Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

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 NOFO or in a Notice from 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

Purpose

The NIAID Division of Allergy, Immunology, and Transplantation's (DAIT) Radiation and Nuclear Countermeasures Program (RNCP) has been tasked with developing safe and effective medical countermeasures (MCMs) and biodosimetry tools for civilians, which can be used 24 hours or later post-exposure during a radiological or nuclear public health emergency. This Notice of Funding Opportunity (NOFO) is intended to elucidate sex-dependent effects that occur after radiation exposure. Historically, radiation studies predominantly utilized male animals, leading to an insufficient sex balance in preclinical study data that were not representative of the general population. Although this practice has changed over time and the inclusion of female animals has increased, the available radiation data powered for sex-dependent variables are still limited. While many studies demonstrate sex trends, they lack statistical power for definitive results and conclusions. This NOFO seeks to ensure studies are well-powered to include both female and male data to better understand underlying sex-related differences to advance radiation preclinical animal models, improve MCM development, increase the safety and efficacy of MCMs, and advance biomarker science to assess radiation injuries.

Background

The mission of the RNCP is to accelerate the development of approaches to diagnose, mitigate, and treat radiation injuries resulting from a mass casualty radiological or nuclear incident. The RNCP was established in 2004 under NIAID/DAIT to help the U.S. Government be better prepared medically to address radiation injuries quickly and effectively during a public health emergency. The program is guided by the NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiation and Nuclear Threats, updated in 2012. To mitigate radiation exposure, the RNCP prioritizes the identification of MCMs to treat acute and long-term radiation injuries involving hematopoietic, gastrointestinal, pulmonary, cutaneous, renal, cardiovascular, and central nervous systems. In addition, the RNCP supports the development of biodosimetry tools to evaluate the degree and impact of radiation exposures after a mass casualty incident. Differential sex-based radiation effects in humans and preclinical animal models have been well documented; however, the underlying mechanisms remain unclear. These inherent sex differences can potentially contribute to differences in radiation sensitivity, efficacy of mitigation, as well as biomarkers of radiation injury and recovery. Therefore, understanding these sex-dependent differences in radiation injury and responses is crucial to development of biomarkers of radiation injury and efficacious medical countermeasures in both sexes.

The RNCP is committed to engaging in research that is rigorous, reproducible, and inclusive. Sex inclusion policies and guidelines established by the NIH Office of Research on Women's Health (ORWH), established in 1990, are of critical importance in ensuring that the NIH and all radiation stakeholders advance predictive and diagnostic biodosimetry/biomarker approaches and develop effective MCMs against radiation in both female and male targets. In 2015, the Sexual & Gender Minority Research Office (SGMRO) was also established in the NIH Office of the Director to advance research on the health and well-being of these diverse communities. Through the NIH Revitalization Act of 1993, guidelines were established to include females in clinical research because female models were largely excluded, overlooked, and oversimplified. Since then, new policies have been adopted to 1) improve the inclusion of sex as a biological variable in preclinical and clinical research designs, analyses, and reporting - NOT-OD-15-102 Sex as a Biological Variable (SABV) Policy (2015); 2) require reporting of disaggregated sex, gender, race, and ethnicity for NIH-defined applicable Phase III clinical trials in Clinical Trial.gov - 21st Century Cures Act (2016); 3) provide guidelines to publish inclusion data by sex, gender, race, and ethnicity - NIH’s Research, Condition, and Disease Categorization (RCDC); and 4) continue to pave the road for inclusion of both sexes in the biomedical sciences research - NIH Inclusion Across the Lifespan (2019).

Radiation studies have been oversimplified by the predominant inclusion of males in preclinical studies, lack of statistical power for SABV, low availability of female nonhuman primates, reporting of data and classification of in vitro specimens (blood, urine, cells, etc.) as combined sex rather than by sex, and limited access to irradiated human samples. Even with these limitations, sex trends are evident in many radiation studies. In atomic bomb survivors from Hiroshima and Nagasaki as well as in Belarus and Ukraine after the Chernobyl nuclear accident, higher esophageal and thyroid cancer incidence has been observed in females compared to males. Other non-cancerous, sex-dependent health outcomes such as increased adult bronchial asthma, high blood pressure, and heart attacks also have been found at higher rates in females following the Chernobyl accident. Cellular and molecular characterization of radiation injury suggests that genomic damage and cell apoptosis may occur more frequently in human and mouse male germ cells after radiation exposure. In addition, differential survival and organ damage sensitivities have been noted in males and females in both mouse and NHP models. MCM efficacy studies also show that sex can impact drug responses and efficacy in normal or irradiated animals. Finally, radiation-induced biomarker studies have shown sex-dependent expression changes, which can impact the selection of robust biomarkers or the design of biodosimetry tools.

To begin to assess sex difference gaps in the RNCP portfolio, a Request for Information (RFI), "Sex Differences in Radiation Research: Animal Models, Underlying Pathways, Biomarkers of Injury, and Medical Countermeasure Responses (NOT-AI-22-040) was published in March 2022. Responses to this Notice were used to help draft the current RFA. Also, in April 2022, the NIAID/RNCP coordinated a "Sex Differences in Radiation Research" workshop with the NIH ORWH, Food and Drug Administration (FDA), FDA Office of Women’s Health (OWH), and the Biomedical Advanced Research and Development Authority (BARDA) Radiological and Nuclear Countermeasures Branch. With 26 speakers and over 150 attendees, current understanding and gaps in sex differences research were discussed. The keynote speakers addressed the differences between sex and gender and why it matters, as both biology and hormones can influence the response to radiation, making it important to consider sexual and gender minority groups since triage and treatment decisions based solely on male and female constructs may impact safety and efficacy outcomes. Sessions included topics such as mechanisms underlying sex-dependent differences in radiation effects observed in animal models, MCM responses, and biomarker advancement. Investigating and elucidating sex-based differences in radiation studies should lead to i) refinement of existing MCM and biomarker signatures in both sexes and ii) identification of novel MCM targets of radiation injury and recovery reflective of sex-based changes.

Research Objectives and Scope

NIAID Radiation and Nuclear Countermeasures Program (RNCP)

This NOFO solicits milestone-driven research to target gaps in knowledge regarding the influence of sex on radiation-induced injuries to improve our understanding of the factors and mechanisms underlying sex differences in health outcomes in the event of a radiation public health emergency. Radiation exposures experienced during a radiological or nuclear incident will likely vary from low to high dose and could involve different dose rates and radiation exposure scenarios, such as prompt gamma and/or neutron exposures, and/or internalized radionuclides.

This NOFO intends to ensure that studies are well-powered to help elucidate sex difference trends previously reported in both animal models and clinical settings to help fill gaps in this research area. To be responsive, examples of proposed studies may include, but are not limited to:

• Examination of mechanistic pathways leading to biological differences between females and males in radiation studies. Studying female and male cells, organs, and biological systems is necessary to improve our understanding of the mechanisms by which sex influences organs/tissues with relevance to a radiation emergency (e.g., bone marrow, GI tract, oral mucosa, skin, lung, kidney, etc.), and its involvement in radiation pathogenesis in those tissues and organs affected by total and/or partial body radiation exposure.
• Investigation of sex differences in acute and delayed effects of radiation exposures. Various types of exposures affect disease risk across different timescales, ranging from an immediate outcome at the time of exposure to a delayed outcome that becomes evident at a later stage in life.
• Investigation of the influence of sex on severity of radiation injury, management, and outcomes. Sex factors influence the course of many diseases, including risk and protective considerations, presentation of injury, treatment efficacy, and damage recovery.
  • Determine sex-related effects of MCM efficacy when administered at least 24 hours post-irradiation, as delays in administration of therapeutics would be anticipated in a radiological or nuclear incident. Radiation exposure type, dose level, and dose rates proposed for the study must be relevant to an attack or accidental exposure incident. Also, routes of MCM administration should be consistent with use in a mass casualty setting (i.e., oral, subcutaneous, intramuscular, inhaled, topical, transdermal, etc.), and any products proposed for study must have a favorable safety profile.
  • Determine sex-related differences in biodosimetry/biomarkers of radiation injury to improve the identification of robust biomarkers for diagnosis and/or radiation injury prediction. These sex-agnostic biological responses should accurately, quickly, and non-invasively assess large numbers of potentially irradiated people (triage tool), to guide medical management of a radiation public health emergency, or to predict radiation injury/outcome. Ex vivo studies using human samples are allowed.
• Determination of the impact of reproductive status, reproductive maturity, pheromones, and hormones on radiation injury.
• Identification of sex-linked sensitivity in radiation injury animal models in response to total and/or partial body irradiation. Fully evaluate dose-response relationships, the effects of radiological sources, and standard operating procedures.
• Identification of sex differences using emerging technologies such as organ-on-a-chip, cell and patient-derived organoids, etc.

Milestones

The research plan must include detailed, explicit, and quantitative annual milestones. These milestones will be used by NIAID program staff to assess annual progress and support funding decisions.

NIH Office of Research on Women's Health (ORWH)

The Office of Research on Women’s Health (ORWH) is part of the NIH Office of the Director, and works in partnership with the 28 NIH Institutes, Centers, and Offices (ICOs) to ensure that women's health research is part of the NIH scientific framework and supported throughout the biomedical enterprise. ORWH uses a multidimensional framework to represent the intersection of factors that underlie patterns of disease and determinants of health outcomes in populations.

ORWH is interested in supporting biomedical research that considers sex and/or gender influences and includes adequate plans for collecting and reporting sex-specific data. There is a crucial need to address sex and/or gender influences in basic, translational, interdisciplinary, behavioral, clinical, and/or health services research relevant to women's health, and, where appropriate, include both sexes to better understand the influence of SABV on health and disease. Integrating the purposeful accounting for SABV in biomedical research, from the most basic to the clinical and applied efforts, will fill gaps in our knowledge, and will inform more effective and personalized approaches for women and men. For additional guidance, please review the 2019-2023 Trans-NIH Strategic Plan for the Health of Women (https://orwh.od.nih.gov/about/trans-nih-strategic-plan-womens-health-research).

Applications including the following areas of study will be considered non-responsive and will not be reviewed:   

• MCMs administered prophylactically (pre-irradiation) or less than 24 hours after exposure.  
• Proposed research in radiation dose ranges or exposure parameters that are not relevant to a radiation accident or attacks such as the use of very low dose/dose-rate exposure or fractionated radiation exposures, unless information gained would be directly applicable for MCM, biomarker or biodosimetry development.
• Role of sex-related influence on carcinogenesis.
• Studies focused on HIV/AIDS-related research.
• Performance of clinical trials (all phases).
• Applications lacking preliminary data and/or milestones. 

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 Government

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant Organizations

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

• 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 their 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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 notice of funding opportunity 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.

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:

Maryam Rohani, DDS, Ph.D.
Telephone: 301-761-6656
Email: [email protected] 

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

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

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

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

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

The PD(s)/PI(s) and key personnel should include within the biosketches their appropriate expertise in radiation biology, dosimetry, statistics, and/or health physics. Designated personnel must have sufficient level of effort to support successful completion of the proposed studies. Adequate bioinformatics expertise is also needed to enable compliance with the data and other resources-sharing requirements.

R&R or Modular Budget

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

Within the budget section, include funds to support travel for the PD(s)/PI(s), and if necessary, the minimum number of additional relevant staff, to participate in a once yearly, 1-day program progress meeting with NIAID and other US Government Program staff, to be held in the Rockville, MD area.

R&R Subaward Budget

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

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

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

Specific Aims: List in priority order the broad, long-range objectives and goals of the proposed project. Concisely describe the work to be completed.

Research Strategy: Use this section to summarize the research strategy, including significance, innovation and approach of the application and explain the rationale for selecting the methods to accomplish the specific aims. Applicants are required to provide preliminary data suggesting a potential sex difference that needs further exploration. In addition, provide an overview of the scientific problem to be addressed and the potential of the proposed research to close the gaps in knowledge on the influence of sex on radiation-induced injuries.

Describe specifics of the irradiator(s), including dosimetry methodology and calibration approach to be used at the institution(s) where radiation will be employed. Describe statistical plans to ensure that the proposed study is adequately powered to address SABV policy.

Milestones (required): Briefly describe for all years of the award, detailed, explicit, and quantitative milestones that will be achieved in each year of the Research Project. For example, it is not appropriate to state only that "countermeasure A will be tested for its ability to mitigate radiation damage," or that “specific aim A studies will be initiated.” An appropriate milestone might include, but not be limited to the following: "These studies will demonstrate a statistical sex difference (P<0.05) when MCM A is subcutaneously administered at 24 hours post-exposure in an appropriate animal model". These milestones will be used by NIAID program staff to assess long-term planning by the PD/PI. Milestones will also be used by NIAID program staff to assess yearly progress and recommendations of continued funding.

Letters of Support: Provide any letters of support from collaborators that are specific to the Research Projects.

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.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• After allowing time for publication and any other appropriate first use and access needs, recipients will be expected to share data collected under this award through ImmPort (https://www.immport.org/home).

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-defined 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.

Delayed Onset Study

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

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

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

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.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) 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. See Section III of this NOFO for information on registration requirements.

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.

See more tips for avoiding common errors.

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

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

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.

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 the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this NOFO:

• To what extent do the preliminary data suggest a potential sex difference that needs further exploration?

Investigator(s)

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

Specific to this NOFO:

• To what extent does the project include personnel with the appropriate expertise in radiation biology, statistics, dosimetry, and/or health physics?
• To what extent have the designated personnel allocated a sufficient level of effort to support successful completion of the proposed studies?
• To what extent will the bioinformatics expertiseenable compliance with the data- and other resources-sharing requirements?

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

• To what extent is the dosimetry methodology adequately described and are plans for dosimetry calibration appropriate?
• Are the proposed milestones detailed, explicit, and quantitative, detailing an approach that is achievable each year of the Project? Are they quantifiable and reasonably attainable?

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?

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 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

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.

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) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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 National Institutes of Allergy and Infectious Diseases (NIAID), 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 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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases 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.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 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: Recipient 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.

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, 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 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 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 and 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 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 as a whole, 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:

• The timely submission of all abstracts, manuscripts, and reviews (co)authored by members of the grant and supported in part or in total under this Agreement.  The PI is requested to submit manuscripts to the Project Scientist right after acceptance for publication so that an up-to-date summary of program accomplishments can be maintained, and press conferences and press releases prepared.
• Attendance at yearly annual U01 meeting.
• Defining the details and goals of the project as a whole.
• Overseeing/performing the scientific activities.
• Sharing new information and materials with the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other NIAID approved mechanisms.
• Recipients will be expected to participate in a NIAID-sponsored, program-wide dosimetry harmonization effort to ensure accurate radiation exposures.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• The Project Scientist will advise in the selection of sources or resources (e.g., determining where a particular reagent may be found); provide advice and guidance on technical issues; coordinate or participate in the collection and/or analysis of data; advise on the management and technical performance; review milestones prior to award and during the project period, and request revised milestones. If applicable, review annual progress towards achieving the previously agreed upon milestones to ensure successful completion of the project.
• NIAID program scientist will negotiate milestones with the PD/PI to assess long-term planning for the development of the candidate radiation medical countermeasures. Milestones also will be used by NIAID program staff to assess yearly progress and recommendations of continued funding.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Research design and protocol development, data collection, final data analysis and interpretation, preparation of publications, as well as collaboration with other awardees, with assistance from the NIAID Project Scientist when appropriate.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between 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.

4. Reporting

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 $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.

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: [email protected] (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: [email protected]

Lanyn P. Taliaferro, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5479 
Email: [email protected] 

Rajeev K Agarwal, Ph.D.
ORWH - Office of Research on Women's Health
Phone: 301-451-7058
E-mail: [email protected]

Maryam Rohani, DDS, Ph.D.
National Institute of Allergy and Infectious Diseases(NIAID)
Telephone: 301-761-6656 
Email: [email protected] 

Svetlana Alperovich
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6895 
Email: [email protected] 

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.