[House Hearing, 116 Congress]
[From the U.S. Government Publishing Office]
BEYOND THE MILLION VETERANS PROGRAM: BARRIERS TO PRECISION MEDICINE
=======================================================================
HEARING
before the
SUBCOMMITTEE ON HEALTH
of the
COMMITTEE ON VETERANS' AFFAIRS
U.S. HOUSE OF REPRESENTATIVES
ONE HUNDRED SIXTEENTH CONGRESS
FIRST SESSION
__________
WEDNESDAY, JUNE 26, 2019
__________
Serial No. 116-23
__________
Printed for the use of the Committee on Veterans' Affairs
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://www.govinfo.gov
______
U.S. GOVERNMENT PUBLISHING OFFICE
40-824 WASHINGTON : 2021
COMMITTEE ON VETERANS' AFFAIRS
MARK TAKANO, California, Chairman
JULIA BROWNLEY, California DAVID P. ROE, Tenessee, Ranking
KATHLEEN M. RICE, New York Member
CONOR LAMB, Pennsylvania, Vice- GUS M. BILIRAKIS, Florida
Chairman AUMUA AMATA COLEMAN RADEWAGEN,
MIKE LEVIN, California American Samoa
MAX ROSE, New York MIKE BOST, Illinois
CHRIS PAPPAS, New Hampshire NEAL P. DUNN, Florida
ELAINE G. LURIA, Virginia JACK BERGMAN, Michigan
SUSIE LEE, Nevada JIM BANKS, Indiana
JOE CUNNINGHAM, South Carolina ANDY BARR, Kentucky
GILBERT RAY CISNEROS, JR., DANIEL MEUSER, Pennsylvania
California STEVE WATKINS, Kansas
COLLIN C. PETERSON, Minnesota CHIP ROY, Texas
GREGORIO KILILI CAMACHO SABLAN, W. GREGORY STEUBE, Florida
Northern Mariana Islands
COLIN Z. ALLRED, Texas
LAUREN UNDERWOOD, Illinois
ANTHONY BRINDISI, New York
Ray Kelley, Democratic Staff Director
Jon Towers, Republican Staff Director
SUBCOMMITTEE ON HEALTH
JULIA BROWNLEY, California, Chairwoman
CONOR LAMB, Pennsylvania NEAL P. DUNN, Florida, Ranking
MIKE LEVIN, California Member
ANTHONY BRINDISI, New York AUMUA AMATA COLEMAN RADEWAGEN,
MAX ROSE, New York American Samoa
GILBERT RAY CISNEROS, Jr. ANDY BARR, Kentucky
California DANIEL MEUSER, Pennsylvania
GREGORIO KILILI CAMACHO SABLAN, W. GREGORY STEUBE, Florida
Northern Mariana Islands
Pursuant to clause 2(e)(4) of Rule XI of the Rules of the House, public
hearing records of the Committee on Veterans' Affairs are also
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of converting between various electronic formats may introduce
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C O N T E N T S
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Wednesday, June 26, 2019
Page
Beyond The Million Veterans Program: Barriers To Precision
Medicine....................................................... 1
OPENING STATEMENTS
Honorable Julia Brownley, Chairwoman............................. 1
Honorable Neal P. Dunn, Ranking Member........................... 2
WITNESSES
Dr. Carolyn Clancy, MD, Deputy Under Secretary for Health for
Discovery, Education, and Affiliated Networks, Veterans Health
Administration, U.S. Department of Veterans Affairs............ 3
Prepared Statement........................................... 23
Accompanied by:
Dr. Rachel Ramoni, DMD, ScD, Chief Research and Development
Officer, Office of Research and Development, Veterans
Health Administration
Dr. Sumitra Muralidhar, PhD, DirectorMillion Veteran Program,
Office of Research and Development, Veterans Health
Administration
Dr. Magali Haas, MD, PhD, CEO and President, Cohen Veterans
Bioscience, Member - Coalition to Heal Invisible Wounds........ 5
Prepared Statement........................................... 26
Mr. Matt Kuntz, Executive Director, National Alliance on Mental
Illness - Montana.............................................. 7
Prepared Statement........................................... 31
STATEMENT FOR THE RECORD
National Association of Veterans' Research and Education
Foundation..................................................... 37
Sanford Health................................................... 39
SHEPHERD Therapeutics and SHEPHERD Foundation.................... 41
BEYOND THE MILLION VETERANS PROGRAM: BARRIERS TO PRECISION MEDICINE
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Wednesday, June 26, 2019
Committee on Veterans' Affairs,
U. S. House of Representatives,
Washington, D.C.
The Subcommittee met, pursuant to notice, at 3:15 p.m., in
Room 210, House Visitors Center, Hon. Julia Brownley
[Chairwoman of the Subcommittee] presiding.
Present: Representatives Brownley, Lamb, Dunn, Radewagen,
and Barr.
OPENING STATEMENT OF JULIA BROWNLEY, CHAIRWOMAN
Ms. Brownley. Thank you all for being here today to discuss
the current state of VA's pursuit of precision medicine.
Precision medicine has been described as an innovative approach
that takes into account individual differences in people's
genes, environments, and lifestyles. Not only is VA uniquely
designed to pursue this cutting-edge research, its patient
population would benefit most from its development.
According to VA's National Center for Veterans Analysis and
Statistics, veterans of color are predicted to increase from
23.2 percent to 32.8 percent by 3037, while women veterans
continue to be the fastest growing population of veterans and
are projected to be the only group of veterans that will
continue to grow through 2037.
The manner in which veterans receive health care should
reflect their increasing diversity. In the past, VA conducted
studies using only white men and some methods of treatment were
approved based on these heavily skewed trials. This was not
unique to VA; the medical research field as a whole has
operated in this manner.
However, what is unique to VA is its ability and
willingness to regain its position as the Nation's best
research institution, a research institution that attracts the
Nation's most talented physicians and investigators, and
delivers the most progressive and effective treatments
available.
In an effort to facilitate this transformation, VA launched
the Million Veterans Program in 2011 to pursue its goal of
collecting genetic material from 1 million veterans. Currently,
with 750,000 veterans enrolled, it is the largest collection of
its kind. Because of this rich database of information and VA's
access to millions of veterans' health records, VA is becoming
an increasingly attractive option as private industry
determines where to focus its research dollars.
VA has limited resources, a stagnant budget, and the
Administration has sought to slowly gut the National Institutes
of Health, which is one of VA's biggest interagency partners.
That is why it is increasingly important that VA's Office of
Research and Development remain a competitive contender for
private funds. It must also retain access to the technology and
research infrastructure that private research partners can
provide.
This is not to say that VA's Research Department under the
guidance of Dr. Ramoni has not thrived. The work of VA
employees to facilitate partnerships with private foundations
such as Cohen Veterans Bioscience and other Government agencies
like the Department of Energy to fill gaps in resources should
be commended.
Today's hearing should serve as an opportunity for the
agency to tout those achievements, but also for the Members of
this Subcommittee to learn more information on ways in which
Congress may assist. Not only will VA's increasingly diverse
patient population benefit from advances in precision medicine,
but some aspects of precision medicine could transform the way
in which VA treats those veterans suffering from what have
traditionally been thought of as invisible wounds.
Advancements in the understanding and discovery of
biomarkers leads many to believe that the trauma leading to a
TBI or PTSD can affect a person's genetic sequencing in a way
that could assist physicians as they diagnose veteran patients.
Additionally, Dr. Haas has suggested that there may be
hundreds of types of PTSD. If these variations can be
identified, then veterans could receive effective treatment on
the first try as opposed to the trial-and-error treatments the
VA is currently forced to offer.
And, as chair of the Women Veterans Task Force, I am eager
for VA investigators to identify diagnostic biomarkers for
TBIs. Traumatic brain injuries are disproportionately
misdiagnosed in women veterans as depression, thus denying
much-needed treatment to this growing population.
Due to the incredible impact precision medicine could have
on veterans' health care, I am thankful for each of our
witnesses' willingness to join us in today's discussion. I am
hopeful that at the end of this hearing we can better
understand exactly what barriers VA's Office of Research is up
against as it continues to modernize its processes and pursue
increasingly important partnerships.
I will now yield 5 minutes to Ranking Member Dunn for his
opening comments.
OPENING STATEMENT OF NEAL P. DUNN, RANKING MEMBER
Mr. Dunn. Thank you very much, Chairwoman Brownley.
A little over a year ago, I chaired my first VA Research
meeting and at that meeting three basic concerns were raised
about the VA's research program. The first concern was that the
VA Research was not sufficiently focused on veteran-specific
conditions and concerns. The second was that the VA medical
facilities weren't complying with the VA's policy by
administering grants from outside entities, as Chairwoman
Brownley mentioned, through VA non-profit research and
education corporations, to the extent that is possible. And the
third concern was that the VA is not efficiently translating
bench discoveries to bedside in order to advance the treatment
of veterans.
There have been a number of changes made to the VA's
research program since that hearing and perhaps the single most
significant change is the appointment of Dr. Carolyn Clancy as
the Deputy Under Secretary for Discovery, Education, and
Affiliated Networks, with the oversight responsibility to the
Office of Research and Development.
Dr. Clancy will be testifying for the VA today and was
recently named one of Modern Health Care's 50 Most Influential
Clinical Executives, an honor recognizing leaders who work in
health care industries, deemed by their peers and an expert
panel to be one of the most influential leaders in research
today. So, congratulations to you for that, Dr. Clancy.
I do wish to point out that our three primary concerns
still have to be met, so we will address those. Another one of
our witnesses this afternoon is Mr. Matt Kuntz, the Executive
Director of the National Alliance on Mental Illness from
Montana. Mr. Kuntz's written statement powerfully lays out the
very real stakes for this issue, which is veterans' lives.
Research is an important tool at the VA's disposal to
improve and save lives for veterans and for all Americans, and
it is incumbent on us to make sure that the VA is using that
tool to its highest potential. During this afternoon's hearing,
we will discuss several recommendations for how we can do that
and, with our collective work, I am confident that the VA's
best breakthroughs are still ahead, and that those
breakthroughs will be able to make a difference in the quality
and longevity of veterans' lives and all Americans.
And at that point, I now yield back, Chairwoman Brownley.
Ms. Brownley. Thank you, Dr. Dunn.
On today's panel we have Dr. Carolyn Clancy, Deputy Under
Secretary for Health for Discovery, Education, and Affiliated
Networks at the Department of Veterans Affairs. Dr. Clancy is
accompanied by VA's Chief Research and Development Officer, Dr.
Rachel Ramoni, and the Director of the Million Veterans
Program, Dr. Sumitra Muralidhar.
Dr. Magali Haas will offer testimony on behalf of the
Coalition to Heal Invisible Wounds. And also Mr. Matt Kuntz
joins us today on behalf of the National Alliance on Mental
Illness.
I appreciate all of you and your willingness to join us
today and look forward to receiving your testimony. And, to
that end, Dr. Clancy, you are now recognized for 5 minutes.
STATEMENT OF CAROLYN CLANCY
Dr. Clancy. Thank you. Good afternoon, Chairwoman Brownley,
Ranking Member Dunn, and distinguished Members of the
Subcommittee. As you noted, I am accompanied by Drs. Ramoni and
Muralidhar
As Deputy Under Secretary for Health for Discovery,
Education, and Affiliated Networks, I am pleased to be here to
share our vision and deliverables in the field of precision
medicine.
My office was created precisely because Secretary Wilkie
and Dr. Stone recognized that aligning and elevating our
academic missions is absolute vital to making sure that all
veterans, irrespective of background, get cutting-edge care,
and there are studies to support that in the academic arena. So
we are very excited about that. And we are committed to
ensuring that veterans are among the first to benefit from
cutting-edge care.
And I am sure that you know that Secretary Wilkie, as a
result of his prior position at the Department of Defense, is
probably more attuned to the growing diversity of the veteran
population now and in the future than most would be, and is
usually the first to come out with statistics like the ones
that you cited.
Since its inception, VA Research has measured its success
based upon real-world impact. The pacemaker and liver
transplantation are well-known examples of early VA research
advances that transformed health care. Fewer people know that
the Gleason grading system, which is used worldwide to predict
the prognosis of a man with prostate cancer, was created by Dr.
Donald Gleason, a VA pathologist.
More recently, VA conducted the foundational trial that
established active surveillance as a safe, long-term
alternative to prostatectomy in men with low-risk prostate
cancer.
By continuing to advance the precision of medical care, we
can go beyond, way beyond general predictions like low, medium,
and high-risk prostate cancer, to specific predictions that
will guide an individual veteran's care. One of the ways we are
making this vision a reality for veterans is through our
partnership with the Prostate Cancer Foundation. Our first
milestone is to ensure that men with metastatic prostate cancer
receive DNA sequencing, and already this effort has identified
men who based on their genetic variations are benefitting from
precision therapies.
New precision medicine treatments are first made available
through clinical trials and in February of 2018 we began the
Access to Clinical Trials, or ACT for Veterans Initiative, in
collaboration with the National Association of Veterans
Research and Education Foundations. Through this effort, we
have set a goal to start up industry-sponsored clinical trials
100 days faster than our current average by the end of fiscal
year 2021.
In October of last year, the Office of Research and
Development welcomed a new Director of the Office of Research
Protections, Policy, and Education, she and her team
immediately began working towards that goal in a fairly
relentless fashion, including opening the door to relying on
commercial institutional review boards, which are used by many
industry-sponsored clinical trials.
Precision medicine treatments are grounded in the discovery
of the relationship between genetic variations and disease. One
of VA's major investments, of course, is the Million Veterans
Program that you referenced, and today, 8 years after it began,
it is the largest mega-bio bank in the world. Over 750,000
veterans from all 50 states, Guam, and Puerto Rico have
enrolled, and we also have their clinical electronic data,
which makes it literally a unique resource in the world.
Because of the richness of the data, VA researchers have
begun to shed light on the genetics of a range of conditions
that impact veterans' health, including alcohol use disorder
and post-traumatic stress disorder, or PTSD. It is a source of
hope to veterans living with the invisible wounds of war and it
is our job to turn that hope into treatments.
For example, on one end of the spectrum, we are partnering
with the Department of Defense to follow thousands of veterans
with mild traumatic brain injury experienced in combat. Each of
these participants undergoes intensive bio sampling and
imaging, enabling us to identify biomarkers associated with
brain injury and co-morbidities like PTSD.
On the clinical end of the spectrum, we now have a study in
progress, the Prime Care Study, a trial which is determining
whether matching veterans with depression to medications based
on their genetic variation leads to improved outcomes.
These studies exist because our veteran partners are
willing to continue to serve our Nation through participation
and research. And an essential step to realize our promise to
participants to advance precision medicine is to establish a
modern computational infrastructure that can scale to support
hundreds of analyses occurring in parallel.
To that end, we are working with the University of Chicago
on the Open Commons Consortium to pilot a VA Data Commons where
de-identified data from MVP and electronic health record data
will be broadly available to approved VA and non-VA
researchers. Our goal is to have the infrastructure and
services to support a minimum of 100 parallel projects in the
VA Data Commons by the end of fiscal year 2021.
On behalf of ORD, the many VA researchers, and the veterans
who participate in VA Research, I thank you for your attention.
My colleagues and I look forward to answering your questions.
[The prepared statement of Carolyn Clancy appears in the
Appendix]
Ms. Brownley. Thank you, Dr. Clancy.
Dr. Haas, you are now recognized for 5 minutes.
STATEMENT OF MAGALI HAAS
Dr. Haas. Good afternoon, Chairwoman Brownley, Ranking
Member Dunn, and distinguished Members of the Subcommittee. I
am Dr. Magali Haas, CEO and President of Cohen Veterans
Bioscience. I am the wife of a veteran and I am representing
the Coalition to Heal Invisible Wounds.
It is an honor to testify before the Subcommittee on the
topic of advancing precision therapies for veterans alongside
Dr. Clancy and my fellow Coalition Member Matt Kuntz.
Cohen Veterans Bioscience is a national, nonpartisan
501(c)(3) public charity that operates as a translational
research organization. We are dedicated to fast-tracking the
development of diagnostic tests and personalized therapeutics
for the millions of veterans and civilians who suffer the
devastating effects of trauma-related and other brain
disorders. We partner closely with the Department of Defense,
the VA, the NIH, FDA, and other agencies, as well as academia,
foundations, and industry partners, to advance this mission.
We share this mission, because today more military
servicemembers are dying after they come home by suicide than
on the battlefield, and many more are suffering the chronic
effects of post-traumatic stress and traumatic brain injury.
For these invisible wounds, we have inadequate treatment
options for far too many.
In an effort to close this gap, we are partnering with the
Department of Defense to fund and operate an ambitious program
to conduct a multi-center, adaptive platform trial to test
multiple therapies in parallel under a design approach that is
cutting-edge. The VA is a critical partner in this effort, and
we need VA Research sites to participate in the program
starting this fall.
I am testifying today on behalf of the Coalition to Heal
Invisible Wounds, which advocates for policy reforms to widen
and expedite the pipeline for new therapies and diagnostics for
PTSD and TBI, and suicide prevention.
The Coalition's focus since its founding in 2017 has been
to empower the Veterans Health Administration, the largest
integrated health care system in the United States, and one
that is home to an established scientific enterprise that
conducts more than $1 billion of research each year, to be
positioned as a leading clinical research partner.
We ask today that the Subcommittee bolster the VA's efforts
to overhaul its clinical trial start-up practices. According to
industry data, VA sites take an average of 265 days to activate
a site, versus 141 days for non-VA sites. Because of these
lengthy delays, many clinical research sponsors do not even
attempt to bring clinical research to the VA and have not done
so for decades. Sponsors that do engage face a non-streamlined
decisions and protocol-review process and significant wait
times for site initiations that can cost overruns.
When sponsors are unable or unwilling to conduct studies at
VA sites, it means that veterans lack access to the frontier of
medicine for many disease conditions, particularly oncological
research. For many individuals with cancer, investigational
therapies are the only last, best hope for a patient. What
happens when a cancer study does not open in a VA facility, a
veteran suffering from that form of cancer is denied this path
and is more likely to die sooner.
And if we can't launch the PTSD adaptive platform trial in
a timely fashion within VA sites this year, we stand to fail in
establishing scientific evidence that supports the proper
utilization of existing and new therapeutics for these
conditions. Without better treatments for PTSD and TBI, we
cannot effectively combat the suicide and opioid epidemics.
We believe that with targeted reforms the VA can become 100
days faster on average at clinical trial startup by 2021. The
Coalition calls this the 100 Days Faster Initiative; for us,
faster is shorthand for efficiency, improved quality,
performance metrics, and adoption of cutting-edge technologies
and best-in-class solutions.
A hundred days matter. These reforms will require
systemwide engagement and implementation, and will extend
throughout numerous functions within the VA. It is thereby
imperative that Congress provide the VA statutory guidance to
achieve the 100-days-faster objective to ensure prioritization
around this focus.
We recommend that guidance focus on four reforms, some of
which are partially underway at the VA already: allow the use
of commercial institutional review boards, or IRBs, in
sponsored clinical research; create and make permanent
research-specific capacities within both the Office of
Information Technology and the Office of Privacy and Records
Management, and refocus the role of the Research and
Development Committee.
In conclusion, the Coalition thanks the Subcommittee for
its work to strengthen the VA's capacity to support the
development of precision medicine. Veterans have earned the
right to world-class health care and we strongly believe that
the VA has the potential to be a world-class research partner,
enabling better health care for servicemembers and veterans.
Thank you.
[The prepared statement of Magali Haas appears in the
Appendix]
Ms. Brownley. Thank you, Dr. Haas.
Mr. Kuntz, you are now recognized for 5 minutes.
STATEMENT OF MATT KUNTZ
Mr. Kuntz. Chairwoman Brownley, Ranking Member Dunn, and
distinguished Members of the Subcommittee, on behalf of NAMI,
the National Alliance on Mental Illness, I would like to extend
our gratitude for the opportunity to share with you our views
and recommendations regarding ``Beyond the Million Veterans
Program: Barriers to Precision Medicine.'' The entire NAMI
community applauds the Committee's dedication in addressing the
critical issues around veterans' brain health.
NAMI is the Nation's largest grassroots mental health
organization dedicated to building better lives for millions of
Americans affected by mental illness. NAMI advocates for access
to services, treatment, support, and research, and is steadfast
in its commitment to raising awareness and building a community
of hope for all of those in need.
To start out with the scientific justification, the VA
serves over 1.8 million veterans in a treatment system based
upon mental health diagnostic categorization that the former
Director of the National Institute of Mental Health has deemed
not to be predictive of treatment response. This is not the
VA's fault; this is the state of the science. But it is
incumbent on Congress and VA to push the state of the science
forward to take better care of America's heroes.
From the ground, how it looks, is like my stepbrother,
Specialist Chris Dana. We lost him to PTSD after serving in
Iraq. And I will tell you flat out, the Montana National Guard,
who he served with, and our family did not understand the
extent of his injury until after we lost him.
And for another example, my friend Commander John Scott
Hannon, 23 years in the Navy Seals, retired to come back home
to Montana to live one gulch over from me in the woods. And he
battled with a number of brain conditions and got treatment for
years, but what lost him was the final diagnosis, was the
bipolar disorder. And I sat down with his sister a few months
after his death and she said, if we had just known about the
bipolar disorder earlier--he addressed, he worked on everything
else, but we didn't even know this was the case. And that is
what I see day in and day out.
Or like my friend Mike Franklin. He was a fellow West
Pointer and Army infantryman, a Navy chaplain, and then a
college counselor. And just as interesting as that goofy resume
would suggest, but he suffered from treatment-resistant
depression, which affects about 30 percent of the people that
depression, and none of the standardized treatments would work
for him, and the treatments would just fail and fail. And my
last conversation with him was, ``Mike, please keep trying. We
will find research; we will find something.'' But he could not
keep going.
And that is the reality on the ground while we wait for
precision medicine to catch up.
There has been scientific progress in the past 10 years, as
discussed, and especially the emergence of transdiagnostic
biomarkers for brain health conditions. For me, that has kind
of changed the paradigm for how we think about this. It shows
that the traditional diagnostic categories aren't going to line
up exactly with the biosignatures; we should not expect them
to.
And there are some really good examples of precision mental
health care happening in research around the country. Dr. Amit
Etkin's work at the Palo Alto VA on treatment-resistant PTSD
was an amazing study, Dr. Madhukar Trivedi and his work at the
University of Texas Southwestern on finding biosignatures to
better treat depression, is real steps forward.
Some of the recommendations that we have. NAMI Montana and
NAMI National were real good partners in helping write the
Precision Mental Health Initiative and the Commander John Scott
Hannon Act, and that is on the Senate side. And we really like
that model for moving forward.
On a local level, we would like to ensure that the Veterans
Equitable Resource Allocation model supports precision mental
health initiatives. If local VA administrators are not
incentivized to do this, this will fail. So ensuring that VERA
reflects that reality.
And on a really simplistic note, using machine learning to
take some of the pain of the article-drafting process off of VA
researchers, I have toured around the country with the COVER
Commission looking at VA researchers and clinicians, and some
of them cannot publish because they don't have time. They have
the data that we paid for, that we are ready for, and they
can't publish because it takes too much time, and using machine
learning to help ease some of that.
And, in conclusion, I just want to say this means so much
to me personally. When we lost my stepbrother Chris, there was
just no hope, and to see Committees like this looking to
improve the brain health treatment system for our veterans is
incredibly important.
Thank you.
[The prepared statement of Matt Kuntz appears in the
Appendix]
Ms. Brownley. Thank you, Mr. Kuntz. And this Committee
offers its condolences to you for the loss of your stepbrother
Chris. Thank you for being here today.
Mr. Kuntz. Thank you, ma'am.
Ms. Brownley. I now recognize myself for 5 minutes. And the
first question I had was really to Dr. Haas. In my opening
comments, we talked a little bit about your summation that
there could be lots of different variations of post-traumatic
stress. So where are we in that research? I mean, if there are
possibly a hundred versions of these, is there--can you just
kind of describe where we are? Is this a hypothesis? Is this
science-based that you know this already or you believe through
my research we can determine whether this is true or not?
Dr. Haas. So we believe that there are multiple forms or
underlying mechanisms that can lead to a presentation that we
call PTSD, post-traumatic stress disorder, and the science is
essentially still in its nascency on some fronts. If we are
looking at this in terms of what do we understand about the
molecular basis and circuit basis of disease, that science is
still in its discovery form.
We have the earliest findings now for genetics that are
emerging out of both the Million Veterans Project and also from
the Psychiatric Genetics Consortium. The first date were just
published last year on this, showing genome-wide significant
findings that there is a genetic underpinning PTSD. And so,
with different genes, we can expect them. There are different
pathways and therefore different mechanisms, that different
people have vulnerability to PTSD in the wake of trauma. That
is the tip of the iceberg.
Matt Kuntz mentioned the data from Palo Alto, Dr. Etkin's
work. He has been working on a biomarker that is identifying a
subset of patients that have a different underlying circuit and
they all have the same diagnosis of PTSD. They look the same in
terms of symptoms, but you can differentiate them based on
their circuit using resting-state FMRI.
So that is suggesting to us, and that work needs to be
validated, that there are subsets and subtypes within PTSD.
That is the type of emerging evidence that suggests that we are
going to see more. But if you look across other brain disorders
and diseases, we see this as a systematic principle of science
and health care and disease. We are seeing that in cancer
already. We no longer just talk about lung cancer, we talk
about lung cancer subtypes, we do the same in cardiovascular
disease. We do this in every other field of biology except in
brain disorders.
Ms. Brownley. So when you talk about identifying the
circuit, does that mean that the man or woman when they sign up
to serve, that circuit exists before they have actually served
our country?
Dr. Haas. So at this time we don't know whether this is a
preexisting circuit or one that--
Ms. Brownley. I see.
Dr. Haas [continued]. --becomes emergent in the course of
exposures. Also, even with your genetics, it is vulnerability,
it is a probability, but it doesn't mean that you are going to
get a given condition.
Ms. Brownley. Thank you.
Dr. Clancy, I wanted to ask you, as Chair of the Women
Veterans Task Force, when I read through your testimony and the
others, you know, the first thing that came to mind was the
inclusion of women and minorities into clinical trials, but
even in terms of broadening the database that we have
currently.
And so I guess my question is twofold. One, you know, how
do we sort of incentivize inclusion of clinical trials for
women and minorities? And then, certainly in terms of women
veterans, infertility is a big issue and many women are often
diagnosed with an unexplained infertility, and that seems to be
a higher diagnosis rate than for men. And I was just in a
hearing this morning where I was told that ALS, which is very--
seems to be more prominent in the veteran community than the
civilian community, I was told that we don't know why that is
true.
So I guess my question is inclusion, infertility, and are
we looking at things like ALS. And I have no more time left,
but I will give you a few minutes.
Dr. Clancy. So some of this we would like to take for the
record to give you a complete accounting of what is known. As
you know, all federally-funded research has to be inclusive of
women and minorities. I believe that the diversity of the
veteran population is precisely why the Prostate Cancer
Foundation came to us for the collaboration that we undertaking
now, which has been underway for a couple of years. And it is
hard for me to convey the energy and excitement around this
right up to Dr. Stone and the Secretary, which I think is
phenomenal.
I would need to learn a little bit more, but we would be
happy to get you information about infertility.
ALS, in my mind, represents a very large question mark. I
do know that it is a presumption for some veterans as a
condition of military exposure, but we still have a lot to
learn, because that disease itself--I can tell you that I
personally have a relative who has ALS, a woman, who she has
not quite been in the same territory as Stephen Hawking, but
has had a pattern of disease which is very, very different, and
I think that underscores all of the points that Dr. Haas is
making that understanding--and that Matt made as well about
shifting how precision medicine and understanding more about
genetic variation is going to help us redefine how we think
about diagnoses and disease. That we will probably look back on
this time in the not-too-distant future as kind of, you know,
the Ice Age or something, because all of our diagnoses,
particularly in mental health, are based--and much of a
neurological diseases are based on careful categorization of
symptoms and signs, but we didn't have the imaging and
biomarkers that we needed.
Ms. Brownley. Thank you, Dr. Clancy.
Dr. Dunn.
Mr. Dunn. Thank you very much. I appreciate your comments
on that, I think you are right too.
Dr. Clancy, I am going to sort of do a lot of rapid-fire
questions here, if I can, because I have so many. Have we
started doing the sequencing on all these bio-bank?
Dr. Clancy. Yes, we have started that sequencing.
Mr. Dunn. Where is that being done?
Dr. Clancy. I am going to turn to Suma for specifics here.
Dr. Muralidhar. Contracted vendor--
Mr. Dunn. I couldn't hear.
Dr. Muralidhar. Sorry. Contracted vendor Personalist is out
in California.
Mr. Dunn. All right. And what is the status of the VA,
Department of Veterans Affairs partnership on the computing?
This is the quantum computing; we were going to start comparing
the data in the records to the sequencing.
Dr. Muralidhar. So we have just completed the IRB approvals
for the three projects. Our first three projects are--
Mr. Dunn. This is the national single IRB?
Dr. Muralidhar. Yes, this is the VA central IRB.
Mr. Dunn. So it is done?
Dr. Muralidhar. The projects have completed central IRB
approval.
Mr. Dunn. Good.
Dr. Muralidhar. And the computing environment is tested and
ready in the Department of Energy oak Ridge National
Laboratory. And the first three projects are focused on
assessing suicide risk, especially acute suicide risk, which is
of the great relevance for us. The second is on prostate
cancer, to distinguish between lethal and nonlethal.
Mr. Dunn. We have got a lot of that.
Dr. Muralidhar. Yes. And then the third one is on the total
cardiovascular disease burden.
Mr. Dunn. Outstanding, good. We look forward--one--are
there interim updates on this or are we just sort of waiting
for the research papers?
Dr. Muralidhar. We are just waiting to get the work
started.
Mr. Dunn. Okay. So, Dr. Clancy, why does the Office of
Research and Development have to enter into a partnership with
the VA National Clinical Oncology Program given they are both
VA entities? I mean, I thought the partnership existed ipso
facto.
Dr. Clancy. So this is interesting, because it gets to your
earlier point in your opening statement about getting to rapid
translation and impact on veterans' lives.
Traditionally--and, I mean, this is true everywhere--you
know, first we do the research and then we make the
publications, then the word gets out and it is incorporated
into textbooks. And, in my former life, we documented that that
time lag is about 17 years. That was not VA-specific, but in
general scientifically.
Mr. Dunn. I agree.
Dr. Clancy. The important part about this collaboration
with the Prostate Cancer Foundation is that we are really
pushing the boundaries of that history, right? So where we have
got researchers working along--
Mr. Dunn. So let me interrupt you, just because in the
interest of time. I am very, very familiar with the Prostate
Cancer Foundation, I have been working with them for years.
Great translation work, much, much faster, very, very
accelerated. I couldn't agree with you more. Let's do more
along that line.
Dr. Haas, and perhaps Mr. Kuntz as well, what do you think
is the single greatest barrier to VA researchers? What is the
biggest barrier they are facing, researchers in the VA?
Dr. Haas. Having time carved out for their research is
the--
Mr. Dunn. So are clinical duties interfering with research?
Dr. Haas. Yes, other duties in general. Yes, they have
reported that repeatedly to us that they don't have the ability
to focus--
Mr. Dunn. Mr. Kuntz, do you agree with that?
Mr. Kuntz. Yes, sir, and that is why I highlighted the
Veterans Equitable Resource Allocation, so those clinician
researchers are on the ground.
Mr. Dunn. I am concerned, I will tell you. It is not
intuitive to me that following this equitable research
distribution across the VISNs is going to speed up the research
or make more time available to the researchers. We will
consider that, but not in the next minute and a half.
Dr. Clancy, can you quantify the impact that your research
program has on your department's ability to recruit and retain
clinician researchers?
Dr. Clancy. It is phenomenal. I will tell you why, because
frankly a young physician emerging from training today from
residency, surgery, whatever, if they want a terrific career in
research, their best shot is to come to VA, and I think many of
them know that, because we value and put a very high premium on
physicians who both see patients and actually do research. So
it is a tremendous recruiting tool for us.
I will say that we--you have probably just highlighted some
issues about the tension between clinical productivity and
appropriate documentation--
Mr. Dunn. Yeah, I am familiar with that.
Dr. Clancy [continued]. --as well--yes, as well as carving
out time for research, but we are happy to take that and get
back with you.
Mr. Dunn. So a hot-button issue is one we hear about
frequently, is service dogs for veterans with PTSD. Could you
give us an update on that study and when we are going to hear
some recommendations?
Dr. Clancy. The final data collection was completing this
month and we should have results for you in a year.
Mr. Dunn. We would love that; we would love that.
Dr. Clancy. Yes.
Mr. Dunn. Oh, gosh, I have got so many questions here,
Chairwoman, and I have 7 seconds. Which one is the best one?
Based on the Shepherd Therapeutics statement for the record,
over 60 cancers disproportionately affect veterans and
servicemembers, 25 of those are rare cancers. What specifically
is the VA doing to identify treatment options for cancers that
tend to be associated more with veterans? And this sounds like
a great use of the Million Veterans Project, frankly.
Dr. Ramoni. So I would say that that is something that our
Post-Deployment Health Group is looking at very closely in
terms of which truly are disproportionately affecting veterans.
And then that is one of the reasons why NCI wanted to partner
with us, National Cancer Institute wanted to partner with us is
our ability to find rare cancers because we have such a large
database.
Now, whether they will be represented in the Million
Veterans Program, they may be so rare that they are small in
number in MVP, but throughout our system, I agree, we have a
great opportunity to shed light on those conditions.
Mr. Dunn. Let me say that I think Chairwoman Brownley and I
would love to help in any way we can, removing regulatory
barriers or underscoring things that you need underscored in
order to make progress.
Thank you very much, Madam Chair.
Dr. Ramoni. Thank you.
Ms. Brownley. Thank you, Dr. Dunn.
Mr. Lamb?
Mr. Lamb. Thank you, Madam Chairwoman. If I could just pick
right, there where Dr. Dunn left off. Is VA starting any sort
of database to track the specific types of cancer that patients
are diagnosed with and possibly collect tissue samples for
further research and integration with the genetic information,
is that sort of collection going on of the tissue samples in
particular?
Dr. Clancy. So all veterans with cancer are entered into
cancer registries locally, as are patients everywhere. I don't
know that we have yet made that connection with MVP, but I
actually think it is a terrific idea. There are technical
issues related to creating the kind of repository of tissue
samples that frankly have been a big challenge for our
colleagues at NIH and others as well, but I think it is a
fabulous idea.
Mr. Lamb. What are the--is there a way you could briefly
summarize the obstacles to doing that?
Dr. Clancy. I would have to take that for the record. I am
familiar with it only because it really came up when I was
running a research agency at HHS, but it has been very tricky
to figure out how we would store them and guarantee safety. I
am sure you have read stories where issues with samples that
have been lost have been sort of a hot-button issue. But do you
want to add?
Dr. Ramoni. Yes. So one of the challenges is, for example
just in cancer, there are about 400,000 cases a year, so the
size of a bio-bank that you would need to have at the ready and
to be able to fund in perpetuity is one of the barriers. So to
ensure that you can fund that kind of bio-bank forever,
essentially, is one of the barriers.
One of the options--
Mr. Lamb. Sorry to interrupt--
Dr. Ramoni. Yes.
Mr. Lamb [continued]. --does that type of thing exist
anywhere else or would the VA be the first to do something like
that?
Dr. Ramoni. I would have to come back to you with that, but
I don't believe that such a database with that many cancers
exists anywhere.
Mr. Lamb. But you are saying 400,000 per year just within
the VA patient population?
Dr. Ramoni. Yes. So VA has 8 percent of the cancers in the
country, so when you think about that, that is just an enormous
number. So that is one of the challenges and that is only
talking about cancers and not other conditions, for instance,
invisible wounds of war.
So the alternative that I think we should explore is the
fact that many of these individuals do have pathology samples
already extant in the VA in various repositories across the
country. So while they wouldn't be specifically collected for
research, we could have essentially a virtual biobank of
pathology stores, and that is the direction that we are looking
for, in addition to capturing some of those images, like slide
images, and the radiological images to pair with, for instance,
MVP data.
Mr. Lamb. Okay, thank you. Yeah, that is--we are looking
sort of to the future with a whole generation of veterans now
exposed to burn pits especially, that is kind of what is
motivating my question here. So--
Dr. Ramoni. Yes.
Mr. Lamb [continued]. --we will stay in touch with you
about that.
Dr. Ramoni. Thank you.
Mr. Lamb. Dr. Clancy, I also just wanted to say, I am very
happy to hear about the research at the Philadelphia Medical
Center on opioids and genetic predictors there. So if there is
anything, we can ever do to help accelerate that program or if
you have results to share at any point, please let us know.
Dr. Clancy. Absolutely.
Mr. Lamb. The last thing I just wanted to ask is, I see
there being an IT side to this whole thing as well. Obviously,
we are in the process now of building this new health record
system for the VA. When and if the science advances enough from
the Million Veterans Program or otherwise, I could see a future
in which clinicians are using their electronic health record
system to look at maybe genetic information about the patient
who is in front of them and whether they would reject certain
drugs or not, you know, to help them speed through that
appointment. Is that something that is being talked about at
your level with Cerner to make sure there is room for that in
the system that is being built, do you know?
Dr. Clancy. So we are actively working with Cerner to make
sure that the system will be able to accommodate our research
needs.
Mr. Lamb. Okay.
Dr. Clancy. I think it is safe to say that they probably
don't have a customer with the extent and depth of the research
that we support, at least on paper. And in person, they are
excited about it, but we do have people who are getting way
down into the technical weeds to make sure that that happens.
Some piece of that that we are excited about, although we
have not found the perfect solution yet, nor has anyone else,
is the notion of trial matching. So that, you know, today any
patient's entry into a clinical trial depends on a light bulb
going on over a doctor's head and then needing to go look
things up. If you think about how Amazon and other companies
work, we could be pushing that information to the encounter to
at least lift some of the burden and, frankly, to make the
information, how would I say, more patient-friendly--
Mr. Lamb. Uh-huh.
Dr. Clancy [continued]. --but that is exactly the kind of
thing that we need to be doing and, you know, an electronic
record that supports our needs has to have those needs as well.
Mr. Lamb. Okay. Well, I am sure you know we have the
separate Subcommittee on IT--
Dr. Clancy. Yes.
Mr. Lamb [continued]. --and are frequently in dialogue with
all the players. So if you run into any roadblocks there or
there is a way, we can help the conversation with Cerner or
otherwise, please let us know.
Dr. Clancy. Thank you.
Mr. Lamb. Thank you, Madam Chairwoman. I yield back.
Ms. Brownley. Thank you, Mr. Lamb.
And I now recognize Mrs. Radewagen for 5 minutes.
Mrs. Radewagen. Thank you, Madam Chair.
Dr. Haas, why does it take VA sites so much longer to
activate a clinical trial than non-VA sites? And what are the
barriers to using commercial IRBs?
Dr. Haas. It takes longer because the current system
doesn't allow the utilization of commercial IRBs, among other
factors. So when a sponsor goes to the VA to conduct a trial,
they have to go through multiple reviews, and the current
centralized process is significantly slower than the commercial
IRB process is.
Why--the second question was why the central IRB--
Mrs. Radewagen. What are the barriers to using commercial
IRBs?
Dr. Haas. As far as I understand, both Drs. Clancy and Dr.
Ramoni are committed to utilizing a central IRB, a commercial
central IRB process, but they continue to run into major
challenges. And, at a minimum, we believe that Secretary Wilkie
should facilitate the successful and timely implementation of
this reform, it is actionable, and the enactment of legislation
may also be necessary, but there are no overt reasons why it
cannot be implemented.
Mrs. Radewagen. And, Dr. Clancy, do you agree with that
assessment? And do you support the 100-days-faster initiative
and why?
Dr. Clancy. Absolutely. And, not only that, I am pleased to
say that we have got work in progress to make that happen. The
finalizing of the new common rule for research that affects all
participants in research and so forth, which has to be in place
this fall, next fall, or early 2020?
Dr. Ramoni. Early 2020.
Dr. Clancy. Early calendar year 2020, for a system our size
is one big, heavy lift. And so the leader whom Dr. Ramoni
recruited hit the ground running like I can't even describe,
and I think we will get that done.
When I worked at HHS, we used a commercial IRB in a
different manifestation, but nonetheless had very good luck
with it, and there is no reason we can't do this here.
Mrs. Radewagen. Thank you, Madam Chair. I yield back the
balance of my time.
Ms. Brownley. Thank you, Mrs. Radewagen.
Mr. Barr, I recognize you for 5 minutes.
Mr. Barr. Thank you, Madam Chairwoman.
My grandfather served on a destroyer in Navy in World War
II and he was diagnosed with cancer as a young veteran, and he
received treatment and was in remission, and then at age 59 he
was diagnosed with multiple myeloma and passed. This was in
1977 when I was a young child. And of course we have had a lot
of advances in the diagnosis of cancer and the treatment of
cancer, and obviously servicemembers in eras since World War II
have, you know, better treatment outcomes and hopefully better
diagnostics. But we think that my grandfather was exposed to
radiation on that destroyer--we don't know for sure, but we
think that was probably what caused his cancer. In Vietnam,
obviously, Agent Orange is something that we think is a cause
and then now, in the post-911 generation, burn pits, but
radiation throughout the eras.
My question to you all is, what advances in precision
medicine are helping with diagnosis? And how is the VA doing in
terms of--in conjunction with DoD, how are they doing in terms
of, you know, identifying risk factors for cancers with
servicemembers, and how is the VA trying to detect these
cancers earlier because of servicemembers' exposures to these
various risks.
And I will start with Dr. Clancy.
Dr. Clancy. Sure, and I will start off and then turn to Dr.
Ramoni.
So at baseline, as a foundational element of course,
veterans receive the, you know, current state of the science,
recommended screening tests for cancers, which sounds fairly
basic, but it is surprising because not all Americans do for
one reason or another, so that is colorectal cancer screening,
breast cancer and lung cancer and so forth, all of which is
good stuff.
Linking that back to exposures as a result of service is
trickier for sure. A lot of our ability to do that is obviously
dependent on the precision of the records of where people
served. Now, depending on their job classification, those
records may be more available or not, but that is why it is
very important that we have a research collaboration as part of
our Health Executive Committee where VA and DoD come together
on a regular basis to explore those very issues.
For some conflicts, the first Gulf War is a good example,
there is very, very little information about where people
served because of the short-term nature of the deployment and
we just don't have very good information. For other issues, it
is a matter of our records available and so forth.
But obviously, as you pointed out with burn pit exposure,
people are very, very worried about that, which is why we are
trying to beef up the registry and encourage people to come in
for exams and so forth.
Do you want to add anything?
Mr. Barr. Dr. Ramoni?
Dr. Ramoni. So I would agree with Dr. Clancy that getting
accurate records of exposures is key to our ability to
understand the impacts of those exposures. There are well-known
associations with Agent Orange and cancer and prostate cancer,
have more severe cancer if you are exposed to it, to Agent
Orange, Camp Lejeune exposures. But for the multiplicity of
things people were exposed to in their deployments to Iraq and
Afghanistan, we need to understand much more.
And we are committing to--you know, we are in the process
of putting together 2021 priorities and we are committing to
better understand the effects of military exposures, and, in
particular, there is a dearth of information on the clinical
side. So we have a lot of epidemiologic research, we have basic
science research, but there is an enormous gap for the clinical
research that will lead to translation much more quickly.
Mr. Barr. Thank you. And in my remaining time, of course,
with precision medicine, there is tremendous opportunity, and
what we are told is that oncology in particular there is
potential with the use of molecular diagnostics at the time of
diagnosis to help establish genetic characteristics of cancer.
Is the VA performing this type of molecular testing for cancer
patients at the moment of diagnosis?
Yes. And what is the promise of that? Explain that to us.
Dr. Clancy. So it is unknown what the promise is right at
this moment. There are some diagnostics that are well
recognized, for example, there are certain types of lung tumor
variants that have turned out to be very important, and we are
working actively with several organizations that are
facilitating access to industry funding for additional research
in this area, which is terrific. At the moment for lung cancer,
those appear to be a small minority of patients, although it is
amazing to meet people who tell you they were diagnosed with
stage 4 lung cancer 7, 8 years ago and, you know, here they are
just doing fine now, which still blows my mind.
For other areas, we are still in a much more exploratory
phase. So I am thinking about relatives who have shared their
results of testing with me. When I say to them, gosh, this is
like a lot of markers and tests, and did you ask what they are
for? And they all said, well, yes, but they are not sure yet,
but they are testing just in case. And we haven't quite
advanced to that level yet, but the number of tests that are
actually approved and recommended in terms of the evidence that
we have got that it makes a difference is still a fairly short
list.
We do have a partnership with the Sanford Health System
actually looking at a cancer survivorship cohort, which may
have helped the situation you described with your grandfather,
but that was just launched about a year ago. So we will have
more to report on that as it progresses.
Mr. Barr. Thank you. I yield back.
Ms. Brownley. Thank you, Mr. Barr.
And, Dr. Dunn, do you have some words--
Mr. Dunn. I confess, I do.
Ms. Brownley. Good.
Mr. Dunn. Thank you so much, Chairwoman Brownley.
Ms. Brownley. Absolutely.
Mr. Dunn. So one of the things, we talk about translation
and speeding up the translation to bedside, and I think that a
lot of that is about the system, how we work as clinicians with
researchers. And you made a point earlier that it used to be 10
to 15 years, you know, somebody would do work away in a lab, a
dusty, old lab, you know, find some facts out, write a paper,
add a chapter to a textbook, and then some young, brilliant
scientist comes along, reads it, and applies it to patients.
Now it is much quicker. We actually--you know, we bring a sick
patient to the scientist and say, what do you know, what do you
have. And then I think that the Million Veteran Project is an
ideal resource for that kind of translational research that
quickly gets in there and really hits the literature very
quickly.
And I think, by the way, you have partnered well with PCF
on that. And there is a similar group, by the way, that does
breast cancer research in the same way, translational very
fast, and that is another group that I think you could find
very easily.
So one thing that I was reading in your memo about the
three principal lines of science that we were talking about,
researching with--you know, the 31 alpha, beta, and gamma
research projects, then the three exemplar projects with the
DOE, which you mentioned earlier, and the MVP project itself,
how are we doing on those three-generally on those three lines
of research? And I am not sure who to ask that question to.
Dr. Muralidhar. Sure. So from the 31 alpha, beta, and gamma
projects, we have about five or six projects that are pretty
mature and already yielding results. And, for example, there
was one project on the genetics of cholesterol and we found--
Mr. Dunn. Genetics of what?
Dr. Muralidhar. Cholesterol, lipids--
Mr. Dunn. Okay.
Dr. Muralidhar [continued]. --high cholesterol. And--
Mr. Dunn. I guess I will need to read that paper.
Dr. Muralidhar. Yes, it has some very interesting findings.
First of all, that they have discovered some new genetic
variants in the subgroup of African-Americans and Hispanics, so
it is different from what is seen in the Caucasian population.
Mr. Dunn. Have you published that paper?
Dr. Muralidhar. Yes, it came out in Nature Genetics last
November. We can send you a link.
Mr. Dunn. I would love that.
Dr. Muralidhar. Yes, we will. And what they found very
interesting in that is there are genetic variations in three
genes, which could be potential therapeutic targets, and then
there are drugs out there already in the market that could be
applied to these. And so we are now investigating how we can
translate that discovery pretty quickly into the clinic.
And another example is one where we are also piloting
returning genetic results to men with metastatic prostate
cancer, where knowing specific variants in their DNA repair
genes, for example, can then direct them to a particular
treatment that would work better with them.
And so that is--
Mr. Dunn. I am familiar with that, that is great.
Dr. Muralidhar. And also in familial hypercholesterolemia,
FH, an inherited form of high cholesterol, where you can begin,
you know, intensive treatment earlier on if you knew that you
have the genes for that. So we are also piloting that with MVP.
So there are two projects that can see immediate
translation from MVP.
The three exemplar projects with DOE that I mentioned, with
the Department of Energy, are just about to begin. So we are
going to have milestones within the first year. Within a year
we hope to report back to you some of the findings on the
predictive algorithms for suicide risk or prostate cancer.
Mr. Dunn. That would be exciting. You know, it is great to
see that kind of progress happening and happening in short
timeframes, relatively speaking.
What mechanisms do we have to inform the patients at the
VA, the veterans in the VA health system, that we have some of
these research projects available? That maybe they want to
participate in the research, or maybe they just want to benefit
from the very cutting-edge work that you are doing. Is there an
information portal saying the VA is studying this, we have
expertise maybe in the VA in Miami in this and the VA in LA on
a different subject?
Dr. Clancy. So what I am less clear about, but very hot on
finding out, so I will be meeting with all of our chiefs of
staff, I guess the second week in July, just to ask that very
question, is how much local facilities tout what they are
doing, because there is nothing like home team pride, right?
Right here at the Philadelphia or whatever VA we are doing
something really amazing. I happened to meet a couple of
researchers from the amazing Philadelphia VA last week at our
research day here over in the Rayburn Building.
We certainly--VSO conventions are a very big place for us
to share a lot of these findings and also, by the way, to
enroll people in MVP. But I think that we could exploit other
opportunities as well. We also have a blog that goes out to a
lot of veterans, although I am told, since we don't make the
printed copy anymore, we may not be reaching everyone. That is
a different topic.
But, in any case, I think there are other venues that we
could explore for that, because I do think it is a point of
pride.
Mr. Dunn. Yeah, getting the word out is almost as important
as actually, you know, making the great discovery.
And I will make one request of you and then I yield back,
and the request is, next time you have a research day here on
the Hill, let me know. All right? I would love to come.
Dr. Clancy. Absolutely, you can count on it.
Mr. Dunn. Thanks so very much. I yield back.
Ms. Brownley. Don't just let Dr. Dunn know exclusively,
but--yeah, I am going to yield myself a little bit more time
too.
And so I want to know exactly how we can tear down the
barriers and what Congress barriers are to enhancing, hastening
the research that the VA is doing. So I know we have talked
about the commercial review boards moving to that. I honestly
don't understand why the VA can't just mimic a commercial
review board, why we have to make it so complicated. That, you
know, it goes back to this idea of every head of a medical
center has full decision-making power and authority over so
many programs that we are trying to kind of standardize, you
know, across the board.
So that is one, if that is what we have to do, let's do it.
I think there were probably some mention of some other
important--I think, Dr. Haas, you talked about some targeted
reforms that are needed. And I am not sure I have that in my
head, but if there is--if we are only talking about changing
statutory guidance, that is one thing, but if we need
legislation, that is another thing. And certainly I think I do,
and I think the Committee does, has a big interest in if we can
move forward legislation to tear down some of these barriers,
it doesn't seem to be there are costs really associated with
that, if we can do that, I think we need to start rolling up
our sleeves and getting that work done.
So, Dr. Clancy, I am just looking to you as our resource,
so that we can begin that work.
Dr. Clancy. So, thank you for that. And I cannot overstate
how much your interest in having this hearing and, frankly,
just the level of questions and the depth of interest will be
for our efforts for sure.
I think we will just move ahead with commercial IRBs. I see
one--or commercial IRB--I see one little wrinkle, but I think
that is easy, it feels easy now to more or less adjudicate,
which is what is their relationship between commercial IRB and
our internal office of oversight and review, but if that is an
issue I will bring that back to you. I am just not sure that I
am seeing that need of legislative guidance and so forth. But
we will certainly bring back the intensity of interest here,
which means more to me than I can tell you.
Ms. Brownley. Well, and I think--I mean, I don't know--I
believe I know where you stand on this, but I think we are also
interested in opening up more opportunities with private
industry--
Dr. Clancy. Yes.
Ms. Brownley [continued]. --and the research that they are
doing that, you know, I think together collectively we can make
more progress and perhaps make faster progress.
Dr. Clancy. Well, that is a very, very important signal for
us and we will certainly make the most of it.
Ms. Brownley. Okay. But in terms of what we need to do, you
know, to include that particular area too I think is really
important.
And I wanted to go back to Mr. Lamb's questioning with the
electronic health record. So it seems to me in reading the
testimony that one of the things needed is that the Department
of Energy's computer structure, whatever, to manage the data
that we have so far--I am not a computer scientist, nor am I a
doctor, nor am I a researcher, so forgive me for not having the
right terminology, but that if that is the case and if we are
using the Department of Energy to help to manipulate that data,
if the electronic health record is going to be, you know, sort
of finalized in the next 7, 8, 9 years it is going to be to
finalize it, I guess the question that I am trying to ask
without being a technical expert here is, if the VA were to
change or to do their own in-house computer system to manage
this data, or they are going to continue to use the Department
of Energy or the Department of Energy changes their process,
does that have to be compatible and interactive with an
electronic health record to get to where we want to go?
Dr. Clancy. Well, certainly for speeding up ease of
identifying relevant patients, being interactive is absolutely
necessary. And I would say it is also necessary to make sure
that we can translate rapidly.
I will say that the computational needs for research writ
large are pretty immense, so even NIH is exploring lots of
different venues from investing in their own--you know, the
Cancer Institute has had like a very robust investment in bio-
informatics for quite a few years, but they are working with
Google too. And we are having conversations with Google and a
number of other companies. And, you know, frankly, they are
delighted to have them, because they don't have access to
specific patient data. Obviously, that needs to be negotiated
to make sure all the Ts are crossed and Is are dotted and so
forth, and privacy is protected, but nonetheless I think there
is just immense opportunity.
Ms. Brownley. Just the concern I have is if there are
different entities that you are working with and we ultimately
want that to be compatible with our health records, if that is
changing constantly, the health record to be interoperable
between DoD and VA right now is complicated enough, that really
adds, at least it seems to me, another very complicated level
that will take some level of sophistication to make all that
happen.
Now, I am just expressing that concern.
Dr. Clancy. I think Dr. Ramoni had something to add.
Dr. Ramoni. So, you know, we have all highlighted how rich
VA data are and currently those data are held in a VistA
system. One of the key factors in ensuring that we continue to
derive value from that data for our veterans is that that
historical data be maintained and that it not simply be mapped
to the new system, because you lose information when you kind
of map it to a new system. So, for research to continue, it is
important that we maintain those historical data well before--
you know, for people even who have passed on, it is still
important that we have that information.
So it may exceed the clinical needs for that information at
this point, but we still need it for research.
Ms. Brownley. Very good, very good. And then I guess the
last question that I had is just--you know, just to help me
understand how this fits into the larger research arena is, you
know, how does the VA's research budget compare to the National
Institutes of Health, the Food and Drug Administration, other
governmental agencies, do you have any idea?
Dr. Clancy. Well, yes. So our budget for this current year
is just under $800 million. I would guess that that is
comparable to almost twice that amount in NIH dollars, because
we pay people's salaries from different lines. In fact, I used
to review grants at VA before I came to VA and I was always
surprised by the budget numbers, because they didn't quite make
sense to me, in part because I was used to looking at budgets
that paid for every single minute of everyone's time.
So that would put us at one and a half to $2 billion in
equivalent buying power, I believe, which would put us in the
scope of some of their larger institutes. I guess the Cancer
Institute is in the ballpark of 5 to $7 billion. The entire
National Institutes of Health, which is immense, is somewhere
in the $30 billion.
Ms. Brownley. But the research component is--
Dr. Clancy. Oh, they are all research.
Ms. Brownley. Yes.
Dr. Clancy. Yes.
Ms. Brownley. So, okay. Well, I think that is it for me, I
think I don't have any further questions.
Mr. Dunn, do you have any closing remarks you would like to
make before we--
Mr. Dunn. Yes, I thank the panel for your patience. I know
we dinged you on your schedule today; we dinged ourselves, so
we know we dinged you too, but it is our fault, and I
appreciate your patience and your willingness to come and
educate us. And I would like you to think that this actually is
not a waste of your time, because we need the information in
order to make decisions.
And so thank you for your efforts on our behalf and the
behalf of your patients.
Mr. Kuntz. Thank you.
Dr. Clancy. Well, thank you for your interest. This has
really been phenomenal.
Ms. Brownley. Well, and I appreciate all of you being here.
Mr. Kuntz, we didn't ask you a question, but your testimony was
invaluable. So thank you very, very much for being here.
And, Dr. Clancy, I am very serious about following up with
how we can break these barriers down to be able to do what we
need to do within the VA, but to open up this sort of treasure
chest that we have to the private industry, so that we can
really help and move towards some of these successes. Clearly,
suicide and post-traumatic stress and traumatic brain injury,
we know that all of these things lead ultimately to suicide.
Cancer, obviously for our veterans, these are areas that our
veteran community needs very, very desperately. And if we could
truly be the leaders in all of this, I think it would be quite
extraordinary.
So I really commend all of you for the work that you are
doing, and this is really a high point in what the VA does, and
so I thank all of you and your expertise.
And, with that, all Members will have 5 legislative days to
revise and extend their remarks, and include extraneous
material. And, without objection, the Subcommittee stands
adjourned.
Thank you.
[Whereupon, at 4:27 p.m., the Subcommittee was adjourned.]
A P P E N D I X
----------
Prepared Statement of Carolyn Clancy, M.D.
Good afternoon, Chairwoman Brownley, Ranking Member Dunn, and
distinguished Members of the Subcommittee. Thank you for the
opportunity to discuss VA's Million Veteran Program and Precision
Medicine research efforts. I am accompanied today by Dr. Rachel Ramoni,
Chief Research and Development Officer, and Dr. Sumitra Muralidhar,
Director of the Million Veteran Program.
Introduction
Precision medicine is the prevention, diagnosis, prognosis, and
treatment of health conditions that considers individual variability in
biology, environment, and lifestyle. Advances in biomedical research,
informatics, computational science, and medical care are converging in
the 21st century to reveal the complexity of human physiology and
enable us to decode that information to improve health and well-being.
VA is the largest and most diverse health care system in the United
States and has some of the richest data in the world. In combination,
those two factors give VA the ability and the responsibility to lead
the world in the practice of precision medicine. VA Research, in close
partnership with clinical operations and education, is the discovery
engine that drives the evolution towards ever more precise care of our
Veterans.
As Deputy Under Secretary for Health for Discovery, Education, and
Affiliate Networks, which includes the Office of Research and
Development (ORD), I am pleased to be here to share our vision,
investments, and deliverables in the field of precision medicine.
Strategic Priorities that Reflect VA Research Values
For more than 90 years, VA has conducted research within its health
care system. In establishing VA Research, Congress recognized both the
need to study Veterans' unique concerns and how essential research is
to excellent clinical care. This was prescient: VA Research has
resulted in three Nobel prizes, seven Lasker Awards, and numerous other
national and international honors.
Today, ORD continues to honor its statutory commitment through the
execution of three strategic priorities, which Dr. Rachel Ramoni, VA's
Chief Research and Development Officer, articulated in early 2018 and
includes the following:
1.To increase Veterans' access to high quality clinical trials;
2.To increase the substantial real-world impact of VA research; and
3.To put VA data to work for Veterans.
VA's Commitment to Real-World Innovation
Since its inception, VA Research's discoveries have contributed to
real-world impact. The pacemaker and liver transplantation are well-
known examples of early VA research advances that transformed health
care. Fewer people know that the Gleason grading system, which is used
worldwide predicting the prognosis of a man with prostate cancer, is
named for its creator, Donald Gleason, who was a pathologist at the
Minneapolis VA Health Care System. More recently, VA conducted the
foundational trial that established active surveillance as a safe
alternative to prostatectomy in low-risk prostate cancer. Importantly,
this work not only led to several publications in the prestigious New
England Journal of Medicine, but it also reshaped the care we provide.
VA is ahead of the curve in adhering to this best practice, which
improves the quality of life of men with prostate cancer.
The promise of ever more precise medicine is that we can go beyond
general predictions like low-, medium-, and high-risk prostate cancer
to specific predictions that will guide an individual Veteran's care.
One of the ways that ORD is making this vision a reality for Veterans
who are cared for by the Veterans Health Administration (VHA) is
through our partnership with the VA National Clinical Oncology Program
Office and the Prostate Cancer Foundation. The beachhead of this effort
is six VA medical centers that will act as hubs of best-in-class care.
The next phase will include adding hubs and extending from hubs to
spokes. The first precision oncology milestone is to ensure that men
with metastatic prostate cancer receive Deoxyribonucleic acid (DNA)
sequencing. Already, this effort has identified men who, based on their
genetic variations, will benefit from precision therapies that are
known to be effective against the specific type of cancer they have.
The Million Veteran Program: A Partnership with Veterans
One of ORD's major investments in precision medicine is the Million
Veteran Program (MVP). The program was launched in 2011 with a goal to
enroll at least one million Veteran partners by 2021 to build the
world's largest research database of genetic, health, lifestyle, and
military exposure information.
Enrollment
MVP has achieved its goal of being the largest program of its kind
in the world, with over 750,000 Veterans enrolled. MVP includes
Veterans from all 50 states, Guam, and Puerto Rico. MVP makes it easy
for Veterans to become a part of the program by having enrollment sites
at 58 VA medical centers; 83 community-based outpatient clinics; and
Veterans Service Organization conventions.
To ensure that all can benefit from precision medicine, we must
understand the genetic basis of diseases in diverse racial and ethnic
populations. Most genetic research to date has been conducted in
Caucasian populations. Findings in this group sometimes do not
translate well to other groups. MVP demographics track well with that
of Veterans enrolled in VA health care. Approximately 18 percent are
African American, and 7 percent are Hispanic. To enhance our ability to
serve all Veterans, MVP is repeating the genetic analysis of samples
from African American participants using a genetic test (genotyping
chip) enriched for genetic variants found in the African American
population.
Science
To put these data to work for Veterans, we must make use of the
best technologies and engage the best researchers. MVP is at an
important transition point, moving from a program focused exclusively
on enrolling a diverse set of Veteran partners to a program that is
both enrolling participants and making discoveries that will benefit
those Veterans. At present, MVP is undertaking three primary scientific
lines of effort:
1.Thirty-one alpha, beta, and gamma research projects have been
funded by ORD to both make discoveries and to establish the resources,
processes, and infrastructure necessary to responsibly support large-
scale science. The research topics span diseases of high relevance to
Veterans such as suicidality, posttraumatic stress disorder (PTSD),
multi-substance abuse, schizophrenia and bipolar disease, Gulf War
Illness, traumatic brain injury (TBI), Alzheimer's Disease, tinnitus,
and Parkinson's Disease. They also include chronic diseases highly
prevalent in Veterans such as cardiovascular and cardiometabolic
diseases, chronic kidney disease, cancer (prostate, breast, lung, and
multiple myeloma), osteoarthritis, and age-related macular
degeneration.
2.Three exemplar projects are being conducted in collaboration with
the Department of Energy (DOE). These data science-intensive projects
focus on suicide, prostate cancer progression, and cardiovascular
disease risk prediction. Over 75 researchers from VA and DOE national
laboratories are engaged in these projects. Each project includes a
requirement to work collaboratively with VHA clinical operations to
ensure real-world impact. For example, more accurate prostate cancer
progression risk predictions will improve our ability to identify those
Veterans with low-risk prostate cancer who should undergo surgery
versus active surveillance. The suicide risk prediction project will
use the power of artificial intelligence (AI) to improve the precision
of VA's Recovery Engagement and Coordination for Health - Veterans
Enhanced Treatment (REACH VET) algorithm, which is used to identify
Veterans at highest risk of suicide.
3.ORD is funding two projects to determine the feasibility and
value of offering to return important individual genetic results to MVP
participants, following re-consenting of the MVP participant and
validating the MVP finding in certified clinical laboratories. The
first is the return of genetic variants for familial hypercholesteremia
(FH), which is genetic high cholesterol. Veterans found to have FH will
be offered treatment, which reduces the risk of serious health problems
like heart attacks and stroke. The second project will reach out to
Veterans with a diagnosis of metastatic prostate cancer and harmful
variants in three DNA repair genes. This information will guide
treatment options and participation in clinical trials. These projects
are in the regulatory review phase and are expected to launch by the
end of Fiscal Year (FY) 2019.
Since the initiation of the MVP science effort in 2017, VA
researchers have presented over 100 abstracts at national and
international scientific and medical meetings, and over 15 peer-
reviewed original scientific papers have been published. Six recent
publications are in high-impact journals such as Nature Medicine,
Nature Genetics, and Nature Communications. These communicate novel
discoveries in the genetics of high blood pressure, high cholesterol,
alcohol use disorder, and PTSD.
MVP Data Access
MVP exists because our Veteran partners are willing to continue to
serve our Nation through participation in research. Respecting the
concerns voiced by Veterans in focus groups and surveys, MVP committed
to not distribute its datasets. Instead, researchers come to the data
to conduct their work in a secure environment. Thus, an essential first
step to realize our promise to MVP participants to advance precision
medicine among Veterans is to establish a modern computational
infrastructure that can scale to many studies occurring in parallel. To
this end, ORD is establishing a pilot with the University of Chicago
and the Open Commons Consortium to make de-identified MVP and
electronic health record data broadly available to approved VA and non-
VA researchers in a VA Data Commons. Continued investment in
information and technology modernization will support projects in the
VA Data Commons within the next two years.
To complement this effort, ORD is in the process of large-scale
curation of the data contained within the electronic health record
using natural language processing and other advanced computational
techniques. What we mean by curation is transforming the wealth of
disparate and identifiable information contained within electronic
health records into valid descriptors of an individual's health
conditions, such as metastatic prostate cancer, Gulf War Illness, and
PTSD. Having these curated data means that research projects can begin
more quickly and that we can share more meaningful de-identified data
with non-VA collaborators while protecting Veterans' privacy. By the
end of FY 2021, we pledge to create a library of at least 1,000 curated
health conditions.
Beyond MVP: Big Data, Biomarkers, and the Invisible Wounds of War
While MVP is a substantial VA Research investment in precision
medicine for Veterans, it is by no means the only such effort. The
individual projects are too numerous to enumerate in this statement, so
I highlight some exemplars focused on healing the invisible wounds of
war.
In 2017, ORD funded the Precision Medicine for Mental Health
(PRIME) Care clinical trial which is conducting genetic testing to
guide the selection of antidepressant medication among 2,000 Veterans
with major depressive disorder. The trial will determine both how
Veterans and clinicians use this information and whether it improves
outcomes. As of May 2019, the study was past the halfway point in
recruitment.
The Chronic Effects of Neurotrauma Consortium (CENC), pronounced
``sen-see,'' is a nationwide effort to understand the mechanisms of
combat-associated mild traumatic brain injury (mTBI), to evaluate how
co-morbidities like mental health conditions may be affected by combat-
associated mTBI, and to study treatment and rehabilitation strategies
for the short- and long-term effects of combat-associated mTBI. It
includes a longitudinal study with intensive biosampling and imaging
for biomarker development. CENC is funded by VA and the Department of
Defense (DoD). Data from CENC are available through the Federal
Interagency Traumatic Brain Injury Research (FITBIR) Informatics
System, which shares TBI research data, methodologies, and associated
tools. As of March 1, 2019, the consortium has submitted approximately
171,000 records on over 2,000 subjects who are enrolled in CENC
studies. In addition, CENC is in the process of uploading over 1,500
Magnetic Resonance Images to FITBIR. Notably, the epidemiologic
components of CENC already are yielding important findings, such as
that women Veterans with diagnoses of TBI, PTSD, or depression had a
significantly increased risk of dementia compared to women Veterans
without these diagnoses.
The Translational Research Center for TBI and Stress Disorders
(TRACTS) study is another longitudinal study with biomarker collection
to understand the complex changes in the brain, thinking, and
psychological well-being that result from TBI and PTSD. TRACTS focuses
on Veterans who served in Operation Enduring Freedom/Operation Iraqi
Freedom.
Expanding Veterans' Access to Clinical Trials
Clinical trials are essential to both generating the evidence
necessary to bring precision medicine research discoveries into the
clinic and to provide hope when Veterans reach the limits of what
standard medical care can provide. To achieve their goal to increase
Veterans' access to high quality clinical trials, ORD launched the
Access to Clinical Trials (ACT) for Veterans initiative in 2018 with
the support of several non-profits including the National Association
of Veterans' Research and Education Foundations (NAVREF), Us Against
Alzheimers, Lungevity, and Cohen Veterans Bioscience. ACT's goal is to
get VA clinical trial startup times to within 25 percent of industry
standards by the end of FY 2021.
Policy, infrastructure, and education must also evolve to support
the changing landscape of clinical trials, especially in light of the
single Institutional Review Board (IRB) review mandate that will take
effect on January 20, 2020. To lead this change, in late October 2018,
ORD welcomed Dr. Molly Klote, a retired Army colonel, as Director of
the Office of Research Protections, Policy, and Education. In December
2018, she and her team began a ``moonshoot'' initiative that identified
13 regulatory steps needed to be ready to meet the new national
mandate. They have thus far completed 7 of those required elements and
are on track to complete all by Jan 2020
Policy changes
The use of commercial IRBs was prohibited in VHA Directive 1200.05,
Requirements for the Protection of Human Subjects in Research. This
will be revised to allow their use in circumstances where a third party
pays the IRB fees. This update will dramatically increase VA's ability
to participate in multi-site clinical trials and to offer Veterans the
benefit of these trials. Master service agreements with the country's
two largest commercial IRB companies are being finalized. The item
remaining to realize these groundbreaking agreements is the Federal
Information Security Modernization Act (FISMA) data rating for data
that will need to be transferred to the commercial IRB to complete
their reviews.
Additionally, to facilitate our ability to partner with DoD to help
Servicemembers and Veterans, ORD is hosting a meeting on August 23,
2019, to document differences in regulatory, legal, privacy,
contracting, human resources and information security as it relates to
data sharing and clinical trial operations. At that point, we will
begin needed updates to the VA/DoD research handbook. DoD and VA
already allow for reliance on each other's IRBs.
Infrastructure
ORD is in the process of contracting to purchase a commercial off-
the-shelf, VHA-wide research management platform to support multisite
trials, increase efficiency, standardize process, and allow more
complete tracking and oversight of research and the research review
process. We anticipate a contracting decision by mid-July 2019. In
addition, ORD is standing up a process to review and approve
applications from VHA facilities to rely on non-affiliated IRBs for
research studies to support the single IRB review mandate. Finally, VA
Central IRB is doubling its capacity by adding a second national
expansion panel to decrease the wait time to receive IRB review. We
anticipate stand up by the end of this fiscal year. Future panel will
be added as the review demand is assessed.
Education
In addition to numerous regular education Webinars, ORD will be
hosting a workshop on August 20-21, 2019, to prepare local VA medical
center IRB personnel for research and regulatory requirements for the
shift to single IRB review.
Conclusion
On behalf of ORD and the many VA researchers across the country, I
thank you for your attention. As the Deputy Under Secretary for Health
for Discovery, Innovation, and Affiliate Networks, I am fortunate to
represent these superlative individuals in sharing the progress we have
made towards fulfilling our commitment to discover and bring the
advances of precision medicine to our Nation's Veterans. My colleagues
and I look forward to responding to your questions.
Prepared Statement of Dr. Magali Haas
Introduction
Dr. Magali Haas, PhD. CEO and President of Cohen Veterans
Bioscience and co-founder of the Coalition to Heal Invisible Wounds.
Good afternoon, Chairwoman Brownley, Ranking Member Dunn, and
distinguished Members of the Subcommittee. Thank you for the honor to
testify before the Subcommittee and for the opportunity to discuss the
barriers to precision medicine. It is also a pleasure to testify
alongside Dr. Carolyn Clancy, Deputy Under Secretary for Health for
Discovery, Education and Affiliated Networks with the Veterans Health
Administration Department of Veterans Affairs (VA), and with fellow
Coalition Member, Matt Kuntz.
Cohen Veterans Bioscience
Cohen Veterans Bioscience (CVB) was founded in 2014 under its
original name of Orion Bionetworks to address brain disease research
and in 2015 expanded its focus in response to the clear need to provide
optimized care for our nation's Veterans suffering from post-traumatic
stress disorder (PTSD) and traumatic brain injury (TBI). We are a
national, nonpartisan research 501(c)(3) public charity organization
dedicated to fast-tracking the development of diagnostic tests and
personalized therapeutics for the millions of Veterans and civilians
who suffer the devastating effects of trauma-related and other brain
disorders. CVB is leading the way in responding to this critical
challenge by organizing a multi-stakeholder complementary network of
international subject-matter experts and employing the most innovative
scientific tools to support a common roadmap for identifying diagnostic
biomarkers, building predictive disease models and developing
treatments for PTSD and TBI. We are rethinking how we study brain
disease, how we define it, how we identify new targets and how we
advance precision medicine approaches, and our portfolio of projects
exemplifies our commitment to accelerating the field of brain health.
Our portfolio includes several large-scale programs, specifically
in the area of PTSD and TBI, which allow us to rapidly and empirically
develop and test new diagnostics and treatments that will speed
personalized medicine approaches to clinicians and will directly
benefit the Veteran and civilian communities. Examples of our research
programs are listed below:
Adaptive Platform Trial in Post-traumatic Stress
Disorder: The only approved medications for the treatment of PTSD are
the selective serotonin reuptake inhibitors (SSRIs) sertraline
(Zoloftr) and paroxetine (Paxilr), which were approved over 17 years
ago\1\. However, their efficacy for treating PTSD is limited, with
response rates rarely exceeding 60% and only 20-30% of patients
achieving complete remission\2\. The VA 2017 Consensus Statement of the
PTSD Psychopharmacology Working Group concluded that there is a
deficient pipeline of new PTSD medications and an assessment of recent
trial failures has generated concerns about how to best identify new
targets for medication development and optimally design clinical
studies\3\. The high failure rate of previous clinical trials can be
attributed not only to the lack of validated biomarkers for PTSD, which
prevents clinicians from predicting whether a patient will respond to a
given therapeutic in a clinical trial, but also, and most critically,
to the field's historical use of traditional clinical trial designs,
which lack the ability to implement prospectively planned modifications
to one or more aspects of the trial based on the heterogeneity of the
patient population.
---------------------------------------------------------------------------
\1\ Jeffereys M. Clinician's guide to medications for PTSD. Sep 12,
2011. Available at: http://www.ptsd.va.gov/ professional/ pages/
clinicians-guide-to-medications-for-ptsd.asp. Accessed October 20,
2011.
\2\ Berger W et al. Pharmacologic alternatives to antidepressants
in posttraumatic stress disorder. Prog Neuropsychopharmacol Biol
Psychiatry. 2009; 33:169-180.
\3\ Krystal J. et al., It Is Time to Address the Crisis in the
Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement
of the PTSD Psychopharmacology Working Group, J. Biological Psychiatry
(2017). http://www.biologicalpsychiatryjournal.com/ article/S0006-
3223(17)31362-8 /abstract.
---------------------------------------------------------------------------
In September 2018, Cohen Veterans Bioscience was granted a research
award by Advanced Technology International (MTEC Consortium Manager) on
behalf of the U.S. Army Medical Research and Materiel Command
(MRMC)\4\. The award is for a three and a half year study to
comparatively test the efficacy and safety of pharmacotherapeutics for
PTSD via a well-powered adaptive platform trial (APT). Cohen Veterans
Bioscience will lead this program and serve as a Clinical Coordinating
Center, establishing a clinical trial infrastructure for the trial's
governance structure that includes a Joint Steering Committee with
representatives from the VA, the National Institute of Mental Health,
the FDA, and the Defense Health Agency's Psychological Health Center of
Excellence. This clinical trial is scheduled to start in the spring of
2020 and will incorporate biological measurements to support a
precision medicine approach to PTSD treatment. During the period of
performance, at least two active drugs (pending selection) will be
tested simultaneously incorporating biological measurements to support
a precision medicine approach to PTSD treatment. The APT will also
incorporate extensive biomarker testing to identify and enable the
validation of more precise diagnostics, biomarkers that can predict the
response to specific treatments, or biomarkers that could be used for
stratifying patients in clinical trials. The results of this trial aim
to identify a drug to move forward for Phase 3 testing starting in 2023
and ultimately lead to an alternative FDA- approved drug or changes to
clinical practice guidelines for the treatment of military- related
PTSD.
---------------------------------------------------------------------------
\4\ Cohen Veterans Bioscience Adaptive Clinical Trial press
release. October, 2018. Available at: https://
www.cohenveteransbioscience.org /2018/10/04/ cvb-receives-resarch-
award-dod-ptsd-clinical-trial/. Accessed on June 24, 2019.
---------------------------------------------------------------------------
Research Alliance for PTSD/TBI Innovation and Discovery
Diagnostics (RAPID-Dx):
RAPID-Dx is CVB's flagship biomarker discovery collaborative, with
the aim to fast- track the development of objective diagnostics for
PTSD, TBI and other trauma-related brain disorders. Developing
biomarker-based diagnostics is essential to shifting diagnosis &
treatment of PTSD and TBI from a syndromic, symptom-based approach to a
biological, mechanistically-based one that targets the effects of
trauma at their molecular roots. To date, no biomarkers have been
sufficiently validated and independently replicated to allow for use in
stratifying these highly heterogenous patient populations, predicting
disease course, or supporting diagnostic development. To advance
discovery and validation, CVB is coordinating a multi-disciplinary,
multi-institution, public private partnership program that will bring
together large, well-characterized cohort studies of PTSD and TBI,
encourage collaboration amongst investigators to share large biomarker
and imaging legacy datasets in a centralized, cloud-based platform, and
support large- scale analyses of stored biosamples on high performance
bioassay platforms. This will ultimately inform precision medicine
approaches for more effectively treating veterans and others suffering
from trauma-related brain disorders.
Digital Health: In July 2018, we announced the formation
of Early Signal, LLC, a wholly owned, non-profit subsidiary of Cohen
Veterans Bioscience.\5\ The new subsidiary allows CVB to continue its
innovative approach to translational research by advancing needed
diagnostics and precision medicine for brain disorders including PTSD,
TBI and MDD, and expands our capabilities in digital health and data-
driven research. Early Signal has developed a leading digital health
platform for recording and analyzing a range of information, reported
from wearables and other sensors, directly related to the well-being of
patients living with brain disorders. By tracking variables such as
sleep, physical activity, stress and cognition, we aim to better
understand what changes in patients with brain disorders over time and
to use this multifactorial data to improve the ability of clinicians to
diagnosis a wide range of brain disorders and to treat them using
precision medicine approaches.
---------------------------------------------------------------------------
\5\ Cohen Veterans Bioscience press release. September, 2018.
Available at: https://www.cohenveteransbioscience.org /2018/09/06/
cohen-veterans-bioscience-expands-digital-health-platform- with-early-
signal-expertise/. Accessed June 24, 2019.
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The Coalition to Heal Invisible Wounds
CVB is a founding co-chair of the Coalition to Heal Invisible
Wounds, which launched in February 2017.\6\ The Coalition advocates for
policy reforms to widen and expedite the pipeline for new therapies and
diagnostics for PTSD and TBI. By deepening public-private cooperation
and adopting targeted reforms, the VA and Department of Defense (DoD)
can become leading partners in delivering new therapies and diagnostics
to doctors.
---------------------------------------------------------------------------
\6\ The Coalition's members are Cohen Veterans Bioscience (co-
chair), the Military Veterans Project, NAMI Montana, Otsuka America
Pharmaceutical Inc. (co-chair), and Tonix Pharmaceuticals. More on the
Coalition to Heal Invisible Wounds is available at invisiblewounds.org.
---------------------------------------------------------------------------
Doctors need better tools to diagnose and treat Servicemembers and
Veterans suffering from PTSD and TBI. Only 16 percent of IAVA members,
as surveyed in 2017, believe troops and Veterans are getting the care
they need for mental health injuries, and stigma remains the top reason
Service members and Veterans are not seeking care.\7\ The Coalition's
mission is guided by four overlapping concerns:
---------------------------------------------------------------------------
\7\ ``IAVA 2017 Annual Member Survey: A Look into the Lives of
Post-9/11 Veterans'' Published October 2017. Available at: https://
iava.org/wp-content /uploads/2016/ 05/IAVA--Survey--2017--
v11update.pdf.
1.A staggering 6,000 Veterans have committed suicide each year from
2008 to 2016. In 2016, the suicide rate was 1.5 times greater for
Veterans than for non-Veteran adults.\8\
---------------------------------------------------------------------------
\8\ ``VA National Suicide Data Report 2005-2016.'' Published
September 2018. Available at: https://www.mentalhealth.va.gov /docs/
data-sheets/ OMHSP--National--Suicide--Data--Report--2005-2016--
508.pdf.
---------------------------------------------------------------------------
2.Treating the underlying condition can help reduce the risk of
suicide, but a 2015 Journal of the American Medical Association (JAMA)
study found that about two-thirds of Veterans receiving prolonged
exposure therapy, considered by Stanford researchers to be ``the gold
standard of behavioral therapy for PTSD,''\9\ ``retained their PTSD
diagnosis after treatment.''\10\
---------------------------------------------------------------------------
\9\ Stanford Medicine News Center. ``Biology may make certain PTSD
patients unresponsive to behavioral therapy.'' April 3, 2019. Available
at: http://med.stanford.edu/news/ all-news/2019/04/ biology-may-
affect-ptsd- patients-response-to-therapy.html.
\10\ Steenkamp, MM, et. al. ``Psychotherapy for Military-Related
PTSD: A Review of Randomized Clinical Trials.'' Journal of the American
Medical Association. 2015 Aug 4. pp. 489-500.
---------------------------------------------------------------------------
3.Treatment-resistant PTSD is a common clinical problem in
Veterans, since currently ``available medications are often ineffective
in usual clinical practice.''\3\
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\3\ Krystal J. et al., It Is Time to Address the Crisis in the
Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement
of the PTSD Psychopharmacology Working Group, J. Biological Psychiatry
(2017). http://www.biologicalpsychiatryjournal.com/ article/S0006-
3223(17)31362-8/abstract.
---------------------------------------------------------------------------
4.The VA found in 2016 that ``most [PTSD] patients are treated with
medications or combinations for which there is little empirical
guidance regarding benefits and risks,'' and there is ``no visible
horizon for advancements in medications that treat.PTSD.''
The lack of clinical research in PTSD and TBI has led to treatment
regimens that resemble trial and error. In 2013, while still serving as
Director of the National Institute of Mental Health, Dr. Tom Insel
stated that ``the diagnostic system [for mental disorders] has to be
based on the emerging research data, not on the current symptom-based
categories.''\11\ In Veterans mental health, precision medicine has a
simple meaning: we want diagnostics and therapies that work.
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\11\ ``Post by Former NIMH Director Thomas Insel: Transforming
Diagnosis.'' NIMB Director's blog. Posted April 29, 2013. Accessed May
9, 2018. https://www.nimh.nih.gov/ about/directors/ thomas- insel/
blog/2013/ transforming-diagnosis.shtml.
---------------------------------------------------------------------------
The lack of precision medicine in PTSD care contributes to the high
rate of treatment- resistant PTSD in Veterans. Clinicians need new
tools to diagnose precisely those suffering from PTSD and TBI, which
can only be achieved by systematic reviews of existing evidence, and a
greater investment in both basic and translational research and in
large-scale and well controlled clinical trials. It also requires
improved clinical trial processes and clinical trials that include
Veterans. We owe Veterans our commitment to prioritize clinical
research.
The 100 Days Faster Initiative
We ask today that the Subcommittee help the VA overhaul its
clinical trial startup practices. According to data from two major
contract research organizations, in the last four years VA sites have
taken an average of 265 days to activate a site (from receipt of
registration and contract to active).\12\ Non-VA sites have averaged
141 days. Because of these lengthy delays, many clinical research
sponsors do not attempt to bring clinical research to the VA, and have
not done so for decades.
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\12\ Personal communications with contract research organizations
in July 2018 and January 2019.
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The lack of clinical trials at VA sites means that Veterans lack
access to the frontier of medicine for many disease conditions. For
Veterans suffering from PTSD, TBI, hearing loss, alcohol and other
substance use disorders (SUDs), cancer, and other conditions, a
clinical trial may be the next or only available treatment option. This
is most acute in oncology, where only a small fraction of the hundreds
of clinical trials annually in the United States use VA sites. Of
34,000 oncology clinical trials in the United States listed on
clinicaltrials.gov, fewer than 800 have taken place at a VA
facility.\13\ What happens when a cancer study does not open in a VA
facility? A Veterans suffering from that form of cancer is more likely
to die sooner. Countless birthday, anniversaries, graduations, births,
and other milestones missed in part because of inadequate clinical
trial procedures at VA sites.
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\13\ Source: Clinicaltrials.gov search of clinical trials conducted
in oncology at VA sites. Accessed June 24, 2019.
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We believe that timely and high impact reform is within reach. The
VA Office of Research and Development (ORD) and the National
Association of Veterans Research and Education Foundations (NAVREF),
have led a multi-stakeholder review of the causes of clinical trial
startup delays. Both CVB and the Coalition have engaged in this review,
called Access to Clinical Trials (ACT) for Veterans, which has
identified numerous areas ripe for immediate reform.
We believe that with targeted reforms, the VA can become 100 days
faster, on average, at clinical trial startup by 2021. We call this the
100 Days Faster Initiative, and last month organized a multi-
stakeholder letter to the House and Senate Committee leadership calling
for congressional support of the goal. Achieving this goal would build
the institution of the VA, bringing it to near-parity with leading
clinical research institutions in the United States.
As the causes of clinical trial startup delays extend throughout
numerous functions within the VA, it is imperative Congress provide the
VA statutory guidance to achieve the 100 days faster objective.
Informed by the ACT for Veterans process and other engagement with
leading stakeholders in the clinical research community, we recommend
that the Subcommittee develop legislation that provides for the
following reforms:
1.Allow the use of commercial Institutional Review Boards (IRBs) in
sponsored clinical research.
Slow and inconsistent reviews by IRBs constitute a major factor in
start-up delays. IRB reviews ensure that clinical trials abide by clear
ethical guidelines and protect the well- being of research
participants. VHA Handbook 1200.05, revised January 2019, states: ``A
VA facility may not use a commercial IRB as an IRB of Record.'' Yet,
commercial IRBs accredited by the Association for the Accreditation of
Human Research Protection Programs (AAHRPP) are widely employed outside
of the VA and are highly regarded in the research community for
thorough and timely procedures. Over the past two years, the VA ORD has
been exploring policy changes to allow the use of commercial IRBs as
another option to local IRBs or the VA Central IRB. The VA should
immediately remove all barriers to allowing the use of commercial IRBs
in sponsored clinical research.
2.Authorize and provide performance benchmarks for Office of
Research Reviews within the Office of Information Technology (IT)
A centralized information security analysis would allow for a more
thorough and appropriate review, while reducing delays that often occur
at the local level. Local information security officers (ISOs) have
variable levels of knowledge related to clinical research data storage
and transfer requirements, and limited time to understand the research
requirements which leads to security requirements for the same study
that differ by VA clinic.
Since 2018, the VA Central Office, Office of IT, has hired ten ISOs
to assist local ISOs with clinical research approvals, covering the
entire national research program for activities across all of the more
than 100 VA sites. Codifying this function within the Office of IT and
requiring that it fulfill specific objectives, such as developing an
approved vendor list, would allow for a more thorough and appropriate
review, while reducing delays that often occur at the local level.
3.Authorize and provide performance benchmarks for Office of
Research Reviews within the Office of Privacy (IT)
Similar to information security reviews, a centralized privacy
review would allow for a more thorough and appropriate review, and
standardize outcomes. Medical Center privacy officers have variable
levels of knowledge related to clinical research privacy requirements,
and thus privacy protocols can vary significantly between clinical
trial sites. Similar to the Central Office IT Team, the VA should hire
dedicated privacy officers dedicated to multi-site clinical research.
Codifying this function within the Office of Privacy and requiring that
it fulfill specific objectives would allow for a more thorough and
appropriate review, while reducing inconsistencies that often occur at
the local level.
4. Refocus the Role of the Research and Development Committee
Stakeholders both within and outside of the VA have identified the
R&D Committee as worthy of refocusing toward other aspects of the
research and development process, including identifying emerging
research needs at local VA facilities, and removing the R&D Committee's
role as the final approval for a clinical trial site. Unique to VA
facilities, after a trial sponsor has secured all of the required
substantive approvals for a trial site, the local Research and
Development (R&D) Committee provides the final approval before a site
can begin its trial (VHA Directive 1200.01). This is a unique
requirement, not found at academic and other institutions that host
clinical trials, and can delay start-up by several weeks.
Taken together, these four reforms would help the VA make
substantial progress toward improving its average clinical trial start-
up period by 100 days. We look forward to working with the Subcommittee
to identify other steps Congress can support toward this goal.
Conclusion
The Coalition to Heal Invisible Wounds thanks the Subcommittees for
its work to strengthen the VA's capacity to support the development of
precision medicine. Veterans have earned the right to world-class
health care, and an implicit promise of world-class health care is a
strong research function. We strongly believe that the VA has the
potential to be a world-class research partner, enabling better
healthcare for Servicemembers and Veterans. Achieving the 100 Days
Faster Initiative would provide significant initial progress toward
that goal. On behalf of CVB and the Coalition to Heal Invisible Wounds,
I thank you for your attention to these matters.
Prepared Statement of Matt Kuntz, J.D.
I. Introduction
Chairwoman Brownley, Ranking Member Dunn and distinguished members
of the Subcommittee, on behalf of NAMI, the National Alliance on Mental
Illness, and NAMI Montana, I would like to extend our gratitude for the
opportunity to share with you our views and recommendations regarding
``Beyond the Million Veterans Program: Barriers to Precision
Medicine.'' NAMI Montana and the entire NAMI community applauds the
Committee's dedication in addressing the critical issues around the
veterans' brain healthcare system. NAMI is the nation's largest
grassroots mental health organization dedicated to building better
lives for the millions of Americans affected by mental illness. NAMI
advocates for access to services, treatment, support and research, and
is steadfast in its commitment to raising awareness and building a
community of hope for all of those in need.
NAMI works closely with many partners to accelerate research and
advance treatment for mental health conditions. For example, NAMI
Montana is a member of the Coalition to Heal Invisible Wounds
(Coalition). The Coalition was founded in February 2017 to connect
leading public and private scientific investigators of new post-
traumatic stress disorder (PTSD) and traumatic brain injury (TBI)
treatments with policymakers working to improve care for veterans.
Coalition members support innovators at all stages of the therapy
development lifecycle, from initial research to late-stage clinical
trials.
In addition to serving as the Executive Director of NAMI Montana, I
am also the Director of the Center for Mental Health Research and
Recovery (CMHRR) at Montana State University. While the CMHRR does have
statewide suicide prevention research, none of that research funding
presents a conflict with this testimony. I have also been appointed to
the Creating Options for Veterans' Expedited Recovery (COVER)
Commission. This testimony does not reflect the views of Montana State
University, the Montana University System, or the COVER Commission.
I. Overview
With our commitment to promote innovation to accelerate research
and advance treatment for mental health conditions, NAMI remains very
supportive of the research and development of psychiatric biomarkers
for brain health conditions, and we encourage Congress to make the
necessary investments in research to begin to accomplish this goal.
NAMI continues to advocate for VA to work in coordination with the
Department of Defense (DoD) to develop and carry out a longitudinal
research study which will identify biomarkers or non-survey diagnostic
tools, which will enable clinicians to make a more precise diagnosis.
NAMI advocates for improving mental health and brain condition
diagnostics because an accurate, quick, and early diagnosis has the
potential to save countless lives and is a critical step to effective
care. Currently, the only tools available to diagnose a mental health
condition are survey-based. This results in a large amount of
misdiagnosis of conditions, and therefore lack of timely and
appropriate treatment. We are dedicated to working with the VA,
legislators, and researchers to improve the process and get veterans
the treatment and care they need for their recovery. Earlier
identification of conditions will lead to better treatment for these
conditions, which is a necessary component to reducing suicides among
Veterans.
II. Background
A. Scientific Justification
Suicide is the 10th-leading cause of death in the United States,
and Veteran suicide is a national concern. According to the VA National
Suicide Data Report, in 2016, the suicide rate was 1.5 times greater
for Veterans than for non-Veteran adults. According to the authors of
Suicide Among Soldiers: A Review of Psychosocial Risk and Protective
Factors, ``The fact that the vast majority of suicides occur among
people with a current mental disorder makes this risk factor a prime
target for screening and prevention efforts.''\1\
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\1\ Nock, Matthew K., et al. ``Suicide among soldiers: a review of
psychosocial risk and protective factors.'' Psychiatry: Interpersonal &
Biological Processes 76.2 (2013): 97-125.
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However, the state of the science in the screening, diagnosis and
treatment of mental health conditions is in flux. A strong analysis of
this issue is given by Dr. Thomas Insel, MD, et al. in the paper
introducing the National Institute of Mental Health's Research Domain
Criteria effort. At the time this article was published, Dr. Insel was
the Director of the National Institute of Mental Health (NIMH):
Current versions of the DSM and ICD have facilitated reliable
clinical diagnosis and research. However, problems have increasingly
been documented over the past several years, both in clinical and
research arenas. Diagnostic categories based on clinical consensus fail
to align with findings emerging from clinical neuroscience and
genetics. The boundaries of these categories have not been predictive
of treatment response. And, perhaps most important, these categories,
based upon presenting signs and symptoms, may not capture fundamental
underlying mechanisms of dysfunction. One consequence has been to slow
the development of new treatments targeted to underlying
pathophysiological mechanisms.
History shows that predictable problems arise with early,
descriptive diagnostic systems designed without an accurate
understanding of pathophysiology. Throughout medicine, disorders once
considered unitary based on clinical presentation have been shown to be
heterogeneous by laboratory tests-e.g., destruction of islet cells
versus insulin resistance in distinct forms of diabetes mellitus. From
infectious diseases to subtypes of cancer, we routinely use biomarkers
to direct distinct treatments. Conversely, history also shows that
syndromes appearing clinically distinct may result from the same
etiology, as in the diverse clinical presentations following syphilis
or a range of streptococcus-related disorders.\2\
---------------------------------------------------------------------------
\2\ Insel, Thomas, et al. ``Research domain criteria (RDoC): toward
a new classification framework for research on mental disorders.''
(2010): 748-751.
The critical nature of this issue to the VA's services is one of
both severity (veteran suicide) and scope. According to the VA's Office
of Research and Development, ``More than 1.8 million Veterans received
specialized mental health care from VA in fiscal year 2015.''\3\
---------------------------------------------------------------------------
\3\ Office of Research & Development website. Department of
Veterans Affairs. Accessed on June 19, 2019. https://
www.research.va.gov/ topics/ mental--health.cfm
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Therefore, the VA serves almost 2 million veterans a year in a
treatment system based upon mental health diagnosis categorizations
that the former Director of the National Institute of Mental Health has
deemed not to be ``predictive of treatment response''\4\ (emphasis
added). The ramifications of that dramatic flaw in the VA's mental
health treatment system presents a glaring fissure in our ability to
prevent veteran suicides.
---------------------------------------------------------------------------
\4\ Insel, Thomas, et al. ``Research domain criteria (RDoC): toward
a new classification framework for research on mental disorders.''
(2010): 748-751.
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B. Personal Justification
My family lost my stepbrother Specialist Christopher Dana to a
post-traumatic stress injury in March of 2007. His post-traumatic
stress injury stemmed from a brutal tour in Iraq as a HUMVEE machine
gunner with the Montana National Guard. The Montana National Guard
medical professionals had no idea that Chris was struggling with a
brain health condition until he took his life. I will not go into depth
about Chris's story now. However, I can't help but wonder what a more
effective system for screening, diagnosing, and treating brain health
conditions would have done for Chris.
Instead I will focus the personal side of this testimony on two of
my dear friends, John Scott Hannon and Mike Franklin, who tragically
died by suicide, and how their stories relate to precision mental
health.
1. Commander John Scott Hannon
(a) Obituary
Commander John Scott Hannon USN (Ret.), affectionately known to his
family as ``Scott,'' was born April 11, 1971, in Nairobi, Kenya. Born
to a U.S. Diplomatic Corps family, he grew up living in Tanzania, the
Soviet Union, England, Belgium, as well as McLean, VA, and Helena, MT.
In 1989, Scott enlisted in the U.S. Navy and qualified as a Gunner's
Mate in 1990. He graduated with BUD/S Class 173 in March 1991 and, upon
completion of SEAL Qualification Training, was assigned to SEAL Team
Two. From 1995 to 1998, Scott completed multiple deployments in Europe,
Middle East and Asia with SEAL Team Five, where he was top ranked SEAL
Assistant Platoon Leader. He served with SEAL Team Three in the Pacific
and Southwest Asia and was named top ranked SEAL Platoon Commander.
From 2000 to 2003, Scott was assigned to SEAL Delivery Vehicle Team Two
operating mini submarines and became Task Unit Commander. Scott was the
top-rated officer during a six-month advanced maritime special
operations course, the most demanding joint training available in the
military, and was hand-selected to lead a covered unit in a sensitive
``Preparation of Battlespace'' mission. In 2003, he joined the Naval
Special Warfare Development Group, commonly known as SEAL Team Six, and
was eventually responsible for all aspects of curriculum development
and individual certification. John Scott graduated in 1995 from the
University of Colorado with a B.A. in Political Science. He attended
school on a Naval Reserve Officers Training Corps (NROTC) scholarship.
From 2006 to 2008, he received a scholarship to attend the Tuck
Business School at Dartmouth College, then worked as a Special
Operations and Policy Staff Officer at the U.S. Special Operations
Command (USSOCOM) until he retired in 2012.\5\
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\5\ https://www.veterans.senate.gov/ imo/media/doc/hannon.bio.pdf
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John Scott's supervisory, technical and safety qualifications
include Military Freefall Specialist, Static Line Parachutist, NSW
Sniper (Honor Graduate), Naval Gunfire Forward Controller, Lead
Climber, High Performance Small Boat Coxswain, Diving Supervisor, Cast
Master, Rope Master, Live Fire Range Supervisor, Joint Special
Operations Planner, Amphibious Operations Planner, Advanced High Risk
Survival & Hostage Survival, Advanced Combat Trauma Care Provider, Long
Range MAROPS, Expeditionary Warfare Staff Planning, Customized Military
Mobile Force Protection and others. Scott was also awarded the Joint
Service Commendation medal, Defense Meritorious Service medal, Navy and
Marine Corps Commendation medal (3), Joint Service Achievement medal,
and the Navy, Marine Corps Achievement medal (2) and Joint Meritorious
Service Award, and Bronze Star Medal (Gold Star in lieu of the Second
Award). After 23 years of military service, Scott retired to his family
home near Helena, Montana. In addition to VA Montana treatment for
Post-Traumatic Stress Disorder, Traumatic Brain Injury, severe
depression and bipolar disorder, he was a committed volunteer with a
number of local organizations. He was involved with the Montana chapter
of NAMI, speaking candidly at events about his wartime injuries. Scott
also rescued and rehabilitated injured wild animals at Montana Wild,
provided training support for the Lewis and Clark Search and Rescue,
worked with at-risk youth with Habitat for Humanity and collaborated
with the Prickly Pear Land Trust to help veterans access nature
trails.\6\
---------------------------------------------------------------------------
\6\ Id.
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John Scott was open about his invisible wounds of war and found
solace and recovery in many of the causes that also allowed him to give
back to his fellow veterans and his community. He was passionate about
improving veterans' access to mental health care and integrating
service animals into mental health care. Scott worked closely with
Montana Wild and VA Montana to develop a group therapy program for
veterans that involved birds of prey. Scott was embraced on his journey
to recovery by his family, friends, and community. He died from his
invisible wounds of war on February 25, 2018.\7\
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\7\ https://www.veterans.senate.gov/ imo/media/doc/hannon.bio.pdf
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(b) Relationship to Precision Medicine
I became friends with John Scott and his family after they asked me
to help him connect to resources and build social support. I was there
for many of the good times and hard times throughout his battle with
brain health conditions.
A few months after John Scott's death, I met with his family at
their ranch near Helena. We laughed and cried. We especially talked
about how frustrating it was that he had worked so hard for recovery
only to lose his life at the end. John Scott had come to a good place
with his post-traumatic stress injury. He had overcome addiction. He
was learning to live with his mild traumatic brain injury, but it was
the dramatic highs and lows of bipolar disorder which could not be
overcome.
I will never forget the words that John Scott's sister Kim Parrott
said that day. ``I just wish we had known about the bipolar disorder
earlier.'' I couldn't agree more that the missed diagnosis, the missed
factor in brain health treatment, could have made a significant
difference if it had been factored into his treatment from the start.
2. Mike Franklin
(a) Obituary
Mike Franklin, age 59, died September 20, 2014 of depression after
a long and courageous battle. Born and raised in Anderson, South
Carolina, he was a true Southern gentleman who fell in love with
Montana's Rocky Mountains.
Where he worked last was what he loved most: his job at Carroll
College for the last 11 years as the Director of Counseling Services.
He loved the students and his colleagues. In the 15 years before coming
to Carroll College he served as a U.S. Naval chaplain and earned a
master's degree at Yale University. He spent three years as a Methodist
minister after earning his Master of Divinity from Duke University and,
true to his nature, he was still in contact with the parishioners of
the small parish he ministered to 29 years ago. Prior to finding his
calling as a spiritual minister, he served as a U.S. Army officer for
five years after graduating from West Point. He graduated from T.L.
Hanna High School in Anderson, SC in 1973 where he played football, the
start of a passion for intense sports. He found joy in parachute
jumping, rugby, skiing, kayaking and river boarding in rivers above his
skill level and hiking off the beaten path.
Who he loved last and loved best was his wife Georgia Lovelady,
whom he married on July 9, 2011 on the campus of Carroll College. A
close second was his dog and constant companion, Gracie, who died in
May, four months before his own death. Mike was generous in all ways
including with his time, his knowledge, and mentoring others. He was
unfailingly kind, gregarious, spiritual, and funny (including two
stints of stand-up comedy at the local brewery). He reached out to
others even when he himself was struggling.
Mike is survived by so many who loved him dearly. If love alone
could have kept him from the depths of depression, he would have sailed
above his mental illness.
(b) Relationship to Precision Medicine
My friend Mike Franklin had treatment-resistant depression. This
condition is described by the Depression Task Force that authored
``Treatment Resistant Depression: A Multi-Scale, Systems Biology
Approach.''
An estimated 50% of depressed patients are inadequately treated by
available interventions. Even with an eventual recovery, many patients
require a trial and error approach, as there are no reliable guidelines
to match patients to optimal treatments and many patients develop
treatment resistance over time. This situation derives from the
heterogeneity of depression and the lack of biomarkers for
stratification by distinct depression subtypes. There is thus a dire
need for novel therapies.\8\
---------------------------------------------------------------------------
\8\ Akil, Huda, et al. ``Treatment resistant depression: a multi-
scale, systems biology approach.'' Neuroscience & Biobehavioral Reviews
84 (2018): 272-288.
One of the Depression Task Force's members is Dr. Joshua Gordon MD,
PhD. Dr. Gordon is now the Director of the National Institute of Mental
Health. From that position, Dr. Gordon is able to advance the
Depression Task Force's vision of developing more effective depression
treatments based upon more specific measurements and categorization-
---------------------------------------------------------------------------
precision medicine.
Recent advances in methodologies to study genetic and epigenetic
mechanisms, as well as the functioning of precise brain microcircuits,
prompt new optimism for our ability to parse the broad, heterogeneous
syndrome of human depression into biologically-defined subtypes and to
generate more effective and rapidly-acting treatments based on a
knowledge of disease etiology and pathophysiology and circuit
dynamics.\9\
---------------------------------------------------------------------------
\9\ Akil, Huda, et al. ``Treatment resistant depression: a multi-
scale, systems biology approach.'' Neuroscience & Biobehavioral Reviews
84 (2018): 272-288.
This is exactly the kind of breakthroughs that will save the lives
of veterans with treatment-resistant depression like my friend Mike
---------------------------------------------------------------------------
Franklin.
III. Scientific Progress
A.The emergence of transdiagnostic biological indications of brain
conditions and susceptibility for brain conditions expand the paradigm
of thinking about how these biosignatures can be used beyond the
traditional psychiatric diagnostic categories.
The scientific search for biological signatures to guide the
screening, diagnosis, and treatment of psychiatric conditions has
evolved beyond the traditional diagnostic categories into more of a
transdiagnostic viewpoint. As described by Beauchaine and Constantino:
An emerging consensus in the psychopathology research community is
that complex functional interactions among a limited number of neural
and hormonal systems - far fewer in quantity than syndromes defined in
the psychiatric nomenclature - give rise to many if not most mental
health conditions.\10\ From this perspective, endophenotypes might be
more effectively reconstrued as markers of genetic liability to
transdiagnostic vulnerability traits (e.g., impulsivity, irritability,
anhedonia). As Skuse noted over 15 years ago, `.a focus on traits,
rather than syndromes, is appropriate and could in due course
contribute to the redefinition of traditional psychiatric syndromes.'
When reframed in this way, common neural correlates of psychopathology
among what have traditionally been considered as distinct disorders are
no longer a nuisance in our quest for greater specificity, but are
instead opportunities to better understand common etiologies.\11\
---------------------------------------------------------------------------
\10\ Beauchaine, Theodore P., and John N. Constantino. ``Redefining
the endophenotype concept to accommodate transdiagnostic
vulnerabilities and etiological complexity.'' Biomarkers in medicine
11.9 (2017): 769-780.
\11\ Beauchaine, Theodore P., and John N. Constantino. ``Redefining
the endophenotype concept to accommodate transdiagnostic
vulnerabilities and etiological complexity.'' Biomarkers in medicine
11.9 (2017): 769-780
This is a critical move forward for the scientific research of
biosignatures that can affect the care of brain health conditions. I
have included a couple of block quotes below from this line of research
in Functional Magnetic Resonance Imaging, Genetics, and Blood Plasma.
Interestingly, the transdiagnostic nature of these measurements also
make it clear that these units of analysis will not replace, but will
only add to additional insights and to a variety of treatment
occupations: psychiatrics, psychologists, primary care providers,
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therapists, peer support specialists, etc.
1. Functional Magnetic Resonance Imaging
Neuropsychological performance, gray matter volume, and now
functional brain activation evidence converge to implicate
transdiagnostic disruptions in the neurocircuits underlying general
cognitive control capacity. Functional disruptions parallel the
multiple demand network and its interface with the salience network.
Essentially, networks intrinsic to adaptive, flexible cognition are
vulnerable to a broad spectrum of psychopathology. These findings
highlight a common intermediate phenotype, which could be leveraged to
advance therapeutics. Multimodal interventions that target the
foundation of intact, dynamic cognition seated in these frontal-
parietal-cingular-insular networks could be powerful for ameliorating
not only symptomatic distress but also the often-pervasive functional
impairments and diminished quality of life prevalent across psychiatric
disorders.\12\
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\12\ McTeague LM, Huemer J, Carreon DM, Jiang Y, Eickhoff SB, Etkin
A. Identification of Common Neural Circuit Disruptions in Cognitive
Control Across Psychiatric Disorders. Am J Psychiatry. 2017;174(7):676-
685. doi:10.1176/appi.ajp.2017.16040400
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2. Genetics
In recent years, there has been considerable progress in our
understanding of the genetics of common neuropsychiatric disorders, for
which neurobiological leads have been elusive. It is now clear that
these disorders are highly polygenic, involving thousands of common as
well as rarer genetic variants that, together with environmental risk
factors, collectively increase an individual's chances of developing
such a condition. It is also apparent that many of these risk variants
are shared between neuropsychiatric diagnoses. As sample sizes have
grown, both common and rare genetic risk loci for neuropsychiatric
disorders have been identified with high confidence. Associations
between neuropsychiatric disorders and common variants identified by
GWAS appear to largely reflect regulatory genetic variation, which
might operate on specific gene transcripts, in circumscribed cell
populations and at particular developmental stages. For some
neuropsychiatric phenotypes, particularly those with clear
neurodevelopmental features, stronger effects on risk may be conferred
by rare and de novo CNVs and exonic mutations that can result in
hemizygous loss of gene function. With even greater sample sizes, and
comprehensive genotyping through whole genome sequencing, many more
genetic risk loci for neuropsychiatric disorders will be identified in
coming years. Translating these discoveries into an understanding of
molecular, cellular and neurophysiological mechanisms underlying
neuropsychiatric conditions will require the expertise of researchers
in many areas of neuroscience.\13\
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\13\ Bray NJ, O'Donovan MC. The genetics of neuropsychiatric
disorders. Brain Neurosci Adv. 2019;2:10.1177/2398212818799271.
doi:10.1177/2398212818799271
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3. Blood Plasma
Of the six molecules most commonly studied as plasmatic markers of
schizophrenia, major depressive disorder or bipolar disorder, five
(BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same
across diagnoses. Meta-analyses showed variation in the levels of these
molecules to be robust across studies, but similar among disorders,
suggesting them to reflect transdiagnostic systemic consequences of
psychiatric illness.\14\
---------------------------------------------------------------------------
\14\ Pinto, Jairo Vinicius, Thiago C. Moulin, and Olavo B. Amaral.
``On the transdiagnostic nature of peripheral biomarkers in major
psychiatric disorders: a systematic review.'' Neuroscience &
Biobehavioral Reviews 83 (2017): 97-108.
B.Examples - Precision Mental Health to Advance Care for Post-
---------------------------------------------------------------------------
Traumatic Stress Injuries and Depression
Dr. Amit Etkin MD, PhD, and his team at the Palo Alto VA and
Stanford University are tackling some of the most critical questions
about how to improve the diagnosis and treatment of psychiatric
conditions. The group recently published the results of its
groundbreaking study, ``Using FMRI Connectivity to Define a Treatment-
Resistant Form of Post-Traumatic Stress Disorder.''\15\ As stated in
that research:
---------------------------------------------------------------------------
\15\ Etkin, Amit, et al. ``Using fMRI connectivity to define a
treatment-resistant form of post-traumatic stress disorder.'' Science
translational medicine 11.486 (2019): eaal3236.
---------------------------------------------------------------------------
``We found that a subgroup of patients with PTSD from two
independent cohorts displayed both aberrant functional connectivity
within the ventral attention network (VAN) as revealed by functional
magnetic resonance imaging (fMRI) neuroimaging and impaired verbal
memory on a word list learning task. This combined phenotype was not
associated with differences in symptoms or comorbidities, but
nonetheless could be used to predict a poor response to psychotherapy,
the best-validated treatment for PTSD.''\16\
---------------------------------------------------------------------------
\16\ Id.
---------------------------------------------------------------------------
The ``Establishing Moderators and Biosignatures of Antidepressant
Response for Clinical Care for Depression (EMBARC)'' has made
significant strides in their analysis of depression.\17\ That effort
and related efforts by Dr. Madhukar Trivedi's team at the University of
Texas Southwestern have identified potential biosignatures involving
inflammation,\18\ \19\blood,\20\ and advanced imaging.\21\
---------------------------------------------------------------------------
\17\ National Institute of Health, National Library of Medicine,
Clinical Trials.gov website. Accessed on June 19, 2018. https://
clinicaltrials.gov/ ct2/show/ NCT01407094
\18\ Jha, Manish, and Madhukar Trivedi. ``Personalized
antidepressant selection and pathway to novel treatments: clinical
utility of targeting inflammation.'' International journal of molecular
sciences 19.1 (2018): 233.
\19\ Czysz, Andrew H., et al. ``Can targeted metabolomics predict
depression recovery? Results from the CO-MED trial.'' Translational
psychiatry 9.1 (2019): 11.
\20\ Furman, Jennifer L., et al. ``Adiponectin moderates
antidepressant treatment outcome in the combining medications to
enhance depression outcomes randomized clinical trial.'' Personalized
medicine in psychiatry 9 (2018): 1-7.
\21\ Cooper, Crystal M., et al. ``Cerebral blood perfusion predicts
response to sertraline versus placebo for major depressive disorder in
the EMBARC trial.'' EClinicalMedicine (2019).
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IV. Recommendations
NAMI offers the following recommendations to help reduce barriers
to precision medicine.
A.Enact the Precision Mental Health initiative in the bipartisan
Commander John Scott Hannon Veterans Mental Health Care Improvement Act
of 2019 (S. 785).
On March 13, 2019, Senators Jon Tester (D-Mont.) and Jerry Moran
(R-Kan.) introduced the Commander John Scott Hannon Veterans Mental
Health Care Improvement Act of 2019. The bill was named after my
friend, Navy SEAL Commander John Scott Hannon, who served for 23 years
and fought a courageous battle with post-traumatic stress, traumatic
brain injury and bipolar disorder. NAMI believes that this legislation
has the potential to increase access to mental health care, expand
diagnostic research and authorize new programs to combat veteran
suicides.
Significantly, the legislation also includes a requirement for the
VA to implement an initiative to identify and validate brain and mental
health biomarkers among veterans (Section 305). The initiative would be
modeled after the National Institutes of Health's All of Us program,
with a focus on post-traumatic stress disorder, traumatic brain injury,
depression, and severe anxiety disorders. NAMI believes that if
enacted, this initiative has the potential to have a have a lasting
effect on the future of the diagnosis and treatment for mental health
conditions.
B.Ensure that the Veterans Equitable Resource Allocation (VERA)
model supports precision healthcare initiatives.
The next stage of developing Precision Medicine in the VA requires
both research and translation into clinical practice. This will require
the participation of VA facilities outside of the flagship
institutions. This will be essential not only for assuring the right
number of participating veterans, but also to ensure that a diversity
in the types of veterans are included. Precision medicine will be
specific enough that groups that are not included in the research will
not benefit from all of the findings.
NAMI recognizes that VERA is critical to how facility
administrators are measured. The VERA model must be aligned to support
a broadscale research and translational initiative. If precision
medicine efforts are not properly incentivized in VERA, NAMI fears that
the lack of local incentivization will stunt precision medicine efforts
in the VA.
C.Structure VA research data in a manner where a machine learning
natural language processing program can generate the beginnings of the
first draft of a research article based on the data in the system.
The success of the VA's Precision Medicine efforts will depend on a
variety of factors. There are issues of safety, regulation,
investigator recruitment, technology, etc. One of the issues that is
easily overlooked is that there will have to be a lot of papers written
about the VA's Precision Medicine results. Published articles are
critical to how the VA makes its own internal treatment decisions
through Clinical Practice Guidelines.\22\ Published articles are also
essential to have the lessons learned in the VA's Precision Medicine
efforts translate over to clinicians in the community.
---------------------------------------------------------------------------
\22\ See e.g. VA/DoD Major Depressive Disorder Clinical Practice
Guidelines, Version 3.0-2016. Available at https://
www.healthquality.va.gov/ guidelines/MH/mdd/
VADoDMDDCPGFINAL82916.pdf
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In my time at the COVER Commission, I have met VA researchers who
have data that they do not have the time to write manuscripts to
publish. This presents a serious wasted opportunity to advance
veterans' mental health care. NAMI recognizes that the VA does not have
as many clinician researchers as would be ideal to tackle the enormous
challenge of addressing mental health challenges amongst veterans.
Therefore, the VA must take as much of the ``busy work'' as possible
out of the process of writing papers to enable the researchers to focus
on their clinical work.
While there may not have been a lot of options to do this in the
past, the current machine learning natural language processing
technology has made an additional option available. NAMI recommends
that VA consider this technology.
The extent of this ``not having time to write up the data'' problem
is only going to get worse as the amount of actionable medical data
increases as the world moves toward precision medicine. It's a problem
that can and should be partially resolved through technology. We can't
afford to have critical veteran medical research data left outside of
the research community. There is just too much at stake.
V. Conclusion
Thank you again for the opportunity to testify in front of this
honorable Committee. Your attention to this issue means a lot to me,
our entire NAMI organization, veterans and their families. We look
forward to working with you to save the lives of America's heroes.
STATEMENTS FOR THE RECORD
National Association of Veterans' Research and Education Foundations
The National Association of Veterans' Research and Education
Foundations is the 501(c)(3) nonprofit membership organization of
research and education foundations affiliated with Department of
Veterans Affairs (VA) medical centers. These nonprofits, also known as
the VA-affiliated nonprofit research and education corporations (NPCs),
were authorized by Congress under 38 USC Sec. Sec. 7361-7366 to provide
flexible funding mechanisms for the conduct of research and education
at VA facilities nationwide. Currently, there exist 81 NPCs supporting
research and education activities at almost 100 VA medical centers.
NAVREF's mission is simple-we exist to advance the success of the
NPCs. Together, NAVREF and the NPCs serve not only the Veteran, but the
team of VA research and educational experts committed to improving the
lives of Veterans. Ultimately, NAVREF envisions a nation in which
Veterans receive the finest care based on innovative research and
education. We believe that by working closely with Congress, VA
leadership, NPC boards and leaders, and the great researchers and
scientists working across the country in VA medical centers that our
lofty vision can be achieved.
NAVREF has been encouraged by the leadership of Dr. Carolyn Clancy
throughout her various roles across the Veterans Health Administration,
but we are especially pleased to have her leading the recently
established office of Discovery, Education, and Affiliate Networks,
which oversees research and development. We strongly support the
transformation efforts of VA's Chief Research & Development Officer,
Dr. Rachel Ramoni, and the three high-level priorities she established
last year-enhancing access to high quality clinical trials, driving
substantial real-world impact, and putting VA data to work for
Veterans. We look forward to continued collaboration with Dr. Clancy,
Dr. Ramoni, and the first-rate team they've assembled at the Office of
Research and Development (ORD) to address these priorities.
NAVREF's top priority initiative is to bring more clinical trials
to Veterans in VA medical centers. It is critical that Veterans have
the same level of access to these cutting-edge therapies as their
counterparts outside the VA. In some therapeutic areas-most prominently
in oncology-clinical trials are the standard of care, yet many Veterans
do not have access to this life-altering research.
In December 2017, ORD and NAVREF embarked on a new e?ort to
increase Veterans' access to clinical trials. The initiative, titled
Access to Clinical Trials for Veterans (ACT for Veterans), kicked o?
with a Stakeholder Summit in April 2018 which brought together
representatives from industry, VA Central O?ce, VA medical centers,
patient advocacy groups, and the NPCs to participate in facilitated
discussions centered around study start-up. It was important for all of
us to hear industry's perspective on doing business with VA, so that we
could understand where we needed to direct our energy to effect
meaningful change. Since that initial meeting, five top priorities were
identi?ed, and workgroups were commissioned to address these
priorities. NAVREF continues to solicit external stakeholder feedback
at every step of the process. In February 2019, a Workgroup Summit was
held in Washington DC which allowed the ?ve workgroups to come
together, present their respective products, and receive feedback on
those deliverables.
Throughout this effort, ORD has been a steady partner, devoting
time and manpower to every workgroup and completing additional tasks in
support of ACT's objectives. But ORD cannot do this alone. Properly
supporting clinical research requires a much broader effort across VA
and VHA. One of the most important steps taken over the last ten years
to support industry-sponsored clinical trials at VA medical centers was
the establishment of the Specialty Team Advising Research (STAR) within
the Office of General Counsel. Prior to the establishment of STAR, all
legal reviews of research agreements (such as Non-Disclosure Agreements
and Cooperative Research and Development Agreements) were handled by
regional attorneys who had broad portfolios of higher priority matters
and limited experience handling research issues. Timelines for review
were understandably lengthy and unpredictable, such that some
pharmaceutical companies were unwilling to work with VA sites. The
establishment of STAR-a dedicated team of attorneys specializing in
medical research matters-quickly reduced the backlog of agreements and
led to predictable and reasonable timelines.
Similar to the legal delays that occurred ten years ago, clinical
trials are now challenged by the unpredictability of reviews from the
local offices of information security and privacy. Most VA hospital-
based information security officers and privacy officers have limited
expertise in research, which has many unique aspects that differ from
the typical health care delivery setting. Therefore, they require
additional time to review research proposals and frequently give
inconsistent answers to the same question from site-to-site. This
unpredictability causes delays and creates uncertainty among
pharmaceutical companies seeking efficient, consistent trial sites. The
solution for information security and privacy reviews should be the
same as for legal reviews-centralization and standardization.
In 2018, the Office of Information Technology established a team of
three Information Security Officers (ISOs) at the VA Central Office to
assist local ISOs with clinical research approvals. This is a good
first-step to clearing the obstacle currently faced at local sites with
ISO reviews. NAVREF urges VA to make permanent the Office of Research
Reviews within OIT and to create a similar permanent office for privacy
reviews. These offices need to be given the people, resources, and
authority necessary to accomplish their intended mission of supporting
research activity and reducing review timelines so that industry
sponsors are compelled to bring clinical trial opportunities to
Veterans at VA medical centers.
Another primary component of extended start-up timelines at VA
facilities is the use of VA institutional review boards (IRB). IRBs
play a critical role ensuring human research is conducted ethically and
appropriately without causing harm to research participants. VA IRBs
have a proud history of high-quality reviews that put the veteran's
well-being first. However, the extended timeframe for these reviews
exceeds typical industry expectations and can lead pharmaceutical firms
to avoid VA sites. The Department of Defense faced a similar dilemma
several years ago and successfully addressed the situation by allowing
the use of commercial IRBs. VA should do the same and allow the use of
commercial IRBs. The commercial IRB industry has demonstrated the
highest standards of protections for patients-research-based risk
protections, health information privacy protections, and information
security protections. They undergo rigorous accreditation processes in
order to safely and effectively conduct timely research reviews across
the United States and the world.
As part of the ACT for Veterans initiative and to comply with the
single Institutional Review Board (IRB) review mandate that will take
effect on January 20, 2020, ORD is seeking policy change to allow for
the use of commercial IRBs. Within VA, a risk assessment will need to
be completed to determine whether Veterans' health information should
be shared with commercial firms outside of the VA information network.
As stated previously, commercial IRBs have a strong history of
protecting patient data and privacy-they could not survive without
privacy and security as foundational elements of their business. The
DoD has acknowledged that commercial IRBs are sufficiently trustworthy
to be considered minimal risk when it comes to handling the health
information of military personnel. VA should make the same
determination. The importance of giving Veterans access to potentially
life-changing medical therapies should be heavily weighted when
conducting these risk-reward assessments.
SUMMARY
NAVREF supports the ACT for Veterans initiative and ORD's
priority efforts to enhance access to clinical trials for Veterans;
NAVREF supports centralization of VA privacy and
information security reviews of research protocols to enhance
efficiency, increase predictability, and reduce timelines;
NAVREF supports VA's ability to allow use of commercial
IRBs, especially for multi-site industry-sponsored trials already using
an accredited commercial IRB.
Thank you again for your attention to these matters. We greatly
appreciate your continuing support of the VA research program and your
support of the VA-affiliated nonprofit corporations. We look forward to
working with you to achieve our vision of a nation in which Veterans
receive the finest care based on innovative research and education.
Sanford Health
We applaud the Chairman for holding this oversight hearing on a
critical topic to our Veterans. Serving those who served our nation is
an important mission for Sanford Health. We want to ensure that our
nation's heroes have access to the most cutting-edge personalized
medicine. In March, we announced a bold impactful partnership with the
U.S. Department of Veterans Affairs that will help the VA meet new and
emerging needs for Veterans, their families and caregivers.
About Sanford Health
Sanford Health, one of the largest health systems in the United
States, is dedicated to the integrated delivery of health care, genomic
medicine, senior care and services, global clinics, research and
affordable insurance. Headquartered in Sioux Falls, South Dakota, the
organization includes 44 hospitals, 1,400 physicians and more than 200
Good Samaritan Society senior care locations in 26 states and nine
countries. Nearly $1 billion in gifts from philanthropist Denny Sanford
have transformed how Sanford Health improves the human condition.
The Sanford Health Department of Veterans and Military Services
helps Veterans and military personnel obtain health care services,
navigate care and insurance coverage, identify wellness services and
search for employment opportunities. The Department also offers family
support services and veteran community outreach.
The PHarmacogenomics Action for cancer SuRvivorship (PHASeR) Initiative
On March 12, 2019, the U.S. Department of Veterans Affairs and
Sanford Health announced a new initiative aimed at improving patient
care and lowering costs related to adverse reactions to medications,
which research shows costs up to $30 billion per year. Veterans across
the United States will receive free pharmacogenetic testing through a
partnership between the VA and Sanford Health called PHarmacogenomics
Action for cancer SuRvivorship (PHASeR).
Pharmacogenetic testing can be a critically important tool for
physicians in prescribing the proper medications at an optimized
dosage. People respond to medications in different ways and frequently,
their bodies will not respond to the prescribed medication properly.
This difference in the ability of our bodies' to break down medications
is partly determined by our genes. Leveraging this test means VA
physicians are better-equipped to determine optimal therapy and dosing
thereby avoiding intolerance to certain medications.
The tests are free to veterans and require no taxpayer resources.
The program is made possible by a $25 million gift from Denny Sanford
and a matching fundraising effort from Sanford Health.
The VA-Sanford Health partnership allows veterans to gain access to
the testing at their local VA facility while Sanford Health will
process the tests and supply confidential results to VA physicians. The
program has started with patients who have survived cancer. A pilot is
being conducted at the Durham VA Medical Center, Durham, North
Carolina. To date, 25 Veterans have participated in the program. By
2020, the program will reach 250,000 U.S. veterans at 125 sites.
The two organizations are working together to embed the results
into the patients' electronic health record, so that physicians get
notified of potentially conflicting medications in the future. The
program also supports genetic counseling for both patients and
physicians.
Real-World Implications: Patrick McGuire, Navy Veteran
Patrick McGuire, 45, a Navy Veteran and stage 4 lung cancer
survivor, is one of the first participants at the Durham VA Health Care
System launch site. He was diagnosed with cancer in 2015. He underwent
multiple surgeries for tumors in his brain and lungs in addition to a
host of other ailments. He was initially treated outside of the VA and
was prescribed medications that did not interact well with him. After
seeing VA doctors, his condition improved, and he had fewer adverse
reactions to treatment.
Following his final chemotherapy treatment, McGuire used a
wheelchair for several months due to the loss of muscle and strength.
He was unable to swallow from the radiation damage to his esophagus. He
worked hard in physical therapy and progressed to a walker and cane.
Against all odds, he recovered. Today, he rarely uses his cane at all.
Benefits of Pharmacogenetics
Pharmacogenetics saves lives, improves quality and efficiency and
saves money.
It is estimated that nearly 50 percent of antidepressants
are ineffective for a particular patient and approximately 25 percent
of people cannot appropriately use clopidogrel for antiplatelet
treatment after cardiovascular intervention.
Some chemotherapy and immunosuppressant drugs used to
treat cancer and autoimmune disorders can build up in the bodies of
people who have reduced functions of the TPMT and DPYD enzymes. A
genetic test to identify the level of enzyme function in patients can
help oncologists adjust dosages to prevent sometimes life-threatening
toxicity levels due to accumulation of the medicines in the body.
As cancer treatment becomes more effective, patients are
more likely to survive and go on to have other health conditions
requiring various medications with strong pharmacogenetic implications:
Plavix (clopidogrel) is an anti-platelet medication
prescribed after cardiovascular intervention to inhibit the formation
of clots which lead to costly and potential deadly adverse events such
as heart attack or stroke. Plavix requires activation by an enzyme
called CYP2C19 to provide benefit, but if a patient does not have the
right pharmacogenetic profile to metabolize CYP2C19 correctly, a
different drug may be needed to prevent these adverse events.
Certain anti-depressants are prescribed for depression,
anxiety, insomnia, and neuropathic pain that require CYP2C19 and CYP2D6
enzymes to properly regulate the medication. A genetic variant could
lead to the lack of efficacy for these drugs or an increase in
dangerous side effects.
Some patients have genetic variants that lead them
metabolizing certain opioids too quickly or too slowly. Pharmacogenetic
testing can help identify the right dose of the right pain medication.
Long-Term Benefits for the Government and Medical Research
Data generated from this program is available to researchers within
the VA to further expand upon the understanding of how a person's
genetic makeup impacts their ability to metabolize medications -
yielding better care for our veterans. It can also be expanded to other
medical areas outside of cancer survivorship. VA is at the cutting edge
of providing this care to patients.
Additionally, the initiative may be able to save money by avoiding
medications that are ineffective or cause expensive and debilitating
side effects - a win-win for both patients and taxpayers.
SHEPHERD Therapeutics and SHEPHERD Foundation
Testimony of David Hysong
Founder & CEO
I am honored to provide testimony before the House Veterans Affairs
Committee with my family's deep connection to the military and my
professional and personal experience developing therapeutics for rare
cancers that require advancements in precision medicine.
My father attended Embry Riddle Aeronautical University and
commissioned in the United States Air Force as a helicopter pilot. He
flew Hueys, served as the Special Air Mission Aircraft Commander of the
Presidential Airlift Wing, received the Air Force Meritorious Service
Medal for hazardous rescue, and twice received the Air Force
Commendation Medal.
I too have my own connection with the military. While completing
graduate school at Harvard University, I was selected for the Navy's
SEAL Officer Selection process four years ago. After successfully
completing the process, my military experience was cut short by my
diagnosis of adenoid cystic carcinoma, or ACC, at 27 years old. While
my cancer was successfully resected, if it returns there will be no
approved modern therapies with which to treat it. If it returns, it
will likely metastasize to areas including my bones and brain. I'm not
one to go down without a fight. I am determined to not just beat this
but help millions of others do the same.
Unfortunately, over 60 cancers may disproportionately affect our
nation's veterans and service members. Sixty-seven percent are rare and
only 25 of these rare cancers have an FDA approved targeted therapy.
Many of those cancers are potentially caused by service-related
exposures such as asbestos, burn pits, radiation and Agent Orange. Even
children of veterans who were exposed to Agent Orange have an increased
risk of certain cancers, according to a 2018 National Academy of
Sciences study. In addition, rare cancers occur more frequently among
Hispanics, Asians and Pacific Islanders compared with non-Hispanic
blacks and whites. These populations frequently suffer from worse
outcomes and shorter survival times, and African American cancer
patients have a lower 5-year survival rate than white patients.
Regardless of ethnicity, age or exposures, the vast majority of new
cancer patients - over 80% - who lack even one FDA-approved targeted
therapy for their cancer are rare cancer patients.
SHEPHERD's research has shown that at least 380 forms of cancer
meet the most conservative estimate of what constitutes a rare cancer,
the American Cancer Society's metric of fewer than 6 new diagnoses per
100,000 people per year. Those 380 forms compose 95 percent of all
forms of cancer, which collectively will afflict over 550,000 new
patients this year. As more diagnostic testing is provided for all
cancer patients, the molecular subtyping will enable precision
diagnosis and hopefully, one day, precision treatment. This means the
number of ``rare'' cancers will continue to rise as a greater
proportion of all cancer types, which makes precision medicine and
targeted therapeutics critical to saving lives.
Yet, current clinical trials - often a cancer patient's best option
for treatment - lack rare cancer patients. Our analysis of all clinical
trials between 2012 and 2016 showed that 74.89 percent of all trials
did not include even one rare cancer. Only around 13 percent of all
rare cancers were specifically named as a focus of a phase 3 clinical
trial in those five years. More than four times as much money in that
timeframe was spent on non-rare cancer trials than on trials which
included a rare cancer. For minorities, those discrepancies are
amplified, as minorities are less likely than Caucasians to be included
in clinical trials, which can lead to underrepresentation of key
biological variables that make drugs less effective among those
populations. As data presented at a recent MIT conference showed, only
three percent of the U.S. population is represented in clinical trials.
These trials fail to capture the genetic diversity present in the
population as well as in many forms of cancer.
This is why I encourage the Department of Veterans Affairs to
explore ways to improve how the VA engages with investigators. At
SHEPHERD Therapeutics, I have built a team of researchers in rare
disease and oncology who are developing therapies which can tackle
multiple rare cancers by leveraging shared biology. This approach will
enable targeted therapeutic development for many rare cancer patients
who are currently neglected by a drug development market that favors
common cancers because they produce the greatest financial rewards.
As of February 2019, 182 cancers lacked an FDA-approved targeted
therapy and 181 of them were rare cancers. That means that in 2019
almost 200,000 new rare cancer patients will face their diagnosis
without a modern treatment, and current reimbursement policies
contribute to this failure. While CMS decided in March 2018 to ensure
that Medicare and Medicaid patients whose cancer recurs after treatment
can receive molecular diagnostics, patients ideally should receive
molecular diagnostics when they are first diagnosed to best inform
treatment decisions. Diagnostics are especially important for cancers
without good treatment protocols, as the tests may identify genetic
drivers that can be addressed with existing therapies. Many patients do
not know to request molecular diagnostics, and cannot afford to pay for
testing. Even at large NCI care centers, molecular diagnostics is
frequently covered only by donations and internal hospital funding and
policy. This increases the gap between the quality of care afforded to
those who have access to large NCI care centers, and the care provided
to the majority of cancer patients who are treated at community
hospitals. In addition to supporting patient care, this data can be
vital to NIH, DoD and the VA by advancing scientific understanding of
what causes a disease, the types of therapies which may work on it, and
the appropriate patient population for molecularly-targeted clinical
trials.
With approximately 20 million veterans, plus the millions more in
their families and those who are currently serving in the military
today, the gap in rare cancer therapeutic options is disturbing.
Millions of lives are touched by rare cancers for which there are no
treatment options. This must end. As a patient and CEO of a therapeutic
company working hard to change the current paradigm for drug
development to advance targeted treatments, I urge you to make the
necessary changes in a collaborative fashion with the VA, DoD and NIH
to ensure patients are no longer neglected. The VA can take a critical
role in collaborating with researchers to share data, cell lines and
discoveries to advance the development of targeted therapeutics. Our
veterans deserve this care. Thank you.