Required Application Instructions

It is critical that applicants follow the 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

This FOA invites applications for cooperative agreement translational research projects to discover, develop, and characterize novel therapeutics (small molecule or biologic) to reduce mortality or morbidity resulting from acute exposures to chemical agents identified by the U.S. Government (USG) as threats to the population. These chemical threat agents are toxic compounds that could be released by a deliberate terrorist attack against civilians, or by industrial accidents or natural disasters causing mass casualties. With the goal of treating or preventing injuries resulting from exposures to these toxic chemicals, NIH CounterACT lead identification cooperative agreement projects will support studies for up to 3 years to identify a lead compound and generate the tools, proof-of-principle efficacy, and early safety/toxicity data necessary to transition the proposed therapeutic(s) towards advanced drug development.

The NIH CounterACT program is part of the larger NIH Biodefense program, coordinated by NIAID, which also includes biological and radiation/nuclear threats. The overall program is part of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), which coordinates medical countermeasures-related efforts across the Department of Health & Human Services (HHS) and other USG agencies.

The overarching goal of the CounterACT program is to integrate cutting-edge research with the latest technological advances in science and medicine to enhance the nation's medical response capabilities during chemical emergencies. This is a trans-NIH effort, involving partnerships with the NEI, NIAID, NIAMS, NICHD, NHLBI, NIEHS, NLM, and NINDS to execute the overall NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Chemical Threats.

The NIH has developed a comprehensive CounterACT Research Network that includes Research Centers of Excellence (U54), individual research projects (U01), exploratory and developmental translational research projects (R21), SBIR projects, contracts, and Interagency Agreements with the Department of Defense (DoD). The network conducts basic, translational, and preclinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents, and supports their movement through the regulatory process in collaboration with other federal departments, agencies, and initiatives, such as HHS Biomedical Advanced Research & Development Authority (BARDA), FDA Medical Countermeasures Initiative (MCMi), and the Defense Threat Reduction Agency (DoD DTRA).

CounterACT Lead Identification U01 Program Directors/Principal Investigators (PDs/PIs) will become members of the CounterACT research network, and will be able to utilize its resources, such as the CounterACT Preclinical Development Facility (CPDF). They will also be expected to participate in annual meetings of the CounterACT Network to share information and ideas.

The civilian chemical threat spectrum includes chemical warfare agents (e.g., sarin), toxic industrial chemicals (e.g., cyanide), pesticides (e.g., parathion), and other chemicals. These agents are included on the current Department of Homeland Security (DHS) Chemical Threat Risk Assessment (CTRA) list, which is for USG official use only and cannot be included in this FOA. Applicants are strongly urged to contact the Scientific/Research staff listed in this FOA to determine if their proposed threat agent(s) is of interest to the NIH. Once it is determined the chemical is on the CTRA list, the NIH then conducts an additional prioritization analysis on the proposed chemical threat. Applications that propose research on chemical threats that are not determined to be a priority to the NIH will not be considered for funding. Therefore, it is critical to contact NIH staff early, before time and effort are invested in developing an application to support research on a chemical or group of chemicals that is not a priority to the NIH.

Antidotes that are specific to a chemical will be considered; however, applicants should also consider research on acute effects and pathologies that are common to several chemical threat agents, so that the therapeutics being developed will have a broader spectrum of activity against more than one chemical.

These chemical threats have a variety of effects. Classes of chemicals encompass cholinesterase and GABA-inhibitors that can induce prolonged and uncontrolled excitation of the nervous system, metabolic/cellular poisons that prevent cellular respiration, vesicating agents that cause moderate to debilitating ocular, dermal, and mucosal injuries, and pulmonary compounds that corrosively injure, irritate, or react with the lining of the respiratory tract. Not all of these may be considered a priority to the NIH. Therefore, it is critical to contact NIH staff to discuss the chemical threat and the type of effect that is being proposed for study.

Many of the chemical threat agents of interest are extremely hazardous to humans. This FOA will only consider supporting studies deemed safe for research personnel and the environment by appropriate official institutional biosafety review. 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 that are already certified and legally authorized to work with restricted chemical agents, such as the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) and certain contract research organizations, when applicable. Applicants are strongly encouraged to contact the Scientific/Research Contacts listed in this FOA for further information on working with restricted chemical agents.

This FOA will only support 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. Projects supported by this FOA are expected to generate at least one lead compound by the end of the project period. Compounds that may become leads could be from a variety of sources including high-throughput screens, drug discovery databases, and FDA-approved drugs that may be re-purposed. For the purpose of this FOA, lead compounds are defined as biologically active and synthetically feasible compounds where specificity, affinity, potency, target selectivity, efficacy, and safety have been established. Lead compounds resulting from research supported by this FOA must have sufficiently strong preliminary preclinical safety/toxicity and in vivo efficacy data to support and promote a promising pathway toward more advanced development (not supported by this FOA). The research supported by this FOA is intended generate lead compounds that are excellent candidates for optimization. Possible support for these advanced drug development activities could be obtained through other avenues such as the program described in the companion FOA "CounterACT Optimization of Therapeutic Lead Compounds (U01)" (PAR-16-331), as well as other government, commercial, or non-profit sources.

The research proposed under this FOA should culminate with the identification of at least one lead compound within the project period. There are several kinds of studies and metrics that can lead to the identification of a lead compound. See Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies for a description of some of the studies used to identify lead compounds. Depending on where in the identification process you begin, the scientific scope of research covered in this FOA includes, but is not necessarily limited to:

• Basic mechanistic research to identify molecular mechanisms of acute toxicity, relevant therapeutic targets, and biological markers of toxicity and exposure. Note that mechanistic research will be considered for funding, however, there must be a feasible research plan that results in the identification of a lead compound within the project period and budget limitations. Therefore most of the proposed mechanistic research should be focused on confirmation of suspected molecular targets rather than studies based on no a priori knowledge.
• Development and utilization of screening assays for the identification of candidate lead compounds. The assay should be validated and the method of validation well-justified, e.g., appropriate pharmacology, robustness, relevant pathology, etc.
• In vitro demonstration of target engagement and appropriate biological activity of candidate therapeutics to counteract the effects of the threat agent
• Development and utilization of animal models to demonstrate preliminary proof-of-concept efficacy. Animal models should demonstrate an important clinical benefit and should simulate the ultimate clinical use of the candidate therapeutic in humans.
• Demonstration of acceptable preliminary safety, pharmacodynamic/pharmacokinetic (PD/PK), and drugability properties of the candidate therapeutic

The scope of therapeutic discovery and early development research covered in this FOA can also be described by Technology Readiness Levels (TRLs). The TRL covered in this FOA generally falls under TRL 3.

Applicants that have already identified a lead compound and are ready for more advanced optimization research and development activities may explore funding opportunities available through the CounterACT Optimization of Therapeutic Lead Compounds U01 Announcement (PAR-16-331) and HHS BARDA Broad Agency Announcements.

Important links to specific FDA Guidance and other regulatory information relevant to medical countermeasure research and development can be found under the Related Information section on the CounterACT website.

Milestone-driven research is used to ensure research is focused on a well-defined goal, thus 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 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.

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 applications. Unmet milestones and an incomplete data package that prevents an adequate interpretation of progress will have a negative impact on the approval of the annual non-competing applications.

Partial budget reductions and/or restrictions in a given project year may also occur if aspects of the project are deemed futile, but others still show promise.

See Section IV.2 below for more specific instructions on developing appropriate milestones.

This FOA will only support the development of lead compounds that can be used to reduce mortality or serious morbidity during a chemical emergency. The primary focus of research should be on identifying lead compounds that are effective when administered after a chemical exposure has occurred (post-exposure efficacy). Lead compounds that are only effective if administered prior to the chemical insult (prophylaxis efficacy) will be of lowest priority.

Regulatory Considerations: It is neither ethical nor feasible to perform human clinical trials to establish the efficacy of proposed therapeutic product(s) for injuries resulting from exposure to chemical threats. Therefore, a scientifically sound method in animals is usually required to demonstrate that a candidate medical countermeasure provides the intended protection. As such, most research supported by this FOA would typically follow the FDA Guidance for Industry - Product Development Under the Animal Rule. Additionally, research and development of combination therapies of two or more new drugs that have not been individually approved previously for the specified indication would need to abide by the FDA Guidance for Industry - Co-development of Two or More New Investigational Drugs for Use in Combination. Therefore, in most cases, it is usually advantageous that information in these and other FDA Guidance be reviewed in consultation with a partner possessing a history of regulatory experience especially with the FDA Animal Rule. Information on how to formally engage and interact with the FDA and/or principles of good meeting management practices (GMMPs) with the agency is available in the FDA Guidance for Industry - Formal Meetings Between the FDA and Sponsors or Applicants, which describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such recognized meetings.

Applicants are strongly urged to consider addressing effects of sex and age alone or in combination as biological variables in the proposed preclinical studies (see NOT-OD-15-102). 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.

Critical elements of a well-designed study include adequate scientific rigor, control of bias, reproducibility, dose-response, confirmation of mechanism, and transparency of reporting. As such, the NIH urges applicants to consider and directly address these elements in their application(s). Please see NOT-OD-15-103 for more information on enhancing reproducibility through rigor and transparency.

The NIH encourages the awardees and/or their collaborators to obtain and retain any Intellectual Property (IP) developed around the lead compound during the project period as appropriate. Recipients of awards are encouraged to work closely with their institutional Technology Transfer (or Industry Relations) Office 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 and in accordance with the NIH Grants Policy Statement to ensure that appropriate royalty agreements, patent filings, and all other necessary IP arrangements are managed in a timely manner and that commercialization plans are developed and updated over the course of the project, consistent with achieving the goals of the program. 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.

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 in response to 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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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. While there is no limit on the number of scientifically distinct applications an applicant organization may submit, the submitting PD/PI of the applicant organization is limited to no more than one active individual or Multiple PDs/PIs CounterACT Identification of Therapeutic Lead Compounds (U01) Cooperative Agreement award at a time.

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).

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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
• 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]

All page limitations 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 an application to this FOA.

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

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

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

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. Applications that exceed this limit will be withdrawn. This attachment should be entitled "IP_Strategy.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.

A goal of this program initiative is to advance research towards the development of products that will mitigate mortality or morbidity after exposure to threat chemicals. Accordingly, 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, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any questions that may constrain or impede its ability to operate and move the compound forward consistent with achieving the goals of the program. 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.

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

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

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

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

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

Research Strategy: Proposed projects should have a strong biological rationale for the intended approach and the proposed studies must exhibit methodological rigor. A well-structured application should, therefore, include clear and rational experimental approaches that can yield significant data in support of the proposed indication. Applicants to the program are urged to consider the rationale for the chosen model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results. These criteria should also be addressed when describing all supporting data and in the design of the proposed studies within the Research Strategy section (as appropriate). This section should also describe how the proposed research will enhance medical response capabilities during a chemical emergency. If a potential therapeutic hit(s) was pre-identified, this section should also contain a detailed description of the compound to include chemical structure information, potential for drugability, and proposed concept of use, i.e., how and when it will be administered to humans in the context of a civilian-based chemical emergency event. The lack of structural information for the pre-identified potential therapeutic hit(s) may adversely affect the assessment of the potential to develop a drug product. NIH has multiple safeguards to protect the integrity of and to maintain confidentiality in peer review.

Milestones: Annual milestones must be proposed in response to this announcement. Milestones should describe the goal of the work and not just state that the work will be completed. The proposed milestones (with associated timelines) should be regarded as criteria for evaluating the progress and direction of the project. Applicants will, therefore, be expected to refer to these milestones in annual progress reports. The proposed milestones will be periodically revisited and may be revised when necessary as challenges are encountered or new information becomes available based on the trajectory of the research and the field at large. Given the high-risk and 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 that can be used for evaluation by NIH. These should be measures that would be recognizable as appropriate endpoints in the specific scientific area. Examples of acceptable milestones are available on the NIH CounterACT website. A Gantt chart or table may be used to document the timeline associated with the proposed milestones over the course of the proposed project period. The timeline and milestones information should be placed at the end of the Research Strategy.

Letters of Support:

• Many of the chemical threat agents of interest to this announcement are extremely hazardous to humans. Applicants must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment. This must be addressed in the application, including a description of adequate protection and safeguards if required. Special biosafety certifications may be required to conduct research with some restricted chemical threat agents, e.g., chemical warfare nerve agents. A formal letter of support (and estimated budget, if applicable) must also be provided for all proposed collaborative, consultative, and contract arrangements. This is critical for those contracted partnerships specifically for the utilization of restricted chemicals.
• If applying from an academic institution, include a letter of support from the technology transfer official who will be managing existing and future intellectual property associated with this project.
• 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, consistent with achieving the 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.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-D application packages for use with due dates on or before January 24, 2018.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or 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: All instructions in the SF424 (R&R) Application Guide must be followed.

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). 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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) 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. See Section III of this FOA for information on registration requirements.

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. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 study reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents, i.e., clinical impact? Was the selection of the animal model and/or potential therapeutic(s) based on sound and rigorous scientific rationales, e.g., target/pathway activity? How strong are the preliminary data supporting the choice of the proposed injury mechanism and/or therapeutic(s) for the indication, i.e., biological relevance? What is the likelihood that completion of all proposed research objectives will lead to the identification of a lead therapeutic compound for the intended indication and proposed concept of use? Are there any IP constraints that would impede the development of the proposed compound(s)? If so, is it significant enough to jeopardize the success of the project?

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?

Are the scientific and/or administrative leadership qualifications and time commitment of the PD/PI adequate? Is there adequate statistical and/or regulatory support for the experimental design, analysis, and interpretation of the generated preclinical data? Is there adequate personnel to manage existing and future intellectual property associated with this project?

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?

Is the therapeutic approach innovative for this indication? For example, a drug that is commonly used for one indication may be tested for effectiveness against the toxicity of a chemical threat agent (drug repurposing). Or the tests used to characterize a therapeutic may not be innovative, but they are essential for determining if a new innovative therapeutic approach is viable.

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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?

Is the overall timeline reasonable for the work proposed? Have the investigators considered the rigor of their experimental design and statistical analysis? Will the planned studies and expected result support the proposed indication? If provided, based on the available information presented for compound structure, potential for drugability, and IP strategy for the pre-identified therapeutic hit(s), what is the potential to develop a product?

Are the proposed annual milestones robust and associated with clear, quantitative criteria for success that allows go/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 ultimate goal of the project to identify a therapeutic lead compound?

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 children, justified in terms of the scientific goals and research strategy proposed?

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?

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.

For research that involves human subjects but does not involve one of the six 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 six 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 project 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 children 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.

Not Applicable

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 (GDS).

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. 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.

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.

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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. 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. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 NIH purpose 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.
• 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.
• Preparation of all materials, e.g., Pre-PreIND, Pre-IND, Techwatch meeting packages, in support of interactions with regulatory agencies and advanced developers
• 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.

NIH Staff have substantial programmatic and scientific involvement that is above and beyond the normal program 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 Scientist(s) from NIH Program staff who are assigned an administrative role for the project and have expertise in the implementation of the CounterACT research program.
• NIH Project Scientists will have substantial scientific-programmatic involvement during 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.
• NIH Project Scientists will facilitate the establishment of contacts and collaborations between awardees of the CounterACT research 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 research program is the coordination of research efforts across different funding mechanisms and research structures, and coordination among efforts aimed at different countermeasures. NIH Project Scientists will have the primary responsibility for this overall coordination.
• Additionally, an agency Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Official may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

• None; all responsibilities are divided between awardees and NIH staff as described above.

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 individual awardee 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 does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 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.

A final progress report, 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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

For questions related to pulmonary injury research:
Srikanth S. Nadadur, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-5327
Email: [email protected]

For questions related to dermal/vesicant-induced injury research:
Hung Tseng, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]

Kristopher Bough, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-9800
Email: [email protected]

Geoffrey Schofield, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1235
Email: [email protected]

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

Tijuanna E. DeCoster, Ph.D., MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

William W. Darby
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]

Andrew Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-0610
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.