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 How to Apply - 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.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose/Research Objectives

Rapid advances in genotyping and next generation sequencing technologies have led to the identification of genetic variants that are associated with a wide variety of congenital defects including structural congenital anomalies (SCAs), intellectual developmental disabilities (IDDs) and inborn errors of metabolism (IEMs). The purpose of this initiative is to promote the screening, functional validation and characterization of congenital anomalies-associated genetic variants identified through public facing databases and individual efforts using in-silico tools, appropriate animal models, in vitro systems or multi-pronged approaches. The ultimate goal is to enhance the translation of basic knowledge gained from functional genomic approaches into the development of new, innovative, and efficacious strategies for the molecular diagnosis, treatment, and prevention of human birth defects.

Background

Annually, almost five percent of all live births in the United States (more than 180,000 babies) involve babies born with congenital anomalies when broadly defined to include structural, functional, and metabolic abnormalities. Congenital anomalies are the leading cause of death in children within the first year of life and account for half of all pediatric hospitalizations. Congenital anomalies have a great impact on public health, socioeconomics, and family life.

The genomic revolution holds promise for enabling the discovery of effective and targeted therapies based on the underlying genetic classification of conditions – the basis for precision medicine. Studies of developmental biology are revealing the underlying genetic networks essential to cell/tissue differentiation, morphogenesis, organogenesis, as well as functions of cells and cellular organelles. Disruptions in these fundamental developmental processes result in congenital anomalies. The combined efforts of basic scientists studying the genetic networks and physician scientists sequencing patient cohorts together place the field of congenital anomalies research on the verge of major advances.

The NIH has made significant investment in genomic studies and technologies to identify DNA sequence variations associated with a wide variety of congenital anomalies. Among others, the Gabriella Miller Kids First Pediatric Research Program (Kids First), the Center for Mendelian Genomics (CMG), Pediatric Cardiac Genomics Consortium (PCGC), Deciphering Developmental Disorders (DDD) and the Undiagnosed Disease Network (UDN) are generating large-scale clinical and genetic data from patients and their families with syndromic and organ-specific developmental disorders. Data generated through whole genome sequencing, SNP and SV analysis, and whole-exome sequencing are available to the research community through several databases such as the Database of Genotypes and Phenotypes (dbGaP), the Kids First Data Resource Portal, the European Genome-phenome Archive and ClinVar.

Despite an explosion of data resources, researchers face a challenging gap between identifying congenital anomaly-associated sequence variations and recognizing which of these variations have functional effects on the phenotype of interest. In order to pursue mechanistic studies of how specific genetic variants affect developmental pathways and gene networks leading to the observed phenotype, researchers must have effective methods to screen potential variants to identify the causal ones. Faster, less expensive, and more accurate gene-to-function screens are critical for accelerating the translation of genomic findings into greater understanding of human congenital anomalies.

Scope

This initiative encourages screening and functional validation of genomic variants associated with congenital anomalies and invites grant applications proposing to identify and prioritize genomic variants through in-silico analyses and/or cell-based assays, and followed by functional validation and deep mechanistic studies of causal variants in appropriate model systems.

Criteria for responsive applications:

Applicants may propose non-hypothesis driven screening of variants to establish association with congenital anomalies under investigation, or hypothesis-driven mechanistic studies to generate critical information on how variant functions affect the disease phenotypes, or a combination of both types of studies.

Variant selection:

• Genomic variants may be selected from those available through public databases or identified via individual/group efforts such as ClinGen Expert Curation Panels.
• Genomic variants must be statistically associated with the congenital anomaly under investigation.
• Genomic variants may affect coding and/or non-coding regions.
• Genomic variations including, but not limited to single base pair substitutions, copy number variations (insertions or deletions) and chromosomal rearrangements can be investigated.
• Applicants are encouraged to use available genomic, gene expression and phenotypic databases and resources, such as the International Genome Sample Resource-IGSR, the Encyclopedia of DNA Elements-ENCODE data portal, the Gene Expression Omnibus-GEO data resource, Genotype-Tissue Expression (GTEx) -database, model organism databases, and appropriate bioinformatics tools for variant selection.
• Variant selection criteria may include, but are not limited to the following categories:
  • Variants prioritized based on existing clinical phenotyping data.
  • Variants selected through functional prediction or variant interpretation tools (e.g. CiviC, Open Cravat).
  • Variants known to be associated with gene expression patterns in relevant tissue(s) and cell types that could reasonably be connected to normal biology and the disorder in question.
  • Variants that currently lack functional annotation and need improved and/or high?throughput functional assays to establish a connection with the human phenotype of interest.
  • Novel variants associated with functionally annotated genes but lacking an established connection with the human phenotype in question.
  • Variants known to be associated with epigenomic changes such as DNA methylation, histone modifications or DNase I hypersensitivity occurring in disease relevant cell types and potentially influencing gene regulation involved in the trait of interest.

Model Systems:

Novel and/or high throughput screening strategies to validate genomic variants may be based on:

• Model organisms including but not limited to Drosophila, C. elegans, Xenopus, zebrafish, chick, mouse, or rat.
• In vitro model systems include, but are not limited to, organoids, and patient-derived or genome engineered induced pluripotent stem cells and their differentiated derivatives of defined genotype.
• A combination of in vitro and in vivo model systems (cell or tissue-based culture systems).
  
  In order to determine the optimal model systems best suited to study human conditions of interest, the investigators are encouraged to use the existing resources for animal models or in vitro systems. These include, but are not limited to, the database of Drosophila Genes and Genomes (FlyBase), core data resource for C. elegans and other nematodes (WormBase), Xenopus Biology & Genomics Resource (Xenbase), Zebrafish Model Organism Database (ZFIN), Mouse Gene Expression Database [(GDX], ), Chick Gene Expression Database (GEISHA/Aviport), Rat Genome Database (RGD), the Collaborative Cross mouse strains, and the NIH Center for Regenerative Medicine (NIH CRM) databases.

Assays:

• Assays should allow for direct functional measures of normal and altered biological processes and/or anatomic structure.
• Assays should typically be conducted in vivo (in a relevant animal-model) and/or in vitro (in cell- or tissue-based models).
• Functional assays conducted in vitro or cell-free biochemical assays should be verified in vivo in an animal model.

Providing multiple lines of convergent evidence supporting functionality using a combination of in silico, in vitro, and in vivo models is encouraged.

Applicants are encouraged to provide a timeline for achieving the major goals stated in the application and describe metrics for evaluating achievement of the goals and what action will be taken, and when, if a goal is not met or significantly delayed.

Non-responsive applications: Projects with the following properties will be considered non-responsive, and will not be reviewed:

• Projects proposing large scale sequencing of birth defects cohorts will be considered non-responsive to this FOA. Investigations should be focused on existing sequence data available through publicly available databases or identified via individual/group efforts such as ClinGen Expert Curation Panels.
• Projects that do not test the function of human genomic variants.
• Projects that do not test genomic variants associated with congenital anomalies.
• Projects proposing only cell-free biochemical assays to validate genomic variants.
• Assays conducted exclusively in in vitro systems.
• Assays not validated in an animal model

Research Interests of Participating NIH Institutes and Office

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

A high priority goal for NICHD, as stated in Theme 1 of the 2020 NICHD Strategic Plan, is to address the problem of birth defects by advancing our understanding of their etiology in order to improve prevention and treatment.

For this NOFO, NICHD encourages applications proposing to screen, functionally validate, and characterize genetic variants associated with children born with the following conditions:

• Structural congenital anomalies (SCAs)
• Intellectual developmental disabilities (IDDs)
• Inborn errors of metabolism (IEMs)

Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from NICHD are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII. Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with NICHD's program priorities.

National Institute of Dental and Craniofacial Research (NIDCR):

NIDCR encourages applications proposing studies that will generate insights into the developmental etiology of rare or common human congenital anomalies, affecting dental, oral, and craniofacial structures. Data available on the NIDCR-supported FaceBase Hub (www.facebase.org) may be utilized to support variant prioritization.

Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from NIDCR are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII. Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with NIDCR's program priorities.

Office of Research Infrastructure Programs (ORIP):

ORIP encourages applications that are relevant to ORIP's mission to support research infrastructure and research-related resource programs, such as development of new technologies for generation and distribution of animal models of human diseases. The technologies to create animal models of human genetic variants associated with human congenital anomalies and related materials must have broad application to multiple NIH Institutes or Centers (ICs) to align with the ORIP’s trans-NIH mission. The following are examples of potential research topics:

• Improving methods to rapidly and efficiently generate non-mosaic germline and somatic human genomic variants to model disease-specific genomic alterations (coding and not coding), including robust phenotyping to assess if species genetic changes recapitulate a human phenotype. Tools for a conditional and tissue specific genome modifications are of special interest.
• Approaches for generation of complex genetic mutations or larger structural variants (SV) (deletions, duplications, inversions).
• Combining model organism genomic modifications with phenotyping assays including detailed molecular analysis (omics profiling) which should be sufficiently integrative to assist high throughput interpretation of disease processes shared in model organisms and human patients.
• Assess the effect of species genetic background of specific animal model species used to model a variant on the presentation and penetrance of a given phenotype.

Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from ORIP are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII. Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with ORIP's program priorities.

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

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 Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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 How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• 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 registrations; 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 How to Apply - 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:

Reiko Toyama, Ph.D.
Telephone: 301-435-2723
Email: toyamar@nih.gov   

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Research Strategy:

Applicants should:

1) Describe the human congenital anomaly under investigation and the dataset from which variants will be selected, as well as the public database through which these data are accessible, where applicable.

2) Describe how in-silico analysis, in vivo analysis and/or cell-based assays will be used to identify and prioritize variants. Include an explanation of how gender differences will be accounted for.

3) Describe the assay(s) and/or model system(s) that will be used to validate the selected variants. Explain why this approach is expected to recapitulate or otherwise inform the phenotype under study. Using a combination of in silico, in vitro, and in vivo models is encouraged. If conducting in vitro or cell-free biochemical assays, explain how this will be verified in an in vivo animal model.

4) Explain why the data generated from this project will be of high value to the human congenital anomalies research community and/or potentially inform the development of strategies for the molecular diagnosis, treatment, or prevention of human congenital anomalies.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-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.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

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

PHS Human Subjects and Clinical Trials Information

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 How to Apply- 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 How to Apply- 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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply 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 How to Apply 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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

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

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.

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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

Consistent with the 2023 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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. 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 2 CFR Part 200.301.

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

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Reiko Toyama, Ph.D.
Telephone: 301-435-2723
Email: ToyamaR@nih.gov

Zubaida Saifudeen, PhD
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: (301) 827-3029
E-mail: zubaida.saifudeen@nih.gov

Oleg Mirochnitchenko, Ph.D.
Office of Research Infrastructure Programs (ORIP)
Telephone: (301) 435-0748
Email: oleg.mirochnitchenko@nih.gov

Center for Scientific Review

Email: FOA_ReviewContact@csr.nih.gov

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Mindy Bixby
Telephone: 301-402-3204
Email: mindy.bixby@nih.gov

Gabriel Hidalgo. MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: hidalgoge@mail.nih.gov

Section VIII. Other Information

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

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 2 CFR Part 200.