Eligible Applicants: Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

Agency Name: Teresa M Parker-Reeser Grants Officer

Description:

The FY24 TBIPHRP TRA intends to accelerate the conversion of research findings in psychological health and/or TBI into clinical applications. Funded research outcomes should lead to the development of health care products, technologies, and/or clinical practice guidelines that improve patient outcomes. Additional information about translational research can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829707/ and https://ncats.nih.gov/about/about-translational-science.

Applications may include preclinical applied research (including animal research) and clinical research (including pilot/exploratory clinical trials). The FY24 TBIPHRP TRA may also support ancillary studies that are associated with an ongoing or completed clinical trial and projects that optimize the design of future clinical trials. This award may not be used to support studies requiring an exception from informed consent (EFIC). Clinical trials may be designed to evaluate promising new products, pharmacologic agents (drugs or biologics), diagnostics, devices, therapies, clinical guidance, behavioral interventions, emerging approaches and technologies, and/or new indications for products currently U.S. Food and Drug Administration (FDA)-approved or -cleared.

Basic research is not allowed: 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.

Preliminary data are required: Applications must include preliminary and/or published data to support the proposed research project.

The FY24 TBIPHRP TRA allows funding for a pilot/exploratory clinical trial as PART of the funded research project where limited clinical testing of a novel knowledge product,5 intervention, or device is necessary to inform the next step in clinical translation. Such pilot/exploratory clinical trial studies should be small, make up only a portion of the research proposed in the Statement of Work (SOW), and be utilized to establish the feasibility of a potential approach or to aid in device or intervention refinement. Applications that include large-scale clinical trials do not meet the intent of the mechanism. Applications that consist entirely of a pilot/exploratory clinical trial or multiple pilot/exploratory clinical trials may be administratively withdrawn.

A clinical trial is defined in 45 CFR 46.102 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.

Studies that do not seek to measure safety, effectiveness, and/or efficacy outcome(s) of an intervention are not considered clinical trials. For more information, a Human Subject Resource Document is provided at https://cdmrp.health.mil/pubs/pdf/Human%20Subjects%20Resource%20Document.pdf.

For the purposes of this funding opportunity, research that meets the definition of a clinical trial is distinct from clinical research. Clinical research encompasses research with human data, human specimens, and/or interaction with human subjects. Clinical research is observational in nature and includes:

(1) Research conducted with human subjects and/or material of human origin such as data, specimens, and cognitive phenomena for which an investigator (or co-investigator) does not seek to assess the safety, effectiveness, and/or efficacy outcomes of an intervention. Research meeting this definition may include but is not limited to: (a) mechanisms of human disease, (b) diagnostic or detection studies (e.g., biomarker or imaging), (c) health disparity studies, and (d) development of new technologies.

(2) Epidemiologic and behavioral studies that do not seek to assess the safety, effectiveness, and/or efficacy outcomes of an intervention.

(3) Outcomes research and health services research that do not fit under the definition of clinical trial.

Excluded from the definition of clinical research are in vitro studies that utilize human data or specimens that cannot be linked to a living individual and meet the requirements for exemption under §46.104(d)(4) of the Common Rule.

Applications that include a clinical trial as part of the proposed research will have additional submission requirements and review criteria. For more information, see Section II.D.2, Content and Form of the Application Submission and Section II.E.1, Criteria. Funded clinical trials are required to post a copy of the informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in 32 CFR 219.

Multi-Institutional Clinical Research/Trials: As of January 20, 2020, U.S. institutions engaged in non-exempt cooperative research must rely on a single Institutional Review Board (IRB) to review and approve the portion of the research conducted at domestic sites (45 CFR 46.114(b)). If the proposed, non-exempt research involves more than one U.S.-based institution, a written plan for single IRB review arrangements must be provided at the time of application submission or award negotiation. 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 application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical research/trials.

Research Levels: The FY24 TBIPHRP TRA offers funding for two Research Levels (refer to Section II.D.5 Funding Restrictions). Only one Research Level category may be chosen per application. It is the responsibility of the applicant to select the level that aligns with the scope of the proposed research. The Research Level should be selected based on the research scope and not on the amount of the budget. The following are generalized descriptions of the scope of the research appropriate for each Research level:

• Research Level 1: Research Level 1 is intended to support smaller scope, less complex preclinical and/or clinical research. Pilot clinical trials as part of the proposed research are allowed. The maximum period of performance is 3 years. The application’s direct costs budgeted for the entire period of performance should not exceed $500,000.

• Research Level 2: Research Level 2 is intended to support larger scope, more complex preclinical and/or clinical research. Pilot clinical trials as part of the proposed research are allowed. The maximum period of performance is 4 years. The application’s direct costs budgeted for the entire period of performance should not exceed $1.0M.

o Early-Career Investigator Partnering Option: The FY24 TBIPHRP TRA (Research Level 2 only) includes an Early-Career Investigator Partnering Option that is structured to accommodate two Principal Investigators (PIs), one of whom is an Early-Career Investigator. The combined direct costs budgeted for the entire period of performance in the applications of the Initiating PI and Partnering PI should not exceed $1.0M.

o The PIs may have experience in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the application. One PI will be identified as the Initiating PI and will be responsible for most of the administrative tasks associated with application submission. The other investigator will be the Partnering PI. At least one of the Initiating or Partnering PIs must be an Early-Career Investigator.

o The intent is not to create a mentor-mentee arrangement. 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. o If recommended for funding, each PI will be named to an individual award within the recipient organization(s). For individual FY24 TBIPHRP TRA submission requirements for the Initiating and Partnering PI, refer to

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

Rigor of Preclinical Research Design: All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. The standards are described in SC Landis et al., 2012, A call for transparent reporting to optimize the predictive value of preclinical research, Nature 490:187-191 (www.nature.com/nature/journal/v490/n7419/full/nature11556.html). 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. Projects that include research on animal models are required to submit Attachment 9, Animal Research Plan, as part of the application package to describe how these standards will be addressed. Applicants should consult the ARRIVE guidelines 2.0 (Animal Research: Reporting In Vivo Experiments) to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The ARRIVE guidelines 2.0 can be found at https://arriveguidelines.org/arrive-guidelines.

If animal models are proposed, consider the following:

• Pairing clinical populations to animal models in order to validate the clinical relevance and development of prevention, assessment, and treatment solutions is encouraged.

• Proposed animal models should be well justified, supported within the literature, and clearly align with clinical relevance to the human condition.

Relevance to Military Health: Relevance to the health care needs of Service Members, their Families, 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 of Service Members, their Families, 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.

Collaborations between researchers or consultants at military or Veterans organizations and non-military organizations 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, their Families, 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 2.

Awards supported with FY24 funds will be made no later than September 30, 2025.

The CDMRP expects to allot approximately $17.05M to fund approximately six TRA Research Level 1 applications and eight TRA Research Level 2 applications. Funding of applications received is contingent upon the availability of federal funds for this program, the number of applications received, the quality and merit of the applications as evaluated by peer 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 FY24 funding opportunity will be funded with FY24 funds, which will expire for use on September 30, 2030.

Grantor Contact Information: CDMRP Help Desk Phone: 301-682-5507 Email: help@eBRAP.org