HT9425-23-S-BAA1-9 April 2024.pdf

FY23 – FY27 DOD USAMRDC Broad Agency Announcement for Extramural Medical Research

I. OVERVIEW OF THE FUNDING OPPORTUNITY

United States Army Medical Research and Development Command

DEPARTMENT OF DEFENSE

BROAD AGENCY ANNOUNCEMENT

for Extramural Medical Research

Funding Opportunity Number: HT9425-23-S-BAA1

Announcement Type: Initial

Assistance Listing Number: 12.420 Military Medical Research and Development

KEY DATES

Release/Posted Date: October 1, 2022

Closing Date: September 30, 2027, 11:59 p.m. Eastern Time

This funding opportunity announcement is a broad agency announcement (BAA). It is continuously open for a 5-year period, from October 1, 2022 through September 30, 2027, 11:59 p.m. Eastern Time.

This Broad Agency Announcement must be read in conjunction with the General Submission Instructions, which are available for downloading from Grants.gov. The General Submission Instructions are located under the “package tab” and can be downloaded by selecting the “Download Instructions” icon when previewing the submission package.

Table of Contents

I. OVERVIEW OF THE FUNDING OPPORTUNITY

I.A. New for Fiscal Year 2023 – Fiscal Year 2027

II. DETAILED INFORMATION ABOUT THE FUNDING OPPORTUNITY

II.A. Program Descriptions

II.A.1. Military Infectious Diseases Research Program II.A.2. Combat Casualty Care Research Program II.A.3. Military Operational Medicine Research Program

II.B. Award Information II.B.1. Clinical Trial Support II.B.2. Use of Military and Department of Veterans Affairs Populations or Resources II.B.3. Technology Requirements and Standards II.B.4. Data Sharing II.B.5. Funds Available and Anticipated Number of Awards II.B.6. Award Amounts and Periods of Performance II.B.7. Mechanisms of Support

II.C. Eligibility Information II.C.1. Eligible Applicants II.C.2. Cost Sharing II.C.3. Other

II.D. Proposal/Application Submission Information II.D.1. Where to Obtain the Proposal/Application Submission Package II.D.2. Content and Form of Proposal/Application Submission II.D.3. Unique Entity Identifier (UEI) and System for Award Management 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 and Selection Information II.E.1. Criteria for Research Proposals/Applications Without a Clinical Trial II.E.2. Proposal/Application Selection Process II.E.3. Integrity and Performance Information II.E.4. Notification of Proposal/Application Review Results

II.F. Federal Award Administration Information II.F.1. Federal Award Notices II.F.2. Administrative and National Policy Requirements II.F.3. Reporting Requirements

II.G. Federal Awarding Agency Contacts

II.G.1. eBRAP Help Desk II.G.2. Grants.gov Contact Center

II.H. Other Information II.H.1. Contractor/Recipient Qualification II.H.2. Proprietary Information II.H.3. Administrative Actions

II.I. Checklist for Research Proposal/Application Submission Without a Clinical Trial

APPENDIX I: RESEARCH AREAS OF INTEREST

I. Military Infectious Diseases Research Program II. Combat Casualty Care Research Program III. Military Operational Medicine Research Program

APPENDIX II: CLINICAL TRIALS

I. Important Aspects of Clinical Trials II. Full Proposal/Application Submission Components for Studies With a Clinical Trial III. Review Criteria for Research Proposals/Applications With a Clinical Trial IV. Checklist for Research Proposal/Application Submission With a Clinical Trial

APPENDIX III: DOD AND VA WEBSITES

APPENDIX IV: PROCEDURES FOR ACQUISITION, PROCESSING, STORAGE, AND

SHIPMENT OF BIO-FLUIDS

APPENDIX V: NATIONAL INSTITUTE OF MENTAL HEALTH DATA ARCHIVE —

INFORMED CONSENT

APPENDIX VI: TECHNOLOGY READINESS LEVELS AND KNOWLEDGE

READINESS LEVELS

APPENDIX VII: ACRONYMS AND ABBREVIATIONS

APPENDIX VIII: FY23–FY27 USAMRDC BAA ADDENDUM – FY22 NEW PROGRAM

INCREASES

I.A. New for Fiscal Year 2023 – Fiscal Year 2027

The Fiscal Year 2023 – Fiscal Year 2027 (FY23 – FY27) U.S. Army Medical Research and Development Command’s (USAMRDC) Broad Agency Announcement (BAA) for Extramural Medical Research contains several changes from previous USAMRDC BAAs. Read each section carefully. Note the following:

• The open period of the BAA is 5 years and will be amended annually with any updates.

• The “Research Areas of Interest” can be found in Appendix I.

• 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, United States Code, Title 31, Sections 6301-6308 (31 USC 6301-6308), which provides the legal criteria to select a procurement contract or an assistance agreement. The award type, along with the start date, will be determined during the negotiation process.

• For assistance agreements:

○ The total period of performance may be proposed for up to a maximum of 4 years in length; additional periods may be considered.

○ Any assistance agreement (grant or cooperative agreement) awarded under this BAA will be governed by the award terms and conditions that conform to the Department of Defense’s (DOD) implementation of Office of Management and Budget guidance in Code of Federal Regulations, Title 2, Part 200 (2 CFR 200), “Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.” DOD implementation is located in Chapter XI of 2 CFR.

• For contract awards:

○ The total period of performance may be proposed for up to 5 years in length; additional periods may be considered.

○ Any contract awarded under this BAA will be governed by the various provisions of the Federal Acquisition Regulation (FAR) and the Defense Federal Acquisition Regulation Supplement (DFARS).

• For other transactions:

○ Regarding Other Transaction Agreements (OTAs) that utilize the authority within

10 USC 4021 and 4022, the period of performance will be dependent upon each specific award made.

II. DETAILED INFORMATION ABOUT THE FUNDING

OPPORTUNITY

The USAMRDC’s mission is to provide solutions to medical problems of importance to the American Service Member at home and abroad, as well as to the general public at large. The scope of this effort and the priorities attached to specific projects are influenced by changes in military and civilian medical science and technology (S&T), operational requirements, military threat assessments, and national defense strategies. Extramural research and development programs play a vital role in the fulfillment of the objectives established by the USAMRDC.

General information on the USAMRDC can be obtained at https://mrdc.health.mil/.

This BAA is intended to solicit extramural research and development ideas using the authority provided by 10 USC 4001. The BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in 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 basic and applied research to support scientific study and experimentation directed toward advancing the state-of-the-art or increasing knowledge or understanding rather than focusing on development of a specific system or hardware solution. Research and development funded through this BAA are intended and expected to benefit and inform both military and civilian medical practice and knowledge. This BAA utilizes competitive procedures in accordance with 10 USC 2302(2)(B) for the selection for award of S&T proposals/applications. For the purposes of this BAA, S&T includes activities involving basic research, applied research, advanced technology development, and, under certain conditions, may include activities involving advanced component development and prototypes.

The selection process is highly competitive, and the quantity of meaningful submissions (both pre-proposals/pre-applications and full proposals/applications) received typically exceeds the number of awards that available funding can support.

This BAA provides a general description of USAMRDC’s research and development programs, including Research Areas of Interest, evaluation and selection criteria, pre-proposal/ pre-application and full proposal/application preparation instructions, and general administrative information. Specific submission information and additional administrative requirements can be found in the document titled, “General Submission Instructions,” which is available on Grants.gov along with this BAA.

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

The management agent for this BAA is the Congressionally Directed Medical Research Programs (CDMRP). The CDMRP manages the electronic Biomedical Research Application Portal (eBRAP) system, pre-proposal/pre-application and full proposal/application receipt and review, and other key process oversight. Refer to Section II.G, Federal Awarding Agency Contacts, for additional information.

https://mrdc.health.mil/

The USAMRDC’s supporting acquisition office, the U.S. Army Medical Research Acquisition Activity (USAMRAA), will be the awarding and administering office for proposals/applications selected for funding, unless approval is obtained from the USAMRAA Senior Contracting Official to allow another federal acquisition office to execute and administer an award.

II.A. Program Descriptions

II.A.1. Military Infectious Diseases Research Program

Infectious diseases (IDs) pose a significant threat to the operational effectiveness of current and future U.S. Forces. Current and future forces must be prepared to deploy globally and (potentially) on short notice. The U.S. Armed Forces may be called on to operate in areas of the world where infectious diseases present substantial and immediate health risks to DOD personnel. Current national military strategy specifies a worldwide force protection capability that requires surveillance, prevention, diagnosis, and treatment to protect the U.S. Armed Forces against potential infectious disease threats. Future operational scenarios pose increased impact of IDs as natural environmental disease barriers become degraded, enabling rapid spread of diseases across dense urban environments and the population existing within. For example, highly communicable bacterial and viral diseases, multi-drug resistant organisms, and vector-borne diseases will pose significant challenges in dense urban environments during Multi- Domain Operations (MDO).

The mission of the Military Infectious Diseases Research Program (MIDRP) is to plan, coordinate, and oversee the DOD requirements-driven medical solutions that PREVENT, PREDICT, and TREAT infectious diseases threats to the total force maximizing Warfighter readiness and performance.

The vision of the MIDRP is to defeat infection:

• Prevent naturally occurring infectious disease threats to eliminate their impacts on operational readiness of DOD personnel.

○ Prevention is the most desirable infectious disease countermeasure because it prevents disease from occurring (vs. treatment post-infection), is the most cost-effective approach, and reduces unit loss rate.

• Treat naturally occurring infectious disease threats to eliminate their impacts on operational readiness of DOD personnel.

○ Diagnosis centers on prediction of infection to identify the infectious disease BEFORE it is a problem and is integral to appropriate treatment, especially in settings of austere medical capabilities or during near-peer conflict with overwhelming numbers of casualties. Improved diagnosis and treatment of infectious disease casualties is necessary to protect the U.S. Armed Forces. Due to the ever-increasing resistance to presently available treatments, continued countermeasure development needs to be pursued.

Research Areas of Interest to the MIDRP are found in Appendix I.I. Applicants are urged to read and consider these before preparing their proposals/applications.

II.A.2. Combat Casualty Care Research Program

The Combat Casualty Care Research Program (CCCRP) provides integrated capabilities for current and future operations to reduce the mortality and morbidity associated with major combat-related trauma across the spectrum of combat casualty care, including point-of-injury and pre- or out-of-hospital care, the spectrum of en route care, and facilities-based treatment. A primary emphasis of the CCCRP is to identify and develop medical techniques, knowledge products, and materiel1 (medical devices, drugs, and biologics) for early intervention in life-threatening battle injuries and prolonged care.2 Because battlefield conditions impose severe constraints on available manpower, equipment, and medical supplies available for casualty care, the CCCRP places an emphasis on medical interventions that can be used within the battle area or as close to it as possible before or during medical evacuation. Preferred medical techniques and materiel that can be used by combat medics must be easily transportable (i.e., small, lightweight, and durable in extreme environments and handling). Devices must be easy to use and require low maintenance, with self-contained power sources as necessary. The CCCRP is interested in existing technologies for which concept and/or patient care efficacy have already been demonstrated, but require improvement to meet military requirements. Development and validation of in vitro and in vivo assessment models that represent military-relevant conditions in wounded Service Members, as well as those that incorporate a systems biology approach, are of interest to the CCCRP when they can be used to identify and describe the safety and efficacy of novel technologies in patients in a predictable manner.

Research efforts are needed in principles, therapies, and technologies to enhance self- and buddy aid, also referred to as tactical care; techniques, methods, or materiel to improve basic and advanced life support for all injured persons; monitoring, sustainment, and management of all injured casualties during episodes of delayed care or prolonged care; and enhanced capability for triage of large numbers of casualties and staged treatment in the field. The principal causes of death among Service Members who die within the first hour of wounding are hemorrhage and traumatic brain injury (TBI). TBI can also occur as a result of blast injuries sustained during training.

The CCCRP supports additional aspects of casualty care. These include drugs, devices, and/or novel surgical techniques to decontaminate, debride, protect, monitor, repair, and/or stabilize complex bone and soft tissue wounds to mitigate secondary tissue damage; improvements to blood products and blood product delivery; novel solutions for non-compressible hemorrhage;

treatments for moderate, severe and penetrating TBI; treatments and best practices for management of severe burn injury, to include burn shock and dysregulated metabolism following burn, and care of specialized tissues; acute and chronic pain; regenerative medicine;

and, advanced resuscitative care, organ support and critical care solutions. The CCCRP is also interested in the development of sensors; diagnostic and prognostic algorithms; data gathering or capture modalities; processors and autonomous care solutions to improve our capability for

1 Materiel is defined as equipment and supplies of a military force.

2 Prolonged care is defined as field medical care, applied beyond “doctrinal planning timelines” by a North Atlantic

Treaty Organization (NATO) Special Operations Combat Medic or higher in order to decrease patient mortality and morbidity. It utilizes limited resources and is sustained until the patient arrives at an appropriate level of care.

Rasmussen TE, Baer DG, Cap AP, et al. 2015. Ahead of the Curve. J Trauma Acute Care Surg 79:S61-64.

remote triage, monitoring, and management of casualties; and products to maintain casualties during prolonged evacuation. Regenerative medicine solutions with potential for early in-theater use will also be considered.

The CCCRP also focuses on the innovations required to reset our wounded Service Members, both in terms of duty performance and quality of life. Innovations developed from CRMRP-supported research efforts are expected to improve restorative treatments and rehabilitative care to maximize function for return to duty (RTD) or civilian life. Medical technologies (drugs, biologics, and devices) and treatment/rehabilitation strategies (methods, guidelines, standards, and information) that will significantly improve the medical care that our wounded Service Members receive within the DOD healthcare system are of particular interest. Implementation of these technologies and strategies should improve the rate of RTD of Service Members, the time to RTD, clinical outcome measures, and quality of life, as well as reduce the hospital stay lengths, clinical workload (patient encounters, treatments, etc.) of caregivers, and initial and long-term costs associated with restorative and rehabilitative or acute care.

The CCCRP supports the conduct of military-relevant clinical research aimed at translating knowledge or materiel from basic and preclinical trauma research into clinical practice. This includes, but is not limited to, single- and multi-center clinical trials performed in the civilian setting to clarify the safety, efficacy, and optimal use of products stemming from the previously mentioned research areas. Comparative effective clinical studies may be encouraged in areas of trauma care where a number of potential known approaches exist and require further investigation to inform selection of the most promising technologies. Novel manufacturing technologies necessary to translate innovative therapies or devices into clinical development are a focus.

The CCCRP supports the conduct of military-relevant, large-data research projects, including the use of large databases of common elements from trauma research projects (preclinical, translational, and clinical). Such studies should directly contribute to or effectively enable the data-driven conduct of combat casualty care. Examples include, but are not limited to, post-hoc analysis of data from completed trauma research projects, meta-analyses of a number of otherwise separate but completed studies, and the ability to harmonize data from planned or ongoing but otherwise separate research studies. All projects should adhere to a core set of reporting standards for rigorous study design.

The CCCRP also supports research related to sustainment of critical expeditionary medical skills. Innovations related to optimized learning, memory permanence, training effectiveness, and sustainment of perishable expeditionary medical skills supplying a comprehensive medical simulation training inventory. Importantly, this program also addresses psychosocial and physiological effects posed by virtual and augmented environments. This ensures the implementation and execution of immersive training events and promotes effective teaching while negotiating scientifically determined safety considerations. Goals include creating standardized training protocols and procedures that promote the effective transfer of knowledge and fosters development of critical medical abilities, while mitigating untoward effects (e.g., cybersickness) produced by modern digital teaching tools, timing, and technologies.

Research related to injuries caused by novel and emerging weapons systems or unique combat environments is also considered. CCCRP supports research in combined injury that focuses on the care of casualties that have sustained both polytrauma and or burn injuries in addition to injuries related to a chemical, biological, radiological, or nuclear scenario. Work is also considered related to medical countermeasures for acute ionizing radiation injury in the areas of post-exposure mitigation and pre-exposure prophylaxis.

The Research Areas of Interest to the CCCRP are found in Appendix I.II. Applicants are urged to read and consider these before preparing their proposals/applications.

II.A.3. Military Operational Medicine Research Program

The mission of the Military Operational Medicine Research Program (MOMRP) is to protect, optimize, sustain, and enhance the readiness and performance of Service Members and their families by developing effective biomedical countermeasures against operational stressors, as well as to prevent and mitigate physical and psychological injuries and threats during training and operations. The MOMRP supports Army Biomedical Performance Enhancement, Human Dimension, MDO, Soldier Lethality, Dense Urban Environment/Subterranean Operations, Army Modernization Priorities, with emphasis on Soldier Lethality and informing Future Vertical Lift Platform Development, Health Services Support, Protection and Survivability, and the DOD Total Force Fitness concepts.

The MOMRP supports research focused on addressing and delivering actionable solutions across the military lifecycle for critical biomedical problems facing the military today and in the future.

Service- and platform-specific issues are addressed through close coordination with all Services to prevent unnecessary duplication of effort.

The MOMRP is divided into four Research Areas of Interest (with examples of types of research efforts shown in parentheses): (1) Environmental Health and Protection (detecting, monitoring, countermeasure development and performance optimization while operating in extreme environmental [heat/cold/altitude/underwater] and during contaminant/toxicological exposures);

(2) Injury Prevention and Treatment (validated military performance and readiness assessment tools and metrics, physiological mechanisms, diagnostic capabilities, and optimal treatment of neuromusculoskeletal injury, neuromusculoskeletal injury return-to-duty standards and strategies, neurosensory related injury, and countermeasures against aviation stressors; primary [blast overpressure], secondary [penetrating ballistic fragments or debris], tertiary [accelerative injury], quaternary [burns or exposure to toxic substances], and quinary [illnesses, injuries, or diseases caused by chemical, biological, or radioactive substances] blast injury mechanisms [auditory and non-auditory], blunt trauma, and accelerative injury prevention strategies; and understanding the bioeffects and mitigation of emerging directed energy threats);

(3) Physiological Health and Performance (biomedical performance enhancement, performance and recovery nutrition, weight balance optimization, cognitive health and performance sustainment in the face of operational challenges, restorative sleep and fatigue management, resilience to operational and environmental stressors, and the medical aspects of manned-unmanned teaming); and (4) Psychological Health and Resilience (Post-Traumatic Stress Disorder [PTSD], adjustment disorders and other clinical disorders; combat operational stress reactions (COSR), suicide prevention and risk reduction, resilience, alcohol and substance misuse prevention, and violence prevention within the military).

More information on these Research Areas of Interest can be found in Appendix I.III.

Applicants are urged to read and consider these before preparing their proposals/applications.

The MOMRP is particularly interested in proposals/applications and products that incorporate integrated biomedical approaches (e.g., systems biology). Proposals/applications are encouraged to leverage existing resources and infrastructure to support lifecycle logistics and sustainability as well as consider integrated biomedical approaches (e.g. systems biology).

Guidance for research studies targeting military families and children: (1) In accordance with Department of Defense Instruction (DoDI) 1402.5 and Army Directive 2014-23, Child Care National Agency Check and Inquiries, background investigations are required for all individuals who have regular contact with military dependents under 18 years of age. All individuals who regularly interact with children under 18 years of age in Army-sponsored and -sanctioned programs are required to undergo specific initial background checks and periodic re-verifications. Investigators who propose work involving contact with military dependents under 18 years of age should plan for the additional time and funds required for such investigations.

(2) Per Department of Defense Education Activity (DoDEA) Administrative Instruction 2071.3, DoDEA approval is required for research studies involving DoDEA school personnel, school facilities, students, sponsors, and/or data. Investigators proposing to conduct any research activities involving DoDEA schools should plan for the additional time (~3-6 months) and effort required to obtain approval from DoDEA to conduct such activities. Procedures and requirements for the review and approval of a research study request can be found at https://www.dodea.edu/datacenter/research/requests.cfm. (3) Per Army Regulation AR 608-18, “The Family Advocacy Program,” the Family Advocacy Research Subcommittee will review, coordinate, and recommend approval and dissemination of all family advocacy research, evaluation projects, and research publications within the Department of the Army.

II.B. Award Information

This BAA may be used to support applied research, preclinical research, clinical research, and clinical trials/testing (or equivalent). BAA proposals/applications that include a clinical trial have additional proposal/application and review requirements (see Appendix II). The proposed research must be relevant to active-duty Service Members, Veterans, military beneficiaries, and/or the American public.

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 https://www.dodea.edu/datacenter/research/requests.cfm 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 32 CFR 219. Note: Food and Drug Administration (FDA)-regulated clinical investigation is always a clinical trial, but not all clinical trials are FDA clinical investigations.

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 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 processes following submission of all required and complete documents to the OHRO. 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, 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 application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical research/trials.

Research Involving Animals: All research funded by the BAA involving new and ongoing research with animals must be reviewed and approved by the USAMRDC OHARO 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 Application Instructions, Appendix 1, 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 S.C. Landis et al., “A call for transparent reporting to optimize the predictive value of preclinical research,” Nature 2012, 490:187-191 https://ebrap.org/eBRAP/public/Program.htm

(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 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.

II.B.1. Clinical Trial Support

Investigator(s) proposing a clinical trial should refer to Appendix II for a detailed description of the requirements for such a proposal/application. The pre-proposal/pre-application submission process should be performed as described in Section II.D.2.a. Full proposal/application submission is described in Appendix II. Refer to Appendix II, Section IV, Checklist for Research Proposal/Application Submission With a Clinical Trial, in preparing the full proposal/application.

For projects proposing a clinical trial:

• If an Investigational New Drug (IND) or Investigational Device Exemption (IDE) is required for the study, the IND/IDE application must be submitted to the FDA by the proposal/application submission. 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 12, Regulatory Strategy (Appendix II), for further details.

• 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.

• Clinical trials must be initiated no later than 12 months after the award date.

Note: The government reserves the right to withhold or withdraw funding if an IND or IDE is necessary to conduct the study but has not been obtained within 6 months of the award date.

II.B.2. Use of Military and Department of Veterans Affairs Populations or Resources

Principal Investigators (PIs) are encouraged to integrate and/or align their research projects with DOD and/or Department of Veterans Affairs (VA) research laboratories and programs and existing clinical trial networks. Collaboration with the DOD or VA is also encouraged. 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 III.

Use of DOD or 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. Use Attachment 2: Supporting Documentation, to provide relevant documentation to demonstrate access to DOD or VA https://www.nature.com/articles/nature11556 https://arriveguidelines.org/arrive-guidelines https://arriveguidelines.org/arrive-guidelines populations or resources. Refer to the General Submission Instructions, Appendix 1, for additional information.

45 CFR Section 46.114 (Cooperative Research) of the Common Rule requires any institution located in the United States that is engaged in cooperative research to rely upon approval by a single IRB for that portion of the research that is conducted in the United States. For multi-site studies with collaborating VA institutions engaged in non-exempt human subjects research, and for which the use of a single IRB is determined to be not appropriate for the particular research context, a memorandum from the VA Office of Research and Development approving exception of the single IRB requirement must be sought and provided to the OHARO OHRO during the human research protection official review of the project.

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 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://mrdc.health.mil/assets/docs/orp/ conducting_research_military_Pop_dod_may_2021.pdf.

Guidance for Research Studies Involving U.S. Army Special Operations Command (USASOC): Per USASOC policy 24-18, studies involving USASOC Soldiers as human subjects require additional review by the USASOC Research Advisory Committee (RAC) and Human Subjects Research Board (HSRB).

II.B.3. Technology Requirements and Standards

Any technology-based research products/prototypes (such as devices, mobile apps, software, information technology (IT) infrastructure, etc.) that expect to interact with military health IT systems should conform with accepted industry and DOD Information Management/IT standards for interoperability, cybersecurity, as well as the DOD Architecture Framework (DoDAF) and viewpoints, as follows:

a. DoDAF and viewpoints

b. DoDI 8500.01 March, 14, 2014, “Cybersecurity”

c. DoDI 8510.01 March 12, 2015, “Risk Management Framework (RMF)” https://mrdc.health.mil/assets/docs/orp/conducting_research_military_Pop_dod_may_2021.pdf https://mrdc.health.mil/assets/docs/orp/conducting_research_military_Pop_dod_may_2021.pdf

d. Any products expected to provide data to Military Health System (MHS) Genesis, the new DOD Military Electronic Health Record system (which is the military version of Cerner Millennium commercial-off-the-shelf electronic health record), should be aimed toward meeting the Health Level 7 and Fast Healthcare Interoperability Resources standards in order to ultimately provide integration with MHS Genesis.

e. All software-based research products including computer code, software code, data, and metadata should be provided as deliverables, and electronic versions need to be able to be uploaded to standards-based electronic repositories. Metadata (i.e., the data dictionary and data model) as well as data (i.e., cases) generated in the research should be provided in an industry standard format for access by the government in an open source data repository of electronic deliverables.

f. Any information systems that are owned or operated by the contractor that processes, stores, or transmits Federal contraction information, not intended for public release, is subject to the basic safeguarding requirements detailed under FAR 52.204-21, Basic Safeguarding of Covered information Systems

g. OTAs may establish non-standard requirements.

II.B.4. Data Sharing

The USAMRDC intends that information, data, and research resources generated under awards funded by this BAA be made available to the research community and to the public at large. The government reserves the right to identify repositories for submission of data for archive. For additional guidance, refer to the General Submission Instructions, Appendix 2, Section K.

A number of research areas utilize Common Data Elements (CDEs) to facilitate the sharing of data to promote collaboration, accelerate research, and advance knowledge in specific topic areas. In accordance with the White House Office of Science and Technology Policy memorandum, “Increasing Access to the Results of Federally Funded Research,” and Executive Order (EO) 13625 and the National Research Action Plan (NRAP) responding to the EO, “Improving Access to Mental Health Services for Veterans, Service Members, and Families” (August 31, 2012), federally funded research is required to be conducted in a manner that promotes public access to scientific data. In cases of psychological health and TBI, use of CDEs is required under the NRAP. The USAMRDC strongly encourages applicants to incorporate CDE measures appropriate to each field of study, such as:

• 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 (https://www.phenxtoolkit.org/index.php) in all studies involving human subjects, as applicable.

• Spinal cord injury research CDEs developed through the collaboration of the International

Spinal Cord Society, the American Spinal Injury Association, and the National Institute of Neurological Disorders and Stroke CDE team, as referenced at Spinal Cord Injury | NINDS Common Data Elements (nih.gov).

https://www.phenxtoolkit.org/index.php https://www.commondataelements.ninds.nih.gov/Spinal%20Cord%20Injury https://www.commondataelements.ninds.nih.gov/Spinal%20Cord%20Injury https://www.commondataelements.ninds.nih.gov/Spinal%20Cord%20Injury

TBI research data elements must be reported using the National Institute of Neurological Disorders and Stroke (NINDS) TBI CDEs or entered into the Federal Interagency Traumatic Brain Injury Research (FITBIR) data dictionary as new, unique data elements (UDEs). For the most current version of the NINDS TBI CDEs, go to http://www.commondataelements.ninds.nih.gov. Assistance will be available to help the researchers map their study variables to specific CDEs and ensure the formats of the CDEs collected are compatible with the FITBIR Informatics System. Use of the TBI CDEs is required wherever possible in an effort to create standardized definitions and guidelines about the kinds of data to collect and the data collection methods that should be used in clinical studies of TBI. Use of UDEs is strongly discouraged and subject to program approval.

If the project includes the collection of bio-fluids, such as blood, saliva, urine, etc., the PI may be required to include a set of collection variables and patient phenotypic data in order to standardize the quality of bio-fluid studies. The suggested procedures for acquisition, processing, storage, and shipment of bio-fluids can be found in Appendix IV.

For projects involving TBI, PIs may be required to report data to the FITBIR informatics system (https://fitbir.nih.gov/).

For studies that will enroll subjects with psychological health disorders, awardees may be requested to submit data to the National Institute of Mental Health Data Archive (NDA) https://nda.nih.gov/. The NDA is a data repository run by the National Institute of Mental Health (NIMH) that allows researchers studying mental illness to collect and share de-identified information with each other. Such studies may require the inclusion of specific language in the informed consent form which references the NDA (see Appendix V).

OTAs may establish unique data sharing requirements.

II.B.5. Funds Available and Anticipated Number of Awards

The funding amount for this BAA is unspecified, and the number of awards is indeterminate and contingent upon funding availability. Selection of research projects is a highly competitive process and is based on the evaluation of the proposal/application’s technical merit, programmatic considerations, and the availability of funds. The quantity of meaningful submissions received normally exceeds the number of awards that the available funding can support. Any funding that is received by the USAMRDC and is appropriate for a research area described within this BAA may be utilized to fund proposals/applications.

II.B.6. Award Amounts and Periods of Performance

There are no specified funding limitations identified for a proposal/application submitted under this BAA. A budget should be commensurate with the nature and complexity of the proposed research. Researchers should submit budgets that include the entire period of performance of the research project. Budgets should include all direct and indirect costs, based on supportable, verifiable estimates. The budget for the full proposal/application should not differ significantly from the Pre-Application Budget Summary Form provided in the pre-proposal/pre-application submission.

http://www.commondataelements.ninds.nih.gov/ https://fitbir.nih.gov/ https://nda.nih.gov/

Period of performance may differ depending upon the type of funding mechanism awarded under this BAA. For an assistance agreement, the total period of performance may be proposed for up to 4 years in length; additional periods may be considered. For research and development contract awards, the total period of performance may be proposed for up to 5 years in length;

additional periods may be considered. For OTAs that utilize the authority within 10 USC 4021 and 4022, the period of performance will be dependent upon each specific award made. Because the nature and scope of each proposed research project will vary, it is anticipated that the size and duration of each award will vary. Start dates will vary, depending on when proposals/applications were submitted and reviewed and the negotiation process. However, no proposal/application submitted under this BAA will be considered for funding after 24 months from the date of submission.

Organizations seeking additional or continuation funding must work with their respective PIs to submit new pre-proposals/pre-applications and be invited to submit full proposals/applications.

Refer to the General Submission Instructions, Section III.A.5, for additional information regarding the Research & Related Budget.

II.B.7. Mechanisms of Support

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. Refer to the General Submission Instructions, Appendix 2, Section D, for additional information.

Proposers awarded a Grant, Cooperative Agreement, Technology Investment Agreement (TIA), or Other Transaction for Research or Prototypes based on their response to this BAA shall follow the applicable rules and regulations governing these various award instruments, but, in all cases, should appropriately identify any potential restrictions on the government’s use of any Intellectual Property contemplated under the award instrument in question, refer to Attachment 8: Data and Research Resource Sharing Plan. This includes both noncommercial Items and commercial Items.

II.B.7.a. Procurement Contract: A legal instrument that, consistent with 31 USC 6303, reflects a relationship between the federal government and a state government, local government, or other entity/contractor when the principal purpose of the instrument is to acquire (by purchase, lease, or barter) property or services for the direct benefit or use of the federal government.

Contracts are primarily governed by the following regulations:

a. FAR

b. DFARS

II.B.7.b. Grant: A legal instrument that, consistent with 31 USC 6304, is used to enter into a relationship:

a. The principal purpose is to transfer a thing of value to the recipient to carry out a public purpose of support or stimulation authorized by a law or the United States, rather than to acquire property or services for the federal government’s direct benefit or use;

b. In which substantial involvement is not expected between the federal government and the recipient when carrying out the activity contemplated by the grant; and

c. No fee or profit is allowed.

II.B.7.c. Cooperative Agreement: A legal instrument that, consistent with 31 USC 6305, is used to enter into the same kind of relationship as a grant (see definition “grant”), except that substantial involvement (collaboration, participation, or intervention in the research) is expected between the federal government and the recipient when carrying out the activity contemplated by the cooperative agreement. The term does not include “cooperative research and development agreements” as defined in 15 USC 3710a. No fee or profit is allowed.

II.B.7.d. Other Transactions for Research: The USAMRDC will also consider the use of Other Transactions for Research as a vehicle for award under this BAA. In accordance with 10 USC 4021, “Research projects: transactions other than contracts and grants,” such other transactions shall not be entered into unless the following conditions are satisfied:

1. To the maximum extent practicable, no other transaction entered into shall provide for research that duplicates research being conducted under existing programs carried out by

DOD.

2. The funds provided by the government under another transaction authorization shall not exceed, to the extent that the Secretary of Defense determines practicable, the total amount provided by other parties to the other transaction.

II.B.7.e. Other Transactions for Prototypes: The USAMRDC will also consider the use of Other Transactions for Prototypes as a vehicle for award under this BAA. In accordance with 10 USC 4022, Prototype projects; transactions other than contracts and grants: “No official of an agency shall enter into a transaction (other than a contract, grant, or cooperative agreement) for a prototype project under the authority of 10 USC 4022 unless one of the following conditions is met:

(A) There is at least one nontraditional defense contractor or nonprofit research institution participating to a significant extent in the prototype project.

(B) All significant participants in the transaction other than the Federal Government are small businesses (including small businesses participating in a program described in section 9 of the Small Business Act (15 U.S.C. 638)) or nontraditional defense contractors.

(C) At least one-third of the total cost of the prototype project is to be paid out of funds provided by sources other than the federal government.

(D) The senior procurement executive for the agency determines in writing that exceptional circumstances justify the use of a transaction that provides for innovative business arrangements or structures that would not be feasible or appropriate under a contract, or would provide an opportunity to expand the defense supply base in a manner that would not be practical or feasible under a contract.”

In accordance with 10 USC 4022(f), any other transaction for prototypes awarded under this BAA may provide for the award of a follow-on production contract or transaction to the participants in the transaction without the use of competitive procedures.

Additional information can be found in the most current version of the Other Transactions Guide for Prototype Projects at https://www.acq.osd.mil/asda/dpc/cp/index.html.

II.C.…