National Research Action Plan
August 2013
i
Executive Summary
On August 31, 2012, President Obama issued an Executive Order (the Order) directing the
Departments of Defense (DoD), Veterans Affairs (VA), Health and Human Services (HHS), and
Education (henceforth referred to as “the agencies”), to develop a National Research Action Plan
(NRAP) on posttraumatic stress disorder (PTSD), other mental health conditions, and Traumatic
Brain Injury (TBI) “to improve the coordination of agency research into these conditions and
reduce the number of affected men and women through better prevention, diagnosis, and
treatment.”
Section 5 of the Order highlights how a limited understanding of underlying mechanisms of
PTSD, the long-term consequences of TBI, and warning signs for tragic outcomes such as
suicide is hampering progress in prevention, diagnosis, and treatment. Therefore, the NRAP
includes research strategies to accelerate discovery of underlying mechanisms and rapidly
translate this understanding into actionable tools for prevention, early diagnosis, and better
treatment. The Order also calls for the establishment of a comprehensive longitudinal study of
100,000 service members focused on PTSD, TBI, and related injuries. To attain these goals, the
Order urged research agencies to improve data sharing as appropriate and with appropriate
privacy and confidentiality protections, and harness new tools and technologies (e.g., electronic
health records). Importantly, the Order directs the NRAP to improve coordination between
agencies and ultimately reduce the number of affected individuals.
In this NRAP, the agencies outline coordinated research efforts to accelerate discovery of the
causes and mechanisms underlying PTSD, TBI, and other co-occurring outcomes like suicide,
depression, and substance abuse disorders. It describes research to rapidly translate what is
learned into new effective prevention strategies and clinical innovations: biomarkers to detect
disorders early and accurately; and efficacious and safe treatments to improve function and
quality of life and to promote community participation and reintegration. The NRAP also
describes research to accelerate the implementation of proven means of preventing and treating
these devastating conditions. Many collaborative efforts are already under way.
To achieve these goals, the NRAP agencies have identified key cross-cutting research priorities
spanning conditions that will be pursued over the next 12 months. Examples of these priorities
include the need to:
Perform ongoing portfolio analyses of existing and emerging diagnostics, therapeutics
and outcome measures for PTSD, TBI, and related injuries using the agencies’
“Interagency Research Continuum Approach” model.
Continue to develop processes to standardize, integrate, and share data as appropriate.
The recent directive from the White House Office of Science and Technology Policy on
Increasing Access to the Results of Federally Funded Scientific Research and the recent
Executive Order on Making Open and Machine Readable the New Default for
Government Information posit that open sharing of machine-readable data fuels scientific
discovery and innovation, and specify that public agencies will be held accountable for
ensuring their data are standardized, integrated, and shared where appropriate.
Initiate a process to define a minimum set of general and topic-specific common data
elements (CDEs) that can be adopted for PTSD and suicide prevention research to
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potentially integrate with the Federal Interagency TBI Research CDEs. The agencies
commit to reporting on progress in reducing delays and barriers currently impeding the
timely sharing of data resources created and owned by federal agencies.
Increase the inventory of scarce research resources (e.g., tissue samples, blood, and
cerebrospinal fluid), facilitating access for scientific purposes (with appropriate human
subjects’ protections related to privacy and confidentiality). To accomplish this, the
agencies will leverage existing pathology archives to initiate development of a virtual
tissue (brain) repository for PTSD, TBI, and suicide research. Activities will also include
(1) incorporating appropriate agreements either between the investigator and resourcing
agency (material transfer agreement) or between agencies (interagency agreement) and
(2) processes for securing consent to obtain brain tissue from donor (premortem) or
representative (postmortem).
Build new tools and technologies to understand the underlying mechanisms of PTSD,
TBI, suicide, and other conditions. Appropriate NRAP-participating agencies will
continue to fund innovative research for the Brain Research through Advancing
Innovative Neurotechnologies Initiative. The DoD will leverage the Brain Research
through Advancing Innovative Neurotechnologies initiative efforts and continue to fund
complementary work.
Adapt existing research initiatives to maximize their impact. The comprehensive 100,000
service member study called for by the Order (Army STARRS) has been established. The
agencies will explore the feasibility of a longitudinal follow-up of Army STARRS to find
actionable factors that can be used to improve early detection, and effective prevention
and treatment of suicide, PTSD, TBI, and comorbidities. The follow-up study will
include the ability to consent for the donation of postmortem brains and begin to establish
necessary procedures for timely collection and preservation of tissue.
Continue to leverage existing and emerging information technology to improve existing
care for individuals with PTSD, TBI, suicidality, and other conditions. Agencies already
harnessing information to answer research questions will continue to evolve the learning
health care system model and provide lessons learned to agencies interested in
developing this model.
Utilize tools for agencies to coordinate and share the research they support. The agencies
will identify a common database and explore the feasibility of utilizing it to share the
research they support with other federal agencies and with researchers outside of the
federal government, where appropriate.
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NRAP Vision for the Future
The agencies anticipate that basic insights,
garnered through NRAP efforts, will help
lead to translational advances in the
prevention, diagnosis, and treatment of
PTSD, TBI, suicidal behaviors, and co-
occurring conditions, including substance
abuse, in service members, Veterans, and
their families. Subsequently, better
preventive and therapeutic interventions
would be expected to help lead to
improved health, function, and quality of
life for people experiencing these
conditions, and their families.
Funding and Prioritization
The agencies intend to focus and collaborate on
the topics identified in this document. These
efforts will be supported within existing agency
budgets. The agencies will follow their
established planning, programming, and
budgeting processes and priorities will be
supported as feasible within available
resources. In a time of constrained resources,
the agencies will continue to direct resources to
high-priority activities.
The ability to leverage existing and emerging
information technology will be a key factor in
successfully coordinating and accelerating research
under the NRAP. Transparent and accessible
information about the agencies’ ongoing and
planned efforts will guide the agencies and
researchers alike to reduce overlap, eliminate
redundancies, identify gaps, and focus new
research questions. Publicly accessible databases
that contain information about funded grants (e.g.,
National Institutes of Health [NIH] Research
Portfolio Online Reporting Tools, which is used by
VA and NIH) act as repositories for government-sponsored research. A new commitment will be
to analyze the costs, benefits, and utility of moving the DoD’s medical research onto the NIH
Research Portfolio Online Reporting Tools system as well as related systems such as Electronic
Research Administration Commons, thus promoting a higher level of transparency and analysis
across agencies and for the public. Beyond the transparent sharing of data about funded studies, a
commitment will be made to promote the standardization and sharing of de-identified study level
(raw) data, with the appropriate consent, confidentiality and privacy protections within legal
authority. Many smaller studies are able to involve only a modest number of participants;
therefore, the ability to share study data when appropriate will increase the power for analyses
and potentially accelerate research progress. In addition, large-scale studies supported by each
agency provide a platform for rich secondary data analyses when study-level data are shared.
Central repositories such as the Federal Interagency Traumatic Brain Injury Research
Informatics System may be leveraged in these data-sharing efforts. The agencies have begun
discussions to determine how to more efficiently share data; details can be found in the report.
This NRAP will complement the 2013 Interim Report of the Interagency Task Force on Military
and Veterans Mental Health (May 2013) to ensure that Veterans, service members, and their
families receive necessary mental health services and support. Close collaborations between the
agencies will expedite fulfillment of the strategies outlined in the NRAP. The DoD, VA, HHS,
and the Department of Education understand the
gravity and urgency of the problems and are committed
to advancing the health of our military and nation
through their collective research. To ensure progress
and success, the agencies will schedule formal joint
review and analysis of efforts. Further, continued
analysis of needs using the Interagency Research
Continuum Approach is planned. The Agency research
working group co-chairs will be responsible for
overseeing the formation of any necessary new
workgroups or initiatives to deliver on the plans of this
NRAP. Collectively, these activities will support the
Order’s research goals to prevent suicide, to reduce the
number of individuals affected by PTSD, TBI, and
comorbidities, and to improve the quality of life of
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those who do experience these conditions through better-coordinated and synchronized efforts to
accelerate progress in prevention, diagnosis, and treatment.
Key Themes Specific to PTSD, TBI, and Suicide Prevention Research
Beyond the research priorities spanning conditions (presented previously) and looking deeper into specific
research needs for PTSD, TBI, and or suicide prevention, the themes highlighted here are examples of topics
described in greater detail in the full report. Please note that the bullets under each research area are organized
along the Interagency Research Continuum Approach, described earlier, and are not placed in order of
importance or priority. Also note that all of these research areas are expected to include consideration of co-
occurring disorders, including substance use disorders.
PTSD: Biomarkers, Mechanisms, and Treatment Research
Replicate and confirm emerging data on promising biomarker candidates and other diagnostic tools for
PTSD, including genome-wide associations, plasma molecules, and methylation patterns.
Optimize risk and resilience screening tools and test new PTSD prevention and treatment interventions
that target underlying mechanisms and causal pathways.
Enhance current PTSD evidence-based treatment delivery to be briefer, more durable, and more
efficacious in treating service members, Veterans, and their family members, including individuals with
multiple mental and physical health issues, including substance abuse.
TBI: Biomarkers, Diagnosis, Mechanisms, and Treatment Research
Determine whether blast-induced TBI is a unique pathobiological entity and, if so, define the
neuropathology of blast injury and in a subsequent step evaluate appropriate imaging technologies for
their ability to identify the blast pathology in histologically characterized brain tissue. Utilize these
imaging tools in service members and Veterans to determine whether blast, or repetitive blast injury, is a
risk factor for chronic neurodegeneration or other chronic neurologic disorders.
Develop a more precise system for classifying and staging TBI to enhance diagnosis and prognosis and
enable targeted therapies and personalized medicine.
Support validation studies of proteomic, imaging, neurophysiologic and other potential biomarkers and
diagnostic tools to improve accurate diagnosis, monitor course of illness and enable evaluation of
promising pharmacologic and nonpharmacologic treatments, including rehabilitation treatments, for their
ability to increase functional outcomes such as community participation and reintegration.
Suicide Prevention Research
Add a longitudinal component to the Army STARRS project to identify modifiable psychosocial and
environmental risk and protective factors, clinically actionable biomarkers, and neurobiological
mechanisms for preventing suicide and continue to support the Military Suicide Research Consortium to
rapidly translate findings and develop effective interventions.
Optimize clinical suicide risk assessment tools to guide decisions on intervention, referral, and follow-up.
Develop and test rapid, brief, and effective prevention and treatment interventions for suicide (including
suicide ideation and attempts) applicable to a variety of settings, with rigorously designed randomized
controlled trials that address comorbid problems.
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Table of Contents
Executive Summary ......................................................................................................................... i
List of Acronyms ........................................................................................................................... vi
Background ..................................................................................................................................... 1
PTSD: Biomarkers, Mechanisms, and Treatment Research .......................................................... 8
TBI: Biomarkers, Diagnosis, Mechanisms, and Treatment Research ......................................... 15
Suicide Prevention Research......................................................................................................... 23
Comprehensive Longitudinal Mental Health Study ..................................................................... 29
Sharing PTSD, TBI, and Suicide Prevention Research ................................................................ 32
Electronic Health Records and Research and Clinical Care ......................................................... 36
Conclusion .................................................................................................................................... 39
Documents Consulted ................................................................................................................... 40
Appendix: The Executive Order ................................................................................................ A-1
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List of Acronyms
Army STARRS Army Study to Assess Risk and Resilience in Servicemembers
BRAIN Brain Research through Advancing Innovative Neurotechnologies
CAP Consortium to Alleviate PTSD
CDC Centers for Disease Control and Prevention
CDE Common Data Element
CENC Chronic Effects of Neurotrauma Consortium
CNS Central Nervous System
DHP Defense Health Program
DoD Department of Defense
ED Department of Education
EHR Electronic Health Record
FITBIR Federal Interagency Traumatic Brain Injury Research
FOA Funding Opportunity Announcement
GWAS Genome-Wide Association Studies
HHS Department of Health and Human Services
HIV Human Immunodeficiency Virus
IOM Institute of Medicine
MHRN Mental Health Research Network
MSRC Military Suicide Research Consortium
mTBI mild Traumatic Brain Injury
MVP Million Veteran Program
NAASP National Action Alliance for Suicide Prevention
NADHAP National Addiction and HIV Data Archive Program
NIDA Brain Research through Advancing Innovative Neurotechnologies
NIDRR National Institute on Disability and Rehabilitation Research
NIH National Institutes of Health
NIMH National Institute of Mental Health
NINDS National Institute of Neurological Disorders and Stroke
NRAP National Research Action Plan
Order Executive Order
PTSD Posttraumatic Stress Disorder
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RDoC Research Domain Criteria
RePORTER Research Portfolio Online Reporting Tools
TBI Traumatic Brain Injury
TBIMS Traumatic Brain Injury Model Systems Centers Program
TBIMS-NDB TBIMS National Database
TRACK-TBI Transforming Research and Clinical Knowledge in TBI
VA Department of Veterans Affairs
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Background
Since September 11, 2001, more than 2.5 million service members have deployed to Iraq and
Afghanistan in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New
Dawn. Military forces sent to fight those wars have exhibited a number of unique features,
including: (1) an all-volunteer military that has experienced multiple deployments to the war
zone, (2) substantial use of the reserve components of the military and National Guard,
(3) deployment of high numbers of women and parents of young children, and (4) a high number
of military personnel surviving severe injuries that in previous wars would have resulted in
death. The Armed Forces Health Surveillance Center data list 266,810 cases of TBI occurring in
the military between 2000–2012. Over 80% of these were the result of non-combat injuries.
Among combat injuries, blast is a common cause. Military service exposes service members to a
variety of stressors, including exposures to death, risk to life, sustained threat of injury or actual
injury, and the day-to-day family stress inherent in all phases of the military life cycle and its
transitions. Stress is a major contributor to both the onset and exacerbation of substance abuse
and mental health problems and is related to a variety of negative physical health outcomes. A
comprehensive assessment of the physical, psychological, social, and economic effects of
deployment on service members, their families, and communities is provided in the 2013
Institute of Medicine (IOM) report “Returning Home from Iraq and Afghanistan: Assessment of
Readjustment Needs of Veterans, Service Members, and Their Families.”
Though significant and continuing improvements in outer tactical vests (body armor) and
helmets have limited fatal injuries, many service members return with a traumatic brain injury
(TBI), symptoms or diagnosis of posttraumatic stress disorder (PTSD), suicidal thoughts or
behaviors, and/or related comorbidities. These comorbidities or co-occurring conditions are
defined herein as mental health disorders, including depression; substance abuse related to
alcohol, tobacco, and other drugs, including the misuse and abuse of prescription drugs; and
chronic pain, each of which can complicate the prevention and treatment of PTSD, TBI, and
suicidal behaviors. One study of returning Veterans who were seen in Department of Veterans
Affairs (VA) health care facilities revealed that nearly one-third of them received at least one
mental health or psychosocial diagnosis. Another study estimated that only 23% to 40% of
returning service members who screen positive for a mental disorder seek mental health care.
Family members are also impacted by the multiple stressors associated with deployment and
reintegration. Overall, the need for mental health, and substance abuse, and chronic pain services
for service members, Veterans, and their family members is anticipated to increase in coming
years as the Nation endures the effects of more than a decade of military conflict. Additional
sections of the President’s August 31, 2012 Executive Order (the Order) address steps the
agencies are taking to improve education and awareness, and access to services and treatment.
An interagency Task Force (described in the following paragraphs) published their first report on
these efforts in May 2013. These ongoing efforts are outside the scope of this National Research
Action Plan (NRAP).
Researchers are attempting to answer questions across the research continuum from basic science
aimed at understanding the disorders that are the focus of this Order through prevention,
treatment, follow-up care, and services research directed at improving the delivery and modality
of care. However, fundamental gaps in scientific knowledge remain that highlight the critical
need for advancing the research described here. For example, the lack of an objective measure of
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mild (mTBI) makes it difficult to adequately diagnose individuals or to determine risk of injury.
Improved techniques are needed to determine when and what symptoms are attributable to the
traumatic (physical) event, to understand the brain events that give rise to the post-concussive
syndrome concurrent with PTSD symptoms, and to elucidate the neural basis of the interaction
between mTBI, PTSD, depression, and suicidality. To this point in time, there has not been a
definitive study of the neuropathologic effects of blast injury in those who have died.
A significant concentration of the country’s best scientists and resources have led to major
advances in other threatening health conditions, such as the conversion of human
immunodeficiency virus infection from a fatal illness to a manageable chronic illness and a 60%
drop in stroke rates over the past 60 years. A similar concerted scientific attack is warranted to
determine the neural basis of PTSD and the functional deficits associated with TBI. Without
such an effort, the burden of illness due to PTSD and TBI in service members, Veterans, and
their families will continue. Current PTSD pharmacotherapy and medications are inadequate,
with somewhat limited success in treating individuals with PTSD. Evidence-based approaches
for reducing suicide risk are also limited, and the relationships between PTSD, TBI, suicide, and
co-occurring conditions are not well understood. Researchers must also evaluate the impact of
context, including the population (e.g., active duty, Reserve/Guard, Veterans, and families) and
setting (e.g., deployed austere environments versus medical centers) in their studies.
The federal research funding agencies specified in the August 31, 2012 Order including the
Departments of Defense (DoD), VA, Health and Human Services (HHS), and Education (ED)
(henceforth referred to as “the agencies”), have distinct but complementary missions; hence,
their existing funded research programs collectively address a broad range of mental health
issues and can be successfully leveraged to establish and advance the NRAP to benefit service
members, Veterans, and their families. The Order (see Appendix) sets the stage for the agencies
to join forces in identifying related research priorities to better understand and reduce symptoms
and to maximize function and community reintegration through optimal prevention, screening,
diagnosis, and treatment advances. This report summarizes the interagency response to Section 5
in the Order.
Critical to the development of this NRAP was an understanding of the agency-specific activities
related to the requirements specified in the Order. This background was provided in a Joint
Review and Analysis meeting (January 2013) on research related to PTSD, TBI, suicide
prevention, and substance abuse. Agency representation at the meeting included DoD, VA, ED
(represented by the National Institute on Disability and Rehabilitation Research [NIDRR]), and
HHS (represented by the National Institute of Health’s [NIH’s] National Institute of
Neurological Disorders and Stroke [NINDS], National Institute of Mental Health, and National
Institute on Drug Abuse).
A variety of activities are under way in support of the NRAP, including funded research projects
within the agencies’ complementary portfolios in PTSD, TBI, and suicide prevention research
that also address comorbidities such as substance abuse. The DoD’s Systems Biology Initiative
and the Millennium Cohort and Family Cohort Studies, the VA’s Million Veteran Program, and
NIH’s biomarker and mechanistic research programs all hold promise to inform advancement of
prevention and treatment interventions. Notably, the DoD alone has invested more than $100
million in TBI biomarker discovery and development since 2007; other agencies have also
supported this increased focus. The DoD and the Centers for Disease Control and Prevention
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(CDC) are partnering with the Brain Trauma Foundation to develop a clinically meaningful
classification system of mTBI/concussion that will enable improved clinical assessment of
current status and prognosis. Suicide prevention research includes the DoD’s Military Suicide
Research Consortium (MSRC) and the National Institute of Mental Health and Department of
the Army’s Study to Assess Risk and Resilience in Servicemembers (Army STARRS) program.
The agencies also support research that contributes to a better understanding of the mental health
needs of military/Veteran families and the best ways to prevent, treat, and provide services for
them (see text box).
On April 2, 2013, President Obama
announced the NIH Brain Research through
Advancing Innovative Neurotechnologies
(BRAIN) initiative. The BRAIN initiative
will involve the NIH, the Defense Advanced
Research Projects Agency, the National
Science Foundation, and several private
laboratories and foundations working
toward the next generation of tools for
decoding the intricate language of the
brain. This unique project aims to give
scientists a more complete set of tools and
information for understanding how the brain
functions, and how we think, learn, and
remember both in health and in the context
of neurological and psychiatric conditions
that are the focus of the Order and of great
concern to service members, Veterans, and
their families.
Research shows that behavioral health disorders, especially substance use disorders (SUDs),
frequently co-occur in people experiencing the target problems discussed in the Order (TBI,
PTSD, and suicide). Despite strict prohibitions on illicit drug use in the military, as well as a
broad, random drug testing program, there are indications of rising rates of drug use (to include
prescription drug misuse and abuse, as well as heavy alcohol use, and tobacco use), among the
active duty population. These concerns are not limited to active duty—research shows SUDs are
rarely treated in young Veterans. Comorbidities can complicate efforts to effectively intervene
with other, targeted health conditions. However, the results of long-term randomized controlled
trials have shown that substance abuse prevention can have a positive effect on a wide array of
behaviors. In addition, SUD treatment can mitigate negative mood and in some cases, treatment
for PTSD has been shown to improve SUD outcomes, while integrated treatments addressing
both SUDs and PTSD can improve both conditions. Suicide risk may also be lowered by
treatment of SUDs.
A few factors complicate the matter of addressing SUDs and conducting research in military or
Veteran populations: (1) concerns about confidentiality of military medical records; (2) impact of
zero tolerance policies for illicit drugs and SUDs on the careers of service members; (3) lack of
appropriate screening and assessment protocols specifically for SUD issues, and (4) uncertainty
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about how SUDs may impact a Veterans’ disability claims. Although current illegal drug use is
less prevalent in Veterans than in the general population, there are still subpopulations for which
there is concern. For example, research shows that Veterans with PTSD are more likely to
receive opioid prescriptions and thus may have higher risk of addiction and other negative
consequences. In addition, the presence of co-occurring disorders, common among Veterans,
often complicates treatment.
It is expected that all initiatives supported by this action plan will address comorbidities when
they exist including SUDs through coordination, goal setting, and common efforts. The agencies
are independently and jointly funding studies focused on substance abuse research in military
personnel, Veterans, and their family members. There have also been collaborations established
that include joint reviews and analyses of portfolios and joint funding opportunities (e.g., 2010
NIH-VA Request for Applications [RFA] and 2013 NIH-DoD RFA). Substance abuse research
funded by the agencies spans the research continuum from basic science through implementation
research.
Data-sharing efforts include the DoD/NIH Federal TBI Research Informatics System for TBI
clinical research (a central repository for TBI-related clinical research data that will also link to
existing databases to facilitate sharing of information), the VA computing infrastructure, and
NIDRR’s TBI Model Systems National Database (TBIMS-NDB), which contains prospective
data on the clinical progress and outcomes of individuals with moderate to severe TBI. The VA
Polytrauma Rehabilitation Centers have partnered with NIDRR to establish a VA TBI Database
that includes many of the same data elements found in the TBIMS-NDB. The U.S. Army
Research Institute of Environmental Medicine has developed the Total Army Injury and Health
Outcomes Database, which is a versatile system that joins multiple personnel and health data sets
from various DoD agencies and links data on demographics, health outcomes, health habits, and
chemical exposures. Finally, research may benefit in multiple ways from the use of aggregate,
de-identified electronic health record data by providing information to better understand the
scope of a problem being investigated and whether implementation of evidence-based practices
is effective.
Recently initiated activities include two joint DoD/VA consortium efforts to support PTSD and
TBI biomarker studies (the Consortium to Alleviate PTSD, and the Chronic Effects of
Neurotrauma Consortium), new treatment studies to be generated from the basic research
biomarker studies, and new treatment response studies to be incorporated into clinical trials. New
and planned initiatives also include joint agency RFAs for research that are aimed at improving
the health of service members, Veterans, and their families.
The agencies have collaboratively developed an interagency approach for strategic research
planning that builds upon the framework initially developed by the DoD. This “Interagency
Research Continuum Approach” is a research framework within which studies can be organized
along a progression that includes seven topic areas: foundational science, epidemiology,
etiology, prevention and screening, treatment, follow-up care, and implementation (services)
research (Figure 1). This also facilitates analysis of gaps and identification of future areas
of focus. Please note that “comparative effectiveness” research (listed under Treatment in Figure
1) refers to research that evaluates the effectiveness of different treatment options, procedures, or
tests for specific diseases, conditions, or disorders; for example, the effectiveness of
psychotherapies for PTSD.
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Funding and Prioritization
The agencies intend to focus and collaborate on
the topics identified in this document. These
efforts will be supported within existing agency
budgets. The agencies will follow their
established planning, programming, and
budgeting processes and priorities will be
supported as feasible within available
resources. In a time of constrained resources,
the agencies will continue to direct resources to
high-priority activities.
Figure 1. The Agencies’ Interagency Research Continuum Approach
The integration of research findings into health care systems through evidence-based practices is
needed to address the Order’s goal of improving access to mental health and substance abuse
services. The Order established the Military and Veterans Mental Health Interagency Task Force
to oversee efforts aimed at improving capacity and enhancing quality of care for service
members, Veterans, and their families. It is anticipated that the efforts of the Task Force will
enable the service systems to become the platform to integrate and embed emerging evidence-
based practices and develop “learning health care systems” in which the health care providers,
systems, and patients participate in the generation of knowledge on trends in health and illness,
the testing and identification of best practices, and the assessment of the impact of practice
changes.
The Task Force may also identify existing or
new interagency working groups to address the
planning, performance, and completion of the
tasks outlined in the NRAP. Such entities have
already been utilized with success. However, the
closer engagement required by the proposed plan
would benefit from agency-specific/unique
capabilities in personnel, programs, and funding
to enhance the translation of research findings to
clinical use. Coordination of strategic research
and development plans would enable agencies to
synchronize program announcements based upon
the outcomes of research that may be funded by
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other agencies in earlier stages (e.g., NINDS funds a discovery project on biomarkers that the
other agencies could leverage into epidemiological and clinical validation studies across a wide
patient population).
The sections that follow elucidate the results of the agencies’ Interagency Research Continuum
Approach to address the research areas specified in the Order. The NRAP describes some of the
highest priorities for accelerating discovery of the causes and mechanisms underlying PTSD,
TBI, and other outcomes like suicide, depression, and substance abuse. It describes research to
rapidly translate what is learned into new clinical innovations including the development of
biomarkers to detect brain disorders early and accurately; highly effective prevention strategies;
and highly efficacious and safe treatments. The NRAP also describes research to widely
implement proven means of preventing and treating these devastating conditions. Across these
efforts, the NRAP strives to achieve the same level of urgency, specificity of deliverables and
timelines, as well as accountability, as expressed in the Order.
In addition to the detailed research priorities specific to each section of the Order, the agencies
have identified the following cross-cutting actions that will be pursued within the next
12 months:
Perform ongoing portfolio analyses of existing and emerging diagnostics, therapeutics
and outcome measures for PTSD, TBI, and related injuries using the agencies’
“Interagency Research Continuum Approach” model.
Continue to develop processes to standardize, integrate, and share data as appropriate.
The recent directive from the White House Office of Science and Technology Policy on
Increasing Access to the Results of Federally Funded Scientific Research and the recent
Executive Order on Making Open and Machine Readable the New Default for
Government Information posit that open sharing of machine-readable data fuels scientific
discovery and innovation, and specify that public agencies will be held accountable for
ensuring their data are standardized, integrated, and shared.
Initiate a process to define a minimum set of general and topic-specific common data
elements that can be adopted for PTSD and suicide prevention research to potentially
integrate with the Federal Traumatic Brain Injury Research common data elements. The
agencies commit to reporting on progress in reducing delays and barriers currently
impeding the timely sharing of data resources created and owned by federal agencies.
Increase the inventory of scarce research resources (e.g., tissue samples, blood, and
cerebrospinal fluid), facilitating access for scientific purposes (with appropriate human
subjects’ protections related to privacy and confidentiality). To accomplish this, the
agencies will leverage existing pathology archives to initiate development of a virtual
tissue (brain) repository for PTSD, TBI, and suicide research. Activities will also include
(1) incorporating appropriate agreements either between the investigator and resourcing
agency (material transfer agreement) or between agencies (interagency agreement) and
(2) processes for securing consent to obtain brain tissue from donor (premortem) or
representative (postmortem).
Build new tools and technologies to understand the underlying mechanisms of PTSD,
TBI, suicide and other conditions. Appropriate NRAP-participating agencies will
continue to fund innovative research for the BRAIN Initiative. The DoD will leverage the
BRAIN initiative efforts and continue to fund complementary work.
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Adapt existing research initiatives to maximize their impact. The comprehensive 100,000
service member study called for by the Order (Army STARRS) has been established. The
agencies will explore the feasibility of a longitudinal follow-up of Army STARRS to find
actionable factors that can be used to improve early detection, and effective prevention
and treatment of suicide, PTSD, TBI, and comorbidities. The follow-up study will
include the ability to consent for the donation of post mortem brains and begin to
establish necessary procedures for timely collection and preservation of tissue.
Continue to leverage existing and emerging information technology to improve existing
care for individuals with PTSD, TBI, suicidality and other conditions. Agencies already
harnessing information to answer research questions will continue to evolve the learning
healthcare system model, and provide lessons learned to agencies interested in
developing this model.
Utilize tools for agencies to coordinate and share the research they support where
appropriate. The agencies will identify a common database to explore the feasibility of
utilizing it to share the research they support with other federal agencies and with
researchers outside of the Federal government, where appropriate.
The co-chairs (DoD, VA, HHS, and ED) of the Interagency Research Committee (responsible for
writing this NRAP) or their designees will be responsible for overseeing the formation of any
necessary workgroups or initiatives to deliver on the plans of this NRAP and provide the Task
Force with yearly progress reports related to achieving the NRAP goals.
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PTSD: Biomarkers, Mechanisms, and Treatment Research
In response to a traumatic event, people commonly experience PTSD-like symptoms, e.g.,
hyperarousal or reliving the event. Afterwards, many individuals progressively improve and
symptoms recede. Those who continue to experience distress may develop PTSD. They may also
report symptoms that reflect a variety of comorbid conditions including TBI, depression, and
substance abuse. Symptoms typically vary from person to person. The overall goals of PTSD
research studies are to (1) reduce the number of individuals who develop PTSD following trauma
(through early diagnosis and preventive interventions) and (2) reduce the number of individuals
with chronic PTSD (through treatments that also address substance-related and other
comorbidities).
Areas of research focus include:
Mechanisms. The mechanisms underlying the development of PTSD and comorbid conditions
following traumatic exposure need to be better elucidated to enable the identification of
individuals at risk. These mechanisms may be revealed through a variety of research activities
including neuroimaging, animal studies, post-mortem analyses, and laboratory-based
investigations focused on identifying physiological and neurochemical contributions, and other
psychological, contextual, and environmental factors, including pre-existing conditions (e.g.,
substance abuse). As cognitive science evolves to reveal how dysfunction in memory, learning,
and attention processes contribute to the development, prevention, and treatment of mental
illness, researchers need to translate these findings into prediction models and novel prevention
and treatment interventions. The National Institute of Mental Health (NIMH) has launched the
Research Domain Criteria (RDoC) project, which will be enhanced to define basic dimensions of
functioning (e.g., fear circuitry) to be examined across units of analysis from the level of genes
to neural circuits to behaviors that are predictive of symptoms and/or reflect the etiology or
persistence of a disorder. Information gathered from the RDoC project will pave the way for
understanding the mechanisms responsible for phenotypes involved in disorders like PTSD and
developing and testing new interventions.
Biomarkers for early diagnosis. Research is needed to identify and characterize biomarkers that
can predict increased vulnerability to the development of PTSD, indicate changes in the
spectrum of symptoms associated with worsening function, and demonstrate at the biologic level
a positive response to intervention. A biomarker (biological marker) is an objectively measured
indicator that ideally is capable of reflecting normal, at risk, and disease states. Cognitive
markers, e.g., cognitive tests of attention, memory, and executive functioning, may be among the
most promising predictors for PTSD. Biosignatures are an extension of the biomarker concept
that combine different measures across biological, environmental, and social influences that will
be valuable in identifying the complex origins of disorders such as PTSD. Similar to the way
physicians assess heart disease risk in patients by coupling blood test panels for cholesterol and
triglyceride levels with measures of hypertension and high blood pressure, scientists can develop
a biosignature for PTSD by combining cognitive measures and imaging data, serum and
cerebrospinal fluid markers, and highly relevant physiological markers for related symptoms.
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Consortium to Alleviate PTSD (CAP)
The CAP is a new research effort focused on
biomarker discovery and development with the
aim of identifying biomarkers for subacute and
chronic PTSD that can be used for therapeutic
and outcome assessment. With funding from
DoD and VA, this represents a major investment
to advance knowledge related to biomarkers and
clinical utility. A CAP award is expected to be
finalized by September 2013.
Researchers funded through the large-scale DoD
Systems Biology Initiative have identified
candidate biomarkers that may signal the presence
of PTSD in humans. Building upon this effort is
the joint DoD and VA CAP award (see text box),
which will enable investigators to jointly pursue
the Order requirements related to establishing
surrogate and clinically actionable biomarkers for
early PTSD diagnosis and treatment effectiveness.
NIMH is also supporting a substantial number of
research projects focused on identifying
biomarkers to predict increased vulnerability to PTSD. In addition, with the consent of
participating Veterans, the VA’s Million Veteran Program is building one of the world’s largest
databases of genetic, military exposure, lifestyle, and health information, providing a platform
for biomarker research. Another ongoing program that features a substantial amount of
biomarker research is Army STARRS, which is described in more detail later in this report.
Biomarkers for targeted treatment. The identification and validation of biomarkers for PTSD
will ultimately enable practitioners to assess the effectiveness of prevention and treatment
interventions. Clinicians would be able to match individuals with the most effective prevention
and treatment protocols based on the individual’s clinical profile, which may include
medications, psychotherapy, and integrative and complementary medicine treatments alone or in
combination. Research may also reveal populations at risk for specific comorbidities,
subsequently enabling the development and testing of interventions to prevent these problems as
well as effectively treat these conditions if they occur. Thus, another important goal of the NRAP
is to facilitate the development of more personalized treatments; that is, individually tailored
interventions with measurable responses (see text box “Vision for Moving PTSD Treatment
Research into Practice”).
Treatments. Psychotherapies and pharmacological medications are widely used to treat PTSD.
When evidence-based psychotherapy treatment for PTSD is provided, up to 60% of patients
respond successfully. However, individual preferences play an important role in the selection of
intervention. Individuals who do not respond to one treatment may be reluctant to try other
treatments, and preferences relative to the types of therapies available (e.g., pharmacotherapy,
psychosocial therapy, and complementary and alternative medicine) may have a significant
impact on overall outcome. The use of combined therapies holds promise to address urgent
mental health needs. In addition, individuals with PTSD commonly present with substance use
disorders. Therefore, treatment research described in this NRAP will examine ways to optimally
treat comorbid conditions (e.g., integrative versus sequential treatments). TBI will also be
examined as a comorbid condition for the military and Veteran population with PTSD.
There are no medications developed specifically for the treatment of PTSD. The two medications
approved by the U.S. Food and Drug Administration for PTSD (the antidepressants sertraline
and paroxetine) show modest efficacy. Many medications are used “off-label” to treat PTSD
symptoms but lack scientific evidence that they are beneficial. Few treatment interventions target
underlying biological causes or mechanisms of the disease. Investment by the pharmaceutical
industry in new medications for PTSD has declined in recent years. Federal stakeholders will
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pursue the development of therapeutics targeting biomarkers and mechanisms uncovered in the
course of research as well as assess the utility of repurposed or off-label treatments. A well-
studied example of this would be prazosin’s ability to treat sleep disturbances in individuals with
PTSD (prazosin is approved for treating hypertension). Further, new partnerships (e.g., public–
private collaborations) will be pursued to aid in the identification of potential pharmacological
targets for the prevention and treatment of PTSD. All of these research efforts would be
enhanced by the development of a virtual tissue (brain) repository for PTSD. The value of tissue-
based study presents opportunities to understand underlying biology impossible to discover in
vivo.
The agencies’ Interagency Research Continuum Approach for PTSD research and the major
focus areas in each of the seven topic areas are shown in Figure 2. For the VA, NIMH, and
NIDA, the numbers of studies represent the numbers of projects active in FY12, and Follow-Up
Care research for NIMH and NIDA was included in Treatment and/or Services Research. For the
DoD, the grant numbers represent the cumulative number of active studies funded from FY07–
FY12.
Vision for Moving PTSD Treatment Research into Practice
The aspirational vision is to provide practitioners with the most effective ways to prevent or treat PTSD in the
civilian and military populations, including service members, Veterans, and their families. Individuals
exposed to traumatic events would routinely participate in systematic evaluation on broad dimensions of risk
with progressively intensive diagnostic evaluations. Individualized and staged interventions would be
planned to minimize severity of acute stress and prevent the development of PTSD. Results would then be
weighted/combined in an automated algorithm to determine risk for PTSD and associated comorbidities
(especially substance related) to inform care and follow-up. Evaluations would inform interventions targeted
at mitigating negative psychological symptoms and consequences. Individuals seeking care for PTSD would
undergo a thorough medical, psychiatric, and substance abuse history and assessment to yield a health risk
profile indicative of the underlying cause/type of impairment. The individual would then be matched to
receive treatment known to target/address the specific underlying cause/type of his/her disorder. Throughout
a course of treatment, effectiveness of any administered treatment(s) would be measured. Researchers
would have knowledge of both fixed and modifiable systems, circuits, and molecules to focus treatment
development and refinement studies. New interventions thus will move faster from discovery/development to
use in clinical care, thereby expanding treatment options.
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Follow-Up Plan to Achieve the Vision for PTSD Research:
It is anticipated that findings from ongoing and newly initiated studies will directly inform future
research specifically in areas of underlying mechanisms and biomarkers that in turn will inform
prevention and treatment intervention advances. Notably, the agencies are dedicated to
discussing/sharing new findings, reassessing goals, and informing new collaborative activities
with each other (e.g., a meeting on biomarkers in high-risk cohorts and joint portfolio reviews).
As studies conclude, the agencies will review research findings that pertain to prevention and
health promotion and treatment interventions for PTSD and co-occurring conditions to identify
those that warrant further investigation or those that are appropriate to implement within health
care systems. The actions presented in the following time frames form the vision for PTSD
research. Please note that the bullets within each time frame are organized by the order in the
Interagency Research Continuum and are not placed in order of importance or priority.
Immediate Actions (within 1 year)
Fund new exploratory research on structural and/or functional changes in the brain
immediately following trauma exposure to identify early changes indicative of the future
development of PTSD and comorbidities.
Review emerging genomic and molecular findings on causal pathways and changes that
contribute to PTSD and perform critical replication of preliminary findings.
Continue to expand NIMH RDoC efforts by funding new applications to develop and test
neural system measures that may be applicable to the spectrum of posttraumatic stress
symptoms and comorbid psychiatric conditions.
Increase the inventory of scarce research resources (e.g., tissue samples, blood, and
cerebrospinal fluid), facilitating access for scientific purposes (with appropriate human
subjects’ protections related to privacy and confidentiality). To accomplish this, the
agencies will leverage existing pathology archives to initiate development of a virtual
tissue (brain) repository for PTSD research. Activities will also include (1) incorporating
appropriate agreements either between the investigator and resourcing agency (material
transfer agreement) or between agencies (interagency agreement) and (2) processes for
securing consent to obtain brain tissue from donor (premortem) or representative
(postmortem).
Establish preliminary sex-specific risk allele biomarkers for PTSD to enrich and enhance
risk prediction measures. This will aid in the identification of new targets for the
development of prevention and treatment interventions.
Publish program announcements, complete review of applications, and fund studies from
interagency funding opportunities addressing PTSD biomarkers, substance abuse
prevention, and wellness interventions for service members, Veterans, and their families.
Convene an interagency biomarker working group to explore early findings from ongoing
biomarker efforts and plan data-sharing opportunities to facilitate additional analyses of
both published results and raw data.
Continue research to improve and optimize the effectiveness and delivery of:
− Current evidence-based prevention and treatment interventions (including
psychotherapies, combination therapies, and adjunctive treatments) and available
medications for PTSD and comorbidities; and
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− Service modalities for PTSD and comorbidities (e.g., telemedicine and
web-based).
Continue research on the safety and efficacy of medications, psychotherapeutics, and
combination treatments targeting underlying mechanisms of PTSD and comorbidities.
Short-Term Actions (2–4 years)
Disseminate findings (e.g., peer-reviewed publications, conferences, and briefings) from
at least three genome-wide association studies with military, Veteran, or other high-risk
cohorts to determine genetic patterns associated with PTSD and comorbidities.
Identify and confirm whether potential biomarkers have clinical value for PTSD by
utilizing studies that contain phenotypic and genetic data (e.g., Million Veteran Program,
Marine Resiliency Study, and South Texas Research Organizational Network Guiding
Studies on Trauma and Resilience).
Establish a validated PTSD assay from the DoD’s systems biology effort for objective
diagnosis and monitoring of treatment response.
Identify brain circuitry changes related to treatment response and disseminate findings
(e.g., peer-reviewed publications, conferences, and briefings) from at least two
translational trials.
Leverage results from biomarker research (e.g., data emanating from CAP-funded
projects) and embed follow-on biomarker studies in select clinical trials to explore
biological changes or markers that are associated with treatment response to better match
individuals to treatments.
Disseminate findings (e.g., peer-reviewed publications, conferences, and briefings) from
translational trials that are targeting either (1) a putative mechanism in PTSD with the
novel use of medications (e.g., CRF [corticotropin releasing factor] antagonist and
mifepristone) or (2) comorbidities with PTSD.
Conduct research to optimize psychotherapeutic intervention approaches (e.g.,
repackaging, shortening, or integrating them) to achieve more rapid and long-lasting
benefit.
Disseminate findings (e.g., peer-reviewed publications, conferences, and briefings) from
randomized controlled trials aimed at improving and optimizing PTSD treatment (e.g.,
psychotherapeutic and combination psychotherapeutic and pharmacological treatment
protocols, including those for comorbid conditions).
Long-Term Actions (5–10 years)
Looking to the future, the agencies are striving to deliver research results that will move the field
closer to realizing the PTSD vision (summarized earlier) of optimal prevention, diagnosis, and
treatment for each individual. Realizing this vision requires continued investments in relevant
research and a commitment by the agencies to important high-priority collaborative endeavors in
the coming years. A forward leaning, aggressive vision is essential to achieve the “long-term
actions” described here; however, steps toward these items are already under way or as noted in
the following paragraphs will begin in shorter time frames, and the pace toward full
implementation will be accelerated under the NRAP.
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Focus areas for consideration in this longer term horizon include:
Develop the systematic ability to combine data from valuable DoD, NIH, and VA cohort
studies for a deep longitudinal view of putative biomarkers, to enhance clinical measures
and improve the classification and prediction of PTSD. While some analyses can occur in
shorter time frames, early phase work toward more systematic combined analyses will be
dedicated to understanding the existing barriers to achieving this objective and
developing plans for implementation. Over the longer term, efforts will focus on working
to overcome the barriers and conducting analyses.
Identify the requirements that would be needed to potentially establish a coordinated
clinical treatment registry across VA, DoD, and civilian health care systems and clinical
trials to collect common clinical and other measures that may lead to improved treatment
outcomes. Ultimately, this effort could enhance clinical measures and improve the
classification and prediction of PTSD by integrating and analyzing individual-level data
from prior PTSD risk studies with a large number of acute trauma patients to develop
models for combining clinical and biomarker data to predict risk of PTSD onset and
lessen the severity of the disorder in those with PTSD. To achieve this objective from the
present state of disparate service and research funding systems, early phase work in a
shorter time frame will be focused on assessing the landscape of such systems, including
their capabilities and limitations. Later phase efforts will concentrate on the institution of
commonalities so that analyses can occur. Any such effort would include a clear policy
process to ensure informed consent of patients.
Enhance new and emerging infrastructure (e.g., NIMH experimental medicine project for
Fast Fail Trials in Mood and Anxiety Spectrum Disorders, VA and DoD clinical trials
infrastructure) to accelerate the testing of novel and repurposed pharmacological
interventions. This may include partnering with pharmaceutical companies that identify
compounds that may have the potential to treat underlying PTSD mechanisms. Initial
work on this objective will include the identification of potential targets. This will be
followed by further work on partnership development. Partnership development will take
time to establish the working relationships in a structured way (Cooperative Research and
Development Agreements for data use, sharing, intellectual property, etc.), as well as
move compounds to trials.
As new efficacious interventions are developed, the next steps will focus on determining how to
enhance treatment-seeking behavior and reduce barriers to care, as well as utilizing standardized
training procedures for professionals to implement evidence-based interventions with fidelity in
health care systems and evaluate on an ongoing basis.
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TBI: Biomarkers, Diagnosis, Mechanisms, and
Treatment Research
TBI is a complex and heterogeneous injury that includes a spectrum of severities ranging from
mild (also known as a concussion) to moderate, severe, and penetrating. It can result in
temporary symptoms or enduring disabilities, depending on factors such as the severity and
location of the injury, the age at injury, and the number of injuries over time. Common issues
resulting from TBI include: (1) the post-concussion syndrome of attention/concentration deficit,
headache, dizziness, sleep disorder, depressed mood, irritability; (2) longer-term difficulties with
cognition, behavioral and mental health, communication, and sensory processing (common after
moderate or severe TBI); and (3) chronic traumatic encephalopathy as a result of repeated mTBI,
which has also been linked with other delayed, neurodegenerative diseases such as Alzheimer’s-
type dementia, amyotrophic lateral sclerosis (Lou Gehrig’s disease), and Parkinson’s-like
symptoms.
Currently 266,810 cases of TBI have occurred in the military 2000–2012. Most of these are mild
TBI and approximately 15%–20% are deployment related. Most of the combat wounds observed
in the conflicts in Operation Enduring Freedom/Operation Iraqi Freedom were caused by
explosive weapons, such as improvised explosive devices. The effects of these blast exposures
on the brain are not well understood. It is unclear whether blast injury is similar to the
pathologically characterized impact injuries or acceleration/deceleration injuries. Therefore, any
existing unique neuropathological features of blast injury are critical to define in order to guide
research efforts aimed toward helping those exposed to blast TBI in the military. Animal models
of blast injury could be exceedingly valuable to study relevant injury mechanisms if there is a
clinically significant human pathology to model. A neuropathology laboratory has been
established at Uniformed Services University of the Health Sciences (USUHS) for the purpose of
defining the pathology of blast injury funded by the USUHS-NIH Center for Neuroscience and
Regenerative Medicine and the U.S. Army Medical Research and Materiel Command. Clear
consent is required for the comprehensive examination of brain tissue in deceased military
personnel. Due to the sensitive nature of requesting consent for brain examination at the time of
death, access to tissue has remained a barrier for understanding blast-related injuries.
Challenges for TBI research and clinical care include imprecise diagnostic tools and criteria used
to classify the severity and type of TBI; a limited understanding of the impact of co-occurring
conditions; gaps in understanding of mechanisms underlying injury and recovery, including the
effects of gender, ethnicity, and socioeconomic background; paucity of research data on the
social, psychological, and economic impacts of TBI on families and communities; uncertainty
about the ability of preclinical models to reproduce the spectrum of injuries and co-occurring
conditions; and a nascent understanding of ways to harness neuroplasticity to increase repair and
recovery. Notably, a military context that poses a unique challenge is the role of multiple
mechanisms (“blast-plus”) as compared to single mechanism injuries (e.g., motor vehicle
accident or sports concussion). To facilitate treatment advances for service members and
Veterans with TBI, it will be necessary to better understand both the mechanism of underlying
injury and its long-term health needs.
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Chronic Effects of Neurotrauma
Consortia (CENC)
The DoD and VA are jointly sponsoring the CENC
award, which will fund a large consortia to:
Establish the association of the chronic effects of
mTBI and common comorbidities;
Determine whether there is a causative effect of
chronic mTBI/concussion on neurodegenerative
disease and other comorbidities;
Identify diagnostic and prognostic indicators of
neurodegenerative disease and other comorbidities
associated with mTBI/concussion; and
Develop and advance methods to treat and
rehabilitate chronic neurodegenerative disease and
comorbid effects of mTBI/concussion.
A CENC award is expected to be finalized by September
2013.
Areas of research focus include:
Diagnostic tools and definitions. Current definitions of TBI as well as the tools currently used to
diagnose it are imprecise. The DoD and CDC, in partnership with the Brain Trauma Foundation,
have funded an effort to develop a clinically meaningful classification system of
mTBI/concussion that will enable improved clinical assessment of current status and prognosis.
The International TBI Common Data Elements (CDEs) Project has recommended a battery of
instruments to be used in TBI epidemiological and interventions research, but evidence
demonstrating the utility or superiority of the recommended instruments over other measures is
limited. NINDS has funded “Transforming Research and Clinical Knowledge in TBI” (TRACK
– TBI), a pilot project to evaluate the utility and feasibility of the CDEs. DoD has funded the
data analysis component of TRACK – TBI. These three successful interagency collaborations
underscore the value and need for additional research to create more precise classifications of
injury type and severity and more sensitive diagnostic tools to ultimately enable personalized
medicine for TBI. There is also the opportunity for leveraging emerging imaging modalities and
body fluid-derived biomarkers for improved diagnostics, but validation will be required before
they are ready for clinical use.
Biomarkers for identification, management, and treatment effectiveness. Preliminary evidence
supports the potential for use of bodily fluid (e.g., blood, serum, and cerebrospinal fluid)
biomarkers to detect mTBI/concussion. Animal studies have indicated that changes in gene
expression in white blood cells may
identify inflammation related to TBI.
However, identification of sensitive and
specific biomarkers requires a more precise
classification system for TBI, similar to the
systems used for spinal cord injury and
cancer. Biomarkers may inform research
and clinical investigation as well as the
management of both acute and chronic
stages of TBI. Of particular interest are
biomarkers indicative of the potential
neurodegenerative effects of TBI, such as
chronic traumatic encephalopathy and
dementia. In short, biomarkers to detect
injury, predict short- and long-term
outcomes, and monitor response to
treatment are all needed. Studies are under
way to identify and test biomarkers, but
none are currently ready for clinical use.
There is an urgent need to systematically evaluate existing and emerging biomarker technologies
for their ability to improve accurate diagnosis, detect acute and chronic illness, identify patterns
of recovery, predict outcomes, and monitor the response to treatment.
Mechanisms. Following TBI, most patients show some degree of functional improvement over
time. However, relatively little is known about the mechanisms that underlie recovery or about
ways to harness neuroplasticity to optimize improvements. Research is needed to identify
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patterns of brain structure and function that are associated with either recovery or poor response
to treatment. Given emerging evidence regarding the chronic effects of TBI, a better
understanding of the relationship between neurotrauma and neurodegeneration is needed for the
development of effective medical and rehabilitation interventions (see text box on the CENC).
The nature of brain injuries incurred in the current military conflicts has highlighted the need to
better understand the effects of repetitive brain trauma on neuropathology, neurological function,
and mental health. The fielding of blast and impact sensors is anticipated to enable more precise
identification of those exposed to possible concussive events. Once these devices have been
validated as accurate in identifying possible events, they can then be correlated with clinical
findings to determine whether injury severity can be accurately predicted.
Preclinical modeling. While basic science is essential to improving diagnostics and treatments
for TBI, the ability to model TBI in animals has been less successful. None of the treatments
found to be effective in preclinical animal models have successfully progressed through a Phase
III clinical trial for clinical use in humans. The limited human postmortem brain tissue samples
available for study have not allowed for sufficient comparison with animals. The differences in
mass, shape, and white/gray matter ratios between rodent and human brains make it difficult to
reproduce the effects of TBI in a manner that physically and structurally scales from rodents to
humans. Animal models rarely address the short- and long-term comorbidities and/or chronic
effects associated with TBI nor do they clearly address the recovery/rehabilitation phase.
Systems biology approaches that integrate animal and human findings with computational
modeling of injury mechanisms and high performance computing have the potential to enable
previously impossible levels of cross-correlation and analysis of research data. However,
challenges in collecting human postmortem brain tissue have impeded progress in this area. A
coordinated military, Veteran, and civilian tissue repository effort to make postmortem tissue
available for research purposes is critical. Notably, the DoD has established the first DoD brain
tissue repository to study TBI in service members. To guide the development and validation of
animal models, especially for blast and mTBI, further postmortem human tissue research will be
needed, and efforts to encourage donation of postmortem tissue with appropriate consent will
help to advance this research.
Treatments. Over 30 clinical trials of TBI pharmacological therapies have failed to produce a
U.S. Food and Drug Administration-approved treatment for acute TBI. There is limited evidence
of the effectiveness of both pharmacological and nonpharmacological interventions, including
rehabilitation treatments, due in part, to underpowered studies and the limited validated
assessment tools that are sensitive enough to detect treatment effects. Research on treatment
efficacy and effectiveness has also been hampered by difficulties in defining the active
ingredient of many experience-based treatments that are commonly used in rehabilitation. The
concurrent application of multiple treatments, including pharmacological and
nonpharmacological interventions, poses another challenge. Rigorous definitions of
rehabilitation treatments are needed as well as research regarding the customization of therapies
to an individual’s injury, predisposing factors, and co-occurring conditions.
Assessment. The International CDE Project for TBI has recommended a battery of “gold
standard” outcome measures and assessments for TBI research; however, collectively these take
several hours to implement. A shorter assessment tool that is both comprehensive and sensitive
across the range of injury severities is clearly needed. Possibilities include several computer-
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assisted outcome assessment tools that have recently been developed. The NIH Toolbox for
Assessment of Neurological and Behavioral Function is a multidimensional set of brief measures
that assess cognitive, emotional, motor, and sensory function in individuals from 3 to 85 years of
age. The NINDS-funded Neuro-QOL is a set of self-report measures that assesses the health-
related quality of life of adults and children with neurological disorders, and the NIDRR-funded
TBI-QOL measures health-related quality of life specifically for people with TBI. These tools
have the potential to fill an important gap by providing a comprehensive assessment of
functional outcomes and quality of life following treatment while also being brief, freely
accessible, and reliable. However, these tools need further validation before they are ready for
clinical use in persons with TBI.
Co-occurring and pre-existing conditions. Major challenges to mechanistic and treatment-related
research on TBI include difficulties in distinguishing the effects of PTSD and other
comorbidities, such as sensory, endocrine, cognitive, behavioral, and sleep dysfunctions, from
the central nervous system injury itself. In other words, the symptoms and sequelae of TBI can
overlap with many other disorders. Of concern are reports of suicide in persons, including
Veterans who have sustained TBI, who were found to have tau deposits in the brain diagnostic of
chronic traumatic encephalopathy. Additionally, evidence is emerging that pre-existing factors,
be they physical, social, cultural, or health-related, have an effect upon the course and outcome
of TBI. The common approach to intervention—independently treating symptoms associated
with each diagnosis—is known to be less than optimal and is, in many cases, ineffective.
Research is needed to identify effective integrated, team-based models of treatment for persons
with TBI that address both pre-morbid and co-occurring conditions.
Substance abuse is a known co-occurring condition with TBI with detrimental outcomes for
persons with TBI and their families. For the general population of persons receiving health care
services, Screening, Brief Intervention, Referral to Treatment (SBIRT) is standard of care for
alcohol and tobacco, according to U.S. Prevention Services Task Force reports. However, despite
being standard of care, SBIRT is not always implemented. NIDRR and other agencies within
Department of Education have funded the development of an adapted SBIRT protocol for
persons with TBI. Initial studies of this adapted protocol have concluded that the addition of
multimedia educational components to the standard SBIRT protocol is having an impact on
knowledge and beliefs, which in turn reduce substance abuse. Additional research investigating
substance abuse in persons with TBI is needed including, but not limited to, further validation of
best practices for screening, brief intervention, and referral to treatment.
The agencies’ Interagency Research Continuum Approach for TBI research and the major focus
areas in each of the topic areas are shown in Figure 3. For the NIH, VA, and NIDRR, the
numbers of studies represent the numbers of projects active in FY12. For the DoD, the grant
numbers represent the cumulative number of studies active between FY07 and FY12.
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Vision for Accelerating TBI Research to Improve Health Care
and Outcomes
The aspirational vision for TBI research is to identify evidenced-based therapies that are effective in
maximizing short- and long-term health and function, community participation and reintegration for
persons with TBI in civilian and military populations, including service members, Veterans, and their
families. Effective treatments, including rehabilitation treatments, would be personalized to address the
specific type of injury and co-occurring conditions (especially substance related), considering patient
preferences for care. A clinically relevant classification system for TBI across the spectrum of injury
severities, age, gender, and chronic conditions, including mild single and repetitive injuries would be
available to advise patients about their diagnosis, prognosis, and treatment options. More sensitive,
reliable, and efficient tools (“gold standards”) would be available for evaluating the effectiveness of
treatments on an individual’s physical, cognitive, and psychosocial functioning and quality of life.
Follow-Up Plan to Achieve the Vision for TBI Research:
Data generated from ongoing and newly initiated studies are anticipated to directly inform future
research specifically in the areas of diagnosis, mechanisms, and biomarkers that in turn will
inform prevention and treatment intervention advances for TBI. The agencies are holding
regularly scheduled meetings dedicated to discussing/sharing new findings, reassessing goals,
and updating collaborative activities among the partners. Specific follow-up actions are
presented in the following time frames. Please note that the bullets within each time frame are
organized by the order in the Interagency Research Continuum and are not placed in order of
importance or priority.
Immediate Actions (within 1 year)
Complete the current DoD-CDC-Brain Trauma Foundation mTBI/concussion
classification project to clarify what is known and unknown about mTBI and the critical
gaps that need to be addressed. Identify a process for developing a clinically relevant
system to replace the current mild/moderate/severe nomenclature.
Increase the inventory of scarce research resources (e.g., tissue samples, blood, and
cerebrospinal fluid), facilitating access for scientific purposes (with appropriate human
subjects’ protections related to privacy and confidentiality). To accomplish this, the
agencies will leverage existing pathology archives to initiate development of a virtual
tissue (brain) repository for TBI research. Activities will also include (1) incorporating
appropriate agreements either between the investigator and resourcing agency (material
transfer agreement) or between agencies (interagency agreement) and (2) processes for
securing consent to obtain brain tissue from donor (premortem) or representative
(postmortem).
Facilitate coordination of portfolio analysis and collaboration on research projects of
shared interest by exploring the possibility of participation of the DoD and NIDDR in the
NIH Electronic Research Administration system, which provides support for the full life
cycle of grants administration functions for the NIH, VA, and several other agencies.
Determine whether point of injury blast and impact sensors can be correlated to
mechanism and severity of brain injury.
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Establish an interagency working group to review and report on existing and novel
diagnostic tools and treatments for TBI to improve the evidence base for TBI
management.
Coordinate within and between agencies involved in the Brain Research through
Advancing Innovative Neurotechnologies initiative to ensure a balance of basic and
translational science so that more maturely developed technologies can be utilized
clinically as soon as possible.
Continue to support clinical trials that are evaluating the effectiveness of therapies to
improve outcomes and quality of life following TBI.
Short-Term Actions (2–4 years)
Support research focused on systematically characterizing blast neuropathology related to
military service and comparing and contrasting it to the neuropathology of impact TBI.
Test neuroimaging technologies to establish a means of identifying pathobiological
markers of TBI regardless of mechanism in service members and Veterans. If there are
verifiable and clinically significant differences between blast- and impact-induced TBI,
develop scalable animal and in vitro models, if feasible, to identify and leverage
biological pathways for study of therapies and the process of recovery.
Develop a better understanding of the quantitative relationship between the level or
number of repetitions of blast exposure and severity of TBI in animal models and
humans.
Determine whether co-occurring and pre-existing conditions exacerbate impact- and
blast-related neuropathology.
Develop initiatives for basic and clinical research focused on increasing the
understanding of mechanisms of recovery after TBI and discovering ways to harness
neuroplasticity to improve outcomes.
Support validation studies of proteomic, imaging, neurophysiologic, and other potential
biomarkers and diagnostic tools using the TBI CDEs, the FITBIR Informatics System
and existing TBI clinical networks (e.g., TRACK-TBI, TBIMS, CENC, and VA Centers
of Excellence). These studies may focus on early diagnosis, neuro-anatomic correlation
of symptoms, classification of degrees of injury, markers of neural patterns of good
recovery vs. poor recovery, or biomarkers in studies of therapeutic target engagement.
Continue to support the FITBIR Informatics System as a national resource for TBI
research and enhance the system to include with appropriate consent advanced analytical
tools, pipelines for importing and exporting data (especially neuroimaging data);
electronic data capture for emergency rooms, intensive care units, sports, and battlefields;
and legacy data.
Promote collaboration, meta-analysis and sharing of de-identified individual TBI study
data in CDE format across agencies through the population of existing federal databases
with FITBIR data, where possible, appropriate, and permissible. Activities to support this
collaboration include implementing the use of global unique identifiers, the TBI CDEs,
and consent forms that allow for data sharing across agencies for new studies, when
possible, appropriate, and permissible.
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Develop efficient, affordable, comprehensive, valid, and sensitive tools for assessing
functional outcomes and quality of life over time. Evaluate the utility of the NIH Toolbox
for Assessment of Neurological and Behavioral Function, the Neuro-QOL, and the TBI-
QOL and other tools that meet scientific standards to improve clinical assessment and
enable measurement of treatment effectiveness specific to the TBI population.
Long-Term Actions (5–10 years)
Develop a more precise system for classifying and staging TBI to enhance diagnosis and
prognosis and enable targeted therapies and personalized medicine. The approach will be
to (1) support natural history and other prospective, observational studies and (2) share
data from these studies, with appropriate privacy protections, to enable computational
analysis of large, high-quality data sets that include impact and blast injuries, military and
civilian populations, acute and chronic phases, and the entire spectrum of age, severity,
and the continuum of care.
Determine the acute and chronic effects of TBI as well as the genetic, gender, ethnic, and
environmental (epigenetic, socioeconomic, and cultural) protective and risk factors that
influence susceptibility to injury and subsequent outcomes including the development of
chronic traumatic encephalopathy, Alzheimer’s and other neurodegenerative diseases.
The approach will be to utilize new and existing longitudinal research initiatives (e.g.,
CENC, TBIMS-NDB, and Million Veteran Program) to study the chronic effects of TBI,
including medical, neurological, psychiatric, and psychosocial complications, and to
study genetic and epigenetic protective and risk factors.
Identify causal relationships between posttraumatic alterations in brain function and
symptoms, functional outcomes, and quality of life through greater integration of basic
and clinical research. Integrate preclinical and clinical research to investigate causal
relationships for all ages, injury types, and severities and for acute, subacute, and chronic
stages. This will provide a foundation for developing targeted treatments and
pharmacodynamic biomarkers.
Evaluate promising pharmacological and nonpharmacological treatments, including
rehabilitation treatments for their ability to increase functional outcomes such as
community participation and reintegration.
Develop and test models for optimal team-based, integrated treatment of TBI and co-
occurring conditions to improve upon the existing practice of independently treating
biological targets and/or symptoms of each condition.
Conduct research on the social, psychological, and economic effects of deployment-
related TBI on military families and on communities. Diverse indicators of family and
community well-being should be examined.
Conduct research on the long-term health needs of service members and Veterans with
TBI and the resources needed for long-term care and planning.
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Suicide Prevention Research
Suicide prevention is a major research priority that benefits from and is dependent on cross-
agency, collaborative efforts to maximize the ability to effectively address the problem. Suicide
is the 10th leading cause of death in the United States, claiming twice as many lives per year as
homicide. Suicide attempts are up to 30 times more common than suicide deaths and are more
frequent among younger persons. Having made a suicide attempt is one of the most highly
predictive factors for later suicide death. Individual characteristics, such as a history of childhood
abuse and mental and/or substance use disorders, can interact with current or ongoing stressors
(e.g., relationship disruptions, financial or social losses, and shameful experiences) to increase
suicide risk. Civilian and military suicide rates have been rising in recent years. Because
individuals become suicidal for many different reasons, and not all individuals in suicidal crises
will be seen in health care settings, multiple intervention approaches in multiple contexts are
needed. Interventions are also needed to address how to identify and promote effective help-
seeking behavior and reduce/treat underlying co-occurring mental health disorders.
Research indicates that no single factor has emerged as predictive of suicide in the military
population. Some factors (such as repeated deployment) that have been hypothesized to be
contributing to the increase in suicides in recent years have not been demonstrated to drive this
increase (e.g., many suicides precede deployment). Almost half of the accidental and
undetermined deaths investigated in the Army during 2006–2009 involved drugs or alcohol, and
three-quarters of these deaths involved prescription drugs; however, the exact role of substance
use in these deaths is not understood. Some studies have shown an association between suicide
and TBI. However, the low base rate of suicide makes disentangling this challenging. Overall,
factors leading to suicide are extremely complex, and research is under way to better understand
the role of concussions and other comorbid factors.
Many individuals who die by suicide are seen in health care systems close to the time of death.
Evidence demonstrates that providing continuity of care through transitions (within a health care
system and from military to civilian settings) is important. Other health care system
improvements that reduce suicide risk for individuals include providing 24-hour crisis services;
increasing treatment adherence and managing patients with comorbid substance use disorders;
and for practitioners, providing regular training to frontline clinical staff on the management of
suicide risk. Other factors that may help reduce suicide have been identified; e.g., limiting access
to lethal means significantly lowers suicide risk. Furthermore, treatments such as
psychotherapies focused on mitigating suicidal thoughts among suicide attempters have been
shown to reduce attempts by half in the 12 months following treatment. Small proof-of-concept
studies show promise for fast-acting medications (e.g., ketamine) in reducing suicide ideation,
but more research is needed. Longer-term research is needed to better understand the factors that
build resilience and offer protection from suicidal behaviors and promote wellness and recovery.
The agencies have an ongoing partnership focused on suicide prevention research efforts
1
in
many areas directly relevant to the Order. The U.S. Army and NIMH jointly initiated Army
1
When not specified otherwise, the efforts described for suicide prevention research include preventing completed
suicides as well as suicide behaviors to include suicide attempts and suicide ideation.
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Military Suicide Research Consortium
The DoD MSRC represents a unique collaboration among
the world’s experts in suicide research, including military,
VA, and academic partners to produce evidence-based
effective suicide prevention interventions. The MSRC
complements the Army STARRS epidemiological study.
The goal of MSRC research is to develop effective risk
assessment methods, and prevention and treatment
interventions to decrease suicide among active duty
service members and Veterans. Funded projects are
examining strategies to reduce suicide risk, to prevent re-
attempts, and to understand bereavement among military
families after a Veteran or active duty member of the
military has died by suicide. In addition, the MSRC has
developed an extensive data warehouse containing
thousands of peer reviewed journal articles on military
and Veteran mental health disorders, risk assessment
and prevention, focused in particular on suicide and
suicide-related research.
Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
2
to examine how
psychosocial, biological, and genetic factors convey risk/resilience for suicide, as well as related
conditions (e.g., mental health disorders and substance-related disorders). The Military Suicide
Research Consortium (MSRC) was created by the DoD to develop and validate effective
interventions to prevent suicide among active-duty service members and Veterans (see text box).
The National Action Alliance for Suicide Prevention’s Research Prioritization Task Force is co-
chaired by the NIH and the National
Council for Suicide Prevention. The
Research Prioritization Task Force is
developing a proposed agenda by
September 2013 to inform both the public
and private sectors efforts to reduce
suicide attempts and deaths in the next
10 years. The Defense Suicide Prevention
Office’s Translation and Implementation
of Evaluation and Research Studies, which
involves the DoD, military services, VA,
and NIMH, translates knowledge accrued
from evaluation and research studies into
practical guidelines for military leaders,
chaplains, and clinical and nonclinical
support personnel, which will benefit
service members, Veterans, and their
families. The NIMH is also developing a
research study portfolio analysis tool that
will have the capacity to conduct systematic searches and analyses of funded studies among the
agencies and private sector foundations, which will contribute to the Interagency Research
Continuum Approach for suicide prevention.
Findings emanating from the VA’s nationwide suicide prevention program, Mental Illness
Research Education and Clinical Centers, and Centers of Excellence will contribute to an
understanding of what is working within the VA health care systems and identify factors for
targeted research. A joint VA-DoD database of suicide history and health care information is
being developed to serve programmatic evaluation needs. The National Action Alliance for
Suicide Prevention’s Research Prioritization Task Force will continue to solicit findings on
research advances from the agencies, including the VA National Centers of Excellence in
Suicide Prevention.
The agencies’ Interagency Research Continuum Approach for suicide prevention research,
including the major focus areas within each topic area, is shown in Figure 4. For the VA, NIMH,
and NIDA, the numbers of studies represent the numbers of projects active in FY12, and Follow-
Up Care research for NIMH was included in Treatment and/or Services Research. For the DoD,
the numbers represent the cumulative number of active studies funded from FY07–FY12.
2
Additional details on Army STARRS are presented in the Comprehensive Longitudinal Mental Health Study section of
this report.
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Vision to Advance Suicide Prevention
Research
The aspirational vision for suicide prevention research is to
achieve a significant reduction in attempted and completed
suicides in the civilian, military, and Veteran populations
through evidence-based prevention and treatment advances.
There is hope that with new knowledge gained from research
applied to practice, an individual who has made a suicide
attempt or has suicidal thoughts would receive lifesaving care.
Such an individual would seek help early through available
resources such as a 24-hour hotline (Veterans Crisis Line) or
online resources (Veterans Crisis Line website or VA
Community Provider Toolkit). Modifiable risk and protective
factors (e.g., reduced substance use and improved problem
solving) could be targeted to avert reattempts. Evidence-based
prevention programs that build resilience, reduce risk, and
prevent the emergence of suicidal behaviors would be
implemented in diverse systems of care and populations, with
positive impact on suicide prevention.
Follow-Up Plan to Achieve the Vision for Suicide Prevention Research:
Critical research to meet the
priorities of the Order includes
enhanced use of surveillance data
and longitudinal studies; testing
screening approaches; timely and
comprehensive sharing of data
with appropriate safeguards; and
the development and testing of
new prevention and treatment
interventions when targets are
identified. Research focused on
alcohol and substance use in the
military, including Veterans and
their families, is also important.
Beyond the actions identified in
the following paragraphs,
additional information relevant to
suicide prevention activities is
found in the Comprehensive
Longitudinal Mental Health Study
section of this report. The following plan describes how the vision for suicide prevention
research can be met over time. Please note that the bullets within each time frame are organized
by the order of the Interagency Research Continuum and are not placed in order of importance or
priority.
Immediate Actions (within 1 year)
Develop and test theoretical models to advance the science of understanding precursors
and causes of suicide and its prevention.
Increase the inventory of scarce research resources (e.g., tissue samples, blood, and
cerebrospinal fluid), facilitating access for scientific purposes (with appropriate human
subjects’ protections related to privacy and confidentiality). To accomplish this, the
agencies will leverage existing pathology archives to initiate development of a virtual
tissue (brain) repository for suicide prevention research. Activities will also include
(1) incorporating appropriate agreements either between the investigator and resourcing
agency (material transfer agreement) or between agencies (interagency agreement) and
(2) processes for securing consent to obtain brain tissue from donor (premortem) or
representative (postmortem).
Continue the development of integrated surveillance and survey database management
systems across the DoD and VA.
Disseminate findings (e.g., peer-reviewed publications, conferences, and briefings) from
completed evidence synthesis reviews related to suicide prevention addressing key
questions such as risk factors and assessment, and prevalence of co-occurrence of suicide
with mTBI.
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The MSRC will identify the next set of research studies aimed at developing and testing
suicide prevention interventions in clinical trials.
Disseminate emerging findings and translate findings into next steps for intervention
research utilizing programs such as the Defense Suicide Prevention Office’s Translation
and Implementation of Evaluation and Research Studies.
Initiate novel efforts to create clinical tools with high specificity and sensitivity to
identify at-risk individuals using minimally intrusive techniques.
Evaluate research findings as they become available to determine what type of follow-up
most effectively enhances treatment adherence and decreases suicidal behavior in high-
risk individuals.
Continue ongoing investigations aimed at encouraging implementation of evidence-based
suicide assessment and management techniques in current care delivery settings
(e.g., counseling and addictions treatment). Future research efforts will focus on
improving provider training, developing and testing quality improvement measures, and
assessing patient satisfaction.
Short-Term Actions (2–4 years)
Empirically establish whether screens for suicide prevention can be used with adult
patients and high-risk young adult/pediatric populations in health care settings
(emergency medicine, primary care).
Develop and test rapid, brief, and effective prevention and treatment interventions for
suicide applicable to a variety of settings, with rigorously designed randomized controlled
trials that address comorbid problems.
Initiate an interagency collaboration between Army STARRS and the MSRC that will
build upon the strengths of each program and facilitate rapid translation of Army
STARRS findings into intervention research efforts.
Develop and test evidence-based “chain-of-care” practices for individuals transitioning
from inpatient to outpatient treatment and to specialty follow-up care.
Investigate the utility of psychological autopsies to discover previously unknown risk
factors or comorbidities for further clinical investigation.
Develop and test return-to-duty and return-to-work protocols with evidence-based criteria.
Long-Term Actions (5–10 years)
Looking to the future, the agencies are working together to support research to reduce suicide in
the civilian, military, and Veteran populations. Reaching this goal will only be possible by
sustaining investments in relevant research and determining the best ways for agencies to focus
on new high-priority, collaborative endeavors in the coming years. Priorities for consideration in
this longer-term horizon include the following:
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Examine long-term outcomes of prevention interventions delivered early in life to
determine whether these interventions impact behaviors related to suicide through
existing and future longitudinal studies.
Conduct multisite, rigorously designed, randomized controlled trials that test rapid-
acting, brief interventions that address suicide risk factors, prevent suicide ideation and
attempts, and can be utilized in emergency care settings through existing partnerships
with consortiums and joint interagency partnerships.
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Comprehensive Longitudinal Mental Health Study
In addition to the broad research goals of the NRAP, the Order also directs DoD and HHS to
engage in a “comprehensive longitudinal mental health study with an emphasis on PTSD, TBI, and
related injuries to develop better prevention, diagnosis, and treatment options. The agencies shall
continue ongoing collaborative research efforts, with an aim to enroll at least 100,000 service
members by December 31, 2012, and include a plan for long-term follow-up with enrollees through
a coordinated effort with the Department of Veterans Affairs.” Ongoing collaborative efforts that
can be leveraged to address these requirements are highlighted in the following paragraphs.
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
The Army and NIMH jointly initiated Army STARRS to examine how psychosocial, biological,
and genetic factors convey risk/resilience for suicide, as well as related conditions. Army
STARRS’ component studies (Historical Administrative Data Study, New Soldier Study, All
Army Study, Soldier Health Outcomes Study, and the Pre/Post Deployment Study) examine
historical and administrative data collected by the Army in conjunction with original data
collected from soldiers in all phases of Army service. As of late 2012, more than 100,000
soldiers volunteered to participate in Army STARRS.
Discussion of emerging findings as well as strategic planning is ongoing involving both
scientists and federal agencies involved in relevant activities. Meetings held have included the
DoD and VA and their funded scientists, as well as those funded by NIH. Plans to share Army
STARRS data with the broader scientific community have also been established to maximize the
utility of these data to improve the lives of service members, Veterans, and their families.
Army STARRS’ Historical Administrative Data Study provides an example of the types of
analyses possible utilizing existing aggregate data on soldiers to address questions regarding
readjustment. The Historical Administrative Data Study includes de-identified data maintained in
multiple Army and DoD data systems that have been integrated to find factors that protect
soldiers’ well-being and factors that suggest mental health risk. To ensure confidentiality,
personally identifiable information is removed, and analyses are performed only on aggregate
de-identified data.
Follow-Up Plan:
Army STARRS will continue through June 2014. Interim Progress Reports are provided to the
Secretary of the Army, Chief of Staff of the Army, and Vice Chief of Staff of the Army to
accelerate dissemination of actionable results to commanders who have the capacity to enact
needed changes. These Interim Progress Reports include the most recent civilian and VA
findings to give the appropriate context of actionable results to senior Army leaders. Findings
will also be published and disseminated through peer-reviewed publications. One goal is for
Army STARRS’ data to inform new and better targeted diagnostic and intervention tools.
The action plan for Army STARRS includes several activities to maximize short-term results
from this unique study and to ensure that the data platform is established as a critical national
resource now and for the future, with all appropriate governance, intellectual property, and
custody rights vested in the appropriate federal agency.
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Immediate Actions (within 1 year)
Develop tools to better identify elevated risk for suicide or other adverse mental health
outcomes. The Army might then be able to use this information to develop targeted
approaches to mitigate risk and ensure the health of soldiers. This research will also
inform our understanding of suicide in the overall population, leading to more effective
prevention and treatment interventions for service members and civilians.
Continue ongoing data collection and analyses, including initial biomarker assays;
analyses focused on psychiatric and substance abuse disorders to inform better prevention,
diagnosis, and treatment options; exploring patterns of suicide risk in the New Soldier
Study, All Army Study, and Pre/Post Deployment Study; comparing data from the
Soldier Heath Outcomes Studies to matched controls to better understand the acute and
chronic factors that contribute to suicide attempts and deaths; and disseminating findings.
Explore the feasibility of a longitudinal follow-up of the comprehensive Army STARRS
to find actionable factors that will lead to early detection and effective prevention and
treatment of suicide, PTSD, TBI, and comorbidities. The study will include clear consent
for the donation of postmortem brains and begin to establish necessary procedures for
timely collection and preservation of tissue.
Short-Term Actions (2–4 years)
Continue strategic planning for the next phase of Army STARRS.
Establish data-sharing agreements to enable the project to continue in a manner that
fosters collaboration across agencies, service branches, and scientists.
Long-Term Actions (5–10 years)
Conduct a longitudinal follow-up with Army STARRS participants through Army, DoD,
VA, and civilian records and recontact individuals (regardless of participant status and
source of health care) to conduct studies focused on identifying surrogate and clinically
actionable biomarkers, neurobiological mechanisms that may lead to suicidal behavior in
blast-exposed individuals, and psychosocial and environmental risk factors for risk and
resilience to suicide, PTSD, TBI, and comorbidities as these conditions may emerge with
the passage of time and transitions that occur as part of military service. The overall goal
is to rapidly translate findings and develop effective interventions.
Summary: The ability to monitor some cohort of the more than 100,000 enrolled participants
over the long term capitalizes on the initial Army STARRS investment. To make this monitoring
study feasible, data on emerging mental disorders and suicidal behaviors, and service member
and Veteran health care use need to be integrated. Establishing Army STARRS as a national
resource offers great hope for better understanding the long-term impact of traumatic events,
particularly service members’ experiences with combat, related military stressors, and transition
to civilian life. Finally, the ongoing and planned scientific objectives of Army STARRS are
directly relevant toward addressing the complex issues of PTSD, TBI, suicide prevention, and
related comorbidities called for throughout the Order.
Additional Collaborative Efforts
Other ongoing collaborative efforts can be leveraged to address the requirements of Section 5c in
the Order, including The Millennium Cohort Study (which includes service member and family
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cohorts), and the Million Veteran Program (MVP). Funded by the DoD and supported by
military, VA, and civilian researchers, the Millennium Cohort Study is the largest prospective
health project in military history. It was designed to examine the effects of military service on
physical and mental health outcomes and includes longitudinal cohorts of more than 200,000
service members and 10,000 spouses. The MVP is a landmark national research program that is
building one of the world’s largest medical databases by collecting blood samples and health
information from one million Veteran volunteers. Data collected from the MVP will be stored
anonymously for research to study how genes affect health. More than 175,000 Veterans have
already enrolled in the MVP (May 2013), and 50 VA medical centers nationwide are currently
participating.
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Sharing PTSD, TBI, and Suicide Prevention Research
The data-sharing requirements described in the Order impact both sharing of information related to
funding activities across agencies and, where appropriate, research study-level data. The
development and adoption of Common Data Elements (CDEs) for research present the potential
for streamlining information sharing. Within NRAP activities, a task will be to define a minimum
set of general and topic-specific CDEs that may be adopted in PTSD, TBI, and suicide prevention
research. The general CDEs may also be applied to research on co-occurring conditions (where
demographic data are collected, etc.). The effort should result in a minimum set of defined
demographic CDEs for research purposes to best accomplish study objectives while
simultaneously facilitating the comparability of data. Of note, these efforts are not focused on
sharing personally identifiable clinical data across providers of care. Instead, the agencies are
focused on data-sharing activities for research purposes that contain de-identified clinical data
(e.g., Mental Health Research Network and Federal Interagency Traumatic Brain Injury Research
[FITBIR] Informatics System) as well as de-identified data generated through primary research.
Plans must address issues surrounding de-identification and protection from re-identification of
data. Data sharing plans that are developed must also consider understandable language for
informed consent, individual privacy, confidentiality, agencies’ authority, and other policies
related to data use and sharing within a research context.
As data are shared between entities expanding beyond the initial research database, and
particularly relevant to genetic data, maintaining privacy, confidentiality, and data protection will
be paramount, especially for the population covered by the NRAP. It is important to consider how
best to protect the identity and therefore the information of research participants.
In February 2013, Dr. John Holdren, Director of the White House Office of Science and
Technology Policy (OSTP), issued a memorandum to the heads of executive departments and
agencies entitled, Increasing Access to the Results of Federally Funded Scientific Research. That
memorandum requires agencies to develop plans to increase access to the results of federally
funded scientific research including publications and data. Specifically, it requires agencies to
develop policies that “maximize access, by the general public and without charge, to digitally
formatted scientific data created with Federal funds,” with exceptions for protecting
confidentiality, privacy, and proprietary interests.
3
Both the White House memorandum and an
Executive Order issued in May 2013 on Making Open and Machine Readable the New Default for
Government Information posit that open sharing of machine-readable data fuels scientific
discovery and innovation. Consistent with the spirit of this memorandum and Executive Order,
the DoD, VA, HHS, and Department of Education will pursue improved data sharing for research
in TBI, PTSD, and related injuries and neurological conditions, and suicide prevention in concert
with emerging government-wide efforts to increase access to the results of federally funded
scientific research, aligned with protecting human subjects’ privacy and confidentiality.
Furthermore, responsibility for ensuring data sharing is not limited to data resources created as the
result of taxpayer-funded extramural research but may extend to data resources created and
owned by federal agencies themselves. The agencies intend to promote transparency with regard
3
The memorandum also specifies that each agency shall submit its draft plan to OSTP within 6 months of its
publication. Since the memo was released on February 22, 2013, the estimated response date of the agencies is
August 22, 2013. All wording regarding data sharing in the NRAP is subject to and could be superseded by the
final plans of the agencies in response to this OSTP memorandum.
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to their federal data repositories where doing so does not supersede the protection of privacy,
confidentiality, or other legal authority.
Sharing Funding Information Across Agencies
Accessible electronic information about ongoing and planned efforts supported by the federal
government is a key component to coordinating and accelerating research. Transparent and
accessible information can guide funding agencies and researchers alike to reduce overlap,
eliminate redundancies, identify gaps, and focus new research questions. Electronic access to
funded databases that yields information about grants funded in different areas of research allows
the entire scientific community to increase understanding of ongoing efforts and hone
development of the next generation of scientific questions. Publicly accessible databases that
contain information about funded grants (e.g., NIH Research Portfolio Online Reporting Tools,
which is used by the VA and NIH) act as repositories for government-sponsored research. Some
of the DoD research portfolio information is available on publicly accessed websites; however, a
new commitment will be to move the DoD’s medical research onto the NIH Research Portfolio
Online Reporting Tools via Electronic Research Administration Commons, thus promoting an
even higher level of transparency and analysis. The agencies will continue the annual review and
analysis process; the most recent meeting was held in January 2013. These efforts serve to foster
interagency collaborations and cross-pollination among researchers, with the ultimate goal of
accelerating research progress and reducing/preventing redundancy of efforts.
Sharing De-identified Research Study-Level Data as Appropriate
Access to study-level data for the purpose of secondary data analysis is important for research in
general. Data sharing with appropriate consent, confidentiality, and privacy protections within
legal authority allows for an increase in the amount of data that can be combined or compared by
the community of scientists. Many small-sized studies are able to involve only a modest number
of participants; therefore, the ability to share data when appropriate will increase the power for
analyses and potentially accelerate research progress. In addition, large-scale studies supported
by each agency provide a platform for rich secondary data analyses when data are shared. The
agencies are committed toward ensuring that data produced with federal funding are shared,
where appropriate and within legal authority, with consent and proper de-identification to
prevent risk for identification (protecting individual privacy).
Examples of study-level, data-sharing efforts include:
The FITBIR Informatics System has been established to provide a central repository for
TBI-related clinical research data. FITBIR was funded by the DoD and subsequently
developed and managed by the NIH. De-identified clinical data are entered into FITBIR
utilizing the TBI CDEs, which were developed to allow more precise comparisons of TBI
research data. Research data from newly funded NINDS and Defense Health Program
TBI clinical research projects are required to be entered into FITBIR. Although not
required, clinical research data from previously funded projects can also be entered into
FITBIR. Additionally, the TBI CDE project is developing data standards to allow
expansion of FITBIR to preclinical work, enabling advancement of preclinical
knowledge and improved modeling of TBI. This data repository standardizes the
collection of research data and allows access to researchers outside of the original
research studies to re-analyze and compare data across studies.
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Vision for Research Data Sharing
De-identified research data sharing, ideally, would be
collaborative and promote team science to more rapidly and
effectively fill gaps in knowledge that will ultimately improve
health care and outcomes. The scientific community would
be able to submit and access research data in a
participatory manner to test new hypotheses, combine data
sets for meta-analyses, and compare and contrast findings
across disorders, the lifespan, and the continuum of care.
Research data elements would be standardized to the
greatest extent possible and also aligned with clinical data
elements to enable greater integration of research and
clinical practice.
The standardization and sharing of de-identified study-level (raw) data by the NIH. Many
types of research grants supported by the NIH are required to have plans for sharing de-
identified data acquired as part of a study. For example, an investigator-initiated
application with direct costs greater than $500,000 in any single year is required to
address data sharing. Furthermore, any NIH study conducting genome-wide association
studies, used to identify common genetic factors that influence health and disease, is
required by NIH policy to (1) share de-identified data (genotypic and phenotypic)
through a centralized repository and (2) submit documentation that describes how the
institutions have considered the interests of the research participants (e.g., privacy and
confidentiality). The purpose of this NIH policy is to maximize investments and foster
science for the benefit of the public. This requirement is supported by resources such as
the NIH genome-wide association studies website (http://gwas.nih.gov).
The National Institute on Disability and Rehabilitation Research established the
longitudinal TBI Model Systems National Database (TBIMS-NDB) to provide a data
repository for clinical data on persons with moderate or severe TBI who receive
treatment in the Model Systems network of centers. This database has been shown to be
nationally representative of persons with moderate to severe TBI who receive inpatient
rehabilitation. It offers decades of information on clinical progress and outcomes
following TBI. The National Institute on Disability and Rehabilitation Research and the
VA have also partnered to create a VA Polytrauma Rehabilitation Centers TBI Database
that includes many of the same data elements found in the TBIMS-NDB.
The VA computing infrastructure allows for de-identified study data to be accessible to
VA researchers. While not limited to PTSD or TBI, this environment allows appropriate
sharing of research data within the VA. Notably, VA study-level data sharing is defined
in data use agreements and carefully considers safeguarding Veteran stakeholders
information related to de-identification.
The NIH Toolbox for the Assessment of Neurological and Behavioral Function
(http://www.nihtoolbox.org). This brief set of measures, assessing cognitive, emotional,
motor, and sensory function from 3–85 years of age, meets the need for a standard set of
measures that can be used as a “common currency” across diverse study designs and
settings. The NIH Toolbox can be used in many types of research, including research
seeking to measure changes in neurological and behavioral function over time and
evaluating intervention and treatment effectiveness.
Follow-Up Plan:
The overall goal for the NRAP related to
de-identified data sharing is centered on
accelerating research progress. The major
emphasis is on sharing data, as
appropriate, describing funded research
studies to facilitate an understanding of
what is being supported across agencies,
increase transparency in the public
domain, and reduce redundancy. Planned
compilation of funded research studies
and common coding of categories of
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research across the spectrum from basic to implementation research will allow researchers to
search for various topics across agencies to identify ongoing work (e.g., all studies that examine
PTSD and suicide attempts) and facilitate the next generation of research questions. Joining with
the NIH and VA, the DoD will pursue utilization of Electronic Research Administration
Commons, IMPAC II, and related systems for research study portfolio management.
The agencies have begun discussions related to determining how to enhance research data-
sharing efforts as appropriate. Data-sharing efforts will require close and continued collaboration
between federal agencies dedicated to addressing challenges specific to research to meet the
overall goal to increase access to study-level data.
Some exemplars of the type of activities that will meet the requirements of the Order are as
follows:
Continue to convene the joint DoD/VA/HHS/ED strategic portfolio reviews in the areas
of TBI, PTSD, suicide prevention, and substance abuse research.
Explore expansion of the Psychiatric Genomics Consortium
(https://pgc.unc.edu/index.php) to include PTSD cohorts. Research funded by federal
agencies may deposit de-identified genotypic and phenotypic data to facilitate meta-
analyses, replication, and extension of early findings.
Improve the delivery of health care services in the private sector by sharing research
findings and data through agencies (e.g., Agency for Healthcare Research and Quality),
consensus development conferences (e.g., NIH Consensus Development Program), and
practice-based research.
Develop a minimum set of defined CDEs for adoption and use in PTSD, TBI, and suicide
prevention research.
Plan to expand FITBIR to include preclinical research data. CDEs for preclinical models
will be developed. Methods will be developed to enable researchers with existing or even
completed research to more easily align their data with the CDEs, which may be
expanded to relevant mental health elements. Entry of data into FITBIR is a requirement
for all DoD-funded TBI research projects and will be a requirement for NIH TBI clinical
research projects.
Facilitate the collaboration of FITBIR with TBIMS-NDB, the International TBI Research
Initiative, and other related/relevant data repositories that can be leveraged for research,
as permissible.
Encourage use of the National Addiction and HIV Data Archive Program (NADHAP)
(http://www.icpsr.umich.edu/icpsrweb/NAHDAP/) for the purpose of archiving data.
Researchers can use the NADHAP to upload data sets relevant to substance abuse and
military and Veteran populations and use data from the NADHAP for the purpose of
secondary data analysis.
Encourage use of NIH Funding Opportunity Announcement PAR-13-080, “Accelerating
the Pace of Drug Abuse Research Using Existing Data.” The purpose of this Funding
Opportunity Announcement is to invite applications proposing the innovative analysis of
existing social science, behavioral, administrative, and neuroimaging data to study the
etiology and epidemiology of drug-using behaviors (defined as alcohol, tobacco,
prescription, and other drugs) and related disorders, associated HIV risk behaviors,
prevention of drug use and HIV, and health service utilization.
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Electronic Health Records and Research and Clinical Care
An electronic health record (EHR) is an evolving concept defined as a systematic collection of
electronic health information about individuals or populations. It is a record in digital format that
is theoretically capable of being shared across different health care settings. In some cases this
sharing can occur by way of network-connected, enterprise-wide information systems and other
information networks or exchanges. Current and future sharing capabilities will be limited to the
extent that the systems can be integrated. EHRs may include a range of data, including
demographics, medical history, medication and allergies, immunization status, laboratory test
results, radiology images, vital signs, personal stats such as age and weight, and billing
information.
EHRs primarily support clinical workflows but may also serve as a data resource that
supplements research. In addressing the Order’s requirement related to EHRs, the agencies have
focused on research applications, specifically those related to existing VA and DoD EHRs, such
as enhancing the ability to query records to understand targeted populations prior to study,
improving the ability to scope proposed problems and develop hypotheses, and identifying sites
that can serve as recruiting centers within large systems such as the VA. A fundamental
requirement of the use of EHR data in research is the protection of an individual’s confidentiality
and privacy. For example, including information on participation in a particular research study in
the medical record may have far-ranging privacy implications as medical record information is
shared. Therefore, implementations of EHR use for research purposes must ensure
confidentiality within the health care setting as well as the research setting while satisfying the
need for an accurate continuous care record.
EHRs can provide valuable data for tracking and improving patient care. Various population
health management systems have been implemented to reduce re-hospitalization and
comorbidities in civilian populations at risk for diseases such as diabetes, chronic obstructive
pulmonary disease, and cardiovascular disease. Algorithms implemented via such systems
provide feedback to clinicians to improve patient engagement and are delivered through the
clinical EHR. It is conceivable that in the future similar strategies could be used to identify
individuals requiring a particular “prevention” intervention or treatment related to TBI or PTSD,
as well as those eligible for clinical trials. One example of this is the Mental Health Research
Network (MHRN) established by NIMH. Currently, the MHRN consists of 11 research sites at
member institutions affiliated with nonprofit, integrated health care delivery systems. MHRN
member institutions belong to a consortium of 16 health care delivery organizations with
integrated research divisions known as the HMO Research Network. In addition to MHRN,
HMO Research Network has attracted other NIH-funded research programs including the Cancer
Research Network and the Cardiovascular Research Network, as well as several programs
funded by the Agency for Health Care Research and Quality.
The parent HMOs for MHRN members provide care for approximately 11 million individuals
and offer substantial resources that are useful for the conduct of mental health research. These
resources include data for large, well-defined, and diverse patient populations; long-established
administrative and medical records; long-standing patient privacy and confidentiality
protections; physician and patient web portals; biospecimen resources; linkages to other data
systems such as population-based patient registries; and capacity for rapid identification and
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Vision for Using Health Data to Improve
Outcomes
Ideally, an individual’s EHR would be continuous or accessible
across care providers, systems of care, and individuals’
lifetimes. Individuals would be able to access records in a
participatory manner to improve accuracy and continuity of care.
A population dashboard utilizing EHR would be used to monitor
trends in health and illness in relation to practice changes. EHRs
would also be used by health care providers to identify patients
meeting certain risk profiles based on trends emerging from
other patients with similar histories. Research studies aimed at
improving patient outcomes will build on EHR information with
appropriate protections and informed consent in research
studies aimed at improving patient outcomes. Overall, it is
hoped that data-driven systems would effectively and efficiently
improve the mental health and substance abuse care of service
members, Veterans, and civilians.
accrual of subjects to longitudinal retrospective and prospective cohorts for observational studies
or clinical trials. To date, MHRN investigators have enhanced a Virtual Data Warehouse to
harmonize mental health diagnosis and treatment data across all sites of the MHRN, establishing
standard definitions for key exposures and mental health outcomes. They also developed
procedures for distributing standard programs and aggregating data across sites. Other
accomplishments include conducting observational studies using the Virtual Data Warehouse to
analyze practice variation across multiple sites; organizing patient-reported outcomes data across
sites; implementing a centralized online platform for administration of standardized clinical
measures across multiple sites; and developing procedures for online electronic informed consent
and protection of personally identifiable information and transfer of sensitive data. Procedures
have also been established for the multisite collection of biological specimens, including consent,
and specimen collection and use.
Since current International Classification of Diseases diagnostic codes (versions 9/10) do not
define TBI using the VA/DoD definition, it is difficult for the agencies to use retrospective data
for epidemiological and systematic
analyses. Hurdles(e.g., “big data”
approaches to identifying new
patterns and disease processes and
time courses) must be addressed
while preserving individual privacy
and confidentiality. It is anticipated
that EHRs might have the capability
to address these needs and will also
contribute to the creation of a
continuous “learning” health care
system. The VA is currently
exploring the strategy of point-of-
care research based on clinical care
outcomes obtained directly from
EHRs and using these outcomes data
to generate knowledge about
treatment choices. For example,
clinicians could utilize the PTSD Checklist in clinical practice and log outcomes from treatment
over time in the EHR. With appropriate confidentiality and consent procedures, the PTSD
Checklist results could then be extracted from the medical record to determine the impact of
treatment and inform treatment choices.
EHRs and Research
The Order directs making better use of EHRs to gain insight into the risk and mitigation of
PTSD, TBI, and related injuries. This is relevant across research activities, and the agencies are
dedicated to determining potential EHR applicability among ongoing/new efforts and assessing
where EHR use is feasible and appropriate. However, the work related to meeting the Order
requirement is not in concert with a predetermined time line, as specific barriers may have to be
addressed (outside the scope of this NRAP) and authority for data use may have to be modified.
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While the action plan for addressing the topics of PTSD, TBI, and suicide prevention will be
coordinated through the agencies respective research offices, agency stakeholders (e.g., Military
Health System, Tricare Management Activity) and other experts will be required to address the
objectives for EHR use in research, including medical informatics, privacy, confidentiality of
records, and information technology. Together, the agencies will work with the Office of the
National Coordinator for Health Information Technology to advance information and
cooperation for emerging developments in EHRs related to the support of research, including to:
Develop a model for a population dashboard(s) that could be voluntarily used in health
systems utilizing EHRs to monitor trends, patterns, as well as impact of events on
TBI/PTSD and mental health.
Consider expanding the MHRN to include additional health systems and investigators to
focus on improvements in the prevention and treatment of TBI, PTSD, and mental health
and substance abuse.
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Funding and Prioritization
The agencies intend to focus and collaborate on
the topics identified in this document. These
efforts will be supported within existing agency
budgets. The agencies will follow their
established planning, programming, and
budgeting processes, and priorities will be
supported as feasible within available
resources. In a time of constrained resources,
the agencies will continue to direct resources to
high-priority activities.
Conclusion
The vision for PTSD, TBI, and suicide prevention
research described here will be achieved through
close, continued collaborations across agencies
and throughout the scientific community. Agency
collaborations will occur formally through joint
portfolio review and analyses of efforts aligned
with the NRAP. All of these activities will
support the research goals outlined in Sections 5a
and 5b of the Order, which include preventing
suicide; reducing the number of individuals
affected by PTSD, TBI, and substance-related
and other comorbidities; and improving the
quality of life of those who do experience these
conditions through better coordinated and synchronized efforts to accelerate progress in
prevention, diagnosis, and treatment. Additionally, Army STARRS and other large collaborative
efforts (e.g., Millennium Cohort Study and Million Veteran Program) are responsive to Section
5c of the Order, which directs that the DoD and HHS engage in a comprehensive longitudinal
mental health study with an emphasis on PTSD, TBI, and related injuries to develop better
prevention, diagnosis, and treatment options. New large collaborations (e.g., Consortium to
Alleviate PTSD and Chronic Effects of Neurotrauma Consortium) will also directly respond to
the Order and contribute to our goal to advance effective diagnosis and prevention and treatment
interventions. The agencies look forward to fulfilling this NRAP with the anticipation that it will
directly benefit Veterans, military service members, and their families.
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Documents Consulted
The following documents were referenced in preparation of this report:
2013 Interim Report of the Interagency Task Force on Military and Veterans Mental
Health, Issued in May 2013.
Army Health Promotion Risk Reduction Suicide Prevention Report. Issued in July 2010.
Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury.
IOM. 2009. Washington, DC: The National Academies Press.
Increasing Access to the Results of Federally Funded Scientific Research. Memo issued
in February 2013 by Dr. John Holdren, Director of the Office of Science and Technology
Policy.
Making Open and Machine Readable the New Default for Government Information.
Executive Order issued on May 9, 2013, by President Barack Obama.
National Institute of Mental Health Strategic Plan. Issued in August 2008.
Psychological Health and Traumatic Brain Injury Portfolio Review and Analysis Report.
(Summary of the meeting sponsored by the DHP and held on July 28, 2010, at Fort
Detrick, Maryland.)
Psychological Health and Traumatic Brain Injury Portfolio Review and Analysis Report.
(Summary of the meeting sponsored by the DHP and VA, and held on
November 30–December 1, 2011, at Fort Detrick, Maryland.)
Psychological Health and Traumatic Brain Injury Portfolio Review and Analysis Report.
(Draft summary of the meeting sponsored by the DHP, VA, NIH, and ED, and held on
January 6–7, 2013, at Fort Detrick, Maryland.)
Returning Home from Iraq and Afghanistan: Assessment of Readjustment Needs of
Veterans, Service Members, and Their Families. IOM. 2013. Washington, DC: The
National Academies Press.
Returning Home from Iraq and Afghanistan: Preliminary Assessment of Readjustment
Needs of Veterans, Service Members, and Their Families. IOM. 2010. Washington, DC:
The National Academies Press.
Substance Use Disorders in the U.S. Armed Forces. IOM. 2012. Washington, DC: The
National Academies Press.
Toward Precision Medicine: Building a Knowledge Network for Biomedical Research
and a New Taxonomy of Disease. IOM. 2011. Washington, DC: The National
Academies Press.
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Appendix: The Executive Order
The White House
Office of the Press Secretary
For Immediate Release August 31, 2012
Executive Order – Improving Access to Mental Health Services for
Veterans, Service Members, and Military Families
EXECUTIVE ORDER
IMPROVING ACCESS TO MENTAL HEALTH SERVICES FOR VETERANS, SERVICE MEMBERS, AND
MILITARY FAMILIES
By the authority vested in me as President by the Constitution and the laws of the United States of
America, I hereby order as follows:
Section 1. Policy. Since September 11, 2001, more than two million service members have deployed to
Iraq or Afghanistan. Long deployments and intense combat conditions require optimal support for the
emotional and mental health needs of our service members and their families. The need for mental
health services will only increase in the coming years as the Nation deals with the effects of more than a
decade of conflict. Reiterating and expanding upon the commitment outlined in my Administration's 2011
report, entitled "Strengthening Our Military Families," we have an obligation to evaluate our progress and
continue to build an integrated network of support capable of providing effective mental health services
for veterans, service members, and their families. Our public health approach must encompass the
practices of disease prevention and the promotion of good health for all military populations throughout
their lifespans, both within the health care systems of the Departments of Defense and Veterans Affairs
and in local communities. Our efforts also must focus on both outreach to veterans and their families and
the provision of high quality mental health treatment to those in need. Coordination between the
Departments of Veterans Affairs and Defense during service members' transition to civilian life is
essential to achieving these goals.
Ensuring that all veterans, service members (Active, Guard, and Reserve alike), and their families receive
the support they deserve is a top priority for my Administration. As part of our ongoing efforts to improve
all facets of military mental health, this order directs the Secretaries of Defense, Health and Human
Services, Education, Veterans Affairs, and Homeland Security to expand suicide prevention strategies
and take steps to meet the current and future demand for mental health and substance abuse treatment
services for veterans, service members, and their families.
Sec. 2. Suicide Prevention. (a) By December 31, 2012, the Department of Veterans Affairs, in
continued collaboration with the Department of Health and Human Services, shall expand the capacity of
the Veterans Crisis Line by 50 percent to ensure that veterans have timely access, including by
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telephone, text, or online chat, to qualified, caring responders who can help address immediate crises
and direct veterans to appropriate care. Further, the Department of Veterans Affairs shall ensure that any
veteran identifying him or herself as being in crisis connects with a mental health professional or trained
mental health worker within 24 hours. The Department of Veterans Affairs also shall expand the number
of mental health professionals who are available to see veterans beyond traditional business hours.
(b) The Departments of Veterans Affairs and Defense shall jointly develop and implement a national
suicide prevention campaign focused on connecting veterans and service members to mental health
services. This 12 month campaign, which shall begin on September 1, 2012, will focus on the positive
benefits of seeking care and encourage veterans and service members to proactively reach out to
support services.
(c) To provide the best mental health and substance abuse prevention, education, and outreach support
to our military and their family members, the Department of Defense shall review all of its existing mental
health and substance abuse prevention, education, and outreach programs across the military services
and the Defense Health Program to identify the key program areas that produce the greatest impact on
quality and outcomes, and rank programs within each of these program areas using metrics that assess
their effectiveness. By the end of Fiscal Year 2014, existing program resources shall be realigned to
ensure that highly ranked programs are implemented across all of the military services and less effective
programs are replaced.
Sec. 3. Enhanced Partnerships Between the Department of Veterans Affairs and Community Providers.
(a) Within 180 days of the date of this order, in those service areas where the Department of Veterans
Affairs has faced challenges in hiring and placing mental health service providers and continues to have
unfilled vacancies or long wait times, the Departments of Veterans Affairs and Health and Human
Services shall establish pilot projects whereby the Department of Veterans Affairs contracts or develops
formal arrangements with community based providers, such as community mental health clinics,
community health centers, substance abuse treatment facilities, and rural health clinics, to test the
effectiveness of community partnerships in helping to meet the mental health needs of veterans in a
timely way. Pilot sites shall ensure that consumers of community-based services continue to be
integrated into the health care systems of the Department of Veterans Affairs. No fewer than 15 pilot
projects shall be established.
(b) The Department of Veterans Affairs shall develop guidance for its medical centers and service
networks that supports the use of community mental health services, including telehealth services and
substance abuse services, where appropriate, to meet demand and facilitate access to care. This
guidance shall include recommendations that medical centers and service networks use community-
based providers to help meet veterans' mental health needs where objective criteria, which the
Department of Veterans Affairs shall define in the form of specific metrics, demonstrate such needs.
Such objective criteria should include estimates of wait-times for needed care that exceed established
targets.
(c) The Departments of Health and Human Services and Veterans Affairs shall develop a plan for a rural
mental health recruitment initiative to promote opportunities for the Department of Veterans Affairs and
rural communities to share mental health providers when demand is insufficient for either the Department
of Veterans Affairs or the communities to independently support a full time provider.
Sec. 4. Expanded Department of Veterans Affairs Mental Health Services Staffing. The Secretary of
Veterans Affairs shall, by December 31, 2013, hire and train 800 peer to peer counselors to empower
veterans to support other veterans and help meet mental health care needs. In addition, the Secretary
shall continue to use all appropriate tools, including collaborative arrangements with community based
providers, pay setting authorities, loan repayment and scholarships, and partnerships with health care
workforce training programs to accomplish the Department of Veterans Affairs' goal of recruiting, hiring,
and placing 1,600 mental health professionals by June 30, 2013. The Department of Veterans Affairs
also shall evaluate the reporting requirements associated with providing mental health services and
reduce paperwork requirements where appropriate. In addition, the Department of Veterans Affairs shall
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update its management performance evaluation system to link performance to meeting mental health
service demand.
Sec. 5. Improved Research and Development. (a) The lack of full understanding of the underlying
mechanisms of Post Traumatic Stress Disorder (PTSD), other mental health conditions, and Traumatic
Brain Injury (TBI) has hampered progress in prevention, diagnosis, and treatment. In order to improve
the coordination of agency research into these conditions and reduce the number of affected men and
women through better prevention, diagnosis, and treatment, the Departments of Defense, Veterans
Affairs, Health and Human Services, and Education, in coordination with the Office of Science and
Technology Policy, shall establish a National Research Action Plan within 8 months of the date of this
order.
(b) The National Research Action Plan shall include strategies to establish surrogate and clinically
actionable biomarkers for early diagnosis and treatment effectiveness; develop improved diagnostic
criteria for TBI; enhance our understanding of the mechanisms responsible for PTSD, related injuries, and
neurological disorders following TBI; foster development of new treatments for these conditions based on
a better understanding of the underlying mechanisms; improve data sharing between agencies and
academic and industry researchers to accelerate progress and reduce redundant efforts without
compromising privacy; and make better use of electronic health records to gain insight into the risk and
mitigation of PTSD, TBI, and related injuries. In addition, the National Research Action Plan shall include
strategies to support collaborative research to address suicide prevention.
(c) The Departments of Defense and Health and Human Services shall engage in a comprehensive
longitudinal mental health study with an emphasis on PTSD, TBI, and related injuries to develop better
prevention, diagnosis, and treatment options. Agencies shall continue ongoing collaborative research
efforts, with an aim to enroll at least 100,000 service members by December 31, 2012, and include a plan
for long term follow up with enrollees through a coordinated effort with the Department of Veterans
Affairs.
Sec. 6. Military and Veterans Mental Health Interagency Task Force. There is established an
Interagency Task Force on Military and Veterans Mental Health (Task Force), to be co chaired by the
Secretaries of Defense, Veterans Affairs, and Health and Human Services, or their designated
representatives.
(a) Membership. In addition to the Co-Chairs, the Task Force shall consist of representatives from:
(i) the Department of Education;
(ii) the Office of Management and Budget;
(iii) the Domestic Policy Council;
(iv) the National Security Staff;
(v) the Office of Science and Technology Policy;
(vi) the Office of National Drug Control Policy; and
(vii) such other executive departments, agencies, or offices as the Co-Chairs may designate.
A member agency of the Task Force shall designate a full time officer or employee of the Federal
Government to perform the Task Force functions.
(b) Mission. Member agencies shall review relevant statutes, policies, and agency training and guidance
to identify reforms and take actions that facilitate implementation of the strategies outlined in this order.
Member agencies shall work collaboratively on these strategies and also create an inventory of mental
health and substance abuse programs and activities to inform this work.
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(c) Functions.
(i) Not later than 180 days after the date of this order, the Task Force shall submit recommendations to
the President on strategies to improve mental health and substance abuse treatment services for
veterans, service members, and their families. Every year thereafter, the Task Force shall provide to the
President a review of agency actions to enhance mental health and substance abuse treatment services
for veterans, service members, and their families consistent with this order, as well as provide additional
recommendations for action as appropriate. The Task Force shall define specific goals and metrics that
will aid in measuring progress in improving mental health strategies. The Task Force will include cost
analysis in the development of all recommendations, and will ensure any new requirements are supported
within existing resources.
(ii) In addition to coordinating and reviewing agency efforts to enhance veteran and military mental
health services pursuant to this order, the Task Force shall evaluate:
(1) agency efforts to improve care quality and ensure that the Departments of Defense and Veterans
Affairs and community based mental health providers are trained in the most current evidence based
methodologies for treating PTSD, TBI, depression, related mental health conditions, and substance
abuse;
(2) agency efforts to improve awareness and reduce stigma for those needing to seek care; and
(3) agency research efforts to improve the prevention, diagnosis, and treatment of TBI, PTSD, and
related injuries, and explore the need for an external research portfolio review.
(iii) In performing its functions, the Task Force shall consult with relevant nongovernmental experts and
organizations as necessary.
Sec. 7. General Provisions. (a) This order shall be implemented consistent with applicable law and
subject to the availability of appropriations.
(b) Nothing in this order shall be construed to impair or otherwise affect:
(i) the authority granted by law to an executive department or agency, or the head thereof; or
(ii) the functions of the Director of the Office of Management and Budget relating to budgetary,
administrative, or legislative proposals.
(c) This order is not intended to, and does not, create any right or benefit, substantive or procedural,
enforceable at law or in equity by any party against the United States, its departments, agencies, or
entities, its officers, employees, or agents, or any other person.
BARACK OBAMA
THE WHITE HOUSE,
August 31, 2012