It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The Chemical Countermeasures Research Program (CCRP) was established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID) to lead the research and early development of novel or improved therapeutics to mitigate the acute and long-term health effects of chemicals that have been identified by the U.S. Department of Homeland Security (DHS) as high consequence public health threats. These public health threat agents are highly toxic chemicals that could cause mass casualties after either deliberate terrorism-related release or inadvertently in the event of an industrial accident or natural disaster. The chemical threat spectrum includes chemical warfare agents (e.g., sarin, sulfur mustard), toxic industrial chemicals (e.g., chlorine, phosgene, cyanide), pesticides (e.g., parathion, brodifacoum), pharmaceutical-based agents (e.g., synthetic opioids), and others.

Within the CCRP, the NIH Countermeasures Against Chemical Threats (CounterACT) program supports a network of grants (R21), cooperative agreements (U01), and Centers (U54) that conducts research on the discovery and early development of medical countermeasures (MCMs) to reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents. The scope of research includes basic, translational, and pre-clinical research aimed at the discovery and/or identification of better MCMs against chemical threat agents and it supports their development in preparation for more advanced studies required for regulatory approval to ensure they are effective and safe for use in humans. This Funding Opportunity Announcement (FOA) specifically encourages applications for CounterACT U54 Research Centers of Excellence (RCE).

To ensure that the supported research is consistent with the overall goals of the program, CounterACT RCEs are milestone-driven cooperative agreement awards and will receive continuous and substantial scientific and programmatic attention from one or more NIH staff. The CounterACT U54 RCE must be comprised of: 1) An administrative core that provides oversight and management of the NIH award; 2) A research education core to foster and grow the chemical MCM research and development workforce; 3) Three or more scientifically integrated research projects and a minimum of one scientific core.

NIH CounterACT U54 RCE Program Directors/Principal Investigators (PDs/PIs) will become members of the NIH CounterACT research network, and will be able to utilize its resources, such as the CounterACT Preclinical Development Facility (CPDF). They will also be required to participate in annual meetings of the national CounterACT Network to share information and ideas.

The only chemical agents that will be supported in this U54 program are:

• Blood/Metabolic Agents: hydrogen cyanide, potassium cyanide and sodium cyanide
• Organophosphorus (OP) Chemical Warfare Agents (CWA) and Pesticides: must include at least one CWA (sarin, soman, tabun, VX) and contact the NIH Scientific/Research Contact listed in this Funding Opportunity Announcement for eligible pesticides
• Opioids: carfentanil, fentanyl and related analogs, also see NOT-NS-18-019
• Pulmonary Agents: chlorine and phosgene
• Vesicants: sulfur mustard and lewisite

Applications that propose research on chemical threats that are not listed above will be considered non-responsive and will not be considered for funding.

Many of the chemical threat agents of interest are extremely hazardous to humans. All applications must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment. Special biosafety certifications may be required to conduct research with some chemical threat agents, e.g., chemical warfare agents. Therefore, applicants are encouraged to collaborate with laboratories and contract research facilities that are already certified to work with restricted chemical agents, when applicable. See Section 4.1.24.3 of the NIH Grants Policy Statement for agents regulated under the Chemical Weapons Convention. Applicants are strongly encouraged to contact the relevant Scientific/Research Contacts listed in this FOA for further information on working with restricted chemical agents.

This FOA primarily supports translational research. Translational research is the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. The categories of research supported under this program include but are not limited to:

• Mechanistic research to identify targets for therapeutic development;
• Demonstration of in vitro activity of candidate(s), and generation of preliminary in vivo proof-of-concept efficacy data;
• Identification of lead candidate therapeutics using primary and secondary screening efforts, and other methods as described in PAR-19-039 Identification of Therapeutic Lead Compounds (U01);
• Optimization of lead candidate therapeutics using human-relevant animal models, bioanalytical assay development, laboratory-scale and scale-up manufacturing, and other methods described in PAR-19-040 Optimization of Therapeutic Lead Compounds (U01).

CounterACT RCE should strive to develop a comprehensive drug discovery and development program that includes all the above components (target identification, lead identification, and lead optimization). The development of a pipeline of candidate therapeutics should be designed to support several projects for which the applicant(s) can demonstrate a high level of synergy that increases the probability of achieving the goal of at least one successful lead or optimized lead compound by the end of the project period.

Only mechanistic studies that meet the NIH clinical trial definition will be supported; mechanistic trials are studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. Good Laboratory Practices (GLP) IND-enabling safety studies and pivotal efficacy studies in animals, cGMP production, and other studies required for most clinical trials will not be supported in this FOA. However, in some rare cases when sufficient preclinical studies have been completed, the opportunity for a small mechanistic clinical trial may arise and may be included if this research facilitates the overall goals within the above stated scientific scope of the FOA (i.e. basic research through lead optimization). Phase 1 and higher trials are not supported through this program.

There are two potential goals for the U54 Centers. At the end of the project period a lead compound must be (1) identified or (2) optimized. A lead compound is defined as biologically active and synthetically feasible compounds where preclinical specificity, affinity, potency, target selectivity, efficacy, and safety have been established. An optimized lead compound should be ready to enter advanced development studies such as IND-enabling GLP and GMP level studies. Most of the advanced development activities required for regulatory approval (including Phase 1 human safety trials) are not supported under this FOA but could potentially be supported by other federal agencies or industry once the NIH-supported research is completed. The HHS advanced development agency relevant to this FOA is the Biomedical Advanced Research and Development Authority (BARDA).

For U54 projects that will develop an optimized lead compound the applicant should have the following addressed before exploring the possibility of additional support through BARDA's Broad Agency Announcements (BAAs) program for advanced research:

• At least one lead compound with well understood absorption, distribution, metabolism, and excretion (ADME). Lead compounds are biologically active compounds or hits where affinity, potency, and selectivity have been established.
• Efficacy in an appropriate animal (with males and females) model relevant to the proposed concept of use in humans, i.e., the route and timing of therapeutic administration are consistent with a post-exposure treatment window.
• Initial pharmacology and toxicology studies.
• Stable and scalable synthesis of the lead compound.
• Preliminary regulatory strategy, e.g., a viable Target Product Profile, regulatory expertise, formal communication with the appropriate FDA Review Division.
• Commercialization plan for other indications, if applicable.
• Intellectual Property Rights/Freedom to Operate

Applicants are strongly encouraged to review the most current HHS BARDA Broad Agency Announcement during preparation of the NIH research application to ensure the project outcomes align with the needs of the prospective advanced developer.

RENEWAL APPLICATIONS should aim to have an optimized lead compound(s) ready to transition to advanced development at the end of the project period. SECOND (OR MORE) RENEWALs are not allowed.

Milestone-driven research is used to ensure research is focused on a well-defined goal and achieving that goal with greatest efficiency. As translational research is inherently high-risk, the use of milestones provides clear indicators of a project's continued success or emergent difficulties.

Milestones should describe the goal of the work and not just a statement that the work will be completed. Given the high-risk, progressive nature of therapeutics discovery and development, results at any stage of a project might indicate a dead end. For example, a toxicology study may reveal that a molecule is unsuitable for human use. Thus, the milestone should indicate the desired outcome of a study and not simply that the study was conducted. The milestones must provide objective and quantitative outcomes by which to justify advancing the project. The criteria for success of the studies conducted should be objective measures. These should be measures that would be recognizable as appropriate endpoints in the specific scientific area. They should also have clear success criteria that can be used for evaluation by NIH. For examples of acceptable milestones, see NIH CounterACT-Milestone-Example.

Annual milestones may be modified in negotiations with NIH program officials before an initial award is made, and during the review of annual non-competitive research performance progress reports. Unmet milestones and an incomplete data package that prevents an adequate interpretation of the results will have a negative impact on the review and approval of these annual non-competing applications. Partial budget reductions and/or restrictions in a given project year may also occur if all milestones are not met. If further research on a project is deemed futile, that project may be discontinued.

Applicants proposing research with a specific compound must demonstrate freedom to operate with that compound or drug. The NIH encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy during the project period. Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the therapy development process. PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. It is recognized that in the case of medical countermeasures, commercialization may be challenging. Therefore, applicants are encouraged to discuss alternative strategies with NIH Scientific/Research staff to get further guidance.

In general, the scope of research covered in this FOA can also be described by Technology Readiness Levels (TRLs). The TRLs covered in this FOA should fall between TRLs 3 through 5.

Specific examples of relevant research topics include but are not limited to those listed below:

• Therapies based on acute toxicity of the chemical threat agent, e.g., new approaches to counteract neurological effects, pulmonary edema, relevant anti-inflammatory drugs, surfactants, antioxidants, the development of better skin and eye protectants.
• Natural history animal models of the acute toxicity of chemical threat agents. These studies could include characterization of long-term effects after sub-lethal acute exposures to chemical threats agents, e.g., neuroprotectants for neurodegeneration and other neurological sequelae, drugs to prevent long-term pulmonary fibrosis, etc.
• Studies relevant to the special vulnerabilities of pediatric populations and pregnant women as they relate to the development of therapeutics, e.g., acute effects on the developing brain that have long-term effects, the need for therapeutics dosing schedules and routes of administration that are more suitable for children and pregnant women.
• Basic research on the molecular mechanisms of toxicity for the purpose of identifying novel targets, e.g., the mechanisms of nerve agent-induced long-term neurological effects or seizures with respect to temporal and regional changes, roles of cardiac versus neuronal mitochondria in cyanide toxicity, cellular and molecular basis for agent induced pulmonary edema.
• Alternate routes of administration for new or approved therapies that would be safe, effective, and easy to administer during a mass casualty scenario, e.g., intramuscular route.

MCM that is effective only against a single chemical threat agent will be considered; however, applicants are strongly encouraged to consider a research program that aims to uncover commonality in acute effects and pathologies across multiple chemical threat agents, so that the therapeutics being developed will have a broader spectrum of activity. This latter approach would support discovery of MCMs to treat the toxidromes.

Due to the urgency in need and the lengthy time and expense to bring a new chemical/biologic entity to regulatory approval, applicants are encouraged to consider drugs that are already approved by the United States (U.S.) Food and Drug Administration (FDA) for other indications, i.e., drug repurposing. The identification of existing compounds for repurposing as MCMs holds the potential to expand current response capabilities to chemical threats, as well as potentially mitigating the costs and risks associated with conventional drug discovery. Applicants are strongly encouraged to work closely with their institutional technology transfer office to obtain and retain any IP developed around the proposed repurposing effort. Applicants are urged to contact the Scientific/Research Contacts listed in this FOA for more information related to the FDA as well as to seek out appropriate regulatory expertise in support of the proposed research. FDA Guidance for Industry relevant to this program can be found here.

This FOA will only support research that is clearly relevant to the development of therapeutics that will enhance our medical response capabilities during or after a chemical emergency event. Therapeutics only effective if given prior to chemical insult (pretreatment/pre-exposure), or those that must be given immediately after exposure, will be of low priority without convincing evidence that context of use of the drug is applicable to a mass casualty exposure. Since many chemical threats have rapid modes of action, the drug should act rapidly to counter the toxic effects. The experimental design of proposed studies should be consistent with the timing and route of administration intended for use in humans during a chemical emergency. Therapies that are only effective when administered intravenously (IV) in the pre-hospital setting would be of low priority since their use would be impractical after a mass casualty exposure. However, in some cases, in-hospital IV MCM administration may be appropriate if the concept of use is to treat those victims who survive the acute lethal effects and require further treatment to mitigate potential long-term sequelae. Model development, screening activity, and efficacy studies should be designed and well-justified with these ultimate requirements under consideration.

Special consideration will be afforded to research particularly relevant to the pediatric population and others that are also considered to be especially vulnerable to the adverse health effects of chemical agents, including geriatric, pregnant, and/or individuals with pre-existing medical conditions. Animal models and studies that address vulnerabilities in these special subpopulations will be of high research priority.

There should be a unifying well-defined goal or problem area of research to which each project relates and contributes, thereby producing a synergistic research environment that allows each research effort to share the resources and creative strengths of the others. There is the expectation that support of interrelated projects and collaborating investigators would yield results beyond those achievable if each project were pursued separately without formal interaction among the participating investigators. All investigators should contribute to, and share in, the responsibilities of fulfilling the Center objectives and milestones.

Milestones for the overall Center should be developed. These Center milestones should reflect the overall goals and objectives of the Center and be supported by the milestones proposed in the subprojects. There may only be 3 or 4 Center milestones per year over the course of the entire project period.

Each CounterACT Research Center of Excellence should include the following components:

• One Administrative Core for Center Management and Operations, including the Emerging Science and Scientists Pilot Project Program (ESSP3);
• Three to five interrelated Research and Development Projects;
• Up to three Scientific Cores if needed and well justified and;
• One Research Education Core

Administrative Core for Center Management and Operations

• The PD/PI or Center Director will be responsible for overall planning and management of the CounterACT Center. Each proposed Center Director must commit a minimum effort of 3 person months per year overall to the Center and be a leader of one of the projects and of the Administrative Core. The 3 person months should be a total of the Center Director's efforts on his/her project(s) and core(s). In a multiple PD/PI Center, the combined efforts of the Center Directors must equal a total of 3 months including the administrative core and project commitments.
• The PD/PI and Administrative Core staff will be responsible for managing, coordinating, supervising the entire range of Center activities, and monitoring progress in an effective and efficient manner. It is recommended that both an Administrative and Scientific Program Manager is included to assist the PD/PI. The PD/PI and Administrative Core staff will be responsible for ensuring that appropriate systems are in place to provide for biosafety and security of materials, data, and facilities.

A key component of the Administrative Core is the Emerging Science and Scientists Pilot Project Program (ESSP3). The primary goals of the ESSP3 are to: 1) support innovative research on emerging scientific findings related to the topic of the Center, and 2) recruit new investigators into the field of medical countermeasures research. The ESSP3 should have the following features:

• ESSP3 investigators may only include: (a) early stage investigators (ESIs) or (b) established investigators not previously involved in medical countermeasures research. An ESI is defined as a new investigator who has completed his or her terminal research degree or medical residency whichever date is later within the past 10 years and has not yet competed successfully for a substantial, competing NIH research grant (see NOT-OD-19-072: Updates to NIH Policy on ESI Application Status).
• The ESSP3 investigators should aim to include women and under-represented minorities (see https://diversity.nih.gov/about-us/population-underrepresented)
• ESSP3 research projects are limited to $75,000 direct costs per year (inclusive of all costs, including Core services) and are part of the Administrative Core’s budget. These funds will be restricted to sole support of the ESSP3.
• ESSP3 project periods are limited to two years.
• The Center will be limited to 2-3 ESSP3 research projects at any given point in time.
• NIH CounterACT Center institutions may develop and co-fund joint ESSP3 activities.
• Projects may represent new collaborations with currently funded investigators within the proposed NIH CounterACT Center, as well as researchers within or outside the Center’s academic community.
• The ESSP3 is not intended to support or supplement ongoing research of an established investigator within or outside the Center.
• These pilot feasibility projects should be similar in purpose and scope to small research project grants (R03), and address innovative, interdisciplinary research consistent with the Center's focus.
• Pilot feasibility studies should serve as a mechanism for conducting nimble proof-of-concept studies that allow for maximum flexibility to advance exciting research directions that seem most scientifically fruitful and allow for a greater element of risk than is permitted in standard NIH funding opportunities, e.g. new targets for threat agents, early efficacy and safety, and other studies that will position the investigator(s) for subsequent research that aligns with the Center's scientific goals. Examples of future research applications within the NIH CounterACT program can be found at the program website (see CounterACT Researchers & Projects).
• The CounterACT U54 Center Administrative core should establish and manage a solicitation, review, selection, and monitoring process for ESSP3 projects, including the distribution of yearly sub-award funds. Peer review of the ESSP3 grants will be managed by the Center’s Administrative Core in conjunction with the awarding NIH institute.
• All pilot projects must comply with applicable NIH policies and the evidence that proposed plans for protection of human subjects; inclusion of women, minorities, and children; and assurance of animal welfare must be submitted to the NIH institute Program Official prior to study initiation.

Research and Development Projects

These projects should be scientifically linked. Examples of how these projects could be linked include:

• One effect: A single or multiple therapeutic(s) to treat a single type of effect or toxidrome, e.g., inflammation. This may include therapeutic(s) against one or multiple chemical agents that cause inflammation.
• One chemical threat: A single or multiple therapeutic(s) to treat a single type of chemical threat, e.g. nerve agents. This may include therapeutic(s) against one or multiple kinds of effects caused by nerve agents (e.g., neurological, pulmonary, dermal).

Scientific Core(s)

Scientific Core facilities (minimum of one) may be proposed if they will be utilized by at least two of the projects. Such core facilities should provide services that are already available, fully developed, and cannot be funded through other means for the purposes proposed. Scientific Core facilities may include clinical, statistical, technical, or other supportive activities. In many cases a core for exposing animals to chemical threat agents will be necessary. Exposure cores to be used for chemical threat agents that have restricted use can ONLY be used in facilities that are already certified to work with restricted chemical agents (see Section 4.1.24.3 of the NIH Grants Policy Statement for agents regulated under the Chemical Weapons Convention). For this FOA, these restricted agents include all chemical weapon nerve agents and vesicants.

Research Education

One goal of the CounterACT program is to increase the number and capabilities of researchers and other personnel in applied toxicological research related to chemical threats. In general, the research education core should be multidisciplinary and provide short-term education for technicians, medical or graduate students, postdoctoral fellows, and/or independent investigators, either within or beyond the CounterACT Center. Formal graduate programs are excluded from this FOA.

The proposed core should build on the strengths of the Center investigators, although outside instructors may be incorporated on occasion to provide cross-disciplinary depth.

Proposed activities within the core should facilitate the development of skills in the use of assays, methods, reagents, animal models, or technologies to develop new products through the regulatory process. Some examples include but are not limited to undergraduate, graduate, and post-doctoral mentored research experiences, workshops, symposia and lectures on MCM research and development, programs on rigor, responsible conduct of research, study design, data management, and online educational resources.

Program Oversight

CounterACT Center Steering Committee:

A Steering Committee for each CounterACT Center will make strategic decisions regarding goals and research implementation of the Center to ensure that scientific milestones are met, resources are shared, and productive collaborations are established. The Center Steering Committee will meet as frequently as possible utilizing various modes of communication, and be composed of the PD/PI, subproject investigators and other members with relevant scientific expertise. The NIH program official will serve on this committee.

External Advisory Committee:

Awardees will form an External Advisory Committee. This committee will provide subjective evaluation of the annual progress of the Center and make recommendations to the Center PD/PI. The Committee should meet once per project year. To maintain the largest possible reviewer pool for this FOA, applicants should not propose specific external advisors and should not contact potential members prior to NIH review of the application, for both new and renewal applications.

As a cooperative agreement, implementation will involve the participation of NIH Program staff in the planning and execution of the therapy-directed projects. Applicants are strongly encouraged to consult with the relevant NIH Scientific/Research staff when planning an application. Early contact provides an opportunity for NIH Scientific/Research staff to provide further guidance on program scope, goals, developing appropriate milestones, and budget. Applicants should contact the relevant NIH Scientific/Research staff at least 12 weeks before a due date.

Applications that propose research on chemical threats that are not listed in Section I.B. Chemical Threats of Research Interest (above in this FOA) will be considered non-responsive and will not be reviewed for this FOA.

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

There is no limit on the number of applications from each institution, however only one funded CounterACT Research Center of Excellence is allowed within a School at a University or College at any given time.

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• The specific chemical threat agent(s) that will be studied
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

David A. Jett, Ph.D.
Telephone: 301-496-6035
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Administrative Core	12
Project	12
Core (used for Scientific Core and Research Education Core)	6

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of 1
• Projects: required; minimum of 3, maximum of 5
• Scientific Core: required; minimum of 1 and maximum of 3
• Research Education Core: required; maximum of 1

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Other Attachments:

Intellectual Property Strategy: Applications, with a pre-identified proposed therapeutic(s), are expected to include an Intellectual Property (IP) strategy that is no more than one page (if multiple therapeutics have been pre-identified then no more than one page per compound). Applications that exceed this limit will be withdrawn. This attachment should be entitled "IP_Strategy_CompoundName.pdf" and reflected in the final image. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

Applicants should describe the IP landscape surrounding their proposed therapeutic(s). This should include any known constraints that could impede the development of their medical countermeasure (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar approaches that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program. If the applicant proposes using a compound whose IP is not owned by the applicant's institution, the applicant should address any questions that may constrain or impede its ability to operate and move the compound forward. Applicants should include a letter (see Letters of Support) from the entity that owns the IP indicating whether the entity will provide the compound, if there are any limits on the studies that can be performed with that compound, and agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the therapeutic(s) being developed under this application have been filed, the applicants should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent Office (USPTO) links, if applicable. Applicants should also discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the compound(s) to practical application and for coordinating these efforts (e.g., how IP will be shared, licensing, managing IP) among the institutions.

U54 Center Organizational Structure: Applicants must include a diagram of the organizational structure of the U54 Center. This diagram should demonstrate how the interactions between the different Center components achieve integration and the overarching goals of the Center. The diagram should be provided as a pdf file titled "U54 Center Organizational Structure"

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed research of the overall Center, and summarize the expected outcome(s), including the impact the proposed research will exert on the field.

Research Strategy: The Overall Research Strategy should present the overall vision for the proposed CounterACT Center including the following segments:

• Describe a unifying well-defined goal of the research and development program that leads to the identification (for NEW applications) or optimization (for RENEWAL applications) of a therapeutic compound(s). Include the overall vision of the research even if it is beyond the proposed project period.
• In support of these overall goals, provide Center Milestones; include the year of projected completion. Center milestones should reflect discrete steps towards the overall goal(s) of the Center during the entire project period. They should be supported by annual subproject milestones described below. Milestones toward therapeutic intervention are not a description of specific aims and experiments, but rather are discrete goals that create go or no-go decision points that include quantitative success criteria.
• Describe how the Center research will enhance medical response capabilities during a chemical emergency, including exactly how the therapeutic(s) would be used in a mass casualty situation. The ultimate intended use of a drug should be discussed within the application, including timing and route of administration that are consistent with its effective use in an emergency civilian setting.
• Explain how in vitro and/or in vivo models will be used to advance therapeutic development, and why they are relevant to serious morbidity and/or mortality in humans.
• Describe how each project relates and contributes to the others, including how they would yield results beyond those achievable if each project were pursued separately without formal interaction among the participating investigators. A diagram is often useful in this regard.
• Outline the major strength of the research team in the context of the proposed area of focus; characterize the relevant expertise of team members and the advantages of their respective research environments.
• As the research strategy is prepared, it is important to note that NIH believes that applications that propose preclinical research based on previous preclinical data, will be greatly strengthened if the design, execution, and interpretation of the proposed studies and supporting data are adequately described. Investigators are encouraged, whenever possible, to address these elements directly in their applications. Investigators are urged to discuss these issues with Scientific/Research staff prior to submission of applications.
• For renewal applications only, describe the progress of the CounterACT Research Center to date.

Letters of Support: Include letters of support/agreements for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support for the CounterACT U54 overall should be included with the Overall component. Letters of support for individual scientific projects or cores should be included with those components of the application.

• If restricted chemical agents will be used at collaborating laboratories, the approval to use these by appropriate authorities should be included in the letter of support.
• If applying from an academic institution, include a letter of support from the technology transfer official(s) who will be managing existing and future intellectual property associated with the Center. The letter of support should confirm IP will be managed consistent with achieving goals of the program.
• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions. A letter of support from the technology transfer official(s) who will be managing existing and future intellectual property at each institution should be included and confirm IP will be managed consistent with achieving goals of the program.
• If collaborating with a private entity (e.g., regulatory support), include a letter of collaboration that addresses any agreement to provide service(s), any limits on the services that can be performed, any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place, if applicable. This letter should come from an official within the private entity who has the appropriate authority.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The Data Sharing Plan should be submitted in the Overall component and should apply to all components of the application. A plan for distribution of data or samples generated in Research Projects should be included, and should conform to the NIH policy on data and resource sharing (https://grants.nih.gov/grants/policy/data_sharing).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: Describe institutional commitment; include any relationships to other affiliates, clinical or medical centers at the Center as appropriate.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The PD/PI should be the director of the Administrative Core and should commit at least 1.2 Person Months to these responsibilities, in addition to his/her own CounterACT research and other activities, if applicable.

Budget forms appropriate for the specific component will be included in the application package.

Each proposed Center Director must commit a minimum effort of 3 person months per year overall to the Center and be a leader of one of the projects and of the Administrative Core. The 3 person months should be a total of the Center Director's efforts on his/her project(s) and core(s). In a multiple PD/PI Center, the combined efforts of the Center Directors must equal a total of 3 months including the administrative core and project commitments.

When appropriate, awardees will be expected to collaborate; share novel reagents, assays, and animal models; and share both positive and negative results that would help guide the research and development activities of other CounterACT awardees. These activities will be facilitated by annual meetings of CounterACT investigators. Budgets should include cost for travel to one annual meeting of CounterACT investigators each of the proposed project years, in addition to other anticipated travel associated with the research. Post-doc, junior, and diverse investigators are encouraged to attend these meetings and budgets should be planned accordingly.

The budget for the ESSP3 program should be included in the Administrative Core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: The specific aims should briefly but specifically describe the goals of the Administrative Core.

Research Strategy: The Administrative Core description should:

• Describe the organization of the leadership structure; roles of program managers and other personnel if applicable
• Outline the responsibilities of Core Lead avoid duplication with the standard required item "Multiple PD/PI Leadership Plan" (see below)
• Describe the overall plans for the participation in CounterACT Center Steering Committee and External Advisory Committee, including frequency of meetings, teleconferences, video or web meetings
• Outline the organization and functioning of the Administrative Core, including support staff.
• The following information must be provided for the ESSP3:
• A detailed plan for the process by which pilot projects will be solicited, reviewed, selected, funded, and monitored
• Centers should describe a plan for soliciting applications from early-stage investigators and diverse investigators
• A detailed plan for effective recruitment of women and under-represented minorities (see https://diversity.nih.gov/about-us/population-underrepresented) into the ESSP3 program must be included within the program description.
• A strategy for aligning pilot project data sharing with other Research Center activities for streamlined data management and analysis the distribution of yearly sub-award funds, especially for those that aren't located at the parent institution

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Omit the sharing plans here as they were provided in the Overall section.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: The specific aims should briefly but specifically describe the goals of the Scientific Core.

Research Strategy: The Scientific Core description should:

• The applicant must provide a clear justification for each optional Scientific Core and how it will support the research projects, including how they will be utilized by at least two of the projects.
• Include the description of the Scientific Core, the services to be rendered, and the methodological approaches to be used. This section must clearly present the facilities, techniques, and professional skills that the Core will provide.
• Explain how the Core is justified by the scientific needs of the Center. Describe how the expected contributions of the Core will accelerate progress and promote more effective approaches that will enhance the likelihood of success of the research project(s).
• Explain why support for the indicated functionality in the form of a centralized Core of the Center will be more efficient than if the research projects themselves were to provide the functionality, or how the Core provides added value beyond that which would be provided by acquisition through fee for service or commercial access.
• Describe how each scientific core is essential and supports the overall goals of the center.
• Describe plans and procedures for establishing and managing the Core. Describe the role of the Core Leader and each of the key participants. Describe plans and procedures for quality control and cost-effectiveness of the services and resources provided by the Core to the Center investigators.
• If the Support Core is designed to interface with the ESSP3 sub-awardees, describe the process(es) that will be in place to facilitate coordination, distribution and accessibility to the services, facilities or resources that the Core proposes to provide.
• In the Research Strategy section, a Scientific Core that provides analytical and quantitative services to the applicant's Center should include a Quality Assurance Section. The Quality Assurance Section should document the Center's policy on implementing and assessing the effectiveness of its quality assurance and quality control operations.
• If repositories for cells, tissues, data, or reagents are included, describe methods to obtain, protect, and archive relevant pathological, clinical, and family history information. In addition, appropriate informatics capability should be provided to track data and link to other data sets.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Omit the sharing plans here as they were provided in the Overall section.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: The specific aims should briefly but specifically describe the goals of the research project.

Research Strategy: The Research Strategy section should:

• Follow standard application instructions, including sub-sections describing Significance, Innovation, Approach, and Preliminary Studies for New Applications, or a Progress Report for Renewal Applications.
• Applicants should include a description that clearly states the relevance of the project to the goals of the overall Center.
• Describe the research project in sufficient detail to enable reviewers to judge its scientific merit.
• In support of the Specific Aims of the project, provide annual milestones. Milestones toward therapeutic intervention are not a description of specific aims and experiments, but rather are discrete goals that create go or no-go decision points that include quantitative success criteria.
• (For examples of acceptable milestones, see https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library//CounterACT-Milestone-Example.
• Discuss the ultimate intended use of a drug, including timing and route of administration that are consistent with its effective use in humans in an emergency civilian setting.
• If a potential therapeutic hit(s)/lead(s) was pre-identified, this section should also contain a detailed description of the compound(s) to include chemical structure information and discussion of its potential for drug development, including possible optimization plans to further develop the compound(s). The lack of structural information for the potential therapeutic hit(s)/lead(s) may adversely affect assessment of its optimization potential. NIH has multiple safeguards to protect the integrity of and to maintain confidentiality in peer review.
• Drug development plans, e.g., specific optimization studies, should entail clear and quantitative goals to be achieved. These studies may include, but are not limited to, refining the compound's chemical, biological, and safety properties by addressing properties such as potency, selectivity, ADMET, hERG, Ames activity, etc.
• If a lead product was identified, the proposed plan should address the regulatory strategies necessary to advance the proposed medical countermeasure, e.g., addressing essential elements described in the relevant FDA Guidance for Industry - Product Development Under the Animal Rule (e.g., suitability of the proposed animal species, etc.) Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers (e.g., dose selection and translation to humans), Co-development of Two or More New Investigational Drugs for Use in Combination, etc.
• Regulatory input, preferably from the FDA, should be provided for efforts to develop large animal models, e.g., swine, ovine, nonhuman primates.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Omit the sharing plans here as they were provided in the Overall section.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• A minimum of $50,000 in direct costs per year must be allocated to the Research Education Core activities.
• Include all personnel other than the PD(s)/PI(s) in the Other Personnel section, including clerical and administrative staff.
• Use the section on Participant/Trainee Support Costs to include all allowable categories of funds requested to support participants in the program.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: The specific aims should briefly but specifically describe the goals of the Research Education Core.

Research Strategy: This section must include the following subsections:

Proposed Research Education Program: While the proposed research education program may complement ongoing research training and education occurring at the applicant institution, the proposed educational experiences must be distinct from those research training and research education programs currently receiving federal support. When research training programs are on-going in the same department, the applicant organization should clearly distinguish between the activities in the proposed research education program and the research training supported by the training program. The proposed research education program should plan to create/expand local and remote capabilities for facilitating the development of key skill sets for investigators such as technicians, medical or graduate students, postdoctoral fellows, and/or independent investigators, either within or beyond the CounterACT Center. These skills may be related to the use of assays, methods, reagents, animal models, or technologies.

Core Lead(s): Describe arrangements for administration of the program. Provide evidence that the Core Lead(s) is actively engaged in research and/or teaching in an area related to the mission of NIH, and can organize, administer, monitor, and evaluate the research education program. For programs proposing multiple PDs/PIs, describe the complementary and integrated expertise of the PDs/PIs; their leadership approach, and governance appropriate for the planned project.

Program Faculty: Researchers from diverse backgrounds, including racial and ethnic minorities, persons with disabilities, and women are encouraged to participate as program faculty. Faculty should have research expertise and experience relevant to the proposed program and demonstrate a history of, or the potential for, their intended roles.

Program Participants: Applications must describe the intended participants, and the eligibility criteria and/or specific educational background characteristics that are essential for participation in the proposed research education program. Identify the career levels for which the proposed program is planned.

Recruitment Plan to Enhance Diversity: Fostering diversity in the scientific research workforce is a key component of the NIH strategy to identify, develop, support and maintain the quality of our scientific human capital (NOT-OD-20-031). Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH's ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the researchers, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups identified as underrepresented in the biomedical, clinical, behavioral and social sciences, such as:

A. Individuals from racial and ethnic groups that have been shown by the National Science Foundation to be underrepresented in health-related sciences on a national basis (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27) and the report Women, Minorities, and Persons with Disabilities in Science and Engineering). The following racial and ethnic groups have been shown to be underrepresented in biomedical research: Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, and Native Hawaiians and other Pacific Islanders.

B. Individuals with disabilities, who are defined as those with a physical or mental impairment that substantially limits one or more major life activities, as described in the Americans with Disabilities Act of 1990, as amended. See NSF data at, https://www.nsf.gov/statistics/2017/nsf17310/static/data/tab7-5.pdf.

C. Individuals from disadvantaged backgrounds, defined as those who meet two or more of the following criteria:

• Were or currently are homeless, as defined by the McKinney-Vento Homeless Assistance Act (Definition: https://nche.ed.gov/mckinney-vento/);
• Were or currently are in the foster care system, as defined by the Administration for Children and Families (Definition: https://www.acf.hhs.gov/cb/focus-areas/foster-care);
• Were eligible for the Federal Free and Reduced Lunch Program for two or more years (Definition: https://www.fns.usda.gov/school-meals/income-eligibility-guidelines);
• Have/had no parents or legal guardians who completed a bachelor s degree (see https://nces.ed.gov/pubs2018/2018009.pdf);
• Were or currently are eligible for Federal Pell grants (Definition: https://www2.ed.gov/programs/fpg/eligibility.html);
• Received support from the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) as a parent or child (Definition: https://www.fns.usda.gov/wic/wic-eligibility-requirements).
• Grew up in one of the following areas: a) a U.S. rural area, as designated by the Health Resources and Services Administration (HRSA) Rural Health Grants Eligibility Analyzer (https://data.hrsa.gov/tools/rural-health), or b) a Centers for Medicare and Medicaid Services-designated Low-Income and Health Professional Shortage Areas (qualifying zipcodes are included in the file). Only one of the two possibilities in #7 can be used as a criterion for the disadvantaged background definition.

Students from low socioeconomic (SES) status backgrounds have been shown to obtain bachelor’s and advanced degrees at significantly lower rates than students from middle and high SES groups (see https://nces.ed.gov/programs/coe/indicator_tva.asp), and are subsequently less likely to be represented in biomedical research. For background see Department of Education data at, https://nces.ed.gov/; https://nces.ed.gov/programs/coe/indicator_tva.asp; https://www2.ed.gov/rschstat/research/pubs/advancing-diversity-inclusion.pdf.

D. Literature shows that women from the above backgrounds (categories A, B, and C) face particular challenges at the graduate level and beyond in scientific fields. (See, e.g., From the NIH: A Systems Approach to Increasing the Diversity of Biomedical Research Workforce https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008902/ ).

New applications must include a description of plans to enhance recruitment, including the strategies that will be used to enhance the recruitment of participants from underrepresented backgrounds and may wish to include data in support of past accomplishments.

Renewal applications must include a detailed account of experiences in recruiting individuals from underrepresented groups during the previous funding period. Information must be included on successful and unsuccessful recruitment strategies including aggregate information on the distribution of:

• Individuals who applied for admission to the research education program,
• Individuals who were offered admission to the research education program,
• Individuals who participated in the research education program.

For those individuals who participated in the research education program, the report should include information about the duration of education and aggregate information on the number of individuals who finished the program in good standing. Additional information on the required Recruitment and Retention Plan to Enhance Diversity is available at Frequently Asked Questions: Recruitment and Retention Plan to Enhance Diversity (Diversity FAQs).

Applications lacking a Recruitment Plan to Enhance Diversity will not be reviewed.

Plan for Instruction in the Responsible Conduct of Research: All applications must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). The plan must address the five, required instructional components outlined in the NIH policy: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable); 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics; 3) Faculty Participation - the role of the program faculty in the instruction; 4) Duration of Instruction - the number of contact hours of instruction, taking into consideration the duration of the program; and 5) Frequency of Instruction instruction must occur during each career stage and at least once every four years. See also NOT-OD-16-122. The plan should be appropriate and reasonable for the nature and duration of the proposed program. Renewal (Type 2) applications must, in addition, describe any changes in formal instruction over the past project period and plans to address any weaknesses in the current instruction plan. All participating faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period must be named in the application.

Applications lacking a plan for instruction in responsible conduct of research will not be reviewed.

Evaluation Plan: Applications must include a plan for evaluating the activities supported by the Core. The application must specify baseline metrics (e.g., numbers, educational levels, and demographic characteristics of participants), as well as measures to gauge the short or long-term success of the research education award in achieving its objectives. Wherever appropriate, applicants are encouraged to obtain feedback from participants to help identify weaknesses and to provide suggestions for improvements.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Omit the sharing plans here as they were provided in the Overall section.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CounterACT Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a CounterACT Center that by its nature is not innovative may be essential to advance a field.

Does the CounterACT Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the CounterACT Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Will the proposed therapeutic reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents?

Will the proposed result in at least one lead compound (for NEW applications) or at least one optimized lead compound (for RENEWAL applications)?

How rigorous is the preliminary data supporting the choice of the proposed injury mechanism and/or therapeutics for the indication, i.e., biological relevance?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CounterACT Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Are the scientific qualifications, scientific and administrative leadership capabilities, and time commitment of the PD/PI adequate? For applications involving multiple PDs/PIs, are their designated roles and responsibilities well defined, adequate, and appropriate for achieving the goals of the proposed CounterACT Center?

Are the qualifications of core directors and managers adequate?

Is there adequate statistical and/or regulatory support for the experimental design, analysis, and interpretation of the generated preclinical data?

Are there adequate personnel to manage existing and future intellectual property associated with this project?

Are the proposed facilitators experienced in the types of activities proposed in the Research Education Core?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the CounterACT Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the CounterACT Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Is the overall timeline reasonable for the work proposed? For key experiments, does the application explain assumptions for power analysis, describe statistical analysis methods and criteria for data inclusion or exclusion, and detail the procedures of how blinding and randomization will be conducted? Will projects that propose to identify a lead compound do so within the multi-year proposed project period? Will the planned studies and expected result support the proposed indication?

Are the proposed Center milestones adequate for advancing the goals of the CounterACT Center in a timely manner? Are these milestones described with quantitative success criteria that facilitate go or no-go decisions? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without unnecessary studies? Would achieving all the proposed milestones in the application allow the Center to achieve the proposed goals?

Do the specific aims enhance synergism among the projects and cores? Do they integrate the project into the overall goals, objectives, and milestones of the Center? Does each project relate and contribute to the others, including how they would yield results beyond those achievable if each project were pursued separately without formal interaction among the participating investigators?

Does the Center leadership have a plan for monitoring progress, and ensuring that a strategic plan is implemented in an effective and efficient manner?

Is the Research Education Core well justified, and does it describe a program that will likely increase the number and capabilities of researchers in the field?

Do the proposed efforts sufficiently address key parameters necessary in the successful development of a product (i.e., drug development), such as compound toxicity/safety, pharmacology, chemistry, and pharmacokinetics/metabolism? Based on the provided structural information of a pre-identified therapeutic hit(s)/lead(s), is the proposed optimization plan acceptable and achievable? Are the proposed IP and regulatory strategies appropriate? Are the proposed animal models well justified based on rigorous scientific rationales, particularly from the regulatory aspect, especially for any efforts with large or higher order animal model species?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Are institutional commitments proposed to enable and facilitate the research objectives tangible and adequate?

Is the environment safe for personnel conducting research proposed in this application?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the CounterACT Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed CounterACT Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

How significant is the contribution of the applicants' currently funded CounterACT Research Center to scientific knowledge in the field? How well have the applicants accomplished the specific objectives and milestones proposed in the original CounterACT Research Center application?

Not Applicable

As applicable for the CounterACT Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

As applicable for each individual Core, reviewers will provide an assessment of its strengths and weaknesses. The following items should be evaluated while determining scientific and technical merit, and in providing an overall Impact Score for the Core; however, separate scores will not be given for these items.

For the Administrative Core:

• Is the organization of the leadership structure and overall Center structure provided and is it effective for overall management of the Center? Are the responsibilities of the Core Lead clearly defined?
• Are the overall plans for the ESSP3 (pilot projects program) described in detail and do they clearly address the goals of the program, and do they meet the criteria described in this funding announcement?
• Is there an appropriate plan to establish/utilize a CounterACT Center Steering Committee and External Advisory Committee? Are the overall plans for the participation in these committees described?
• Does the Administrative Core provide an adequate plan to solicit, select, and evaluate promising Emerging Science and Scientist Pilot Projects for sub-award funding that have significant potential to address developing needs, from both within and outside the Center institution? Does the core's strategy for selecting pilot projects suggest potential for meaningful outcomes in the chosen area of chemical countermeasure research? Will the core's evaluation processes enable selection of promising pilot projects for funding and robust monitoring and evaluation of project progress and implementation?

For the Scientific Core(s):

• Do core resources effectively and efficiently support the research activities in a manner that cannot be supported through available resources?
• Does each core provide a specialized resource that is essential for the conduct of project research, or collaborative projects?
• Are the qualifications, experience, and commitment of the Core Lead(s) and other core personnel appropriate?
• Will the quality of services provided enable Center investigators to achieve their research goals?
• If repositories for cells, tissues, data, or reagents are included, are the methods to obtain, protect, and archive relevant pathological, clinical, and family history information adequate? Is there appropriate informatics capability to track data and link to other data sets?

For the Research Education Core:

• Are the proposed educational experiences distinct from those research training and research education programs currently receiving federal support?
• Does the proposed research education program facilitate the development of key skill sets for investigators?
• Is the core leader actively engaged in research and/or teaching in an area related to the proposed program, and able to organize, administer, monitor, and evaluate the research education program?
• Do the faculty have research expertise and experience relevant to the proposed program and demonstrate a history of, or the potential for, their intended roles?
• Is the Recruitment Plan to Enhance Diversity acceptable?
• Is the Plan for Instruction in the Responsible Conduct of Research acceptable?
• Is the plan for evaluating the activities supported by the Core adequate?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Will the proposed therapeutic reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents?

How rigorous is the preliminary data supporting the choice of the proposed injury mechanism and/or therapeutics for the indication, i.e., biological relevance?

For those projects on model development, will the research be clearly aimed at screening for candidate therapeutics, such as studies that develop and validate efficacy screens using the appropriate controls?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Is the overall timeline reasonable for the work proposed? For key experiments, does the application explain assumptions for power analysis, describe statistical analysis methods and criteria for data inclusion or exclusion, and detail the procedures of how blinding and randomization will be conducted? Will projects that propose to identify a lead compound do so within the multi-year proposed project period? Will the planned studies and expected result support the proposed indication?

Are the proposed project milestones adequate for advancing the goals of the project in a timely manner? Are these milestones described with quantitative success criteria that facilitate go or no-go decisions? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without unnecessary studies? Would achieving all the proposed milestones in the application allow the project to achieve the proposed goals?

Do the proposed efforts sufficiently address key parameters necessary in the successful development of a product (i.e., drug development), such as compound toxicity/safety, pharmacology, chemistry, and pharmacokinetics/metabolism? Based on the provided structural information of the pre-identified therapeutic hit(s)/lead(s), is the proposed optimization plan acceptable and achievable? Are there any insurmountable roadblocks that may prevent the development of a therapeutic medical product? Are the proposed IP and regulatory strategies appropriate? Are the proposed animal models well justified based on rigorous scientific rationales, particularly from the regulatory aspect, especially for any efforts with large or higher order animal model species?

Is the ultimate intended use of a drug, including timing and route of administration, consistent with its effective use in humans in an emergency civilian setting?

If a potential therapeutic hit(s)/lead(s) was pre-identified, is a detailed description of the compound(s) to include chemical structure information and discussion of its potential for drug development provided?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Are institutional commitments proposed to enable and facilitate the research objectives tangible and adequate?

Is the environment safe for personnel conducting research proposed in this application?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed CounterACT Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by CSR in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Number of applications from each institution (no limit, however only one funded CounterACT Research Center of Excellence is allowed within a School at a University or College at any given time.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the purpose of NIH is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
• Initial development and proposal of annual milestones and timeline towards the development of the therapeutic(s) that will be achieved during the project period.
• Awardees are responsible for establishing an external advisory committee composed of experts not otherwise associated with the activity.
• Awardees agree to participate in the overall NIH research effort to develop medical countermeasures against chemical threats. This participation includes collaboration and consultation with other CounterACT research awardees and attendance to the annual CounterACT Research Network Symposium. Collaboration may include sharing of information and research materials.
• Timely acquisition of all appropriate proprietary rights in accordance with the NIH Grants Policy Statement, including securing intellectual property rights, and all materials needed for the applicant to perform the project. Awardees will retain primary intellectual rights and/or property to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
• Awardees are responsible for pursuing patent protection.
• Awardees are responsible for providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NIH Research/Scientific staff request raw data, awardees agree to provide the data.
• Preparation of all materials, e.g., Pre-Pre-IND, Pre-IND, BARDA Tech Watch meeting packages, in support of interactions with regulatory agencies and advanced developers. Regarding meetings and interactions with regulatory agencies, awardees agree to communicate meeting dates and agenda to the NIH Research/Scientific staff and invite their participation.
• Awardees agree to communicate study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with regulatory agencies, and other authorities, if applicable.
• Establishing and managing a solicitation, review, and selection process for collaborative ESSP3 sub-award pilot projects with the Research Center's overall focus and milestones, including the distribution of yearly sub-award funds.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• Each project will have the support of one or more Project Scientists from NIH program staff who are assigned an administrative role for the medical countermeasure(s) being studied and have expertise in the implementation of the CounterACT program.
• The NIH Project Scientists will have substantial scientific-programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
• NIH Project Scientists will be responsible for assessing the progress of the projects toward the accomplishment of specified milestones, and for recommending if further funds should be released to the project.
• The NIH Project Scientists will facilitate the establishment of contacts and collaborations between awardees of the CounterACT program and other persons or organizations whose participation will assist with the accomplishment of project goals. These persons or organizations may include the FDA, BARDA, disease voluntary organizations, pharmaceutical companies, or research organizations that can provide essential services on contract.
• An important part of the CounterACT program is the coordination of research efforts across different funding mechanisms and research structures, and coordination among efforts aimed at different medical countermeasures. NIH Project Scientists will have the primary responsibility for this overall coordination.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.
• NIH Project Scientist(s), in consultation with the PD/PIs, may add critical experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NIH.
• NIH Program Scientist(s) participates in meetings together with PD/PIs with regulatory agencies related to the funded project.
• The awarding NIH Institute will approve final selection of ESSP3 awardee pilot projects.

Areas of Joint Responsibility include:

• A Steering Committee will make strategic decisions with regard to goals and research implementation, including the establishment of shared resources and the development of collaborations. The Steering Committee will meet at least bi-monthly.
• The Steering Committee will be composed of the project PI, and other investigators who are leaders of individual projects within the award or leaders of efforts at consortium sites, if applicable, and one or more NIH Project Scientists. The project PI will serve as chairperson of the Steering Committee.
• Each full member will have one vote. The NIH Project Scientists will have a single NIH vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

• Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to dispute resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. Progress reports should briefly describe status of pilot projects, including data and safety monitoring, and should notify NIH of unanticipated problems.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

For questions related to the overall CounterACT program and/or neurological injury research including threat agents of interest:

David A. Jett, Ph.D.
National Institute of Neurological Disorder and Stroke (NINDS)
Telephone: 301-496-6035
Email: [email protected]

For questions related to ocular injury research including threat agents of interest:

Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: [email protected]

For questions related to dermal/vesicant-induced injury research including threat agents of interest:

Hung Tseng, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]

For questions related to pulmonary injury research including threat agents of interest:

Srikanth S. Nadadur, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-5327
Email: [email protected]

For questions related to research on pharmaceutical-based agents including threat agents of interest:

Kiran Vemuri, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-3396
Email: [email protected]

Dave Yeung, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (301) 761-7237
Email: [email protected]

Carole Jelsema, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1248
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: [email protected]

Lisa A. Edwards, MBA
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-0751
Email: [email protected]

Shiella Simmons
National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-9812
Email: [email protected]

Amy Connolly
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-4457
Email: [email protected]

Jason Lundgren
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 669-2973
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.