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.

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

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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO), RFA HG-23-041, invites applications for Clinical Sites (CS) to participate in a Genomic-Enabled learning health system (gLHS) Network. The Network will consist of a Coordinating Center (CC, RFA-HG-23-042) and 4-6 CS working collaboratively with NHGRI to identify and improve approaches for clinical integration of genomic information in a virtuous learning health system cycle of implementation, evaluation, refinement, and re-implementation. The Network will share genomic medicine implementation strategies and identify those most suitable for cross-network implementation; use these strategies to conduct 2-4 intervention projects network-wide and evaluate their impact; and develop and refine successful gLHS implementation strategies as resources that can be broadly shared and adopted, including in resource-limited settings.

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

• Genomic medicine intervention refers to evidence-based, genomic-informed clinical care projects with strong justification for implementation because the approach has been shown to improve outcomes. These could include intervention projects such as electronic health record (EHR)-identification of monogenic disorders, predisposition to hereditary diseases, pharmacogenetic testing, genome sequencing in critically ill infants, etc.
• Genomic medicine implementation strategy refers to how the intervention will be implemented and scaled to multiple health care environments. These could include educational modules, EHR-provided clinical decision support, checklists, formulary or order set changes, etc.
• Implementation science is defined by the National Cancer Institute as the study of methods to promote the adoption and integration of evidence-based practices, interventions, and policies into routine health care and public health settings to improve the impact on population health.
• Implementation science framework refers to strategic or action-planning models that provide a systematic way to develop, manage, and evaluate interventions and make the spread of evidence-based interventions more likely (PMID: 22898128).
• Learning health system as defined by the National Academy of Medicine is one in which an infrastructure supports complete learning cycles that encompass both the analysis of data to produce results and the use of those results to develop changes in clinical practices in a system that will allow for optimal learning.
  • Genomic-enabled learning health system refers to learning health systems currently integrating structured genomic test results into their LHS infrastructure and processes.
  • Genomic-capable learning health system refers to learning health systems able to integrate structured genomic test results into their LHS infrastructure and processes, but not yet having done so.
  • Potential genomic learning health system refers to health systems currently integrating and utilizing structured genomic data in their electronic health record (EHR) but not having completed the full cycle of implementation-evaluation-refinement-re-implementation characterizing true LHS.
• LHS implementation strategies refer to processes and infrastructure needed to support effective LHS learning cycles, such as community and stakeholder engagement, patient and provider education, clinical results reporting, implementation science methods, change management, and a robust data infrastructure that supports EHR integration of structured genomic test results and enables bidirectional analysis and feedback for research and quality improvement.
• Quality improvement is defined by the Centers for Medicare and Medicaid Services as the framework used to systematically improve care. Quality improvement seeks to standardize processes and structure to reduce variation, achieve predictable results, and improve outcomes for patients, healthcare systems, and organizations.
• Structured genomic data refers to machine-readable and computable genomic data from an individual patient, such as genomic test results or variants from genomic sequencing, rather than PDFs or clinical notes reporting genomic results.
• Underserved communities or medically underserved areas/populations are defined by the Health Resources and Services Administration (HRSA) as geographic areas and populations with a lack of access to primary care services.
• "Virtuous learning health system cycle" is an iterative process of implementation, evaluation, refinement, and re-implementation in which healthcare stakeholders deliver evidence-based interventions and learn how to improve from the care delivered.

Background and Objectives

A learning health system (LHS), also called a rapid-learning health system, is one in which an infrastructure supports complete learning cycles that encompass both the analysis of data to produce results and the use of those results to develop changes in clinical practices in a system that will allow for optimal learning (NAM 2015). In an effective LHS, generalizable knowledge can potentially be captured from every patient encounter, used to generate evidence of impact on outcomes, and delivered to clinicians to modify their practice. The LHS concept has gained significant momentum in health systems in recent years due in part to advances in electronic health records (EHRs) and information technology, as well as increased emphasis on rapid translation of new knowledge to improve care. Data are collected on adopted strategies and analyzed to assess impact and identify areas for improvement, and those insights are then used to inform and optimize clinical practice in a virtuous cycle of continuous quality improvement.

Genomic information can be integrated at any step in this process to produce genomic-enabled learning health systems (gLHS). gLHS can facilitate rapid incorporation and evaluation of genomic-informed care, particularly if multiple gLHS collaborate to increase the adoption of evidence-based genomic interventions and assess their impact on delivery of care. Genomic-enabled LHS have begun to adopt the full cycle of implementation, evaluation, refinement, and re-implementation of genomic medicine in true gLHS fashion. Other systems may be considered gLHS-capable, with LHS infrastructure in place and utilized for non-genomic care delivery, but structured genomic data not yet incorporated. Still others may be considered potential LHS, with multiple components of LHS infrastructure in place (such as a system-wide EHR, implementable clinical decision support, computable outcomes) and having incorporated structured genomic data and implemented some genomic medicine interventions, but not having fully adopted other steps of the gLHS virtuous cycle such as evaluation, refinement, and re-implementation.

Leveraging individual health systems data and best practices in collaborative efforts to identify and implement effective genomic interventions requires adoption of common data standards and systems. Fostering interoperability of integrated genomic data across health systems to facilitate genomic medicine implementation was a key recommendation of the 2015 National Academies Genomic-Enabled Learning Health Care Roundtable report. Significant strides in improving genomic data exchange and interoperability have since been made through adoption of standards such as those developed by the Global Alliance for Genomics and Health (GA4GH). Expansion of such efforts through wider adoption of standardized genomic data elements, access procedures, and consent provisions provides an opportunity to expand upon and enable integration of genomic data into health information exchanges (HIE) that share individual-level EHR information among providers, across clinical facilities, and with patients to coordinate and improve clinical care. Expansion to under-resourced settings is also needed to address current barriers to accessing genomic testing and expert consultation and increase the availability of such approaches to all.

The potential for gLHS to move genomic discoveries rapidly into clinical care through systemic implementation was highlighted in the NHGRI 2020 Strategic Vision, particularly the possibility of extending gLHS studies across multiple health systems to reveal common challenges and solutions. To explore successful implementation models and possibilities for collaboration among them, NHGRI convened Genomic Medicine XIV Genomic Learning Healthcare Systems in August 2022. Establishing a network to promote sharing and collaboration across gLHS was a key recommendation of that meeting.

The Network will consist of a CC (RFA-HG-23-042) and 4-6 CS working in collaboration with NHGRI to identify and improve approaches for clinical integration of genomic information in a learning health system virtuous cycle of implementation, evaluation, refinement, and re-implementation. The Network will share genomic medicine intervention projects and implementation strategies most suitable for cross-network implementation; use these strategies to conduct 2-4 intervention projects network-wide and evaluate their impact; and develop and refine successful gLHS implementation strategies as resources that can be broadly shared and adopted, including in resource-limited settings.

This NOFO, together with RFA-HG-23-042, will support a Network to identify and improve approaches for clinical integration of genomic medicine interventions in a virtuous learning health system cycle of implementation, assessment, refinement, and re-implementation. The primary objectives of the Network are to:

1. Share Network members current LHS implementation strategies, identify additional effective practices from other available sources outside the Network, and agree on those most suitable for cross-network application. Similarly, the Network will identify evidence-based genomic medicine interventions and select 2-4 interventions feasible for implementation Network-wide within the practical constraints of this NOFO.
2. Use agreed-upon genomic medicine implementation strategies to conduct 2-4 selected intervention projects network-wide and evaluate their impact. Feasible intervention projects are most likely to be those amenable to efficient system-wide modifications such as EHR prompts or order set changes, conducted as Quality Improvement (QI) projects. QI projects often do not require Institutional Review Board approval (though this is an institutional decision), individual patient recruitment or data collection, or informed consent.
3. Develop and refine successful gLHS implementation strategies to produce gLHS tools and resources that can be broadly shared and adopted, including in resource-limited settings.

Each CS (this NOFO) will be primarily responsible for:

1. Identifying, describing, and sharing with other Network members its LHS strategies that are most likely to be implementable across multiple healthcare systems.
2. Documenting its LHS strategies using state-of-the-art standards, where available, and other methods to maximize their interoperability and transportability to other Network members and other healthcare systems as tools or resources.
3. Identifying and proposing pilot genomic medicine intervention projects with evidence that they improve outcomes and warrant broader implementation.
4. Identifying and including as active partner(s) champions from underserved healthcare settings to contribute their unique expertise and perspectives on such settings, thereby broadening the applicability of Network products and potentially increasing the likelihood they will be widely adopted.
5. Working with NHGRI and other Network members to:
a. agree upon, implement within their own LHS, and evaluate evidence-based genomic medicine intervention projects feasible for Network-wide implementation within the time and budget constraints of this NOFO.
b. assess the efficiency and impact of implementation, refine and re-implement the intervention as applicable, and use lessons learned to improve resulting tools and resources for wider dissemination.
c. improve integration of genomic information into EHRs and enhance interoperability across systems.
d. engage professional societies in considering successful intervention projects and implementation strategies for incorporation into professional practice guidelines.

The CC (RFA HG-23-042) will be primarily responsible for:

1. Collecting, compiling, organizing, and harmonizing (where possible) the shared LHS strategies of the Network CS.
2. Compiling, improving, actively publicizing, promoting use of, and widely sharing tools and resources for gLHS implementation, selected genomic medicine interventions, and other genomic medicine resources as relevant to and with the broader research community, including a website with a user-friendly, easy-to-navigate portal.
3. Coordinating and contributing to Network-wide protocol development, data analysis, and tool and resource development.
4. Assessing and ensuring quality of data collected and resources produced.
5. Managing and securing Network data.
6. Coordinating Network logistics for activities such protocol development and selection, tool and resource dissemination, informational conferences and exchanges with the scientific community, and site implementation through in-person meetings, conference calls, working groups, etc.
7. Coordinating and facilitating outreach and dissemination of resulting tools and resources.

Research Approach

Key goals of the Network will be compiling and disseminating the best available gLHS implementation strategies, evaluating the effectiveness of many of these strategies through pilot intervention projects, improving integration of genomic information into EHRs and its transportability to other systems, enhancing interoperability across systems, and ensuring the applicability of its tools and resources in underserved settings.

CS applicants will be expected to have experience using LHS approaches in their health system, including in underserved communities and settings. They should have experience integrating (or capability to integrate) genomic information into their EHRs and evidence of their ability to extend their genomic medicine approaches to underserved settings and genetically diverse populations. CS applicants will also be expected to have expertise in community and stakeholder engagement, implementation science, change management, and health services research. They should also have demonstrated readiness for change, capacity for their EHR to interact with other systems to enhance interoperability, ability to implement intervention projects in a gLHS model, readiness to work with peers in a network setting, and willingness to adopt agreed-upon gLHS approaches proposed by other CS.

Each CS funded under this NOFO, and the CC as relevant, will review its existing and planned LHS strategies to identify those most suitable for broad implementation across a range of healthcare systems and settings. These should be meticulously documented to permit facile transfer to other users and should employ state-of-the-art standards and other approaches to maximize interoperability and transportability to other Network members and other healthcare systems as gLHS tools or resources. Tools might include algorithms for phenotype classification, genotype report generation, process flow diagrams, etc.; resources might include educational materials, practice guidelines, implementation algorithms, etc.

At the initiation of the program, CS should submit a broad suite of strategies, tools, and resources to the CC for Network consideration. A subset of these will then be selected, using criteria to be established by the Network, for Network-wide implementation. Each CS will implement within their systems the strategies agreed upon Network-wide for adoption, in preparation for carrying out Network-wide intervention projects as described below. Recognizing the rapid evolution of artificial intelligence, machine learning, and implementation science expected during the course of this program, tools and strategies will need to be flexible to incorporate significant innovations. Network members will collaborate in developing and applying processes to identify advances and determine which may merit changes in Network protocols.

Submitted tools and resources, whether selected for Network implementation or not, will be made available to the scientific community at the end of the first program year through a platform and easy-to-navigate portal developed by the CC and other means as desired. Tools and resources that have been selected for Network-wide implementation, evaluation, and refinement will be clearly identified on the dissemination platform. Once developmental phases and evaluation are completed for the selected Network-wide tools and resources, their revised versions will also be widely disseminated. Refined tools and resources should be designed to maximize interoperability and transferability of genomic information across health systems.

Each CS (and the CC if it chooses) will also identify and propose genomic medicine intervention projects with best evidence, as reviewed by the Network, that will improve outcomes. Improved interoperability and communication of genomic findings between clinicians and laboratories will be another goal for the intervention projects, ideally through electronic exchange of structured data that can be readily integrated into EHRs and laboratory systems. Projects proposed for consideration must be feasible to carry out within the limited timeframe and budget of the program, allowing sufficient time for at least one (and preferably more than one) cycle of evaluation, refinement, and re-implementation if warranted. They should also promote equitable and affordable access to genomic medicine interventions, with ongoing monitoring of equity and potential biases in implementation and plans for remediation as needed. Genomic variants forming the basis of interventions should not be limited to or heavily concentrated in one genetic ancestry group but should be applicable to a broad representation of people in their communities. Projects should be designed to demonstrate and enhance the ability to exchange genomic results, recommendations, and workflows across CS. They should also enable a patient’s genomic information to follow them across multiple providers and health systems where appropriate.

The Network will select 2-4 projects that can be implemented in either a pilot mode, to assess feasibility and practicality, or in full-scale mode, to assess impact on outcomes of importance in healthcare delivery such as improvement in provider workflows, patient health outcomes, or reduction in costs. Whether projects will be conducted in pilot or full-scale mode will largely depend on whether full-scale objectives can be achieved within the time and cost constraints of this program. Projects will be selected to cover a range of potential genomic medicine topics, such as (but not limited to) EHR-identification of monogenic disorders, hereditary disease predisposition, pharmacogenomics, or sequencing in critical illness. Other criteria for project selection will be established by the Network but could include generalizability across systems including low-resource settings, community and public health importance of the health problem being addressed, and impact on health inequities.

Each CS and the CC will be responsible for including, as active partner(s) in its investigative team, champion(s) from underserved healthcare settings who will contribute their unique expertise and perspectives on such settings. This champion or champions may be drawn from the research or clinical workforce, the community, or other relevant stakeholders. Involving champions at the outset of and throughout the program will promote dialogue and sharing of perspectives on feasibility of proposed implementation strategies beyond early adopter systems. Such involvement is expected to broaden the applicability of Network products and potentially increase the likelihood they will be adopted across a wide range of settings and populations. The Network will be expected to include engagement with communities and other relevant stakeholders (patients, providers, EHR vendors, healthcare systems, payers, professional societies, etc.) to help prioritize tools and resources to be developed and to prioritize interventions addressing genomic health issues of importance to them.

Network members will work together to assess and ensure the quality of data collected and resources produced. They will also assess the efficiency and impact of each intervention and refine and re-implement the intervention as applicable. Evaluation metrics should include outcomes of value to communities and other relevant stakeholders, to be defined in discussions with those groups. Findings will be used to improve resulting gLHS tools and resources for wider dissemination and use by other health systems. Such resources could include facile approaches for integrating genomic results in the EHR, real-time monitoring of or dashboarding the status of implementation, and tracking the outcomes of interventions. Resources will be designed to help other providers adopt gLHS approaches and potentially facilitate their participation in gLHS-delivered genomic medicine.

The CC will manage all aspects of the Network’s logistics and coordination including working with NHGRI and the Network to schedule meetings and set agendas, secure a venue for in-person meetings (including A/V support), and facilitate virtual and hybrid meetings, make meeting materials and videos (when available) accessible to the Network and others as appropriate, and prepare and distribute minutes and action items for these meetings. The CC will also organize and support travel costs for the External Scientific Panel (ESP), including preparation and timely distribution of agendas and meeting materials.

The CC will be responsible for compiling, evaluating, actively publicizing, promoting use of, and widely sharing tools and resources for gLHS implementation, selected genomic medicine interventions, and other genomic medicine resources as relevant, to and with the broader research community. This will include tool and resource dissemination through multiple means, including informational conferences and exchanges with the scientific community. The CC will also coordinate implementation of the projects at the sites through in-person meetings, conference calls, working groups, etc. It will lead Network-wide efforts to assess and ensure the quality of data and resources produced. It will facilitate the submission to the AnVIL platform of tools and resources developed by the Network. The CS will work with NHGRI and the CC to define the process, timeline, and standards for these submissions, utilizing widely available protocols such as those validated within eMERGE (i.e. PheKB), the PhenX Toolkit, and the AnVIL data model, as appropriate. The CC will also coordinate with the AnVIL staff to catalog, manage, and control access to the data by Network members.

Program Formation and Governance

This NOFO uses the Cooperative Agreement mechanism. Successful applicants will become members of the Genomic-Enabled Learning Health Systems (gLHS) Network comprising investigators funded in response to one of the two related NOFOs (RFA-HG-23-041 and RFA-HG-23-042). Recipients are expected to work collaboratively with all members of the Network to meet Network goals, in addition to the research goals outlined in their individual applications. Close interaction among recipients and the NIH will be required to develop appropriate strategies and tools to carry out this program. A kickoff meeting for the Network will take place soon after awards are made to establish the Steering Committee and start the program’s activities.

NIH
NIH is responsible for organizing and providing overall support and management for the Network. In addition to regular grant stewardship, the NIH Project Scientist(s) will be involved substantially with the recipients, consistent with the Cooperative Agreement mechanism. The NIH Project Scientist(s) will, together, be a voting member of the SC and will have a single vote.

Steering Committee
A Steering Committee will be the main governing body of the Genomic-Enabled Learning Health Systems (gLHS) Network. The Steering Committee will be established to guide the overall scientific direction of the Network and will be composed of the PD/PI(s) from each of the funded CS, the CC, and NIH staff. Major scientific decisions will be determined by consensus, and as needed, by majority vote of the SC, where each funded entity and NIH will have a single vote. It is anticipated that the SC will meet at least twice per month by conference call and up to four times per year during the first year (two in-person and two virtual full-day meetings) as needed for protocol development. During years 2-5, the SC will meet at least monthly by conference call and up to three times per year, two in-person and one virtual full-day meeting. SC meetings are intended to be inclusive and all key collaborators and pre- and postdoctoral trainees, including those from underrepresented groups or those from different but related disciplines, should be encouraged to attend. Working groups will be established to facilitate collaborative work and standardize approaches. All components of the Network will be expected to play an active role in these working groups, which may include (but are not limited to) groups focused on specific cross-Network activities such as clinical informatics and EHR integration, community and health systems stakeholder engagement, and quality assurance and control. Recipients will be expected to accept and implement policies approved by the SC as described in Terms and Conditions of Award.

External Input to the Network
The Genomic-Enabled Learning Health Systems (gLHS) Network will have an External Scientific Panel (ESP). The ESP will provide input on performance, priorities, and overall progress. The ESP will consist of experts in a broad range of subjects, including change management, clinical informatics, community and stakeholder engagement, data science, epidemiology, health services research, implementation science, and other areas as needed. An NHGRI Project 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 submit recommendations for a report for PD(s)/PI(s). The Network SC members will receive and consider the ESP’s comments and will provide a written response to the recommendations. External experts may also be invited as appropriate to participate on an intermittent or regular basis in Network working groups such as community and stakeholder engagement.

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. 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.

Timeline

The first year will be devoted to sharing of implementation projects and implementation strategies, tools, and resources; selection of strategies to be adopted Network-wide for use in intervention projects; harmonization of strategies as needed for maximum interoperability across CS; selection of intervention projects to be implemented Network-wide; and protocol development for these projects. Submitted tools and resources, whether selected for Network implementation or not, should be disseminated to the wider scientific community at the end of year 1. Years 2-4 will involve applying agreed-upon interventions, evaluating their effectiveness, monitoring their equity and potential biases, and refining and re-implementing them as appropriate. At least one, and preferably more than one, complete cycle of implement-evaluate-refine-reimplement must be feasible to complete within the three-year intervention period after protocol development.

Technical Assistance Webinar

NHGRI will conduct a webinar for potential applicants on September 6, 2023 from 12pm to 1pm ET. Information about the webinar will be posted at: https://www.genome.gov/event-calendar/gLHS-NOFO-Webinar. The webinar connections will open 15 minutes in advance of the start time. During the webinar, program and grants management staff will give an overview of the FOA and application submission process and field questions from potential applicants. Please send questions in advance to Robb Rowley at [email protected].

Frequently Asked Questions

Questions and answers from the webinar and other frequently asked questions can be found here: https://www.genome.gov/event-calendar/gLHS-NOFO-Webinar/FAQ.

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

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

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 Institutions)

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

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov 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.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Robb Rowley
Telephone: 301-827-9126
Fax: 301-480-5159
Email: [email protected]

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

Effective management of this center requires a significant commitment by the Program Director(s)/Principal Investigator(s). For an application proposing a single PD/PI, the PD/PI is expected to devote at least 2.4 person months annually to the project. If multi-PDs/PIs are proposed, the aggregate level of effort required is a minimum of 2.4 person months. In the MPI model, PDs/PIs should devote sufficient time to serve his/her proposed role while maintaining the aggregate minimum required level of effort.

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 up to four SC meetings per year during year 1; 2 in person (2 days, 1-2 nights) and 2 virtual. In years 2-5, applicants should budget for up to 3 SC meetings per year, 1 in person and 2 virtual. CS budgets should include personnel costs for twice monthly SC conference calls in the first year, and monthly conference calls in years 2-5.

All Network components are expected to conduct both site-specific and large-scale collaborative analyses and should budget accordingly. Collaborative analyses are expected to be performed on the AnVIL platform. Applicants should budget for costs associated with cloud-based analysis approaches as well as costs related to ensure the data are standardized and harmonized according to the agreed-upon data model. All Network components will need to budget for data storage, compute, and egress charges on AnVIL and can be estimated based on this guidance. NHGRI will continually assess the Network’s utilization of AnVIL.

For budgeting purposes, each CS should assume it will be conducting 3 Network-wide intervention projects. CS budgets should include community engagement and clinical informatics costs as well as any patient-related clinical research costs (clinical costs that are not covered as part of a patient’s existing insurance coverage) such as additional tests, sample and data collection, supplies, etc. recommended by the study protocol.

Budgets should include any funds required to support sharing of scientific data under this NOFO, as per guidance on allowable costs for data management and sharing on its Budgeting for Data Management & Sharing webpage. 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

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Applicants should describe their existing LHS infrastructure, including user-friendly data systems and informatics that support linkage of EHR and structured genomic data in standard formats, permitting interoperability and data sharing within and outside the specific LHS. They should clarify their current stage of gLHS implementation, whether fully genomic-enabled, genomic-capable, or potential, as described above in Definitions. Data systems should permit visualization of findings in user-friendly ways that can be communicated at the point of care to providers and patients with limited knowledge of genomics. Systems should be capable of systematically and continually gathering and applying evidence in real time to guide care, enabling platform-supported, rapid learning cycles and allowing bidirectional analysis and feedback. Accessibility of LHS data within and outside the CS’s investigative group for research should be clearly described, as should average turnaround time for implementation of new clinical processes, practice guidelines or clinical decision support.

Applicants should describe their current LHS implementation strategies and give examples of their current or planned use in a full cycle of implementation-evaluation-refinement-re-implementation to improve clinical care. They should describe tools and resources they are prepared to share with the Network for consideration for refinement and Network-wide implementation, as well as their willingness to adopt agreed-upon tools and resources from other Network members for agreed-upon Network-wide intervention projects. They should provide examples of well-documented tools and resources permitting facile transfer to other users, as well as their willingness to share tools, resources, and documentation for dissemination to the scientific community through a Network website and other means.

Each applicant should propose 2-4 genomic medicine intervention projects for consideration for Network-wide implementation, including available evidence that they improve outcomes and are feasible to carry out within the limited timeframe and budget of the program. Proposed projects should cover a range of potential genomic medicine topics, such as (but not limited to) EHR-identification of monogenic disorders, hereditary disease predisposition, pharmacogenomics, or sequencing in critical illness. No more than half the proposed projects should be in any one area (that is, applicants proposing 4 projects should have no more than 2 in one area; those proposing 2-3 should propose each in a different area. Applicants should describe the current status of implementation in a selected area and document the need for further implementation research in that area. They should propose criteria for selection of intervention projects and an implementation science framework or frameworks for evaluation of the interventions and document their willingness to accept and apply criteria and framework(s) agreed upon by the Network. Evaluation of implementation strategies may address one or more implementation science issues such as informing initial adoption vs. sustainment of the interventions; implementing a full set of interventions across a system of care, de-implementing low-value practices, etc.

Applicants should describe how they will promote equitable and affordable access to genomic medicine interventions in underserved and resource-limited settings, and describe the expertise, experience, and roles of the champion(s) from underserved healthcare settings they will include in their investigative team. They should describe their plans for engagement with communities and other relevant stakeholders, including patients, providers, healthcare systems, payers, etc.

Applicants should propose evaluation metrics for intervention projects and outcomes of value to their various stakeholder communities. If a site-specific advisory group or groups are envisioned, their proposed roles and expertise should be described but potential members should not be named in the application. Applicants should provide evidence of strong support from institutional leadership including but not limited to their chief information officer for LHS implementation and document prior successful QI and change management strategies at their institution. They should also describe existing and planned genetic and genomic data, if any, available for querying and use in intervention projects in their patient population and their capabilities for obtaining CLIA-certified genomic testing or sequencing should those be needed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

NHGRI is committed to the timely release of open-source software and well-documented data analyses including models and tools developed from proposed studies. Applicants should describe in the Resource Sharing Plan a plan for open dissemination of methods, protocols, software, and tools to the community such that they are readily usable and extensible, where applicable. Applicants should also propose plans for sharing experimental protocols and methods. These should be made freely available to biomedical researchers and educators. For software produced by applications responding to this announcement, there is no prescribed license but any software license selected by applicants should allow for unrestricted redistribution and modification of software.

• Methods, protocols, tools, and software should be well-documented and where applicable made available via version-controlled public repositories.
• Solutions that enhance reproducibility when used by the community and ability of the community to integrate into automated pipelines should be emphasized.
• In the Resource Sharing Plan, a plan for sharing software should describe how improvements or tool customizations will be managed and disseminated to the scientific community. Applicants should take responsibility for creating the original and subsequent official versions of a piece of software.

For a list of frequently asked questions about Best Practices for Sharing Research Software, see https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq.
After initial review, NHGRI program staff will conduct an additional administrative review of the plan for resource sharing and may negotiate modifications of this plan with the prospective recipient. The final negotiated version of this plan will become a term and condition of the award.

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

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

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.

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 maximize synergy with ongoing efforts, the Network will adopt and adapt existing standards for data quality assurance and quality control, data sharing, genomic and phenotype harmonization, and other data standards as feasible, working with standards and data models from organizations such as the Global Alliance for Genomics and Health (GA4GH) and with phenotype standardization efforts such as the Human Phenotype Ontology (HPO) and Monarch. The Network will also utilize data collection protocols and consensus measures for phenotypes and exposures such as those recommended by the PhenX Toolkit. To assist in improving data sustainability and utility, applicants are encouraged to align the development of their data sets using the FAIR Guiding Principles. Policies and standards related to data sharing and data integration to be implemented in this Network will be shared with the broader community.

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. Data submitted to the AnVIL will be accessible by the scientific community upon review and approval of a data access request by the NHGRI Data Access Committee.

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 other appropriate and secure resources to enhance dissemination. 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. Investigators must abide by the NIH Security Best Practices and provisions 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 for managing and mediating any loss of data or compromise of data confidentiality.

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

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

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 SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

gLHS Study, Clinical Trial anticipated to start in second year of award.

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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 SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Any instructions provided here are in addition to the instructions 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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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

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

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.

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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Potential for broader application or generalization Programmatic balance among conditions to be studied, healthcare settings, and approaches to be implemented.
• Ability and commitment to investigative group to work effectively in large collaborative efforts or consortia

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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

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

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

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

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Determining research approaches, designing protocols, setting project milestones, and conducting research.
• Submitting well-documented implementation strategies, tools and resources to the CC for review and consideration by the Steering Committee.
• Proposing pilot genomic medicine intervention projects feasible to be implemented Network-wide.
• Participating in group activities, including a study-wide Steering Committee to develop 1) criteria for selecting implementation strategies, tools and resources for use in Network-wide intervention projects; 2) criteria for selecting Network-wide intervention projects; 3) actual selection of implementation resources and intervention strategies and intervention projects; and 4) final Network-wide protocol for intervention projects and metrics for evaluating them.
• Abiding by common definitions, protocols, procedures, etc. as chosen by majority vote of the Steering Committee.
• Collaborating with all Network sites to improve interoperability and transferability of data systems and tools across sites within and potentially outside the Network to facilitate development of nascent genomic Health Information Exchange (HIE).
• Collaborating with all Network sites in making Network findings and procedures as widely available and applicable as possible.
• Sharing research resources, tools, and data of interest with members of the consortium consistent with achieving the goals of the project.
• Ensuring that the software, resources, materials, etc. produced as part of this project are released appropriately according to the Resource Sharing Plan.
• Ensuring that the data produced as part of this project are released appropriately according to the Data Management and Sharing Plan.
• Adhering to policies regarding sharing of genomic and other types of data, data access, and standardized formats; timely publication; and intellectual property established by the NIH, NHGRI, and the Steering Committee (SC) for this program.
• As needed for intervention projects selected, sharing detailed genomic, phenotypic, family history, clinical, and related data derived from EMR systems and collected according to standard and widely available protocols such as those validated within eMERGE (i.e. PheKB) or the PhenX Toolkit through a definitive source such as AnVIL or ClinVar.
• Cooperating with other recipients in the development and design of research methods, protocols, tools, and strategies.
• Working productively with NHGRI and with program staff from other NIH Institutes who may be providing co-funding for projects.
• Accepting and complying with study policies established by NIH, and with additional non-conflicting policies approved by the Steering Committee.
• Cooperating with other recipients in the publication and dissemination of program results and the eventual release to the scientific community of methods, tools, and results, and other resources.
• Preparing abstracts, presentations, and publications in a timely manner.
• Assessing and disseminating data, protocols, consent materials, and methods developed within and outside the Consortium.
• Not disclosing confidential information.
• Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee, External Scientific Panel, and NIH.
• Attending and participating in Steering Committee and other working group meetings and accepting and implementing the decisions, guidelines, and procedures adopted by the Steering Committee, External Scientific Panel, and NIH, as appropriate.
• Interacting with other relevant NHGRI and NIH activities, as needed, to promote synergy and consistency among similar or related projects.
• Collaborating with the Coordinating Center (CC) tasked with a variety of roles, such as: ensuring that consortium products are the highest quality; developing standards; disseminating information; providing logistics, outreach and training, etc.
• For the collaboration to be effective, PDs/PIs are responsible for:
  • Ensuring that the recipient receives the appropriate approvals for sharing data with data repositories such as, AnVIL, dbGaP, and ClinVar and other appropriate public databases.
  • Working with other sites to ensure that collected and submitted data and metadata are standardized using agreed-upon formats and processes, submitted to the AnVIL to be cataloged, maintained, and made accessible as controlled-access data, and disseminated more broadly through dbGaP or ClinVar or other appropriate databases.
  • Submitting datasets generated from the Consortium directly to public data repositories such as AnVIL, dbGaP, and ClinVar, as appropriate and agreed upon with the CC, Steering Committee, and NIH.
  • Providing reports, summary statistics, and data, as appropriate, in a timely fashion as agreed upon by the Steering Committee and NIH.
  • Collaborating with the CC to establish data formats and standards, to track and document collaborations, report findings, etc.
• The clinical trial(s) supported by this award are subject to the plan in the application submitted to NIH and the NIH policy on Dissemination of NIH-Funded Clinical Trial Information (Public Law 110-85 and NOT-OD-16-149). Consistent with 45 C.F.R. 75.322, the recipient will own the data and software developed under this award and be able to continue to use these data and software upon expiration or termination of the award.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

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

The Project Scientist/Scientific Officer (PS/SO) at NHGRI is a dual role held by a NHGRI Program Director. In the Project Scientist role, the Program Director will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. In the Scientific Officer role, the Program Director will be responsible for the normal scientific and programmatic stewardship of the award and manages concerns about bias as it affects the project. The role of NHGRI PS/SO will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the program and that NIH staff will be given the opportunity to offer input to this process. The Project Scientist will participate as a member of the Steering Committee and will have one vote. The PS/SO will be named in the Notice of Award and will have the following substantial involvement:

• Participating with the other Steering Committee members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it.
• Serving as a liaison, helping to coordinate activities among and for the recipients, including acting as a liaison to the NIH, and as an information resource for the recipients about research activities. The PS/SO will also coordinate the efforts of the program with other groups conducting similar studies.
• Attending all Steering Committee meetings as a voting member and assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The PS/SO will be responsible for working with the Coordinating Center as needed to manage the logistic aspects of the program.
• Reporting periodically on the progress of the program to the Director, NHGRI, and to the National Advisory Council for Human Genome Research.
• Serving as a liaison between the Steering Committee and the External Scientific Panel, attending External Scientific Panel meetings in a non-voting liaison member role, and arranging for timely preparation and distribution of meeting minutes.
• Serving as a liaison between the Steering Committee and other federal agencies such as the Food and Drug Administration (FDA) or the Centers for Medicaid and Medicare Services (CMS).
• Serving on working groups of the Steering Committee and the External Scientific Panel, as appropriate.
• Assisting recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
• Providing advice in the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
• Being responsible for the normal scientific and programmatic stewardship of the award, including assessments of how well the recipient has met any milestones required for each year of funding.
• Curtailing, withholding, or reducing support for any recipient that fails to make satisfactory progress toward the work scope that NHGRI approved, has ethical or conflict of interest issues, or fails to comply with the Terms and Conditions of Award. In the event of a decision to terminate, requiring the recipient to submit a close-out plan within two (2) months of the decision.
• Involving NIH or NHGRI staff who may assist the recipient(s) as designated by the PS/SO.
• Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium/Network decides to publish, participating in data analyses, interpretations, and co-authorship of the publication of Consortium results through their role in scientific program management.
• Establishing best practices for IRB interactions, patient consent or assent (as appropriate), and results reporting, and for collecting, formatting, documenting, and sharing data as appropriate.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools for genomic research. The recipients and the Project Scientist will meet as the program Steering Committee at least twice per month by conference call and up to four times per year during the first year, two in person and two virtual full-day meetings, as needed for protocol development. During years 2-5, the SC will meet at least monthly by conference call and up to three times per year, two in person and one virtual full day meeting, to share information on data resources, methodologies, analytical tools, as well as data analyses and preliminary results. SC meetings are intended to be inclusive and all key collaborators and pre- and postdoctoral trainees, including those from underrepresented groups or those from different but related disciplines, should be encouraged to attend.

The Steering Committee will serve as the main scientific body of the program. The Steering Committee will be responsible for coordinating the activities being conducted by the program. The Steering Committee membership will include one NHGRI Project Scientist and the PI from each awarded cooperative agreement. Cooperative agreements with multi-PI arrangements will have a single vote to be decided as desired within the multi-PI award. The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired. It is anticipated that additional coordination mechanisms may be set up with other U.S. and international groups that may collaborate with the program.

To address particular issues, the Steering Committee may establish working groups, which will include representatives from the program and the NIH and possibly other experts. Recipients agree to work collaboratively to:

• Meet at frequency specified in RFA or otherwise agreed to with NIH to share information, experience and expertise across participating sites and centers on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.; and to develop consensus approaches to: recruiting study participants and informed consent; integrating, harmonizing, analyzing data; developing methods, best practices, and standards; and disseminating data to other Consortium members, the broader scientific community, and NIH-designated databases.
• Set research priorities, decide optimal research approaches and protocol designs, and contribute to the adjustment of research protocols or approaches as warranted.
• Inventory, assess and control quality, harmonize, and catalog Consortium data.
• Develop tools and resources for implementation of genomic medicine interventions and finalize them for wider dissemination.
• Establish best practices and standards for data integration and collaborative analyses, as appropriate.
• Generate responses to ESP recommendations.
  

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

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

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

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [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]

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

Robb Rowley, M.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-827-9126
Email: [email protected]

Rudy, Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-219-6235
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

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

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.