[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 
published in electronic form. The printed hearing record remains the 
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of converting between various electronic formats may introduce 
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further refined.

                            C O N T E N T S

                              ----------                              

                        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

                              ----------                              


                        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.

---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \12\ Personal communications with contract research organizations 
in July 2018 and January 2019.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \13\ Source: Clinicaltrials.gov search of clinical trials conducted 
in oncology at VA sites. Accessed June 24, 2019.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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
---------------------------------------------------------------------------
    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.

---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
    \5\ https://www.veterans.senate.gov/  imo/media/doc/hannon.bio.pdf
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \7\ https://www.veterans.senate.gov/  imo/media/doc/hannon.bio.pdf

---------------------------------------------------------------------------
(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, 
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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
---------------------------------------------------------------------------
    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.