The CRRP seeks to enhance medical capabilities at the point of greatest need in order to save the most lives in future combat scenarios, which may be complicated by limited resources, austere conditions, and/or mass casualty events.

The intent of the FY19 CRRP RDTRA is to support research that

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will accelerate the movement of promising ideas into clinical applications, including healthcare products, technologies, and/or practice guidelines.

Applicants may leverage existing resources in translational research to address high-impact research ideas or unmet needs in delivering lifesaving care to the Warfighter during prolonged and en route care in austere and combat environments.

Research of interest may include knowledge products, “knowledge resulting from research with the potential to improve individual or public health,”2 and solutions that can accelerate the introduction of military-relevant health products or technologies into clinical and/or operational use.

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.

Projects should consider the varied expertise levels of the medical providers and the possible diverse environmental conditions in combat situations.

Proposal/application submissions are encouraged to include characteristics relevant to military use in non-hospital settings in theater, but submissions that propose solutions to advance civilian trauma care are not precluded, since civilian trauma care frequently informs and influences trauma care in the military, and vice versa.

Preclinical research, including animal studies, that is already supported by substantial preliminary or published data and strongly validates clinical translation is appropriate for this award mechanism.

Research involving human subjects and human anatomical substances is permitted; however, clinical trials are not allowed under this funding opportunity.

A clinical trial is 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.

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

The anticipated direct costs budgeted for the entire period of performance for an FY19 CRRP RDTRA will not exceed $1,500,00 0. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

The CDMRP expects to allot approximately $13M to fund approximately five to six RDTRA proposal/applications.

Funding of proposal/applications received is contingent upon the availability of Federal funds for this program as well as the number of proposal/applications received, the quality and merit of the proposal/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 FY19 funding opportunity will be funded with FY19 funds, which will expire for use on September 30, 202 5. Awards will be made no later than September 30, 202 0. 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.

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.

Research Involving a U. S. Food and Drug Administration (FDA)-Regulated Drug, Biologic, or Device:
If the study proposed involves the use of a drug or biologic that has not been approved by the FDA for the proposed investigational use, evidence is required that an Investigational New Drug (IND) application that meets all requirements under the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312) has been submitted or will be submitted to the FDA within 60 days of award.

If the investigational product is a device, evidence is required that an Investigational Device Exemption (IDE) application, that meets all requirements under 21 CFR 812, has been submitted or will be submitted to the FDA within 60 days of award..

The Government reserves the right to withdraw funding if the IND or IDE application has not been submitted to the FDA within 60 days of the Department of Defense (DoD) award date or if the documented application status of the IND or IDE has not been obtained within 12 months of the award date.

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 Institutional Review Board (IRB) or Ethics Committee (EC) review.

Local IRB/EC approval at the time of submission is not required.

The HRPO is mandated to comply with specific laws and requirements governing all research involving human anatomical substances, human subjects, or human cadavers that is supported by the DoD.

These laws and requirements will necessitate information in addition to that supplied to the IRB/EC.

Allow a minimum of 2 to 3 months for HRPO regulatory review and approval processes.

Additional time for regulatory reviews may be needed for clinical studies taking place in international settings.

When possible, protocols should be written for research with human subjects and/or human anatomical substances that are specific to the DoD-supported effort outlined in the submitted proposal/application as a stand-alone study.

Submission to HRPO of protocols involving more than the scope of work in the DoD-funded award will require HRPO review of the entire protocol (DoD and non-DoD funded).

DoD human subjects protection requirements may be applied to non-DoD funded work and necessitate extensive revisions to the protocol.

Proposals/applications that involve recruitment of human subjects must indicate the quarterly enrollment targets across all sites in Attachment 5:
Statement of Work (SOW).

Successful applicants will work with USAMRAA to establish milestones for human subjects recruitment.

Continued support for the project will be based upon satisfactory progress in meeting the established milestones.

Refer to the General Submission Instructions, Appendix 1, and the Human Subject Resource 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.

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/nature1155 6. 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 7:
Animal Research Plan, as part of the proposal/ application package to describe how these standards will be addressed.

Applicants should consult the ARRIVE (Animal Research:
Reporting In Vivo Experiments) guidelines to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported.

The ARRIVE guidelines can be found at https://www.elsevier.com/__data/promis_ misc/622936arrive_guidelines.pdf.

Use of DoD or Department of Veterans Affairs (VA) Resources:
If the proposed research involves access to active duty military patient populations and/or DoD 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.

Access to target active duty military patient population(s) and/or DoD resource(s) or database(s) should be confirmed by including a letter of support, signed by the lowest-ranking person with approval authority.

If the proposed research involves access to VA patient populations, VA study resources and databases, and/or VA research space and equipment, VA Principal Investigators (PIs) must have a plan for obtaining and maintaining access throughout the proposed research.

Access to VA patients, resources, and/or VA research space should be confirmed by including a letter of support from the VA Facility Director(s) or individual designated by the VA Facility Director(s), such as the Associate Chief of Staff for Research and Development (ACOS/R&D) or Clinical Service Chief.

If appropriate, the proposal/application should identify the VA-affiliated nonprofit corporation (NPC) as the applicant institution for VA PIs.

If the VA NPC is not identified as the applicant institution for administering the funds, the proposal/application should include a letter from the VA ACOS/R&D confirming this arrangement and identifying the institution that will administer the funds associated with the proposed research.

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 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 access cannot be confirmed at the time of proposal/application submission, 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).

Refer to Section II.D.

2. b.ii, Full Proposal/Application Submission Components, for detailed information.

Research Involving Animals:
All DoD-funded research 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.

Specific documents relating to the use of animals in the proposed research will be requested if the proposal/application is selected for funding.

The ACURO must review and approve all animal use prior to the start of working with animals, including amendments to ongoing projects.

PIs must submit the institutional animal use protocol, IACUC approval of that protocol, and a version of the animal use appendix titled, “Research Involving Animals.” 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.

Federal Interagency Traumatic Brain Injury Research (FITBIR) Data Sharing:
The DoD requires that awardees make traumatic brain injury (TBI) research data generated by this award mechanism available to the research community through the FITBIR Informatics System.

The FITBIR Informatics System is a free resource designed to accelerate research progress by allowing the storage, re-analysis, integration, and rigorous comparison of multiple datasets.

Currently FITBIR eligible research include all studies generating prospectively collected human TBI subject data (e.g., clinical, demographic, phenotypic, imaging, and genomic).

Data reporting to FITBIR is an opportunity for investigators to facilitate their own research and to collaborate with others engaged in similar research.

While there is no direct charge to users of the FITBIR Informatics System, a project estimation tool (https://fitbir.nih.gov/jsp/ contribute/fitbir-costs.jsp) is available to help estimate costs and manpower needs that may be associated with data submission.

FITBIR guidance and policies, as well as the considerable advantages of FITBIR participation to the researcher, are detailed at https://fitbir.nih.gov.

In order to share data with FITBIR, three elements must be included in the proposed research:
1. Updated informed consent language that includes FITBIR data sharing.

Sample consent language is included in Appendix III.

2. Global Unique Identifier (GUID):
FITBIR encourages collaboration between laboratories, as well as interconnectivity with other informatics platforms.

Such community-wide sharing requires common data definitions and standards.

FITBIR allows for de-identification and storage of data (medical imaging clinical assessment, environmental and behavioral history, etc.) of various types (text, numeric, image, time series, etc.).

Use of FITBIR’s GUID system facilitates repeated and multi-user access to data without the need to personally identify data sources.

In order to generate a GUID for a subject, the following personally identifiable information (PII) must be collected in the proposed research:
 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  Country of birth Note that this PII is never sent to the FITBIR system.

PII cannot be extracted from the GUID.

Information on GUID compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations can be found at https://fitbir.nih.gov/content/globalunique- identifier.

3.