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[Senate Hearing 114-]
[From the U.S. Government Publishing Office]

 
                  NIH: INVESTING IN A HEALTHIER FUTURE

                              ----------                              

                       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. 
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    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.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    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.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    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\
---------------------------------------------------------------------------
    \1\ Https://www.nia.nih.gov/budget-files/alzheimers-disease-
research-implementation-milestones-2013-2025.pdf.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \6\ Http://www.cancer.gov/news-events/press-releases/2012/
TobaccoControlCISNET.
    \7\ Http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572143/.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \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.]
```