The DoD Traumatic Brain Injury and Psychological Health Program is offering this Investigator-Initiated Research Grant for Advancing Understanding and Treatment of TBI and Psychological Conditions.

The FY21 TBIPHRP IIRA is intended to support studies that will make an important contribution toward understanding, preventing, and treating TBI and/or psychological health conditions. Research projects may focus on any phase of research from basic laboratory research through translational research, including preclinical studies in animal models and human subjects, as well as correlative studies associated with an existing clinical trial. Research involving human subjects and human anatomical substances is permitted; however, this FY21 TBIPHRP IIRA may not be used to conduct clinical trials.

The IIRA is designed to support research with the potential to yield highly impactful discoveries or major advancements. The application should clearly demonstrate the project’s potential near-term and long-term outcome(s)/product(s) (knowledge and/or materiel) and how they will impact a critical problem or question in the field of research and/or patient care in the FY21 TBIPHRP IIRA Focus Areas(s) addressed.

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 placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. This award may not be used to conduct clinical trials.

Applications proposing clinical trials may be submitted to the following FY21 TBIPHRP funding opportunities:

 Clinical Trial Award (Funding Opportunity Number: W81XWH-21-S-TBIPH1)

 Focused Program Award (Funding Opportunity Number: W81XWH-21-S-TBIPH2)

 Translational Research Award (Funding Opportunity Number: W81XWH-21-TBIPHRP-TRA)

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 Institutional Review Board (IRB) 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.

The FY21 TBIPHRP IIRA may not be used to support studies requiring an exception from informed consent.

For more information on how to distinguish clinical research from clinical trials, see the Human Subject Resource Document at https://ebrap.org/eBRAP/public/Program.htm.

Preliminary data are required. The rationale for a research idea may be derived from a laboratory discovery, population-based studies, a clinician’s firsthand knowledge of patients, or anecdotal data. Applications must include relevant data that support the rationale for the proposed study. These data may be unpublished or from published literature. Any unpublished, preliminary data provided should originate from the laboratory of the Principal Investigator (PI) or members of the research team.

Relevance to Military Health: Relevance to the healthcare needs of Service Members, Veterans, military beneficiaries, and the American public 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 TBI and/or psychological health that has direct relevance to the health and/or readiness of Service Members, Veterans, military beneficiaries, and the American public

 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, Veterans, military beneficiaries, and the American public. 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 2.

Early-Career Investigator Partnering Option: The FY21 TBIPHRP encourages applications that include meaningful and productive collaborations between investigators. The FY21 TBIPHRP IIRA includes a partnering option with a PI who is an Early-Career Investigator. The PIs may have experience in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the application. The Partnering PI Option is structured to accommodate two PIs. One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission. The other investigator will be the Partnering PI. Either the Initiating or Partnering PI may be the Early-Career Investigator. Both PIs should contribute significantly to the development of the proposed research project, including the Project Narrative, Statement of Work (SOW), and other required components. The application is expected to describe how the PIs’ unique experience/ expertise combined as a partnership will better address the research question, how the unique experience/expertise that each individual brings to the application is critical for the research strategy and completion of the SOW, and why the work should be done together rather than through separate efforts. If recommended for funding, each PI will be named to an individual award within the recipient organizations. For individual submission requirements for the Initiating and Partnering PI, refer to Section II.D.2, Content and Form of the Application Submission.

The types of awards made under the program announcement will be assistance agreements. An assistance 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. The level of involvement on the part of the DOD during project performance is the key factor in determining whether to award 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, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the start date, will be determined during the negotiation process.

The anticipated total costs budgeted for the entire period of performance for an FY21 TBIPHRP IIRA will not exceed $750,000. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2022. For additional information refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $11.25M to fund approximately 15 FY21 TBIPHRP Investigator-Initiated Research Award applications. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications 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 FY21 funding opportunity will be funded with FY21 funds, which will expire for use on September 30, 2027.

The FY21 TBIPHRP IIRA is intended to support studies that will make an important contribution toward understanding, preventing, and treating TBI and/or psychological health conditions. Research projects may focus on any phase of research from basic laboratory research through translational research, including preclinical studies in animal models and human subjects, as well as correlative studies associated with an existing clinical trial. Research involving human subjects and human anatomical substances is permitted; however, this FY21 TBIPHRP IIRA may not be used to conduct clinical trials.

The IIRA is designed to support research with the potential to yield highly impactful discoveries or major advancements. The application should clearly demonstrate the project’s potential near-term and long-term outcome(s)/product(s) (knowledge and/or materiel) and how they will impact a critical problem or question in the field of research and/or patient care in the FY21 TBIPHRP IIRA Focus Areas(s) addressed.

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 placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. This award may not be used to conduct clinical trials.

Applications proposing clinical trials may be submitted to the following FY21 TBIPHRP funding opportunities:

 Clinical Trial Award (Funding Opportunity Number: W81XWH-21-S-TBIPH1)

 Focused Program Award (Funding Opportunity Number: W81XWH-21-S-TBIPH2)

 Translational Research Award (Funding Opportunity Number: W81XWH-21-TBIPHRP-TRA)

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 Institutional Review Board (IRB) 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.

The FY21 TBIPHRP IIRA may not be used to support studies requiring an exception from informed consent.

For more information on how to distinguish clinical research from clinical trials, see the Human Subject Resource Document at https://ebrap.org/eBRAP/public/Program.htm.

Preliminary data are required. The rationale for a research idea may be derived from a laboratory discovery, population-based studies, a clinician’s firsthand knowledge of patients, or anecdotal data. Applications must include relevant data that support the rationale for the proposed study. These data may be unpublished or from published literature. Any unpublished, preliminary data provided should originate from the laboratory of the Principal Investigator (PI) or members of the research team.

Relevance to Military Health: Relevance to the healthcare needs of Service Members, Veterans, military beneficiaries, and the American public 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 TBI and/or psychological health that has direct relevance to the health and/or readiness of Service Members, Veterans, military beneficiaries, and the American public

 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, Veterans, military beneficiaries, and the American public. 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 2.

Early-Career Investigator Partnering Option: The FY21 TBIPHRP encourages applications that include meaningful and productive collaborations between investigators. The FY21 TBIPHRP IIRA includes a partnering option with a PI who is an Early-Career Investigator. The PIs may have experience in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the application. The Partnering PI Option is structured to accommodate two PIs. One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission. The other investigator will be the Partnering PI. Either the Initiating or Partnering PI may be the Early-Career Investigator. Both PIs should contribute significantly to the development of the proposed research project, including the Project Narrative, Statement of Work (SOW), and other required components. The application is expected to describe how the PIs’ unique experience/ expertise combined as a partnership will better address the research question, how the unique experience/expertise that each individual brings to the application is critical for the research strategy and completion of the SOW, and why the work should be done together rather than through separate efforts. If recommended for funding, each PI will be named to an individual award within the recipient organizations. For individual submission requirements for the Initiating and Partnering PI, refer to Section II.D.2, Content and Form of the Application Submission.

The types of awards made under the program announcement will be assistance agreements. An assistance 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. The level of involvement on the part of the DOD during project performance is the key factor in determining whether to award 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, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the start date, will be determined during the negotiation process.

The anticipated total costs budgeted for the entire period of performance for an FY21 TBIPHRP IIRA will not exceed $750,000. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2022. For additional information refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $11.25M to fund approximately 15 FY21 TBIPHRP Investigator-Initiated Research Award applications. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications 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 FY21 funding opportunity will be funded with FY21 funds, which will expire for use on September 30, 2027.