[Senate Hearing 116-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2020
----------
THURSDAY, APRIL 11, 2019
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10 a.m. in room SD-124, Dirksen
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
Present: Senators Blunt, Shelby, Alexander, Moran, Capito,
Lankford, Murray, Durbin, Shaheen, and Baldwin.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR
ACCOMPANIED BY:
ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
GRIFFIN P. RODGERS, M.D., M.A.C.P., DIRECTOR, NATIONAL
INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
JON LORSCH, PH.D., DIRECTOR, NATIONAL INSTITUTE OF GENERAL
MEDICAL SCIENCES
DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE
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.
This is always a good hearing for us. I think, in the 4
years that Senator Murray and I have worked on this committee
together, we clearly have made NIH one of our priorities, and
we're glad it has been.
We have increased funding by $9 billion, a 30 percent
increase over 4 years, and hopefully we are not done with that
process yet, but hearing what you are doing with that money
always helps encourage us to not only make those dollars
available, but even more.
We have seen real progress in vaccine research from Ebola
to Zika, we have seen the development of blood tests to detect
different kinds of cancer earlier than had been before, the
first-ever drug used specifically for postpartum depression has
been developed during this period of time. Obviously, what is
happening in immunotherapy, which at our first hearing was
something that had to be explained to all of us and even a few
of your colleagues, as it was developing in the amazing way it
has already.
I think we have seen ways that you have found to encourage
young researchers and hopefully we will be able to hear a
little more about that today, as well.
In my home State of Missouri, research has demonstrated
that interactive therapy can reduce rates of childhood
depression, a discovery of an enzyme responsible for the spread
of cancer, and we have seen research supported that aimed at
improving the scaling-up of immunotherapy and how to make that
more available in a more affordable way for more people.
I am disappointed of course, that the 2020 budget request
would cut the agency by 13 percent. I am confident that this
committee will not do that, but we will talk to you today about
the reasons that we should continue in the direction we are in,
rather than head in another way.
I am deeply concerned about an issue that I have seen
develop, and I hope Dr. Collins, you have a chance to talk
about that too. It is something that the research community
needs to take more seriously, and that is that foreign
governments are initiating systematic ways to influence our
research, and frankly, to take advantage of our research by
stealing it.
There is a Chinese Government program to recruit NIH
(National Institutes of Health) funded researchers to encourage
them to steal intellectual property; cheat the peer review
system; establish shadow laboratories in China; and help the
Chinese Government obtain confidential information about NIH
research grants. That cannot continue to happen, and I look
forward to hearing your discussion of that issue.
Obviously, there is an important balance here, of
protecting our research from both foreign threats and other
kinds of piracy and having the kind of collaborative
environment you want to have to bring the best people into that
research community you can. I know that is a challenge, and I
have seen some challenges that you have faced even recently on
that topic of who should be there and where they should be, but
we benefited from them, they have benefited from us. This is a
system that has worked, and we need to be sure we continue to
protect it. Not everyone is well-intentioned.
I know there is an ongoing FBI investigation, and that it
is investigating specifically what the Chinese government is
trying to do to undermine our research structure. This is a
serious threat to all of the things that make that structure
work.
The NIH Advisory Committee has recommended several steps,
including implementing a broad education campaign about the
requirements to disclose foreign sources of funding, and
developing enhanced cybersecurity protocols.
And while I appreciate those recommendations, I think that
NIH has to be sure that the research community is fully aware
of the threats, and more importantly, how to combat those
threats.
NIH has sent only one letter to the community on the
subject, but I am going to let you talk about that a little
more either in your prepared remarks, or later in questions. It
is a vulnerable environment. It is a critically important time
to look to the future. A number of individuals that are part of
the so-called Thousand Talents program may be few, but I think
we should not just assume that that is the only program out
there trying to do exactly the same thing, either.
So, Dr. Collins, certainly, I am pleased with the
relationship you have had with this committee, with your
leadership, I admire the team that you and your colleagues have
put together. I am excited about the opportunity of the moment
and glad you are here with us again today.
[The statement follows:]
Prepared Statement of Senator Roy Blunt
Good morning. Thank you, Dr. Collins and the Institute Directors,
for appearing before the Subcommittee today to discuss the National
Institutes of Health's fiscal year 2020 budget request.
As Chairman of this Subcommittee, re-prioritizing funding for the
National Institutes of Health after a decade of stagnation has been my
number one priority. Over the past 4 years, we have increased funding
by $9 billion or 30 percent.
This increase has funded significant progress on vaccines for Ebola
and Zika, developed blood tests to detect different types of cancer,
and led to the first-ever drug specifically for postpartum depression.
In my home State of Missouri, NIH research has demonstrated that
interactive therapy can reduce rates of childhood depression,
discovered an enzyme responsible for the spread of cancer, and
supported research aimed at improving cancer immunotherapy.
I am disappointed the fiscal year 2020 budget request cut the
agency by $4.9 billion or 13 percent. This is not a choice I will make
when we write the fiscal year 2020 Labor/HHS appropriations bill.
While my commitment to biomedical research remains strong, I am
deeply concerned about an issue I think NIH and the entire research
community needs to take more seriously. Foreign governments are
initiating systematic programs to influence the American research
enterprise.
There is a Chinese government program to recruit NIH-funded
researchers to steal intellectual property, cheat the peer-review
system, establish shadow laboratories in China, and help the Chinese
government obtain confidential information about NIH research grants.
I understand and support the need to balance protecting against
foreign threats with the collaboration and open access that has long
been prioritized in the medical research community. And in almost every
case, talented foreign researchers have benefited the U.S. research
community and moved medical research forward. As I have said many
times, I believe that any foreign student coming to the United States
for advanced education should be able to stay in the U.S. after that
training is complete.
However, we must recognize that not everyone is well intentioned.
We know from an ongoing FBI investigation that the Chinese government
is trying to undermine the U.S. research infrastructure. This is a
serious threat to NIH peer-review system, to universities and research
institutions' intellectual property, and to corrupting a system that
has long been held as the gold standard in research worldwide.
The NIH Advisory Committee has recommended several steps, including
implementing a broad education campaign about the requirement to
disclose foreign sources of funding and developing enhanced
cybersecurity protocols. While I appreciate the Advisory Committee's
recommendations, I do not think NIH has made the research community
fully aware of the exact threats they face, and more importantly, how
to combat them. In fact, NIH has only sent one letter to the community
on the subject. The research community needs to understand that this is
a serious, immediate, and specific threat, and that some foreign
governments will use any means necessary to obtain a competitive
advantage over the U.S.
In this vulnerable environment, I think it is prudent for NIH to be
even more cautious about ensuring systems and protocols are in place to
protect the research community. But I am unconvinced that is happening
now.
Moving forward, I want to see clear steps taken to ensure all NIH
grantees are trained to understand their roles and responsibilities
within current policy. NIH needs to evaluate their peer-review system
and internal controls through a lens that takes into account national
security threats. And, finally, those who inappropriately share
information from the peer-review process or illegally share
intellectual property need to be held accountable.
While the number of individuals that are part of China's Thousand
Talents program may be few, this program has uncovered a systematic
flaw. We must take this threat seriously and NIH should take definitive
steps today to maintain the integrity of the NIH system.
Thank you.
Senator Blunt. I would like to turn to Senator Murray for
her opening comments.
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Well thank you very much, Mr. Chairman. Dr.
Collins, good to see you and all of your team. Thank you to all
of you for being here today and for the work you are doing.
The National Institutes of Health is perhaps the best
example of an issue, where members on both sides of the aisle
have been able to come together. We have repeatedly worked in a
bipartisan way to provide increased investment in research that
improves the health and well-being of people, invests in our
local communities, and supports our Country's continued
leadership in science.
NIH is the largest funder of basic research in the world
and I am very proud that Chairman Blunt, thank you, and I, and
others on this committee have been able to increase its budget
by $9 billion over the last 4 years, despite opposition, by the
way, from the Trump Administration.
Now we are here today to talk about President Trump's
latest budget, and it stays true to form and proposes severe
cuts across the spectrum of healthcare activities. In his
budget, President Trump proposes steps that would undermine
healthcare protections for 130 million people in this country
living with a pre-existing condition. It strips healthcare away
from tens of millions of people and we should not forget he is
arguing in court for a ruling that would do all of that and
more.
President Trump's budget proposes slashing the Centers for
Disease Control and Prevention, including their work on birth
defects and disabilities, their efforts to combat antibiotic
resistant pathogens, and emerging infectious diseases and more.
It slashes funding for the healthcare workforce training
programs at a time when our Nation is facing a healthcare
provider shortage, particularly in our rural areas, and it
proposes eliminating funding for the Teen Pregnancy Prevention
Program and cutting funding for rural health and maternal and
child health.
And at a time of remarkable possibility in medical
research, a time where we can and should continue leading the
world in medical discovery, the Trump administration wants to
cut funding for NIH.
President Trump's budget offers one small step forward for
pediatric cancer research and a marathon sprint backward for
everything else.
While he proposes increasing pediatric cancer research by
$50 million, he proposes cutting $100 million, twice that
amount, from diabetes research. He proposes cutting $300
million, six times that amount, from Alzheimer's research, and
he proposes cutting over $1 billion, 20 times that amount, from
efforts to discover treatments for every other kind of cancer.
In fact, for every new penny President Trump proposes for
pediatric research, he proposes cutting a dollar from NIH. He
would cut funding from just about everything, which would mean
delaying, or even missing opportunities to find treatments and
cures that could save lives, like a universal flu vaccine, or a
vaccine for HIV.
President Trump's damaging budget is wildly out of step
with the sentiments of Congress, thankfully, and the American
people, and I feel confident working with our chairman that we
will once again reject it.
Now, I do want to say that with that support for NIH,
however, comes the expectation that NIH will lead in all the
fields in which it is involved, including setting the highest
standards for the behavior of the research community it funds.
Last summer, the National Academies of Science,
Engineering, and Medicine released a report that found sexual
harassment is common in all three fields.
Dr. Collins, you and I have had numerous discussions about
this. The report found that almost half of women in medical
school or enrolled as a graduate student in a college of
medicine, and more than half of women faculty in academia
reported having experienced some form of sexual harassment.
The Academies recommended Federal research agencies require
institutes to report when people on grants have violated sexual
harassment policies or have been put on administrative leave
due to harassment allegations. A recommendation the National
Science Foundation has since adopted.
NIH needs to step up and demonstrate greater leadership in
holding its partners and extramural grantees accountable, as
well. It is not acceptable for NIH to defer to its grantee
institutions or other agencies to address harassment, rather
than actually requiring them to report when it happens in
research settings, or by researchers funded by NIH grants,
especially when NIH's funding gives the agency such sway with
the research community.
Harassment undermines scientists and researchers
professional and educational obtainment and erodes the
integrity of the research enterprise. It makes survivors feel
inferior or that they do not belong, and it draws promising
young scientists away from research at great cost to our Nation
and our scientific advancement.
I expect more from NIH on this issue, and Chairman Blunt
and, Dr. Collins, I would like to work with you both on
direction that requires NIH to take meaningful action to
address harassment that occurs in both intramural and
extramural settings, including implementing recommendations
from the Academies report, some of which the National Science
Foundation has already done.
Thank you, Mr. Chairman.
Senator Blunt. Thank you, Senator Murray. As Senator Murray
pointed out, the committee has worked hard on this together, as
Senator Durbin, Senator Alexander, great advocates, along with
Senator Shaheen, and Senator Moran, but the two people at the
top of the committee have also been incredibly important in
encouraging us to move forward.
I might point out that it is not just the current budget,
the past administration actually proposed cutting NIH research
at a time or two, and never proposed, as far as I know,
increasing it, at least it did not get increased. So, we have
sort of had a bipartisan determination to correct a bipartisan
failure to move forward for a long time. We are going to
continue to do that and one of the reasons we will be able to
do that is the great leadership of the Chairman, who joined us
today.
And Chairman Shelby, do you have some comments?
STATEMENT OF SENATOR RICHARD C. SHELBY
Senator Shelby. Thank you. Thank you, Chairman Blunt,
Ranking Member Murray.
First, I would like for my written statement to be made
part of the record.
Senator Blunt. Without objection.
Senator Shelby. And I will be very brief. I am going to
tell you, and I agree with those Senator Blunt and Senator
Murray, this is an important hearing. What you do is more
important than most of what we do in America. I am not
interested in cutting your budget, I am interested in
increasing it; so, are they. We are going to have a big
struggle this year, dealing with the budget, but I think this
is a great investment for America, for the world, for humanity,
what you do.
Sitting at the table here, all of you distinguished in your
own right; we are fortunate to have you, to have your
dedication and we are going to stay with you, and we are going
to continue to do it.
I believe it is not only a financial investment, which is
good for the economy, it is the leading scientist at cutting
edge of scientific research that you had. We all benefit from
it immensely.
Thank you, Mr. Chairman.
[The statement follows:]
Prepared Statement of Senator Richard C. Shelby
Dr. Collins, I want to thank you and your colleagues for coming
today to give us updates on the great work that you are doing at the
National Institutes of Health (NIH).
I have enjoyed our conversations in the past about the importance
of research, and I applaud the job that you have done as Director of
the NIH.
Research institutions in Alabama have done some wonderful
advancements with the funding they receive from the NIH.
Not only do our institutions in Alabama reap the benefits by
attracting the brightest minds to perform the research, but the Alabama
economy as whole capitalizes on the above average wages of researchers
and the buying power they add to local businesses.
It is important to Alabama and the rest of the country that we
continue to increase funding for medical research at the NIH. America
needs to remain at the forefront of advanced medical research, and
investigators want to know that Congress is committed to pursuing new
treatments and cures.
Thank you all for coming today, and I look forward to asking you
some important questions.
Senator Blunt. Well, thank you, Chairman.
Again, Dr. Collins, welcome to you and the directors of
several of the institutes that are with you today. We look
forward to hearing what they have to say as well, but if you
would like to start with your opening statement, this would be
the time to do that.
SUMMARY STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D.
Dr. Collins. Well, thank you.
Let me introduce the people at the table. On my left, your
right, starting over at the end, someone well known to this
particular panel of Senators. We estimate this might be about
his 400th hearing, Dr. Tony Fauci, Director of the National
Institute of Allergy and Infectious Diseases.
Next to him our Director of the National Institute on
Aging, Richard Hodes. Then next to me, Dr. Griffin Rodgers,
Director of the National Institute of Diabetes, Digestive and
Kidney Diseases. On my right, Jon Lorsch, Director of the
National Institute of General Medical Sciences. Next Doug Lowy,
who has stepped back into the role as now Acting Director of
the National Cancer Institute, as Dr. Sharpless has moved over
to FDA (Food and Drug Administration) just in the last few
days. And then on the end of the table, Dr. Nora Volkow,
Director of the National Institute on Drug Abuse. I am honored
to have these colleagues with me today for what I hope is going
to be a really important exchange of ideas and information.
So, Chairman Blunt and full committee Chair Shelby, Ranking
Member Murray, members of the subcommittee, I want to thank you
most sincerely for your strong and consistent, and bipartisan
support of NIH. In fiscal year 2019 we received a most welcome
increase of $2 billion, enabling us to continue our mission of
turning scientific discovery into healing and hope, and we will
have a chance to tell you about some of those things in the
course of this hearing.
I take very seriously the comments that were raised by the
Chairman about foreign influence, and by the ranking member
about sexual harassment. These are issues of incredible
intensity and importance and I hope we can discuss some of
those in the course of the questions.
But I wanted to introduce you today to just a few of the
millions of people who over the years have made medical
research progress possible by volunteering to take part in NIH
funded research. Instead of focusing on the researchers, I am
going to focus on our really important partners, the people who
take part in these clinical studies, and tell you something
about three examples of them.
[The graphic follows:]
Let's begin with Richard Hockfelder. Six years ago, this
retired aerospace engineer had a blood test called hemoglobin
A1c that showed that he was at high risk of developing
diabetes, a pre-diabetes diagnosis. So, he took some
preventative steps like cutting down on carbohydrates and
exercising more to get his health back on track and that work
really well.
[The graphic follows:]
Now he could have kept that success to himself but instead
he decided to help others and he joined NIH's All of Us
research program, which is building an unprecedented resource
to explore what health approaches work best for each
individual, and why. This is precision medicine on a scale we
have never attempted before.
[The graphic follows:]
We are making great progress toward enrolling our goal of 1
million or more people. And you can see from the graph where we
are in less than a year, more than 200,000 people have, in
fact, begun enrollment, and about 50 percent of those are from
traditionally underrepresented racial and ethnic minority
groups. Because we want very much to have an opportunity with
this resource to understand health disparities, it is a very
diverse population.
[The graphic follows:]
Now all the information that they contribute of various
types, will go into a highly secure database that researchers
can get access to, to make discoveries. Success is going to
depend on involvement of people from all walks of life, so we
encourage you to join too. All you have to do is go to
joinallofus.org, and anybody in our country can join this
effort. And we do hope by the next 3 years to take this already
quarter of a million and bring it to a million people. This is
unprecedented. It is already the largest study that we have
mounted in a very long time and we are only a quarter of the
way there.
[The graphic follows:]
Let me turn to another example of somebody who has
volunteered to help us with research. This is Frank Stevens.
Frank belongs to a community with unique biological
characteristics that has been offering to volunteer for
research for years, but too often has not really had that
opportunity. I am talking about individuals with Down Syndrome.
We need to do better for them.
[The graphic follows:]
Frank actually did testify before Congress in October 2017,
that is where this picture is taken. Now Down Syndrome usually
results from having an extra chromosome 21, each year about
6,000 babies are born with this condition in the U.S., and the
average life span has doubled in recent years, but these folks
still face significant health challenges. They include an
increased risk of heart defects, of leukemia, of immune
problems, of autism, and Alzheimer's disease.
[The graphic follows:]
On the other hand, interestingly, Down Syndrome individuals
have a lower risk of coronary artery disease and a lower risk
of solid tumors, even when you age-match. We do not know why
that is and it would be very important to figure that out.
So, because of this studying Down Syndrome may hold the key
not only to helping those who have the condition, but also to
understanding common diseases in all people. And this is a good
example how rare diseases can inform about things that go well
beyond that particular condition. NIH is stepping our efforts
to do just that.
[The graphic follows:]
This should come as good news to Frank and his Mom, you see
here vacationing, and his mom Cornelia, actually herself, has
already shown signs of Alzheimer's disease. Frank faces a
greatly increased risk of that because of his Down Syndrome,
but his Mom already has it, and he wants to try to help her as
well. As Frank once put it, ``My extra chromosome provides a
blueprint for medical research that could reveal answers to
this heartbreaking disease.''
[The graphic follows:]
Well speaking of heartbreaking diseases, I told this
subcommittee last year that we might be on the verge of a cure,
I used the C word, cure, for sickle cell disease. A life-
threatening genetic disorder that bends red blood cells into a
sickled shape because of a mistake in the gene that codes for
one of the hemoglobin proteins, and they are bending then into
this sickled shape that blocks blood vessels, causing
excruciating pain in a sickle cell crisis, and damage to
organs, which sadly shortens the lives of people with this
condition, substantially.
So, we talked about last year, maybe we are on the brink of
something, today I am thrilled to say, I think we have reached
a remarkable milestone.
[The graphic follows:]
Let me introduce you to Janelle. Janelle Stevenson is one
of the brave research participants who has helped make this
happen and whose story was recently featured on CBS's 60
Minutes. Throughout her young life, as you can see, she was
often hospitalized, even at, Christmas; you see there with
Santa Claus next to her bed and has experienced over the course
of her 20 years, just about the worst pain that a human can
imagine from these crises.
[The graphic follows:]
But she decided to take a bold step for herself and for
others with this condition and signed up for a gene therapy
trial at the NIH Clinical Center. This trial, her own bone
marrow stem cells were removed; modified to compensate for that
sickle mutation, and then infused back into her body where they
began producing healthy red blood cells. The transformation has
been pretty incredible.
Here is Janelle, sitting alongside her father, Ray wearing
her white jujitsu uniform. And here she is--remember this is
somebody who was pretty much almost bedridden before this
procedure [Video shown].
So, our Nation needs a lot more stories like this, but that
one certainly heartening to anybody who has wondered are we
going to come to an answer for that first molecular disease,
sickle cell. We have known about it for more than 100 years and
now, a molecular cure for that molecular disease in a very
rigorous research protocol, and the treatment was challenging
to endure, but you can see this is working.
The promise is now real for the nearly 100,000 Americans
who suffer from this devastating disease.
[The graphic follows:]
So, we need a lot more stories like this through the
generosity and courage of people like Richard, Frank, and
Janelle, along with your strong and sustained support. NIH
research is making it possible for these kinds of stories to
emerge every day and the world can look forward to a healthier
and happier future.
So, thank you, Chairman. We 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 have served as the Director of the National
Institutes of Health (NIH) since 2009. It is an honor to appear before
you today.
Before I discuss NIH's Budget request for the upcoming fiscal year
and some of the exciting scientific opportunities on the horizon, I
want to express my gratitude to the leadership and members of this
Subcommittee. In fiscal year 2019, NIH received an increase of $2
billion.I can promise you that we are investing those resources in
groundbreaking research as quickly as we can.
Biomedical research at NIH seeks to push forward the frontier of
knowledge, from basic science to translational research to clinical
trials, and success relies on vision, risk-taking, and a tireless
pursuit of the next scientific question. NIH will continue to invest in
people, programs, infrastructure, and technology with these goals in
mind, consistently striving for breakthroughs that culminate in
improvements in human health and wellbeing. From harnessing new
technologies to supporting the next generation of researchers, NIH will
invest its resources to ensure that the U.S. remains at the forefront
of innovation and discovery.
The fiscal year 2020 President's Budget provides $34.4 billion for
NIH, seeking to fund the highest priority scientific discoveries while
also maintaining fiscal stewardship of Federal resources. This Budget
will prioritize biomedica l research to confront our Nation's greatest
medical challenges, including the opioid crisis, precision medicine,
and pediatric cancer.
As in previous years, the Budget proposes to streamline Federal
research by consolidating activities of the Agency for Healthcare
Research and Quality (AHRQ) into a new National Institute for Research
on Safety and Quality (NIRSQ) within the NIH. The Budget provides NIRSQ
$256 million to support its activities to improve the quality, safety,
effectiveness, and efficiency of healthcare.
America's continuing leadership in biomedical research requires
infrastructure and facilities capable of housing safe, reproducible
research in compliance with all laws and regulations and conducive to
cutting edge research. NIH buildings include inpatient hospital beds,
Biosafety containment facilities, biomedical research laboratories,
animal holding facilities, and even a utility plant. NIH's backlog of
maintenance and repair now exceeds $1.8 billion.
NIH is aggressively using fiscal year 2019 funding to address some
of this backlog and ensure our facilities are both safe for patients
and conducive to cutting-edge research and research support. The fiscal
year 2020 Budget invests in NIH's facilities by again proposing $200
million to support multiple biomedical research infrastructure
priorities at NIH-owned sites.
One of my personal priorities since joining NIH has been to develop
and support the next generation of biomedical researchers. In August
2017, NIH launched the Next Generation Researchers Initiative to
address the challenges faced by researchers trying to embark upon and
sustain independent research careers. I am pleased to report that NIH
met its ambitious goal of funding 1,100 early-stage investigators in
fiscal year 2018. In fact, we funded 1,287, the largest number in
history. The fiscal year 2020 Budget includes a dedicated fund of $100
million in the Office of the Director to support the prioritization of
meritorious applications to support early stage investigators that have
never been funded by an award, or current NIH- supported researchers at
risk of losing support. NIH remains committed to the development,
support, and retention of our next generation of investigators.
This is a remarkable time in biomedical research. Truly exciting,
world class science is taking place through NIH support, and leading to
breakthroughs in multiple areas. I would like to provide just a few
examples of the depth and breadth of the amazing research the fiscal
year 2020 Budget supports.
The fiscal year 2020 Budget continues to invest in Precision
Medicine. Less than 1 year ago, NIH formally launched national
enrollment for the All of Us Research Program. This program is on pace
to enroll one million or more U.S. volunteers in an ambitious effort to
accelerate health research and medical breakthroughs. With this
Committee's long-standing support, we are closer than ever to building
the most diverse biomedical data resource of its kind. By analyzing
individual differences in lifestyle, environment, and biology,
researchers will uncover paths toward delivering precision medicine, an
emerging approach for disease prevention and treatment.
As of April 7, 2019, more than 212,000 people have begun the
enrollment process, and more than 129,000 have completed all the steps
in the protocol. The All of Us Research Program is committed to
engaging individuals from all walks of life, including those who may
not have been asked to participate in research previously, and more
than 75 percent of participants are from communities that have been
underrepresented in biomedical research. This diversity has the power
to revolutionize standards for inclusivity in research and for
generalizability of biomedical research findings across many
communities, with the ultimate goal of spurring discoveries that bring
the promise of precision medicine to all of us. The fiscal year 2020
Budget provides $313 million to support the All of Us Research Program.
Millions of Americans across the Nation have been devastated by
opioid misuse, addiction and overdose. To help bring scientific
solutions to this crisis, and to provide safe and effective options for
the more than 25 million Americans who suffer from daily chronic pain,
NIH launched the Helping to End Addiction Long-term (HEAL) Initiative.
This Committee made a historic investment of $500 million in our work
in fiscal year 2018 and built upon that investment in fiscal year 2019
with an additional investment of $500 million. Through HEAL, NIH will
build on basic science discoveries to accelerate the development of
novel medications and devices to treat all aspects of the opioid
addiction cycle, including chronic use, withdrawal symptoms, craving,
relapse, and overdose. NIH has launched a series of new studies to test
both new non-addictive medications and non-pharmacologica l strategies
for pain management, with the goal of targeted treatments for the
millions of Americans living with chronic pain. The fiscal year 2020
Budget continues the special investment of $500 million that was
started in fiscal year 2018, and supports a total of $1.3 billion for
opioids and pain research across NIH, ensuring that we continue to
respond aggressively to the crisis of pain and addiction in our
communities.
Cancer is the leading cause of death from disease among children
and adolescents in the United States. Although substantial progress has
been made in the treatment of several types of childhood cancer,
progress against other types has been limited. Even when long-term
survival is achieved, many survivors of childhood cancer may experience
long-term adverse effects from the disease or its treatment. More
research is needed to develop new, more-effective, and safer treatments
for childhood cancer. The President recently launched an initiative to
support pediatric cancer research. The fiscal year 2020 Budget provides
$50 million for a data initiative that will support the development of
new, more effective, and safer treatments for childhood cancers, and
will facilitate aggregation of data to create a federated,
comprehensive, and shared resource to support childhood cancer
research.
First identified in 1981, AIDS is one of humanity's deadliest and
most persistent epidemics. Although significant progress has been made
in the fight against new infections and AIDS deaths, the HIV/AIDS
pandemic continues around the world. The development of a safe and
effective HIV vaccine remains a key component to realizing an end to
the HIV/AIDS pandemic. The NIH-wide HIV research program will continue
to sustain the accomplishments already made and secure future advances
to prevent the spread of HIV; improve health outcomes for persons with,
at risk for, or affected by HIV; and ultimately to find a cure for HIV.
The fiscal year 2020 Budget includes $6 million for NIH to support the
President's Ending HIV Epidemic Initiative. The NIH-funded Centers for
AIDS Research and AIDS Research Centers are leveraging critical
relationships with local and State public health services, communities,
and research institutions to develop and refine evidence-based,
community-specific strategies that will help guide this initiative.
The fiscal year 2020 Budget continues to invest in research
progress toward the important but scientifically challenging effort to
develop a universal influenza vaccine. NIH-supported research is
helping advance understanding of how influenza strains emerge, evolve,
infect, and cause disease. These research results are informing design
of new and improved therapies, diagnostics, and vaccines. Influenza
viruses pose an ever-present public health threat and place substantial
health and economic burdens on the U.S. and the world. The fiscal year
2020 Budget will accelerate research progress to achieve the end goal
of a universal influenza vaccine, which is vital to protecting millions
of people from infection and mitigating the public health threat posed
by influenza viruses.
NIH is at the vanguard of biomedical research, leading the world in
support of groundbreaking science. Thank you again for inviting NIH to
testify today. We look forward to answering your questions.
FOREIGN INFLUENCE
Senator Blunt. Thank you, Dr. Collins.
Why don't we talk a little bit about the efforts you have
made on the concern about foreign involvement, about duplicate
labs in other countries, and information being shared that
should not be, and then what we are going to do about it.
Dr. Collins. I would be glad to do that. We are deeply
concerned about the evidence which has been growing and which
we have become increasingly aware of over the course of more
than a year, that there are instances, egregious instances,
where our funding of grants in this country is being taken
advantage of by individuals who are not following the
appropriate rules. This is utterly unacceptable.
We have had multiple opportunities to interact with the
FBI, who have been investigating this vigorously. Some of this
is classified information, some of it is not. And as a result
of that have uncovered what has now led to more than 55
investigations that are ongoing of institutions where we
believe there may be investigators who are double dipping,
receiving foreign government money without disclosing it, or in
some instances, diverting intellectual property that was
rightly the property of the institution where they are working,
to China. Or, maybe most egregiously at all because it violates
such an important principle for us, taking grants that they are
asked to review as part of the peer review process and
distributing those to another country even before those grants
have gone through the full review process, giving therefore an
opportunity for somebody else's ideas to be stolen.
Knowing the seriousness of this, I did something
unprecedented and wrote--first time since I have been NIH
director, to every one of our grantee institutions, and that is
more than 10,000, a very strongly worded letter saying this is
an issue they all need to take with great seriousness, and if
they are not aware of what their own faculty are doing in terms
of these kinds of relationships, need to begin to find that
out.
I think there was initially some surprise and maybe even
denial that that could be happening in these institutions. I
think we are past that now and we are now seeing statements
from some of those institutions, very strongly worded to their
own faculty saying, we realize we have a problem too. There
increasing instances where faculty members have been fired,
have been asked to leave the institution, many of them then,
returning back to their previous foreign base. And I should say
while China has certainly been mentioned a lot, this is not
only China.
So, actions are being taken and you will see more evidence
of that in the press, and particularly in the coming week or
two, to show just what is now necessary in order to respond to
this. We will not rest until we have looked at every possible
example. We have to depend on the universities as our partners
in this, but we are driving this process as vigorously as we
can.
Senator Blunt. Within those 55 instances, how many
different institutions would that involve?
Dr. Collins. That is 55 institutions.
Senator Blunt. 55 different grantee institutions?
Dr. Collins. Yes, and basically, we are triggered by noting
in a grantee that there is a publication that comes out that
seems to involve a lot of authors and a lot of other
institutions that were not mentioned in their grant
applications. Now, maybe that is an appropriate collaboration;
I am not going to tell you that every one of these
investigations is going to reveal something bad happened, but
some of them will.
Senator Blunt. Well, we clearly benefit from having people
from other countries here; to have their skill level here.
Frankly I think we benefit to have them, if they want to stay
here, to let them stay here.
Dr. Collins. Absolutely.
Senator Blunt. It is difficult to look at this from the
point of view of where somebody comes from, but no matter where
they come from, if they are involved in this, we are going to
have to obviously be at a higher level of on-guard, than we
have been.
Dr. Collins. Mr. Chairman, I am totally with you, as are my
colleagues. I am glad you raised, though, the concern though
that we not carry this to the point where anybody who is a
foreign national begins to feel like they are under suspicion,
even if they are honorable contributors to our workforce,
because almost all of those folks are. We need to be careful
that we do not step into something that almost seems a little
like racial profiling.
I think Chinese scientists working in the U.S. have already
written some letters to Science Magazine to express their
concern about not being swept into this same framework where
everybody is under suspicion, because the vast majority of
these folks have been incredibly important and honorable
contributors to our workforce.
Senator Blunt. Now, there is a research synergy that you
achieve by bringing people together from totally different
preparation, styles, and everything else into that research
moment, I think.
Dr. Collins. Yes. Diversity contributes to productivity in
every way, and all kinds of diversity that is true, including
gender diversity, including people from different socioeconomic
backgrounds, and from different countries.
Senator Blunt. Yes. I am sure we are going to have lots of
questions. Let's try to stay with the 5-minute time, but we
can, anybody that wants to stay beyond their first round, we
will get to as many questions as we can possibly get in between
now and the time we are done.
Senator Murray.
DATA COMMONS
Senator Murray. Thank you very much, Mr. Chairman.
You know, many research organizations are now exploring the
best ways to create research data commons. Private sector
communities of companies and extramural research institutions
like, science bound networks, Penn State, and Google's
datacoms.org have demonstrated success, while other Federal
agencies are already further along than NIH in successfully
establishing data commons, like the National Science Foundation
big data innovation hubs. It is really important that we learn
from them, as well as from some less successful attempts at
driving data instruction, like CA Bigg, which saw very little
traction in the community and was widely criticized.
So, Dr. Lorsch, let me start with you. What is NIH doing to
avoid reinventing the wheel, and how is NIH planning to
leverage data commons work that is already being done
extramurally?
Dr. Lorsch. Thank you very much Senator. That is a very
important question. If we can connect disparate types of data,
so, say data from the Jackson Heart Study with data from Dr.
Hodes' Alzheimer's disease databases, the power of that could
be enormous in terms of generating new ideas, new connections
between these diseases, or in that case, between cardiovascular
health and dementias, for example. That might lead to new ideas
about treatments that could be possible or earlier detection
strategies.
This is what we call interoperability, making data that is
in different languages, essentially, able to talk to each other
so the scientists can use that data for these kinds of
discoveries.
We are working very closely right now with our partners in
academia, as well as experts in the tech industry, particularly
through the STRIDES Initiative, which is an arrangement with
Google and Amazon that we have right now, to develop ways to
connect the high-value data sets that NIH has, the Jackson
Heart study, for example and Alzheimer's data together, to
create this interoperability.
We are definitely looking at past examples, both successful
and unsuccessful, to help guide us, and we are definitely
taking a lot of input from experts, particularly in the tech
industry through that STRIDES initiative.
DATA SCIENCE IN OTHER FIELDS
Senator Murray. Okay. Dr. Collins, what is the agency doing
to really encourage and support data science training in other
scientific fields beyond those like genomics and neuroscience,
which really have embraced this?
Dr. Collins. I appreciate that you are raising this issue,
and John Lorsch has been very much a leader in the space.
You see here our website, which will show you our strategic
plan for data science, which has been a way in which we have
tried to put together a lot of ideas. I totally take your point
about not reinventing wheels that have already been tried
either successfully, or otherwise. So, I think we are pretty
well invested in that.
And certainly, a big part of this is training. We are
seeking to bring more fellows to NIH to bring the skill sets
that exist in Silicon Valley and get them excited about
biomedical research, because that is where a lot of the talent
is. We are recruiting a chief data strategist, probably
somebody from the private sector, to help us with that kind of
culture change and recruiting of talent that we know we need.
We need our bench to be a lot deeper, we aim to get it there.
Senator Murray. Okay, good. Thank you. I really appreciate
it.
NCI AWARD PERCENTAGES
Dr. Lowy let me turn to you. While Congress has been
providing the NIH, including the National Cancer Institute,
with more funding each of the past 4 years, the odds of
securing a grant from NCI (National Cancer Institute) have
actually been getting more difficult. Can you tell us what is
driving that trend and what its significance is, and do you
expect it to continue?
Dr. Lowy. Thank you very much, Senator Murray. Thanks to
the generosity of Congress, we have received an increase in our
appropriation for the last several years, approximately 17
percent through 2018, to the regular appropriation during that
time. During that time we have increased the number of awards
made for investigator initiated research by about 20 percent,
the number of new people in the awards system and the NCI by 20
percent, and so this is, I think, very much in line with what
you and your colleagues have had in mind.
On the other hand, we have had over that period a 50
percent increase in the number of grant applications, and so it
has not been possible to keep up with the number of awards that
we would like to make, although we are very pleased we have
been able to make more.
It has led to the success rate for investigator-initiated
research going from 15 percent down to a little bit below 12
percent during that time period, and we certainly hope that we
will be able to increase the success rate going forward. For
example, this year we are planning to put in more money to the
RPG (Research Project Grant) pool than even with the generosity
of Congress is, has added to the NCI regular appropriation.
Senator Murray. Okay thank you, very much. I appreciate
that.
Senator Blunt. Senator Shelby.
PUBLIC SECTOR PARTNERSHIPS
Senator Shelby. Thank you.
Dr. Collins, you previously said that the private sector
research outspends public sector research three to one; three
to one. To prevent overlap, investigators in the public and
private sector, I believe, should coordinate research where
they can so that efforts would not be duplicated so much. I
know there is an accelerated medicines partnership, AMP, going
on, you have talked about it before. Would you give us an
update on this and how we are working together to get the good
results?
Dr. Collins. I am happy to talk about that. Yes, I think it
is a great opportunity to bring the best and brightest of skill
sets in terms of scientists and also the areas of expertise.
NIH is in the basic science in translational arena, but we do
not make pills and the industry does, and we have to figure out
how to do that hand-off so that this ecosystem really
flourishes.
I get invited each year to a meeting of the heads of
research and development of the largest pharmaceutical
companies; we just met this past weekend. And we have
developed, I think, a very functional working relationship
there to identify opportunities for shared collaborative
precompetitive efforts, and AMP that you just mentioned, the
Accelerating Medicines Partnership, is one of those which I
think has been particularly successful.
This allowed us to come together around several diseases,
and that includes Alzheimer's disease, and rheumatoid
arthritis, and lupus, and diabetes, and basically to work
together to identify whether there were areas that we could as
a group do, that neither could do alone, yet make all the data
available. We have to do that, we are NIH.
In those projects which are now almost 5 years along, we
have met every milestone, and everybody who is involved would
say we have accelerated the progress in finding new treatments
for those diseases.
Everyone is a little different in terms of the particular
science that is being supported. My colleagues here are a part
of that so, Dr. Rogers oversees the NIH part of the diabetes
effort, Dr. Hodes oversees the part of the Alzheimer's effort,
Dr. Carter, who is not here, the rheumatoid arthritis and
lupus, and we have just started a new one on Parkinson's. And
we are talking about a new one on schizophrenia where we
desperately need some new ideas, and industry after being a
little reluctant before, is now looking as if they could
embrace that, too. There is a separate project on cancer
immunotherapy called PACT, which is a relationship we have with
industry.
I think we are finding ways, obviously recognizing we have
different goals, to make that happen and that is a personal
priority for me to be sure we do not miss those opportunities.
CYSTIC FIBROSIS
Senator Shelby. What about cystic fibrosis? Where are you
going there, and where do you hope to go? You have come a long
way.
Dr. Collins. Well, this is also something I have a personal
passion about, having had the opportunity to co-discover the
gene for cystic fibrosis exactly 30 years ago. And now to see,
although it took 30 years and I wish it had been faster, the
emergence of highly effective, triple therapy with a very well
designed molecular-based drugs that looks as if something like
90 percent of people with cystic fibrosis are now going to have
a treatment that allows them to live out what could be almost
normal lives. Which is an amazing thing to be able to say.
It took a huge amount of work from NIH funded resources to
try to figure out exactly what the mechanism is for this
disease, and what kind of drug might work, and then a close
partnership with a company called Aurora which then became
Vertex, and now here we are. And it is incredibly gratifying to
see that for all those kids and families that have been waiting
for this all this time.
Senator Shelby. Doctor, you have been very involved in the
National Center for Advancing Translational Sciences, and so
forth.
Dr. Collins. Yes.
RURAL HEALTHCARE ACCESS
Senator Shelby. Could you elaborate on how NIH is
implementing this program to address healthcare access and
delivery in rural areas across the country?
Dr. Collins. So NCATS, the National Center for Advancing
Translational Sciences, is one of our newest entities. I have
been very excited to see this emerge, trying to identify ways
that we can help research projects that sometimes get stuck in
the valley of death actually move across for benefit to people
out in the clinics and the hospitals.
NCATS also runs the CTSAs, the Clinical and Translational
Science Awards, which is this network of 57 centers across the
country. But we are aware that those are generally located in
more urban settings and there is an opportunity and a
responsibility to reach out to rural communities.
NCATS has out right now, a notice of interest out there to
think about how to link up in that way. One possibility is to
link up with the idea states clinical trial research networks,
which are also often times more in an opportunity where there
is a rural setting. And also, to see if there is a way to work
in the pediatric clinical trial network which is also been put
forward as part of the effort to deal with the opioid crisis.
So, we have a lot of connections here that are being built.
There was a meeting at the University of Florida to talk about
this two days ago, I am waiting to hear what the results of
that were.
FUNDING LEVELS
Senator Shelby. Doctor, lastly, could you explain how NIH
determines funding levels for research within its larger
funding number, because all of us advocate for certain diseases
that touch us and touch our friends and family, and
constituents in many ways.
Dr. Collins. In the minus 21 seconds I have, let me see
what I can do to outline.
[Laughter.]
Senator Shelby. Well, I think I am over.
Dr. Collins. It is a critically important question. All of
us around this table work with that issue virtually every week
trying to be sure we have our priorities set. I might point you
to the strategic plan that we put forward a couple of years
ago, which tries to go through in a very clear fashion how
those priorities get set.
May I say, we appreciate the fact that the Congress
generally does not give us a lot of recommendations about
specific disease areas, because we think science is in the best
place to make those decisions along with what the public health
need is, and that is what we try to do every day.
Senator Shelby. Mr. Chairman, could I just, not a question,
make a request? Dr. Vickers invited you to be the keynote
lecturer, I am sure all over the world, but in Birmingham and
at the lecture, Academic Leadership Medicine, Academic
Leadership Series. I hope if you can work that out you would
go; you have been there before. They asked me to do this and I
told them I would follow their request.
Dr. Collins. I will be there.
[Laughter.]
Senator Shelby. Okay. Thank you.
Senator Blunt. That is the right answer, I am sure.
[Laughter.]
Senator Blunt. Senator Durbin.
Senator Durbin. Once again proving all politics is local.
RESEARCH INTEGRITY AND STEWARDSHIP
Dr. Collins, it was about 5 years ago when I visited the
NIH and you and I had a conversation which informed and
inspired me about 5 percent real growth a year in funding on
medical research. The education of a United States Senator is a
daunting task, and I thank you for taking the time to explain
to me how consistency is as important as amounts.
It is a new challenge to you too, in this day and age, to
justify the amount that is being added each year when I look at
the record. And I want to give special shout-outs to our
Chairman here, Senator Blunt, Senator Murray, who just in both
authorizing and appropriating committees, has been a national
leader on the subject, and Senator Alexander who is retiring. I
am hoping that someone with his skill and determination will
replace him to continue this battle, but since fiscal year 2014
we have seen the 30.6 percent increase in NIH funding, a 40.6
percent increase in Department of Defense medical research and
a 33 percent increase in VA (Department of Veterans Affairs)
medical research. The CDC (Centers for Disease Control and
Prevention), 7.4; I wish it could have been more because it is
a deserving agency.
But when you answer the question of the Chairman about the
integrity of the research undertaking and endeavor,
particularly our concern about falsification of data or the
stealing of information, I think it really goes to the heart of
this. Those of us who deeply believe in what you are doing and
believe it is one of the most important parts of our public
lives, really need to count on you, as well, to join in in
proclaiming that integrity is not being compromised and money
is being well spent. Our critics are going to be watching to
find evidence to the contrary.
Would you like to comment on that?
Dr. Collins. I could not agree more. Let me say, I
appreciate your beginning your comments about this importance
of predictable, steady trajectory for support that has been
such a source of encouragement, particularly to young
investigators who are seeking to know whether they had a path
for their careers.
And frankly, things were looking pretty tough for them, 6
or 7 years ago as we had lost a fair amount of purchasing
power. Now to have this, 4 years in a row of a steady upward
trajectory, has changed the dynamic completely in the
institutions that I go and visit, where the postdocs, and the
graduate students, and the junior faculty are now really fired
up about the opportunity.
But you are right, this puts great responsibility on us to
be stewards of every dollar of that and if we find misuse of
that information, to move swiftly to make sure that that is
quickly stopped. We are doing everything I think we can in that
regard, with help from our institutions to root out that
problem and I think we have made a lot of progress, but we are
nowhere near done.
AMYOTROPHIC LATERAL SCLEROSIS
Senator Durbin. I would like to get more specific and
personal in this next question. Tuesday morning a young man
from Chicago named Brian Walleck, and his wife Sondra came in
to see me. A year and a half ago, 18 months ago, he was
diagnosed with ALS, Lou Gehrig's disease, and they wanted to
come and talk to me about their determination to try to spark
more interest, more research, more focus on this disease.
Sadly, the life expectancy of those diagnosed is not long
and they fear that many of the people who are the most
passionate advocates will not be here long enough to fight the
good fight and see good results.
What can you say to the couple and others that face this
particular disease?
Dr. Collins. This is a particularly critical and
heartbreaking condition, as you well know. We have redoubled
our efforts to try to take advantage of some of the newer
discoveries to come up with clinical applications. There is a
consortium now called CReATe, which is Clinical Research in ALS
and Related Disorders for Therapeutic Development.
We have been heartened by the success, which, I think I
talked to this committee last year of a gene therapy for the
infantile version of ALS called spinal muscular atrophy, which
actually has worked quite well. And now the question is could
that same approach be successful, at least for some individuals
with ALS where we know what the genetic mutation is, and there
are families where that is the case.
That is a big area of focus at the present time, but not
the only one. So, we at least now have a consortium to put all
the ideas that we can come up with into this space. It is a
very hard problem, but I think our chances are better now than
ever to make some real forward motion and maybe even some
breakthroughs.
MATERNAL AND INFANT MORTALITY
Senator Durbin. Thank you. My last point is this, as we are
dazzled by your work and the breakthroughs in cystic fibrosis
and other things, we also face the grim reality that this great
Nation, this United States of America, maternal and infant
mortality rates are absolutely unacceptable, particularly among
some segments of our population. We cannot forget the basics
here, and I know you are not, and I hope that you will be able
to tell us--I have run out of time now, but in some other
context, the work that is being done in these two particular
areas.
Dr. Collins. I would be glad to for the record, give you
quite a summary of all the things that are happening there,
particularly supported by National Institute of Child Health
and Human Development which also covers maternal health. We
agree that is a very high priority.
Senator Blunt. Thank you, Senator Durbin.
Senator Moran.
PEDIATRIC CANCER
Senator Moran. Thank you, Mr. Chairman. Dr. Collins, thank
you and your colleagues for joining us today and for the work
that you and your team across the country, do.
Let me start with Dr. Lowy. Doctor, the President has
proposed a Pediatric Cancer Research Initiative, safer
treatments for children, and better data.
What can you tell me about the challenges we face in
fighting cancer among children, as compared to adults? Are
there sufficient numbers of children who were willing to
participate in clinical trials? What are the issues that are
unique to childhood cancers?
Dr. Lowy. Thank you Senator Moran. One of the most
important things to understand is that children who have cancer
are not just small people who have adult cancer, but childhood
cancer is qualitatively different. Whereas adult cancer has
many mutations, often there are just are a few mutations that
arise in children with cancer.
In addition, while there is a tremendous amount of interest
in cancer treatment for adult cancer, there is less involvement
in the private sector, so that NCI has a particular obligation
to do research in this area, and we have substantially
increased the amount of research that we do in this area over
the last few years.
The particular proposal from the President is really along
the lines of something that Senator Murray was asking about,
which is how to efficiently and constructively aggregate data.
And the goal as we envision it is to take pediatric cancer as
an example, where some of the information is still quite
siloed, and by aggregating it and pulling it together with an
interoperable system, to be able to address important questions
in pediatric cancer.
Fortunately, in the terms of participation in clinical
trials, a high percentage of children with cancer participate
in that and a lot of that is through the Children's Oncology
Group sponsored by the National Cancer Institute, and because
all childhood cancers are rare cancers this is actually an
international effort that is part of the COG.
ALZHEIMER'S DISEASE
Senator Moran. Thank you. Thank you very much.
Dr. Hodes, we have recently seen a number of late stage
clinical trials focused on addressing Alzheimer's, that have
shut down, highlighting the difficulty in achieving meaningful
progress in combating Alzheimer's. What is your view on the
current state of Alzheimer's research? Where is the future
potential? And, maybe that is the questions.
Dr. Hodes. Well, beginning with the failures in recent
clinical trials, of course all of us are deeply disappointed at
them, and these are efforts that are generally been targeted at
amyloid protein individuals who already have symptoms. There
are cases where there is very strong evidence to think that
this amyloid pathway still may be important, in particular, in
some of the early onset familial cases, but also by targeting
earlier in disease, and so we are pursuing those specific
areas.
But in addition, thanks very much to the increased funding
that has come from Congress over past years, our understanding
of the processes underlying Alzheimer's has improved
enormously. Last year, for example, some 32 new genes were
identified, more than had previously identified all around.
This has led to the ability to identify from those genes,
bioinformatics, sys-biology, new targets. The number of targets
is illustrated, Francis, we actually have a visual to look at.
This is meant to show at stages from drug discovery, drug
development, the phase one/two trials, the phase three trials,
starting at the left the early stage of discovery, each of
those bars represents a different kind of target currently
under study. You can see the number of targets whether its
inflammation or protein trafficking or proteostasis, that we
are discovering more and more about as potential avenues.
So, the more targets we approach, the greater the
probability and individuals with particular syndromes that we
are going to have success. Out of some 35 clinical trials now
ongoing, 13 are targeting amyloid, the rest have this multitude
of targets.
So, a new generation of investigators, new science is
leading us to this multitude of opportunities to make sure we
have the way paved for a multitude of approaches to Alzheimer's
disease.
NEXT GENERATION RESEARCHERS
Senator Moran. Dr. Collins, the new set of scientists, the
next generation, I cannot think of the young lady's name on
your screen years ago, but you highlighted her as somebody we
are going to lose because of the instability in research
funding. And while I suppose we are always looking for the
concrete evidence that the funds have resulted in a cure or a
treatment, perhaps in the interim, between now and when we find
all those cures and treatments, you can reassure me that the
investment led by this subcommittee has made a difference in
keeping, retaining, and encouraging young people to pursue
careers in science and research.
Dr. Collins. I can, and I appreciate the question very
much. Yes, that was a young woman as a graduate student at MIT
who was about ready to give up.
That was a while ago and look at this curve which shows you
our ability, thanks to you, to be able to ratchet up the awards
that we have given to early stage investigators, that is people
who have not previously been a principal investigator on an NIH
grant. In 2013, that was a little less than 600, last year we
challenged all the institutes to try to really push this
forward and get us to 1100, we got to 1,287, by far the largest
in history. We have made this a priority and every one of those
individuals represents somebody with a lot of energy, a lot of
innovative ideas. This is the most important investment we
could make.
Senator Moran. Senator Shelby would have asked had he not
run out of time, but on his behalf, I would ask if you would
come to Kansas.
[Laughter.]
Senator Blunt. Thanks Senator Moran.
Senator Shaheen.
Dr. Collins. I am going to be on a lot of airplanes here, I
can tell.
[Laughter.]
Senator Shaheen. Well thank you, Chairman and Senator
Murray for holding this important hearing, and thank you Dr.
Collins and to all of you, for the amazing work that you do.
OPIOID EPIDEMIC
I want to begin with you Dr. Volkow, because as I know you
are aware, we have a horrible epidemic in this country of
substance misuse, and in New Hampshire we have been
particularly hard-hit. I appreciate your coming up and meeting
with some of the folks in New Hampshire who address this
challenge.
Can you talk about what you are doing at NIDA (National
Institute on Drug Abuse) that might give us some hope that
there are additional medications, there are additional
therapies on the way that might be able to help us address this
epidemic?
Dr. Volkow. I think my microphone is not working, so can I
borrow yours?
Indeed, this has become an area of priority area, and not
just for NIDA but for the whole NIH and multiple institutes are
working on it. And we have different strategies of research
that are relevant to actually address a crisis.
With respect to medication development, for example, it has
been a unique opportunity to bring in the expertise from the
NCATS (National Center for Advancing Translational Sciences)
Institute, the translational institutes, but also even from the
expertise that comes from the NIAID Institute as it relates to
that development of immunotherapies for addiction.
There are some exciting projects that are likely to bring
us more rapidly alternatives like extended release formulation
that improve the compliance of patients with their medications.
We are also very interested in developing new tools that can be
more effective in reversing overdoses that we are seeing, and
people are reporting a higher dose of naloxone is needed to
reverse overdose, when individuals are overdosing with drugs
like fentanyl.
In the field of expanding access to treatment, we now know,
and we do not need to do anymore research, that medications are
extraordinarily effective in preventing relapse, and in
preventing the overdosing, and in preventing infectious
diseases, including hepatitis C, or in outcomes in Neonatal
Abstinence Syndrome, but they are not being used.
The part of the problem is stigma, but another part of it
is that we do not have sufficient infrastructure. So, we are
working with researchers to develop models of care that they
can advance the healthcare system, on the one side, and adjust
the setting on the other one. These two systems have been
almost like different universes. So, we are using the funding
that we are getting to bring them together and figure out how
we can come with models of care that will treat the individual
and sustain them in care.
And then a third.
Senator Shaheen. There has been an issue in New Hampshire,
as you know.
Dr. Volkow. Yes, I know, and it is also a unique
opportunity. We look at it in terms of preventing overdoses
targeting both of them, as well as taking advantage, you just
made me think, because New Hampshire has been incredible in
terms of coming up with community solutions.
Senator Shaheen. Right.
Dr. Volkow. So, my perspective is how do we learn from
those community solutions so that we can apply them to other
States. We have an initiative called the HEALing Communities
study that aims to do that.
And finally, an extremely important aspect that we have to
keep in mind when we are addressing the crisis is research for
prevention. And why is that so? Because if we do not prevent
opioid use disorders, or we do not do interventions to prevent
other addictions, we will be changing one for the other.
So, we have a very broad portfolio that covers these three
different buckets.
Senator Shaheen. Thank you very much.
DIABETES RESEARCH
Dr. Rodgers, as you know, diabetes is one of the most
expensive diseases in this country, and I was very disappointed
to see that the President's budget actually called for a $280
million decrease in funding for NIDDK (National Institute of
Diabetes and Digestive and Kidney Diseases).
I wonder if you could--I do not think this committee will
go along with that. I think we appreciate that investment in
addressing diabetes research will help us in the long term to
be more cost-effective, as well as to address the challenge
that folks with diabetes face.
Can you talk about some of the breakthroughs that you are
looking at now in terms of the artificial pancreas, which is
really the most hopeful innovation to help folks with Type I,
in particular?
Dr. Rodgers. Absolutely, thank you for the question. Yes,
the FDA recently approved what have been truly breakthroughs
for treatment of patients with type 1 diabetes, such as the
first hybrid, artificial pancreas and the next generation of
continuous glucose monitors that no longer require a finger
stick for calibration, or that those are fully implantable.
I am happy to report that supported and the Special
Diabetes Program have contributed to testing of all of these
FDA approved therapies, and we continue to support cutting-edge
research in this area. We are supporting advances in artificial
pancreas in four very large, international clinical trials now,
conducted at academic medical centers. Research using our
special business funds is developing the next generation of
management technologies.
The goal is to provide the patient and their healthcare
provider with different options to decide what is the best
artificial pancreas that could be used for that individual.
Senator Shaheen. Well, thank you very much. I am out of
time, but I hope that our healthcare system and our health
insurance companies will be willing to cover these kinds of
innovations so people can actually benefit from them.
Dr. Rodgers. I agree.
Senator Shaheen. Thank you.
Senator Blunt. Thank you Senator Shaheen.
Senator Capito.
Senator Capito. Thank you. Thank you, Mr. Chairman and
thank you Dr. Collins and everybody for being here.
FUNDING NEW RESEARCHERS
The first question I was going to ask Dr. Collins, I think,
has been asked a couple of times. We were really lucky to get
Dr. Marie Bernard to come. Dr. Hodes was supposed to come but
doing what he should be doing with his family, and one of the
doctors in the room, researchers in the room expressed his
concern about talented young scientists being frustrated with
not being able to get into the queue.
So, you gave us the statistics of past had been 600, and
now 1287, is that?
Dr. Collins. That is correct. That was for last year and we
are going to aim to make a very good result this year. We are
already starting to count these up and make sure that any
investigator who scores in sort of, the top 25 percent as a
first-time applicant, ought to have a very good chance, a very
high chance of getting funded.
Senator Capito. Would you say those are geographically
pretty much spread across the country then?
Dr. Collins. They are, as much as our grant portfolio is in
general, and of course there are institutions that send more
grants and others that send fewer, and the IDeA (Institutional
Development Award) program helps us by balancing that.
Senator Capito. Right. Right. Thank you.
COORDINATING ALZHEIMER'S RESEARCH
Dr. Hodes, we did have a great visit and you were, as I
said, well represented by Dr. Bernard.
One of the things that we talked about during the visit to
West Virginia University was the work that is being done with
the other institutes at NIH in conjunction with NIA, the
National Institute of Aging, on different aspects of
Alzheimer's. For instance, it was mentioned like a possible
connection of low blood pressure and decreased cognitive
impairment.
Can you talk about what kind of coordinating, you are doing
at the Institute of Aging when you are looking and researching
across the spectrum of NIH?
Dr. Hodes. Thank you. It is a very important question and
part of the success that we are going to have in addressing
Alzheimer's disease, or other complex problems, of course,
would be to recruit the best talent from a diverse area of
science and expertise. So, along the lines of previous
conversation, over the past 4 years about one quarter of all of
the awards have gone to new and early stage investigators.
About one third have gone to new-to-the-field investigators who
never even applied for research in Alzheimer's before, and last
year a particular program, for example, invited grantees of all
institutes whose research was not Alzheimer's directed, but who
proposed a supplement to bring their creativity, their
technology, their genius to the field to do so, and last year
awarded some 300 supplements.
This we expect, and we are following up upon, will bring
these people into the field. We directly fund the research on
Alzheimer's and related dementias across all the institutes of
NIH, so about $200 million last year actually supported awards
to other institutes that are relevant to Alzheimer's and
related dementias.
Senator Capito. Yes, I think that obviously brings an
economy of scale a bit, but knocks down, I am sure like
everybody else has, silos. I am sure NIH has had silos, not as
many maybe.
Dr. Collins. Yes, past tense.
Senator Capito. Past tense. Yes.
Dr. Collins. We hope to knock them all down and we did
pretty well, but we are still watching for them to try to come
back.
Senator Capito. Right. Great.
NEONATAL ABSTINENCE SYNDROME BABIES
Dr. Volkow, as you know, my fellow Senator from New
Hampshire, I know you have been to West Virginia. How many
times now, two or? Three times and thank you for that visit;
those visits that the NAS (neonatal abstinence syndrome)
babies, Lily's Place and others, we do not know what the long-
term effects of all of this is, I do not think. I think a lot
of it may be in the science of the person's--as the child
grows, their own health, but there are always external factors
that are going to be impacting this, what kind of education,
family life, etc. etc.
What are you doing with the NAS babies in terms of
pharmacological research and specialized treatment strategies?
Dr. Volkow. Yes, and this is one of the priority areas for
the HEAL initiative, to actually develop better treatment
interventions that will improve the outcomes for the infants
and that will lead us to understand better what are the
consequences on the one hand, for a newborn that has during
pregnancy their mother was taking opioids, but importantly, as
they grow up in an environment where the mother may still be
taking drugs and be subjected to a social deprivation.
So, on one hand one strategy is can we develop better
treatments for Neonatal Abstinence Syndrome, and we typically
treat them with, for example, morphine. Now, it is said that if
you treat them with that small dose buprenorphine you
significantly decrease the number of days that they actually
have to be given the medication.
Just like we had also shown before that if you treat the
mother with buprenorphine, as opposed to methadone, you
decrease almost by half the number of days that you actually--
the infant that is born out of that mother will have with her
withdrawal symptoms.
We are also funding research, and again, this is in
partnerships with other institutes, including the National
Institute of Child Health and Human Development about non drug
interventions, and this has emerged out of root grass of
communities that have had to deal with the problem. And, for
example there is recognition now that physical contact of the
infant with the mother, could actually decrease the amount of
morphine that is necessary to control withdrawal. So, we are
funding research to develop the evidence about what are the
optimal interventions.
And finally, as it relates to your question about what is
going to happen with these children. There has been already
some research that shows that in infants that are born out of
mothers who were exposed to opiates, if you provide a
supportive environment those children grow up to not have
evidence of cognitive impairments.
But we are actually in the planning phases of launching a
very, very large study that will follow close to 8,000 infants
as they go from infancy to adolescence to evaluate how exposure
to drugs influences brain development trajectories.
Senator Capito. Yes, I mean that sounds very powerful and
the troubling part is, it has to be a long-term study to be
able to see the effect and by that time, the effect has taken
hold.
Thank you so much for your good work. Thank you.
Senator Blunt. Thank you Senator Capito.
Senator Lankford.
Senator Lankford. Thank you, Mr. Chairman. Thank you all.
A quick story. I was sitting on an airplane about 3 months
ago, sitting next to a gentleman flying back to Oklahoma. He
leaned over, introduced himself as a fellow Oklahoman and we
chit chatted for a while, and I said, what brings you to
Washington? He said, ``I come often. I am in an NIH trial, and
I have been for years'' and he smiled, and he said, ``And, I am
still here.''
And from watching his smile and chit-chatting with him on
the two-hour flight back home, it reminded me again of how many
people that are still around, just like he said, because of the
work that you are doing.
So, thanks for continuing that work and for helping folks
that, literally for him, as you know, he had been through
everything to be able to get to your desk, to be able to get to
that spot. So, we appreciate it very much.
BRAIN MAPPING
Dr. Collins give me an update on the brain mapping. I want
to walk through several things we talked about in the past. We
have obviously made significant investments into that. I missed
the very opening statement of this in a previous thing that I
had to be able to get to as well this morning. Tell me where we
are on brain mapping.
Dr. Collins. I would love to talk about this. This project,
which began 4 years ago has very ambitious goals to really
understand, what are the cell types in the brain? There are 86
billion of those cells, so that is a pretty big challenge. And
how are they connected together and how do the circuits in the
brain do the amazing things that they are capable of, and how
can that go awry and result in disorders like Parkinson's
disease or epilepsy, or a long list of others?
We, after 4 years, I would say have met or exceeded every
one of the milestones that was put in place when the original
plan for the 10-year program was put forward.
So, you are asking the question at an appropriate moment.
Right now, we are having a meeting of all the brain
investigators at the Marriott at Wardman Park, and this evening
I will chair a panel that will look at the plan now that is
being revised, we can call it brain 2.0, of what we might be
able to accomplish given the platform that has already been
built.
It is exciting from what we have already learned in terms
of new principles about how brain actually does what it does.
It is exciting by the people that have come into it, and the
latest couple of rounds of grant awards, more than half of them
were engineers, who would not necessarily be coming to NIH with
grant applications, but they are fired up about this too. And
that interdisciplinary part of this is part of the reason that
I think it is turning out to be so successful.
Senator Lankford. Okay, thank you. Well, we will want to
get a detailed update because we want to make sure it stays on
track, obviously, but this is a massive project, as you
detailed before.
Dr. Collins. Yes.
NONADDICTIVE PAIN TREATMENT
Senator Lankford. You have brought together folks from the
outside and from private companies to be able to talk about
alternatives to opioids and developing a nonaddictive pain
treatment.
How are the outside groups, private entities,
pharmaceutical companies, cooperating with you? Is that group
still together, still working?
Dr. Collins. Actually, quite well. We have in fact, put in
place a combination of scientific expertise from academia from
NIH and from industry, and we are now trying to prioritize what
may be, is many as 60 or 70 possible therapeutics that would be
nonaddictive treatment for pain, but which have been slowly
moving through the pipeline.
We at NIH are setting up a clinical trial network for
people with chronic pain syndromes so that these can be tried
out in a rigorous way, and companies are willing to contribute
those.
Senator Lankford. They are staying engaged?
Dr. Collins. They are staying engaged.
Senator Lankford. Okay, that was the risk at the beginning,
to say you are bringing together competitor groups to be able
to say we have got to sit down and solve this right now,
together, so.
Dr. Collins. Yes, I met with the 20 pharmaceutical
companies that have the largest budgets last weekend and they
were all on board.
DUPLICATIVE RESEARCH
Senator Lankford. Okay, thank you. Let me read a GAO report
real quick and I want to be able to get a follow-up from you.
Their statement was, they talked about VA, CDC, NSF
(National Science Foundation), DoD, NIH and they said, ``Each
lack a comprehensive information on health research funded by
the other agencies, which limits their ability to identify
potential areas of duplication in the health research they
fund.''
They made that comment just looking at the broad picture of
all of the research that is happening in multiple different
areas, the Appropriations Committee appropriates.
How is it working to be able to cooperate with VA, DoD,
especially large programs, NSF, to make sure, because as you
would know, grant folks are requesting of everybody. So, they
will have a slightly different name for similar research and go
to as many institutions as they can to be able to see if they
cannot find money to do the research on it.
How are we doing being able to avoid the duplication and
communication on agencies?
Dr. Collins. Senator it is a great question and it is
something we are quite invested in. We have a whole office of
portfolio analysis that has now been working at coming up with
tools to allow us to look, very complicated research portfolios
what are the areas of overlap?
We have done that kind of analysis comparing NIH to NSF,
comparing NIH to the DoD programs, comparing NIH to ARC. It is
very informative to be able to see that in a visual form, and
we have in few instances identified places where there was
duplication and acted upon it.
We have not yet done this as much for VA, but that is next
on the agenda. As long as we have access to the abstracts for
the grants that are being funded, we can do this right away.
Senator Lankford. You are breaking down silos at NIH. The
challenge is going to be for us to break down silos in medical
research across multiple agencies to make sure researchers can
meet with each other, and we know we've got similar research
and we are sharing that information, and we are not duplicating
it.
I will have a question for the record that I will follow up
with you, I know you had an interchange with Representative
Harris on fetal tissue research. HHS is in the process of doing
a review of all fetal tissue right now and I know there is
somewhat of a pause going on as they are waiting for that to be
responded on, but I will do some follow up with some questions
for the record with you on that as well.
Dr. Collins. I will be glad to answer for the record.
Senator Lankford. Thank you.
Senator Blunt. Thank you, Senator Lankford. We will
probably have a chance for a second round, if you want to stay.
Senator Baldwin.
Senator Baldwin. Thank you, Mr. Chairman.
NEXT GENERATION RESEARCHERS INITIATIVE
Dr. Collins, you and I share a passion on a personal
priority of investing in our Nation's next-generation of
researchers. I think most everyone on the subcommittee knows
from my retelling the story that I was raised by my
grandparents, and my grandfather was an NIH-funded scientist, a
biochemist. So, I grew up understanding the importance of the
contributions of our researchers to biomedical leadership.
In 2013, I had a particularly powerful meeting with a high
school student. He was a bone cancer survivor from Fond du Lac,
Wisconsin, and his name is Ian and Ian told me that cancer
research helped save his life. He decided at that point that he
wanted to grow up to be a scientist and to help others who had
the disease. But he was concerned that it would not be possible
for him to break in as a new researcher due to NIH funding
cuts.
Ian inspired me to author the Next Generation Researchers
Act with my colleague, Susan Collins, to improve NIH
opportunities for our new and early-stage researchers.
I am proud to report to you that Ian has graduated from
college and is now working in a lab with a scientist at
Huntsman Cancer Institute in Salt Lake City, Utah studying
pediatric cancers like osteosarcoma.
I applaud NIH's progress in implementing my Next-Generation
Research's Initiative to help support future scientific leaders
like Ian. In fact, as you noted, NIH funded 1287 early-stage
investigators in 2018, as part of this work, the largest number
in history.
I would love it if you could elaborate on NIH's work to
implement this initiative since it was signed into law back in
2016, and your plans for implementing it moving forward, and
any comments you might have about the National Academies
Consensus Study Report on the Next Generation of Biomedical and
Behavioral Sciences researchers.
Dr. Collins. Well Senator, I really appreciate the way you
have drawn attention to this critical issue, and we have named
our initiative the Next Generation Researchers Initiative after
what you authored, because we were totally in sync with this as
one of our highest priorities.
When Ian asked you the question how we were funding,
according to the graph here if it was 2013, less than 600
early-stage investigators, and that was a time where it was
challenging for somebody trying to get their career started to
have confidence that there was going to be a path forward.
And notice what has happened since then, thanks to the
strong support of this committee, and to our prioritizing
early-stage investigators as the most important applicants that
we see, and yes, we are now in 2018, up to 1287. We aim to try
to keep a level in that space going forward. I think that is a
pretty healthy number. This is not one of those where we want
to go up and then go back down again, because there is plenty
of remarkable talent out there.
So, in addition to, of course, trying to be sure that we
are doing this in a fashion that attracts really talented
people, we also are focused on diversity. We want to have more
women in this category, because we still have not achieved the
point where our grantee pool is what it could be, given that
PhD's now are being granted 50-50 to men and women, yet we
still as first-time applicants to NIH, it is about 30 percent
that are women.
We are coming up with ways to try to make this pathway seem
more appealing, and for us to be more welcoming, and of course
that means dealing with the sexual harassment issues that
Senator Murray rightly brought up earlier.
We did support that report from the National Academy and we
have strong agreement with many of its recommendations in terms
of what we need to be doing to sustain this, but as I briefly
said earlier, I am perceiving, and Ian is a great example, of a
good deal of the change in the enthusiasm and excitement out
there in institutions of young graduate students, postdocs,
junior faculty really see, okay this is a good time to be in
science, not a time where we have to worry about our future
quite as much as we did 5 or 6 years ago. So, thank you for the
way you have supported this.
Senator Baldwin. Well, thank you.
I have been concerned that President Trump's budget would
cut NIH funding by over $4 billion, as years of budget cuts are
one of the primary factors in discouraging historically, young
scientists from getting into the field or forcing them to leave
the field to pursue careers in other countries or in other
realms. Yet, no investment in my mind promises greater returns
for America than our investment in biomedical research.
Will the Next Generation Researchers Initiative deliver on
its promise and be able to continue to hit such ambitious
milestones as you are describing, under the administration's
proposal to reduce overall funding for the NIH?
Dr. Collins. Well of course, everything we do depends on
the overall support that we have available. This Congress, and
this particular subcommittee has been very attentive to that
and the opportunities that we have had over these 4 years of
seeing our budgets go up by a total of 30 percent, have made a
lot of these things possible.
We always though, have to adjust based upon the resources
that we have. I will tell you of the institutes at this table
and the others who are not here, this funding of early-stage
investigators is one of our highest priorities. We will seek to
make that happen to the level that we can with the resources
we've got.
Senator Baldwin. Thank you and Chairman Blunt and Ranking
Member Murray, I oppose the President's budget request to slash
funding for NIH, and I look forward to working with both of you
to increase funding both for NIH and for a special focus on the
Next Generation Researchers Initiative in the fiscal year 2020
budget.
Senator Blunt. Well thank you, Senator Baldwin.
Senator Alexander.
Senator Alexander. Thank you, Mr. Chairman. Dr. Collins and
your team welcome.
First I want to once again salute Chairman Blunt and
Senator Murray, and others who have worked over the last 4
years for such steady progress in funding for the National
Institutes of Health. One reason we have done that is because
we had such great confidence in your leadership and that of
your team that you would spend the money well. So, it is a
testimony to you and very important.
OTHER TRANSACTIONAL AUTHORITY
In the opioid's legislation, we did something that you had
asked us to do when we talked about 21st century cures. That
was to give you other transactional authority so you could deal
with such things as a nonaddictive pain medicine.
The committee that Senator Murray and I are ranking on, we
recently had a hearing on pain and that exacerbated-- that
reminded us that when we limit the supply of the most effective
pain medicine, opioids, to millions of Americans, that causes a
lot of worry among people who live with pain every day, and
there are millions of them.
So, my question is, what have you been able to do with the
other transactional authority that we gave you to help find new
nonaddictive painkillers?
Dr. Collins. It was very helpful, in fact essential, to
have that kind of authority to move quickly in this space of
putting together an unprecedented public/private partnership to
try to speed up the development of those nonaddictive pain
medicines.
As I mentioned a couple minutes ago, we are working now
with pharmaceutical companies who were willing to put forward
compounds, we are calling them assets, but basically, they are
untested drug compounds that are ready for clinical trials but
have been slow moving through that pipeline.
We then need to do a very quick review of how to prioritize
these, we cannot test 60 of them, but we might be able to
ultimately run trials on a dozen or so. Which means we need to
have a process of review that is very streamlined, and it needs
to be supported in a way that would be very hard to do with a
traditional grant mechanism.
The other transaction authority is exactly the tool that we
have needed in that space; it has been essential, and so we are
grateful for it.
Senator Alexander. Good. Well, there is--I have an even
higher sense of urgency about the nonaddictive pain medicine
and treatment and accelerating our effort for that.
Let me go back to April 2016, you testified before this
subcommittee and made 10 bold predictions of what might be able
to happen in the world of medical miracles over the next
several years. A lot of them are happening, and you have
mentioned them today. Are you ready to update your 10 bold
predictions for the next 10 years?
[Laughter.]
Dr. Collins. I probably could do that. It would be kind of
fun because there were some things that I do not think I put
down in 2016 that I could now be pretty enthusiastic about. So,
for instance, in 2016, I do not think I would have been bold
enough to say that we would be curing sickle cell disease, and
yet we are now seeing in at least three clinical trials that
NIH is supporting, examples of individuals who are cured.
Senator Alexander. Is that because of CRISPR?
Dr. Collins. That is, CRISPR is in there, and other kinds
of gene therapy making this possible. Some of the things we put
down at that point, I thought were a bit overly optimistic, and
yet maybe I underestimated how quickly things would go. We
earlier talked about the artificial pancreas and, you know, I
put that one down and a year later FDA approved the first one.
REGENERATIVE MEDICINE
Senator Alexander. That is pretty common, right.
Well, what about regenerative medicine? The juvenile
diabetes folks say that the next step is regenerative medicine
might help actually change the cells so you would not have to
use the device. Is that possible?
Dr. Collins. I think that is the ultimate goal. Maybe Dr.
Rodgers would like to make a quick comment, to go from what is
currently a technology that is like a servo mechanism with some
nonhuman materials, into a human version of an artificial
pancreas derived from stem cells.
Senator Alexander. But the impact of that would be
astonishing, wouldn't it?
Dr. Collins. Profound, and it would be your own cells so
this would not be a transplant, it is basically----
Senator Alexander. So, you would not have to prick for your
blood every day?
How would that work Dr. Rodgers?
Dr. Rodgers. Well, that is a great question. Cell
replacement therapy is certainly an area that we are also, in
addition to the artificial pancreas technology looking for a
curative therapy. The goal here would be to stimulate the
person's own beta cells, those cells that are lost due to
autoimmune disease, and get them to replicate to expand them.
Or alternatively, use of the remaining cells, such as the alpha
cells that make glucagon, and trick them into actually becoming
beta cells so that insulin can then be produced as well.
One thing that we are doing in that space, using these
islets, the cells that make insulin, is actually putting them
on a chip. I have actually brought a copy of one to illustrate
for the committee. These islet cells are put on this chip
together with cells that replicate the pancreas environment
blood vessels, as well as components of the immune system. In
that, you can mimic the disease on a chip.
The potential of this is that we may be able to test
therapies in advance and save some of the expense and time
associated with testing novel technologies in humans and get
those that are likely to fail out of the way. So, we really
have a lot of enthusiasm about this type of work.
Senator Alexander. Thank you. My time is up.
But I look forward to you updating your bold predictions,
Dr. Collins.
Dr. Collins. You are on.
Senator Blunt. Alright. We will look forward to the list of
bold predictions.
Dr. Fauci, I am going to take 5 minutes here, and I have
three questions and maybe we can deal with all of them in 5
minutes. One, is measles. What do you think is happening and
how concerned we should be about it?
Two, the antibiotic resistance, the fungus that we are
having problems, big problems in a couple places in the country
now. Then, three would be the President's HIV 10-year
prediction to not have transmission, or not have this as a
problem anymore.
So, start with measles.
MEASLES
Dr. Fauci. Thank you, Mr. Chairman. Measles is really a
formidable problem that is growing. It is a completely
avoidable problem, which is the reason why we in the scientific
and public health field are so frustrated by it.
If you look at the year 2000, we here in the United States
had essentially eliminated measles. By elimination, it means
that there are no transmissible cases in the country over a 12-
month period. Yet over the last several years there has been
increasing numbers of cases of measles, and I will explain in a
moment why that is occurring.
The problem right now, this past 3 months of 2019, we have
had 465 cases of measles in the United States, which is more
than we saw all of last year. And the cause of that is very
clear, it is individuals in the community who are not
vaccinating their children, leaving a vulnerable group such
that when someone comes in from the outside, from another
country where measles might be rampant and into the community,
that if you have that veil of protection that you need when you
need a certain critical percentage of the population is
vaccinated, and for measles that means between 93 and 95
percent.
But look at what is going on now, in the State of
Washington, in the Rockland County, New York and very, very
importantly, in the middle of New York City in the Williamsburg
section, where the Hasidic Jewish community goes down to around
70 percent protection, which means that veil of community
immunity is gone.
That is the reason why we are having this outbreak. It is
very frustrating, because measles is one of the most
transmissible viruses known to man and we have a vaccine
against measles, which is one of the most effective vaccines
known to man, and yet those two are not coming together with
this hesitancy to get vaccinated.
So, our goal and our purpose now, is to try and educate
people to understand the importance of not only protecting
their own children but protecting the community. That is
measles.
CANDIDA AURIS FUNGUS
The fungus that you alluded to; it is called Candida auris.
Fungi in general that we see are mostly, I would not say
benign, but relatively easily treatable. The problem with this
fungus that is now come out about 500 or so cases, is that we
are seeing in hospitals particularly, a fungus that is rather
resistant, if not completely resistant to the antifungal
agents.
This is particularly important for individuals who are
immuno-suppressed, people on cancer chemotherapy, or people who
have underlying immunosuppression. You have read about it in
the front page of the New York Times, but this is becoming a
problem that we have to address, and it falls under the big
umbrella of the anti-microbial resistance.
HIV
Third, the President's announcement at the February 7th
State of the Union Address about ending the HIV epidemic as we
know it in the United States, and this is based on something
that has happened for many years largely supported by this
committee, is the development of the tools to do just that.
We have drugs right now as you well know, I have spoken to
you about this, that if you treated an individual who is HIV
infected and bring down the level of virus to below detectable
level, not only do you save that person's life but you make it
essentially impossible for that person to transmit the virus to
someone else.
And then there is preexposure prophylaxis or PREP, which
means that if you are at high risk of getting infected and you
take one pill a day, you can decrease by 97 percent the
likelihood that you actually will acquire infection.
You put those two things together and you look at the map
of the United States, why it is so unique. We have 3,007
counties in the United States, in 48 of those counties, plus
the Washington District of Columbia, plus San Juan, more than
50 percent of all the infections in the United States come from
that very restricted group.
So, the plan is to take this demographically and
geographically concentrated area, and as I say, put a full
court press on getting into the community and implementing each
of those.
So, I will stop there, and I give you back 10 seconds.
[Laughter.]
Senator Blunt. Well, that is back to the observation
earlier that you have testified before, you have three
questions, exactly have timed them out and land on time.
Senator Murray.
SEXUAL HARASSMENT
Senator Murray. Thank you very much and Dr. Collins I know
you are aware of a recent study in the Journal of American
Medical Association, which found the gender differences, you
talked a minute ago about that, in the amount of NIH funds
awarded to first time female, and male principal investigators
that favored men receiving larger grants than women. And data
shows that in academic medicine, which for years has trained
just as many women as men, the percentage of women in the
workforce decreases at every career stage, such that women make
up only 25 percent of the professorate.
And your conversation with Senator Baldwin indicates you
are aware of a study that also found that women held fewer
grants, submitted fewer applications, and were less successful
at renewing grants than their male counterparts.
So, in light of the National Academy's report last summer,
which showed that sexual harassment is rampant in academic
science and undermines women's professional attainment, in some
cases, leaving women to leave the scientific workforce
entirely, the cumulative effect results in significant damage
to research integrity and a considerable loss of talent in our
country.
So aside from its economic and potential scientific impact
that loss of talent actually represents a significant cost to
our taxpayers. It has been estimated that each newly minted
Ph.D. costs $500,000, and of course it is a personal loss to
women who feel pushed out of the field they love.
So, given all that, can you comment on actions that NIH is
taking to address this attrition of women from the biomedical
workforce?
Dr. Collins. I would be happy to. This is a very critical
issue and there are multiple factors, but certainly the
realization of how prominent and pervasive sexual harassment
has been leads us to push even harder to address this issue. It
is unacceptable, it is morally indefensible, and it drives
talented women away from the workforce who could make wonderful
contributions.
If you look at this graph, it sort of shows you what has
happened as far as the percent of various types of grants that
are going to women. You can see in the career awards, which are
generally people early in their independent phase we are doing
better over time, we are actually doing better with research
project grants, but the curve is way too slow in terms of its
upward movement. That ought to be 50 percent, and it is not
that there is a discrimination against women who apply for
grants, if you look at the likelihood of getting funded, men
versus women, it is almost exactly the same. The problem is we
are not getting the applications.
Senator Murray. They do not apply.
Dr. Collins. And that is clearly an indication that there
is something about our environment that is not welcoming, it
does not feel like to many women, a place they really want to
be. There are lots of factors in there in addition to the
sexual harassment issue, there are family issues, and there are
the issues about who has responsibilities for other parts of
the community that people are coming out of. There is this sort
of concern that if you look around, where are the mentors.
I believe we really need, not just to try to address the
things that are the most egregious as far as the sexual
harassment, but also the gender harassment. The way in which
our culture encourages women, often times to think they do not
belong there by subtle comments that are made, usually by men.
We have to change that, the best way to change that is to get
more women into leadership positions.
Senator Murray. I am looking at your panel, it's great,
but----
[Laughter.]
Dr. Collins. Well, yes, look at our panel, just take a
snapshot here, this is a good example of what we need to
change.
We are actually looking at our intramural program right now
to try to see, are we doing enough there to provide
opportunities for talented women to rise through the ranks or
are we too ossified by people who get into a position and stay
there too long.
We are taking this with great seriousness. I grant you, we
should have done so sooner, and I am apologetic to those who
think we have not done enough. We are determined to do better.
Senator Murray. Okay, I appreciate that. Thank you very
much and of course, we all have to participate, and appreciate
your taking this seriously, look forward to working with you on
it. I think we are losing talent from an early age and it gets
worse as we go on. We have to make sure we have all of our
talent at the table. So, thank you.
Dr. Collins. I agree with you.
METHAMPHETAMINE DEPENDENCE
Senator Murray. Dr. Volkow, my last question. There is a
lot of hope in my home State that opioid-related overdoses may
have peaked, but we have been seeing an alarming increase in
methamphetamine overdoses now, and as you know there is no FDA
approved treatments for methamphetamine dependence.
Can you tell me what NIDA's efforts to development
treatment for methamphetamine addiction is right now?
Dr. Volkow. Well, you are asking me a question that
actually literally makes me extraordinarily anxious and keeps
me awake at night, because we are seeing the numbers of
mortality increasing for methamphetamine and cocaine too, and
even though we funded research to come up with treatments none
of them have reached the outcomes that are actually necessary
to get them approved and show them effective.
However, what is very exciting in the whole area and
possibility, relates to immunotherapies, and in fact, where we
have done the greatest advance is developing monoclonal
antibodies for capturing the drug so that the drug gets
sequestered in the blood and never gets into the brain
obviating any pharmacological effects, happens to be for its
application on methamphetamine.
So, we have brought those antibodies already into humans,
and what we are trying to work right now is the extent to,
which by partnering with some of the scientists who are part of
the NIAID Institute and the Cancer Institute, on developing
longer lived, the monoclonal antibodies extent to which we
could apply them. Because they work, they capture it, the
problem is they are not long-lasting, so you have to repeatedly
immunize.
So, this is one of our priorities as it relates to
medications.
In parallel of course, we are funding research in terms of
behavioral interventions to try to actually improve the
outcomes on individuals that are suffering from methamphetamine
addiction.
Senator Murray. Okay. Thank you very much, I really
appreciate it. And thank you to all of you for being here
today. I appreciate the great work you do.
Senator Blunt. I have just a couple of more things as we
finish up here.
YOUNG RESEARCHERS
Dr. Lorsch, we talked about young researchers. I think you
have also been experimenting with longer research times for
grants. Would you talk about that and talk about whether there
is any impact that your appropriation stream has on being able
to do that?
Dr. Lorsch. Thank you very much, Senator. We have developed
a new program called Maximizing Investigators Research Awards,
or MIRA, which has several goals, but one as you said, is to
give a longer and more stable funding stream to investigators.
We hope that by doing that, and by also giving them more
freedom to basically follow their noses as their research
evolves, we will allow them to do more ambitious research and
to get faster to discoveries through this process.
There are two parts of it; one is the established
investigator part, and the other is the early-stage
investigator part.
The early-stage investigator part is actually particularly
exciting right now because since the program started in 2016,
we have seen a doubling of the number of early-stage
investigators that we fund at the Institute, primarily through
the MIRA program. We have seen a 60 percent increase in the
number of applications from early-stage investigators. So, they
are clearly speaking with their feet that this is the way they
want to see science supported.
And what is particularly exciting is we are actually
funding them at a younger age, so all 3 years of the program,
the median age of funding for early-stage investigators in MIRA
is 37, whereas it is 38 for early-stage investigators funded
through RO1s and we are hoping that trend is going to continue.
What I will say for the record, is that one of my strategic
goals for the Institute is to try to push that age of funding
for MIRA down to 35. I think 37 is still too late to be getting
your first grant award.
Senator Blunt. Well, thank you for that.
NON-ADDICTIVE PAIN MEDICATION
Dr. Volkow, you know we have had a 30 percent increase in
NIH and we are all pleased about, and during that same period
of time we have had a 1300 percent increase in money going to
the opioid fight.
I do not know that we have talked yet today about
alternative research to have pain medicine that is not
addictive. Do you have any more you want to add to that?
Dr. Volkow. There are two components to it, one of them is
in terms of the basic science that Francis was speaking of that
allowed us to identify completely novel treatment targets,
molecules or immunotherapies for management of pain.
And then those interventions that do not rely on biologics
or medicine, and that includes behavioral interventions to
evaluate the extent that they can improve the outcomes, as well
as an area that is very exciting in the whole area of brain
diseases, is the use of neuromodulation technologies like
magnetic resonance, transcranial magnetic resonance
stimulation, or direct electrical stimulation, to modify
certain areas of the brain, in means to improve outcomes.
The research, for example, there are several papers that
have shown positive effects for various chronic pain conditions
that offers an opportunity. There is also, as part of the HEAL
initiative, a project that is going to be evaluating
comprehensive models of care, just as the CDC recommends for
the management of chronic pain, that will determine the extent
for which they are effective and optimize our understanding
about what are the active ingredients and how to sustain them.
And too, at the end recognize that chronic pain is an
extraordinary, difficult condition to treat, and that it is
terrigenous and that we may require to do what is done in
cancer, personalize intervention.
So, doing that research that will enable us to get there
will be very important in helping patients suffering from
severe chronic pain conditions.
Dr. Collins. I just want to weigh in for a minute here and
say how incredibly helpful it was for the Congress to identify
this as an area, both of great need and of great opportunity,
and the $500 million that you put into the budget beginning in
fiscal year 2018 has made it possible for us to solicit truly
bold ideas across all of NIH.
We now have 20 of our institutes engaged in this, more than
40 different funding opportunity announcements, some of which
have already received grants, have been reviewed and are
starting to be funded; some of which are still out there for
solicitations. By the end of this fiscal year we will have put
the largest infusion of research into finding nonaddictive
alternatives for pain that has ever happened at NIH, in
addition to funding a very large amount of efforts to try to
help how to manage opioid use addiction, which is obviously our
National crisis.
We could not have done this at this scale without your
help, and it has made all the difference.
SEPSIS
Senator Blunt. Good. I do not remember the first time I
noticed that somebody's cause of death was sepsis. It does not
seem to me it was that long ago, but it does seem to me that I
see that often now.
What are we trying to do there, and is that an NIH issue
that you are dealing with?
Dr. Collins. It is. Maybe I will ask Dr. Lorsch to say a
little bit about the basic science part, and Dr. Fauci about
the clinical efforts, because those are hand in hand.
Dr. Lorsch. Thank you very much. Sepsis research is
supported jointly by three main institutes, one is NIGMS, one
is Dr. Fauci's Institute, NIAID, each of which fund about a
third of sepsis research, and Heart, Lung, and Blood funds
about a quarter of it and the remainder is Child Health and Dr.
Rodger's institute.
I became concerned a couple of years ago that the pace of
research in the basic part of sepsis understand the mechanisms
underlying the condition was not fast enough. So I put together
a working group of our advisory council, which right now is
examining our portfolio and the field and how it fits in with
the rest of what NIH is funding, and they will be making
recommendations to us at the May council meeting that we will
have next month.
Particularly they are going to be looking at the balance of
research in animal models versus in humans. We are concerned
that perhaps there is too much emphasis on looking at sepsis-
like conditions in mice and not enough in actual human
condition. And we are also looking at ways we can leverage
clinical trials networks that are funded by other institutes
that are already enrolling critically ill patients who may
develop sepsis.
And perhaps, Dr. Fauci wants to say a little bit about
that.
Dr. Fauci. Thank you, Mr. Chairman. The effort against
sepsis as Dr. Lorsch has mentioned, is really multifaceted,
because you have a micro-organism, a pathogen that triggers a
process that is a physiologic and pathological process that
leads to what we now know as sepsis. It is not just the microbe
and it is not just the response; it is a combination of the
two.
NIAD's role is to study specifically the microbe itself,
the virilism of the microbe, the processes that trigger these
physiological and patho-physiological events, as well as
treatment.
And as Dr. Lorsch mentioned, we have a clinical trials
network that we look at these patients, it is very difficult to
actually study them, because when they come in it is such an
acute situation that you have to move very quickly when you are
doing a clinical trial. But we are working with other
institutes, including the National Heart, Lung and Blood
Institute, to do this kind of synergy of multiple approaches to
what is a very complex and heterogeneous problem.
Senator Blunt. Well, Senator Murray, we are about to finish
here, is there anything that we should have asked that we did
not ask Dr. Collins?
Dr. Collins. You did a pretty fine job of covering a lot of
the landscape with the folks who are here. And again, I have to
say how much it has impressed me over the years about how much
the members of this subcommittee have become so deeply
knowledgeable about what we do.
These conversations always end up being full of really rich
details and digging into areas that we love to talk about. So,
many thanks to you for all of the ways in which you have spent
your time on these issues, and of course, we would love to
invite you back out to NIH any time because we always have new
things to show you.
ADDITIONAL COMMITTEE QUESTIONS
Senator Blunt. All right. The record will stay open for one
week for additional questions.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted to Francis S. Collins, M.D. Ph.D.
Questions Submitted by Senator Roy Blunt
china's thousand talents program
Question. I'm very concerned that the NIH research community is not
being adequately informed of the threats they are facing from foreign
government programs specifically designed to undermine U.S. research.
What specific steps are being taken to: (1) better inform the research
community of the specific threat; (2) ensure there is disclosure of
foreign collaborations and affiliations; and (3) implement controls to
protect the integrity of the peer review system?
Answer. NIH shares your concern about foreign government programs
that are designed to undermine U.S. research. NIH is committed to
working with other agencies and offices, including law enforcement, as
well as with the extramural community, to identify and confront the
risks these programs pose and to combat them. As described further
below, NIH is employing a multi-pronged approach addressing individual
situations and developing proactive programs to address these threats.
Informing the Research Community
NIH's efforts to inform and engage the research community are
proceeding across multiple platforms. For example, multiple
communications to the research community over the last several years
have focused on the imperative that applicants and recipients inform
NIH of foreign support, and the obligations and certifications of
reviewers to protect the confidentiality of grant applications, study
section deliberations, preliminary scoring and reviews. For example, an
NIH Guide Notice \1\ issued in March 2018 reminded applicants and
recipients of the requirement to disclose to their institution
significant financial interests, which can include support coming from
foreign governments or other foreign entities; the institution
determines financial conflicts of interest that must be reported to NIH
and managed on an ongoing basis by the institution. On August 23, 2018,
the NIH Director took the unusual action of issuing a comprehensive
statement on protecting the integrity of U.S. Biomedical Research. The
Director also took the unprecedented step of issuing a letter to
officials at approximately 10,000 recipient institutions. This letter
informed the research community that the agency is aware that some
foreign entities have mounted systematic programs to influence NIH
researchers and peer reviewers, as well as to take advantage of the
long tradition of trust, fairness, and excellence of NIH supported
research activities. Furthermore, NIH convened a working group of the
Advisory Committee to the NIH Director on Foreign Influences on
Research Integrity. This panel was comprised of leaders in higher
education, members of the extramural community, and experts in
security, and was charged with assisting the Advisory Committee in
making recommendations to the agency, which are currently being
implemented.
---------------------------------------------------------------------------
\1\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-
160.html.
---------------------------------------------------------------------------
In order to address specific cases brought to the attention of the
agency, NIH has contacted nearly sixty institutions regarding concerns
about scientists who may have failed to disclose foreign affiliations
or significant financial interests stemming from foreign-based entities
or governments. This approach has proven highly effective in both
communicating concerns to the extramural research community,
engendering partnerships to develop best practices, and gaining
compliance with Federal and NIH grants requirements and policies. NIH's
efforts have been widely reported within the science and popular press,
e.g., by the Houston Chronicle,\2\ Science Magazine,\3\ and The Cancer
Letter,\4\ which is expanding our impact. We are actively engaging the
research community and in turn, they are actively partnering with us.
For example, Penn State University,\5\ M.D. Anderson,\6\ and the
University of California San Diego \7\ have posted new guidelines for
faculty. Professional societies such as the American Society for
Biochemistry and Molecular Biology \8\ are acting to share our concerns
across the research community. We appreciate all the members of the
research community who proactively work with us to address these
matters.
---------------------------------------------------------------------------
\2\ https://www.houstonchronicle.com/news/houston-texas/houston/
article/MD-Anderson-fires-3-scientists-over-concerns-13780570.php.
\3\ https://www.sciencemag.org/news/2019/04/universities-will-soon-
announce-action-against-
scientists-who-broke-nih-rules-agency.
\4\ https://cancerletter.com/articles/20190426_3/.
\5\ https://www.research.psu.edu/international_affiliations.
\6\ https://www.mdanderson.org/newsroom/md-anderson-addresses-
national-threat-of-foreign-
influence-.h00-159302256.html.
\7\ https://medschool.ucsd.edu/vchs/research-services/hssppo/
review/Pages/Foreign-Involvement-.aspx.
\8\ http://policy.asbmb.org/2019/01/02/updates-from-the-nih-
advisory-committee-to-the-directors-december-meeting/.
---------------------------------------------------------------------------
Furthermore, NIH regularly communicates with grantees to provide
training and compliance support for issues involving conflict of
interest requirements at NIH-led conferences such as the NIH Regional
Seminars. This information is also communicated by NIH through
professional organizations such as the Federal Demonstration
Partnership, Society for Research Administrators, American Association
of Universities, Council on Governmental Relations, Association of
Public & Land Grant Universities, and the National Council of
University Research Administrators. There have been a number of special
meetings involving these groups and others to address the recent
concerns on foreign influence. In addition, NIH recently developed an
online training module on Financial Conflict of Interest as a resource
for both NIH staff and the extramural community. NIH's outreach and
engagement have facilitated extensive faculty outreach at research
organizations as well as led to developing and sharing best practices.
Moving forward, as Dr. Collins said during the Senate Appropriation
hearing, ``We will not rest until we've looked at every possible
example. We have to depend on the universities as our partners in this,
but we are driving this process as vigorously as we can.'' Additional
institutions will be contacted when new discoveries are made. NIH will
continue to remind the extramural research community of the need to be
transparent regarding other support, financial conflicts of interest
and foreign components, to better address research threats.
Finally, NIH is actively partnering with other Federal departments
and agencies to address concerns related to undue foreign influence on
the biomedical research enterprise. These Federal partners include the
Central Intelligence Agency, Federal Bureau of Investigation, HHS
Office of Inspector General, Department of Defense, Department of
State, and the National Science Foundation.
Ensuring Disclosure of Foreign Collaborations and Affiliations
NIH requires institutions, as the applicants for and recipients of
NIH funding, to ensure that individual investigators make all
appropriate disclosures to their institution regarding other support,
affiliations, and financial interests, whether or not they are
employees of the institution. Institutions, in turn, must ensure that
all applications and reports submitted to NIH are complete and
accurate.
Prior to making an award, NIH requests and reviews updated ``other
support'' information for the program director/principal investigator
and other key personnel identified in the grant application to ensure
that updated information on all financial resources, whether Federal or
non-Federal, foreign, commercial or institutional, available in direct
support of an individual's research endeavors, are known and considered
prior to award. This includes foreign financial support. NIH uses this
information to ensure that sufficient levels of effort are committed to
the project, there is no scientific, budgetary, or commitment overlap,
and only the funds necessary to the approved project are included in
the grant award.
In addition, NIH applicants and recipients must request and receive
approval for the inclusion of any foreign components of an NIH award. A
foreign component is the performance of any significant scientific
element or segment of the project outside of the United States, either
by the recipient or by a researcher employed by a foreign organization,
whether or not grant funds are expended.
Among other obligations, the applicant organization must certify,
and in some cases submit assurances, that they comply with the public
policy requirements provided in the NIH Grants Policy Statement. These
requirements are intended to ensure that recipient organizations handle
their Federal awards responsibly. While NIH maintains oversight of our
awards, we entrust our recipient organizations with the responsibility
and accountability for successfully administering their grant award,
including prudent fiscal management and other requirements spelled out
in the NIH Grants Policy Statement.
NIH will take action and has taken action where appropriate under
its authority to address such concerns as part of its proper oversight,
compliance, and stewardship roles. As an example, when NIH identifies
noncompliance with the terms and conditions of award, it may take
actions consistent with the regulatory requirements found in 45 CFR
75.207 and 75.371 for grants and FAR 52.227-11 for contracts. Depending
on the severity and duration of the noncompliance, NIH may decide to
take one or more actions, which are also described in the NIH Grants
Policy Statement, Section 8.5, Specific Award Conditions and Remedies
for Noncompliance, including imposing specific award conditions,
disallowing costs, withholding future awards for the project or
program, suspending the award activities, making a referral for
suspension or debarment, or terminating the award.
Protecting the Integrity of the Peer Review System
All participants in the NIH peer review system are responsible for
promoting integrity. Maintaining integrity--including obligations of
reviewers to keep application information confidential and secure,
consistent with their certifications--in the peer review process is
essential for ensuring robust exchange of scientific opinions and
providing reliable input to NIH about which research projects it should
support and maintaining public trust in science.
In recent years, NIH has taken numerous steps to protect the
integrity of the peer review process. In addition to issuing several
Guide Notices and blogs on the confidentiality and integrity of peer
review, NIH has referred many cases to the HHS Office of Inspector
General for consideration of further action, including referrals for
debarment or suspension, as well as removed the affected individuals
from peer review service. Also, in the end of 2018, reviewer conflict
of interest certifications were converted to completely electronic
format, enabling more thorough assessment of compliance across the
agency and in cases of individual breaches.
The NIH Office of Extramural Research (OER) has expanded its
internal training for NIH Scientific Review Officers (SROs) to raise
their awareness of integrity concerns. OER held three interactive
training sessions on peer review integrity in the last year, each event
drawing hundreds of SROs. These events covered case studies largely
based on actual events and stimulated lively discussion of the best
course of action in each scenario. The NIH is also working to implement
recommendations from the NIH Advisory Committee to the Director on
Foreign Influences on Research Integrity that focus on peer review
integrity. Further, NIH continues to explore new technologies and ideas
to protect the integrity of the peer review process. For example, a new
dashboard is being developed to assist the Office of the Director in
identifying data needed to review possible peer review integrity
violations. Finally, policies for permissions to access certain
information are being re-assessed. Taken together, these efforts to
communicate internally and externally, as well as modernize controls,
are raising the profile on peer review integrity concerns and reducing
risks.
research on social media impacts
Question. Dr. Collins, as a father of a 14 year old, I understand
the role that cell phones, social media, and video games play in an
adolescent's life. There is a lot of competing research available that
shows the potential mental and emotional effects that media may play.
Conversely, media also may be a resource to find social and emotional
support for teens. Can you discuss what role NIH is playing in this
research? Specifically, can you provide a few examples of what type of
studies you are doing?
Answer. NIH is vigorously pursuing this area of research. Several
NIH Institutes and Centers, including the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), are
researching the effects of increasing use of media by children and
adolescents. New evidence shows that screen time use is growing with
unknown long-term effects on health and development. Early data from
the NIH-funded Adolescent Brain Cognitive Development (ABCD) study
shows that only 37 percent of children in the study met the less than
two hours per day of recreational screen time recommended by American
Academy of Pediatrics (AAP) guidelines. According to the AAP, 95
percent of teens have access to a smartphone, and 45 percent say they
are online ``almost constantly.'' In April 2019, the World Health
Organization issued new guidelines stating that to grow up healthy,
``children under five must spend less time sitting watching screens,''
emphasizing that screen time should be replaced with interactive non-
screen-based activities.
NIH is committed to learning more about this issue. Just last year,
NICHD hosted a workshop on media exposure and early child development,
bringing together experts in this new field to share their individual
perspectives regarding research gaps. Recommendations from some of the
workshop panelists included developing meaningful measures of the
impact of exposures to media, conducting neuroimaging research to look
at the effects on developing brains, and parent education approaches. A
recent NICHD-funded study found that exposure to media violence is a
strong predictor of aggression and that parental monitoring is a
significant factor against aggressive behavior. At the same time,
social media can have positive effects; through its Adolescent Trials
Network, NICHD is exploring the use of an interactive smartphone app as
an intervention to help prevent the spread of HIV. Another study funded
in 2018 is exploring whether books presented on a screen or with
interactive enhancements confer the same benefits to a child's reading
skills and socio-emotional development as print books. Screens also
have been associated with delayed or insufficient sleep, which can lead
to a number of chronic medical conditions in children and adolescents;
another NICHD-funded study is exploring whether the light emitted by
screens and other mechanisms affect children's circadian clocks.
The ABCD \9\ is a longitudinal study of close to 12,000 children
beginning at age 9-10 and continuing through adolescence and into early
adulthood to understand how the experiences of adolescence shape brain,
cognitive, social, and emotional development. When the children are 9
and 10, they are asked questions about how much time they spend on
different activities related to digital media (e.g., watching TV,
playing video games, on social media, texting, video chatting). As they
get older, they will be asked more in-depth questions about technology
use. These data can then be correlated with other assessments within
the study such as structural and functional MRI and measures related to
mental health, cognition, and sleep, as well as be tracked over time as
they mature. This comprehensive data set, led by the National Institute
on Drug Abuse and supported by NICHD, the National Institute on Alcohol
Abuse and Alcoholism, and the National Cancer Institute (NCI), will be
disaggregated by sex, racial/ethnic group, and socioeconomic status, to
allow researchers to address numerous questions related to adolescent
brain development, thus informing future prevention and treatment
efforts and public health strategies.
---------------------------------------------------------------------------
\9\ https://abcdstudy.org/.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Shelley Moore Capito
pulmonary fibrosis
Question. I have a question for you about pulmonary fibrosis, a
devastating disease that affects many people in my State. A major area
of interest in pulmonary fibrosis-related research is patient-centered
clinical research--research that directly addresses issues of most
importance to those suffering from the disease. This would include
studies looking at reducing hospitalizations, improving symptoms, and
prolonging life. For example, researchers are currently examining the
chronic cough that pulmonary fibrosis patients cite as one of the
symptoms that most affects their quality of life.
In the context of pulmonary fibrosis, what are the NIH and the
NHLBI doing to support clinical researchers focused on patient-centered
outcomes, and how they are promoting the use of novel data sources such
as real-world registries, wearables and other technology?
Answer. The NHLBI continues to support a wide array of clinical
trials and fundamental research studies as part of a multi-pronged
approach to identify and enhance treatments for patients who suffer
from pulmonary fibrosis (PF).
In the fundamental discovery science area, NHLBI-funded researchers
are studying the mechanisms of lung fibrosis. One research team
recently found that fibrotic cell invasion in PF could be driven by a
problem with immune checkpoints, which are cell surface proteins that
keep immune responses in check. These same proteins are hijacked by
cancer cells to evade the immune system, and are the target for a new
class of cancer drugs, suggesting that similar drugs could be used to
treat PF.\10\ Another group's research suggests that toxic byproducts
of oxygen consumption (reactive oxygen species) may contribute to lung
injury in idiopathic PF (IPF), which has led to a clinical trial of a
potential new drug.\11\
---------------------------------------------------------------------------
\10\ https://www.ncbi.nlm.nih.gov/pubmed/30763282.
\11\ https://clinicaltrials.gov/ct2/show/NCT03865927.
---------------------------------------------------------------------------
NHLBI supports trials evaluating a number of other potential
therapies that target different aspects of pathology in IPF. Two multi-
site clinical studies are investigating a combination of therapies that
target autoantibodies--which stimulate the immune system to attack the
body's own tissues; in PF, certain autoantibodies are known to cause
acute breathing exacerbations.\12\ NHLBI's Pulmonary Trials Cooperative
supports an ongoing study of antimicrobial therapy to reduce the risk
of hospitalization and death from PF.\13\ Additionally, NHLBI's Centers
for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases
(CADET) program conducts preclinical research to help translate new
understanding of disease mechanisms into better treatment for lung
diseases, and is a developing potential new therapeutics for PF.
---------------------------------------------------------------------------
\12\ https://clinicaltrials.gov/ct2/show/NCT03286556
and https://clinicaltrials.gov/ct2/show/NCT01969409.
\13\ https://clinicaltrials.gov/ct2/show/NCT02759120.
---------------------------------------------------------------------------
The NHLBI also strongly encourages investigators to utilize patient
registries, such as the Pulmonary Fibrosis Foundation's registry,
whenever appropriate to identify, recruit, and retain patients for
clinical research, including intervention trials and studies to better
understand the disease process. Several current funding opportunities
allow PF researchers to leverage existing registries and resources.
The NHLBI also encourages PF researchers to contribute and use
whole genome sequencing data that is available through our Trans-omics
for Precision Medicine (TOPMed) program. TOPMed is one of three massive
datasets that researchers will be able to access and query during a
pilot phase of the NIH Data Commons, a cloud-computing environment that
is part of the NIH Science and Technology Research Infrastructure for
Discovery, Experimentation, and Sustainability (STRIDES) initiative.
The NHLBI is also developing another resource called Data Storage,
Toolspace, Access and analytics for biG-data Empowerment (DataSTAGE)
that will integrate TOPMed and other datasets with analytical tools to
provide computing power that will help researchers explore precision
medicine for PF and other disorders.
The NHLBI and other Institutes continue to support the development
of technologies to ameliorate symptoms such as cough in patients with
chronic lung diseases, including PF, in part through our small business
research programs. For example, researchers supported by the National
Institute on Aging (NIA) are developing a wearable monitoring device to
better assess patients with chronic respiratory disease.\14\
---------------------------------------------------------------------------
\14\ https://projectreporter.nih.gov/
project_info_details.cfm?aid=9465334.
---------------------------------------------------------------------------
The NHLBI also recognizes that aging has a significant impact on
disease progression in patients with fibrotic lung diseases, and that
there is a need for improved methods and tools to account for the
interplay between aging and fibrosis. To this end, the NHLBI developed
an initiative aimed at Deciphering the Molecular Landscape of Lung
Aging in Humans,\15\ which is supporting four projects, including a
Normal Aging Lung Atlas that will catalog dynamic gene expression
changes in aging lung tissue at the single-cell level.\16\
---------------------------------------------------------------------------
\15\ https://grants.nih.gov/grants/guide/rfa-files/rfa-hl-19-
012.html.
\16\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9657483.
---------------------------------------------------------------------------
vascular dementia
Question. Vascular dementia is the second most common form of
dementia, after Alzheimer's disease, affecting almost a third of people
over age 70. The NIH just completed the first randomized clinical trial
demonstrating that lowering of systolic blood pressure significantly
reduces the occurrence of mild cognitive impairment, which is an
established risk factor and often a precursor for dementia.
As the incidence of dementia continues to rise, what is NHLBI doing
to understand the connection between heart health and brain health--
e.g. vascular dementia? What can people do to prevent it?
Answer. Cardiovascular disease (CVD) is increasingly recognized as
an important contributor to cognitive impairment and dementia.
Fortunately, the science also suggests that maintaining a healthy heart
can help maintain a healthy brain. A recent Alzheimer's Disease-Related
Dementias (ADRD) Summit at NIH included a discussion of vascular
dementia and how to continue to move the field forward.\17\
---------------------------------------------------------------------------
\17\ https://meetings.ninds.nih.gov/?ID=21149.
---------------------------------------------------------------------------
NIH is already leveraging several of its long-established cohort
studies to better understand the connections between heart disease and
dementia. NHLBI's Framingham Heart Study began 70 years ago, and has
since expanded to include three generations of participants. The study
has found that many of the risk factors for dementia are the same as
those for heart disease, such as high blood pressure, cigarette
smoking, lack of physical activity, obesity, and diabetes. A recent
NIH-supported analysis of Framingham data found that high blood
pressure during mid-life increases the risk of dementia later,
suggesting that there are potential cognitive benefits from managing
blood pressure in mid-life.\18\
---------------------------------------------------------------------------
\18\ https://www.ncbi.nlm.nih.gov/pubmed/29117954.
---------------------------------------------------------------------------
Several NIH cohort studies focused on minority populations have
added new objectives to better understand the connection between
vascular risk factors and brain health. NHLBI's Jackson Heart Study of
CVD in African Americans was renewed in August 2018, and new clinical
exams beginning in 2020 will include tests of cognitive function as
well as brain imaging. Additionally, the National Institute of
Neurological Disorders and Stroke (NINDS) is supporting projects that
leverage data from cohort studies such as the Reasons for Geographic
and Racial Differences in Stroke (REGARDS) study and the Northern
Manhattan Study (NOMAS). To better understand and prevent risk of
vascular brain disease in women, participants from the NHLBI-supported
Women's Health Initiative are part of the Women's Health Initiative
Strong & Healthy (WHISH), trial which is testing whether increasing
physical activity will reduce the risk of CVD and cognitive decline in
older women.\19\
---------------------------------------------------------------------------
\19\ https://whish.stanford.edu/about/.
---------------------------------------------------------------------------
In the basic research arena, the Molecular Mechanisms of the
Vascular Etiology of Alzheimer's Disease (M\2\OVE-AD) Consortium,
developed by the NIA in collaboration with NINDS, brings together six
multi-disciplinary research teams to use a variety of computational and
animal model approaches to better understand the complex molecular
mechanisms by which vascular and metabolic risk factors influence the
development of Alzheimer's and related dementias, with the ultimate
goal to identify therapeutic targets and biomarkers.\20\
---------------------------------------------------------------------------
\20\ https://www.nih.gov/news-events/news-releases/decoding-
molecular-ties-between-vascular-disease-alzheimers.
---------------------------------------------------------------------------
It is now known that brain changes typically begin years--if not
decades--before people show symptoms, which suggests that a window of
opportunity exists to prevent, slow, or delay the onset of cognitive
decline. A recent analysis of the Framingham Heart Study examined
whether adherence to the American Heart Association's (AHA)
Cardiovascular Health Guidelines was associated with improved brain
health. The analysis found a lower risk of incident stroke, dementia,
cognitive decline, and brain atrophy among participants who adhered to
the AHA recommendations, which includes maintaining a healthy body mass
index, healthy diet, nonsmoking status, normal total cholesterol,
normal blood pressure, and physical activity.\21\
---------------------------------------------------------------------------
\21\ https://www.ahajournals.org/doi/full/10.1161/
strokeaha.115.012608.
---------------------------------------------------------------------------
A 2017 National Academies of Sciences report supported by NIH
concluded that there is encouraging but inconclusive evidence for
several potential approaches to guard against cognitive decline and
dementia, including blood pressure management for people with
hypertension, increased physical activity, and cognitive training.\22\
Recent NIH-funded studies add to the weight of evidence that aggressive
treatment of hypertension may protect against cognitive decline. The
NIH-funded Systolic Blood Pressure Intervention Trial (SPRINT) trial
investigated whether aggressive systolic blood pressure reduction--down
to less than 120 mm Hg, rather the prior target of 140 mm Hg--could
reduce the risk of heart attack, stroke, and death in people over age
50 who have hypertension. A sub-study, the SPRINT Memory and Cognition
IN Decreased Hypertension (MIND) trial, evaluated whether this
aggressive treatment would also lower the risk of dementia. These
studies were stopped early because the treatment clearly protected
against CVD. After about 5 years of follow-up in SPRINT MIND, there was
no significant change in dementia risk, perhaps because of the study's
shortened duration. However, there was almost 20 percent lower risk of
mild cognitive impairment, a well-established precursor of
dementia.\23\
---------------------------------------------------------------------------
\22\ http://www.nationalacademies.org/hmd/Reports/2017/preventing-
cognitive-decline-and-
dementia-a-way-forward.aspx.
\23\ https://jamanetwork.com/journals/jama/fullarticle/2723256.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Cindy Hyde-Smith
opioid addiction
Question. Dr. Collins, how is NIH investing in research to identify
genetic components that may make particular individuals more
susceptible to opioid addiction? What is the current status of the
science in this area? Are additional funds needed to expand this
research?
Answer. Many individuals affected by OUD have a family history of
addiction to opioids or other substances, however, research to date
indicates that OUD does not have a clear pattern of inheritance. The
increased risk among members of an affected family is likely due in
part to shared genetic factors, but it is also likely related to
environment and other non-genetic influences that are shared by family
members.
Separating the complexities of genetic and non-genetic factors that
affect OUD risk is a crucial pillar of efforts to stem the tide of the
opioid crisis and advances NIH's broader goals of understanding the
mechanisms underlying addiction to inform effective prevention and
treatment strategies. Accordingly, NIH has fostered a robust and
multidisciplinary research portfolio to examine the genetic
underpinnings of OUD. There are currently 67 active NIH-funded projects
focused on opioid addiction and genetics, as identified in NIH's public
database, RePORTER. Some of these projects are highlighted below.
One of the common tools in NIH's arsenal to investigate the role of
genetics in disease is a genome-wide association study, or GWAS. A GWAS
involves examining genetic variations (genotypes) across the complete
sequences of DNA, or genomes, of many different people to find genetic
variants associated with a disease or trait (phenotypes). There have
been six GWAS projects studying OUD phenotypes that identify several
single nucleotide polymorphisms (SNPs), or variations in a single DNA
nucleotide, as potentially significant. These variations are being
examined to validate their association with OUD. The National Institute
on Drug Abuse's Genetics Consortium, founded in 1999 to coordinate
efforts of investigators studying substance use disorders and addictive
behaviors, is currently conducting its own GWAS, which includes samples
from more than 10,000 people. Recent work in psychiatry genetics
suggest that sample sizes larger than 10,000 are needed to identify
genome wide significant results.
In addition, NIDA is seeking to leverage resources of commercial
companies to identify genetic variants for prescription opioid misuse
and has issued a Request for Information via FedBizOpps to identify
companies that can execute such an initiative (Solicitation
75N95019R00053: Addressing the Opioid Crisis: Genetic Variants for
Prescription Opioid Abuse).
Current Status of the Science: While research in this field is
still underway, there is already a body of evidence that suggests a few
key themes in the complex interplay between genetics and addiction:
--The dose of methadone needed to successfully treat OUD is affected
by genetic variations in the mu opioid receptor gene and in the
gene for the enzyme that metabolizes methadone.\24,25,26\
---------------------------------------------------------------------------
\24\ Smith AH, Jensen KP, Li J, et al. Genome-wide association
study of therapeutic opioid dosing identifies a novel locus upstream of
OPRM1. Mol Psychiatry 2017;22:346-52.
\25\ Crist RC, Doyle GA, Nelson EC, et al. A polymorphism in the
OPRM1 3'-untranslated region is associated with methadone efficacy in
treating opioid dependence. The pharmacogenomics journal 2018;18:173-9.
\26\ Dennis BB, Bawor M, Thabane L, Sohani Z, Samaan Z. Impact of
ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose
and treatment response in patients with opioid addiction: a systematic
review and meta-analysis. PloS one 2014;9:e86114-e.
---------------------------------------------------------------------------
--Genetic variations in the mu opioid receptor gene are also
associated with risk for heroin addiction and with severity of
heroin addiction.\27,28,29,30\
---------------------------------------------------------------------------
\27\ Schwantes-An TH, Zhang J, Chen LS, et al. Association of the
OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to
Substance Dependence in a Collaborative de novo Meta-Analysis of
European-Ancestry Cohorts. Behavior genetics 2016;46:151-69.
\28\ Hancock DB, Levy JL, Gaddis NC, et al. Cis-Expression
Quantitative Trait Loci Mapping Reveals Replicable Associations with
Heroin Addiction in OPRM1. Biological Psychiatry 2015.
\29\ Zhang Y, Picetti R, Butelman ER, Ho A, Blendy JA, Kreek MJ.
Mouse model of the OPRM1 (A118G) polymorphism: differential heroin
self-administration behavior compared with wild-type mice.
Neuropsychopharmacology : official publication of the American College
of Neuropsychopharmacology 2015;40:1091-100.
\30\ Xu J, Lu Z, Xu M, et al. A heroin addiction severity-
associated intronic single nucleotide polymorphism modulates
alternative pre-mRNA splicing of the ? opioid receptor gene OPRM1 via
hnRNPH interactions. J Neurosci 2014;34:11048-66.
---------------------------------------------------------------------------
--Copy Number Variations (CNVs) (or variability in the number of
times a sequence of DNA is repeated) are associated with opioid
dependence. In one sequence, a chromosomal deletion is
associated with being protective against opioid dependence, and
duplication of the same part of the chromosome increased risk
for opioid dependence.\31\
---------------------------------------------------------------------------
\31\ Li D, Zhao H, Kranzler HR, et al. Genome-wide association
study of copy number variations (CNVs) with opioid dependence.
Neuropsychopharmacology 2015;40:1016-26.
---------------------------------------------------------------------------
--Variations in genes that code for proteins associated with the
signaling of glutamate, a widespread neurotransmitter in the
brain, have also been associated with development of opioid
addiction and regulation of opioid withdrawal.\32,33,34\
---------------------------------------------------------------------------
\32\ Nelson EC, Agrawal A, Heath AC, et al. Evidence of CNIH3
involvement in opioid dependence. Mol Psychiatry 2016;21:608-14.
\33\ Reti IM, Crombag HS, Takamiya K, et al. Narp regulates long-
term aversive effects of morphine withdrawal. Behavioral neuroscience
2008;122:760-8.
\34\ Crombag HS, Dickson M, Dinenna M, et al. Narp deletion blocks
extinction of morphine place preference conditioning.
Neuropsychopharmacology 2009;34:857-66.
---------------------------------------------------------------------------
--A gene coding for a protein that is important for the way neurons
form connections with one another regulates opioid tolerance
and opioid-induced hyperalgesia.\35\
---------------------------------------------------------------------------
\35\ Donaldson R, Sun Y, Liang D-Y, et al. The multiple PDZ domain
protein Mpdz/MUPP1 regulates opioid tolerance and opioid-induced
hyperalgesia. BMC Genomics 2016;17:313.
---------------------------------------------------------------------------
Question. Are additional funds needed to expand this research?
Answer. Investing in research is fundamental, and NIH will continue
to explore opportunities to expand the scope and impact of genetic
research on OUD. For example, an expert panel convened by the NIDA
Genetics Consortium recently highlighted the value in conducting a GWAS
on opioid naive surgical patients to identify genetic variants
associated with persistent opioid use and other opioid-related
outcomes. This would be an opportunity to potentially identify genetic
variants among surgical patients who become opioid dependent.
______
Questions Submitted by Senator James Lankford
fetal tissue/stem cells
Question. During an appropriation hearing in the House of
Representatives, Rep. Andy Harris asked you about the ongoing fetal
tissue research at NIH, but there were some outstanding questions from
his line of questioning. I share Rep. Harris' concern over the use of
fetal tissue research at NIH and would like more information as it
relates to ongoing studies that use fetal tissue research.
From my understanding, you recently extended a fetal tissue
contract with the University of California San Francisco (UCSF).
From where is the tissue obtained that UCSF is providing to NIH?
Answer. UCSF obtained fetal tissue as it became available from
elective and legal abortions performed at the UCSF clinic in San
Francisco and that would otherwise be discarded. Per the June 5, 2019,
statement from the Department of Health and Human Services, the
contract expired on June 5, 2019, and there will be no further
extensions.\36\
---------------------------------------------------------------------------
\36\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
department-of-health-and-human-services.html.
---------------------------------------------------------------------------
Question. How old are the fetuses that were obtained from UCSF that
are used in the study?
Answer. The contract required the delivery of humanized mouse
models. The contractor proposed the collection of human fetal tissue in
order to create the humanized mouse models. NIH did not specify
gestational age of the tissue being collected. As noted above, this
contract expired on June 5, 2019, and there will be no further
extensions.
Question. Why was the decision made to extend this contract before
HHS finished its audit of fetal tissue research?
Answer. The contract with UCSF had an option year that needed to be
exercised prior to the completion of the HHS audit. The contract was
extended to ensure continuity of service until the audit is completed
and a final decision was made about the contract. As noted above, this
contract expired on June 5, 2019, and there will be no further
extensions.
Question. How many studies is NIH conducting with fetal tissue?
Answer. The Estimates of Funding for Various Research, Condition,
and Disease Categories (RCDC) provides official NIH figures on research
spending by category. For fiscal year 2018, RCDC lists 200 grants and
projects that involve research with human fetal tissue.\37\ Please also
see the June 5, 2019, statement from the Department of Health and Human
Services about NIH-supported research using human fetal tissue.
---------------------------------------------------------------------------
\37\ https://report.nih.gov/categorical_spending.aspx.
---------------------------------------------------------------------------
Question. The research conducted by the NIH affords invaluable
knowledge and understanding of the infectious diseases we face today.
Indisputably, NIH funding is vital to improving healthcare and
protecting American lives. That being said, we must ensure that we hold
taxpayers' dollars with highest regard and direct our limited resources
to projects that not only better our country but reflect the will of
the people.
As revealed by the Select Panel on Infant Lives investigation,
Planned Parenthood officials have admittedly changed abortion
procedures to procure intact fetal body parts for sale. The fact that
an industry has been created around the sale of aborted baby parts is
deeply disturbing, and I firmly believe we must do all that we can to
ensure taxpayers' dollars are used responsibly and ethically when it
comes to federally funded research involving fetal tissue.
What steps has NIH taken to partner with hospitals to procure fetal
tissue that has been donated after a spontaneous abortion or
miscarriage as opposed to tissue that is acquired after an elective
abortion?
Answer. NIH funded a major effort through five tissue bank programs
to collect and examine tissue donated from women who had spontaneous
abortions or ectopic pregnancies. The results were published in the
Journal of the American Medical Association in 1995.\38\ From over
22,000 obstetric admissions, tissue from 1,250 spontaneous abortions
and 247 ectopic pregnancies was obtained. Most of the specimens
recovered consisted of maternal or extraembryonic tissue. Of the
embryonic collections, less than 1 percent would have been useful for
clinical use. 71 percent of embryonic samples were degenerated; 79
percent had bacterial contamination (despite use of aseptic collection
techniques); and 40 percent had chromosomal abnormalities.
---------------------------------------------------------------------------
\38\ https://jamanetwork.com/journals/jama/fullarticle/385456.
---------------------------------------------------------------------------
Question. Has NIH considered limiting its procurement of fetal
tissue obtained this way? If not, please explain why.
Answer. NIH-funded research summarized above has established that
fetal tissues from miscarriages (spontaneous abortions) and ectopic
pregnancies are not feasible sources for research. Please also see the
June 5, 2019, statement from the Department of Health and Human
Services about NIH-supported research using human fetal tissue.\39\
---------------------------------------------------------------------------
\39\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
department-of-health-and-human-services.html.
---------------------------------------------------------------------------
Question. Since President Obama's Executive Order 13505 ``Removing
Barriers to Responsible Scientific Research Involving Human Stem
Cells'' in March 2009, NIH has had wide access to human embryonic stem
cells. As you know, this EO revoked a previous EO from President Bush
that outlined ethical principles for stem cell research.
As you know, some may claim that because stem cells themselves are
not human embryos, there is no need to limit the amount available. But
because the cells come from human embryos, NIH has an ethical
obligation to value and honor the human life that contributed to such
cells.
While I have received some information on the types of research in
which NIH uses ``human embryonic stem cells (hESCs)'', I am unaware of
any validated, successful patient treatment from embryonic stem cells.
Additionally, as you know alternatives to embryonic stem cell
research exist. In 2012, the Nobel Prize in Physiology or Medicine was
awarded to two researchers for their discovery of induced pluripotent
stem (iPS) cells, which mimic the qualities of embryonic stem cells but
do not use embryos in any way. Similarly, NIH has had great success in
treating and curing more than 70 diseases using adult stems cells and
iPS cells. Despite this, it is my understanding that NIH continues to
expand its embryonic stem cell research to cell lines not already
included on the NIH Human Embryonic Stem Cell Registry.
How many new cell lines has NIH added to its Registry since EO
13505 was enacted?
Answer. Executive Order 13505 directed NIH to issue new guidance on
research with human stem cells, including human embryonic stem cells
(hESCs).\40\ NIH subsequently issued the NIH Guidelines for Human Stem
Cell Research (Guidelines) on July 7, 2009.\41\ The Guidelines
established strict new criteria for the NIH Director to determine the
eligibility of the use of specific hESC lines in NIH-funded research.
The NIH Director has approved 398 hESC lines for use in NIH-supported
research under this policy, including 10 of the 21 cell lines that were
also eligible for use under the policy of the prior administration. The
NIH Director has also determined that 70 hESC lines are not eligible
for use in NIH-supported research, primarily due to inadequacies in the
embryo donation consent process.
---------------------------------------------------------------------------
\40\ https://www.govinfo.gov/content/pkg/FR-2009-03-11/pdf/E9-
5441.pdf.
\41\ https://stemcells.nih.gov/policy/2009-guidelines.htm.
---------------------------------------------------------------------------
Question. Why has NIH chosen to add more cell lines to its registry
instead of using cells already on the registry?
Answer. Part of the stated purpose of the Executive Order was `` .
. . to expand NIH support for the exploration of human stem cell
research.'' So, NIH developed a new policy, which included stricter new
requirements regarding the embryo donation process. Under current
policy, hESCs can only be used by NIH funded researchers if the embryos
were created using IVF for reproductive purposes, no longer needed by
the parents, and the embryos were donated by those parents with
voluntary, written, informed consent. NIH also included new
requirements that certain information be given to the potential donors
during the consent process, such as what will happen to the embryos,
and how long they have to change their minds.
Some of the newer hESC lines have characteristics that are more
suitable for clinical use, including reduced exposure to animal
products and viruses. Some are also more flexible in their ability to
form different tissue types. There are more than 100 hESC lines
approved under the current policy that have mutations associated with
particular diseases, providing useful cell models for studying those
diseases.
Question. Why has NIH not used IPS cells for research instead of
using hESCs?
Answer. NIH funds a range of stem cell research, using induced
pluripotent stem cells (iPSCs) as well as hESCs. In fiscal year 2018,
NIH awarded $468 million for human iPSC research and $278 million for
hESC research. NIH is currently funding a significant amount of pre-
clinical research using iPSCs. For example, an investigator in the
National Eye Institute's intramural program is developing an iPSC-
derived cell therapy for age-related macular degeneration.\42\ There
are also other investigational cell therapies developed from human
induced pluripotent stem cells (hiPSCs) in clinical trials now (not
funded by NIH) for age-related macular degeneration, graft versus host
disease, and Parkinson's disease.
---------------------------------------------------------------------------
\42\ https://irp.nih.gov/pi/kapil-bharti.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Patty Murray
chief data strategist
Question. For the past 3 years, this committee has urged NIH to
focus on developments in data science as it relates to biomedical
research. What is possible to achieve by harnessing the vast amount of
data produced in science is still unknown. But what we do know, is with
proper leadership, vision, and tools, big data has the potential to
help scientists unlock infinite breakthroughs and discoveries in
biomedical research. At the direction of this committee, in May 2018
NIH released a strategic plan for data science, which includes
recommendations to advance data infrastructure and data stewardship in
support of the data ecosystem at NIH and improve NIH's expertise in
this space.
After a year of efforts to recruit for the new CDS position, NIH
still has not filled this role.
What is the status of the job search for the Chief Data Strategist?
Please include details on the recruitment, number of applicants and
interviews, significant next steps, and timeline for completion. Are
there specific obstacles to filling this role that NIH needs to
address?
Answer. The recruitment for the NIH Chief Data Strategist is
currently open for receiving applications, until filled. The
recruitment for this position opened on May 9, 2018. To date, NIH has
received 59 application packages which met the basic qualifications for
the position, held rating meetings, and conducted interviews. An
external search firm was secured to work in concert with the search
committee to seek and encourage highly qualified candidates to apply.
Over 20 ads were placed online with periodicals, data science
organizations, and diversity associations. Currently, a video is being
produced to highlight the data science activities at NIH, which will be
released to encourage candidates to apply to this position. The
recruitment timeline is currently open ended.
Data science is a burgeoning field of study, involving both private
sector and academic leaders. The NIH is hoping to fill this position
with an individual who has the knowledge and unique skill set needed to
accelerate NIH progress in data science and to expand collaborations
worldwide. As you note, it has been exceedingly challenging to attract
someone that would bring the unique combination of knowledge and skills
to the position. Federal salary limits are one limiting factor and the
constraints related to financial holdings that result from Federal
employment are another. The NIH is committed to filling this position
as soon as possible and is determined to fill the position with the
ideal candidate.
Question. Since the recruitment process is taking a considerable
amount of time, what is NIH doing during this interim period, prior to
hiring a CDS, to move the work forward?
Answer. Executive leadership of data science efforts at the NIH
continues to be provided by the Interim Associate Director for Data
Science, a position temporarily being filled by the Principal Deputy
Director, NIH. The Scientific Data Council, co-chaired by the Director,
National Institute of General Medical Sciences, and the Director,
National Institute of Biomedical Imaging and Bioengineering, is also
providing advice and oversight to ensure forward movement on trans-NIH
data science activities. Other executive staff, including the Directors
of the Center for Information Technology and the National Library of
Medicine have been playing key roles in moving forward critical data
science efforts. The Director of the NIGMS Division of Biomedical
Technology, Bioinformatics, and Computational Biosciences is providing
essential leadership for, and helping to fully operationalize, the
Office of Data Science Strategy (ODSS). Other Office of the Director
staff are also playing key roles for activities that are being led and
funded by ODSS. While we have not yet been able to fill the Chief Data
Strategist position, we have made significant progress in implementing
components of the NIH Strategic Plan for Data Science.
Question. Given the challenges of bringing someone with the
appropriate skills, vision and background into the CDS position, what
alternatives is NIH exploring?
Answer. As noted above, NIH contracted with an external search firm
to work closely with the search committee to seek and encourage highly
qualified candidates to apply. Over 20 ads were placed online with
periodicals, data science organizations, and diversity associations. A
video is being produced to highlight the data science activities at NIH
which will be released to encourage candidates to apply to this
position. In the meantime, NIH leadership is considering whether other
NIH employees could fill this vacancy on a temporary basis.
Question. Has NIH consulted with organizations that face similar
challenges, such as DoD, NASA, and universities attempting to solve
some of the same cutting edge data challenges?
Answer. Yes. Through both formal interagency processes and informal
leadership and staff level conversations, NIH consults and shares
information with other Federal research agencies facing similar
challenges. As part of the search for the CDS, we have also engaged in
extensive outreach, including to other Federal agencies, e.g.,
Department of Energy and the National Science Foundation.
We are continuing efforts to find the best candidate for this
critical position at NIH. Some important new approaches we will be
taking are listed below:
--NIH is about to launch a social media and marketing campaign for
the CDS position--possibly as early as the week of May 28. You
may see Twitter and Facebook posts from NIH, Dr. Collins, the
CDS Search Committee co-chairs, and various other NIH-related
handles. NIH is also asking other Federal government agencies
to help amplify our posts. An executive search firm will be
helping NIH cross-promote on LinkedIn.
--NIH has produced a final cut of a 5-minute video about the
position. View on YouTube here: https://youtu.be/92arhggy4xI.
--Dr. Collins will use his blog to highlight the important of this
position to NIH's future with an embedded version of the video.
--An easier-to-use URL for the position is now available:
www.nih.gov/CDS http://www.nih.gov/CDS.
--NIH will make additional efforts to identify and capitalize on NIH
leadership that have personal connections with Silicon Valley
and other tech company executives/VIPs who may have good
candidates to recommend.
--A slide will be provided for use by NIH leadership in any
presentations they are making to the tech community.
--A 30 second teaser video, based on the YouTube video linked above,
will be released as part of a social media marketing campaign
to attract candidates.
Question. Last year, the Committee assumed that implementation of
certain components of the strategic plan--including developing
performance measures and specific milestones for the plan's
objectives--was delayed due to the open job search. What, if any, steps
in the strategic plan have been implemented to date?
Answer. The NIH has moved forward in implementing multiple
components of the NIH Strategic Plan for Data Science. Currently, a
team of NIH employees detailed to the ODSS is coordinating the efforts
of nearly thirty implementation working groups with members
representing nearly all NIH Institutes and Centers. ODSS has also
established a Technical Implementation Working Group composed of high-
level data science experts across NIH to advise the Office on technical
matters related to implementation tactics. A non-exhaustive summary of
current activities aligned with each goal of the strategic plan is
provided below:
Goal 1: Support a highly efficient and effective biomedical
research data infrastructure.
--ODSS executed a contract with BioTeam, Inc. to develop a basic
needs requirement document that would directly inform the
infrastructure development of a NIH-wide data ecosystem that
meets FAIR principles. The contractor is currently in the
process of collecting data ecosystem use cases and conducting a
gap analysis across high-profile NIH data systems. A final
report is anticipated in September 2019.
--ODSS is providing technical assistance to the NIH Office of Science
Policy (OSP) in the review of current policies regarding Data
Access Committees to streamline and increase the efficiency of
review.
--The National Center for Biotechnology Information and CIT have
developed an initial strategy for a trans-NIH approach to user
authentication and authorization for access to data sets. This
technical solution will be developed into a testable prototype
in the next few months.
--The STRIDES Initiative, a NIH partnership with industry-leading
cloud service providers (currently, Google and Amazon) to
provide discounted cloud storage and compute access to
biomedical researchers, continues to migrate high-value data
sets to cloud platforms. ODSS is providing oversight of this
CIT-managed initiative and has engaged nearly 40 data programs
in both the intra- and extra-mural communities. NIH is
developing the policies and procedures for making this
innovative partnership available to all NIH-funded biomedical
researchers in order to accelerate scientific discoveries
leading to new health technologies.
Goal 2: Promote modernization of the data-resources ecosystem.
--A strategic plan implementation team co-led by NLM and NIGMS
developed new funding opportunity announcements (FOAs) that
will address the objective of separating support for databases
and knowledgebases and sets forth appropriate resource criteria
and review criteria that must be met in order to receive NIH
support. These FOAs are currently under review with an
anticipated release date this summer.
--This April, NIH held a workshop to share criteria for
trustworthiness of data repositories and to educate biomedical
data managers on the CoreTrustSeal certification requirements.
Information from the workshop will be used to promote
sustainable and trustworthy data infrastructures in the
biomedical arena. In a related effort, NLM conducted a
comprehensive analysis of criteria for open-access data sharing
repositories that receive NIHsupport and will soon publish a
public request for information to solicit additional input on
draft criteria.
--The NIH Scientific Data Council is reviewing how NIH could
potentially integrate existing clinical data elements with the
industry-adopted fast healthcare interoperability resources
(FHIR) specification to enable the exchange of healthcare,
clinical and basic research data across different systems.
Goal 3: Support the development and dissemination of advanced data
management, analytics, and visualization tools.
--ODSS is engaged in planning a workshop to bring systems integration
specialists from the private sector so that NIH data scientists
can learn the latest approaches to the optimization of data
analysis tools and algorithms.
--NSF and NIH/ODSS will hold a workshop in June to discuss
opportunities for joint funding of data science research
programs, with a particular emphasis on AI/ML approaches to
solving complex data analysis problems in biology and medicine.
--ODSS executed a contract with FigShare, providing NIH-funded
researchers with access to online open access repository where
researchers can preserve and share their research outputs,
including figures, datasets, images, and videos.
Goal 4: Enhance workforce development for biomedical data science.
--Please refer to NIH's description of efforts in data science
workforce development addressed in the response to a specific
question for the record on this topic.
Goal 5: Enact appropriate policies to promote stewardship and
sustainability.
--The NIH OSP recently completed its analysis of public comments on
proposed provisions for a draft data management and sharing
policy. OSP is in the process of incorporating the public
feedback and will release a draft policy statement for further
public consultation.
Question. The Committee included $30 million to support the Chief
Data Strategist's work in fiscal year 2019. What is the status of NIH's
plan for this funding?
Answer. The NIH has engaged in a multi-step planning process to
identify the most pressing trans-NIH needs for the data science funding
provided by Congress. The $30 million is being used to advance the
trans-NIH data ecosystem--that is, we are working to make currently
siloed data storage and workspaces connect (interoperable) by
establishing standards, building infrastructure and tools to allow
different data repositories to talk to each other, and defining common
data elements and standards.
dpcpsi/office of strategic coordination
Question. The Data Commons Pilot Phase was initiated under the New
Models of Data Stewardship program, implemented in support of the
Strategic Plan for Data Science. This project was supposed to run
through fiscal year 2020 and was tasked with developing a four-year
roadmap for the data commons. What is the status of this roadmap, how
is NIH implementing the associated recommendations, and what are the
next steps for this initiative?
Answer. The NIH Data Commons Pilot, part of the Common Fund's New
Models of Data Stewardship program, aimed to accelerate new biomedical
discoveries by developing and testing a cloud-based platform where
investigators could store, share, access, and interact with digital
objects (data, software, etc.) generated from biomedical and behavioral
research. By connecting the digital objects and making them accessible,
the Data Commons was intended to foster novel scientific research that
wasn't possible before, including hypothesis generation, discovery, and
validation. The program supported the NIH Strategic Plan for Data
Science \43\ goal to develop new, cutting-edge methods for storing,
sharing, and analyzing NIH supported datasets in the cloud.
---------------------------------------------------------------------------
\43\ https://datascience.nih.gov/strategicplan.
---------------------------------------------------------------------------
From 2017-2018, researchers funded as part of the NIH Data Commons
Pilot Phase Consortium (DCPPC) tested the best ways to build and
implement the cloud-based platform described above. They iteratively
experimented with a series of key capabilities needed for the Commons
to operate and meet standards for being FAIR--findable, accessible,
interoperable, and reusable. Three different and high-value test case
data sets helped in setting policies, processes, and architecture for
the Data Commons Pilot Phase.
Development of a roadmap for modernizing the biomedical data
science ecosystem requires trans-NIH coordination, most appropriately
managed by the NIH Office of Data Science Strategy (ODSS). Therefore,
ODSS is developing a broad, trans-NIH data ecosystem strategy informed
by the tools and best practices developed by the DCPPC. The Common Fund
will continue to test, evaluate, and refine a subset of deliverables
from the Data Commons Pilot Phase, working with Common Fund programs to
establish a cloud-based data ecosystem for Common Fund datasets.
dpcpsi/office of data science strategy
Question. Research organizations are exploring the best ways to
create research data commons. Private sector communities of companies
and extramural research institutions, like Sage Bionetworks, Penn
State, and Google's datacommons.org have demonstrated success. Even
other Federal agencies have successfully established data commons, such
as the National Science Foundation big data innovation hubs, and are
further along than NIH. Furthermore, we must ensure NIH is also
learning from less successful attempts at driving data infrastructure,
such as caBIG, which saw little traction in the community and was
widely criticized. As good stewards of taxpayer investments, what is
NIH doing to avoid ``reinventing the wheel'' and how is NIH planning to
leverage data commons work already being done extramurally?
Answer. NIH appreciates the opportunity to highlight how we are
building upon the advances in academia and industry to create a highly
integrated biomedical research data ecosystem. A principle stumbling
block across data science is the compartmentalization of data--from
biomedical research data, disease specific data, health records and
data resulting from clinical trials. These data silos impede discovery
of commonalities across diseases and inhibit a cross-disciplinary
understanding that will rapidly accelerate innovation in the biomedical
research enterprise. Our goal at NIH is to leverage data and
information from different studies and across diseases to empower
investigators to ask new questions and make new discoveries to improve
human health.
To do so, NIH is investing in many data commons efforts, including
NHGRI ANVIL, NCI Cancer Research Data Commons, All-of-Us Research
Program, NIMH Data Archive, NHLBI Data STAGE and others.\44\ We have
recently completed a NIH Data Commons Pilot study and we have
undertaken a comprehensive analysis of this, and the other commons
efforts listed above, to learn from our past and current efforts and to
determine successful approaches with existing capabilities.
---------------------------------------------------------------------------
\44\ NHGRI AnVIL is designed to be an interoperable resource for
the genomics community to co-locate data, storage and computing with
commonly used services for analyzing and sharing data.
NCI Cancer Research Data Commons is a virtual, expandable
infrastructure to provide secure access to cancer-specific data to
allow researchers to analyze, share and store their work, in a cloud
environment.
NIMH Data Archive is a collaborative resource that contains human
subjects research data for Autism research
NHLBI Data STAGE is a digital environment that allows for access to
NHLBI datasets and innovative data analysis capabilities, in a cloud
environment.
All-of-Us Research Program provides a cloud-environment to gather
and serve data from one million or more people living in the United
States.
---------------------------------------------------------------------------
NIH is also working with leading industry partners, including
Google and Amazon, and academic collaborators, to leverage those
experience, expertise and technologies as we work to connect high-value
NIH data systems. An early example of this is the cross-NIH effort to
create an industry-standard system that will allow any NIH researcher a
single-entry point to NIH data resources, with the appropriate
security-enabled data access.
In addition, the National Center for Advancing Translational
Sciences' (NCATS) Biomedical Data Translator program is building an
informatics platform that aims to bridge the current symptom?based
diagnosis of disease with research?based molecular and cellular
characterizations through interrogation of relationships across the
full spectrum of data types (e.g., disease names, clinical signs and
symptoms, to organ and cell pathology, genomics, and drug effects). The
Translator is not a database but rather is focused on identifying data
integration and inclusion barriers and exploring inferential or
predictive models that would provide new insights into biology, health,
and disease. The Translator will find and connect existing data,
provide previously unknown insights into diseases and possible
treatments, and make inferences and predictions even when data are
missing to translate basic data science to clinical and public health
practices.
Together these, and other efforts articulated in the NIH's
Strategic Plan for Data Science, aim to maximize the value of the data
generated through NIH-funded efforts to enable biomedical discovery and
innovation. Doing so is critical for keeping the United States at the
forefront of biomedical research and ensuring continued advances toward
improving the Nation's health.
Question. Beyond the efforts in NIGMS, what is the NIH doing to
encourage, support and incorporate computational science training in
other scientific fields beyond those like genomics and neuroscience
which have already embraced it?
Answer. NIH is committed to training the next generation of
researchers across biomedical related disciplines, including computer
science. Twelve of the agency's Institutes, Centers, and Offices (ICOs)
support a funding opportunity, the Mentored Quantitative Research
Career Development Award (K25), to attract investigators whose
quantitative science and engineering research has thus far not been
focused on questions of health and disease. This funding opportunity
supports professionals with quantitative (e.g., mathematics,
statistics, economics, computer science, imaging science, informatics,
physics, chemistry) and engineering backgrounds to integrate their
expertise with NIH-relevant research. Another cross-NIH effort,
Predoctoral Training in Advanced Data Analytics for Behavioral and
Social Sciences Research--Institutional Research Training Program
(T32), is funding training opportunities for predoctoral students in
data analytics for behavioral and social science research and is
supported by a number of ICOs. Other trans-NIH funding opportunities
are being planned to broaden the expertise of the extramural biomedical
community and will be released in the coming months. Additionally, the
National Library of Medicine recruits data scientists to work in their
institute through several coordinated postdoctoral training programs,
and has a joint program with the National Institute of Dental and
Craniofacial Research to recruit computer scientists to postdoctoral
studies in the dental field. Other ICOs across NIH recruit
computational experts to work in their intramural research programs
based on the lab's specific needs.
Training programs for NIH staff and extramural researchers who are
putting data into Science and Technology Research Infrastructure for
Discovery, Experimentation, and Sustainability Initiative are currently
being offered. These trainings target general use of the cloud
platforms as well as generic [mock/dummy] tool and dataset use in cloud
environments.
NIH has also initiated several fellowships to expand the expertise
of the NIH internal workforce, by bringing computationally-savvy
individuals to work in NIH offices. For example, through Coding it
Forward's Civic Digital Fellowship and the NIH Office of Intramural
Training and Education Graduate Data Science Summer Program, ODSS will
bring 23 data scientists to NIH campus this summer to be placed in
offices and laboratories throughout the agency. Other programs led by
NIH to bring computational experts into the Federal workforce include
the Emerging Leaders in Data Science Fellowship, led by NIAID, and the
Big Data Scientist Training Enhancement Program, co-led by NCI and the
Department of Veterans Affairs.
rare cancers
Question. At least 95 percent of 400 known forms of cancer meet the
American Cancer Society criteria of affecting fewer than 6 Americans
per 100,000 per year, yet in 2018 nearly 80 percent of cancer patients
with no approved targeted therapeutic for their cancer have a rare
cancer. Many of these cancer patients are faced with decades-old
treatment protocols that include harsh chemotherapies which are
frequently ineffective for their cancers. What are NIH, NCI and NCATS
doing to develop more therapeutics for these neglected rare cancers?
Almost 1 in 3 new cancer diagnoses is for a rare cancer. However,
rare cancers suffer from critical gaps in funding, available data, and
basic and translational science. In 2017, over 148 forms of rare cancer
received no direct funding from NIH, and that gap in spending is
associated with a lack of FDA-approved targeted therapies available for
those cancers. Simultaneously, just 34 out of 380 forms of rare cancer
received almost 40 percent of NIH funding that was directed to rare
cancers. What is being doing to encourage greater support for research
into rare cancers?
I understand 95 percent of all cancers are rare forms, and
increased use of molecular subtyping can lead to more accurate
diagnoses of those precise forms. But that is only if this subtyping is
done. I understand molecular diagnostics are seldom used for the
majority of patients and data on cancer subtypes is rarely shared among
researchers and physicians. What can be done to improve molecular
analysis for patients, and to permit patients to anonymously and
publicly share their data with researchers and drug developers?
A key to understanding and developing targeted cancer treatments is
the ability to research tumor cell lines, yet cells lines for rare
cancers are frequently difficult to obtain, especially for smaller
companies, due to high costs or licensing restrictions. When they are
available, they sometimes do not share the genetic profiles of the
cancers they are meant to represent. Why is that? How can we change
that to accelerate research to save lives in the near-term?
Treatment for pediatric cancers carries a tremendous burden for
survivors throughout their childhood and adult lives, frequently due to
the use of caustic chemotherapy agents. There is only one currently
available targeted therapy that is specifically approved for a
childhood cancer, neuroblastoma. What is being done to ensure that
childhood cancers receive appropriate levels of funding for
translational research that turns basic science into new therapies?
Over 550,000 Americans were newly diagnosed with a rare cancer in
2018, but SBIRs, which are a major source of translational funds to
bridge the drug development 'valley of death', primarily fund common
cancers. In fact, in the 5-year span between 2013 and 2017, 262 forms
of cancer, all rare, did not receive any directed funding--that's over
65 percent of all types of rare cancer. What is being done to ensure
that SBIR funding is addressing the critical translational gap for
these neglected rare cancer patients?
Over half a million Americans were newly diagnosed with a rare
cancer in 2018. For over 100 of those cancers, there are no available
datasets in the most significant microarray repository in the world,
GEO. Unfortunately for those patients whose cancers are not
represented, they have an almost 7-fold decreased likelihood of having
a targeted therapy. What is being doing to ensure that all forms of
cancer have significant dataset presence in publicly available data
repositories?
Answer. Rare cancers all qualify as rare diseases, which are
diseases or conditions affecting fewer than 200,000 people in the U.S.
The National Center for Advancing Translational Sciences (NCATS) has
several programs and initiatives focusing on rare diseases, including
rare cancers. Specifically, the Office of Rare Diseases Research (ORDR)
is dedicated exclusively to accelerating treatments and research to
benefit rare disease patients.
Advancing research on rare cancers is an important focus across the
NCI portfolio as well. As our understanding of cancer expands, we now
know it is not one disease, but hundreds, if not thousands, of cancer
types and subtypes--a collection of rare diseases. A quarter of all
cancer deaths each year are due to rare cancers. Although new
treatments are always being developed, finding new effective treatments
for rare cancers is challenging for many reasons. Additionally, this
translational and clinical research is only possible due to NCI's
sustained investment in basic science that advances understanding and
progress for all cancer types, including rare cancers.
Question. What are NIH, NCI and NCATS doing to develop therapeutics
for these neglected rare cancers?
Answer. Several NCI-supported research efforts aim to advance and
accelerate the development of targeted cancer therapies for rare cancer
types and subtypes diagnosed in children and adults. The following
narrative describes some of the major NCI initiatives that may benefit
rare cancer patients, but it is not an exhaustive list of the
Institute's investments in rare cancer research.
The cancer research community continues to recognize that cancer is
made up of a collection of hundreds, if not thousands, of subtypes
defined by these characteristics. NCI-supported research like The
Cancer Genome Atlas \45\ and the Pediatric TARGET (Therapeutically
Applicable Research to Generate Effective Treatments) Initiative,\46\
as well as the Pediatric Cancer Genome Project led by Washington
University and St. Jude Children's Research Hospital,\47\ have been
critical to advancing this field. As a result of these efforts and
other relevant research, ``cancer'' is increasingly recognized as a
collection of rare cancer subtypes, each of which will likely require a
somewhat different treatment. NCI's ongoing efforts include research to
support the development and evaluation of precision approaches to
cancer therapy--including targeted chemotherapy and immunotherapy, and
combination therapy approaches based on the molecular profile of the
cancer.
---------------------------------------------------------------------------
\45\ https://cancergenome.nih.gov/.
\46\ https://ocg.cancer.gov/programs/target.
\47\ https://www.stjude.org/research/pediatric-cancer-genome-
project.html.
---------------------------------------------------------------------------
As part of the Cancer Moonshot, NCI launched the Rare Tumor Patient
Engagement Network in fiscal year 2018, leveraging the unique resources
of the NCI intramural research program and the NIH Clinical Center to
bring together national and international investigators, patients,
advocacy groups, and industry to comprehensively study rare tumors and
provide exceptional patient care. Under the umbrella of this effort,
NCI has also launched the Moonshot Pediatric, Adolescent, and Young
Adult Rare Tumors (MyPART) Network, a collaboration of scientists,
patients, family members, advocates and healthcare providers to find
treatments for rare cancers.\48\ The MyPART Network will collect
samples like blood, saliva, and biopsy tissue from people with rare
tumors to study how rare tumors grow, share data from rare cancer
samples with other scientists, build new ways of testing new
treatments, and design new clinical trials for rare cancers.\49\
Another component of this rare tumors initiative, the NCI Comprehensive
Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) within the
intramural program aims to advance the understanding of rare adult
central nervous system (CNS) cancers by establishing and fostering
patient-advocacy-provider partnerships and networks to improve
approaches to care and treatment. Although all primary adult CNS tumors
can be considered rare, NCI-CONNECT is starting with 12 types, each
with less than 2,000 patients diagnosed a year. NCI-CONNECT intends to
address these challenges and unmet needs by connecting patients,
providers, researchers and community organizations to work in
partnership.\50\
---------------------------------------------------------------------------
\48\ https://ccr.cancer.gov/research/cancer-moonshot.
\49\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor/about/
what-is-mypart.
\50\ https://ccr.cancer.gov/neuro-oncology-branch/connect.
---------------------------------------------------------------------------
The NCI-MATCH Trial \51\ is an important research program for rare
cancers for which there is not a standard of care or cancers that no
longer respond to standard treatment. This nationwide trial, which has
enrolled patients in all 50 States, analyzes patients' tumors to
determine whether they contain gene abnormalities for which a targeted
drug exists and then assigns patients to treatment based on the
abnormality. Using this approach, the NCI-MATCH trial holds promise for
improved treatment options for both common and rare cancers. The trial
originally had ``set aside'' 25 percent of screening accrual to be for
rare cancers, to ensure that more common cancers were not over-
represented. Ultimately 62.5 percent of the over 6,000 patients
screened for MATCH represented rare cancers. However, even with 6,000
patients screened, some trial arms did not complete accrual due to the
low frequency of a particular variant in the population. Thus, patients
continue to be enrolled in these trial arms through the Rare Variants
Initiative. Launched in May 2017, the Rare Variants Initiative casts a
wider net for patients through collaborations with additional
commercial and academic partners that will help find patients with
uncommon genetic variants and let their doctors know they may be
eligible for the MATCH trial.
---------------------------------------------------------------------------
\51\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
nci-supported/nci-match.
---------------------------------------------------------------------------
The mission of the NCI Experimental Therapeutics (NExT) Program
\52\ is to advance clinical practice and bring improved therapies to
patients with cancer by supporting the most promising new drug
discovery and development projects. For those institutions
collaborating with NCI, NCI may leverage its scientific expertise and
various contract and grant resources toward the implementation and
development of submitted projects. The NCI will partner with successful
applicants to facilitate the milestone-driven progression of new
anticancer drugs (small molecules, biologics) and imaging agents
towards clinical evaluation and registration.
---------------------------------------------------------------------------
\52\ https://next.cancer.gov/entryToPipeline/default.htm.
---------------------------------------------------------------------------
Additionally, NCATS supports the Tissue Chip for Drug Screening
Program, which is an innovative program that enables the development of
microphysiologic systems to develop human tissues on bioengineered
chips. This program seeks to better understand human disease, model
human organs and organ systems, and potentially serve as toxicology and
drug screening systems. Many rare disease indications have been
included in the tissue chip program, including tuberous sclerosis,
which is a rare disease that leads to benign tumor growth in the brain.
This program is planning to support development of chips that can be
used to inform potential clinical trials on rare diseases and, in
conjunction with NCI, rare cancers will be included as part of the
research focus.
NCATS also supports the Therapeutics for Rare and Neglected
Diseases (TRND) and the Bridging Interventional Development Gaps
(BrIDGs) programs. TRND supports pre-clinical development of
therapeutic candidates intended to treat rare or neglected disorders
with the goal of enabling an Investigational New Drug application
(IND). TRND works in collaboration with external partners, such as
academia and industry on these projects, and TRND provides scientific
expertise and resources to further therapeutic development. Researchers
working on rare cancers are eligible for assistance from this program.
Similarly, BrIDGs assists researchers in advancing promising
therapeutic agents thought late-stage pre-clinical development toward
an IND and clinical testing. Currently, these programs are working on
several rare cancer-related projects, including work on pancreatic
cancer and core binding factor (CBF) leukemia.
Notable NCATS programs led through the ORDR relevant to rare
cancers include:
--The Rare Diseases Clinical Research Network (RDCRN) \53\ provides
cooperative awards to multi-center multi-disciplinary consortia
who study three or more related rare diseases at a time. This
program has supported research into >250 rare diseases since
its inception, including some rare cancer-related diseases and
conditions. Applications for new consortia members are
currently being considered and awards will be announced around
June-July 2019. Some of the applications being considered
include rare cancers and cancer-related conditions that may be
funded in collaboration with NCI.
---------------------------------------------------------------------------
\53\ https://ncats.nih.gov/rdcrn.
---------------------------------------------------------------------------
--The Bench-to-bedside (B2B) grant program \54\ is run by the NIH
Clinical Center (CC), and NCATS ORDR supports four B2B awards
each year for rare disease indications. These grants are for
intramural/extramural partnerships leveraging the CC and other
resources to facilitate translating bench research toward
clinical trials. Several rare cancer-related B2B grants have
been supported through this program over the past 15 years.
Some examples of rare cancer and cancer-related B2B awards
include, but are not limited to: T-cell adoptive therapy for
viral infection after stem cell transplantation and CAR-
modified CD8+ memory stem cells targeting B-cell malignancies,
among others.
---------------------------------------------------------------------------
\54\ https://clinicalcenter.nih.gov/ccc/btb/.
---------------------------------------------------------------------------
--The Toolkit for Patient-focused Therapies Development (``Toolkit'')
\55\ and the Rare Diseases Registry program (RaDaR) \56\ assist
patients and patient groups, who play a large role in
therapeutics development and research for rare diseases,
including rare cancers. Toolkit and RaDaR provide advice,
tools, templates and best practices for initiating and
furthering rare disease research programs and registries,
respectively. Toolkit and RaDaR are web-based freely accessible
resources that anyone can access and use.
---------------------------------------------------------------------------
\55\ https://rarediseases.info.nih.gov/toolkit.
\56\ https://registries.ncats.nih.gov/.
---------------------------------------------------------------------------
--The Scientific Conferences (R13 and U13) Grant program \57\
provides small grants to help co-fund scientific conferences
and meetings. Priority areas for NCATS include translational
sciences and rare diseases, including rare cancers. In the past
several years, grants have included conferences on rare cancers
and cancer-related indications, including, but not limited to,
cholangiocarcinoma, cancer vaccines, RASopathies, and cancer
immunotherapy, among others.
---------------------------------------------------------------------------
\57\ https://grants.nih.gov/grants/funding/r13/index.htm.
---------------------------------------------------------------------------
Question. What is being doing to encourage greater support for
research into rare cancers?
Answer. The NIH and the NCI rely heavily on scientific peer review,
in which highly trained outside scientists initially review
investigator-initiated research proposals and score them based on
factors such as scientific merit, potential impact, likelihood of
success, and disease burden. Thereafter, the National Cancer Advisory
Board conducts a review of the research proposals. NCI does not
establish predetermined targets for a specific disease area or research
category, and does not set preestablished funding levels for cancer
types or specific areas of cancer research. It is important to note
that NCI and NIH do not consider disease burden to be limited to how
many people are diagnosed with a disease or condition, but rather uses
a broader lens to capture the impact of a health condition as measured
by mortality, morbidity, financial cost, and other indicators.
Accordingly, NIH's Institutes and Centers support special initiatives
based on public health need, including burden of disease. Comprehensive
portfolio analysis and programmatic evaluation are also critical to
these programmatic decisions and development of special initiatives.
Examples span common and rare cancers, such as NCI's RAS Initiative,
which focuses on molecular alterations in the RAS family of genes and
pathways, responsible for driving the development and progression of
several common and rare cancers. Other examples include the Cancer
Moonshot, which is supporting research relevant across cancer types and
scientific areas, and NCI's proposed Childhood Cancer Data Initiative.
In addition, the Institute strives to balance strategic efforts to
address public health needs with its basic scientific research
portfolio. Basic research, which represents approximately half of the
NCI research portfolio, is vital to achieve progress in the cancer
types for which little or no progress has been made. Decades of basic
research investments from NCI and NIH have demonstrated the value of
basic research as a foundation for clinical advances, even though the
basic research may lack a direct initial connection to a specific
disease, the serendipitous discoveries of basic research illuminate
pathways for future clinical breakthroughs.
Question. Molecular diagnostics are seldom used for the majority of
patients and data on cancer subtypes is rarely shared among researchers
and physicians. What can be done to improve molecular analysis for
patients, and to permit patients to anonymously and publicly share
their data with researchers and drug developers?
Answer. Detailed molecular characterization of tumors has
demonstrated the heterogeneity of cancer and can identify genetic
alterations that may allow for the selection of targeted therapies for
patients based on the unique profile of a patient's tumor. This is the
basis for the NCI-MATCH trial mentioned above. However, it is important
to point out that targeted therapies currently only exist for a small
number of known genetic alterations.
Although comprehensive genomic profiling is technically feasible,
its current application in clinical practice is fragmented and there
are barriers to wide-spread profiling. These barriers include cost,
lack of standardized genomic profiling panels and tumor collection,
insufficient evidence of broad-based clinical utility, and lack of
infrastructure to harmonize and share data across the clinical and
research community.
The NCI is addressing several of these barriers. Precision medicine
clinical trials like NCI-MATCH and others seek to provide the evidence
of clinical utility of treating a patient based on a unique
characteristic of the patient's tumor regardless of the type of tumor.
In addition, other NCI research supported through the Cancer Moonshot's
direct patient engagement efforts,\58\ including the Rare Tumor Patient
Engagement Networks mentioned above, will support molecular
characterization of patients' tumors, directly engage patients to
participate in clinical trials, and share tumor profiling data with the
research community and the individual patient participants through a
secure linked network of databases.
---------------------------------------------------------------------------
\58\ https://www.cancer.gov/research/key-initiatives/moonshot-
cancer-initiative/implementation/patient-engagement.
---------------------------------------------------------------------------
The NCI has established the Cancer Research Data Commons as a part
of a larger National Cancer Data Ecosystem to support precision
medicine. The Data Commons will provide an information platform to
support the integration of genetic information about patients and their
tumors with data on how the tumors respond to therapy. The Data Commons
will also incorporate additional data such as imaging and clinical data
from patients to identify approaches to cancer care that will improve
patient outcomes. Other NCI efforts include the development of a cancer
data aggregator to link various data types across the Data Commons and
ultimately allow for analysis of multimodal data sets; and an encrypted
unique patient identifier to link patient level data while protecting
personally identifiable information. The former is critically important
to address patient privacy issues that exist with publicly sharing
their data.
Cost is an important issue outside of the scope of the NCI mission.
However, NCI notes that in March 2018 CMS took an important step in
addressing this barrier by finalizing a National Coverage Determination
that covers diagnostic laboratory tests using Next Generation
Sequencing for patients with advanced cancer.\59\
---------------------------------------------------------------------------
\59\ https://www.cms.gov/newsroom/press-releases/cms-finalizes-
coverage-next-generation-
sequencing-tests-ensuring-enhanced-access-cancer-patients.
---------------------------------------------------------------------------
Question. A key to understanding and developing targeted cancer
treatments is the ability to research tumor cell lines, yet cells lines
for rare cancers are frequently difficult to obtain, especially for
smaller companies, due to high costs or licensing restrictions. When
they are available, they sometimes do not share the genetic profiles of
the cancers they are meant to represent. Why is that? How can we change
that to accelerate research to save lives in the near-term?
Answer. As a public sponsor of biomedical research, NIH, including
the NCI, is committed to supporting national and international efforts
that encourage the sharing and dissemination of important research
resources. NIH also recognizes the need to support reasonable incentive
structures that facilitate commercial development or translation of
basic research findings. Restricted availability of unique research
resources, upon which further studies depend, can impede the advance of
research. Conversely, sharing biomaterials, reagents and data in a
timely manner has been an essential element to stimulate rapid research
progress on many model organisms for biomedical research. The NIH is
interested in continuing to ensure that the research resources
developed with NIH funding are made readily available in a timely
fashion to the research community for further research, development,
and application, which will further the research enterprise and
accelerate the development of products and knowledge of benefit to the
public.
With regard to rare cancers specifically, low incidence rates of
rare cancers mean both patients and researchers face unique challenges.
To address these concerns, NCI supports development of several research
resources and makes them available to the extramural research community
for use in investigator-initiated research projects and NCI-supported
programs. Such resources include the Human Cancer Models Initiative
(HCMI) \60\ and the NCI Patient-Derived Models Repository (PDMR).\61\
Many of NCI's resources are catalogued on the Resources for
Researchers\62\ website which provides information on how to obtain the
resources.
---------------------------------------------------------------------------
\60\ https://ocg.cancer.gov/programs/HCMI.
\61\ https://pdmr.cancer.gov/, https://www.cancer.gov/news-events/
cancer-currents-blog/2018/nci-pdmr-cancer-research-models.
\62\ https://www.cancer.gov/research/resources.
---------------------------------------------------------------------------
The HCMI is a collaborative international consortium that is
generating 1,000 novel, next-generation, cancer models from patient
tumors that are clinically and molecularly characterized. HCMI-
developed models and related genomic and clinical data are available as
a community resource without excessive intellectual property (IP)
constraints. The NCI is contributing to the initiative by supporting
four Cancer Model Development Centers (CMDCs) at the Broad Institute,
Cold Spring Harbor Laboratory, Weill Cornell Medicine, and Stanford
University. These cancer models will serve as valuable resource for
translational cancer research and will contribute to developing
innovative therapeutic strategies, identifying novel diagnostic
markers, and individualizing patient treatment plans. In addition, the
initiative will make resources such as protocols used for model
development, SOPs, and other model-associated support available to aid
the research community to generate additional models. There are
currently 19 models available through the HCMI searchable catalog.\63\
---------------------------------------------------------------------------
\63\ https://hcmi-searchable-catalog.nci.nih.gov.
---------------------------------------------------------------------------
The PDMR is mainatained by the Frederick National Laboratory for
Cancer Research and is a national repository of patient-derived
xenografts developed from patients with solid tumors. These models are
clinically-annotated with molecular information available in an easily
accessible database for the extramural community. Since the launch of
the PDMR in early 2017, 166 public models have been developed from 163
unique patients, and new models continue to be added for cancer types
already existing in the repository. Several new cancer types are now
available in the PDMR collection, including some rare cancers. These
new cancer models are of high value to the research community and
include: several gynecologic cancers (ovarian, vaginal, carcinosarcoma,
and cervical), small cell lung cancer (a subtype of lung cancer that is
a rare disease), Hurthle cell neoplasm (a rare and often aggressive
form of thyroid cancer), Osteosarcomas, chondrosarcoma, squamous cell
skin carcinoma, Merkel cell carcinoma (a rare and aggressive form of
skin cancer), mesothelioma (a rare type of lung cancer). The primary
goal of this repository is to make a publicly available archive and
repository of tumor samples and models that are fully characterized
from a molecular and clinical perspective, and that are easily
accessible to the extramural community at a very modest cost.
NCI also supports pediatric cancer cell lines and models to address
key challenges in the development of new therapies for children with
cancer (all childhood cancers are considered rare diseases). NCI's
Preclinical Testing Consortium (PPTC) \64\ develops reliable
preclinical testing data for pediatric drug candidates that can be used
to inform new agent prioritization decisions. The PPTC consists of a
Coordinating Center and five Research Programs that perform in vivo
testing of pediatric anticancer drug candidates for a particular cancer
(sarcoma and renal, neuroblastoma, osteosarcoma, leukemia, and brain
tumors). The PPTC collaborates with pharmaceutical companies and
academic drug developers to systematically test candidate agents
against well-credentialed panels of genomically characterized childhood
cancer models to identify those investigational agents most likely to
have clinical activity against childhood cancers. For example, in 2011,
the PPTC developed a model for a subtype of pediatric low-grade
astrocytoma (PLGA, a type of brain tumor) with a mutation in a gene
called BRAF and identified a targeted therapy, selumetinib, for
additional research. Building upon these findings, the PBTC conducted a
Phase 1 trial of selumetinib.\65\ In this trial, children with BRAF-
mutated PLGAs responded to treatment by showing tumor shrinkage. Based
on these promising findings, the trial is now in a Phase 2 expansion
with results from several cohorts reported in 2017 showing that
selumetinib is active for patients with two subtypes of BRAF-mutated
PLGAs.\66\
---------------------------------------------------------------------------
\64\ http://www.ncipptc.org/.
\65\ https://clinicaltrials.gov/ct2/show/NCT01089101.
\66\ http://ascopubs.org/doi/abs/10.1200/
JCO.2017.35.15_suppl.10504.
---------------------------------------------------------------------------
Question. What is being done to ensure that childhood cancers
receive appropriate levels of funding for translational research that
turns basic science into new therapies?
Answer. Pediatric cancer research remains a top priority for the
NCI. Each year the Institute identifies the best research opportunities
to build upon the foundation of basic science, further develop the
scientific understanding of genetic drivers of childhood cancers,
identify effective therapies, and enhance the quality of life for
pediatric cancer survivors.
When considering the Institute's investments in any category of
disease research, NCI does not make decisions about funding based on
predetermined targets for a specific disease area or research category.
Rather, NCI relies on technical and scientific peer review, in which
highly trained outside investigators perform an initial review of
research proposals and evaluate them on factors such as scientific
merit, likelihood of success, and potential impact. Thereafter, the
National Cancer Advisory Board, which includes members with pediatric
oncology expertise, also conducts a review of the research proposal.
NCI leadership further evaluates proposals to consider factors such as
scientific novelty and overall representation of the research topic
within the NCI portfolio.
Recognizing that childhood cancers are distinct from adult cancers,
NCI supports numerous targeted programs aimed at advancing research in
pediatric oncology. These efforts include:
--The Children's Oncology Group (COG),\67\ part of NCI's National
Clinical Trials Network (NCTN), develops and coordinates
pediatric clinical trials across more than 200-member
institutions. In addition to conducting late-phase clinical
trials, the COG receives NCI support for the Phase 1 and Pilot
Consortium,\68\ which conducts early-phase trials and pilot
studies to rapidly introduce new anticancer agents into
pediatric care.
---------------------------------------------------------------------------
\67\ https://www.childrensoncologygroup.org/.
\68\ https://www.childrensoncologygroup.org/index.php/phase-1-home.
---------------------------------------------------------------------------
--The Pediatric Oncology Branch (POB) \69\ in NCI's Center for Cancer
Research, part of NCI's intramural research program, conducts
high-risk, high-impact basic, translational, and clinical
research.
---------------------------------------------------------------------------
\69\ https://ccr.cancer.gov/Pediatric-Oncology-Branch.
---------------------------------------------------------------------------
--The NCI-COG Pediatric MATCH Trial,\70\ launched in July 2017, tests
molecularly targeted therapies in children and adolescents with
advanced cancers who have few other treatment options. This
nationwide trial is open to children and adolescents from 1 to
21 years of age and currently has eight treatment arms.
---------------------------------------------------------------------------
\70\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
nci-supported/pediatric-match.
---------------------------------------------------------------------------
--Other efforts include the Pediatric Preclinical Testing Consortium
(PPTC),\71\ the Therapeutically Applicable Research to Generate
Effective Treatments (TARGET) \72\ program, the NCI
Experimental Therapeutics (NExT) Program,\73\ the Childhood
Cancer Survivor Study (CCSS),\74\ the Pediatric Provocative
Questions (PQ) Program,\75\ the Pediatric Brain Tumor
Consortium (PBTC),\76\ the Pediatric Cancer Immunotherapy
Trials Network (CITN),\77\ and the New Approaches to
Neuroblastoma Therapy (NANT) \78\ Consortium.
---------------------------------------------------------------------------
\71\ http://www.ncipptc.org/.
\72\ https://ocg.cancer.gov/programs/target.
\73\ https://next.cancer.gov/.
\74\ https://www.cancer.gov/types/childhood-cancers/ccss.
\75\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-217.html.
\76\ https://www.pbtc.org/.
\77\ https://ctep.cancer.gov/MajorInitiatives/
cancer_immunotherapy_trials_network.htm.
\78\ http://www.nant.org/.
---------------------------------------------------------------------------
--The Childhood Cancer Data Initiative proposed in the President's
Budget will seek to leverage existing Federal authorities to
effectively and efficiently coalesce different types of data
currently collected for pediatric cancer cases across the wide
variety of entities that produce and maintain it. As childhood
cancers represent less than 1 percent of all new cases of
cancer diagnosed in the United States each year, NCI recognizes
the need to study the basic biology of pediatric cancers to
develop relevant preclinical models and support clinical trials
that are accessible to every child with cancer. Furthermore, it
is critical that the data garnered from these studies is
aggregated and appropriately shared. In addition, the
integration of longitudinal data from pediatric cancer patients
into adulthood, and the ability to compare adult and pediatric
data broadly will have a profound impact upon our understanding
of the etiology of cancer and our ability to advance research
that can lead to new and better treatments.
For decades, the foundations of both childhood and adult cancer
treatment were surgery, chemotherapy, and radiation therapy. Recently,
immunotherapy, in which a patient's own immune system is harnessed to
fight cancer, has emerged as a new pillar of cancer treatment. While
some immunotherapy approaches have been effective in treating certain
pediatric cancers, many immunotherapy treatments being developed for
adult cancers will likely not be applicable to childhood cancers.
Therefore, this area remains a critical research focus.
Recent clinical advances in immunotherapy include the 2017 FDA-
approval of Keytruda (pembrolizumab), a checkpoint inhibitor, for
pediatric and adult patients with classical Hodgkin lymphoma that
cannot be cured with existing treatments, as well as pediatric patients
with solid tumors that have specific genetic features known as mismatch
repair deficiency and high microsatellite instability. This approval is
significant because targeting genetic characteristics, rather than
where the cancer originates in the body, creates new options for
patients who might otherwise not be considered candidates for a drug.
NCI is now sponsoring early-phase clinical trials of pembrolizumab in
children with aggressive brain tumors.
In 2017 the FDA also approved KymriahTM
(tisagenlecleucel), a chimeric antigen receptor (CAR) T-cell therapy,
for children with acute lymphoblastic leukemia (ALL). This NCI-
supported discovery was first published in the New England Journal of
Medicine in 2014. NCI is currently sponsoring nine clinical trials of
CAR T-cell therapy in pediatric patients with other types of
cancer.\79\
---------------------------------------------------------------------------
\79\ https://clinicaltrials.gov/ct2/results?cond=&term=CAR+T-
cell&type=&rslt= &recrs=b&recrs=
a&recrs=f&recrs=d&age_v=&age=0&gndr=&intr=&titles=&outc=&spons=National+
Cancer+
Institute&lead=&id=&cntry=&state=&city=&dist=&locn=&strd_s=&strd_e=&prcd
_s=
&prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=.
---------------------------------------------------------------------------
In April 2019, selumetinib was awarded Breakthrough Designation by
the FDA,\80\ following Orphan Drug Designation in February 2018,\81\
for treatment of neurofibromatosis type 1 (NF1), a rare pediatric
disease that can cause malignant tumors. Although Breakthrough
Designation does not guarantee final approval of the drug for this
purpose, it is promising news for the future of this rare pediatric
disease. NCI's POB led the Phase I and II trials of selumetinib,
through an intramural and extramural collaboration. Early results from
the phase II trial are promising--72 percent of the 50 pediatric
patients between the ages of 2 and 18 enrolled in the trial are
responding to the treatment. Not only are some patients seeing their
tumors shrink more than 50 percent, but many patients report less pain
intensity and pain interference, as well as increased strength and
range of motion.\82\ If this trajectory continues, selumetinib will be
the first drug ever approved for this disease.
---------------------------------------------------------------------------
\80\ https://ccr.cancer.gov/news/article/mek-inhibitor-selumetinib-
granted-breakthrough-
designation-by-fda-to-treat-neurofibromatosis-type-one-in-pediatric-
patient.
\81\ https://ccr.cancer.gov/news/article/fda-grants-orphan-drug-
status-to-selumetinib-for-neurofibromatosis-type-1-nf1-treatment.
\82\ https://meetinglibrary.asco.org/record/159508/abstract.
---------------------------------------------------------------------------
Innovative clinical trials would not be possible without the basic
research conducted to understand the biological mechanisms of disease
and to identify molecular targets for therapies. The NTRK family of
genes is one such example. Describing the role of this family of genes
was first made possible as a result of a basic science discovery in the
1980's at NCI's Frederick National Laboratory for Cancer Research by
Dr. Mariano Barbacid. Dr. Barbacid was not studying pediatric cancers,
or any particular cancer type--he was on the hunt for unique genetic
drivers of cancer, called oncogenes. At the time, he could not have
anticipated that his discovery would eventually lead to an effective
therapy for rare cancers diagnosed in children and adults.
This discovery led to the development of an NTRK inhibitor, LOXO-
101 or larotrectinib, which works against unique fusion oncoproteins
that drive certain pediatric and adult cancers. In May 2018, FDA issued
larotrectinib an orphan drug status and Priority Review, and in
November 2018, FDA granted accelerated approval to larotrectinib. This
is the second FDA approval for a precision cancer therapy that is based
on a particular genetic alteration, rather than the site in the body in
which a cancer occurs. Larotrectinib was evaluated in both the NCI
adult and pediatric MATCH phase II clinical trials.
Investigators are hopeful that the story of crizotinib (Xalkori)
will be similar. Crizotinib was first developed to target a protein
produced by the oncogene MET but was later found to inhibit cancer-
causing forms of the ALK gene, found in anaplastic large cell lymphomas
(ALCL), certain neuroblastomas, and some non-small cell lung cancers
(NSCLC). ALCL and neuroblastoma both occur in pediatric patients; the
connection between ALCL and ALK was established in 1994, while the
identification of ALK as a driver of neuroblastoma occurred in 2008.
Crizotinib was first approved for NSCLC in March 2016, and it is part
of the NCI adult and pediatric MATCH trials. In 2018, the FDA granted
breakthrough approval of the drug for ALCL, and COG launched a phase
III trial with crizotinib in combination with chemotherapy for high-
risk neuroblastoma patients.
NCI will continue to support basic, translational, and clinical
research to help develop new and less toxic therapies for children with
cancer. NCI is also committed to supporting cancer survivorship
research to better understand and develop interventions to address the
late effects of cancer and its treatment in childhood, and adolescent
and young adult (AYA) cancer survivors. NCI is currently implementing
new research efforts in this area and is also supporting efforts to
enhance biospecimen collection and biobanking efforts with an emphasis
on pediatric cancer types and subtypes for which treatments have been
least effective. Both activities are aligned with provisions of the
Childhood Cancer STAR Act directed toward NCI.
Question. What is being done to ensure that SBIR funding is
addressing the critical translational gap for these neglected rare
cancer patients?
Answer. Consistent with the statutory mandate established by
Congress, the NCI SBIR/STTR program is one of the largest sources of
early stage technology financing in the United States. The program
supports a diverse portfolio of research, from projects focused
specifically on evaluating new treatments for rare cancers, to the
development of cross-cutting technologies that enable research across
cancer types. The NCI SBIR/STTR program does not direct funding based
upon cancer type or research area. Funding is awarded through a
rigorous and competitive peer review process, to identify the most
promising research applications. NCI, including the SBIR/STTR program,
recognize that there is a clear need to develop more effective
treatments for many rare cancers and rare cancer subtypes that are
refractory to currently available treatment options.
Examples of current SBIR projects focusing on translational and
clinical research for rare cancers include:
--In 2018, NCI awarded a SBIR Phase IIB Bridge Award to Oncoceutics,
Inc., which seeks to develop a new cancer drug, ONC201, for
patients who have been diagnosed with recurrent glioblastoma
and high-grade glioma with limited treatment options and very
poor prognoses, including a pediatric high-grade glioma called
Diffuse Intrinsic Pontine Glioma (DIPG).\83\ Approximately 200-
300 children are diagnosed with DIPG each year in the U.S., and
the median survival time from diagnosis is less than 1 year.
---------------------------------------------------------------------------
\83\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9524880&icde=
44259659&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&pball=.
---------------------------------------------------------------------------
--In 2018, NCI supported PEEL Therapeutics with an STTR award focused
on pre-clinical evaluation of a novel potential therapy for
osteosarcoma, a deadly pediatric bone tumor. The project is led
by Dr. Josh Schiffman, who is also a researcher at the Huntsman
Cancer Institute at the University of Utah.\84\
---------------------------------------------------------------------------
\84\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9559358&icde=44276787.
---------------------------------------------------------------------------
--In fiscal year 2018, NCI also funded a Phase I clinical trial of a
novel first-in-class drug combination of two agents (IV
fenretinide + IV safingol) through an SBIR Fast-Track Phase I/
II award to CerRx, Inc. This trial, conducted at the South
Plains Oncology Consortium based at the Texas Tech University
Health Sciences Center, is testing for the treatment of
multiple relapsed rare cancer types including Non-Hodgkin's
Lymphoma, Peripheral T-Cell Lymphoma, and Esophageal
Adenocarcinoma. If successful, this novel biochemistry may
constitute a broad-based widely active treatment option for
both adult and pediatric malignancies.\85\
---------------------------------------------------------------------------
\85\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9485913&icde=44283562.
---------------------------------------------------------------------------
While these are all important examples of research underway to
support development of new therapies for rare cancers, the SBIR
Program's investment in cross-cutting technologies and tools is equally
important to progress in this field. A notable example of this is NCI's
support of Illumina, Inc. With support from NCI's SBIR program and its
Innovative Molecular Analysis Technologies (IMAT) program,\86\ Illumina
developed the base technology for the Infinium assay for genotyping,
which is being used in the NIH All of Us Research Program, in other
basic and clinical research, as well as by commercial companies like
23andMe and Ancestry.com.\87\ In collaboration with NCI's SBIR/STTR
program, the IMAT program is another opportunity for small businesses
to pursue NCI support. IMAT aims to support the development and
dissemination of novel and potentially transformative next-generation
technologies, and uses a variety of investigator-initiated research
project grant mechanisms to support cross-cutting, research-enabling
disciplines.
---------------------------------------------------------------------------
\86\ https://imat.cancer.gov/, https://imat.cancer.gov/about-imat/
outputs-and-achievements/individual-technologies-and-platforms/
sentrix%C2%AE-beadchip-and.
\87\ https://www.cancer.gov/news-events/cancer-currents-blog/2019/
nci-sbir-working-with-small-business.
---------------------------------------------------------------------------
These SBIR and IMAT examples, along with other NCI research efforts
described in this response, represent important steps NCI is taking to
support basic, translation, and clinical research to make progress for
patients with rare cancers. NCI encourages small businesses interested
in pursuing NCI funding to consider opportunities to apply for SBIR/
STTR \88\ and IMAT support,\89\ as well as support through the NExT
program,\90\ also highlighted in this response.
---------------------------------------------------------------------------
\88\ https://sbir.cancer.gov/funding.
\89\ https://imat.cancer.gov/funding-opportunities.
\90\ https://next.cancer.gov/entryToPipeline/default.htm.
---------------------------------------------------------------------------
Question. What is being doing to ensure that all forms of cancer
have significant dataset presence in publicly available data
repositories?
Answer. There are several data resources available from NCI that
serve as data repositories for all forms of cancers, including rare
cancers. Examples include the Genomic Data Commons (GDC) and the NCTN
Navigator. The GDC \91\ is a data portal that serves as a centralized
location to integrate and store the diverse datasets from NCI programs.
The GDC includes cancer genomic data from over 32,000 cancer cases. All
GDC data is available to qualified researchers free of charge and
includes data from The Cancer Genomic Atlas (TCGA),\92\ where about
one-third of cancer types within the TCGA resource are rare cancers;
Therapeutically Applicable Research to Generate Effective Treatments
(TARGET), where all of the cancers included in this pediatric genomics
resource are considered rare; The Clinical Trials Sequencing Program
(CTSP); and the Exceptional Responders Initiative. The GDC will also
include data from future NCI Center for Cancer Genomics-sponsored
cancer research programs.
---------------------------------------------------------------------------
\91\ https://gdc.cancer.gov/.
\92\ Rare cancer types within TCGA are: mesothelioma, adrenal gland
tumors, testicular germ cell cancer, uveal melanoma, adrenocortical
carcinoma, cholangiocarinoma, chromophobe kidney cancer, adult soft
tissue sarcomas, thymomas, and uterine carcinosarcoma.
---------------------------------------------------------------------------
Finally, the proposed fiscal year 2020 Childhood Cancer Data
Initiative seeks to create a federated data system for pediatric cancer
research to increase the number of cases represented, and all pediatric
cancers are considered rare diseases. The data federation will include
clinical records, genomic information, pathology and outcomes data and
will build upon existing initiatives at NIH and NCI including the GDC
and TARGET.
cancer research and the deadliest cancers
Question. While Congress has been providing the NIH, including the
National Cancer Institute, with more funding each of the past 4 years,
the odds of securing a grant from NCI have actually been getting more
difficult.
(A) What's driving this trend, what's its significance, and do you
expect it to continue?
(B) How much of the progress that you're seeing is occurring in NCI
Cancer Centers and Translational Research centers, is it
disproportionate, and what accounts for their success?
(C) While the progress in cancer research is very encouraging, it
remains elusive for those like cancers of the pancreas, esophagus,
ovary and stomach, where progress remains elusive. What is NCI doing to
address that?
Please provide the number of grants and total grant funding devoted
to research related to cancers of the pancreas, esophagus, ovary,
liver, brain, lung and stomach for each year from fiscal year 2013 to
fiscal year 2018.
Answer. NIH appreciates the additional resources Congress provided
NCI each of the past 6 years (Fiscal Years 2013-2018) to support cancer
research. As members are fully aware, cancer continues to be a leading
cause of death and disability for the Nation, and thus scientists
around the country are motivated to find strategies for combatting the
issue. The additional funding resulted in an approximately 24 percent
increase to NCI's appropriation to support essential research into
understanding and treating what we now recognize as a multitude of
cancer subtypes. Over that same period, NCI received a nearly 50
percent increase in the number of investigator-initiated grant
applications (R01s) indicating that the field continues to attract
researchers to propose novel scientific proposals. Specifically, during
fiscal year 2013, NCI received 4,175 investigator-initiated R01
applications. During fiscal year 2018 NCI received 6,113 R01
investigator-initiated applications, and experienced year-to-year
annual growth in the number of applications throughout the period. We
have also observed that the increases represent a growing number of
unique investigators applying for awards, and only a small portion
(approximately 10 percent) of the increase in applications is driven by
individual investigators submitting multiple applications As a result,
even during an era of significant budget increases, this dramatic
growth in applications had increased competition for NCI funding, and
NCI is taking affirmative steps to improve the chances for applicants
to be funded. Of note, in fiscal year 2019, NCI expects to increase the
investigator-initiated research grant pool by $100 million, an amount
that is greater than the increase NCI received to its fiscal year 2019
base appropriation.
(A) Regarding the increase in applications to NCI, we suspect that
the public health burden in combination with the scientific opportunity
is the likely source of a surging biomedical research workforce in this
area. We are reaping the benefits of decades of investment in basic
science and rapid advances in technology that have resulted in a record
number of oncology drug approvals. This includes significant progress
in the development of cancer immunotherapies and molecularly targeted
therapies. At the same time, we are making gains in cancer prevention
and survivorship. Taking these advances into consideration with the
increasingly interdisciplinary nature of cancer research, that is the
intersection of genomics, data science, biology, and more, this
progress continues to attract more interest and talent to the cancer
research enterprise.
(B) The 70 NCI-designated Cancer Centers serve as anchors of the
United States cancer research enterprise, convening concentrations of
expertise that are vital to rapidly advance progress against cancer.
NCI strives to provide opportunities to participate in cutting edge,
NCI-supported research to every patient across the country, not just
those with easy access to an NCI-designated Cancer Center and thus two
additional pillars of the NCI research infrastructure are the National
Clinical Trials Network (NCTN) and the NCI Community Oncology Research
Program (NCORP), which seek to enroll diverse patient populations from
across the Nation in NCI-sponsored research.
The NCTN is a collection of organizations and clinicians that
coordinates and supports cancer clinical trials at more than 3,000
sites across the U.S. and Canada. The NCTN provides the infrastructure
for NCI-funded treatment, screening, and diagnosis trials, centralizing
many administrative efforts to rapidly facilitate easier enrollment of
patients in clinical trials. For physicians and their patients, a
variety of significant, innovative trials are widely available
throughout the country, in large and small communities alike.\93\
---------------------------------------------------------------------------
\93\ https://www.cancer.gov/research/areas/clinical-trials/nctn.
---------------------------------------------------------------------------
NCORP, which works closely with the NCTN, expands NCI's reach even
further. In addition to designing and conducting cancer prevention,
supportive care and symptom management, screening, and surveillance
clinical trials, NCORP sites recruit patients and participants to NCI-
supported treatment and imaging trials, most of which are conducted
through the NCTN. NCORP is led by 7 research bases and 46 community
sites, and there are over 900 NCORP component sites across the country.
The sites represent collaborations between researchers, public
hospitals, physician practices, academic medical centers, and other
groups that provide healthcare services.\94\
---------------------------------------------------------------------------
\94\ https://ncorp.cancer.gov/about/.
---------------------------------------------------------------------------
Independent investigators fill out the robust research
infrastructure supported by NCI. This includes principal investigators
for NCI's Specialized Programs of Research Excellence (SPOREs),\95\
which represent collaborative translational research projects focusing
on more than twenty organ sites, systems, and pathway-specific themes.
While large programs like NCI-designated cancer centers, clinical
trials networks, data commons, and biorepositories constitute the
backbone of the cancer research enterprise, the majority of research
proposals received and funded by NCI are investigator-initiated,
meaning that the studies are developed by researchers themselves. This
process allows for the scientific ingenuity and intellectual autonomy
that is essential to advance biomedical research. In fiscal year 2018,
NCI supported research at more than 700 institutions across the United
States.
---------------------------------------------------------------------------
\95\ https://trp.cancer.gov/.
---------------------------------------------------------------------------
(C) NCI is committed to making progress against all cancers,
including those that have proved most difficult to treat. Indeed,
recognizing that the incentives that encourage private industry
investment in therapies for more common cancers do not exist for
cancers that occur less frequently, NCI has a responsibility to
encourage and support research on these diseases, and does this through
a variety of mechanisms, including support for disease-specific
steering groups and the convening of scientific meetings and relevant
cross-cutting research areas that seek to identify new scientific
directions and opportunities.
One way in which NCI encourages scientific collaboration and
interdisciplinary research on these disease areas is through the SPOREs
program, mentioned above. These programs include basic and clinical/
applied scientists working together to support projects that will
result in new and diverse approaches to the prevent, detect, diagnose,
and treat cancer. NCI currently supports SPOREs focused on pancreas,
esophagus, ovary, liver, brain, lung and stomach cancers through the
following awards:
--Pancreatic SPOREs are located at the Mayo Clinic, University of
Nebraska Medical Center, and Washington University in St.
Louis.\96\
---------------------------------------------------------------------------
\96\ https://trp.cancer.gov/spores/pancreatic.htm.
---------------------------------------------------------------------------
--Gastrointestinal SPOREs, which include research on cancers of the
esophagus and stomach, are located at Case Western Reserve
University, Dana-Farber Harvard Cancer Institute, Johns Hopkins
University, and Vanderbilt University.\97\
---------------------------------------------------------------------------
\97\ https://trp.cancer.gov/spores/gi.htm.
---------------------------------------------------------------------------
--Ovarian SPOREs are located at Johns Hopkins University, the Mayo
Clinic, Roswell Park Cancer Institute, and University of TX/MD
Anderson.\98\
---------------------------------------------------------------------------
\98\ https://trp.cancer.gov/spores/ovarian.htm.
---------------------------------------------------------------------------
--A hepatobiliary (liver) cancer SPORE is located at the Mayo
Clinic.\99\
---------------------------------------------------------------------------
\99\ https://trp.cancer.gov/spores/hepatobiliary.htm.
---------------------------------------------------------------------------
--Brain SPOREs are located at Dana-Farber Harvard Cancer Institute,
Duke University Medical Center, Northwestern University at
Chicago, University of California, Los Angeles, University of
California, San Francisco, and University of Texas/MD
Anderson.\100\
---------------------------------------------------------------------------
\100\ https://trp.cancer.gov/spores/brain.htm.
---------------------------------------------------------------------------
--Lung SPOREs are located at the University of Colorado Cancer
Center, University of Texas/Southwestern Medicine, and Yale
University.\101\
---------------------------------------------------------------------------
\101\ https://trp.cancer.gov/spores/lung.htm.
---------------------------------------------------------------------------
Between June 2017 and May 2018, the FDA approved several therapies
for cancers that are the focus of SPORE research, advances made
possible through NCI or NIH-supported research.\102\ The approved
treatments include: \103\
---------------------------------------------------------------------------
\102\ https://www.ncbi.nlm.nih.gov/pubmed/29440428.
\103\ https://www.ascopost.com/issues/june-3-2018-narratives-
special-issue/fda-oncology-drug-
approvals-granted-between-june-2017-and-may-16-2018/.
---------------------------------------------------------------------------
--Rucaparib (Rubrical), a maintenance treatment for recurrent
ovarian, fallopian tube, or primary peritoneal cancers;
--Lutetium Lu 177 Dotatate (Lutathera) for gastroenteropancreatic
neuroendocrine tumors;
--Trastuzumab-DKST (Ogivri), a biosimilar, to treat patients with
certain types of metastatic stomach cancer and breast cancer;
--Pembrolizumab (Keytruda) for patients with recurrent locally
advanced or metastatic, gastric or gastroesophageal junction
adenocarcinoma whose tumors express a certain biomarker;
--Olaparib tablets (Lynparza) for maintenance treatment of patients
with recurrent ovarian, fallopian tube, or primary peritoneal
cancer who responded to certain chemotherapies; and
--Several approvals to treat various subtypes of non-small cell lung
cancer (NSCLC):
--Osimertinib (Tagrisso)
--Durvalumab (Imfinzi)
--Alectinib (Alecensa)
--Dabrafenib (Tafinlar), in combination with Trametinib (Mekinist)
As these approvals indicate, the scientific community recognizes
that within each type of cancer, there are unique subtypes, and when
possible, physicians should rely on genetic and molecular markers to
guide treatment. NCI's investments in basic research--understanding the
underlying mechanisms that give rise to cancer--enable rapid advances
of precision medicine in cancer treatment. Investigators are continuing
to identify disease subtypes, which often uncovers tumors with similar
genetic profiles that occur in various sites throughout the body. Such
advances led to the FDA approval of FoundationOne CDX Next Generation
Sequencing, a genetic test to detect alterations in 324 genes and two
genomic signatures in any solid tumor type.\104\ These developments
benefit all cancer patients, including those with difficult to treat
cancers.
---------------------------------------------------------------------------
\104\ https://www.ascopost.com/issues/june-3-2018-narratives-
special-issue/fda-oncology-drug-
approvals-granted-between-june-2017-and-may-16-2018/.
---------------------------------------------------------------------------
Precision medicine is the foundation for the NCI MATCH (Molecular
Analysis for Therapy Choice) Trial, a precision medicine trial that is
expected to provide new research ideas to advance treatments in all
cancer types.\105\ This study is analyzing patients' tumors to
determine whether they contain gene abnormalities for which a targeted
drug exists, and with that information, the study assigns treatment
based on the genetic abnormality. As of April 2019, 443 pancreatic
cancer patients, 235 gastroesophageal cancer patients, 666 ovarian
cancer patients, and 345 liver and hepatobiliary cancer patients, 131
patients with brain and other central nervous system tumors, and 707
patients with various types of lung cancers have been screened for this
trial.
---------------------------------------------------------------------------
\105\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/nci-match.
---------------------------------------------------------------------------
Patients who are not assigned to an NCI MATCH treatment arm may be
eligible for the NCI DART, or the Dual Anti-CTLA-4 & Anti-PD-1 blockade
in Rare Tumors Trial. This study will also assess whether their tumors
respond to two cutting-edge immunotherapy agents. DART is the first
federally funded immunotherapy trial devoted entirely to rare
cancers.\106\
---------------------------------------------------------------------------
\106\ https://www.swog.org/sites/default/files/docs/2017-11/
DARTrelease.pdf.
---------------------------------------------------------------------------
As this background demonstrates, NCI will continue to support
research on cancers of the pancreas, esophagus, ovary, liver, brain,
lung and stomach through multiple research mechanisms.
Question. Please provide the number of grants and total grant
funding devoted to research related to cancers of the pancreas,
esophagus, ovary, liver, brain, lung and stomach for each year from
fiscal year 2013 to fiscal year 2018.
Answer. The information requested is provided in the tables below
(Table 1--Fiscal Year 2018-2016 and Table 2--Fiscal Year 2015-2013).
Brain cancer, liver cancer, lung cancer, ovarian cancer and pancreatic
cancer are Research, Condition, and Disease Categories (RCDC) and the
data provided include the total number of projects--grants (including
subprojects and supplements), contracts, and intramural research--for
the NIH for those cancer types. Total funding is broken out as total
NIH and total NCI funding. The data are publicly available and can be
found at: https://report.nih.gov/categorical_spending.aspx.
Additionally, it is important to clarify that RCDC category
listings are not budget line items. The category represents a list of
projects selected for funding following the rigorous NIH peer review
process. Each category list provides a look back at projects funded in
a given fiscal year. NIH does not allocate funding prospectively by
category, and the RCDC categories do not add up to the total NIH budget
because projects can be applicable to more than one category, and
categories are by their nature overlapping (e.g., neurosciences and
brain cancer). RCDC is not intended to account for the entire NIH
budget across thousands of research topics. More information is
available on the RCDC FAQ page: https://report.nih.gov/rcdc/
faqs.aspx#q18.
Esophageal cancer and stomach cancer are not currently RCDC
categories. Therefore, the data provided for those sites are estimated
based on NCI data for grants and intramural research projects. Although
every attempt was made to provide data that is closely matched to the
method used to assemble RCDC data for the other cancer sites. However,
it is not comparable because there are no esophageal or stomach cancer
RCDC categories.
[The information follows:]
down syndrome and the include project
Question. As a part of the INCLUDE Project, NIH has hosted
scientific workshops to solicit input from the Down syndrome community
on research between Alzheimer's disease and Down syndrome. What other
topics does NIH plan to cover in future workshops and how will NIH plan
to engage the Down syndrome community to ensure their robust
participation in these workshops?
Answer. The new, trans-NIH effort, Investigating Co-occurring
conditions across the Lifespan to Understand Down syndrome, or INCLUDE,
was launched in summer 2018. As a key component of the INCLUDE project,
the NIA is supplementing an Alzheimer's clinical trials network to
include adults with Down syndrome to learn more about the development
of commonly co-occurring conditions in individuals with Down syndrome
that are also seen in the general population, such as dementia and
Alzheimer's disease. In addition, working through its established
Pediatric Trials Network, in fiscal year 2019 (NICHD will create a new
pediatric clinical trials infrastructure for Down syndrome. Such a
resource will also ensure that new therapies can be brought to trial as
they emerge in the future. To bolster these efforts, NIH is planning
two major scientific workshops within the year to address the
development of a cohort in Down syndrome, and how to include people
with Down syndrome in clinical trials. These efforts can take advantage
of the research registry for Down syndrome, DS-Connect,\107\ a Web-
based health registry that serves as a national health resource for
people with Down syndrome and their families, researchers, and
healthcare providers. Funded by NICHD since 2013, with over 4,400
participants, the registry facilitates information sharing about
research and upcoming trials for individuals with Down syndrome, their
families, and researchers.
---------------------------------------------------------------------------
\107\ https://dsconnect.nih.gov/.
---------------------------------------------------------------------------
Question. How is NIH going to use the INCLUDE Project and other
investments in Down syndrome research to support the pipeline of early
investigators in this field?
Answer. One of the immediate successes of INCLUDE was to attract
new researchers and talent into the field. In fact, many of the
recipients of awards in fiscal year 2018 were investigators who had not
previously had a research focus on Down syndrome. Since the purpose of
the INCLUDE project is to investigate conditions that affect both
individuals with Down syndrome and the general population, researchers
with subject matter expertise other than Down syndrome now have the
opportunity to submit applications in response respond to one of
INCLUDE's three major components: to conduct targeted, high-risk, high-
reward basic science studies on chromosome 21; assemble large study
populations (cohorts) of individuals with Down syndrome; and include
individuals with Down syndrome in new and existing clinical trials.
These opportunities are widely disseminated across the Down syndrome
community through the public-private Down Syndrome Consortium that
includes the Trans-NIH Working Group, 16 national and international
organizations whose missions focus on Down syndrome, and individuals
with Down syndrome and family members. The consortium also works toward
implementing the NIH Research Plan on Down Syndrome,\108\ which set
research goals for Down syndrome.
---------------------------------------------------------------------------
\108\ https://www.nichd.nih.gov/publications/product/441.
---------------------------------------------------------------------------
In addition, NIH continues to fund from its baseline a wide range
of research related to Down syndrome, across many of the NIH institutes
and centers, nearly tripling its total funding for Down syndrome-
related research over the last few years. For example, NICHD is funding
an early-stage investigator studying children with Down syndrome, to
develop outcome measures for early childhood communication. In the
future, we anticipate initiatives that will be focused on support for
trainees to continue to build a pipeline of investigators studying Down
syndrome.
Question. People with Down syndrome have a unique disease spectrum
that offers many opportunities for research. As the NIH works to set up
a clinical trials network as a part of the INCLUDE Project, how do you
plan to work with the Down syndrome community to encourage people with
this condition to participate in clinical trials?
Answer. Over the coming year, NICHD plans to work with NIA and
other partners to coordinate building an infrastructure for a clinical
trials network in Down syndrome across the lifespan. At the same time,
full inclusion of individuals with Down syndrome into ongoing clinical
studies that have been enrolling people without Down syndrome will
ensure that they will reap the benefits of therapeutic agents already
in development. Working through its established Pediatric Trials
Network that has enrolled over 7,000 children, in fiscal year 2019
NICHD will create a new pediatric clinical trials infrastructure for
Down syndrome. This resource will also ensure that new therapies can be
brought to trial quickly and efficiently as they emerge in the future.
In parallel, NICHD will create and fund a training program, working
with its pediatric trials experts, as well as specialists in Down
syndrome, to help teach investigators how to recruit and work with
individuals with Down syndrome and their families.
Further, through the INCLUDE project, NIA is supplementing an
Alzheimer's clinical trials network to include adults with Down
syndrome to learn more about the development of dementia and
Alzheimer's disease. To bolster these efforts, NIH is planning two
major scientific workshops within the year to address the development
of a cohort in Down syndrome, and how to include people with Down
syndrome in clinical trials. These efforts will take advantage of the
research registry for Down syndrome, DS-Connect,\109\ a Web-based
health registry that serves as a national health resource for people
with Down syndrome and their families, researchers, and healthcare
providers. Funded by NICHD since 2013, the registry facilitates
information sharing about research and upcoming studies for both
individuals with Down syndrome and researchers.
---------------------------------------------------------------------------
\109\ https://dsconnect.nih.gov/.
---------------------------------------------------------------------------
Question. We are pleased to see so many NIH Institutes and Centers
participating in the INCLUDE Project. What kind of feedback have you
been getting from the Institutes on this project, particularly as it
may offer lessons learned for other trans-NIH initiatives?
Answer. INCLUDE involves research projects or programs funded by 14
NIH Institutes and Centers. INCLUDE will investigate conditions that
affect both individuals with Down syndrome and the general population,
such as Alzheimer's disease/dementia, autism, cataracts, celiac
disease, congenital heart disease, and diabetes. This approach is
creating new synergies among the NIH institutes and centers that study
these conditions. To give just two examples from the first round of
awards, NICHD is funding a project that will sequence the genomes of
children with Down syndrome who also have congenital heart defects or
leukemia. The results will be publicly available, allowing researchers
globally to test hypotheses and find new gene variants that are
associated with both Down syndrome and these additional conditions. NIA
is developing a Down syndrome module for its Alzheimer's disease
research centers with the goal of learning more about the development
of dementia that will lead to potential treatments.
Question. I recently learned that people with Down syndrome rarely
get solid tumor cancers. For example, women with Down syndrome most
likely would not ever need to get a mammogram because they are highly
unlikely to develop breast cancer. The connection between Down syndrome
and cancer seems like a promising research opportunity. Can you tell us
about some of the topics that NIH is prioritizing in the INCLUDE
Project?
Answer. NIH was grateful to have the opportunity to dedicate more
resources in fiscal year 2018 toward research related to Down syndrome
through the INCLUDE project. In its first year, over $22 million was
spent on projects under this new initiative alone. This figure was in
addition to the baseline funding of $37 million for Down syndrome for a
total of approximately $60 million. Awards were made to a wide range of
investigators across the country,\110\ covering all aspects of the
INCLUDE project: research to improve the understanding of the biology
of Down syndrome, research focused on connecting large study
populations (or cohorts) of individuals with Down syndrome and
enrolling new participants at different ages, and identifying existing
clinical trials that seek to address conditions common in individuals
with Down syndrome to bolster recruitment and inclusion in more
clinical studies.
---------------------------------------------------------------------------
\110\ https://www.nih.gov/include-project/funding.
---------------------------------------------------------------------------
INCLUDE involves research projects or programs funded by 14 NIH
Institutes and Centers, investigating conditions that affect both
individuals with Down syndrome and the general population, such as
Alzheimer's disease/dementia, autism, cataracts, celiac disease,
congenital heart disease, and diabetes. This approach is creating new
synergies among the NIH institutes and centers that study these
conditions. To give just two examples from the first round of awards,
NICHD is funding a project that will sequence the genomes of children
with Down syndrome who also have congenital heart defects or leukemia.
The results will be publicly available, allowing researchers globally
to test hypotheses and find new gene variants that are associated with
these conditions. NIA is developing a Down syndrome module for its
Alzheimer's centers with the goal of learning more about the
development of dementia and lead to potential treatments.
Question. I was pleased to learn that one of the aims of the
INCLUDE Project is to encourage scientists studying other topics like
cancer, Alzheimer's, and autoimmune disease to add research on Down
syndrome to their work. What kind of feedback have you gotten from the
research community on these opportunities?
Answer. One of its immediate successes of INCLUDE was to attract
new researchers and talent into the field. In fact, many of the
recipients of awards in fiscal year 2018 were investigators who had not
previously had a research focus on Down syndrome. Since the purpose of
the INCLUDE project is to investigate conditions that affect both
individuals with DS and the general population, researchers with
subject matter expertise other than Down syndrome now have the
opportunity to submit applications. These opportunities are widely
disseminated across the Down syndrome community through the public-
private Down Syndrome Consortium that includes the Trans-NIH Working
Group, 16 national and international organizations whose missions focus
on Down syndrome, and individuals with Down syndrome and family
members. The response has been robust, demonstrating excitement among
investigators who previously have not been involved in Down syndrome
research.
antibiotic resistance
Question. We have been hearing warnings for decades that overuse of
antimicrobials is reducing their effectiveness, and that appears to be
borne out by reports of a new superbug, Candida Auris.
Where does NIH see the greatest opportunities for medical research
to provide solutions to the threat posed by antimicrobial resistance?
Answer. NIAID is the lead institute for antimicrobial resistance
(AMR) research at NIH. NIAID supports a comprehensive portfolio of
basic, translational, and applied research on AMR to better understand
pathogenicity and the mechanisms by which resistant pathogens overcome
antimicrobials, and to develop novel diagnostics, therapeutics, and
vaccines. Recent advances in AMR research have created a number of
scientific opportunities, particularly to: (1) accelerate the
development of new antimicrobials with novel mechanisms of action; (2)
identify ways to enhance or target the body's immune system to better
fight infection; (3) manipulate microbial communities to prevent or
treat colonization by harmful pathogens; and (4) develop state-of-the-
art antivirulence strategies and rapid diagnostics to help control the
spread of AMR. NIAID is pursuing these opportunities for both bacterial
and fungal pathogens.
NIAID is supporting development of a number of novel antimicrobial
agents, including a group of novel forms of a class of antibiotics
(tetracyclines) that are not susceptible to existing resistance
mechanisms in bacteria. One of these compounds, XERAVATM, recently
received FDA approval to treat complicated intra-abdominal infections.
NIAID funding also has led to the discovery of a new class of
antibiotics, malacidins, that are being investigated for further
therapeutic development. In addition, NIAID is providing CARB-X
(Combating Antibiotic Resistant Bacteria-X), a public-private
partnership led by BARDA within HHS with in kind and technical support.
CARB-X is currently funding 35 innovative projects--including 13 that
represent new classes of antibiotics.
NIAID currently is exploring several alternatives to traditional
antimicrobials that leverage advances in basic research on
pathogenesis, drug resistance, immune system function, and the
microbiome. NIAID-supported scientists are exploring the use of
protective bacterial strains and fecal microbiota transplant to prevent
and treat bacterial infections. NIAID grantees also are investigating
ways to boost the ability of an individual's own immune system to fight
infection. This includes the use of modified immune cells to control
invasive fungal infections, and studies by NIAID investigators to boost
the immune system's ability to fight the bacterial species Klebsiella
pneumoniae infection using targeted antibodies. NIAID also is advancing
the development of candidate vaccines against bacterial and fungal
pathogens, including strains that exhibit drug resistance. One such
experimental vaccine, NDV-3, exhibited protection in animal models
against Staphylococcus and Candida species, including Candida auris (C.
auris). NDV-3 also was shown to be safe and well-tolerated in a Phase 1
clinical study. Vaccines that confer protection against bacterial and
fungal pathogens have the added benefit of mitigating the use of
antimicrobial drugs and potentially avoiding the development of AMR.
NIAID also is supporting the development of novel diagnostic tools
to help control the emergence and spread of drug-resistant pathogens.
The NIAID Antibacterial Resistance Leadership Group (ARLG) oversees
clinical research on antibiotic resistance, including antimicrobial
stewardship, infection prevention, and improved diagnostics. ARLG
efforts include the development of a master protocol for evaluating
multiple diagnostic tests using samples from a single patient. NIAID
support also has contributed to the development of several novel
diagnostics capable of distinguishing between numerous infectious
agents, including a sepsis diagnostic that simultaneously tests for 24
bacterial and fungal species, and a pneumonia diagnostic that can
detect a number of different bacterial and viral species as well as
seven genetic markers of AMR. Both diagnostics have received FDA
clearance. In addition, NIH, in partnership with BARDA, is supporting
the AMR Diagnostic Challenge competition. The Diagnostics Challenge
aims to accelerate the development of raid, point-of-need diagnostic
tests that can help inform treatment and facilitate antibiotic
stewardship. Submissions for Step 3 of the Challenge are due in January
2020, and final results of the competition are anticipated in July
2020.
Question. There are already a number of superbugs like MRSA and C-
R-E that pose challenges in hospitals and other healthcare settings,
what is significant about Candida Auris?
Answer. Candida are fungi that can be found on the skin, mucous
membranes, and in the intestinal tract. For people with certain risk
factors, excessive growth of these fungi can cause invasive
candidiasis--a serious infection that can affect the blood, heart,
brain, eyes, bones and other parts of the body. C. auris is a newly
emerging fungal species that is challenging to diagnose and is often
resistant to multiple antifungal drugs. While most C. auris infections
are treatable with existing antifungal drugs, the presence of C. auris
infections resistant to three of the main classes of antifungal drugs
is extremely concerning. In addition, C. auris is extremely difficult
to eliminate from contaminated surfaces, and it can spread from person-
to-person. Drug development for fungal pathogens poses an especially
challenging problem. Unlike antibacterial drugs, which mostly target
bacterial pathways that are very different than those in humans, many
fundamental biochemical and cellular processes are similar in fungi and
humans. Thus, many fungal drug candidates may pose a safety risk to
humans because they could also target the similar human pathways, with
potentially toxic side effects.
AMR research supported by NIAID is especially critical in light of
the emergence of novel AMR pathogens such as C. auris, which exhibits a
unique multidrug resistance that has not been seen in other species of
Candida. A major component of NIAID-supported research on C. auris is
focused on developing an improved understanding of resistance
mechanisms to better inform therapeutic development efforts. This
includes genomic analysis of C. auris--including isolates from two
recent outbreaks--as well as efforts to better understand host-pathogen
interactions and resistance mechanisms for particular antifungal drugs.
NIAID also is screening antifungal compounds for in vitro effectiveness
against C. auris. Of 15 compounds tested to date, 11 showed activity
against C. auris. NIAID also supports studies of a broad-spectrum
antifungal with activity against C. auris and other Candida species. In
addition, NIAID scientists have developed animal models to study C.
auris infection and to screen investigational therapeutics, three of
which showed activity against C. auris. Two of these investigational
therapeutics are currently in various stages of clinical development.
Question. This is clearly a problem that goes far beyond the NIH or
even the United States. How is NIH working its your other Federal and
international partners?
Answer. NIAID works closely with its Federal partners, including
the Centers for Disease Control and Prevention (CDC), BARDA, and FDA to
monitor the spread of drug-resistant pathogens and further the
development of promising diagnostics, therapeutics, and vaccines for
AMR pathogens. NIAID continues to support CARB-X, the BARDA-led public-
private partnership to incentivize the early development of
antibiotics, vaccines, and diagnostics to combat resistance to
antimicrobials that also is supported by the United Kingdom and
Germany. NIAID also participates in the Transatlantic Task Force for
Antimicrobial Resistance (TATFAR), which was established in 2009 with
the goal of enhancing communication and cooperation in: 1)
antimicrobial stewardship; 2) prevention and control of AMR; and 3)
enhancement of the antimicrobial drug development pipeline. NIAID,
through TATFAR, has aligned clinical trial networks with the European
Union to expand access to patients in a clinical trial to optimize the
antibacterial drug colistin for carbapenem-resistant Enterobacteriaceae
(CRE) and in a clinical trial to evaluate an antibody for use against
Pseudomonas. These collaborative efforts are helpful in gathering a
sufficient number of patients to conduct critical AMR clinical studies.
In addition, the NIAID-supported ARLG has established collaborations in
19 countries and has recently established a collaboration with the
Combatting Bacterial Resistance in Europe (COMBACTE) consortium to
enable joint design and implementation of clinical research on
antibiotic resistance. NIAID will continue to build on recent progress
in AMR research, including studies on C. auris, and is committed to
supporting partnerships with academia, industry, and Federal and
international partners to develop novel strategies to combat the spread
of AMR in bacterial and fungal pathogens.
new kinds of investigators
Question. How have the BRAIN initiative and efforts around
Alzheimer's disease helped recruit new investigators from various
disciplines with diverse skill sets and backgrounds to work in these
areas, and what have been the results? Is this something that could and
should be replicated in other parts of NIH?
Answer. The challenge, allure, and importance of understanding the
brain and its disorders have always attracted scientists and clinicians
with diverse skills and backgrounds. The Brain Research through
Advancing Innovative NeuroTechnologies (BRAIN) Initiative, which is
advancing the frontiers of technology and of brain science, has
attracted an even wider breadth of skill and talent. The Initiative has
engaged the full spectrum of neuroscientists and clinicians, including
neurologists, neurosurgeons, and psychiatrists, and recruited experts
from disciplines that include behavior, chemistry, cell biology,
mathematics, nanoscience, optics, and physics, as well as computer
science and informatics. More than a quarter of researchers at the
BRAIN Initiative Annual Investigators meeting this April were
engineers, which reflects the strong emphasis on technology
development. About a quarter of principal investigators are also early
stage investigators, receiving their first independent NIH funding, and
many other project leaders and members of research teams are entirely
new to neuroscience.
To recruit this broad spectrum of investigators, the Initiative has
emphasized the importance of diverse expertise since its inception.
Funding opportunity announcements explicitly call for innovative and
diverse approaches, with integration of technology developers and
neuroscientists, and of theorists, computational biologists, and
experimentalists. Peer review panels are attuned to this priority of
the Initiative. Extensive outreach has reinforced this emphasis.
NIH has also been particularly successful in encouraging early-
stage investigators as well as established investigators not previously
focusing on Alzheimer's disease and related dementias (AD/ADRD) to
apply for AD/ADRD-related research funding. An internal NIA analysis
has shown that between 2015 and 2018, over a quarter of the Institute's
Research Project Grant (R01) equivalent AD/ADRD awardees were either
NIH-designated New Investigators (i.e., this was their first
competitive NIH grant) or Early-Stage Investigators (not only was this
their first competitive NIH grant, but they were also within 10 years
of their terminal degree). Approximately one third of the R01 AD/ADRD
awardees had not previously applied for AD/ADRD funding from NIH--just
below half of whom were established investigators previously pursuing
other lines of research. We anticipate that the success of these
investigators in securing funding will ensure an active pipeline of
energetic researchers looking at AD/ADRD from new perspectives for
years to come.
Recognizing the importance of bringing fresh perspectives, NIA also
released a notice in 2018 inviting researchers holding non-AD/ADRD
grants from other NIH Institutes and Offices to apply for supplemental
funding for new research that was relevant to both AD/ADRD and the
topic of their research grant. The response was robust. Over 300
supplements were awarded to investigators representing some 25 NIH
Institutes, Centers, and Offices, broadening the spectrum of research
and inspiring investigators to think creatively about how their area of
study could interface productively with research on AD/ADRD.
Although each disease and field of medicine presents unique
challenges, NIH is certainly learning from Alzheimer's disease research
and the BRAIN Initiative on the value of bringing in diverse expertise
and new investigators and the strategies to accomplish that. Just as
the Human Genome Project stimulated many areas of science and medicine
beyond genetics, we expect the knowledge, technology, and strategies
stimulated by the BRAIN Initiative and the aggressive goals of
Alzheimer's and related dementias research will have much broader
implications. NIH will continue to track progress in multi-disciplinary
collaborations to ensure best practices are promulgated.
methamphetamine treatment
Question. Parts of the U.S. are seeing an alarming increase in
methamphetamine overdoses over the past few years. As you know, there
are currently no FDA-approved treatments for methamphetamine
dependence. What can you tell me about NIDA's efforts to develop
treatments methamphetamine addiction?
Answer. NIH is committed to addressing the alarming increase in
methamphetamine overdoses, which rose fivefold from 1999 to 2017. As
mentioned, there are currently no FDA-approved treatments for
methamphetamine dependence and the most effective treatments are
behavioral therapies, such as cognitive behavioral therapy and
contingency management. While drug targets exist for methamphetamine
that are analogous to those used in treating opioid addiction, alcohol
addiction, and nicotine addiction, targeting them has not been
similarly successful, necessitating a novel drug development approach.
NIH, primarily through NIDA, continues to invest in tackling
methamphetamine addiction, investing roughly $49 million on
methamphetamine research in fiscal year 2018. NIDA takes a multi-
pronged approach to this challenge, balancing its portfolio across
basic research on the health effects of use, epidemiology of use and
addiction, and efforts aimed at developing new treatments. This
strategy allows researchers to test promising treatments and to
leverage our increasing understanding of methamphetamine's mechanism of
action to devise new ones. Importantly, as part of this portfolio, NIDA
supports clinical trials using a wide range of potential approaches,
from targeting signaling pathways involved in building tolerance to
methamphetamine, to exploring immunotherapy and anti-inflammatory
approaches, to testing effective pharmacotherapies for opioid use
disorder that might have potential to help in methamphetamine use.
Much of the research in this area to date has involved testing
drugs that are already approved for other conditions, such as
antidepressants and medications for opioid use disorder. While none of
the drugs tested to date were sufficiently effective to warrant use in
routine treatment, one potentially promising therapy uses antibodies
that bind to methamphetamine and block it from reaching the brain, thus
preventing both the euphoric effects and the brain changes that lead to
addiction. NIDA is also supporting the study of behavioral
interventions using mobile apps that might help individuals with
methamphetamine addiction adhere to treatment and remain abstinent.
While many of the trials are still in the fairly early stages, some
have yielded preliminary analyses that may offer hope for patients
suffering from methamphetamine dependence.
______
Questions Submitted by Senator Richard J. Durbin
new funding
Question. Over the past 4 years, this Committee has provided NIH
with more than $9 billion in increased funding, a 30 percent increase.
Dr. Collins, what has this 30 percent increase meant to NIH? What new
initiatives or projects have you been able to establish as a result of
the new funding? How many new and promising grants have you been able
to fund with the additional funding?
Answer. These resources have supported a broad range of research
conducted both through NIH's intramural research program and through
the tens of thousands of extramural researchers in institutions across
the country. This truly exciting, world class science is leading to
breakthroughs in multiple areas.
More than two-thirds of the NIH budget supports extramural research
grants, and funding for these grants grew 33 percent over the last 4
years, slightly faster than the 30 percent overall budget increase.
Funding for research project grants (RPGs), which are the classic
mechanism of support for investigator-led research into specific
biomedical research questions, grew by 37 percent over this period.
This funding increase allowed NIH to increase the number of RPG awards,
while also compensating researchers for the effects of biomedical
research inflation. The total number of RPG awards grew by 7,010, or 20
percent, from fiscal year 2015 through fiscal year 2019. Meanwhile, the
number of new and competing awards grew by 2,135, or 22 percent. This
increase allowed the RPG success rate to rise from 18.3 percent in
fiscal year 2015 to an estimated 20.3 percent in fiscal year 2019 in
spite of an increase of more than 10 percent in the number of
applications. Increased resources have allowed NIH to initiate or
expand a number of critical research programs. The following list
highlights just a few examples:\111\
---------------------------------------------------------------------------
\111\ Estimates for Alzheimer's Disease and antimicrobial
resistance are from NIH estimates of support for research, condition,
and disease categories (RCDC), available on the NIH website at https://
report.nih.gov/. These estimates show research support for 288
research, condition, and disease categories ranging alphabetically from
Acquired Cognitive Impairment to Youth Violence Prevention, including
project detail for completed years.
---------------------------------------------------------------------------
--All of Us. Initiated in fiscal year 2016, the NIH All of Us
Research Program is a historic effort to gather data from one
million or more people living in the U.S. to accelerate
research and improve health. All of Us, funded in part with
amounts authorized by the 21st Century Cures Act, is a key
element of the Precision Medicine Initiative (PMI), which seeks
to take into account individual differences in lifestyle,
environment, and biology to enable prevention and treatment
strategies tailored to individuals. All of Us will serve as a
national research resource to support thousands of studies,
covering a wide variety of health conditions. As of early April
2019, more than 212,000 people had begun the enrollment
process, and more than 129,000 had completed all the steps in
the protocol.
--Cancer Moonshot. Resources authorized by the Cures Act for the Beau
Biden Cancer Moonshot are catalyzing progress in a number of
areas to improve diagnosis and treatment of a broad range of
cancers. Investments in the rapidly advancing field of cancer
immunotherapy are particularly promising in harnessing the
body's own immune system to fight off the disease. Resources
are also being used to create a national ecosystem for sharing
and analyzing cancer data to facilitate efficient data
analysis, to overcome drug resistance of cancer cells, and to
minimize the debilitating side effects of some cancer
treatments.
--Brain Research through Advancing Innovative Neurotechnologies
(BRAIN) Initiative. The BRAIN Initiative, which is also
supported in part with Cures Act funding, seeks to develop and
apply technologies that will revolutionize our understanding of
the human brain in health and disease. The initiative has
supported research identifying the gene expression patterns of
different subtypes of brain cells that can identify what makes
different types of cells unique, demonstrating the use of
neurotechnologies with clinical applications, such as deep
brain stimulation, and mapping functional circuits across the
brain, paving the way for an unprecedented level of
understanding of the human brain and improving human health.
--Helping to End Addiction Long-Term (HEAL). The HEAL Initiative,
first funded in fiscal year 2018, aims to bring scientific
solutions to address the crisis of opioid addiction and to
provide safe and effective options for the more than 25 million
Americans who suffer from daily chronic pain. Through HEAL, NIH
is building on basic science discoveries to accelerate the
development of novel medications and devices to treat all
aspects of the opioid addiction cycle, including chronic use,
withdrawal symptoms, craving, relapse, and overdose. In
addition, studies on integrating prevention and treatment
approaches into practice, including the HEALing Communities
study, will inform understanding of how the implementation of
promising and evidence-based strategies and treatments can
decrease opioid use disorder and overdose deaths.
--Alzheimer's Disease. Overall NIH funding for research into
Alzheimer's Disease and related dementias (AD/ADRD) has grown
almost threefold over the last 4 years, from $631 million in
fiscal year 2015 to $2,468 million in fiscal year 2019.1
Approximately 70 funding opportunity announcements (FOAs)
relating to AD/ADRD are currently active, including new
clinical and preclinical studies. A new NIH-supported clinical
trials consortium is expected to accelerate and expand studies
for therapies in Alzheimer's Disease and related dementias. The
Alzheimer's Clinical Trial Consortium (ACTC) will encompass 35
sites across the United States, and will address the timeframe,
complexity and expense of the recruitment process and site
activation for Alzheimer's trials to find new and effective
ways to treat or prevent these devastating disorders.
--Combatting Antimicrobial Resistance. NIH-funded research to combat
the rising public health problem of drug-resistant bacteria has
nearly doubled since fiscal year 2015.1 Antibiotic resistant
bacteria cause at least 2 million infections and 23,000 deaths
each year in the United States, according to the CDC. These
efforts include the Antimicrobial Resistance Diagnostic
Challenge, a $20 million Federal prize competition seeking
innovative, rapid point-of-care laboratory diagnostic tests to
combat the development and spread of drug resistant bacteria.
Five finalists in the competition were announced in December of
2018.
--The Challenge is a joint effort between the National Institutes
of Health and the HHS Office of the Assistant Secretary for
Preparedness and Response (ASPR) in support of the National
Action Plan for Combating Antibiotic Resistant Bacteria.
NIAID and ASPR's BARDA are each contributing $10 million to
the Challenge. The Challenge also was developed with
technical and regulatory expertise from the CDC, the FDA,
and NIH Office of the Director.
--Universal Flu Vaccine. In fiscal year 2018, NIH unveiled a
strategic plan to guide future basic, translational, and
clinical research investments in areas essential to creating a
safe and effective universal influenza vaccine. Along this
path, NIH is funding basic research to understand the
transmission, natural history, and disease process of
influenza. Several universal flu vaccine strategies are already
being tested in NIH-supported clinical trials.
--Down Syndrome. The INCLUDE (INvestigation of Co-occurring
conditions across the Lifespan to Understand Down syndromE)
project, launched in fiscal year 2018, is a new trans-NIH
research initiative on critical health and quality-of-life
needs for individuals with Down syndrome. INCLUDE will assemble
a large study population of individuals with Down syndrome and
include individuals with Down syndrome in existing clinical
trials. Individuals with Down syndrome are at higher risk for
certain diseases such as Alzheimer's Disease, but at lower risk
for others such as coronary artery disease and solid tumors,
raising the possibility that better understanding Down syndrome
will yield health benefits for the general population as well.
e-cigarettes
Question. Big Tobacco says e-cigarettes are a ``safe'' alternative
to cigarettes, a way to get people to stop smoking. They make this
claim despite never having conducted a clinical trial in the U.S. to
prove it. So, while we don't actually know if e-cigarettes help adults
quit, we do know that they are causing kids to start vaping and
smoking. In 2018, youth use of e-cigarettes increased by 78 percent
among high school students, and 48 percent among middle-school
students. Today, nearly 4 million children are using e-cigarettes. This
dramatic uptick is due to products like JUUL and kid-friendly flavors--
fruit medley, fruity pebbles, choco milkshake, smurf, gummy bear. 81
percent of kids vaping started with a flavored product. What is even
more alarming is that there's evidence to suggest that e-cigarettes are
actually causing kids to start smoking cigarettes! Dr. Collins, Dr.
Lowy, and Dr. Volkow, are you alarmed by what you've seen with the
massive increase in youth use of e-cigarettes? Just last week, the FDA
reported that some people were having seizures as a result of e-
cigarette use. What do we know about the health effects of e-
cigarettes, especially for children?
Answer. Any increase in nicotine use among adolescents is alarming.
While youth cigarette smoking is at an all-time low, overall nicotine
use through vaping is rising and reversing these gains. There is a
perception that vaping is harmless because it does not involve the
burning of tobacco--the source of carcinogenic tar in combustible
cigarette smoke. While the long-term health impacts of e-cigarette use
are unknown, emerging data from toxicological, animal, and human
studies point to some concerning precursors to disease endpoints and
health effects. For example:
--Chemicals that are known carcinogens--for example, formaldehyde--
have been found in e-cigarette aerosol and are found in
increasing amounts at higher heat levels.\112\
---------------------------------------------------------------------------
\112\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954153/.
---------------------------------------------------------------------------
--Primary exposure to e-cigarette aerosol may increase oxidative
stress and inflammation, important risk factors for cancer,
cardiovascular, and pulmonary health consequences.\113\ For
example, earlier this year, NCI-supported researchers published
findings that people who vaped were nearly twice as likely to
experience wheezing compared to people who didn't regularly use
tobacco products.\114\
---------------------------------------------------------------------------
\113\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768608/.
\114\ https://www.ncbi.nlm.nih.gov/pubmed/30760629.
---------------------------------------------------------------------------
--E-cigarette use may cause lasting changes to gene expression.
Preliminary results from a study of nearly 100 e-cigarette
users led by NIEHS intramural investigators suggest that e-
cigarette use may cause unique patterns of DNA modifications in
blood cells which could alter gene expression in these cells.
--Nicotine exposure during adolescence can cause addiction and harm
the developing brain. NIDA, along with NCI, NIAAA, and other
NIH Institutes and Centers, is leading the Adolescent Brain and
Cognitive Development Study, which will examine the effects of
environmental factors, including nicotine use, on the
developing brains of adolescents.
FDA recently reported on 35 cases of seizures among people who have
used e-cigarettes, including youth and young adults, between 2010 and
2019. Although seizure is a known potential consequence of nicotine
poisoning, FDA cautioned that it does not know if there is a direct
relationship between e-cigarette use and seizure risk, or how e-
cigarette use behavior, use of other substances, or underlying
conditions may have contributed to these seizures.\115\ Despite those
unknowns, NIH agrees with the FDA that it is important to share
information on potential serious risks with the public as it becomes
evident.
---------------------------------------------------------------------------
\115\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm635157.htm.
---------------------------------------------------------------------------
Several studies, some funded by an FDA-NIH partnership, demonstrate
that e-cigarette use among never-smoking youth is a risk factor for
future cigarette smoking.\116\ One found that non-smoking youth who try
e-cigarettes are more likely to use combustible tobacco products in the
future than never users of e-cigarettes.\117\ This is particularly
worrisome considering that viewing e-cigarette advertising is
associated with initiating e-cigarette use among youth,\118\ and
exposure to e-cigarette ads on social media sites increases the
likelihood of subsequent e-cigarette use among youth who had never used
e-cigarettes.\119\
---------------------------------------------------------------------------
\116\ https://jamanetwork.com/journals/jamapediatrics/fullarticle/
2634377;https://www.ncbi.
nlm.nih.gov/pubmed/26348249;https://www.ncbi.nlm.nih.gov/pubmed/
26811353;
https://www.ncbi.nlm.nih.gov/pubmed/27296866.
\117\ https://jamanetwork.com/journals/jama/fullarticle/
2428954?resultClick=3,.
\118\ https://www.ncbi.nlm.nih.gov/pubmed/29582078.
\119\ https://www.ncbi.nlm.nih.gov/pubmed/29432916.
---------------------------------------------------------------------------
Research regarding e-cigarettes and other electronic nicotine
delivery systems (ENDS) (an umbrella term which includes JUUL), is of
high interest to NIH. NIH recently developed and published two trans-
NIH Funding Opportunity Announcements--one calling for research on the
population, applied, and clinical impacts of ENDS \120\ and the other
on basic science studies of the health effects from ENDS.\121\ NHLBI
also organized a two-day meeting of scientific experts in 2015 that led
to two grant solicitations, one in 2017 and one in 2018. Twenty
research projects have been awarded through these programs, including
animal studies on the effect of e-cigarettes on young versus old
hearts,\122\ the susceptibility of adolescent airways to e-cigarette
exposure,\123\ and the cardiopulmonary health of individuals in
households where family members smoke e-cigarettes.\124\ In addition,
NIH is studying how prevention and cessation approaches developed for
combustible cigarettes might be adapted for similar purposes in e-
cigarettes. By furthering our understanding of how they are used, how
they affect the body, and how we can implement strategies to prevent
and reduce their use, NIH aims to find ways to reverse this alarming
trend and reduce the harms associated with it.
---------------------------------------------------------------------------
\120\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-612.html.
\121\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-476.html.
\122\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9624711&icde=
44343194&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
\123\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9567413&icde=
44343005&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
\124\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9564974&icde=44342386.
---------------------------------------------------------------------------
infant mortality
Question. Too often in our country, new moms and infants--
especially women and babies of color--are dying from preventable health
problems. The U.S. is one of only 13 countries where our maternal
mortality rates are worse today than they were 25 years ago.
Nationwide, more than 700 women die every year as a result of
pregnancy--more than 70,000 others experience severe, near-fatal
complications. In Illinois, 73 women die every year due to pregnancy-
related complications--70 percent of these deaths are deemed
preventable. We are also losing babies. Annually, more than 23,000
babies die in the U.S., many due to preventable factors. Education and
income offer no protection--a black woman with an advanced degree is
more likely to lose her baby than a white woman with less than an
eighth-grade education. Dr. Collins, why is this happening in the year
2019? What research is NIH doing with respect to infant and maternal
mortality, especially for women and babies of color?
Answer. NIH supports a large and diverse portfolio of research in
maternal health, pregnancy and pregnancy outcomes, and infant
mortality, including stillbirth and Sudden Infant Death Syndrome
(SIDS). For example, in fiscal year 2018, NIH funded approximately $303
million on research related to maternal health.\125\ The NICHD is
holding a number of workshops aimed at looking at the high rate of
maternal mortality in the U.S., with a focus on the factors that are
contributing to maternal deaths in black women. The first, in April
2019, was a forum for members of community-based and healthcare
provider groups about community engagement strategies to improve
maternal health. Participants learned how patient-provider interactions
and the process for making clinical care decisions affect maternal
healthcare experiences at the local level. The second workshop, to be
held May 2019, will bring scientific experts together to discuss
research needed to address maternal mortality in the U.S. Participants
will examine data quality and trends, the populations
disproportionately affected, social determinants of maternal mortality,
and clinical causes of this serious public health issue. Among the
issues to be discussed are potential causes of the disparities in
maternal mortality, such as medical mistrust, neighborhood environment,
and the cultural frameworks needed to improve maternal health outcomes.
A third workshop, to be held in early 2020, will focus on research
needed by the medical community to address maternal mortality due to
co-morbid conditions such as obesity, hypertension and diabetes,
conditions prevalent in black women. Finally, as requested by Congress,
NICHD has also contracted with the National Academies of Sciences,
Engineering, and Medicine to conduct a study on the choice of birth
setting, including risk factors, social determinants that influence
risk, and maternal health outcomes.
---------------------------------------------------------------------------
\125\ https://report.nih.gov/
categorical_spending_project_listing.aspx?FY=2018&ARRA=
N&DCat=Maternal Health.
---------------------------------------------------------------------------
In the meantime, NICHD continues to fund investigator-initiated
prevention research on the factors that promote healthy pregnancy,
e.g., weight gain in pregnancy, lifestyle interventions, and efforts to
reduce exposure of pregnant women to risk factors. For example, a
recent NICHD-funded study showed that health outcomes associated with
short interpregnancy intervals vary by age. Compared to younger
mothers, mothers over 35 are at higher risk of death and serious
illness if they conceive 6 months or less after the birth of a previous
child.
NICHD also supports a range of research projects related to
pregnancy loss and other adverse pregnancy outcomes, determinants
(e.g., biomarkers) of healthy pregnancies, and disparities among racial
and ethnic groups and geographic regions. Among NICHD's research
priorities are the development of specific algorithms that include
physiological, biochemical, and genetic markers to predict pregnant
women at risk for pregnancy loss and/or stillbirth, improving the
chances for intervention. One NICHD-supported study published in 2018
found that, in an animal model, Zika virus infection caused early loss
of one-quarter of the pregnancies. Unfortunately, many causes of
pregnancy loss are still unknown and could result from chromosomal
factors, problems with the placenta, fetal infection, and maternal
disorders. Environmental exposures also may influence pregnancy loss.
For example, population-based research conducted in NICHD's intramural
division found that excessive exposure to high ozone levels during the
last week of pregnancy, and exposures to extremes in temperature,
increased the risk of stillbirths.
NICHD has a longstanding program of research on newborn screening,
part of the highly successful, nationwide newborn screening public
health effort that allows infants with serious or even fatal conditions
to be identified for early treatment. The research component, The
Hunter Kelly Newborn Screening Research Program, was originally
established as a provision of The Newborn Screening Saves Lives Act of
2007. Research under the program, led by NICHD, focuses on identifying,
developing, and testing new newborn screening technologies in order to
improve existing tests and develop new tests, and developing and
testing innovative interventions and treatments for conditions that can
be detected through screening, but which are not yet treatable. In the
past year, a NICHD-funded study developed a newborn screening tool to
detect Niemann-Pick Disease, a rare but fatal disorder. Niemann-Pick
disease type C (NPC) is a rare but fatal disorder that is caused by
defects in how the body stores cholesterol. Because NPC symptoms vary
widely, the disease often goes undetected, causing the brain and body
to degenerate beyond the point of treatment. NICHD-supported
researchers found that one bile acid is increased 101-fold in patients
with NPC, and quickly developed a method to detect this bile acid in
dried blood spots; the method helps to detect Niemann-Pick disease in
patients after birth, allowing doctors to treat them as soon as
possible.
In the meantime, NICHD continues to fund research to uncover the
causes of SIDS. Among the many research grants that NICHD recently
funded are hippocampus and brain stem studies in SIDS infants, cardiac
channel mutations, and respiratory and autonomic mechanisms potentially
underlying SIDS. In addition, NICHD's leadership of the Safe to Sleep
public education campaign, working with its many collaborators, allows
us to translate scientific findings on Sudden Unexpected Infant Death
and Sudden Infant Deaths Syndrome (SUID-SIDS) into audience-tailored
actionable messages. These efforts provide training, education, and
support for parents and families, healthcare providers, and other
infant caregivers in applying safe infant sleep practices. We
collaborate closely with our Federal HHS partners to ensure consistent
public communication. NICHD also supports focused activities with
health departments in areas with high SUID-SIDS rates to train service
providers and community leaders on effective risk-reduction practices
and outreach tactics. For instance, one currently funded grant is
exploring ways of enhancing safe sleep practices of urban low-income
mothers.
big pharma
Question. All 210 drugs approved by the Food and Drug
Administration (FDA) between 2010 and 2016 received NIH funding. But
today, Americans are being hit twice by Big Pharma--we pay the highest
prices in the world for many drugs, and we fund the development of them
in the first place, mostly from NIH. On top of that, drug companies
exploit another government-granted reward, the patent system. Two of
the costliest cancer drugs are Rituxan and Revlimid. Both were
developed with NIH funding, and both have received over 40 years of
monopoly protection--because both of these medications has been issued
more than 94 patents. The top 12 best-selling drugs in the United
States each have an average of 71 patents, and their prices have
increased by an average of 70 percent over the last 5 years. In fact,
74 percent of all new drug patents are for drugs already on the
market--extending monopolies well-past the 20-year patent term. In
fiscal year 2017, the NIH executed 328 licensing agreements to transfer
government- and taxpayer-funded intellectual property to industry to
bring these inventions to market. Dr. Collins, do you believe drug
companies are abusing the patent system? Do you believe that the
practice of ``evergreening''--by which brand-name pharmaceutical
companies obtain follow-on patents for often superficial or peripheral
applications, such as a pill coating, to forestall generic
competition--places a burden on the patient and societal benefits of
innovative research?
Answer. The mission of the NIH is to seek fundamental knowledge
about the nature and behavior of living systems and the application of
that knowledge to enhance health, lengthen life, and reduce illness and
disability. Much of the research supported by the NIH is basic in
nature, and the findings are published to inform the broader research
community. The commercial sector may also use this information to
inform their product discovery efforts. An analysis of 210 FDA approved
drugs (2000-2016) and the published research associated with these
drugs suggests that nearly 90 percent of the public sector funding
underlying first-in-class drugs supported basic research of biological
mechanisms, rather than drug-specific research (Cleary et al., PNAS,
March 6, 2018). Every drug, whether first-in-class or a competing
follow-on, was associated directly or indirectly with NIH-funded
research. When the patent and regulatory exclusivity periods for these
drugs end, they become generic.
The NIH licenses technologies arising from the NIH intramural
research program. Only 35 (11 percent) of the 328 license agreements
executed by the NIH in fiscal year 2017 were exclusive licenses. In
2018, NIH executed 329 license agreements, of which 26 (8 percent) were
exclusive. The category of exclusive licenses often includes more than
one exclusive license for a patented technology based on separate
fields of use, e.g. a potential cancer therapy where one company
develops it for blood cancers, another for solid tumors, and a third
only in combination with its existing brand name drug. The category of
non-exclusive license agreements includes commercial use of patented
technologies and licenses for non-patented research materials such as
cell lines, animal models and antibodies, which companies use in their
research and development programs. NIH does not charge fees to transfer
these non-patented research materials to non-profit researchers.
Thus, NIH funding supports much basic research that is ultimately
used by many for-profit researchers to develop new drugs for the
prevention and treatment of disease conditions. Non-profit researchers
make use of these published findings to further the understanding of
biological processes and sometimes the development of new drugs. The
innovative output of the US biomedical sector depends on this
foundational government support. NIH manages the licensing of its own
inventions in a manner that balances public health needs with
incentives required by the private sector to bring new products to
market. The NIH has no comment on the patent system because it is
beyond the purview of NIH.
cost of specialty oncology drugs
Question. The cost of specialty oncology drugs has increased more
than 500 percent from 2006 to 2015, which is only expected to continue.
Several studies and clinical trials, including those supported by NCI,
have demonstrated significant cost savings from examination of de-
escalation in dose, schedule, or duration of oncology medications, or
simply by taking medication with or without food. Such trials can be
self-financing, in that the relative savings from the optimized doses
could be put toward the trial operation. For example, the NCI recently
supported an international randomized study comparing a 75 percent dose
reduction (with food) to standard dosing for the prostate cancer drug,
abiraterone, which demonstrated no decline in efficacy with the lower
dose. Separately, the National Eye Institute funded a study in 2011 to
examine optimal dosing for ranibizumab.
Does NIH believe that there may be a potential clinical benefit for
patients to the study of optimal drug dosing and frequency regimens, in
particular for oncology medications?
Answer. The NCI conducts and supports research to identify when
patients will benefit from treatment, and when multiple therapies will
not provide patient outcomes. Reducing the frequency and number of
therapies a patient receives during cancer treatment not only reduces
healthcare costs but often minimizes the risk of side effects,
complications, and long-term (late) effects. Researchers are
capitalizing on advances in molecular and genetic profiling of cancers
to develop clinical studies that will help to identify when it is
appropriate to de-escalate doses, adjust treatment schedules, or
shorten the duration of oncology therapies.
The mission of the NCI clinical trials programs includes an
emphasis on filling gaps in the national cancer research effort and
avoiding duplicating on-going private sector efforts. Research
questions focused on de-escalation of standard therapies, or
distributing less therapy, are not likely to be answered by industry-
sponsored trials--leaving a research gap that the NCI's clinical trials
program seeks to fill. Removing or de-escalating well-accepted standard
therapies in oncology requires significant care. Randomized trials are
the gold standard, but require large numbers of patients and rigorous
study design. NCI has supported several de-escalation studies through
its National Clinical Trials Network, including recent trials in breast
cancer and head and neck cancer.
The Trial Assigning Individualized Options for Treatment (TAILORx)
was a large phase 3 trial designed to evaluate the benefit of
chemotherapy for patients with certain early stage breast cancers and
an intermediate risk of recurrence based on the 21-gene breast cancer
assay, Oncotype DX. Between 2006 and 2010, more than 10,000 patients
were screened and more than 6,700 with a moderate risk of recurrence
were randomized between hormonal therapy alone vs. hormonal therapy
plus chemotherapy. The trial was designed to show that hormonal therapy
alone is as effective at preventing recurrence, second cancers, or
death as hormonal therapy plus chemotherapy. The trial results,
published in the New England Journal of Medicine in July 2018,
demonstrated that hormonal therapy alone and hormonal therapy with
chemotherapy were similarly effective in this patient population,
although some benefit of chemotherapy was found in some women over 50
years old.\126\ This de-escalation trial demonstrated that chemotherapy
could be safely dropped from therapy for this early stage breast cancer
patient population--saving thousands of patients the burden and
toxicity associated with chemotherapy treatment.
---------------------------------------------------------------------------
\126\ https://www.ncbi.nlm.nih.gov/pubmed/29860917.
---------------------------------------------------------------------------
Human papillomavirus (HPV)-driven head and neck (oropharyngeal)
cancers have significantly better survival rates than tobacco and
alcohol-induced head and neck cancers. HPV-positive (HPV+) patients are
typically younger, healthier, and often likely to survive their
disease. The goal of de-escalation trials for patients with HPV+
oropharyngeal cancers is to see if short and long-term toxicity can be
reduced while maintaining high survival rates. The Phase 3 NRG/RTOG-
1016 trial was designed to see if the medication cetuximab therapy plus
radiotherapy (RT) was as effective at controlling HPV+ oropharyngeal
cancers as standard cisplatin therapy with RT, but with fewer side
effects. The study opened in 2011 and closed in 2014, having screened
987 patients for HPV+ tumors and randomizing 849 patients between the
two therapeutic approaches. However, the trial's results, which were
published in Lancet in January 2019, confirmed that cisplatin and
radiation should remain the standard of care for HPV-related
oropharyngeal cancers.\127\ This trial demonstrated the importance of
testing such hypotheses to ensure that patients continue to receive the
best care for their disease.
---------------------------------------------------------------------------
\127\ https://www.ncbi.nlm.nih.gov/pubmed/30449625.
---------------------------------------------------------------------------
In addition to de-escalating, investigators also seek to identify
the optimal dosing schedule for cancer therapies. For example, a recent
collaboration between NCI intramural investigators in the Center for
Cancer Research (CCR) and the University of Chicago Comprehensive
Cancer Center seeks to identify when the interval between cancer
therapy doses can be safely increased. This research uses
pharmacological modeling, which predicts the effect of different doses
and timing based on knowledge of disease processes and the rate at
which drugs are cleared from the body. Initial results suggest that,
following the initial treatments, the interval between later doses of
two cancer therapeutics can be increased without sacrificing efficacy
in most patients. The treatment schedule identified by this work would
result in a potential 70 percent cost savings for treatment with the
medications Pembrolizumab, which is used to treat a number of cancers
including melanoma and non-small cell lung cancer, and Nivolumab, which
is approved for treatment of non-small cell lung cancer.\128\ Advances
in precision medicine, or choosing a therapy based on a cancer's
particular genetic and molecular profile, may also ultimately help to
contain healthcare costs. Recent work by several researchers in NCI's
CCR have focused on classifying several types of cancer, including
melanoma,\129\ diffuse B-cell lymphoma,\130\ and liver cancer \131\
into discrete subtypes based on gene expression patterns, as well as
identifying molecular similarities between different tumor types.
Identifying these different subtypes allows researchers and clinicians
to better predict which treatments are likely to be effective for a
patient and limit the use of expensive therapies with little hope of
activity and potentially drive down costs.
---------------------------------------------------------------------------
\128\ American Society for Clinical Oncology 2019 Annual Meeting,
Poster #107, Abstract #3115: A modeling and simulation study of less
frequent dosing of nivolumab 480 mg. Peer, Cody J.; Goldstein, Daniel
A.; Figg, William D.; Ratain, Mark J.
\129\ https://ccr.cancer.gov/news/milestones-2019/article/
predicting-immunotherapy-responses.
\130\ https://ccr.cancer.gov/news/milestones-2019/article/sorting-
lymphoma-subtypes.
\131\ https://ccr.cancer.gov/news/milestones-2018/article/
different-and-the-same.
---------------------------------------------------------------------------
As NCI leaders discussed in a recent article feature in the Journal
of the American Medical Association (JAMA), the costs of conducting the
clinical trials required for drug approvals contribute to the list
prices of pharmaceutical products. The average per-patient costs have
increased dramatically during the past two decades, an important factor
in the total costs of drug discovery and development. Therefore, NCI is
working to ensure that trials are appropriately sized to answer the
scientific questions they pose, developing trials with fewer patients
whenever possible. For example, in some trials of highly active agents,
it may be possible to evaluate the drug without traditional control
trials arms, instead relying on ``synthetic'' control groups created
from data from previous trials. NCI is also considering the use of
novel end points for clinical trials that are based on the agent's
mechanisms of action and conducted through the aggregation of new and
existing data.\132\
---------------------------------------------------------------------------
\132\ https://jamanetwork.com/journals/jama/fullarticle/2723062.
---------------------------------------------------------------------------
NCI will continue to work closely with the FDA and other Federal
agencies and support research on the best therapeutic approaches for
patients.
childhood trauma
Question. So many children nationwide grow up in homes where they
witness violence or drug misuse, or face abuse or neglect. I see this
all over Chicago, but also in rural communities in my state. With the
Adverse Childhood Experiences (ACEs) study, we now understand how this
toxic stress from these situations can have serious, long-term impacts
on the developing mind. Studies show that exposure to multiple ACEs or
traumatic experiences increases the likelihood of chronic disease
development, mental illness, drug use, poverty, and violence.
Thankfully, there are interventions that can help children cope with
this trauma, and process the experiences they have faced. This
Subcommittee has included my language with Senator Capito each of the
past 2 years to prioritize these trauma-informed best practices in more
Federal grant programs. And Section 7132 of the SUPPORT for Patients
and Communities Act established a Federal interagency task force to
identify and disseminate such trauma-informed best practices. Dr.
Collins, what research is NIH doing to study childhood trauma and its
impact on long-term mental health and other outcomes, as well as
interventions to mitigate the impact of such adversity? What more do we
need to study?
Answer. NIH, acting largely through NICHD, and NIMH, supports
research on the mental and physical health effects of trauma, including
funding investigator-initiated research related to improving our
understanding of childhood trauma and its long-term impact and
broadening the evidence-base needed to improve treatments,
interventions, and mental health services for trauma survivors.
The NICHD Pediatric Trauma and Critical Illness Branch was
established in 2012 to coalesce the science in trauma, injury and
critical illness across the Institute and to grow the field in these
areas across the continuum of care.\133\ Of particular interest are
studies that examine interactions between physical and psychological
trauma, emergency medical services to children, injury prevention and
the provision of critical care medicine to the most vulnerable
children.\134\ The Branch's research portfolio on psychological trauma,
traumatic stress, violence, and child maltreatment supports projects
that examine the psychological processes that co-occur with physical
trauma, which affect treatment, recovery, and well-being. To grow and
maintain the pipeline of research experts in this area, NICHD also
supports research training programs, such Career Development Awards,
focused on training in child maltreatment research, and a national
physician scientist training program for pediatric trauma surgeons and
intensive care physicians.\135\
---------------------------------------------------------------------------
\133\ https://www.nichd.nih.gov/sites/default/files/publications/
pubs/Documents/Pediatric
Trauma_Action_Agenda.pdf.
\134\ https://injuryprevention.bmj.com/content/injuryprev/21/6/
441.full.pdf.
\135\ https://www.nichd.nih.gov/research/supported/pcctsdp.
---------------------------------------------------------------------------
Recently, NICHD called for research resource-related projects on
the epidemiology and prevention of injury, receiving an excellent
response from the field. Among the projects funded is a study on the
value of pediatric readiness in the emergency care of injured children.
Its major goal is to construct a large, multi-State dataset to
determine if pediatric readiness in emergency medicine will result in
improved quality of care, patient health outcomes, and costs of care
for injured children. This project will produce the largest population-
based, pediatric trauma database, a unique research resource that would
fill important knowledge gaps in pediatric trauma care and help to
identify a re-engineered, high-value emergency care system for injured
children that optimizes quality, outcomes, and costs. A second project
was funded to provide a research and treatment resource for the
management of psychological distress in children who have been
hospitalized for a physical trauma. The researchers are developing
multi-media therapeutic modules to ameliorate post-traumatic stress
symptoms and associated psychological impairment in children after an
injury to improve health related quality of life.
NICHD's hallmark program is the Capstone Centers for Child
Maltreatment Research and Training. In 2018, funding was awarded to
three new centers (for a total of four) to serve as national resources
for research on the prevention, screening and treatment of child abuse
and neglect.\136\ This program has already been productive; findings
recently released from the first center showed that adverse childhood
experiences, including being abused and having parents with mental
health issues, are associated with higher out-of-pocket healthcare
costs later in life.
---------------------------------------------------------------------------
\136\ https://www.nichd.nih.gov/newsroom/news/100418-child-
maltreatment-research.
---------------------------------------------------------------------------
NIMH recognizes that psychological trauma is an emotionally
painful, shocking, stressful, and sometimes life-threatening
experience. The cumulative nature of adverse childhood experiences can
increase the risk for poor mental and physical health outcomes.\137\ To
better understand trauma-related risk trajectories and how early life
adversity shapes emotional, cognitive, and brain development, NIMH is
supporting a landmark study on the developmental precursors of mental
illnesses.\138\ Researchers are following mothers and their infants
over the first 3 years of life to characterize development across
multiple levels of analysis, from environmental risk to physiology to
neural circuits to behavior. This research has the potential to define
the contributions of modifiable factors (psychosocial adversity,
inflammation, and early caregiver support) to the earliest indicators
of risk for psychopathology, and may pave the way for innovative early
interventions, and a greater understanding of childhood trauma.
---------------------------------------------------------------------------
\137\ https://www.ncbi.nlm.nih.gov/pubmed/16311898.
\138\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9518320.
---------------------------------------------------------------------------
There remain many unanswered questions in the field of childhood
trauma. Currently, NIMH supports over 120 human and animal research
projects related to post-traumatic stress disorder (PTSD) across the
lifespan. Through a robust traumatic stress research program that
includes basic, translational, and services and intervention
research,\139\ NIMH seeks to gain a deeper understanding of how
exposure to traumatic stress affects individuals, and how to improve
ways of identifying those at risk before adverse reactions develop.
Current NIMH priorities also include testing preventive interventions
to preempt PTSD, developing new treatments for PTSD, and making
existing PTSD treatments more effective and accessible.
---------------------------------------------------------------------------
\139\ https://www.nimh.nih.gov/about/organization/dtr/traumatic-
stress-research-and-
dimensional-measurement-and-intervention-program/index.shtml.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Jack Reed
childhood cancer
Question. As you know, there is strong bipartisan support for the
Childhood Cancer STAR Act, which was signed into law last year. For
fiscal year 2019, we provided $30 million to fund this law, the largest
piece of which we anticipated would be dedicated to developing a
national childhood cancer biorepository. What progress have you made in
this area, and how much of the $30 million provided by Congress do you
anticipate investing in the biorepositories this year?
Answer. NCI appreciates the strong bipartisan support for childhood
cancer research demonstrated through passage of the Childhood Cancer
STAR Act, and NIH is committed to implementing its provisions. At NCI,
efforts are underway to implement the childhood cancer survivorship
research and biospecimen and biorepository research provisions, as well
as other provisions focused on enhancing pediatric expertise on NCI
advisory boards, and continued reporting on childhood cancer research
activities.
NCI continues to make progress in expanding and enhancing
biospecimen collection and related research. For many years, NCI has
supported the Children's Oncology Group (COG) and the COG
Biorepository, and these efforts serve as NCI's central effort to bank
biospecimens from children and adolescents with cancer for future
research use. The Institute is hosting a scientific meeting in May 2019
to bring together representatives from across the COG, including those
involved in the COG Biorepository, and subject matter experts from
across the childhood cancer research community who focus on specimen
collection for cancer subtypes that are most refractory to treatment.
NCI has invited colleagues from the Centers for Disease Control and
Prevention's National Program of Cancer Registries to this meeting, as
well as members of the childhood cancer advocacy community.
This meeting will provide an opportunity to discuss specimen
collection and biobanking challenges, particularly those related to
specimen sharing across institutions, standardization of specimen
annotation, and specimen quality control. The meeting will also focus
on opportunities to further enhance specimen collection and storage, to
encourage greater collaboration across institutions, to collect
additional high-priority specimens outside the context of clinical
trials, and to ensure that any new specimen collection efforts are
complementary to those underway, such as ongoing collection and
analysis of specimens at relapse through the NCI-COG Pediatric MATCH
trial.\140\
---------------------------------------------------------------------------
\140\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/pediatric-match.
---------------------------------------------------------------------------
We look forward to the valuable guidance and input this discussion
will provide to the entire childhood cancer research community, which
may inform any additional new biospecimen collection efforts or
biorepository resource enhancements in fiscal year 2019, fiscal year
2020, and beyond, to further implement these provisions of the STAR
Act. While NCI is committed to making significant investments to
advance this important work, we also recognize that the STAR Act
authorization of $30 million per year covers all sections of the
legislation, including aspects of the law that are directed at other
entities within the Department of Health and Human Services.
In fiscal year 2019, NCI is making several new investments to
support biospecimen collection and analysis that align with STAR Act
provisions. These include biospecimen analysis studies within NCI
pediatric and the adolescent and young adult (AYA) clinical
trials;\141\ the NCI Pediatric Oncology Branch MyPART (My Pediatric and
Adult Rare Tumor) Network;\142\ and the Center for Pediatric Tumor Cell
Atlas, part of the Cancer Moonshot Human Tumor Atlas Network. The
Center, located at the Children's Hospital of Philadelphia, will focus
on three high-risk cancer subtypes that combined, account for 50
percent of all pediatric cancer deaths: high-grade glioma, high-risk
neuroblastoma, and very high risk acute lymphoblastic B-cell precursor
leukemia.\143\ NCI has also prioritized additional new funds in fiscal
year 2019 for our National Clinical Trials Network Groups, including
COG, to improve patient enrollment in clinical trials. Efforts are also
underway through the Cancer Moonshot to perform retrospective analysis
on pediatric biospecimens. The retrospective analysis involves
additional sequencing of specimens from several completed COG trials,
allowing for in-depth annotation of these specimens to support future
research. These investments are all in addition to NCI's long-term
commitment to supporting specimen collection through COG clinical
trials, and specimen storage through the COG Biorepository.
---------------------------------------------------------------------------
\141\ https://www.cancer.gov/about-nci/organization/ccct/funding/
biqsfp.
\142\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor.
\143\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9627531&icde=0.
---------------------------------------------------------------------------
There is a compelling need for the childhood cancer research and
advocacy community to discuss opportunities specific to biospecimen
collection and biorepository resources. Understanding these insights is
best before we develop any new funding opportunity announcements to
ensure that these rare and much needed research participant
contributions are maximally impactful. With that principle in mind, NCI
anticipates that fiscal year 2020 STAR Act implementation activities
will expand emphasis on biorepositories, whereas fiscal year 2019 STAR
Act implementation activities will include greater emphasis on
survivorship research.
Question. Can you provide additional details on the President's
childhood cancer initiative and how it will coordinate with the STAR
Act programs? Can you confirm that this $50 million request is in
addition to the $30 million in funding that we secured in fiscal year
2019 (and which we are seeking on a bipartisan basis to build on in
fiscal year 2020)?
Answer. There are approximately 16,000 children and adolescents
diagnosed with cancer in the United States each year. The President's
Budget proposes an additional $50 million in fiscal year 2020, to
continue for 10 years and provide a total of $500 million to support
the Childhood Cancer Data Initiative. This initiative focuses on the
critical need to obtain and analyzing data to learn from children with
cancer. This information, spanning the spectrum of tumor analysis to
clinical care and outcomes of each child, will underpin our ability to
develop new approaches to cure children with cancer.
The additional resources of $50 million in fiscal year 2020 will
allow the NCI to expand efforts to collect data, to make strides in
federating existing sources of data, to ensure that data concerning
childhood cancers are appropriately accessible and used, and to
incentivize the cancer research community to develop new treatments for
children with cancer. The initiative is a promising opportunity to
enhance our ability to improve outcomes for children with cancer--first
by learning from every one of these children in an intentional and
organized manner and second by developing more efficient ways to share
and use the information. We envision that it will aggregate the
necessary information to foster essential research while also
increasing available information about each child's illness. Such
information will include extensive sequencing of tumors and additional
clinical information regarding each child's response to treatment.
NCI is hopeful that the Childhood Cancer Data Initiative will also
serve as a force multiplier for efforts aligned with implementation of
the Childhood Cancer STAR Act. NCI-supported biospecimen collection and
associated data would all contribute to the aggregated data resources
NCI plans to develop through the initiative. NCI would also aim to
integrate data collected though new and continued childhood cancer
survivorship research projects and ongoing longitudinal studies (e.g.,
Childhood Cancer Survivor Study, St. Jude Lifetime Study) through the
initiative. New data linkages and resources may also enable the cancer
research community to establish additional cohorts to complement the
Childhood Cancer Survivor Study, allowing NCI to study the long-term
effects of new immunotherapy and targeted chemotherapy treatments. NCI
is also exploring opportunities to leverage data collected through NCI
and CDC cancer registries programs, including data collected though
CDC's early case capture efforts for pediatric and young adult cancer
cases. This program is a central piece of CDC's STAR Act
implementation, and the Childhood Cancer Data Initiative has the
potential to further build upon that work.
In summary, NCI will continue these important research efforts with
whatever resources are available to us. If appropriated, the
President's Budget request envisions the $50 million proposed for the
Childhood Cancer Data Initiative as additional new resources. In the
current fiscal year, NCI is supporting implementation of the STAR Act
provisions that are directed toward the Institute. For example, in
addition to continuing to conduct and support childhood, AYA cancer
survivorship research, NCI is expanding support in this area for new
research projects. Specifically, NCI issued a new request for
applications in fiscal year 2019. We estimate that we will allocate
approximately $4.8 million per year for 5 years, to this survivorship
research priority, subject to receiving meritorious applications and
future fiscal year funding, among other considerations. NCI is also
working to enhance biospecimen collection, biobanking, and related
resources for childhood and AYA cancers, with an emphasis on those
cancer types and subtypes for which treatments are least effective, as
specifically encouraged in the STAR Act.
suicide
Question. CDC reported in June 2018 that the suicide rate has risen
30 percent since 1999. Given this national crisis, can you discuss what
research is being conducted on suicide prevention research at the NIMH
and how does NIMH set research priorities specific to suicide and
suicide prevention?
Answer. Suicide prevention research continues to be a top priority
for NIH.\144\ Over the past several years, NIH has steadily increased
its support for suicide research. NIH spent approximately $46 million
on suicide research in fiscal year 2015, $52 million in fiscal year
2016, $68 million in fiscal year 2017, and $96 million in fiscal year
2018.
---------------------------------------------------------------------------
\144\ https://www.nimh.nih.gov/about/director/messages/suicide-
prevention.shtml.
---------------------------------------------------------------------------
As the lead Federal agency for research on mental disorders, the
National Institute of Mental Health (NIMH) within the NIH takes a
central role in research aimed at identifying at-risk individuals and
developing new treatments and interventions, ultimately to improve
quality of life and prevent death. NIMH recognizes that comprehensive
suicide prevention efforts require multiple approaches, with the
following research projects exemplifying some of our most promising
tools.
Identifying At-Risk Individuals:
--Implementing Universal Screening: The Emergency Department Safety
Assessment and Follow-up Evaluation (ED-SAFE) study
demonstrated that a three-item screening tool improved
providers' ability to identify adults at risk for suicide.\145\
This study showed that when screening was conducted for all
patients--regardless of the reason for their emergency
department (ED) visit--suicide risk detection increased nearly
twofold. If these findings remain true when scaled up, the
public health impact could be tremendous, because
identification of risk is the first and necessary step for
preventing suicide.
---------------------------------------------------------------------------
\145\ https://www.ncbi.nlm.nih.gov/pubmed/26654691.
---------------------------------------------------------------------------
--Maximizing Electronic Health Records: Building on the Army Study to
Assess Risk and Resilience in Servicemembers (Army
STARRS),\146\ the largest study of mental health risk and
resilience ever conducted among military personnel, researchers
from NIMH partnered with the Department of Veterans Affairs
(VA) and other collaborators to develop predictive models of
suicide risk among veterans receiving VA healthcare. This
research demonstrated the feasibility of developing algorithms
to identify patients within the VA system whose predicted
suicide risk was 20-30 times higher than average. Suicide
prevention coordinators at each VA facility work with these
patients and their clinicians on suicide-focused clinical
assessment and ways to enhance treatment. Other healthcare
systems are beginning to use data from electronic health
records in novel ways to help identify people with suicide
risk, including many of the 13 healthcare systems across the
United States that are part of NIMH's Mental Health Research
Network.\147\
---------------------------------------------------------------------------
\146\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286426/.
\147\ https://www.ncbi.nlm.nih.gov/pubmed/29792051.
---------------------------------------------------------------------------
Developing New Treatments and Interventions:
--Strengthening Mental Health Support: NIMH continues to support
research to identify effective interventions for individuals at
risk for suicide. One such intervention is Safety Planning
Intervention (SPI), in which a clinician collaborates with the
patient to identify specific strategies to decrease the risk of
suicidal behavior, such as ways to reduce the patients' access
to lethal means during a time of crisis, and to identify
personalized coping strategies. NIMH is supporting an
evaluation of the implementation of the Zero Suicide approach,
including SPI, in 145 community mental health clinics across
New York.\148\ In addition, NIMH's ED-SAFE study, which focused
on ED patients at risk for suicide, found that brief
interventions in the ED, plus follow-up phone calls to the
patient by a clinician, reduced suicide attempts by about 30
percent during a 12-month period.\149\
---------------------------------------------------------------------------
\148\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9514242.
\149\ https://www.ncbi.nlm.nih.gov/pubmed/28456130.
---------------------------------------------------------------------------
--Deploying Fast-Acting Pharmacologic Interventions: NIMH research
has also supported the study of fast-acting treatments for
individuals with acute suicide risk. Ketamine, an anesthetic
that has been around for decades, is emerging as a rapid onset
intervention. NIMH researchers showed that suicidal ideation
(in the context of major depressive disorder) was reduced
within 40 minutes of a ketamine infusion and remained improved
for up to four hours post-infusion.\150\ A subsequent meta-
analysis reported that a single infusion of ketamine reduces
suicidal ideation for up to one week.\151\ In March 2019, the
FDA approved SpravatoTM, an esketamine nasal spray
(a form of ketamine), in conjunction with an oral
antidepressant, for treatment-resistant depression.\152\ This
treatment is only available at a trained doctor's office or
clinic to mitigate potential risks. The makers of
SpravatoTM are also conducting clinical trials of
intranasal esketamine in participants at imminent risk for
suicide.\153\
---------------------------------------------------------------------------
\150\ https://www.ncbi.nlm.nih.gov/pubmed/20673547.
\151\ https://www.ncbi.nlm.nih.gov/pubmed/28969441.
\152\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm632761.htm.
\153\ https://www.ncbi.nlm.nih.gov/pubmed/29656663.
---------------------------------------------------------------------------
NIMH's overall research priorities continue to be informed by
strategic planning and include the input of stakeholders, advisory
committees, and NIMH leadership. In developing these priorities, NIMH
strives to balance public health needs and scientific opportunities,
taking into consideration portfolio balance among other factors. For
example, specific to suicide prevention, the stakeholder-informed
Prioritized Research Agenda for Suicide Prevention is an available
resource that can be used to help identify gaps in the NIMH suicide
prevention portfolio.\154\ NIMH only funds research which is judged
highly meritorious and follows a two-stage peer review process.
---------------------------------------------------------------------------
\154\ https://theactionalliance.org/resource/prioritized-research-
agenda-suicide-prevention-action-plan-save-lives.
---------------------------------------------------------------------------
Question. The recently released action plan from the National
Action Alliance for Suicide Prevention outlines the need to develop a
prioritized approach for allocating funds and monitoring future suicide
research to ensure that available resources are directed towards
research with the greatest likelihood of reducing suicide deaths. Has
NIH reviewed these recommendations and, if so, what does NIH plan to do
with the recommendations?
Answer. NIMH is working with scientists and stakeholders to address
the increasing incidence of suicide across the country, focusing on
identifying research gaps, challenges, and opportunities to inform how
to make change now and in the longer-term. Under the leadership of
former NIMH Director Thomas Insel, M.D., the Research Prioritization
Task Force (RPTF) aimed to advance the efforts of the National Action
Alliance for Suicide Prevention (NAASP), a public-private partnership
among Federal agencies, State governments, private companies, and
national suicide prevention advisory and advocacy groups. As part of
the RPTF, NIMH helped to develop the Prioritized Research Agenda for
Suicide Prevention.\155\ The Agenda identifies research gaps, such as
limitations in understanding of the etiology and course of suicidal
ideation and behavior, the need for new interventions specifically
targeting suicide, better matching of existing treatments to individual
needs, and implementation of effective suicide prevention practices.
---------------------------------------------------------------------------
\155\ https://theactionalliance.org/resource/prioritized-research-
agenda-suicide-prevention-action-plan-save-lives.
---------------------------------------------------------------------------
NIMH has initiated research opportunities to address research gaps
identified in the Agenda, such as studies to develop and test screening
approaches for use in EDs to identify youth at risk for suicide, and
develop methods to help assign youth who screen positive to appropriate
interventions.\156\ NIMH also partnered with other NIH Institutes and
Centers to support projects leveraging existing data sets to improve
our understanding of risk trajectories and subgroups at risk for
suicide, while addressing suicide research gaps in mortality
outcomes.\157,158\ To further address gaps in the research workforce,
NIMH issued a notice of special interest to expand the number of mental
health researchers--both established scientists, as well as early
career scientists--who engage in suicide research.\159\
---------------------------------------------------------------------------
\156\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
070.html.
\157\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
400.html.
\158\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
410.html.
\159\ https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-
026.html.
---------------------------------------------------------------------------
In addition, NIMH partners with NAASP to support their Zero Suicide
initiative.\160\ Zero Suicide is a commitment, a goal, and a campaign
to prevent suicide attempts and deaths among individuals receiving
treatment within healthcare systems. NIMH is funding several projects
aimed at Zero Suicide to create a stronger basis for dissemination and
large-scale implementation of effective risk detection, intervention,
and service delivery strategies for suicide prevention in real world
settings.\161\ This effort is also consistent with the NIMH Strategic
Plan for Research, Objective 4, improving public health through more
practice-ready suicide prevention interventions.\162\
---------------------------------------------------------------------------
\160\ http://zerosuicide.sprc.org/.
\161\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-
800.html.
\162\ https://www.nimh.nih.gov/about/strategic-planning-reports/
strategic-objective-4.shtml.
---------------------------------------------------------------------------
______
Questions Submitted by Senator Patrick J. Leahy
migraines
Question. Migraine is currently the second leading cause of all
global disability. Unfortunately, due in part to limited research and
treatment, inappropriate opioid prescriptions for migraine present
Americans with ongoing risks of opioid use disorders and have worsened
outcomes in patients. The NIH website on disease burden shows
``migraine'' to have received by far the lowest level of research
funding in 2015, among those diseases with the highest burden. In 2017,
only 53 extramural investigators were funded for headache research,
compared to 315 for epilepsy and 385 for schizophrenia, each of which
has far lower burden than migraine. While migraine grant proposals are
eligible for consideration under the HEAL RFAs recently issued for pain
research, I am very concerned that these will fail to attract enough
investigators to this historically under-funded research area.
Does NIH have plans to issue specific RFA programs for headache
disorders research, comparable in scope to the BACPAC group of RFAs for
research on back pain?
Answer. NIH recognizes the burden of headache disorders as
prevalent and disabling conditions for patients around the country.
NIH has identified priority areas of need unique to headache
research, including fundamental mechanisms to guide new treatment
development and advancing treatments through the clinical pipeline.
Importantly, headache research is an area with trans-NIH interest for
which funding has increased from $18 million in 2010 to $32 million in
2018. NIH has supported important research that is providing exciting
new therapies for headache. Basic research on potassium channels, delta
or kappa opioid receptors, and TRP channels has fundamentally increased
our understanding of trigeminal nociceptors and their involvement in
initiating a migraine, giving us new targets for potential treatments.
NIH investigators also provided the foundation for development of
calcitonin gene receptor protein (CGRP) antibodies now used for
migraine therapy. In addition, NIH sponsored research also led to
efforts exploring the promising avenue of vagus nerve stimulation for
headaches. Lastly, a pivotal trial on pediatric migraine is shifting
clinical practice toward safer and more effective therapies. These
exciting advances are all examples of NIH efforts toward relieving the
burden of headache disorders.
In addition, NIH's long-standing programs in these specific areas
will be greatly enhanced by the recently launched HEAL (Helping to End
Addiction Long-term) initiative and its efforts to advance the research
agenda for pain and care across pain conditions. Through HEAL, NIH
released many funding opportunity announcements for research on
biomarker discovery, device and drug development, clinical trials on
effectiveness of interventions and pragmatic trials for implementation
of effective therapies for pain conditions. Headache research fits
within the scope of all these initiatives and NIH has made strong
efforts to network with and encourage the headache research community
to submit applications to these solicitations. Furthermore, the
infrastructure and resources being established through the HEAL
initiative will be available to enhance pain research across all
conditions which will greatly inform new areas of mechanisms for
headache research.
The HEAL BacPac Initiative was designed to fill a unique need for
another highly prevalent pain condition for which much of the research
framework is inadequate. Back pain is unique in that it lacks accurate
diagnostic tools and assessments, a clear classification scheme based
on causality, understating of the underlying mechanisms, and effective
treatment approaches. Unlike the case for back pain, the diagnostics
and classifications for headache disorders are better established and
our understanding of the mechanisms of headaches is moving forward
through existing programs and can be further advanced through HEAL with
the participation of the headache research community.
cardiovascular disease
Question. Over the past half-century, we have witnessed
unprecedented progress in addressing cardiovascular disease, yet recent
trends show that declines in heart disease and stroke mortality rates
have slowed for all races and are increasing substantially among
certain population groups such as rural, middle-aged white Americans.
The American Heart Association recently announced new alarming data
that shows that nearly half (48 percent) of U.S. adults have some form
of cardiovascular disease.
As our Nation's population ages, there is an urgent need for action
to improve innovation in the treatment of cardiovascular disease. What
is NIH doing to address the high rates of cardiovascular mortality,
especially in rural areas like my home State of Vermont?
Answer. The NIH is committed to ensuring that all Americans benefit
from the life-saving advances made possible by federally funded
research--regardless of their race, age, sex, income, or where they
live. The National Heart, Lung, and Blood Institute (NHLBI) leads NIH's
support for research on cardiovascular disease (CVD). Over the past 50
years, research funded by the NHLBI has helped bring about a 71 percent
decline in deaths from CVD nationwide. However, CVD remains the
Nation's leading cause of death, with the highest mortality
concentrated in certain groups, including African Americans, American
Indian/Alaska Natives, and rural communities. We are supporting
research to determine what causes these health disparities and how to
correct them.
High blood pressure is a leading risk factor for heart disease and
stroke. Given that blood pressure medication dosing and adherence is a
major challenge in rural and underserved communities, NHLBI is
supporting innovative methods to help patients connect with
pharmacists. For example, NHLBI's Collaboration Among Pharmacist and
Physicians toto Improve Outcomes Now (CAPTION) study embedded
pharmacists within 32 primary care physicians' offices in 15 states,
serving high-risk socioeconomic and racial groups. After 9 months,
patients treated through this physician-pharmacist team approach had
sustained reductions in blood pressure, compared to patients who
received usual care.\163\ Another recent NHLBI-funded study found that
having blood pressure screenings and pharmacist consultations in
barbershops helped men lower their blood pressure.\164\ Innovative
programs like these could be adapted and used in rural settings to
reduce hypertension and other cardiovascular risk factors.
---------------------------------------------------------------------------
\163\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063695.
\164\ https://www.ncbi.nlm.nih.gov/pubmed/29527973.
---------------------------------------------------------------------------
A new NHLBI program launched in March 2019, Disparities Elimination
through Coordinated Interventions to Prevent and Control Heart and Lung
Disease Risk (DECIPHeR) will help bring evidence-based interventions
like these to communities with a high burden of CVD. DECIPHeR
researchers will form partnerships with local healthcare systems,
government agencies, and community organizations so researchers and
community members can work together to design, test, and sustain
effective approaches to deliver proven treatments.\165\
---------------------------------------------------------------------------
\165\ https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-20-
003.html.
---------------------------------------------------------------------------
NHLBI also recently solicited proposals for new large cohort
studies to address research on heart, lung, blood, and sleep disorders,
with an emphasis on groups that are currently not well represented,
including rural communities.\166\ We expect to fund three such cohorts
later this year.
---------------------------------------------------------------------------
\166\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-577.html.
---------------------------------------------------------------------------
NHLBI also supports research to address CVD through telehealth.
This could include the use of audiovisual technology to deliver remote
care for patients who live in remote areas or have other challenges
accessing primary healthcare centers. For example, an ongoing NHLBI-
funded study is evaluating the effectiveness of traditional center-
based cardiac rehabilitation combined with telemedicine-guided
rehabilitation at home.\167\ NHLBI is also funding a study to collect
national data on the use of telemedicine in intensive care units to
identify best practices.\168\
---------------------------------------------------------------------------
\167\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9588024.
\168\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9061809.
---------------------------------------------------------------------------
Rural patients have traditionally been underrepresented in
cardiovascular clinical trials, yet have a higher burden of CVD than
patients from metropolitan areas. We are working to increase enrollment
of rural patients in NHLBI's Cardiothoracic Surgical Trials Network,
which has made significant contributions in advancing the evidence base
for cardiothoracic surgery. Dartmouth-Hitchcock Medical Center in New
Hampshire and Maine Medical Center were recently linked to the network
to expand its reach into rural communities of Northern New
England.\169\
---------------------------------------------------------------------------
\169\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9755050.
---------------------------------------------------------------------------
nih pain consortium
Question. Pain is a significant public health issue affecting an
estimated 69.6 million Americans each year. According to the Institute
of Medicine, the total incremental cost of healthcare due to pain
management in the U.S. is estimated to range from $560 billion to $635
billion, amounting to approximately 2.8 to 3.5 percent of our Nation's
total GDP. This cost estimate combines the direct medical costs of pain
management care as well as the economic costs related to lost
productivity and disability programs. With little known about
alternatives for treating and managing relief from pain, medical
providers are often limited to prescribing highly addictive opioids or
muscle relaxants to help patients mitigate symptoms from pain.
Unfortunately, addiction to opioid painkillers has ravaged the
Nation, and the number of opioid prescriptions has tripled in the past
20 years alone. In 1996, the National Institutes of Health (NIH)
established the NIH Pain Consortium to develop a strategy for research
on pain. Since then, the NIH has worked to expand research in this
area, while incorporating the work and expertise of stakeholders to
find ways to better serve patients.
Has the NIH Pain Consortium approached research on exploring opioid
alternatives to treating and managing both acute and chronic pain? If
so, please describe past, present, and ongoing projects in this area.
If not, please describe if the NIH plans to develop more research
focused on finding opioid alternatives to treating and managing acute
and chronic pain.
Answer. The NIH recognizes the significant public health crisis and
individual burden of pain and supports research to better understand,
manage and treat acute and chronic pain to relieve the burden of pain
and reduce our reliance on prescription opioid medications.
The NIH Pain Consortium is a collaboration of 27 Institutes,
Centers, and Offices (ICOs) across the NIH charged with promoting and
coordinating pain research across the agency. In 2018 the NIH Pain
Consortium ICOs collectively spent $605 million on a wide range of
research collectively aimed at understanding the mechanisms of pain,
new targets for treatment, and more. NIH has existing programs to
support development of novel and non-addictive treatments for acute and
chronic pain, from early-stage drug target discovery of molecular
pathways of pain signaling, exploration of receptors and channels as
potential non-addictive analgesic targets, and testing of novel
treatments in preclinical behavioral models. Through these programs,
NIH researchers identified nerve growth factor receptor and pain-
related ion channel targets, which have led to industry-sponsored
clinical trials for safe pain treatments for musculoskeletal pain and
other pain disorders. NINDS supported early development of calcitonin
gene receptor protein, the precursor to a compound recently approved to
treat migraine. NIH programs for discovery of new formulations,
combinations of medicines, and re-purposing molecules developed for
other disorders are being expanded rapidly to find new pain
medications. Through the NIH Blueprint Neurotherapeutics Program, which
provides support for small molecule drug discovery and development, NIH
currently is funding research to develop a non-addictive treatment for
headache and non-opioid analgesics for diabetic nerve pain.\170\
---------------------------------------------------------------------------
\170\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9325694&icde=36528658
&ddparam=&ddvalue=&ddsub=&cr=3&csb=default&cs=ASC&pball=.
---------------------------------------------------------------------------
The NIH Pain Consortium worked with the Interagency Pain Research
Coordinating Committee to develop the Federal Pain Research Strategy
\171\ (FPRS), which outlines a long-term strategic plan to guide NIH
and other Federal agencies in making their funding decisions to advance
pain research. The development of safer opioids and new, non-opioid
analgesics were considered high priority research areas in this
strategy.
---------------------------------------------------------------------------
\171\ Federal Pain Research Strategy: https://iprcc.nih.gov/sites/
default/files/iprcc/FPRS_
Research_Recommendations_Final_508C.pdf.
---------------------------------------------------------------------------
The NIH Pain Consortium, with the FPRS as a guide, has been
involved in developing and implementing the recently released NIH HEAL
(Helping to End Addiction Long-term) Initiative,\172\ which aims to
enhance research to better treat addiction and opioid overdose and to
improve pain care, thereby reducing our reliance on opioids. HEAL
supported projects will increase our understanding of pain, expand and
accelerate the development of non-addictive treatments, and rapidly
advance new treatments to the clinic. Through HEAL, NIH supports
biomarker discovery and validation to inform early phase clinical
testing of potential non-addictive pain therapies. To improve success
in bringing medications to the clinic, HEAL will facilitate the sharing
of data on past and future drug development efforts across the
biopharmaceutical industry and academia. To accelerate testing of novel
pain treatments in humans, NIH is establishing the HEAL Early Phase
Pain Clinical Network to test new, non-addictive pain treatments
through clinical trials. The HEAL initiative also is establishing a
pain management effectiveness research network to support large
clinical trials to test the effectiveness of pharmacological and non-
pharmacological treatments across many pain conditions.
---------------------------------------------------------------------------
\172\ The NIH HEAL Initiative: https://www.nih.gov/research-
training/medical-research-initiatives/heal-initiative.
---------------------------------------------------------------------------
NIH is working with Federal partners to provide the infrastructure
through the NIH Health Care Systems Research Collaboratory for
implementation of non-pharmacological treatments into healthcare
systems, with the ultimate goal to embed evidence-based best pain
management practices in clinics. These efforts represent unprecedented
expansion of the NIH pain research portfolio.
______
Questions Submitted to Douglas Lowy, M.D.
Questions Submitted by Senator Shelley Moore Capito
childhood cancer
Question. There is strong bipartisan support for childhood cancer
here in Congress, as evidenced by the overwhelming support for the
Childhood Cancer STAR Act that was signed into law last year. I was
very pleased to see the President highlight the vital need to invest
more in childhood cancer during his State of the Union and in his
Budget Submission to Congress.
How does the President's childhood cancer initiative coordinate
with the STAR Act programs? Is your $50 million request for increased
childhood cancer funding in addition to the $30 million we are working
to provide for the STAR Act?
Answer. There are approximately 16,000 children and adolescents
diagnosed with cancer in the United States each year. The President's
Budget proposes an additional $50 million in fiscal year 2020, to
continue for 10 years and provide a total of $500 million to support
the Childhood Cancer Data Initiative. This initiative focuses on the
critical need to obtain and analyze data to learn from children with
cancer. This information, spanning the spectrum of tumor analysis to
clinical care and outcomes of each child, will underpin our ability to
develop new approaches to cure children with cancer.
The additional resources of $50 million in fiscal year 2020 will
allow the NCI to expand efforts to collect data, to make strides in
federating existing sources of data, to ensure that data concerning
childhood cancers is appropriately accessible and used, and to
incentivize the cancer research community to develop new treatments for
children with cancer. The initiative is a promising opportunity to
enhance our ability to improve outcomes for children with cancer--first
by learning from every one of these children in an intentional and
organized manner and second by developing more efficient ways to share
and use the information. We envision that it will aggregate the
necessary information to foster essential research while also
increasing available information about each child's illness. Such
information will include extensive sequencing of tumors and additional
clinical information regarding each child's response to treatment.
The Childhood Cancer Data Initiative should also serve as a force
multiplier for efforts aligned with implementation of the Childhood
Cancer STAR Act. NCI-supported biospecimen collection and associated
data would all contribute to the aggregated data resources NCI plans to
develop through the initiative. NCI would also aim to integrate data
collected though new and continued childhood cancer survivorship
research projects and ongoing longitudinal studies (e.g., Childhood
Cancer Survivor Study, St. Jude Lifetime Study) through the initiative.
New data linkages and resources may also enable the cancer research
community to establish additional cohorts to complement the Childhood
Cancer Survivor Study, allowing NCI to study the long-term effects of
new immunotherapy and targeted chemotherapy treatments. NCI is also
exploring opportunities to leverage data collected through NCI and CDC
cancer registries programs, including data collected though CDC's early
case capture efforts for pediatric and young adult cancer cases. This
program is a central piece of CDC's STAR Act implementation, and the
Childhood Cancer Data Initiative has the potential to further build
upon that work.
In summary, NCI will continue these important research efforts with
whatever resources are available to us. If appropriated, the
President's Budget request envisions the $50 million proposed for the
Childhood Cancer Data Initiative as additional new resources. In the
current fiscal year, NCI is supporting implementation of the STAR Act
provisions that are directed toward the Institute. For example, in
addition to continuing to conduct and support childhood, adolescent,
and young adult (AYA) cancer survivorship research, NCI is expanding
support in this area for new research projects. Specifically, NCI
issued a new request for applications in fiscal year 2019. We estimate
that we will allocate approximately $4.8 million per year for 5 years,
to this survivorship research priority, subject to receiving
meritorious applications, among other considerations. NCI is also
working to enhance biospecimen collection, biobanking, and related
resources for childhood and AYA cancers, with an emphasis on those
cancer types and subtypes for which treatments are least effective, as
specifically encouraged in the STAR Act.
______
Questions Submitted by Senator Richard J. Durbin
ethyl oxide
Question. I'd like to ask about Ethylene Oxide--or EtO--a gas that
is widely used for the sterilization of certain medical devices. EtO is
a carcinogen. The National Cancer Institute acknowledges that exposure
to this gas has been linked to certain types of cancer, including
lymphoma, leukemia, and breast cancer. Illinois has three large
facilities that currently use EtO, including Sterigenics in
Willowbrook, Illinois, which was recently ordered to stop using EtO,
after the Environmental Protection Agency measured alarmingly high
levels of the gas in neighboring communities. Late last month, the
Illinois Department of Public Health issued a report which showed
higher rates of certain types of cancers around the Sterigenics
facility--including Hodgkins lymphoma and breast cancer in women, and
pediatric lymphoma in young girls. While we do not know yet if these
cancers are definitively linked to the Sterigenics EtO emissions, they
are certainly cause for concern. Dr. Lowy, what do we know about
exposure to EtO? What do you make of reports like the one released by
the Illinois Department of Public Health?
Answer. The NCI supports a wide range of research to understand
associations between exposures and cancer risk, including environmental
exposures like ethylene oxide (EtO). NCI is committed to supporting
research to increase our understanding of the complexity of cancer risk
factors and working with other government agencies responsible for
regulating such environmental exposures.
NCI-supported research has contributed to the body of knowledge
that has led to the classification of EtO as a carcinogen. EtO is used
primarily to produce other chemicals, including antifreeze, and in
smaller amounts, EtO is used as a pesticide and a sterilizing agent.
The ability of EtO to damage DNA makes it an effective sterilizing
agent but also accounts for its cancer-causing activity. Because EtO is
highly explosive and reactive, the equipment used for its processing
generally consists of tightly closed and highly automated systems,
which decreases the risk of occupational exposure. Despite these
precautions, workers and people who live near industrial facilities
that produce or use EtO may be exposed to EtO through uncontrolled
industrial emissions. The general population may also be exposed
through tobacco smoke and the use of products that have been sterilized
with EtO, such as medical products, cosmetics, and beekeeping
equipment.\173\
---------------------------------------------------------------------------
\173\ https://www.cancer.gov/about-cancer/causes-prevention/risk/
substances/ethylene-oxide.
---------------------------------------------------------------------------
In 2000, the National Toxicology Program, part of the National
Institute of Environmental Health Sciences, upgraded EtO from
``reasonability anticipated carcinogen'' to a ``known human
carcinogen.'' \174\ As an analysis conducted by the EPA reaffirmed last
year, lymphoma and leukemia are the cancers most frequently reported to
be associated with occupational exposure to ethylene oxide. Stomach and
breast cancers may also be associated with ethylene oxide
exposure.\175\
---------------------------------------------------------------------------
\174\ https://www.niehs.nih.gov/news/newsroom/releases/2000/may15/
index.cfm.
\175\ https://www.tandfonline.com/doi/full/10.1080/
15376516.2017.1414343.
---------------------------------------------------------------------------
Because the evidence indicating the carcinogenicity of EtO is well-
established, NCI has a limited role in responses to suspected cases of
EtO exposure. In these instances, NCI resources may provide data for
investigators to determine whether EtO exposure may be contributing to
high cancer rates. For example, those investigating such claims may use
data collected by the NCI Surveillance, Epidemiology, and End Results
(SEER) Program to inform conclusions about how EtO exposure has
affected cancer incidence. The SEER Program collects information on
cancer incidence, prevalence, and survival from specific geographic
areas representing 34 percent of the U.S. population. The SEER research
datasets, drawn primarily from State cancer registries, include SEER
incidence and population data associated by age, sex, race, year of
diagnosis, and geographic areas. SEER also provides analytical tools
and methodological expertise in collecting, analyzing, interpreting,
and disseminating population-based statistics.\176\ Another resource
for those investigating instances of EtO exposure is the NCI Cancer
Atlas, an exploratory tool that enables users to construct comparative
maps, graphs, and charts of cancer statistics and risk factors. The NCI
Cancer Atlas can help with the development of new methods of displaying
geospatial data for clear communication to the public and for
examination of complex multivariate data by researchers.\177\ Both the
SEER Program and the NCI Atlas can act as resources to inform State and
local health departments when assessing cancer incidence and
surveillance.
---------------------------------------------------------------------------
\176\ https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf.
\177\ https://gis.cancer.gov/gis-nci/gis_nci.html.
---------------------------------------------------------------------------
Federal agencies with the authority to research and monitor the
effects of hazardous substances on human health are the U.S.
Environmental Protection Agency (EPA), the CDC, and the Agency for
Toxic Substances and Disease Registry (ATSDR). While the EPA identifies
certain chemicals as hazardous air pollutants and regulates facilities
with these emissions,\178\ the CDC is the lead Federal agency on
addressing public health concerns about potential harmful exposures.
ATSDR conducts research on the health impacts of specific sites and
provides information and recommendations to Federal and State agencies,
including CDC and EPA.\179\ The National Center for Environmental
Health (NCEH), part of CDC, conducts research to investigate the
effects of the environment on health by tracking and evaluating
environment-related health problems through surveillance systems. NCEH
partners with State, local, and tribal health State departments to
conduct health surveillance, epidemiologic studies, communication and
education, standard setting and guidelines, and technical support.\180\
---------------------------------------------------------------------------
\178\ https://www.epa.gov/haps.
\179\ https://www.atsdr.cdc.gov/about/index.html.
\180\ https://www.cdc.gov/nceh/information/about.htm.
---------------------------------------------------------------------------
With technical assistance from CDC, State and local health
departments determine whether a particular exposure is responsible for
certain cancer cases. NCI assists CDC by supporting epidemiological
research on cancer surveillance and studies of cancer incidence,
including those programs mentioned above.
NCI will continue to work with other Federal agencies to provide
epidemiological data and other research findings to inform their
investigation of EtO exposure.
______
Questions Submitted to Anthony Fauci, M.D.
Questions Submitted by Senator Roy Blunt
antimicrobial and antibiotic resistance
Question. Fauci, there was a New York Times article on April 7th
describing the rise of drug-resistant germs. The article highlighted
that just like bacteria, fungus is now becoming resistant to drugs
developed to treat them. Over the past 4 years, the Labor/HHS bill has
included specific funds to combat antibiotic resistance, most recently
including $550 million in fiscal year 2019 for NIH, 50 percent more
than you had in fiscal year 2016. Can you discuss the threat of
antibiotic resistant germs and fungus and explain what research your
Institute is focusing on in this area?
Answer. The emergence of antimicrobial resistance (AMR) in a range
of bacterial and fungal pathogens is a public health threat of great
concern. Each year in the United States, there are more than 2 million
infections with antibiotic-resistant bacteria and at least 23,000
deaths as a direct result of these infections. Fungal infections also
are a serious problem in healthcare settings, and infections with drug-
resistant fungi are more difficult to treat. A drug-resistant form of a
fungal pathogen, Candida auris (C. auris), recently has emerged in the
United States and elsewhere, and has led to severe illness in
hospitalized patients. The National Institute of Allergy and Infectious
Diseases (NIAID) is the lead Institute of the NIH for basic,
translational, and clinical research confronting the critical issue of
AMR in bacterial and fungal pathogens.
Advances in AMR research have created opportunities to develop
state-of-the-art diagnostics to detect and help limit the spread of
AMR, accelerate the development of new antimicrobials, identify ways to
use the immune system to eradicate bacterial or fungal pathogens, and
manipulate microbial communities to prevent or treat infections. NIAID
has used recent funding increases provided by Congress to expand its
comprehensive AMR research portfolio and accelerate research in each of
these areas of scientific opportunity.
NIAID supports research to develop rapid point-of-need diagnostics
to inform appropriate treatment and identify resistance to commonly
used drugs. NIAID research has led to the development of several novel
diagnostics capable of distinguishing between numerous infectious
agents. These include two Food and Drug Administration (FDA)-cleared
diagnostics: one that tests for 24 bacterial and fungal species that
cause sepsis, and another that can detect a number of different
bacterial and viral species that cause pneumonia along with seven
genetic markers of AMR. In addition, the NIAID Antibacterial Resistance
Leadership Group, which oversees clinical research on antibiotic
resistance, is developing a master protocol to allow for the evaluation
of multiple diagnostic tests using samples from a single patient. NIH
also is partnering with the Biomedical Advanced Research and
Development Authority (BARDA) to support the Antimicrobial Resistance
Diagnostic Challenge competition to identify innovative and rapid
point-of-need diagnostic tests that inform appropriate antibiotic
treatment and facilitate antimicrobial stewardship. Submissions for
Step 3 of the Challenge are due in January 2020, and final results of
the competition are anticipated in July 2020.
NIAID's investments in AMR research are advancing the development
of promising new therapeutic candidates for drug-resistant infections.
NIAID-supported researchers have developed a method to synthesize novel
forms of a class of antibiotics (tetracyclines) that are not
susceptible to existing bacterial resistance mechanisms. One of these
compounds, XERAVATM, recently received FDA approval to treat
complicated intra-abdominal infections. NIAID funding also has led to
the discovery of a new class of antibiotics, malacidins, that are being
investigated for further therapeutic development. In addition, NIAID
provides in-kind and technical support for CARB-X (Combating Antibiotic
Resistant Bacteria-X), a public-private partnership led by BARDA. CARB-
X is currently funding the development of 35 innovative projects,
including 13 that represent new antibiotic classes.
NIAID also supports the development of antifungal therapies,
including those that may be effective against drug-resistant fungi. One
fungal pathogen of particular concern is C. auris, which can cause
serious infections that can affect the blood, heart, brain, eyes,
bones, and other parts of the body. While most C. auris infections are
treatable with existing antifungal drugs, the presence of C. auris
infections resistant to the main classes of antifungal drugs is
extremely concerning. NIAID is facilitating preclinical screening of
candidate therapeutics for effectiveness against C. auris and has
identified several lead candidates. NIAID also is supporting
investigation of a broad-spectrum antifungal with activity against C.
auris and other Candida species.
NIAID-supported investigators are exploring approaches that
leverage the immune system to combat drug-resistant infections. One
novel approach uses antibodies to boost the ability of an infected
individual's own immune system to fight infection. NIAID also is
advancing the development of candidate vaccines against bacterial and
fungal pathogens, including strains that exhibit drug resistance. This
includes an experimental vaccine to protect against Staphylococcus and
Candida species, including C. auris and Staphylococcus aureus (S.
aureus). Vaccines against these bacterial and fungal pathogens could
help prevent infections, thus avoiding the use of antibacterial or
antifungal drugs and limiting the potential for development of AMR.
NIAID also supports research investigating the use of beneficial
bacteria to prevent or treat colonization with pathogenic AMR bacteria.
NIAID funds studies on the use of fecal microbiota transplants to
replenish beneficial gut microbiota and prevent and treat bacterial
infections. This strategy may be particularly effective for difficult-
to-eradicate infections such as the bacterial species Clostridium
difficile. In addition, NIAID scientists discovered that the use of
probiotic digestive supplements containing Bacillus bacteria prevented
S. aureus bacteria from growing in the gut and nose of healthy
individuals.
NIAID recognizes that a multi-pronged, multi-disciplinary approach
is necessary to address the serious threat posed by drug-resistant
microbes. NIAID will continue to support the development of improved
tools and strategies to identify, prevent, and treat infections with
AMR pathogens.
ending hiv initiative
Question. The President's budget proposes to end HIV transmission
in the United States in 10 years. Dr. Fauci, can you discuss what is
necessary to reach this goal, how an HIV vaccine could help achieve it,
and where you are in the development of a vaccine?
Answer. The fiscal year 2020 President's Budget has proposed a new
initiative of the Department of Health and Human Services (HHS) on
Ending the HIV Epidemic to address the ongoing public health crisis of
HIV in this country. The goals of the initiative are first reducing
numbers of new HIV infections in the United States by 75 percent within
5 years, and then by 90 percent within 10 years. The initiative will
leverage critical scientific advances in HIV prevention, diagnosis,
treatment, and care by coordinating the highly successful programs,
resources, and infrastructure of the NIH, the Centers for Disease
Control and Prevention, the Health Resources and Services
Administration, and the Indian Health Service.
The initiative is coordinated by the HHS Office of the Assistant
Secretary of Health. During the initial phase of the initiative, the
focus will be on geographic areas and demographic groups in 19 States,
Washington, DC, and Puerto Rico, where the majority of new HIV cases
are reported, as well as in 7 States with a disproportionate occurrence
of HIV in rural areas. The initiative includes four pillars to help
reduce HIV infections:
--Diagnose all individuals with HIV as early as possible after
infection;
--Treat HIV infection rapidly and effectively to achieve sustained
viral suppression;
--Prevent at-risk individuals from acquiring HIV, including through
the use of pre-exposure prophylaxis (PrEP); and
--Rapidly detect and respond to emerging local epidemics of HIV
infection to further reduce new infections.
Advances in HIV treatment and prevention research suggest that,
theoretically, the HIV epidemic in this country could be ended by
expanding access to treatment to all persons with HIV and PrEP to all
those at high risk. The Administration has developed a practical,
achievable plan to focus on the places and populations in the United
States that are most affected by HIV. Lessons learned and effective
strategies emanating from this initiative would ultimately be applied
to profoundly reduce HIV incidence nationwide through Federal, State,
and local health departments and nongovernmental organizations. NIH-
supported research through the Centers for AIDS Research (CFARs) and
AIDS Research Centers will play a critical role in developing best
practices for the initiative by collecting and disseminating data on
the effectiveness of approaches used to achieve the initiative's four
pillars. The fiscal year 2020 President's Budget includes $6 million
for NIH CFARs to support the HHS Ending the HIV Epidemic initiative.
The development of a safe and effective HIV vaccine remains a key
component to realizing an end to the HIV pandemic. If an HIV vaccine
were to become available, it would add another key HIV prevention tool
to complement the ongoing efforts on HIV diagnosis, treatment, and
pharmaceutical-based prevention through this initiative. NIAID is the
lead for HIV vaccine research at the NIH. Currently, NIAID-supported
scientists around the world are following two complementary paths to
accelerate the development of an HIV vaccine.
The first approach to HIV vaccine development builds upon prior
partial success of the RV144 vaccine regimen. In 2009, the findings of
a large international clinical trial of the RV144 vaccine regimen
showed for the first time that an HIV vaccine approach could confer
modest protection against HIV. Today, NIH and our global partners are
continuing to build upon the findings from the RV144 trial. Two large
HIV vaccine efficacy clinical trials are now ongoing in southern
Africa, one to evaluate an experimental vaccine regimen based on the
one used in the RV144 trial, and another to assess an experimental
``mosaic'' vaccine candidate designed to induce immune responses
against a wide variety of global HIV strains. Results from these trials
are expected in 2022 and 2021, respectively.
NIAID scientists also are pursuing a second, theoretical path that
involves studying the body's immune response to HIV infection and
finding various ways to generate and enhance that response through
vaccination. One theoretical approach involves designing vaccine
strategies to generate cellular immune responses capable of protecting
against HIV infection. Another promising strategy seeks to identify
potential HIV vaccine targets by uncovering the molecular structure of
the virus. An additional theoretical approach involves the design of a
vaccine that elicits broadly neutralizing antibodies, or antibodies to
HIV that can target multiple different HIV strains. Studies are
underway to determine whether delivery of such antibodies could provide
long-acting protection against HIV infection, similar to the way a
traditional vaccine approach would work. Two large clinical trials with
sites in the Americas, Europe, and Africa are currently evaluating
VRC01, a broadly neutralizing antibody developed by the NIAID Vaccine
Research Center. In addition, planning is underway for early phase
clinical trials of a three-pronged antibody capable of binding to three
different critical sites on the surface of HIV. NIAID scientists and
public-private partners are developing this ``tri-specific'' antibody
with the expectation that it could eventually be used for long-acting
HIV prevention and treatment. NIAID scientists also are conducting a
Phase 1 clinical trial of a therapeutic HIV vaccine regimen that uses
an adjuvanted DNA vaccine ``prime'' followed by a viral vector
``boost'' in participants with HIV. The goal of this vaccine strategy
is to achieve prolonged undetectable levels of HIV, eliminating the
need for lifelong anti-retroviral therapy.
These scientific advances and ongoing investigations provide
cautious optimism that the development of a safe and effective HIV
vaccine is making headway. It is important to note that even a
moderately effective HIV vaccine could substantially slow the HIV
pandemic, if optimally implemented with current treatment and
prevention modalities. NIAID is committed to the goal of developing a
safe and effective HIV vaccine that would complement the HHS Ending the
HIV Epidemic initiative and help end the HIV pandemic.
______
Questions Submitted to Richard J. Hodes, M.D.
Questions Submitted by Senator Roy Blunt
alzheimer's disease
Question. Dr. Hodes, Dr. Randy Bateman, a researcher at Washington
University in St. Louis, has developed a blood test that can detect the
build-up of the Alzheimer's protein amyloid years before symptoms
appear. This is a significant step toward predicting who will develop
dementia. Further, another Washington University researcher, Dr.
Gregory Van Stavern, has developed an eye scan that detects changes in
the retina that may be able to predict Alzheimer's before dementia
begins. These tools could ultimately save millions in healthcare costs
because instead of paying thousands of dollars for a PET scan or a
spinal tap, you will be able to detect the disease through only a blood
test. Can you talk about the progress of this breakthrough as well as
other potential ways to better detect Alzheimer's disease?
Part of the issue with the recent drug failures is that may be
targeting individuals too late in the disease progression process. Two
years ago, you and I visited the Alzheimer's prevention trial in
Medellin, Colombia that focuses on a family that is genetically
predisposed to early-onset Alzheimer's disease. Can you discuss what
research your Institute is supporting to prevent or delay Alzheimer's
disease?
Answer. Early detection of pathology consistent with Alzheimer's
disease or a related form of dementia (AD/ADRD) opens a ``window of
opportunity'' for us to target the disease before clinical symptoms
appear. NIA supports studies exploring a variety of methods to detect
AD/ADRD pathology prior to the appearance of symptoms, as well as to
identify early, subtle signs of disease while cognitive abilities are
still largely intact.
The work of Dr. Bateman, who is affiliated with the NIA-supported
Charles F. and Joanne Knight Alzheimer's Disease Research Center
(Knight ADRC) at Washington University, uses subtypes of the amyloid
beta protein in the blood to infer the presence of damaging amyloid
buildup in the brain. Specifically, they have found that the ratio of
two subtypes, amyloid beta 42 and 40, can indicate elevated brain
amyloid. Multiple companies have now begun commercial development of
diagnostic tests based on the amyloid beta 42/40 ratio.
Other researchers are also working to identify blood-based
biomarkers for early detection of AD/ADRD. For example, investigators
with NIA's Intramural Research Program recently used advanced machine
learning techniques to identify a panel of 26 blood and brain
metabolites that were--when present in altered concentrations in
blood--consistently associated with brain atrophy, cerebrospinal fluid
measures of Alzheimer's pathology, cognitive performance, and disease
risk before clinical symptoms appeared. Another team is using changes
in autoantibodies--part of the body's immune response--as blood-based
biomarkers to detect early AD/ADRD. Still another is testing special
``indicator cells'' as a biosensor for AD pathology.
Dr. Van Stavern, also affiliated with the Knight ADRC, used a
noninvasive eye scanning technique, optical coherence tomography (OCT)
angiography, to detect thinning in the retina as well as alterations in
retinal blood flow among older people without clinical symptoms of AD/
ADRD. These findings correlated with elevated levels of amyloid and tau
proteins as detected by PET scan and cerebrospinal fluid examination.
Other ongoing, NIA-supported research using ocular biomarkers to
detect early AD/ADRD includes a study correlating amyloid and tau
levels in the fluid of the eye with OCT and cognitive testing for early
detection of Alzheimer's disease. Elsewhere, NIA-supported
investigators are using an innovative imaging method to detect
Alzheimer's pathology, disease progression, and treatment response in
people with Alzheimer's and in mouse models of the disease. In this
study, individuals drink a solution made with curcumin, a component of
the spice turmeric. The curcumin acts as a tracer, ``lighting up''
amyloid in the eye and enabling its detection with a custom-built high-
definition scanning instrument.
In addition, NIA-supported investigators are exploring changes in
smell, gait, personality, and even driving behaviors as early warning
signs of incipient dementia. Ultimately, we hope to be able to
intervene either with or prior to the earliest appearance of symptoms
and thereby avoid progression to the later, devastating stages of
disease.
Research to prevent or delay AD/ADRD symptoms in at-risk and/or
presymptomatic individuals remains a high priority at NIA. The
Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's
Disease Trial in Medellin, Colombia is one such study. Recruitment for
this trial of the anti-amyloid agent Crenezumab among members of a
family at very high genetic risk for developing the disease has been
completed, and we anticipate reporting results in 2022. This study is
one of several being conducted by the API, the goal of which is to
identify pre-symptomatic interventions that will postpone, slow, or
prevent the disease's progression.
Another major initiative, the Dominantly Inherited Alzheimer's
Network Trials Unit (DIAN-TU), is an international partnership
dedicated to designing and managing clinical trials for individuals at
high genetic risk of developing AD.
The recently funded DIAN-TU Primary Prevention Trial is a 4-year
study of two drugs, Solanezumab and Gantenerumab--antibodies that
interact with different forms of amyloid--in 160 asymptomatic
individuals at high genetic risk. Investigators will determine whether
it is possible to prevent amyloid deposition in this population and if
doing so will prevent the cascade of pathology associated with AD and,
ultimately, dementia, in people who are otherwise certain to get the
disease.
In addition to these highly visible initiatives, NIA also supports
studies of physical activity and exercise, diet, and cognitive training
to prevent cognitive decline and dementia. Participants in many of
these studies are at well-established risk of developing dementia but
do not yet show evidence of cognitive decline.
A new, NIA-funded Alzheimer's Clinical Trial Consortium (ACTC) will
help investigators harness best practices and latest methods for both
treatment and prevention trials. The ACTC includes 35 sites in the
United States and will address the complexity, time, and expense of
participant recruitment and site activation to find new and effective
ways to treat or prevent these devastating disorders.
______
Questions Submitted to Nora Volkow, M.D.
Questions Submitted by Senator Roy Blunt
opioid research and data collection from samhsa
Question. Dr. Volkow, our Committee has invested significant
resources into opioid treatment, prevention, education, and research.
In particular, we now provide States with $1.5 billion in flexible
State Opioid Response grants and require States to report to SAMHSA on
how they are spending this funding. I believe it is incredibly
important that we understand what opioid programs are working and how
to replicate those programs across the country. Can you discuss (1)
whether NIH researchers have access to this valuable State-by-State
data; and (2) what research your Institute is undertaking to better
understand what programs work and which do not in opioid prevention and
treatment?
Answer. (1) NIH researchers can gain access to data collected in
conjunction with SAMHSA grants, such as the State Targeted Opioid
Response and State Opioid Response (STR and SOR) grants, through State
substance use agencies.
(2) Determining which prevention and treatment approaches are most
effective is central in addressing the opioid crisis, and this is
precisely the goal of our HEALing Communities Study. Launched in
partnership with SAMHSA on April 18, 2019, this multisite
implementation research study tests the impact of an integrated set of
evidence-based interventions across healthcare, behavioral health,
justice, and other community-based settings. The ultimate goal is to
generate the evidence needed to determine the most effective strategies
for preventing and treating opioid misuse and opioid use disorder (OUD)
within highly affected communities. This Study will examine the
effectiveness of coordinated systems of care designed to reduce
overdose fatalities and events; decrease the incidence of OUD; increase
the number of individuals receiving medication to treat OUD, retained
in treatment, and receiving recovery support services; and increase the
distribution of naloxone.
The HEALing Communities Study includes at least 15 communities in
each of four participating States to measure the impact of these
targeted strategies. The four institutions leading this research--
University of Kentucky, Boston Medical Center, Columbia University, and
The Ohio State University--were required to demonstrate their
partnership with State governments, and specifically how they plan to
leverage SAMHSA funding (such as STR and SOR funding) to provide
evidence-based prevention and treatment services. RTI International,
based in North Carolina, will serve as the study's coordinating center,
and will be responsible for data analysis, health economics research,
and widespread dissemination of research findings over the course of
the study, under provisions that safeguard the privacy and
confidentiality of respondents. The data generated by this Study will
inform best practices for other States looking to maximize the impact
of their SAMHSA grant funds.
Question. What barriers exist for NIH and SAMSHA to partner on data
sharing and how can we help make sure this data is available to the
research community?
Answer. NIH has benefitted from a long-standing partnership with
SAMHSA that facilitates the translation of sound research into
effective practice and policy. SAMHSA and NIH are in regular contact
regarding the need for data to be available to researchers. Currently,
researchers access data compiled for monitoring SAMHSA grants through
State substance use agencies. This is occurring in a number of recently
awarded NIH-funded studies. For example, there are currently five
studies underway to test approaches for expanding medications for OUD
in the context of SAMHSA STR and SOR grants issued under RFA-DA-18-005
(with another three studies underway with support from the Arnold
Foundation). In addition, NIH's National Center for Complementary and
Integrative Health recently funded five projects examining the impact
of behavioral and complementary health interventions within the context
of States' plans for using SAMHSA's STR and SOR grant funds.
NIH continues to be committed to working with SAMHSA to find
innovative ways to mutually share data and to ensure the data are
available to the research community in order to maximize the impact of
the research.
SUBCOMMITTEE RECESS
Senator Blunt. The subcommittee stands in recess.
[Whereupon, at 11:45 a.m., Thursday, April 11, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]