Part 1. Overview Information

Key Dates

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) 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 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

A. Overview

The Chemical Countermeasures Research Program (CCRP) was established in 2006 by the National Institute of Allergy and Infectious Disease (NIAID/NIH) to promote the discovery and/or advancement of medical countermeasures (MCMs) to treat and/or prevent serious morbidities and mortality during or after mass casualty, high consequence, public health events involving the release of highly toxic chemicals. In support of these goals, the CCRP seeks to promote research to identify mechanisms of toxic effects and application of the fundamental information gained to support discovery and early-stage development of MCMs. To learn more, see Supporting Fundamental Chemical Toxicology Research to Inform Medical Countermeasure Developments: The National Institutes of Health Chemical Countermeasures Research Program, published in Chemical Research in Toxicology.

Almost 200 chemicals of concern (CoC) have been identified by the U.S. Department of Homeland Security (DHS) as high consequence public health threats. There is an urgent unmet need to gain a clear understanding of the physiological mechanisms involved in the initiation and downstream events of injury from acute exposure to these chemicals.

CoCs are organized within toxidromes established by the U.S. Government. Toxidromes group chemicals based on their primary modes of toxicity. One benefit of this approach is that a single MCM may be effective against multiple different chemical threats. The CoC toxidromes (with examples) are:

Pulmonary (e.g., chlorine, phosgene, ammonia, sulfur dioxide, chloropicrin, acrolein)

Ultrapotent Synthetic Opioids (e.g., fentanyl, carfentanil, acetylfentanyl, sufentanil, remifentanil)

Vesicants (e.g., nitrogen mustard, phosgene oxime)

Blood agents (e.g., hydrogen sulfide)

Anticoagulants (e.g., brodifacoum, bromadiolone)

Hemolytic/Metabolic (e.g., arsenic trioxide, thallium sulfate, arsine)

Cholinergic Agents (e.g., parathion, phorate, aldicarb)

Convulsant (e.g., picrotoxin, TETS, strychnine)

Only projects that include chemicals that have been identified by the DHS as CoC will be supported by this NOFO.

The ExRC will serve as a state-of-the-art facility to provide analytical and technical expertise to CCRP supported investigators and will serve as a resource to expose experimental models of choice to toxic chemicals to characterize molecular, cellular, and physiological pathways mediating acute injury, delayed onset of injury after acute threat agent exposure, and early-stage development of MCMs. These fundamental research efforts should ideally support successful transition to MCM development with broader applicability across the threat spectrum to enhance national health preparedness and security in the event of mass chemical casualty incidents.

Objectives:

This NOFO supports the ExRC, with existing infrastructure to accommodate and coordinate toxic threat agent exposures, experimental design, and offers analytical support for CCRP supported investigators.  The primary purpose of the ExRC is to develop and standardize exposure protocols and experimental models for a select list of Department of Homeland Security CoC and make these resources available and accessible to currently funded CCRP investigators as a collaborative research effort.

The ExRC will be a state-of-the-art exposure facility for diverse toxic chemicals with appropriate safety and security monitoring for quality control, rigor, and reproducibility. It should provide:

1. Support for in vivo exposures including but not limited to whole-body, nose-only, and/or user-defined needs, with capacity for specific animal models. In vitro exposures and those seeking to use engineered microphysiological systems are also supported.
2. A centralized resource to facilitate protocol standardization and support high quality data collection and submission to CCRP investigators.   
3. Investigator training in techniques that may include, but are not limited to bronchoscopy, pulmonary function testing, neurotoxicity testing, telemetry, air-liquid interface culturing, and live-imaging.
4. Dedicated expertise that may include, but are not limited to aerosol generation, safety monitoring, analytical instrumentation, and veterinary care, as well as tissue collection and pathology.  Comprehensive knowledge of microfluidics, vasculature, and live data collection.

ExRC Structure:

The ExRC will be structured into three Cores (Administrative, Research, and Coordination). Investigators are encouraged to convene a diverse, multidisciplinary, skilled team to support the resource with the necessary expertise to cover distinct real-world routes of threat agent exposure (e.g., pulmonary, ingestion, and dermal) and different model systems.

• The PD/PI or ExRC Director will be responsible for overall planning and management of the ExRC. The ExRC Director must commit at least 30% of full-time appointment to the ExRC, overall, including role as Director of the Administrative Core.  In a multiple PD/PI ExRC, the combined efforts of the Directors must equal at least 30% of full-time appointment including the Administrative Core and project commitments.
• The PD/PI and Administrative Core staff will be responsible for managing, coordinating, supervising the entire range of ExRC activities, and monitoring progress in an effective and efficient manner. It is recommended that both an Administrative and Scientific Program Manager are included to assist the PD/PI. The PD/PI and Administrative Core staff will be responsible for ensuring that appropriate systems are in place to provide for biosafety and security of materials, data, and facilities.

I. Administrative Core

This core is the managing component of the ExRC, charged with supervising ExRC governance and policies, and enacting continual improvements in the quality and efficiency of its activities.  Program management aspects include strong communication and coordination strategies to support the CCRP such as prioritizing needs, capacity, handling, and completion of reasonable requests in a timely fashion. The Administrative Core is responsible for overseeing all decision-making processes, managing the ExRC budget, interacting with the NIH, and responding to evolving needs of CCRP supported investigators.

The Administrative Core will:

• Establish an ExRC Steering Committee consisting of Core Leads, NIH program staff, and other stakeholders, that meets as needed to advise on significant facility decisions.
• In accordance with NIH program staff and the ExRC Steering Committee, the Administrative Core will institute an External Advisory Committee (EAC) that will provide guidance to the ExRC and the Steering Committee. The Administrative Core and Steering Committee will share EAC recommendations with CCRP investigators using the ExRC. 
• Provide oversight to and coordination with all ExRC Cores.  The Administrative Core will also work with the Steering Committee to develop and maintain standard operating procedures for participating CCRP supported investigators. 
• Keep NIH program staff informed of the prioritization process in accommodating requests from CCRP supported investigators.
• Help build complementary relationships with participating strategic partners (e.g., Biomedical Advanced Research and Development Authority, BARDA), while maintaining intellectual property considerations.
• Develop and maintain a user-friendly submission portal for ExRC use requests jointly with the Coordination Core.
• Meaningfully incorporate participant experiences, perspectives, needs, and priorities into decisions and activities of the ExRC.
• Provide usage and resource availability updates at the annual CounterACT Research Symposium to enhance communication and collaboration with the broader CCRP community.
• Evaluate facility operations (e.g., capacity, handling, and data transfer).

II. Research Support Core

The Research Core will develop standardized exposure protocols for a minimum of two in vivo models (e.g., rat, mice) and four to six threat agents representing CoC toxidromes, with planned expansion for eight to ten threat agents.  These models should include establishing and maintaining efficient data systems and infrastructure necessary for timely collection and transfer of high-quality exposure and physiologic measures, and other specialized research needs.

The Research Support Core will assist participating CCRP supported investigators with exposures and data collection and expand our knowledge of CoC.  The Research Support Core will:

• Provide expertise to CCRP supported investigators in the design of studies, proper use of analytical equipment, data collection, and transfer policies.  Participating investigators are required to have the appropriate scientific expertise to conduct CCRP research but may vary in their ability to select or design optimal inhalation or in vitro strategies for toxicodynamic studies.
• Supply input on exposures, and expert advice to participating investigators in complementary fields such as, but not limited to environmental engineering, veterinary medicine, respiratory mechanics, pathology, physiology, and microfluidic dynamics.

III. Coordination Core

The Coordination Core will facilitate ExRC activities for CCRP supported investigators to coordinate toxicant exposures, data collection, and transfer.  The Coordination Core will:

• Provide an online portal for the ExRC with the CCRP supported community, similar to other IC data portals, that supports scheduling and online activities (e.g., NHLBI Catalyze, NIEHS Chemical Effects in Biological Systems). 
• Interact with CCRP supported investigators to identify their needs and work with the Research Core to modify exposure protocols to address intended outcome measures by the investigators. 
• Plan and schedule pilot studies, coordinate animal shipments, maintain animal colonies prior to and after exposure as needed.  Schedule access to investigators as needed for tissue harvesting, physiological monitoring, sample shipment, etc.

Core Formation and Guidance

The administrative structure of the ExRC will provide leadership and assistance to the CCRP. The award funded under this NOFO will be a cooperative agreement (see Section VI: Award Administration Information). Because this is a cooperative agreement, extensive collaboration and management input from the NIH will occur regarding ExRC activities.  This overall structure is intended to ensure that participating CCRP supported investigators and non-NIH funded stakeholders are well-served by the ExRC resource.

ExRC governance will rest with the Steering Committee, with advice from the External Advisory Committee. The EAC will be named by the Steering Committee, the NIH, and other stakeholders and advise on processes and substantive issues that arise during operations.  The Steering Committee may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific functions as needed.    

The Steering Committee will be composed of:

• The PD(s)/PI(s) of the ExRC
• Internal and external expertise in veterinary medicine, pathology, physiology, respiratory mechanics, microfluidics, and aerosol generation, as needed, based on studies proposed
• NIH Program Official(s) from the CCRP and other participating Institutes
• Other relevant stakeholders as appropriate

The Steering Committee will identify scientific and policy issues that need to be addressed at the facility, and emergent issues in chemical threat agents research that can be addressed by the ExRC.

A. Special Biosafety Certification

Many of the chemical threat agents of interest are extremely hazardous to humans. All applications must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment (See letters of support in Section IV). Applicants are strongly encouraged to contact the Scientific/Research Contacts listed in this NOFO for further information if the research proposal uses restricted chemical agent(s).

B. Annual Countermeasures Against Chemical Threats (CounterACT) Research Symposium

Recipients funded under this NOFO must participate in the annual research symposium of CCRP funded projects. Participation includes presentation of progress achieved under the CCRP award. Recipients may be asked by the NIH to host the annual meeting for the purpose of information exchange, sharing scientific progress, and formation of potential research collaborations. If requested to host the meeting, recipients may request funding support for this activity via an administrative supplement request to the NIH and CCRP.

C. Applications Not Responsive to NOFO

• Studying chemicals not on the DHS CoC list.
• Studying health outcomes after prolonged, persistent, or chronic chemical exposure, i.e., the CCRP only supports research on health effects after a single acute exposure event.
• Assay development and/or screening activities towards discovery or optimization of candidate MCMs or “hits”.
• Development of diagnostics and/or detection technologies.

Responsive applications will demonstrate expertise in toxic chemical exposures, with strengths in three major areas: (1) leadership and project management of large, complex studies of DHS CoC; (2) building, operation, and oversight of analytical tools to study toxicants of interest; and (3) evaluation of facility operations. Applications that do not demonstrate the expertise above will be deemed not responsive and will not receive further consideration for award.

Due to the unique requirements of this project, applicants are strongly encouraged to consult with the Scientific Research Contacts listed here early in the application planning process. 

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

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

3. Additional Information on Eligibility

Number of Applications

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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 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:

Leroy Worth Jr, PhD
Telephone: 984-287-3340
Email: worth@niehs.nih.gov

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

Overall Component

When preparing the application, use Component Type ‘Overall’.

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project Strategy: Briefly describe the overall theme, goals, and objectives of the ExRC, including:

• Organizational structure
• Synergy among Cores

Facilities and Other Resources: All aspects of Facilities and Other Resources should be covered here, for Overall Component.  Indicate, however, to which Cores the specific items listed here would be relevant (and group them accordingly). In addition to the information required in the standard instructions, applicants should describe relevant institutional facilities, resources, and services that can be leveraged for accomplishing the goals of the proposed project (e.g., analytical equipment, data storage, consultative and statistical resources, etc.).  Specify on what basis such resources will be available to participating CCRP supported investigators (e.g., freely available, fee-for-service, etc.).  Applicants should also describe any institutional resources or commitments that could be leveraged to support the ExRC. 

Other Attachments: Applicants must provide the following additional materials in support of their application. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks). 

Attachment 1: A table listing available partnerships and infrastructures that will support the ExRC in assisting participating CCRP supported investigators. Use file name “Partnerships and Infrastructure”.  Do not exceed 1 page.  Examples include partnerships or existing collaborations with organizations that provide aerosol generation, microfluidic devices, analytical instrumentation, data collection and storage, veterinary care, and/or pathology services.

Attachment 2: Summary of Senior/Key Personnel. Use file name “Summary of Personnel”.

An attachment must be included summarizing which personnel fulfill the required and strongly encouraged areas of expertise listed in Section I. Funding Opportunity Description. Do not exceed 2 pages. This includes:

• Leadership and project management of toxicology research
• Developing and managing aerosol generation
• Maintenance and use of microphysiological systems
• Building and validating relevant instrumentation to support analytical projects
• Developing and maintaining data collection and storage systems
• Assessing network and facilities operations

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

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

Describe the knowledge and prior experiences of the PD(s)/PI(s) in leading and managing large, complex programs involving teams of scientists, including projects involving chemical toxicants and/or threat agents. The contact PD/PI must commit and maintain through the life of the award a minimum of 30% full-time appointment to this program. For applications with multiple PDs/PIs, a minimum of 20% full-time appointment is required for the Contact PD/PI and 10% for each additional PD/PI. The required levels of effort may reflect an aggregate of the effort across the entire project. 

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

Budget (Overall)

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

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

PHS 398 Research Plan (Overall)

Specific Aims: List each aim for the ExRC and how it supports the objectives of this research program as described in Section I. Funding Opportunity Description.   

Research Strategy: Describe the overall goals of the ExRC for the proposed performance period of the application, including:

• Overall strategy, methodology, and analyses to accomplish the specific aims of the project.
• The ExRC objectives for facilitating toxicant exposures for participating CCRP investigators; maintaining and coordinating an analytical resource for participants; providing data management and transfer to investigators.
• A succinct outline of the structure and function of each Core based on the requirements described in Section I. Funding Opportunity Description, and how the ExRC will coordinate activities across the Cores.
• Plans to work with other members of the ExRC Steering Committee and NIH, with guidance from the EAC, to define a mode of operation that best matches the specific capabilities of individual investigators accepted to use the resource.  Clearly define efforts to ensure fair, equitable, cost-effective, and timely distribution of ExRC resources to participating CCRP investigators.
• Any innovations and improvements to enhance the quality, efficiency, and evaluation of ExRC-wide operations; assist CCRP supported investigators to improve the efficiency of analytical resources provided by the ExRC; and transition to a sustainable regional resource to serve the broader CCRP community.

Integration and collaboration between ExRC and CCRP supported investigators is essential to accomplish the goals of this project.  Highlighting the synergy and expertise of the ExRC team (and not duplicative of the information provided in individual bio-sketches), applicants should describe:

• Prior experience of the team in working as part of a research network or other collaborative activities that meet individual and group goals, including examples of prior collaboration and/or participation in networks or consortia.
• Their team’s experience and expertise in the proposed approaches, and ideas for potential alternatives to performing the various ExRC tasks of this NOFO.  Additional tasks that are not detailed here, but in the applicant’s view, are essential to ExRC operations should be noted and potential approaches described.

Letters of Support:

Many of the chemical threat agents of interest to this announcement are extremely hazardous to humans. All 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.  A formal letter of support (and estimated budget, if applicable) must also be provided for all proposed collaborative, consultative, and/or contractual arrangements. 

Institutional commitments to sustaining ExRC functions beyond NIH grant support should be clearly documented.  Letters should be included that reflect any additional resources and partnerships that will be employed to achieve the goals of the ExRC, including transition to a sustainable regional resource for the CCRP community.

All letters of support for the entire application should be provided under Overall component. 

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.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component. 

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type ‘Admin Core.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

Research & Related Other Project Information (Administrative Core)

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

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

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• The ExRC PD/PI (contact PD/PI for applications with multiple PDs/PIs) must be designated as the Administrative Core Lead.   

Budget (Administrative Core)

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

ExRC Administrator: Based on the complexity of the ExRC, applicants may propose and budget for an ExRC Administrator to manage day-to-day operations.

Travel Funds: Include travel support for the PD(s)/PI(s) and U2C ExRC Core leads (up to four persons) to attend the Annual CounterACT Research Symposium for each of the proposed project years. We strongly encourage a principal member of each Core to attend these meetings and budgets should be planned accordingly.

PHS 398 Research Plan (Administrative Core)

Specific Aims: Outline the specific aims for the Administrative Core.

Research Strategy: In lieu of the standard Research Strategy subsections (Significance, Innovation, Approach), use the subsections defined below to describe the administrative and organizational responsibilities of the proposed Administrative Core. Applications should also highlight aspects of the proposed activities of the Administrative Core that speak to the significance and innovation of the approaches.

Sub-section A. Leadership and Participant Engagement ExRC Organization

Outline the organization of the leadership structure and overall ExRC structure (provide relevant organizational diagrams). Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating sites.

Address the major responsibilities of the Administrative Core:

• Establishing an EAC consisting of scientific and stakeholder group representatives/expertise. Please refer to Program Formation and Governance in Section I. Funding Opportunity Description for more information on the EAC role. The EAC should meet in-person or virtually at least once a year, beginning in the first or second year of the award. Specific committee members should not be named in the grant application.
• Establishing a Steering Committee that will serve as the main scientific body of the program. Please refer to Program Formation and Governance in Section I. Funding Opportunity Description for more information on the Steering Committee responsibilities. Plan to include at least one in-person meeting with the EAC and Steering Committee beginning in the second year of the award. Specific Steering committee members should not be named in the grant application.
• Support activities performed by the core, spanning from communication with investigators, to development and implementation of study protocols.
• Foster synergy and integration of the three cores of the ExRC; provide efficiency in management of collaborative project efforts (including logistical services and organizational support) involving multiple institutions, if required.
• Assist in the development and design of research approaches, procedures, policies, and strategies to be applied to this program.
• Develop and maintain an investigator portal that is equipped to receive applications from potential CCRP investigators seeking to use the ExRC.
• Identify and solve operational problems involving data collection, quality assurance, and refinement of protocols.
• Develop and implement plans for coordinating, facilitating, and supporting research activities of CCRP investigators.
• Develop and implement plans for assessing the outcomes of the ExRC.

Sub-section B. Dissemination and Training

Propose a plan for dissemination and training to include:

• Acquiring and maintaining analytical resource materials for participants.
• Developing and implementing an equipment training program for participants.
• Adhering to policies regarding data access, publication, and intellectual property established by the NIH and the Steering Committee.

Sub-section C. Center Logistics and Communication

Describe the communication strategies to ensure bidirectional exchange of logistical information, findings, and insights, including lessons learned and best practices between:

• ExRC Cores
• ExRC leadership (multiple PD(s)/PI(s)) and additional key personnel within the ExRC
• ExRC and advisory committees (the Steering Committee and EAC)
• ExRC and CCRP supported investigators
• ExRC and the NIH CCRP

State who will be the lead for each level of communication.

Sub-section D: Research Oversight and Progress Evaluation

Explain how leadership of the Administrative Core envisions oversight of the ExRC activities. Describe how the Administrative Core will support planning and evaluation activities for the ExRC, including plans for the evaluation of progress on a regular basis. Describe how these evaluations will be used to prioritize activities to ensure that the main goals of the ExRC will be achieved in collaboration with staff from the individual Cores. Progress evaluation should include consideration of outcomes for CCRP investigators. Identify potential problems and alternative strategies to accomplish goals. Describe what action will be taken if progress is insufficient, if an overall ExRC timeline or Research Support Core benchmark is not met or significantly delayed. Describe how the core will access and transfer data, protocols, and methods developed to participating CCRP investigators.

 Research Support Core

When preparing your application, use Component Type ‘Research Support.'

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

SF424 (R&R) Cover (Research Support Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Use "Research Support Core" as the title for this component.
• Proposed Project Start/Ending Dates

Research & Related Other Project Information (Research Support Core)

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

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

Project /Performance Site Location(s) (Research Support Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Research Support Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons who are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Research Support Core)

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

The budget should include a detailed justification for key personnel under this core. The person months for each member of the center staff related to this core should be included here. It is possible to have overlapped personnel under different components if their total efforts do not exceed 100%.

Include costs to administratively manage resource costs for any consultant or subcontractor directly supporting this core's activities (e.g., subject matter expert, project manager, information services).

PHS 398 Research Plan (Research Support Core)

Specific Aims: Describe the specific aims of the Research Support Core and how these goals will assist investigators conduct toxicant exposure studies. The aims should address not only the delivery of services or materials, but also the processes for ensuring the consistent quality of services or materials, fair access by participants and efficient use of the resources. Also, describe in the specific aims how the resource award will be managed to achieve success.  

Research Strategy: Describe the function of the Research Support Core as a resource to participating CCRP supported investigators. The research strategy must clearly present the facilities, techniques, and professional skills that the core will provide to participants. Describe how the Research Support Core will work with the Administrative Core to ensure that the application process for investigators is efficient and not burdensome. The inclusion of a timeline for establishing the various components of the core is strongly encouraged.

Coordination Core

When preparing your application, use Component Type ‘Coordination Core.’

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

SF424 (R&R) Cover (Coordination Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Use "Coordination Core" as the title for this component
• Proposed Project Start/Ending Dates

Research & Related Other Project Information (Coordination Core)

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

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

Project /Performance Site Location(s) (Coordination Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Coordination Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons who are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Coordination Core)

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

The budget should include a detailed justification for key personnel under this core. The person months for each member of the center staff related to this core should be included here. It is possible to have overlapped personnel under different components if their total efforts do not exceed 100%.

Include costs to administratively manage resource costs for any consultant or subcontractor directly supporting this core's activities (e.g., subject-matter expert, project manager, information services).

PHS 398 Research Plan (Coordination Core)

Specific Aims: Describe the specific aims of the Coordination Core and how these goals will assist investigators conduct toxicant exposure studies. The aims should address not only the delivery of data, but also the processes for ensuring the consistent quality of data, fair access by participants and efficient use of the resources. Also, describe in the specific aims how the resource award will be managed to achieve success.  

Research Strategy: Describe the function of the Coordination Core as a resource to participating CCRP investigators. The research strategy must clearly present the facilities, techniques, and professional skills that the core will provide to participants and means for data management and secure transfer. Describe how the Coordination Core will work with the Administrative Core to ensure that the application process and data transfer for investigators is efficient and not burdensome. The inclusion of a timeline for establishing the various components of the core is strongly encouraged. Instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.  

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

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

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

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.

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

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier 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.

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.

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

Prior Consultation with Scientific/Research Staff

Consultation with relevant NIH Scientific/Research staff is strongly encouraged, not later than the Letter of Intent due date. This is not the same as the Letter of Intent and should be included as a separate communication to the Scientific/Research Contacts (see Section VII). If requested by the applicants, staff can advise whether the proposed project meets the goals of this NOFO and the mission of the CCRP and discuss responsiveness questions. Staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this NOFO.

To expedite review, applicants are requested to notify NIEHS Referral Office by email at worth@niehs.nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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

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

Significance

Does the proposed [Center] address the needs of the research [programs/projects/network/consortium/resource] that it will [coordinate/administer/serve]? Is the scope of activities proposed for the [Center] appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research [program/projects/network/consortium/resource]?

Specific to this NOFO: How will this project make a significant contribution to the overall goals and objectives of the CCRP?  How will the ExRC’s conceptual design and overall operating plan provide the required strategy and resources to advance the field of chemical threat agent research? See Section IV. Application and Submission Information.

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the [Center]? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing [adjective] research? Do the investigators demonstrate significant experience with coordinating collaborative [basic or clinical] research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their [leadership approach, governance, plans for conflict resolution, and organizational structure] appropriate for the [Center]? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this NOFO: How appropriate is the PD(s)/PI(s) record of coordinating, working collaboratively, and providing data to investigators to the success of this project? How does the PD(s)/PI(s) prior experience in managing complex projects align with the goals of this project? How applicable are the PD(s)/PI(s) prior experience toward the proposed route(s) of exposure, e.g., expertise in aerosol generation and characterization, and acquiring respiratory mechanics data? If the Center is multi-PD(s)/PI(s), how appropriate are their plans for conflict resolution? How feasible are their Leadership and succession plans and how will they contribute to the success of the project? See Section IV. Application and Submission Information.

Innovation

Does the application propose novel [organizational concepts, management strategies, or instrumentation] in coordinating the research [program/projects/network/consortium/resource] the [Center] will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of [organizational concepts, management strategies or instrumentation] proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research [program/projects/network/consortium/ resource] the [Center] will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the [program/projects/network/consortium/resource], as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the [program/projects/network/consortium/ resource] is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the [program/projects/network/consortium/resource]? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this NOFO: How do the overall strategy, operational plan, and structure of the ExRC align with the goals of this project? How appropriate are plans for workflow and the proposed timeline to the success of this project?How meritorious are the individual cores, and how do they complement the other components of the ExRC? How will the ExRc establish an identify as a CCRP Resource? See Section IV. Application and Submission Information.

Environment

Will the institutional environment in which the [Center] will operate contribute to the probability of success in facilitating the research [program/projects/network/consortium] it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the [Center] proposed? Will the [Center] benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this NOFO: How will the institutional environment in which the ExRC operates contribute to the probability of success in facilitating the research projects it serves? How will the ExRC benefit from unique features of the institutional environment, infrastructure, or personnel? How appropriate are resources available within the scientific environment and how will they support secure electronic information handling? How obtainable or appropriate are resources, equipment, and infrastructure and how adequate are they to allow quick continuation of Coordinating Center functions? How appropriate are data infrastructure and information technology (in place or obtainable) and how adequate are they to support the goals of the project? How will institutional resources and infrastructure be committed or leveraged to support the project?

How relevant are special biosafety precautions for working with highly toxic chemicals to the goals of the project? If working with restricted chemical agents, are all institutional approvals in place? Are appropriate formal letters of collaboration and proposed collaborative arrangements (and estimated budget) provided with the application? See Section IV. Application and Submission Information.

Overall Impact - Cores

Reviewers will provide an overall impact score for each Core to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria.

Review Criteria for the Administrative Core

• How well-matched is the purposed Administrative Core to the needs of the ExRC?
• How appropriate are the proposed strategies and processes that will be used to manage the ExRC, and how applicable are they to scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting, etc.?
• How suitable is the ExRC structure, including its internal and external procedures for managing the activities of the ExRC?
• How appropriate are plans for establishing the EAC, and for the EAC to serve in an advisory capacity?
• How applicable are the Director’s leadership and research qualifications and how suitable are they to lead the Administrative Core?
• How appropriate are plans for establishing and maintaining effective communication with participating CCRP investigators? With NIH?
• How appropriate is the environment for the Administrative Core to support the overall ExRC? Is there evidence of institutional support for the management of the ExRC?
• How reasonable is the ExRC sustainability plan?
• How stringent and feasible are the proposed metrics to assess ExRC success and outcomes relevant to the CCRP?

Review Criteria for the Research Support Core

• How effective are the core activities in supporting research productivity?
• How appropriate is core leadership and technical expertise, and how do they align with proposed goals?
• How sufficient are staffing, allocated space, equipment, and other resources available to the core, and how will they meet  the anticipated demand for services?
• How will services provided advance the current understanding of toxicity mechanisms of CoC?

Review Criteria for the Coordination Core

• How efficient and capable are the core activities in supporting data handling and transfer?
• How are prioritization plans for scheduling and investigator requests for data services adequate and fair?
• How does the core provide leadership and technical expertise to ensure that it meets its stated goals?
• How appropriate are staffing, allocated space, equipment, and other resources available to the core, and how will they meet the anticipated demand for its services?
• How will the services provided advance the current understanding of toxicity mechanisms of chemical threat agents?

Additional Review Criteria - Overall

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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed 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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] 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 NIEHS, 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 will receive a written critique.

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned/administered by the NIH Institutes most relevant to the routes of exposure, toxidrome(s), and specific CoCs proposed.  Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by appropriate national Advisory Council. 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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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.

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

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, Recipients, and Activities, including of note, but not limited to:

• Federal wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

•  For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgment 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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.”

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 Part 75, 2 CFR Part 200 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 recipients 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 recipients for the project, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Setting project timelines and operations of the ExRC.
• Suggesting research approaches and aiding participating investigators in protocol design.
• Establishing and coordinating activities for the following committees and panels:
  • An EAC that will provide guidance to the Steering Committee and PD(s)/PI(s) and participate in reviewing CCRP investigator proposals
  • A Steering Committee that will provide guidance to the PD(s)/PI(s) and make decisions on behalf of the PD(s)/PI(s)
• Providing protocols and data in a timely fashion as agreed upon by the Steering Committee.
• Disseminating data and protocols to participating CCRP investigators.
• Adhering to policies regarding data access and intellectual property established by the NIH and Steering Committee.
• Abiding by common definitions, protocols, and procedures, as chosen by majority vote of the Steering Committee.
• Accepting and complying with study policies established by NIH and with additional non-conflicting policies approved by the Steering Committee.
• Submitting periodic facility progress reports in a standard format, as agreed upon by the Steering Committee and NIH.
• Attending and participating in Steering Committee meetings and accepting and implementing decisions by the NIH, as appropriate.
• Facilitating collaborative interactions between ExRC personnel, NIH staff, Steering Committee members, EAC members, and external stakeholders as appropriate to foster ideas that accelerate progress towards the goals of the ExRC.
• Organizing and participating in regular meetings or phone calls of the Steering Committee, EAC, or other committees as needed. The membership, frequency, and governance of these meetings will be negotiated with NIH staff after funding decisions have been made.  
• Completing quarterly and annual progress reports and providing written evidence of progress when requested by NIH staff. This will include and is not limited to information on evaluations, sample capacity, toxicants being studied, and data transfer status. Much of this information should be extracted from data the CCRP investigators submit to the ExRC, but some information will need to be collected specifically for these reports. The frequency, timing, and method for collecting this information will be determined in close collaboration with NIH and participating CCRP investigators.
• Collaborating with CCRP investigators and other stakeholders to make the CCRP community aware of this resource.

The NIH Program Official will be responsible for the normal scientific and programmatic stewardship and final approvals of the award and will be named in the award notice. The Program Official will: 

• Evaluate progress of the ExRC (including data sharing activities) through reviews of technical or progress reports, site visits, or external consultants to determine that performance is consistent with the terms and conditions of the award.
• Develop metrics and guidelines for data transfer.
• Work with the Project Scientist(s) and ExRC PD(s)/PI(s) to establish procedures to correct unanticipated programmatic or financial deficiencies in recipient's performance.  
• Review performance after project completion. 

NIH Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards as described below:

• Participating with the other Steering Committee members in addressing issues that arise with planning, operation, assessment, and data transfer. The Project Scientist(s) will assist and facilitate the group process but will not direct it.
• Serving as a liaison, helping to coordinate activities within the ExRC.
• Attending all Steering Committee meetings as a voting member, assisting in developing operational guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action.
• Engaging in consultations with the Program Official to promote interactions between recipients (e.g., organizing and holding meetings of CCRP investigators).
• Participating as a non-voting member in EAC meetings.
• Ensuring compliance with the CCRP mission and NIH policies and procedures.
• Monitoring the facility on a regular basis. Monitoring may include regular communication with ExRC PD(s)/PI(s), periodic site visits, meetings, fiscal review, and other stewardship activities.
• Formally assessing ExRC progress on an annual basis to advise the Program Official.  

NIH program staff may consult with independent experts as necessary. If justified, future timelines may be revised based on data and information obtained during the previous budget period. Decisions regarding continued funding will be based on overall ExRC progress, CCRP portfolio balance and program priorities, the number of actively participating investigators, and availability of funds.

The exposure requirements of CCRP investigators will be developed in consultation with Steering committee recommendations. 

Areas of Joint Responsibility include:

The Steering Committee will meet twice during the first year of ExRC operations and subsequently once per year and monthly on conference calls as needed to share information on data resources, methodologies, and analytical tools. PD(s)/PI(s), key co-investigators, and trainees, including those who are members of under-represented minority groups or those from different but related disciplines, are encouraged to attend these meetings.

The Steering Committee will serve as the main scientific body of the program. Steering Committee membership will also include PD(s)/PI(s) of the ExRC, and other staff as needed (ex-officio). The Steering Committee may add additional members, and other CCRP staff may attend the Steering Committee meetings as desired. The Steering Committee may establish working groups as needed to address issues, which will include representatives from the CCRP and the NIH and possibly other experts. The ExRC Recipient agrees to work collaboratively to:

• Participate in processes for participant selection and assignment for evaluation.
• Provide for secure, accurate, and timely data transfer.
• Participate in governance of the ExRC as a member of the Steering Committee.
• Membership, frequency, and governance will be negotiated with NIH staff after funding decisions have been made.
• Changes to existing policies and procedures may be developed jointly by the recipient and NIH staff and must follow relevant HHS, PHS, and NIH policies.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient'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.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. If additional Data Management and Sharing requirements need to be added, please insert what requirements are desired.

When multiple years are involved, recipients 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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 – Award Term and Condition 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.

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

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Srikanth Nadadur, PhD

National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3296
Email: nadadurs@niehs.nih.gov 

Dave Yeung, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7237
Email: dy70v@nih.gov     

Shardell Spriggs, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-443-8189
Email: shardell.spriggs@nih.gov

Houmam H Araj
NEI - NATIONAL EYE INSTITUTE
Phone: (301) 435-8166
E-mail: ha50c@nih.gov

Leroy Worth Jr, PhD

National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3340
Email: worth@niehs.nih.gov

Clark Phillips

National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-4037
Email: clark.phillips@nih.gov

Jason A. Lundgren
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2973
Email: Jason.Lundgren@nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov
 

 Karen Robinson Smith
NEI - NATIONAL EYE INSTITUTE
Phone: 301-435-8178
E-mail: kyr@nei.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.

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 and 2 CFR Part 200.