W81XWH-22-S-TBIPH2-FPA-GG2.pdf

This Broad Agency Announcement must be read in conjunction with the General Submission Instructions, which are available for downloading from the Grants.gov funding opportunity announcement by selecting the “Package” tab, clicking “Preview,” and then selecting “Download Instructions.”

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 1

I. OVERVIEW OF THE FUNDING OPPORTUNITY

Broad Agency Announcement for Extramural Research (Program Specific) for the Department of Defense

Defense Health Program

Congressionally Directed Medical Research Programs

Traumatic Brain Injury and Psychological Health Research Program

Focused Program Award

Announcement Type: Modified

Funding Opportunity Number: W81XWH-22-S-TBIPH2

Assistance Listing Number: 12.420 Military Medical Research and Development

SUBMISSION AND REVIEW DATES AND TIMES

• Pre-Proposal/Pre-Application Submission Deadline: 5:00 p.m. Eastern time (ET), September 1, 2022

• Invitation to Submit a Proposal/Application: October 13, 2022

• Proposal/Application Submission Deadline: 11:59 p.m. ET, December 08, 2022

• End of Proposal/Application Verification Period: 5:00 p.m. ET, December 13, 2022

• Peer Review: February 2023

• Programmatic Review: April 2023

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 2

TABLE OF CONTENTS

I. OVERVIEW OF THE FUNDING OPPORTUNITY

II. DETAILED INFORMATION ABOUT THE FUNDING OPPORTUNITY

II.A. Program Description

II.A.1. FY22 TBIPHRP Focus Areas

II.B. Award Information

II.C. Eligibility Information

II.C.1. Eligible Applicants

II.C.2. Cost Sharing

II.C.3. Other

II.D. Proposal/Application and Submission Information

II.D.1. eBRAP and Grants.gov

II.D.2. Content and Form of the Application Submission

II.D.3. Unique Entity Identifier (UEI) and System for Award Management (SAM)

II.D.4. Submission Dates and Times

II.D.5. Intergovernmental Review

II.D.6. Funding Restrictions

II.D.7. Other Submission Requirements

II.E. Proposal/Application Review Information

II.E.1. Criteria

II.E.2. Proposal/Application Review and Selection Process

II.E.3. Integrity and Performance Information

II.E.4. Anticipated Announcement and Federal Award Dates

II.F. Federal Award Administration Information

II.F.1. Federal Award Notices

II.F.2. Administrative and National Policy Requirements

II.F.3. Reporting

II.G. Federal Awarding Agency Contacts

II.G.1. CDMRP Help Desk

II.G.2. Grants.gov Contact Center

II.H. Other Information

II.H.1. Administrative Actions

II.H.2. Proposal/Application Submission Checklist

APPENDIX I: ACRONYM LIST

APPENDIX II: DOD and VA WEBSITES

APPENDIX III: SAMPLE NDA CONSENT LANGUAGE

APPENDIX IV: SAMPLE FITBIR CONSENT LANGUAGE

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 3

II. DETAILED INFORMATION ABOUT THE FUNDING

OPPORTUNITY

Proposal/application submission by extramural organizations through Grants.gov requires use of the Workspace interface, which separates the application package into individual forms. Applicants must create a Workspace in Grants.gov, complete the required forms, and submit their application Workspace package.

This Funding Opportunity Announcement is a Broad Agency Announcement (BAA) through the Fiscal Year 2022 (FY22) Traumatic Brain Injury and Psychological Health Research Program (TBIPHRP) for the Focused Program Award (FPA). For the remainder of the announcement, this BAA will be referenced as the FY22 TBIPHRP FPA. Specific submission information and additional administrative requirements can be found in the document titled “General Submission Instructions,” available in Grants.gov along with this BAA.

This BAA for the FY22 TBIPHRP is intended to solicit extramural research and development ideas using the authority provided by United States Code, Title 10, Section 4001(10 USC4001). This BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in Federal Acquisition Regulation (FAR) 6.102(d)(2) and 35.016 and in Department of Defense Grant and Agreement Regulations (DoDGARs) 22.315. In accordance with FAR 35.016, projects funded under this BAA must be for clinical research not related to the development of a specific system or hardware procurement. Research and development funded through this BAA is intended and expected to benefit and inform both military and civilian medical practice and knowledge.

This BAA is intended for extramural applicants only. For definitions and additional information, see Section II.C.1, Eligible Applicants.

II.A. Program Description

Proposals/applications to the FY22 TBIPHRP FPA are being solicited by the U.S. Army Medical Research Acquisition Activity (USAMRAA) using delegated authority provided by 10 USC 4001. The execution management agent for this BAA is the Congressionally Directed Medical Research Programs (CDMRP) at the U.S. Army Medical Research and Development Command

(USAMRDC).

In FY07, Congress appropriated funding for traumatic brain injury (TBI) and psychological health research in response to the TBIs sustained and psychological health issues experienced by our deployed forces in Iraq and Afghanistan. The TBIPHRP complements ongoing Department of Defense (DOD) efforts toward promoting a better standard of care for TBI and psychological health in the areas of prevention, detection, diagnosis, treatment, and rehabilitation.

Appropriations for the TBIPHRP from FY07 through FY21 totaled $2.047 billion. The FY22 appropriation is $175 million (M).

The TBIPHRP’s vision is to optimize the prevention, assessment, and treatment of psychological health conditions and/or traumatic brain injuries. Proposed research can be aligned with TBI, DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 4 psychological health, or both. The program seeks to fund research that accelerates solutions to improve the health, well-being, and healthcare of Service Members, Veterans, military beneficiaries, and the American public. Proposed research must be relevant to active-duty Service Members, Veterans, military beneficiaries, and/or the American public.

In April 2021, the TBIPHRP held a Stakeholders Meeting to engage TBI and psychological health academic, clinical, lived experience (consumers), and government subject matter experts in an open-dialogue forum to identify critical issues and underfunded areas in TBI and psychological health research and care. This meeting was attended by representatives from non-profit organizations, academia, government agencies, and the public. Outcomes from this meeting were considered by the TBIPHRP Programmatic Panel in development of the FY22 program. The FY21 Stakeholders Booklet and Meeting Summary, including presentation materials can be found at https://cdmrp.army.mil/tbiphrp/.

II.A.1. FY22 TBIPHRP Focus Areas

The FY22 TBIPHRP has identified the following Focus Areas for funding under the FY22 TBIPHRP FPA. To meet the intent of the award mechanism, proposals/applications must address at least one sub-area (e.g. 1a, 1b, 2a, 2b etc.) within one of the three FY22 TBIPHRP FPA Focus Areas listed below. Bulleted items are provided to indicate additional context regarding programmatic intent but not required to be specifically addressed by applications.

Proposed research must be hypothesis driven and can be aligned with TBI, psychological health, or both. Selection of the appropriate FY22 TBIPHRP FPA Focus Area(s) is the responsibility of the applicant.

1. Understand: Research will address knowledge gaps in foundational science, epidemiology, and etiology of psychological health conditions and/or TBI.

a. Understanding of risk, protective, and biological factors contributing to an individual’s vulnerability to, response to, and long-term outcomes psychological health conditions and/or TBI. Studies with a biomarker component are allowed. Research of interest includes, but is not limited to:

• Understanding psychological health trajectories associated with trauma and suicidality that incorporate internal and external factors. For example, factors could include time course, demographic characteristics, career course, history of trauma exposure, and community and cultural factors.

• Understanding how the approach to psychiatric diagnosis in the military relates to occupational impairment and/or military separation

• Understanding the role of genetics, endophenotypes, health demographics, previous injuries or repetitive exposures, psychological health conditions, pathophysiology, and environmental factors (e.g., extreme temperatures/pressures) on TBI.

https://cdmrp.army.mil/tbiphrp/

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 5

• Understanding the contribution of pre- and post-injury patient, family1 and caregiver education, as well as cultural, demographic, stigma, and bias factors that may relate to treatment-seeking and adherence.

• Development and analysis of computational models from clinical data to forecast the long-term and/or late effects of brain exposures, such as TBI, and co-occurring conditions.

• Development and analysis of communication and tools/technology adoption that would facilitate clinical translation and identification of risk factors, educational barriers, social determinates of health, and other factors that may impede clinical translation.

b. Understanding sexual harassment and assault prevention, perpetration, victimization, and response. Methodologies that ensure anonymity for participants are encouraged.

Research of interest includes, but is not limited to:

• Understanding processes of shame, stigma, and institutional betrayal among sexual assault victims and their units/teams and evaluation of approaches to mitigate these experiences. Experiences of marginalized groups, male victims, and victims of intimate partner and family1 violence are of particular interest.

• Understanding how organizational-level factors influence interpersonal and individual conditions, choices, behaviors, and psychological health as they relate to sexual assault and harassment prevention, perpetration, and response. Measurement and analysis of organizational-level factors, such as culture and climate, beyond aggregating individual perceptions are encouraged. Research could include the progression from sexual harassment to sexual assault and factors influencing sexual harassment.

• Understanding barriers to reporting sexual assault and factors that contribute to retaliation within units/teams and evaluation of approaches to mitigate barriers, prevent retaliation, and improve psychological health outcomes of victims. Research could include data from influencers, bystanders, and perpetrators, as well as environmental, structural, and demographic factors (e.g., workplace culture, climate, senior leader diversity, age, gender).

• Understanding the psychological consequences of intimate partner and family violence.

2. Prevent and Assess: Research will address the prevention or progression of psychological health conditions and/or TBI through population, selective, and indicated prevention approaches. Efforts that focus on primary prevention (including protection), screening, diagnosis, and prognosis are within scope.

1 “Family” should be broadly defined to include not just spouses, but also parents, significant others/fiancés/partners, children, caregivers, or close friends.

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 6

a. Identification and validation of biomarkers or other objective markers for diagnosis, prognosis, or monitoring of psychological health conditions and/or TBI, repetitive exposures, and associated sequelae (e.g., chronic migraine, dizziness, neurocognitive symptoms, sleep, post-traumatic headache, secondary complications). When appropriate, evaluation of U.S. Food and Drug Administration (FDA)-cleared/approved products for new indications or in intended populations/context is encouraged.

b. Approaches or tools to prevent or reduce risk of psychological health conditions and/or TBI. Research of interest includes, but is not limited to:

• Translation of environmental sensor outputs to conditions within the brain.

• Development of innovative materials and technologies that can prevent or reduce risk of TBI.

• Generation of physiological evidence regarding the safety, efficacy, and utility of candidate neuroprotective measures. Animal models, if used, should be validated and well justified within the literature and should demonstrate clear alignment to clinical populations.

• Validation of objective tools/methods for assessing and real-time health status monitoring of psychological health conditions and/or TBI.

• Development of clinical decision-making frameworks or tools that incorporate objective assessments and long-term outcomes to return to activity/duty decisions.

c. Development of injury thresholds and exposure standards.

d. Development, evaluation, and implementation of cross-cutting prevention approaches targeting upstream factors or leveraging communities and peers to address multiple adverse outcomes such as suicide, multiple forms of violence, and alcohol and substance misuse. Examples of upstream factors could include social connectedness, inclusiveness, culture, problem-solving, emotional regulation, communication, underlying health disparities, financial stability, geographical isolation, rural challenges, and environmental extremes. Research of interest may include, but is not limited to:

• Optimized messaging for successful dissemination and implementation.

• Inclusion of families and evaluation of family impact.

• Culturally acceptable approaches to reducing access to lethal means and promoting means safety for suicide and violence prevention.

e. Solutions to increase readiness and resilience in individuals, small teams, families, and communities to ameliorate the potential negative impacts of specific military and life stressors. Research of interest includes, but is not limited to:

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 7

• Effective pharmacologic or non-pharmacologic prevention interventions. Solutions for prevention of acute stress reactions (ASRs) and Posttraumatic Stress Disorder (PTSD) may be proposed.

• Preparation of Service Members and units for missions and to help reset between deployments within the Sustainable Readiness Model.2

• Effective solutions to support relationships and parenting, prepare families for potential secondary trauma exposure, and empower families to access tailored support and resources.

f. Solutions to address aspects of workplace culture and climate (e.g., leadership attitudes, group characteristics, group identification factors) that are associated with increases in harmful behaviors. Research of interest includes, but is not limited to, solutions to provide and incentivize positive options and substitutes for alcohol and substance use and promote pro-social behavioral norms.

3. Treat: Research will address immediate and long-term treatments and improvements in systems of care, including access to and delivery of healthcare services. Treatment topics may include novel treatments and interventions, personalized medicine approaches, length and durability of treatment, rehabilitation, relapse, and relapse prevention.

a. Interventions that promote sustained functional recovery, including interventions administered acutely, during the post-acute phase, or during the chronic phase of injury.

Research of interest includes, but is not limited to:

• Rapid assessments and treatments for psychological health conditions. Interventions addressing adjustment disorders, ASRs, and PTSD may be proposed.

• Interventions focused on sensory and motor dysfunction after brain injury.

• Interventions that address neurodegenerative processes associated with TBI.

• Interventions that restore cognitive reserve and functioning.

• Novel therapeutic candidates based on evolving changes of pathophysiology and/or theoretical mechanisms of psychological health conditions and/or TBI.

• Interventions and/or the delivery of healthcare services to improve the ability to treat co-occurring psychological health conditions and/or TBI.

• Personalized medicine approaches to treatment that may include tailoring treatment to the biological and endophenotypic elements present. Treatment approaches may consider how TBI, PTSD, depression, or other psychological health conditions are interrelated.

2 https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/ARN9412_AR525_29_FINAL.pdf https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/ARN9412_AR525_29_FINAL.pdf

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 8

• Considerations for sequencing and optimal combinations of pharmacologic and non-pharmacologic interventions.

• Effective, early interventions for delivery in rural or other resource-limited environments (e.g., far-forward military environments), and/or by non-clinicians (e.g., peers, teams, first responders/medics).

b. Validated individual-, peer-/unit-/team-, leader-, family-, caregiver-, community-, and enterprise-level methods for reducing barriers to care for psychological health conditions and/or TBI challenges (e.g., PTSD, suicidal ideation or behaviors, alcohol and substance use, anxiety, depression) and understanding mechanisms of change in help-seeking behavior.

c. Implementation, follow-up, and services research to increase provider adoption and availability of evidence-based treatments, as well as treatment engagement, follow-up care, and understanding of long-term outcomes. Research of interest includes, but is not limited to:

• Clinical effectiveness studies comparing new/novel capabilities to existing evidence-based treatments and/or the standard of care.

• Identification and evaluation of methods for successful dissemination and implementation of interventions.

d. Effective community-level postvention strategies to address social connectedness during reintegration of individuals into workplace teams or the community following a sexual assault, suicide event, or other severe trauma. Proposed research should also consider preventing subsequent suicides or other counterproductive behaviors among individuals and community members.

II.B. Award Information

The intent of the FY22 TBIPHRP FPA is to optimize research and accelerate solutions to a critical question related to at least one sub-area within one of the three FY22 TBIPHRP FPA Focus Areas. The award mechanism supports development of a synergistic, multidisciplinary research program with the potential to have a significant impact on psychological health conditions and/or TBI through clinical applications, including healthcare products, technologies, and/or practice guidelines. Proposals/applications may propose applied/preclinical/clinical research and clinical trials. Clinical trials may be designed to evaluate promising new products, new indications, pharmacologic agents (drugs or biologics), devices, clinical guidance, and/or emerging approaches and technologies. Hypothesis-driven health services research, implementation science, and follow-up care research are also within scope for this mechanism.

Proposed clinical trials should demonstrate feasibility or inform the design of more advanced trials that determine efficacy in relevant patient populations.

Key aspects of this award include:

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 9

Overarching Challenge: FPA proposals/applications must describe a unifying, overarching challenge that will be addressed by the set of research projects proposed. The overarching challenge must be relevant to a critical problem or question in the field of research and/or patient care in at least one sub-area within one of the three FY22 TBIPHRP FPA Focus Areas.

Research Projects: Proposals/applications shall include multiple, distinct research projects led by individual project leaders that address complementary aspects of the overarching challenge.

Applicants are strongly encouraged to submit a minimum of four research projects; additional studies are allowed. While individual projects must be capable of standing on their own high scientific merits, they must also be interrelated, synergistic, and align with the overarching challenge to advance a solution beyond what would be possible through individual efforts. The exploration of multiple hypotheses or viewpoints of the same line of questioning is encouraged.

This award mechanism is not intended to support a series of research projects that are dependent on the success of one of the other projects. Each project should propose a unique approach to addressing the overarching challenge and be capable of producing research findings with potential to impact the field and/or patient care. Individual research projects may include applied research, preclinical research, clinical research and clinical trials. Proposed research projects should not include basic research.3 Preliminary data should be included to support each project’s hypothesis/objective(s). There should be a clear intent to progress toward translational/clinical work over the course of the effort.

Implementation: The research strategy to address the overarching challenge must be supported by a detailed implementation plan that identifies critical milestones and outlines the knowledge, resources, and technical innovations that will be utilized to achieve the milestones. A robust statistical plan and statistical expertise should be included where applicable. A plan for assessing individual project performance and progress toward addressing the overarching challenge must be included in the implementation plan. Plans to include an External Advisory Board (EAB) are encouraged; however, applicants must be careful to avoid potential conflicts of interest (COIs) during review of the proposal/application by ensuring no contact with, recruiting of, or naming of specific EAB members in the proposal/application. For multi-institutional collaborations, plans for communication and data transfer among the collaborating institutions, as well as how data, specimens, and/or products obtained during the study will be handled, must be included. An appropriate intellectual and material property plan agreed to by participating organizations is required in the proposal/application’s supporting documentation.

Research Team: The overall effort will be led by a Principal Investigator (PI) with demonstrated success in leading large, focused projects. The PI is required to devote a minimum of 20% effort to this award. The PI should create an environment that fosters and supports collaboration and innovation in a way that engages all members of the team in all aspects of the research plan. The research team assembled by the PI should be highly qualified and multidisciplinary, with identified project leaders for each of the complementary and synergistic research projects. The resources and expertise brought to the team by each project leader should combine to create a robust, synergistic collaboration. The TBIPHRP Science Officer assigned to a resulting award should be invited to participate in research team meetings (e.g., annual

3 Basic research is defined as research directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications toward process or products in mind.

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 10 meetings of the entire research team). The plan for such meetings should be noted in the proposal/application.

Milestone Meeting: The PI will be required to present an update on progress toward accomplishing the goals of the award at a Milestone Meeting to be held in the National Capital Area after the conclusion of year 2 of the period of performance. The PI may bring up to three additional members of the research team to the meeting. The Milestone Meeting will be attended by members of the TBIPHRP Programmatic Panel, CDMRP staff, the USAMRAA Grants/Contracts Officer, and other DOD stakeholders.

Relevance to Military Health: Relevance to the healthcare needs of Service Members, DOD beneficiaries, and Veterans is a key feature of this award. Investigators are encouraged to consider the following characteristics as examples of how a project may demonstrate relevance to military health:

• Explanation of how the project addresses an aspect of psychological health conditions and/or TBI that has direct relevance to the health and/or readiness Service Members, DOD beneficiaries, and Veterans

• Description of how the knowledge, information, products, or technologies gained from the proposed research could be implemented in a dual-use capacity to benefit the civilian population and also address a military need

• Use of military or Veteran populations, samples, or datasets in the proposed research, if appropriate

• Collaboration with DOD or Department of Veterans Affairs (VA) investigators or consultants

Applicants are encouraged to integrate and/or align their research projects with DOD and/or VA research laboratories and programs. Collaborations between researchers at military or Veterans institutions and non-military institutions are strongly encouraged. These relationships can leverage knowledge, infrastructure, and access to unique data and research resources that the partners bring to the research effort, ultimately advancing TBI and psychological health research of significance to Service Members, DOD beneficiaries, and Veterans. A list of websites that may be useful in identifying additional information about ongoing DOD and VA areas of research interest or potential opportunities for collaboration can be found in Appendix II.

Use of DOD or VA Resources: If the proposed research involves access to VA or DOD patient populations, resources, or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Refer to Section II.D.2.b.ii, Full Application Submission Components, for detailed information. Refer to the General Submission Instructions, Appendix 1, for additional information.

Access to certain DOD or VA patient populations, resources, or databases may only be obtained by collaboration with a DOD or VA investigator who has a substantial role in the research and may not be available to a non-DOD or non-VA investigator if the resource is restricted to DOD

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 11 or VA personnel. Investigators should be aware of which resources are available to them if the proposed research involves a non-DOD or non-VA investigator collaborating with the DOD and/or VA. If the proposal/application is recommended for funding, the government reserves the right to withdraw or revoke funding until the PI has demonstrated support for and access to the relevant population(s) and/or resource(s).

Conducting DOD-Funded Human Research with Military Populations: There are unique requirements and prohibitions for compensating DOD-affiliated personnel for study participation and for conducting research with military families/children and U.S. Army Special Operations Command populations. Additional information regarding conducting DOD-funded human research with military populations can be found at https://cdmrp.army.mil/pubs/pdf/ Conducting%20Research%20Military%20Pop%20DOD_June%202021.pdf.

The anticipated direct costs budgeted for the entire period of performance for an FY22 TBIPHRP FPA will not exceed $5M. Refer to Section II.D.6, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2023. For additional information refer to Section II.F.1, Federal Award Notices.

The USAMRDC executes its extramural research program primarily through the awarding of contracts and assistance agreements (grants and cooperative agreements). The type of instrument used to reflect the business relationship between the organization and the government is at the discretion of the government, in accordance with the Federal Grant and Cooperative Agreement Act of 1977, as amended, 31 USC 6301-6308, which provides the legal criteria to select a procurement contract or an assistance agreement. An assistance agreement (grant or cooperative agreement) is appropriate when the federal government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States, instead of acquiring property or service for the direct benefit and use of the U.S. government. An assistance agreement can take the form of a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304).

Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305) and the award will identify the specific substantial involvement. Substantial involvement may include collaboration, participation, or intervention in the research to be performed under the award.

A contract is required when the principal purpose of the instrument is to acquire property or services for the direct benefit or use of the U.S. government.

The award type, along with the start date, will be determined during the negotiation process.

Please see Appendix 2, Section E, of the General Submission Instructions for more information.

The CDMRP expects to allot approximately $31M to fund approximately four FY22 TBIPHRP FPA proposals/applications. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications https://cdmrp.army.mil/pubs/pdf/Conducting%20Research%20Military%20Pop%20DOD_June%202021.pdf https://cdmrp.army.mil/pubs/pdf/Conducting%20Research%20Military%20Pop%20DOD_June%202021.pdf

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 12 received, the quality and merit of the applications as evaluated by scientific and programmatic review, and the requirements of the government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY22 funding opportunity will be funded with FY22 funds, which will expire for use on September 30, 2028.

This BAA may support applied research, preclinical research, clinical research, and clinical trials/testing (or equivalent). FPA proposals/applications that include a clinical trial have additional proposal/application and review requirements. This BAA may not be used to support studies requiring an exception from informed consent (EFIC). For more information, see Section II.D.2, Content and Form of the Proposal/Application Submission and Section II.E.1, Criteria.

A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or another control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. Funded trials are required to post a copy of the Institutional Review Board (IRB)-approved informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in the Code of Federal Regulations, Title 32, Part 219 (32 CFR 219).

Clinical research is defined as: (1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies; (2) epidemiologic and behavioral studies; and (3) outcomes research and health services research. Note: Studies that meet the requirements for IRB review Exemption 4 are not considered CDMRP-defined clinical research. IRB Exemption 4 refers to research involving the collection or study of existing de-identified specimens or data, if these sources are publicly available.

If the proposed clinical trial involves the use of a drug that has not been approved by the FDA for the proposed investigational use, then an Investigational New Drug (IND) application to the FDA that meets all requirements under 21 CFR 312 may be required. It is the responsibility of the applicant to provide evidence from the IRB of record or the FDA if an IND application is not required. If an IND application is required, evidence that an IND application has been submitted or IND authorization without clinical hold status has been secured must be included in the FY22 TBIPHRP FPA proposal/application. The IND application should be specific for the product (i.e., the product should not represent a derivative or alternate version of the investigational agent described in the IND application) and indication to be tested in the proposed clinical trial. For more information on IND applications, the FDA has provided guidance at https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/ap provalapplications/investigationalnewdrugindapplication/default.htm.

https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 13

If the investigational product is a device, then an Investigational Device Exemption (IDE) application to the FDA that meets all requirements under 21 CFR 812 may be required. It is the responsibility of the applicant to provide evidence if an IDE application is not required or the device qualifies for an abbreviated IDE application. If an IDE application is required, evidence that an IDE application submission or IDE authorization without clinical hold status has been secured must be included in the FY22 TBIPHRP FPA proposal/application. The IDE application should be specific for the device (i.e., should not represent a derivative or modified version of the device described in the IDE application) and indication to be tested in the proposed clinical trial. For more information on IDE applications, the FDA has provided guidance at https://www.fda.gov/medical-devices/how-study-and-market-your-device/investigational-device-exemption-ide.

Innovative Clinical Trial Design: When appropriate, the TBIPHRP encourages the use of innovative clinical trial design approaches (e.g., Bayesian, adaptive, clinical bio-equivalence, seamless, exploratory/phase 0, basket, stepped wedge) that improve efficiency and ability to determine clinical benefit while maintaining validity, integrity and ethical considerations.

Research Involving Human Anatomical Substances, Human Subjects, or Human Cadavers: All DOD-funded research involving new and ongoing research with human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Human and Animal Research Oversight (OHARO)Office of Research Protections (ORP),OHARO’s Office of Human Research Oversight (OHRO), prior to research implementation. This administrative review requirement is in addition to the local IRB or Ethics Committee (EC) review. Local IRB/EC approval at the time of submission is not required.

Allow up to 3 months to complete the OHRO regulatory review and approval process following submission of all required and complete documents to the OHRO. Refer to the General Submission Instructions, Appendix 1, and the OHRO Resources and Overview document available on the electronic Biomedical Research Application Portal (eBRAP) “Funding Opportunities & Forms” web page (https://ebrap.org/eBRAP/public/Program.htm) for additional information.

Research Involving Animals: All research funded by the FY22 TBIPHRP FPA involving new and ongoing research with animals must be reviewed and approved by the USAMRDC OHRO Animal Care and Use Review Office (ACURO), in addition to the local Institutional Animal Care and Use Committee (IACUC) of record. IACUC approval at the time of submission is not required. Allow at least 3 to 4 months for ACURO regulatory review and approval processes for animal studies. Refer to the General Submission Instructions, Appendix 1, for additional information.

If the proposed research involves more than one institution, plans for the multi-institutional structure governing the research protocol(s) should be outlined. In addition, a written plan for single IRB review arrangements must be provided for research conducted in the United States involving more than one institution. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements. Communication and data transfer between or among the collaborating institutions, as well as how specimens and/or imaging products obtained during the study will be handled, should be included in the appropriate sections of the https://www.fda.gov/medical-devices/how-study-and-market-your-device/investigational-device-exemption-ide https://www.fda.gov/medical-devices/how-study-and-market-your-device/investigational-device-exemption-ide https://ebrap.org/eBRAP/public/Program.htm

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 14 application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical research/trials.

Rigor of Experimental Design: All projects should adhere to accepted standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. Core standards are described in Landis, S.C., et al., “A call for transparent reporting to optimize the predictive value of preclinical research,” Nature 2012, 490:187-191 (https://www.nature.com/articles/nature11556). While these standards are written for preclinical studies, the basic principles of randomization, blinding, sample-size estimation, and data handling derive from well-established best practices in clinical studies. Applicants should consult the Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines 2.0 (ARRIVE) guidelines to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The ARRIVE 2.0 guidelines can be found at https://arriveguidelines.org/arrive-guidelines.

Optimizing Research Impact Through Community Collaboration: Research funded by the FY22 TBIPHRP should be responsive to the needs of the psychological health conditions and/or TBI lived experience, family, and care provider communities. Through the establishment and utilization of effective and equitable collaborations and partnerships, the translational and impact potential of the proposed research can be maximized. For the FY22 TBIPHRP FPA, inclusion of Community-Based Participatory Research (CBPR) approaches is encouraged for all projects and REQUIRED for studies recruiting human subjects. The inclusion of CBPR can be documented in Attachment 11, CBPR Letters of Commitment, and Attachment 12, CBPR Statement, if applicable.

CBPR supports collaborative research that involves scientific researchers and community members working together to address diseases and conditions, particularly those that disproportionately affect health disparity populations. Recognizing the strength of each partner, scientific researchers and community members collaborate and contribute equitably their expertise on all aspects of the project, which may include a needs assessment, planning, research intervention design, implementation, evaluation, and dissemination. CBPR features shared responsibility for and ownership of the research project, and the research results are jointly interpreted, disseminated, and fed back to affected communities and may be translated into interventions or policy. CBPR methods are critically important for community-level interventions and conditions affecting health disparity populations. CBPR methods, such as Lived Experience Consultation (LEC), can also have important impacts on translational research and prototype development to identify and augment the potential impact of a research program on people living with psychological health conditions and/or TBI.

CBPR collaborative relationships are often established through integrating community members into research teams as co-researchers, advisors, and consultants. Some examples of CBPR collaborations include:

• LEC: The research team includes at least one team member with lived psychological health conditions and/or TBI experience who will provide advice and consultation throughout the planning and implementation of the research project. LECs may include individuals with a TBI or psychological health condition, their family members, or care partners.

https://www.nature.com/articles/nature11556 https://arriveguidelines.org/arrive-guidelines

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 15

• Partnership with a community-based organization: The research team establishes partnerships with at least one community-based organization that provides advice and consultation throughout planning and implementation of the research project. Community-based organizations may include advocacy groups, service providers, policy makers, or other formal organizational stakeholders.

• Community advisory board (CAB): A CAB is composed of multiple community stakeholders and can take many forms, from a board of LECs to a coalition of community-based organizations or any combination thereof. As with LEC and organizational partners, the CAB provides advice and consultation throughout planning and implementation of the research project.

Additional information on CBPR can be found here:

• Chung B, Jones L, Dixon EL, et al. 2010. Using a community partnered participatory research approach to implement a randomized controlled trial: Planning the design of community partners in care. Journal of Health Care for the Poor and Underserved 21(3):780-795. doi: 10.1353/hpu.0.0345.

• Wallerstein N and Duran B. 2010. Community-based participatory research contributions to intervention research: The intersection of science and practice to improve health equity.

American Journal of Public Health 100(S1):S40-S46. doi: 10.2105/AJPH.2009.184036.

• Patient-Centered Outcomes Research Institute’s Engagement Tool and Resource Repository, https://www.pcori.org/engagement/engagement-resources/Engagement-Tool-Resource- Repository.

Required Data-Sharing for Traumatic Brain Injury or Psychological Health Human Subjects Research: The CDMRP intends that information, data, and research resources generated under this funding opportunity will be made available to the research community (including both the scientific and consumer advocacy communities) and the public at large. For additional guidance, refer to the General Submission Instructions, Appendix 2, Section L.

• All Prospective Human Subject Research

○ Applicants must include language in informed consent documents to allow for submission of de-identified data to a repository or for secondary use/meta-analyses of the data.

○ Applicants are also strongly encouraged to include language in consent forms to allow for optional passive follow-up via electronic health record.

○ As applicable, applicants are strongly encouraged to include secondary outcomes in proposed studies to address potential cross-cutting impacts of interventions.

○ As appropriate, the inclusion of TBI, psychological health, and caregiver/family outcomes measures is encouraged, regardless of the primary focus of the study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962454/pdf/nihms215966.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962454/pdf/nihms215966.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962454/pdf/nihms215966.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837458/pdf/S40.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837458/pdf/S40.pdf https://www.pcori.org/engagement/engagement-resources/Engagement-Tool-Resource-Repository https://www.pcori.org/engagement/engagement-resources/Engagement-Tool-Resource-Repository

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 16

• Psychological Health Research

○ The TBIPHRP requires applicants to incorporate Common Data Elements (CDEs) appropriate to each field of study, such as the PhenX Core and Specialty collections, which are available in the Mental Health Research, Substance Abuse and Addiction, and Research Domains Collections of the PhenX Toolkit, into all studies involving human subjects as applicable. Justification is required if the recommended measure in the PhenX Toolkit is not selected.

○ The TBIPHRP recommends that applicants consider the National Institute of Mental Health (NIMH) Data Archive (NDA) as a data-sharing repository for psychological health human subjects data. The NDA provides an infrastructure for sharing research data, tools, methods, and analyses enabling collaborative science and discovery. The NDA mission is to accelerate scientific research and discovery through data-sharing, data harmonization, and the reporting of research results. Consult the NDA website at https://nda.nih.gov/ for additional information.

○ In order to share data with the NDA, these elements must be included in the proposed research:

– Updated informed consent language that includes NDA data-sharing. Sample consent language can be found in Appendix III.

– NDA Global Unique Identifier (GUID): The NDA GUID is a subject ID that allows researchers to share data specific to a study participant without exposing personally identifiable information (PII) and makes it possible to match participants across labs and research data repositories. In order to generate a NDA GUID for a subject, the following PII must be collected in the proposed research (this PII is never sent to the Federal Interagency Traumatic Brain Injury Research [FITBIR] Informatics System):

Complete legal given (first) name of subject at birth

Complete legal additional name of subject at birth (if subject has a middle name)

Complete legal family (last) name of subject at birth

Day of birth

Month of birth

Year of birth

Name of city/municipality in which subject was born

Sex at birth https://www.phenxtoolkit.org/index.php https://nda.nih.gov/ https://nda.nih.gov/data_structure.html?short_name=ndar_subject01

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 17

– In addition, for research participants aged 18 or over, the following data must be collected. The expectation to collect these data does not preclude the use of other data collection instruments that collect similar data.

Age

DSM-5 crosscutting assessment (adult)

WHODAS 2.0

Patient Health Questionnaire - 9

GAD - 7

- While there is no direct charge to users of the NDA, a project estimation tool is available to help estimate costs and manpower needs that may be associated with data submission.

• Traumatic Brain Injury Research

○ The TBIPHRP requires that awardees make TBI research data generated by this award mechanism available to the research community through the FITBIR Informatics System, a free resource designed to accelerate research progress by allowing the storage, reanalysis, integration, and rigorous comparison of multiple datasets. Currently, FITBIR-eligible research includes all studies generating prospectively collected human TBI subject data (e.g., clinical, demographic, phenotypic, imaging and genetic). Consult the NDA website at https://fitbir.nih.gov for additional information.

○ In order to share data with the FITBIR, these elements must be included in the proposed research:

– Updated informed consent language that includes FITBIR data-sharing. Sample consent language is included in Appendix IV.

– FITBIR GUID: The FITBIR GUID is a subject ID that allows researchers to share data specific to a study participant without exposing PII and makes it possible to match participants across labs and research data repositories. In order to generate a GUID for a subject, the following PII must be collected in the proposed research (this PII is never sent to the FITBIR system):

Complete legal given (first) name of subject at birth

Complete legal additional name of subject at birth (if subject has a middle name)

Complete legal family (last) name of subject at birth

Day of birth

Month of birth https://nda.nih.gov/data_structure.html?short_name=cde_dsm5crossad01 https://nda.nih.gov/data_structure.html?short_name=cde_whodas01 https://nda.nih.gov/data_structure.html?short_name=cde_phq901 https://nda.nih.gov/data_structure.html?short_name=cde_gad701 https://s3.amazonaws.com/nda.nih.gov/Documents/NDA_Data_Submission_Cost_Estimation_Tool.xlsx https://fitbir.nih.gov/

DOD FY22 Traumatic Brain Injury and Psychological Health Focused Program Award 18

Year of birth

Name of city/municipality in which subject was born

Country of birth

– National Institute of Neurological Disorders and Stroke (NINDS) TBI CDEs:

Research data elements must be reported using the NINDS TBI CDEs or entered into the FITBIR data dictionary as new, unique data elements (UDEs).