--Transient receptor potential action channel A1 (TRPA1), which
acts as a signal integrator for sensory nerve cells. The
potential of TRPA1 antagonists as peripherally acting
analgesics is being explored.
--NaV1.7 sodium channels, which play a crucial role in pain
signaling. Their modulation is an attractive mechanism
under study to treat chronic pain.
--Combinatorial approaches utilizing both opioid and non-opioid
systems.
--A current funding opportunity announcement ``Clinical Evaluation
of Adjuncts to Opioid Therapies for the Treatment of
Chronic Pain'' aims to identify novel strategies to reduce
the amount of opioids administered to patients with chronic
pain through combined delivery with other drugs that
provide additive analgesic effects to minimize the dose of
opioids needed for pain control.
--Non-pharmacological strategies for the treatment of pain. Numerous
non-pharmacological interventions have shown promise for the
treatment of pain including:
--Neural stimulation therapies--Several brain, spinal cord and
nerve stimulation therapies--including transcranial
magnetic stimulation, transcranial direct current
stimulation, electrical deep brain stimulation, and
stimulation devices for peripheral nerves/tissues--have
shown promise for the treatment of chronic pain.
--Stem cell therapy--Researchers are exploring the effects of stem
cell transplants to generate new pain signaling neurons to
reduce inflammation and inhibit chronic pain.
--Gene therapy and epigenetics- New technologies using innovative
methods to alter gene expression are providing new targets
for therapeutic development.
--Complementary, integrative health approaches--Treatment
approaches that consider the biopsychosocial nature of
pain, include clinical studies on cognitive behavior
therapy, exercise, complementary therapies, and mindfulness
practices.
Question. Are there factors that predispose or, conversely, protect
against opioid abuse and addiction?
Answer. Although opioid medications effectively treat acute pain
and help relieve chronic pain for some patients, their addiction risk
presents a dilemma for healthcare providers who seek to relieve
suffering while preventing drug abuse and addiction. Little is yet
known about the risk for addiction among those being treated for
chronic pain or about how basic pain mechanisms interact with
prescription opioids to influence addiction potential. To better
understand this, NIDA launched a research initiative on ``Prescription
Opioid Use and Abuse in the Treatment of Pain.'' This initiative
encourages a multidisciplinary approach using both human and animal
studies to examine factors that predispose or protect against opioid
abuse and addiction.
Several genetic variations have been identified that interact with
the way an individual processes and responds to opioid drugs. These
include variations in the m opioid receptor-1 gene (OPRM1) and the
enzyme cytochrome P450 2D6 (CYP2D6). Other genetic factors have been
linked to differences in pain perception and in response to opioid
analgesics. An approach to pain treatment that seeks to integrate these
genetic findings is ``pharmacokinomics,'' in which pharmacogenetic
(genetic differences in the response to drugs) and pharmacokinetic (how
the body processes a drug) information is combined to optimize opioid
dosing to minimize addiction risk. These methods are still in the
developmental phase, but offer the potential to personalize pain
medicine with an eye toward addiction prevention.
Question. Why are there not more medications available for
addiction treatment?
Answer. There are currently three medications approved by the FDA
to treat opioid addiction and no FDA approved medications to treat
cocaine, methamphetamine, or cannabis use disorders. Developing new and
improved treatment options for opioid use disorders remains a high
priority for NIDA due to the scope of the current opioid overdose
epidemic. Many larger pharmaceutical companies have not entered the
addiction market. Some of the possible reasons for this include: the
perception of a small market size, the difficulties in executing
clinical trials in patients with multiple comorbidities--many injection
drug users are HIV or HCV positive and are taking multiple
antiretroviral drugs--and the high bar for obtaining approval for
addiction medications (the current FDA policy is to ask for a clinical
trial endpoint of either abstinence or a pattern of reduced drug use
demonstrated to be a valid surrogate for clinical benefit. However,
there is not yet sufficient research demonstrating that reduced drug
use is a valid surrogate to support use of this alternative end point
for FDA approval. NIDA is engaging in strategic partnerships with
pharmaceutical and biotechnology companies, private and public
foundations, small businesses, and other Federal agencies to address
these challenges. For example, NIDA, together with the FDA, academic
and industrial partners, are working towards establishing endpoints
``other than abstinence'' (OTA). One possible alternative measure is
``reduced drug use''; however, additional evidence that a reduction in
drug use is linked to improved patient outcomes will be required by the
FDA to support its use. To this end, in 2013, NIDA issued an RFA
entitled: ``Identifying Health Outcomes Associated with changes in use
of Illicit Drugs'' and this year a new program announcement was
published on this topic. Results so far include a recent publication
which found that reduced use of cocaine, as well as abstinence,
decreased endothelial dysfunction--a marker of heart disease risk--
characteristic of chronic cocaine use.
Despite these challenges, promising treatments are in development.
Some of the most promising findings from basic and clinical research
aimed at developing new treatments for opioid addiction include:
--Lofexidine--NIDA has awarded a series of grants to support the
development of lofexidine as an adjunctive treatment for use in
opioid detoxification. It is anticipated that an NDA for this
drug will be filed with the FDA within the year.
--Opioid vaccines--NIDA supports the development of vaccines to treat
opioid addiction and prevent relapse. Multiple studies have
reported encouraging preclinical results with anti-opioid
vaccines. Additional development in this area is ongoing.
--Buprenorphine implants--NIDA supported a Phase III clinical trial
of buprenorphine implants, a novel formulation that provides
stable round the clock dosing for 6 months. Based in part on
this NIDA supported study, a New Drug Application (NDA) was
submitted to the FDA. The sponsor (Braeburn Pharmaceuticals)
recently performed additional studies requested by FDA with
positive results, and a revised NDA was filed in September
2015.
Question. Why is it so difficult to treat?
Answer. Opioid addiction is a complex brain disorder that is
influenced by many interacting factors including individual genetics,
as well as social, behavioral, and environmental factors. While our
understanding of the brain circuits involved in addiction is rapidly
increasing, the development of medications that treat brain disorders
is notoriously difficult. This is because it is often difficult to get
enough of a medication across the blood brain barrier and into the
brain without causing toxic effects in the rest of the body. As a
result, many promising treatment strategies fail during human clinical
trials. However, new tools are being developed to help predict which
medications will fail due to human toxicity or failure to cross the
blood brain barrier.\14,15\ In addition, new technologies to more
directly modulate brain circuits--such as transcranial magnetic and
deep brain stimulation hold promise for new treatment strategies.
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\14\ Kamimura H, Ito S. Assessment of chimeric mice with humanized
livers in new drug development: generation of pharmacokinetics,
metabolism and toxicity data for selecting the final candidate
compound. Xenobiotica. 2015 Oct 7:1-13
\15\ Griep LM et al. BBB on chip: microfluidic platform to
mechanically and biochemically modulate blood-brain barrier function.
Biomed Microdevices. 2013 Feb;15(1):145-50.
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It is also important to note that when prescribed and administered
properly, Medication Assisted Treatments (treatment with methadone,
buprenorphine, or naltrexone in combination with psychosocial
treatment) have proved effective in helping patients recover from
opioid use disorders. They are safe, cost-effective, and reduce the
risk of overdose as well as the risks of infectious-disease
transmission and engagement in criminal activities. Nevertheless, MATs
have been adopted in less than half of private-sector treatment
programs, and even in programs that do offer MATs, only 34.4 percent of
patients receive them. Ongoing NIDA research is working to develop
improved strategies for the implementation of these evidence-based
interventions. This includes research to tailor treatment interventions
to individuals with unique needs, including those in the criminal
justice system or with HIV.
Question. Are there barriers to research?
Answer. NIDA research is working to address the barriers mentioned
above related to the development of new mediations (described in part
c.) and increasing implementation of evidence based treatment
strategies (described in part d).
______
Questions Submitted by Senator Jack Reed
overdose prevention
Question. On June, I introduced the Overdose Prevention Act to help
combat the growing number of overdose deaths. Last year in Rhode
Island, nearly 250 people died due to an overdose and so far this year,
there have been over 130 overdose deaths. Unfortunately, this is not
unique to Rhode Island. We are seeing a spike in overdose deaths due to
heroin and prescription drugs across the country. My legislation would
expand access to naloxone, which reverses the effects of an overdose.
What is NIDA doing to look at ways we can better prevent overdose
deaths?
Answer. NIDA is an active partner in the initiative of the
Secretary of Health and Human Services to address the complex problems
of prescription opioid and heroin abuse, and the associated overdose
epidemic, through improving education of healthcare providers on pain
management and proper opioid prescribing; increasing the implementation
of evidence-based prevention and treatment strategies; and increasing
availability and adoption of the effective overdose-reversal drug
naloxone (see part b. below).
Over-prescription of opioid medications has been a major driver of
the opioid epidemic, and thus improving how physicians and other
healthcare providers treat pain is a crucial part of preventing opioid
abuse. Unfortunately, pain management is inadequately covered in most
medical, dental, and nursing schools, and for the past two decades
there has been an overreliance on powerful, highly addictive opioids
even in chronic non-cancer pain conditions for which these drugs may
not be ideal. Thus as part of the NIH Pain Consortium, NIDA supports 13
Centers of Excellence in Pain Education (CoEPEs), which develop and
disseminate pain curricula to improve how healthcare professionals are
taught about pain and its treatment. In addition, the NIDAMED
initiative develops continuing medical education (CME) courses for
physicians and other healthcare providers on pain treatment as well as
how to identify and address drug abuse and addiction. NIDA is also
actively researching alternative approaches to pain treatment,
including abuse-resistant formulations of existing opioid medications,
non-opioid mechanisms for pain control (such as the endocannabinoid
system), and nonpharmacological (non-drug) approaches.
Treating opioid use disorders is another crucial component of the
strategy to end the opioid epidemic. Effective treatments exist for
these opioid use disorders, yet they are highly underutilized across
the United States. Ample research shows that, when used at sufficient
dose and for sufficient duration, three medications--methadone,
buprenorphine, and extended-release naltrexone--are highly effective at
reducing opioid use, keeping patients in treatment, and reducing
transmission of infectious diseases such as HIV and hepatitis C as well
as criminal justice involvement. Ongoing NIDA research is working to
develop improved strategies for the implementation of these evidence-
based interventions.
Question. Do you think expanding access to naloxone can play an
important role in reducing overdose deaths?
Answer. Yes, expanding naloxone access is one of the most important
measures that can be taken to prevent death from opioid overdose.
Experimental pilot projects distributing naloxone to first responders,
opioid users, their families, and potential bystanders has shown it to
be a lifesaver in communities where it has been implemented. Defying
the expectations of some critics, these programs have reduced overdose
deaths without causing an increase in opioid abuse in those
communities.
Last year, FDA approved an auto-injector to make naloxone somewhat
easier to administer, however most pilot programs have continued to use
naloxone syringes fitted with an atomizer to enable the drug to be
sprayed in the nostrils (intranasal administration), as this is less
expensive and the easiest mode of administration for laypeople.
Administering a drug formulated for injection intranasally is not
ideal, however. Thus NIDA is working with FDA and drug manufacturers to
support the development and approval of an FDA-approvable formulation
of intranasal naloxone that would match the pharmacokinetics (i.e. how
much and how rapidly the drug gets into the body) of the injectable
version. In executing this project NIDA partnered with two small
companies, AntiOP and Lightlake Therapeutics, which have each partnered
with larger pharmaceutical companies, Indivior and Adapt
Pharmaceuticals (respectively). Both Indivior and Adapt filed new drug
applications (NDAs) with the FDA this year.
CONCLUSION OF HEARING
Senator Blunt. Thank you for being here.
The subcommittee stands in recess.
[Whereupon, at 11:58 a.m., Wednesday, October 7, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]