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.

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) invites proposals that stimulate innovation and advance understanding of when, where, and how best to implement the use and sharing of genomic information and technologies in clinical care provided to all persons irrespective of racial/ethnic background or socioeconomic status. Applications should focus on genomic medicine, defined as using genomic information about an individual as part of their clinical care (e.g., for screening, diagnostic, or therapeutic decision-making) and the health outcomes and policy implications of that clinical use.

NHGRI supports studies that provide generalizable methods and knowledge. Applications for studies relevant only to a particular disease or organ system should be directed to the appropriate Institute or Center. Similarly, projects that focus only on a gene or limited set of genes will not be appropriate for NHGRI funding unless broad applicability is clearly explained and use of a single gene or limited set of genes is well justified. All applications, regardless of focus, should explain how generalizable, broadly useful, and transformative the findings and approaches will be to the field of genomic medicine.

Background

The past decade has seen a significant growth in the implementation of genomics in clinical practice. NHGRI has primarily funded genomic medicine research through multi-disciplinary consortia, which provide rich opportunities for collaboration or ancillary projects and have produced valuable data resources and tools for independent genomic medicine research (for more information about these programs, see https://www.genome.gov/about-nhgri/Division-of-Genomic-Medicine). As the field grows, opportunities for focused research projects outside large-scale coordinated consortium approaches are growing as well. This funding opportunity invites proposals for these type of research projects.

This funding opportunity is a renewal of RFA-HG-20-036.

Scope and Objectives

This NOFO centers on addressing research gaps related to the use of genomic information to advance the application of genomics in clinical care.

In the context of their relevance to genomic medicine, the following are some examples of the areas of research studies that would be appropriate for this NOFO, grouped by category:

Implementing genomic medicine

Implementation research projects would elucidate whether use of genomic information about an individual improves clinical care and/or health outcomes, or how best to implement genomic medicine.

• Understanding facilitators and barriers in implementation of genomic medicine and pharmacogenomics across broad settings, especially their diffusion and sustainability in various clinical settings.
• Identifying and assessing implementation science frameworks that can be used to study genomic medicine in academic clinical settings, non-academic clinical settings, or both.
• Developing computational, health-economic, or other analytical approaches that identify characteristics of participants likely to derive the greatest (or conversely, the least) value from incorporating various types of genomic data into clinical care. Applicants considering health-economic approaches should review NOT-OD-16-025, “Clarifying NIH Priorities for Health Economics Research,” https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-025.html.
• Comparing health care utilization or disease outcomes with and without implementation of clinical decision support tools for genomics.
• Assessing, innovating, scaling, and/or researching the implementation of novel genetic counseling practices to address the need for more healthcare professionals trained in genetic counseling.

Facilitating analysis of clinical genomic data

The pace and volume of genomic data being generated presents challenges and opportunities for methods and tools that facilitate clinical analysis. Projects could involve building and testing tools.

• Methods that automate or otherwise improve the efficiency of clinical annotation and interpretation of genomic variants, especially those that allow for dynamic interpretation as knowledge of variants and clinical recommendations evolve. Applications focused on establishment of a genomics-enabled learning health system should consider the Notice of Funding Opportunity for Genomics-Enabled Learning Health Systems Clinical Sites U01 (NOT-HG-23-044).
• Integrating genomic data from various sources with other data types such as environmental data, family history, social determinants of health, transcriptomics, epigenomics, functional data, or model organism data and assessing genomic data’s contributions to and improvements in predictive value, clinical validity, and/or clinical utility. Applications primarily focused on developing novel approaches to study how genetic variants lead to differences in function and how such functional differences affect health and disease processes are not responsive to this RFA and should respond to the Parent R01 (PA-20-183 for Clinical Trials PA-20-185 for studies not Clinical Trials) or Parent R21 (PA-20-194 for Clinical Trials or PA-120-195 for studies not Clinical Trials).

Improving clinical access and sharing of genomic data

Clinical access and sharing of genomic data is critical to promoting genomic medicine.

• Assessing genomic data integration throughout health systems and how genomic information influences healthcare providers, payers, and regulators.
• Enhancing portability of genomic data that uses standards for genomic information and allows for iterative use (e.g., integration with EHR apps, transporting to other care systems).

NCI areas of interest

• Evaluating the implementation of cancer genomic data in underserved populations and/or assessing the communication of genomic test results and potential uncertainty of interpretation. 
• Assessing the implementation of cancer genomic testing in accordance to clinical guidelines and evaluating cancer outcomes among underserved populations
• Examining utility of germline genetic data for informing cancer screening, prevention and control
• Integrating cancer specific genomic data from various sources with other data types such as environmental data, family history, transcriptomics, epigenomics, functional data, or model organism data and assessing genomic data’s contributions to and improvements in predictive value, clinical validity, and/or clinical utility.
• Assessing cancer genomic data integration throughout health systems and the impact on cancer outcomes.
• Leveraging or enhancing of relevant NCI resources and investments for identifying and recruiting cancer cases, for incorporating data through linkages to existing databases with relevant exposure, administrative, and health-related data, for community engagement, and for cost-effective exposure assessment and genomic profiling.

Investigators new to the field of genomic medicine are encouraged to apply, especially those not previously funded under RFA-HG-20-036. Genomic medicine research is a multidisciplinary field and research teams may include experts from multiple disciplines, including but not limited to the fields of clinical genetics including genetic counseling and nursing, as well as genetic epidemiology, biostatistics, data science, public health, implementation science, health outcomes research, health economics, health equity and disparities, health policy, and molecular genetics.

A health disparity is a health difference that adversely affects disadvantaged populations, based on one or more of the following health outcomes:

• Higher incidence and/or prevalence and earlier onset of disease
• Higher prevalence of risk factors, unhealthy behaviors, or clinical measures in the causal pathway of a disease outcome
• Higher rates of condition-specific symptoms, reduced global daily functioning, or self-reported health-related quality of life using standardized measures
• Premature and/or excessive mortality from diseases where population rates differ
• Greater global burden of disease using a standardized metric. https://www.nimhd.nih.gov/about/strategic-plan/nih-strategic-plan-definitions-and-parameters.html. 

Studies addressing or incorporating health disparities(for example, studies focusing on differences in health outcomes for defined disadvantaged populations that are worse than the White reference population, https://www.nimhd.nih.gov/about/strategic-plan/nih-strategic-plan-definitions-and-parameters.html) are encouraged. For NIH, populations that experience health disparities may include racial and ethnic minority groups, people with lower socioeconomic status, underserved rural communities, and sexual and gender minority groups, and people with disabilities.

Studies that take place outside academic research settings or can demonstrate the ability for findings to be transferable to settings outside academic settings are also encouraged. Where applicable, investigators are strongly encouraged to consider various models for community engagement in research and plan and budget for the implementation of meaningful approaches across various stages of proposed research projects (e.g., generation of research questions and hypotheses, interpretation and translation of findings, dissemination of findings). For example, studies involving tribal participants or data should consider consultation and engagement with tribal leaders at the start of project planning and continue through post-implementation. Applicants are encouraged to get feedback from the communities in which the research will be performed regarding plans for sharing individual level data resulting from the research projects with the scientific community for research purposes. Feedback and recommendations for data access, protection of participant and patient privacy and confidentiality, and management of health information should be integrated into the Data Management and Sharing Plan. Note that any project receiving NIH funding that collects or uses identifiable, sensitive information is automatically deemed issued a Certificate of Confidentiality (CoC).  

NHGRI areas of interest

NHGRI is committed to maximizing the utility of genomics for all populations. Racial and ethnic minority populations, underserved populations, and populations who experience poorer medical outcomes have been vastly underrepresented in genomic research to date.Lack of diversity in health research study populations  is widely recognized to seriously impair investigators' ability to interpret genomic variants and use them in clinical care across the spectrum of race, ethnicity, socioeconomic status, access to care, and health and morbidity. Understanding and use of the vastness of human genetic variation for clinical diagnosis, prevention, and treatment require studying of genomic variation and its health consequences across sociodemographic groups. For this reason, projects are strongly encouraged to include ancestrally diverse   populations and research study participants from groups shown to be nationally underrepresented in the biomedical, clinical, behavioral and social sciences research.  

Population descriptors measuring the complex concepts of race, ethnicity, genealogical ancestry and genetic ancestry are commonly employed in biomedical, health services, genomic and ELSI research. In the United States, there are real and measurable impacts of one’s racial, ethnic or ancestral identity on health, wellness, and life experiences. It may be valid and valuable to use population descriptors in a given analytical context. However, in some cases socially constructed population descriptors like race and ethnicity are used as proxies for human genetic variation in genetic and genomic research, which can lead to conflation between social and biological groups and can cause harm (NASEM Report Using Population Descriptors in Genetics and Genomics Research). Similarly, sex, gender, gender identity and sexual orientation are complex, related constructs that are conceptually distinct (NASEM Consensus Report, Measuring Sex, Gender Identity, and Sexual Orientation). They are commonly studied aspects of human identity that impact health, access to health care services, and experiences with discrimination; however, they are often mismeasured and misrepresented in research. Overall, the scientific questions to be addressed should guide whether and which population descriptors are used in a given study. Investigators should use established theory, frameworks, or scientific evidence to inform their use of population descriptors. To enhance the rigor and replication of proposed research, applications should be transparent in the Research Plan about the use of population descriptors. 

Per NOT-HG-21-022, NHGRI expects applications awarded under this NOFO to share comprehensive metadata and phenotypic, clinical, and environmental exposure data associated with the study; use standardized data collection protocols and survey instruments for capturing data, as appropriate; and use standardized notation for metadata (e.g. controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses. NHGRI strongly encourages investigators that plan to collect phenotype and/or environmental exposure data about their study participants to utilize standard protocols included in the PhenX Toolkit (http://www.phenxtoolkit.org). Where possible and applicable, investigators should adhere to GA4GH standards (https://www.ga4gh.org) and phenotype standardization efforts such as the Human Phenotype Ontology (HPO) and Monarch. Applicants are also encouraged to learn about NHGRI genomic medicine research programs to identify possible synergies (https://www.genome.gov/27551170/division-of-genomic-medicine-current-research-programs/).

In addition, a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) may be needed for new genomic technology methods used in clinical care, separate from the requirement for the test to have been conducted within a CLIA-certified environment. Applicants may wish to consult the following Points to Consider in Assessing When an Investigational Device Exemption (IDE) Might be Needed: http://www.genome.gov/27561291.

To promote progress in the genomic medicine field, awardees will be required to budget for and participate actively and openly in at least one grantee meeting per year with other awardees and NHGRI staff. Substantial information sharing will be required as appropriate and consistent with achieving the goals of the program and is a condition of the award; failure to openly share information may be grounds for discontinuation of funding. These annual meetings will serve as venues to facilitate sharing of research findings; promote the exchange of ideas; enable discussion of opportunities, challenges, and emerging needs; develop expertise and abilities among collaborators newer to genomic medicine; and accelerate progress in genomic medicine. Other investigators in the field may be invited to participate in these grantee meetings.

Data Sharing

NHGRI recognizes that data sharing is essential to advance genomic research and will expect recipients to comply with the NIH Data Management and Sharing Policy (NOT-OD-21-013) and NIH Genomic Data Sharing Policy (NOT-OD-14-124). NHGRI supports the broadest appropriate data sharing with timely data release through widely accessible data repositories, such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL). Please follow the NIH guidance on Writing a Data Management and Sharing (DMS) Plan, and ensure the Plan is in alignment with NHGRI’s data sharing expectations, which are summarized at genome.gov/data-sharing.

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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) 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 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.

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.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. 
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP Guidance materials.

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.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

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

As part of the significance section, applicants should describe the generalizability and broader relevance of the proposed research to genomic medicine beyond any targeted genes, diseases, or clinical settings included in their specific application. Applicants should clarify how their proposed work will improve understanding of how genomic data may impact disease prevention, diagnosis or treatment, and accelerate the appropriate implementation of genomics in clinical settings. As part of the innovation section, applicants should describe the novelty of their research and detail how it is distinct from existing research efforts in genomic medicine.

Stakeholder engagement can enhance the translation of research results into clinical care and public health and address disparities in health and healthcare. Investigators are encouraged to solicit and be responsive to input of stakeholders such as professional societies, payers, public health and regulatory agencies, communities, patients, patient groups, or caregivers regarding study design, conduct, and outcomes, and to collaborate with relevant stakeholders throughout the research process. As relevant to study aims, applicants are encouraged to provide a plan to include stakeholders in the process of prioritizing, designing, and conducting research.

Applicants proposing generation of new genomic data should provide details on the costs, turn-around-time and computational requirements, including data analysis and storage, for the proposed data. They should address plans for return of results to patients and participants. Due to regulatory requirements for using research results in clinical care, applicants should describe which genomic data will be produced in compliance with the Clinical Laboratory Improvement Amendments (CLIA).

Applicants proposing use of existing genomic data should provide details on the source of the data, including quality control metrics, demographics of participants, appropriateness of existing consent for proposed aims and genomic data sharing, and potential for re-contacting the participants to collect additional information as needed.

Applications proposing research into the potential role of genomic information on the reduction of health disparities should clearly identify the evidence for health disparities for the disease(s) or outcome(s) studied, the role of non-genetic factors that may contribute to the health disparities, and how their specific project will inform the potential reduction of health disparities.  Applications that include population groups traditionally under-represented in genomic medicine research should clearly identify the evidence that the population(s) is under-represented in genomic medicine research and the scientific questions that will be addressed within the population(s).

Research projects that will use population descriptors in the analyses should name and define those variables, provide a rationale for their use and note any associated limitations. Variables whose use should be explained include population descriptors related to race, ethnicity, genealogical ancestry, genetic ancestry, sex, gender, and sexual orientation. The rationale should be supported by established theory, frameworks, or scientific evidence. The Research Strategy should describe how planned use of the selected variables relates to the proposed research question(s), and describe any assumptions or limitations associated with their use.

Applications should include plans to participate actively and openly in grantee meetings and in ways that contribute substantially to advancement of the field. The budget should include travel costs for at least one PD/PI and one other key personnel and/or trainee for the yearly grantee meeting.

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.

 The following instructions also apply:

• Applications involving development of methods, software, or other tools for genomic medicine should include detailed plans where applicable with timelines for disseminating them to the community so they are readily usable.
• Methods, tools, and software should be well-documented and where applicable made available via public repositories.

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.
• Please follow the NIH guidance on writing a Data Management and Sharing (DMS) Plan here, and ensure the Plan is in alignment with NHGRI’s data sharing expectations, summarized in the succeeding paragraphs and detailed at genome.gov/data-sharing.
• To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community for research use, through submission of all data to widely accessible data repositories, such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL), through submission of variant interpretations to ClinVar, and through publication in the scientific literature. 
• Per NOT-HG-21-022, NHGRI expects applications awarded under this NOFO to share comprehensive metadata and phenotypic, clinical, and environmental exposure data associated with the study; use standardized data collection protocols and survey instruments for capturing data, as appropriate; and use standardized notation for metadata (e.g. controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses. NHGRI strongly encourages investigators that plan to collect phenotype and/or environmental exposure data about their study participants to utilize standard protocols included in the PhenX Toolkit (http://www.phenxtoolkit.org). Where possible and applicable, investigators should adhere to GA4GH standards (https://www.ga4gh.org) and phenotype standardization efforts such as the Human Phenotype Ontology (HPO) and Monarch. Applicants are also encouraged to learn about NHGRI genomic medicine research programs to identify possible synergies (https://www.genome.gov/27551170/division-of-genomic-medicine-current-research-programs/).
• Where human biological samples will be studied, they are expected to have been obtained using a documented informed consent process that allows for future research use and broad data sharing (NOT-HG-20-011). If new human biospecimens will be collected, or if clinical application is included in the application, the consent process should be described at a high level in the Research Plan and detailed in the Human Subjects Section.
• NHGRI strongly encourages studies that propose to derive genomic data from human specimens and cell lines to obtain participant consent either for general research use through controlled access or for unrestricted access. Similarly, consent language should avoid both restrictions on the types of users who may access the data and restrictions that add additional requirements to the access request process. NHGRI acknowledges that this will not always be possible or appropriate. In addition, individual participants who do not consent to future research use or broad sharing of their data (i.e., submission of their data to a publicly accessible data repository) may still participate in the primary study if consistent with study design. Additional guidance on informed consent can be found in the NHGRI Informed Consent Resource. 

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.

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.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

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 [email protected].

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. As part of the overall impact score, reviewers should consider and indicate how the Plan for Enhancing Diverse Perspectives affects the scientific merit of the project.

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 NHGRI, 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions, consistent with applicable law.

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

Please note that reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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.

• Awardees will provide updates at least annually on implementation of the PEDP.

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: [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]

Christine Chang, MPH
National Human Genome Research Institute (NHGRI)
Telephone: 240-552-1208
Email: [email protected]

Nonniekaye Shelburne, MS, CRNP, AOCN
National Cancer Institute (NCI) 
Telephone: 301-276-6897
Email: [email protected] 
 

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Maricela Trujillo 
National Human Genome Research Institute
Telephone: 301-480-7716 
Email: [email protected]  

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
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 2 CFR Part 200.