Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Primary Issuing Component

National Institute of Neurological Disorders and Stroke (NINDS)

Components of Participating Organizations

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Eye Institute (NEI)
National Institute on Drug Abuse (NIDA)
National Institute of Environmental Health Sciences (NIEHS)

Funding Opportunity Title

Countermeasures Against Chemical Threats (CounterACT) Exploratory/Developmental Projects in Translational Research (R21 Clinical Trial Not Allowed)

Activity Code

R21 Exploratory/Developmental Research Grant

Announcement Type

Reissue of PAR-15-315

Related Notices
Funding Opportunity Announcement (FOA) Number

PAR-18-721

Companion Funding Opportunity

PAR-16-331U01 Research Project Cooperative Agreements
PAR-16-330U01 Research Project Cooperative Agreements
PAR-18-657, U54 Specialized Centers - Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.853, 93.867, 93.846, 93.867; 93.279; 93.113

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages applications for Countermeasures Against Chemical Threats (CounterACT) exploratory/developmental translational research (R21). The mission of the CounterACT program is to foster and support research and development of new and improved therapeutics to mitigate the health effects of chemical threats. Chemical threats are toxic chemicals that could be used in a terrorist attack or accidentally released from industrial production, storage or shipping. They include traditional chemical warfare agents, toxic industrial chemicals, pesticides, and pharmaceutical-based agents. The scope of the research includes basic toxicological research on the chemical threat for the purpose of target and therapeutic hit identification, hit validation, lead optimization, and demonstration of in vivo ADME/Tox and efficacy. Projects supported by this FOA are expected to generate preliminary data that would facilitate the development of competitive applications for more extensive support from the NIH CounterACT Cooperative Agreement programs or other related initiatives. 


Key Dates

Posted Date

March 28, 2018

Open Date (Earliest Submission Date)

April 30, 2018

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

May 30, 2018; May 28, 2019; May 26, 2020, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

November 2018, November 2019, November 2020

Advisory Council Review

January 2019, January 2020, January 2021

Earliest Start Date

July 2019, July 2020, July 2021

Expiration Date

May 27, 2020

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

A. Overview

This FOA encourages applications for exploratory and developmental translational research projects to identify and develop novel medical countermeasures (drug or biologic) to reduce mortality and morbidity resulting from acute exposures to chemical agents identified by the U.S. Government (USG) as threats to the population. Chemical threat agents are toxic compounds that could be released by a deliberate terrorist attack against civilians, or by accidental or natural disaster causing mass casualties. CounterACT Exploratory/ Developmental Projects in Translational Research (R21) will be utilized to support 1-2 year pilot studies to generate preliminary efficacy data for therapeutics to treat injuries resulting from exposure to these chemicals. Pilot studies may include the creation and validation of screening assays for therapy development, identification of candidate therapeutic targets, and development of proof-of-principle efficacy data for the candidate therapy compounds. It is expected that the preliminary data from these R21 projects will be used in support of research applications for transition to related chemical medical countermeasures research and development programs, to include NIH CounterACT supported milestone-driven Cooperative Agreement programs.

B. Background

The CounterACT program is part of the larger NIH Biodefense program and the Chemical Countermeasures Research Program (CCRP) coordinated by the National Institute of Allergy and Infectious Diseases (NIAID). CounterACT and the CCRP are 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 partners.

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, NIEHS, NIDA, and NINDS to execute the overall NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Chemical Threats.

The NIH has developed a comprehensive research and product development program 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) and HHS. The program supports basic, translational, and preclinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents, and guides their movement through the regulatory process in collaboration with other federal departments, agencies, and initiatives, such as the Biomedical Advanced Research and Development Authority (HHS BARDA), FDA Medical Countermeasures Initiative (MCMi), and the Defense Threat Reduction Agency (DoD DTRA).

CounterACT Translational Research R21 Program Directors/Principal Investigators (PDs/PIs) will become members of the CCRP, and will be able to utilize its resources, such as the CounterACT Preclinical Development Facility (CPDF). They will be expected to participate in annual meetings of the CounterACT Network to share information and ideas.

C. Chemical Threats of Research Interest

The civilian chemical threat spectrum includes chemical warfare agents (e.g., sarin, chlorine, sulfur mustard), toxic industrial chemicals (e.g., hydrogen sulfide, cyanide), pesticides (e.g., parathion, brodifacoum), pharmaceutical-based agents (e.g., opioids), 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 for this FOA. Applications that propose research on chemical threats that are not included on the CTRA list will not be selected 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 for this FOA.

Antidotes that are chemical-threat specific 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, i.e., efficacious against more than one chemical threat.

D. Special Biosafety Certification

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 to work with restricted chemical agents, such as the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) and certain contract research facilities, when applicable. Applicants are strongly encouraged to contact the NINDS Scientific/Research Contact listed in this FOA for further information on working with restricted chemical agents.

E. Scientific Scope/Research Topics

The CounterACT R21 program will only support translational research that is clearly relevant to the development of new or improved medical countermeasures that will enhance our medical response capabilities during a chemical emergency. Projects supported by this translational research FOA are expected to generate preliminary preclinical, screening, and/or efficacy data that would facilitate the development of competitive applications for more extensive support from the NIH CounterACT Cooperative Agreement programs or other related initiatives. The scope of research supported under this R21 program includes, but is not limited to:

  • Basic mechanistic research to identify molecular mechanisms of acute toxicity to support identification of relevant biological markers and/or targets for therapeutic development
  • The creation and validation of screening assays for therapy development
  • Identification of candidate therapeutics using primary and secondary screening efforts to generate preliminary proof-of-principle in vitro and/or in vivo efficacy data of the "hits"
  • Creation of animal models to evaluate lethality and serious near- and long-term sublethal morbidities caused by chemical threats after an acute insult that can be extrapolated to various subpopulation groups (e.g., pediatric, pregnant), i.e., natural history. The intended use of the model must be for therapeutic development.
  • Alternate routes of administration and/or dosing regimen for new or already FDA-approved therapies that would be safer, more effective, or easier to administer during a mass casualty scenario or for specific subpopulations (e.g., pediatric and pregnant) that are at higher vulnerability to the adverse effects of chemical intoxication
  • Extending previously observed protective effect of a promising novel and/or already FDA-approved compound(s) for one chemical threat to others, i.e., broadening the spectrum of activity
Applicants interested in more advanced research drug development and/or manufacturing activities of their lead therapy product should explore funding opportunities available through the CounterACT Cooperative Agreement programs and HHS BARDA Broad Agency Announcements.

Since many chemical threats have rapid modes of action, the ideal proposed therapy should have a rapid onset of action to mitigate the effects of chemical toxin exposure and be amenable for mass casualty use.

Novel therapies that have no practical utility "in the field" during a mass casualty scenario may not be considered for funding. Medical countermeasures that are only effective if administered prior to chemical insult (prophylaxis/pre-treatment) or those that must be given within a very short period after exposure will be of low priority (e.g., 1-15 minutes).

The ultimate intended use of the countermeasure must be considered (i.e., concept of use), including timing and route of administration consistent with its effective use in an emergency setting. For example, compounds that are only effective when administered intravenously (IV) would be of low priority since their use would be impractical at the scene of a mass casualty event as first responders may be encumbered by bulky personal protective equipment (PPE), e.g., hazardous material suit.

Therapeutics to prevent long-term or delayed chronic effects after an acute exposure would also be considered, and in this case, may be appropriate for administration after field evacuation and in-hospital. Model development, screening activity, and efficacy studies should be designed and well justified with these countermeasure requirements in mind.

Due to the urgency in need, lengthy time, and expense in bringing a new compound to regulatory approval, applicants are encouraged to consider drugs that are already approved by the Food and Drug Administration (FDA) for other indications, i.e., ?drug repurposing.? Some of these drugs have been shown to be effective in treating victims of chemical exposures, and in some cases, the length of time to regulatory approval for a new indication may be shorter than for a new chemical entity.

Important links to 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.
 
F. Special Considerations
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 R21 mechanism is intended to encourage new exploratory and developmental research projects. By using this mechanism, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research. The premise of these projects may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data. Such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. An example could include the unique and innovative use of an existing methodology to explore a new scientific area.
 
G. Intellectual Property (IP)

The NIH encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy 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. In accordance with the NIH Grants Policy Statement, PDs/PIs are expected 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.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

The budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.

Award Project Period

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years.


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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations
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


Foreign Institutions

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. 

Required Registrations

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility



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)

Section IV. Application and Submission Information

1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide 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.

Letter of Intent

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 electronically 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:

Shardell Spriggs, Ph.D.
Telephone: 301-443-8189
Fax: 301-402-1501
Email: shardell.spriggs@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: If applicable, applications are encouraged to include an Intellectual Property (IP) strategy section that is no more than 1 page. It is advisable that this be prepared in consultation with their institution's technology transfer officials.

This section should describe the IP landscape surrounding their proposed therapeutic candidate(s). Applicants should describe any known constraints that could impede their therapeutic discovery and development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed.  If the applicant proposes using a therapeutic candidate(s) 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 obstacles to achieving the goals of the program and development and commercialization of the therapeutic device . Should NOT require "freedom to operate" - change to more generic such as "address any obstacles to achieving the goals of the program and development and commercialization of the therapeutic candidate." 

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable.

Applicants should discuss future IP filing plans, but any such action must be performed in accordance with the NIH Grants Policy Statement (NIHGPS). For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved. 
 
SF424(R&R) Senior/Key Person Profile

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


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

The proposed budget should include travel support for the PD/PI to attend the Annual CounterACT Network Research Symposium for 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.

R&R Subaward Budget

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


PHS 398 Cover Page Supplement

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


PHS 398 Research Plan

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

Research Strategy: An R21 exploratory/developmental grant application in translational research 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 rational experimental approaches that can yield significant preliminary data in support of more advanced drug discovery and development efforts in future follow-on applications. 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 supporting data (if presented) and in the design of the proposed studies within the Research Strategy section (as appropriate).

In those applications with an already identified candidate therapeutic compound, a description of the proposed product and how it will be ultimately used in humans, i.e., how and when it will be administered in the context of a civilian-based chemical emergency event should be clearly described.

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.  Therefore, when applicable, applicants must include a letter from appropriate Department of Defense (DoD) officials if utilizing such restricted agents under their authority in one's own institution. A formal letter of support (and estimated budget, if applicable) must also be provided for all proposed collaborative, consultative, and/or contract arrangements. This is especially needed for those contracted partnerships specifically for the utilization of restricted chemicals.
 
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.
The following modifications also apply:
  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.


PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) 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 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 with the following additional instructions: 

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

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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.

Post Submission Materials

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.


Section V. Application Review Information

1. Criteria

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.


For this particular announcement, note the following:
 

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

This FOA is encouraging innovative and exploratory R21 translational research applications that may involve nonstandard methodologies applied toward novel therapeutic development approaches. However, it is also recognized that due to the nature of translational research, some studies such as preclinical safety evaluations, those striving to identify potential differences in vulnerabilities of specific subpopulation groups, or those seeking to determine the preclinical efficacy of FDA-approved/unapproved compounds may include standard routine tests and/or previously established models of chemical-induced injuries. While these may not be considered especially innovative, they may nonetheless still be essential to advance the development of medical countermeasures (and scientific knowledge) to achieve the goals of the CounterACT program.

Overall Impact

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).

Scored Review Criteria

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 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 results from the proposed study contribute to reduction of mortality and morbidity during and after emergency events involving the release of chemical threat agents? Will the completion of the exploratory/developmental objectives generate the tools and/or proof-of-principle data necessary to facilitate the development of competitive research applications for further support? Was the selection of the candidate based on sound scientific rationale? If a specific new therapy has not yet been identified, do the proposed translational research aims demonstrate a clear path towards identification of a lead compound by the end of the project period? For those projects focusing solely on model development, is the project clearly aimed at screening for novel 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 inor New Investigators, or 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? 
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 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 timeline reasonable for the work proposed? Does the proposed project use sufficient experimental and statistical rigor? 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?

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?

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 special biosafety precautions for working with highly toxic chemicals adequate? Have all proposed studies been deemed safe for research personnel and the environment by the appropriate institutional biosafety review official?  If working with restricted chemical agents, are all institutional approvals in place Were formal letters of collaboration for all proposed collaborative arrangements (and estimated budget) provided with the application , especially those utilizing restricted chemical agents? 
Additional Review Criteria
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.

Protections for Human Subjects
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.
Inclusion of Women, Minorities, and Children
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.
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
Not Applicable
Revisions
Not Applicable
Additional Review Considerations
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.
Intellectual Property (IP) Strategy
If applicable, reviewers will comment on the following:

Are potential issues regarding the IP landscape for the therapeutic being developed and the freedom to operate addressed?

Do the IP Strategy attachment and related letters of support address potential concerns?

Are there any known constraints that could impede the development of the therapeutic?

Are IP filing plans described?

If multiple institutions are involved, is IP sharing addressed?  
Applications from Foreign Organizations
Not Applicable
Select Agent Research
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).
Resource Sharing Plans
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).
Authentication of Key Biological and/or Chemical Resources:
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.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process 

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the Center for Scientific Review, 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.
The review will be convened by {locus of review}

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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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.


2. Administrative and National Policy Requirements

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.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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

Not Applicable

3. Reporting

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 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.

Section VII. Agency Contacts

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

Application Submission Contacts

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: http://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 Center Telephone: 800-518-4726
Email: support@grants.gov
 

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Scientific/Research Contact(s)
For questions related to the overall CounterACT Program and/or neurological injury research:
Shardell Spriggs, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-443-8189
Email: shardell.spriggs@nih.gov

For questions related to dermal/vesicant-induced injuries: 
Hung Tseng, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: tsengh@mail.nih.gov
 

For questions related to ocular injury research: 
Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: arajh@nei.nih.gov

For questions related to pulmonary injury research:
Srikanth S. Nadadur, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-5327
Email: nadadurs@niehs.nih.gov

For questions related to pharmaceutical based agents:
Kristopher Bough, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-9800
Email: boughk@nih.gov

Peer Review Contact(s)

Carol Jelsema, Ph.D.
Center for Scientific Review
Telephone: 301-435-1248
Email: cj21t@nih.gov

Financial/Grants Management Contact(s)
Tijuanna E. DeCoster, Ph.D., MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231 
Email: decostert@ninds.nih.gov

Andrew Jones
National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-0610
Email: jonesan@mail.nih.gov

Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: kyr@nei.nih.gov

Lisa A. Edwards, MBA
National Institute of Environmental Health Sciences (NIEHS)
Telephone:  919-541-0751
E-mail: archer@niehs.nih.gov

Amy Connolly
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-4457
Email: connolla@mail.nih.gov

Section VIII. Other Information


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.
Authority and Regulations
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.
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