RFA-HG-25-012-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Funding Opportunity Title

Limited Competition: Outcomes of Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network - Clinical Sites (U01, Clinical Trial Required)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of

RFA-HG-19-013

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-HG-25-012

Companion Funding Opportunity

None

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.172

Funding Opportunity Purpose

This Limited Competition Notice of Funding Opportunity (NOFO) invites recipient organizations funded under the Electronic Medical Records and Genomics (eMERGE): Genomic Risk Assessment and Management Network Clinical Sites (RFA-HG-19-013 and RFA-HG-19-014) to participate in the Outcomes of Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the applications will be peer-reviewed, and only meritorious applications will be considered. The eMERGE Network will extend through April 2030 follow-up and collection of outcome data on the roughly 25,000 patients receiving genomically informed risk assessment (GIRA) and management recommendations.

This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite application(s) from eligible organization(s) to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application(s) will be peer-reviewed, and only meritorious application(s) will be considered for funding.

Funding Opportunity Goal(s)

NHGRI supports the development of methods, resources and technologies to improve the health of all humans through advances in genomics research.

Key Dates

Posted Date

Open Date (Earliest Submission Date)

December 30, 2025

Not Applicable

January 30, 2026

Not Applicable

December 2026

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Due Dates for E.O. 12372

Not Applicable

Expiration Date

January 31, 2026

Required Application Instructions

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.

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

This is a Limited Competition Notice of Funding Opportunity (NOFO).Only applications from recipient organizations funded under the Electronic Medical Records and Genomics (eMERGE): Genomic Risk Assessment and Management Network Clinical Sites (RFA-HG-19-013 and RFA-HG-19-014) are eligible to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the applications will be peer-reviewed, and only meritorious applications will be considered. Applications funded under RFA-HG-25-012 will work in collaboration.

Definitions. For the purposes of this NOFO, the following definitions are used:

To advance and accelerate research to ensure maximal scientific benefit is derived, the resulting data will be shared and align with the broad scientific community for research use through community resource databases such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL) or ClinVar.

Background and Objectives The eMERGE Network entered its fourth phase in July 2020 as the eMERGE Genomic Risk Assessment and Management Network (RFA-HG-19-013, RFA-HG-19-014, RFA-HG-19-015; Jul 2020-Apr 2026), encompasses 10 clinical sites and a coordinating center. The eMERGE Network's fourth phase goals are multifaceted:

The eMERGE Network validated PRSs for use across two or more ancestral populations and developed methods to combine PRS, monogenic risk, family health history, and clinical risk factors in novel ways to estimate a patient’s risk of 10 common diseases. The 10 clinical sites recruited patients from various communities along with their clinicians. Clinical and genomic data were combined with family history information gathered from patients to generate standardized risk determinations and individualized care recommendations. The resulting GIRA were returned to patients and their clinicians. Outcome measures were established to assess whether the GIRA influences downstream healthcare utilization, behavior changes, and understanding of disease risk.

By late 2024, the eMERGE Network had recruited and returned a GIRA result to roughly 25,000 patients. As of June 2024, observed proportions of patients at high risk for 8 of the 10 conditions have met or exceeded expected proportions, slightly missing expectations for hypercholesterolemia and asthma. Critical study hypotheses to be tested across all 10 conditions combined include: 1) the proportion of clinicians recommending risk-reducing interventions will be higher in high risk than non-high risk patients; and 2) the proportion of patients undertaking interventions will be higher in high risk than non-high risk patients.

Initial data from multiple sites indicate a statistically significant uptake of risk reducing interventions for several conditions including breast cancer, prostate cancer, and diabetes. Continued patient follow-up beyond 12 months of eMERGE patients is being pursued because screening recommendations for some of the 10 eMERGE conditions involve repeated surveillance in at least some subgroups every 12 months. Other conditions involve longer follow-up intervals in some or all patients. Uptake and sustainability of interventions may differ in those receiving high-risk GIRA results compared to those at lower risk levels or among those differing in demographics (including age), access to healthcare, or social determinants of health.

The objective of the extended follow-up provided by the Outcomes of Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network is to determine whether appropriate uptake and sustainability of interventions persist beyond the initial return of the GIRA. Through multidisciplinary research and scholarship, the eMERGE Network will: 1) extend follow-up of eMERGE patients from a minimum 1 year to a minimum of 4 years; 2) assess longer-term adherence to and outcomes of GIRA-based preventative recommendations among clinicians and patients; and 3) identify correlates of adherence by condition, patient age and other non-genetic factors.

Research Approach This NOFO supports the longer-term assessment of outcomes by extending the follow-up of eMERGE patients for a minimum of 1 year to a minimum of 4 years. The resulting data are expected to improve methods and workflows for assessing genomically informed risk and to identify more effective ways to present these results in a user-friendly manner that minimizes the burden on busy clinicians while maximizing patient understanding and uptake of recommendations by patients and clinicians. Outcome data are expected to identify characteristics of patients, clinicians, and systems associated with uptake, as well as the potential health outcomes, ethical concerns, social issues, and policy implications of integrating this information into patients’ medical care.

In addition, the recipient organization may, but is not required to, propose strategies for gathering community input regarding implementation activities to retain participants and understand how the outcomes may impact the communities that are recruited into the eMERGE research study. Strategies may include, but are not limited to, involvement of a community advisory board, implementation of focus groups, solicitation of feedback on specific deliverables, inclusion of community members in interpretation of research findings, or raising awareness about research findings within their communities.

Research topics NHGRI intends to continue supporting the single, Network-wide, combined risk assessment and management protocol that has been implemented across the various populations represented in the 25,000 patients recruited in the current phase of eMERGE (RFA-HG-19-013, RFA-HG-19-014, RFA-HG-19-015).

Examples of topics that could be assessed in analyzing the eMERGE Network outcomes include, but are not limited to, the following:

Applicants are not limited to addressing this list of outcomes or topics and are strongly encouraged to contact NHGRI program contacts (listed below) to discuss their proposed topic(s) to ensure pertinence to the objectives of this NOFO.

Organization Clinical Sites (CSs) CSs are responsible for conducting the research (patient retention and implementation of all study procedures) and disseminating research findings in collaboration with the CC and NHGRI. In conjunction with the CC and NHGRI, CSs will be responsible for assessing uptake of risk reduction recommendations and other process and health outcomes, and analyzing and interpreting research results. Each CS will participate in a cooperative and interactive manner with all other CSs and the CC in all aspects of the eMERGE Network, including developing Network procedures and working groups, performing quality assessments of data, and assessing clinical uptake and outcomes. As noted above, continued patient involvement is a key aspect of this project. The CSs will work collaboratively with each other and the CC to establish a plan for patient engagement and retention across the eMERGE Network, including patients who are typically more challenging to keep engaged in biomedical research. CSs will also work with the CC to track and obtain follow-up information from patients who are no longer receiving care at one of the funded CSs. The CSs will also work collaboratively with each other and the CC for timely and efficient transmission, in as automated a fashion as possible, of data needed for the CC to continue to monitor retention, data quality, and study outcomes across the entire eMERGE Network.

Coordinating Center (CC) The CC will play a major research role in preparation and distribution of Network-wide datasets for distributed analysis, joint analyses of Network-wide data including analysis of clinical and cost-effectiveness outcomes and subgroup effects, and coordination of protocol updates and implementation among the sites. The CC will ensure that robust and efficient informatics tools are established at the CSs and CC to continue to collect, store, transmit, and analyze the data as required by the current GIRA protocol. The CC will design and implement a detailed quality assessment and control plan to ensure a high-quality data set is captured and shared among the sites. The CC will also be responsible for ensuring data generated by the eMERGE Network are deposited into a publicly accessible data repository such as AnVIL and ClinVar.

The CC will also perform traditional coordination and support activities and will promote standardization of terminologies and methodologies to be used. Maintaining patient involvement throughout the study is key to the success of this project. The CC will be responsible for working with the CSs to establish and implement a plan for continued patient involvement Network-wide, including efforts to retain patients who are typically more challenging to keep engaged in biomedical research. The CC will also work with the CSs to track and obtain follow-up information from patients who are no longer receiving care at one of the funded CSs.

NHGRI

NHGRI is responsible for organizing and providing overall support and management for eMERGE through the NHGRI Program Office and Grants Management Branch. In addition to regular grant stewardship, the NHGRI Project Scientist(s) will be involved substantially with the award recipients, consistent with the Cooperative Agreement mechanism.

Steering Committee (SC) A SC comprising Program Director(s)/Principal Investigator(s) [PD(s)/PI(s)] of the CSs and the CC, and the NHGRI Project Scientist(s), will constitute the main governing body of eMERGE. Major scientific decisions will be determined by majority vote of the SC, with each recipient and NHGRI having one vote that will be done via email or at a Steering Committee meeting. It is anticipated that the SC will meet at least twice per month by conference call. The SC will have primary responsibility for the general organization of eMERGE, conducting and monitoring the combined protocol, reporting results in a timely manner, and disseminating the findings.

Program Formation and Governance Awards made under this NOFO and the companion NOFOs will be cooperative agreements (see Section VI.2., Cooperative Agreement Terms and Conditions of Award). Close interaction among award recipients and the NIH will be required to develop appropriate strategies and tools to carry out this program.

Soon after funding, the eMERGE SC will meet to set Network-wide goals for the four-year project period. The SC is expected to establish working groups to facilitate collaborative work and standardize approaches. PDs/PIs may propose new research collaborations with investigators and organizations outside the eMERGE Network, as long as proposed activities are conducted in accordance with the Network policies and practices. Proposed collaborators will be eligible to attend SC meetings, along with pre- and post-doctoral trainees.

External Input to the eMERGE Network eMERGE will have an External Scientific Panel (ESP). The ESP will provide input on performance and overall progress of eMERGE. The ESP will consist of experts in genomic risk assessment and management, genomic medicine, bioethics, biostatistics, informatics and clinical coordination. An NHGRI scientist will serve as the Executive Secretary to the ESP. The ESP will meet semi-annually (one conference call and one in-person meeting per year) in conjunction with Steering Committee meetings, as appropriate. Following each meeting, the ESP will provide recommendations and a report for PD(s)/PI(s). The eMERGE SC members will receive and consider the ESP’s comments and will provide a written response to the recommendations. Applicants should not propose names of potential advisors in their applications; they will be selected after award.

Clinical Trial Registration The Outcomes of the eMERGE Genomic Risk Assessment and Management Network applications will be submitted as a clinical trial as described in NOT-OD-15-015, Notice of Revised NIH Definition of Clinical Trial. It is expected that the eMERGE Network will be registered in, and results information submitted to, ClinicalTrials.gov by the CC for the eMERGE Network as a whole as described in NOT-OD-16-149, NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.

After the initial review, NHGRI program staff will conduct an additional administrative review of the Data Management and Sharing Plan (DMS Plan) and may negotiate modifications of the DMS Plan with the prospective award recipients. The final negotiated version of the DMS Plan will become a term and condition of the award of the cooperative agreement.

Other Research Opportunities This effort is focused on capturing and analyzing data from the 25,000 patients recruited in the fourth phase of eMERGE (RFA-HG-19-013, RFA-HG-19-014, RFA_HG-19-015). Applicants are encouraged to submit applications to other funding announcements that align with the proposed aims and could be used to augment the ongoing efforts. Applicants could apply to a range of funding announcements including but not limited to Advancing Genomic Medicine Research and Ethical, Legal and Social Implications (ELSI) Research (PAR-23-293, PAR-23-294, PAR-23-295).

Data Management and Sharing Recipients must comply with the NIH Data Management and Sharing Policy (NOT-OD-21-013) and NIH Genomic Data Sharing Policy (NOT-OD-14-124). NIH recognizes Tribal sovereignty and the rights associated with Tribal sovereignty around data collection, data management and sharing of data and has published a supplemental Notice regarding the DMS Plan for AI/AN populations, NOT-OD-22-214. NHGRI supports the broadest appropriate data sharing with timely data release through widely accessible data repositories. 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, which are summarized at genome.gov/data-sharing.

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

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

Renewal

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NHGRI intends to commit $5,800,000 per year in FY 2026 to FY 2029 to fund ten awards.

Award Budget

Application budgets are limited to no more than $330,000 direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is up to four years.

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

Eligible Organizations

This is a limited competition NOFO. Only organizations funded under RFA-HG-19-013 and RFA-HG-19-014 are eligible to apply.

Foreign Organizations/International Collaborations

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.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

Only the PI/PDs associated with the eligible applicant organizations funded under RFA-HG-19-013 and RFA-HG-19-014 are eligible to apply.

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Instructions for Application Submission

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

SF424(R&R) Senior/Key Person Profile

R&R or Modular Budget

CS budgets should include the costs required for active Network participation, including regular teleconferences and meetings of the SC and its working groups. For budgeting purposes, applicants should budget for attendance of 4-5 investigators from each CS at three SC meetings (2 days, 1-2 nights) throughout the project period.

For budgeting purposes, each CS should assume it will be retaining, or working to retain, all the patients recruited in the current phase of their award. CS budgets should include formulating and providing longer-term (up to 4 years) risk management recommendations to high-risk patients and their clinicians. Budgets should also include extracting, cleaning, and harmonizing the data to the Network agreed-upon data model including electronically transferring the data to the CC for Network-wide analysis.

Network-wide data storage and computation costs will be borne by the CC. CS budgets should not include costs for local storage of eMERGE data. Both CSs and CC are expected to conduct both site-specific and large-scale collaborative analyses on the AnVIL platform. CSs will need to budget for compute and egress charges on AnVIL based on Google Cloud Platform pricing. NHGRI will continually assess the utilization of AnVIL and determine whether limited support for site-specific analyses on platforms external to AnVIL is needed.

Budgets should include any funds required to support sharing of scientific data under this NOFO. NIH provides guidance on allowable costs for data management and sharing here. For projects generating genomic data derived from research participants, investigators should consider costs associated with complying with the NIH and NHGRI GDS Policy expectations (e.g., obtaining samples with explicit informed consent for future research use and broad data sharing, implementing processes to seek new consent from study participants, etc.).

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Introduction to Application The Outcomes of Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management study aims to capture and analyze outcome data from roughly 25,000 patients enrolled in the current phase of eMERGE (RFA-HG-19-013, RFA-HG-19-014, RFA-HG-19-015). During Years 1–3, efforts will concentrate on data capture, harmonization, and interim analysis, with Year 4 dedicated to comprehensive study analysis and dissemination of results.

Specific Aims Each Clinical Site (CS) will aim to:

Research Strategy Applicants should detail their plans for the collection, harmonization, and analysis of demographic, clinical, genomic, psychosocial, and healthcare utilization data captured from the 25,000 patients recruited in the current phase of eMERGE (RFA-HG-19-013, RFA-HG-19-014, RFA-HG-19-015) for outcome analysis. This plan should include their strategies for ensuring high data quality and collaborating with the CC on design and implementation of quality assessment and control protocols. They should also include the necessary expertise to be able to capture and harmonize this data. They should also describe their plans for determining whether refinement or revision of current eMERGE GIRA risk stratification is needed and how this will be implemented.

Applicants should describe their approach to patient and clinician follow-up, detailing strategies for recontact and retention, surveys to be conducted, outcomes to be assessed, and milestones to ensure timely follow-up and data submission throughout the follow-up period. Outcome data should aim to characterize patient, clinician, and system factors associated with uptake, and assess the potential benefits and risks of receiving GIRA results. Applicants should also describe key questions they propose to address during this phase. Furthermore, applicants should propose ideas for Network-wide analyses, including potential subgroup analyses and a clear description of the population descriptors they will use for their analyses. Results from this phase could also serve as foundational data for future clinical trials evaluating the clinical utility of GIRA-informed approaches; this should be considered in analysis plans.

Additionally, applicants should describe their plans for monitoring and updating monogenic testing conducted in the current phase of eMERGE, noting that advancements in PRS may prompt the SC to consider refinements to eMERGE GIRAs. For minors recruited in the current phase who will reach the age of majority, applicants should describe their plans for consent and potential involvement of these patients’ parents or guardians (if any) moving forward.

Applicants should describe the informatics expertise and approaches they will employ to maintain version control of GIRA results, support clinical decision tools, and share EMR data with the CC for deposition in data resources such as AnVIL.

Applicants must describe their approach to capturing longitudinal data to measure outcomes, including data collected both within and outside their health system. This should, at a minimum, include details on clinician orders prompted by the GIRA, clinical actions performed on patients, relevant actions taken by patients, and relevant historical data associated with the GIRA.

Applicants should also outline mechanisms for the rapid, timely, and secure extraction and transfer of study data to the CC and/or other designated data repositories.

Multiple PD/PI Leadership Plan and Consortium/Contractual Arrangements Applicants should detail the experience and expertise of the PD(s)/PI(s) and senior/key personnel in capturing and analyzing prospective cohort data. They should highlight prior work within multi-site research networks, emphasizing contributions toward individual study and collaborative goals. They should also describe the CS’s established research program in relevant scientific areas, including expertise in clinical medicine, biostatistics, bioethics, healthcare utilization and policy, programming and data management, quality assurance and data integrity, project management, regulatory knowledge, and outcomes research. Multidisciplinary teams to help address the research questions proposed by the eMERGE Network are encouraged.

Letters of Support The application should include letters of support from institutional and departmental leadership, demonstrating commitment to the Network and agreement to participate under a single IRB for multi-site research. Letters should affirm institutional and departmental commitment to capturing, harmonizing, and sharing patient data, including EMR and questionnaire data. Applicants are encouraged to showcase institutional support, such as protected time, research leadership roles, facilities, and resources dedicated to the CS. Additionally, letters of support should be included for CS(s) involved in capturing outcome data that are outside their existing health system.

Estimated Timeline Years 1–3 will focus on planning for follow-up research opportunities or collaborations, data capture, harmonization, and interim analysis, with Year 4 dedicated to comprehensive analysis and results dissemination. Throughout all four years, award recipients are expected to participate actively in Network-wide data monitoring and analysis. Year 4 will also involve data analysis, publication, and dissemination of findings and methods.

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:

The Resource Sharing Plan should summarize whether and how resources (e.g., educational materials; methods; models; physical products, materials, and reagents; protocols; research findings and products; and software) will be made available. Applicants should include a description of the format, an indication of who will be responsible for implementation and plans for long-term maintenance, whether there will be opportunities for community input and feedback, platform(s) or mechanism(s) that will be used to make resources publicly accessible, and proposed timeline for implementing the Resource Sharing Plan. Resource Sharing Plans should not duplicate other sections of the main Research Plan but should refer to them when appropriate. After initial review, NHGRI program staff may negotiate revisions of this plan with the prospective awardee. The final negotiated version of this plan will become a term and condition of the award.

For more guidance on writing a Resource Sharing Plan, see https://genome.gov/resource-sharing.

In addition to the above expectations, NHGRI expects that plans for sharing software generated under this funding opportunity will meet the following expectations:

Other Plan(s):

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

To assist in improving data sustainability and utility, applicants are encouraged to align the development of their data sets using the Findable, Accessible, Interoperable, Reproducible (FAIR) Guiding Principles (https://www.nature.com/articles/sdata201618). 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.

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 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. Although NHGRI expects project datasets and human variant information from studies selected through this NOFO to be made available through AnVIL and ClinVar, data can be shared in additional appropriate resources to enhance dissemination.

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).

Participants must be consented for broad data sharing in consultation with the involved communities. For additional guidance on informed consent, see the NHGRI Informed Consent Resource. In addition, it is expected that individual-level genomic data generated for the program will be designated in institutional certification documents as General Research Use (GRU) as described at https://osp.od.nih.gov/scientific-sharing/researchers-institutional-certifications/ when submitting datasets to NIH-supported databases.

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.

Data security encompasses confidentiality, data integrity, and availability. Confidentiality includes managing data access to maintain data security and making data accessible to authorized users only for authorized purposes. Data security protection and proper stewardship of human genomic, phenotypic, clinical, and other sensitive information stored and distributed is of the utmost importance. The Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the Data Management and Sharing Policy (DMSP) (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html) as well as the NIH Genomic Data Sharing (GDS) Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-086.html) allows investigators to perform genomic analyses on a cloud platform. The NIH security best practices and provisions (https://www.ncbi.nlm.nih.gov/projects/gap/pdf/dbgap_2b_security_procedures.pdf) should be implemented to protect the privacy and confidentiality of research participants and prevent unauthorized access to data. Investigators are expected to develop policies and procedures for notifying NHGRI, and managing, and mediating any loss of data or compromise of data confidentiality.

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.

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

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

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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

Applic…