The CRRP seeks to enhance medical capabilities and Force readiness at the point of greatest need in order to save the most lives in trauma care scenarios, which may be complicated by combat operations, limited resources, austere conditions, and/or mass casualty events. The intent of the FY22 CRRP RDTRA is to support research that will accelerate the movement of promising ideas into clinical applications, including healthcare products, technologies, and/or practice guidelines. Research under this award mechanism should represent a rapid advancement or innovative “leap ahead” and have the potential for broadly applicable, cross-cutting advances benefiting military health and medicine as well as the general public. Applicants may leverage existing resources in translational research to address high-impact research ideas or unmet needs to enable the delivery of life-saving care to the Warfighter during prolonged and en route care in austere and combat environments. For this award mechanism, the definition of “leveraging” is as follows: An investigator basing a research project on existing resources in order to amplify potential gains in knowledge or accelerate technical maturity. Research of interest may include knowledge products, “knowledge resulting from research with the potential to improve individual or public health and solutions that can accelerate the introduction of military-relevant health products or technologies into clinical and/or operational use. Projects should take into consideration the varied expertise levels of targeted medical providers, available resources, and the possible diverse environmental conditions in combat situations. Proposal/application submissions are encouraged to include characteristics relevant to military use in the pre-hospital, combat operational setting. Submissions that propose solutions to advance civilian trauma care are not precluded, since civilian trauma and trauma care in the military are mutually influential, and may be co-occurring in certain situations.

Impact is a key component of this award mechanism. The potential impact of the research, both short-term and long-term, in addressing the FY22 CRRP Focus Area(s) should be clearly described. High-impact research will, if successful, lead to the rapid development and translation of applicable advances for improving medical readiness, mitigating fatalities, optimally treating life-threatening injuries, and promoting positive long-term outcomes for military health and medicine, as well as the general public.

Applications in response to this BAA may not be used to support fundamental basic research. For this BAA, 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. Applied and preclinical research, including animal studies, that is already supported by substantial preliminary or published data, and is designed to validate clinical translation, is appropriate for this award mechanism.

This BAA may be used to support preclinical research, clinical research, and small-scale clinical trials (e.g., first in human, phase 1/1b). Phase 2 and phase 3 clinical trials for U.S. Food and Drug Administration (FDA) licensure of drugs and definitive/pivotal testing for device clearance by the FDA will NOT be permitted under this BAA. This BAA may not be used to support studies requiring an exception from informed consent (EFIC).

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. (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.

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. Funded trials are required to post a copy of the IRB-approved informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in Code of Federal Regulations, Title 32, Part 219 (32 CFR 219).

The proposed research must be relevant to active-duty Service Members, Veterans, military beneficiaries, and/or the American public.

Awards funded under this mechanism may propose a base award with a potential option year (not required) to be considered for funding with a future appropriation, if available. Applicants are required to select one of the following funding options when applying:

1. CRRP RDTRA: The period of performance of the CRRP RDTRA will be 2 years. The anticipated total costs budgeted for an FY22 CRRP RDTRA will not exceed $2.2M. This does not include the option for a third year.

2. CRRP RDTRA with Option (if applicable): The CRRP RDTRA with Option may be funded in two phases over a 3-year period. The first phase of performance of the CRRP RDTRA will be 2 years. The second phase will be the additional Option year, for the potential of 3 years in total. Each phase must be a distinct, but related, research effort with a non-overlapping period of performance, research outcomes/milestones, and budget. The Option must clearly be a follow-on effort stemming from the work completed during the base CRRP RDTRA. Research products from the CRRP RDTRA shall be leveraged in the subsequent option phase, if planned. The anticipated total costs budgeted will not exceed $2.2M for an FY22 CRRP RDTRA and $1.0M for the Option period of performance. A virtual milestone review meeting will be conducted on or about month 18 of the CRRP RDTRA period of performance to evaluate progress against the proposed Statement of Work (SOW). Exercise of the Option is contingent on the availability of sufficient future congressional appropriations to the CRRP, alignment of the proposed research during the Option period to that fiscal year’s congressional language, acceptable performance by the recipients, and relevance to current program priorities.

For projects proposing a clinical trial:

• If an Investigational New Drug (IND) or Investigational Device Exemption (IDE) is required for the CRRP RDTRA or CRRP RDTRA with Option base period of performance, the IND/IDE application must be submitted to the FDA by the FY22 CRRP RDTRA proposal/ application submission deadline. It is the responsibility of the applicant to provide evidence from the IRB of record or the FDA if an IND/IDE is not required. Refer to Attachment 9, Regulatory Strategy, for further details.

• If an IND or IDE is required for the Option period of performance, applicants must provide documentation of communication from the FDA indicating the IND or IDE application is active/safe to proceed prior to the conclusion of the base period of performance.

• If the clinical trial of an investigational product will be conducted at international sites, evidence that an application has been submitted to the relevant national regulatory agency of the host country(ies) is required by the above deadlines.

• If the clinical trial is proposed in the CRRP RDTRA, or during the base period of the CRRP RDTRA with Option, the trial must be initiated no later than month 9 of the initial period of performance.

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 CDMRP expects to allot approximately $8.71M to fund approximately four CRRP RDTRA proposals/applications. Funding of proposals/applications received is contingent upon the availability of federal funds for this program as well as the number of proposals/applications received, the quality and merit of the proposals/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 initially funded with FY22 funds, which will expire for use on September 30, 2028.

Applications received in response to both the extramural FY22 CRRP RDTRA BAA and the intramural program announcement will be evaluated and considered for funding together. The government reserves the right to fund any combination of extramural and/or intramural proposals/applications.

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.

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 Research Protections (ORP), Human Research Protection Office (HRPO), 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 HRPO regulatory review and approval processes following submission of all required and complete documents to the HRPO. Refer to the General Submission Instructions, Appendix 1, and the Human Research Protections Office Resources and Overview document available on the eBRAP “Funding Opportunities & Forms” web page (https://ebrap.org/eBRAP/public/Program.htm) for additional information.

If the proposed research involves more than one 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.

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 (www.nature.com/nature/journal/v490/n7419/full/nature11556.html). While these standards were written for preclinical studies, the basic principles of randomization, blinding, sample-size estimation, and data handling derive from well-established best practices in research and should be applied consistently across translational studies. Projects that include research on animal models are required to submit

Attachment 8, Animal Research Plan, as part of the proposal/ application package to describe how these standards will be addressed. Applicants should consult the Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines 2.0 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.

Use of DOD or Department of Veterans Affairs (VA) Resources: If the proposed research involves access to active-duty military or Veteran patient populations and/or DOD or VA resources or databases, the proposal/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 Proposal/Application Submission Components, for detailed information. Refer to the General Submission Instructions, Appendix 1, for additional information.

Research Involving Animals: All research funded by the FY22 CRRP RDTRA involving new and ongoing research with animals must be reviewed and approved by the USAMRDC ORP 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.