National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
U01 Research Project – Cooperative Agreements
See Section III. 3. Additional Information on Eligibility.
This Notice of Funding Opportunity (NOFO) solicits applications for a Coordinating Center to participate in forming a network of genomic-enabled learning health systems (gLHS) 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.
October 06, 2023
|Application Due Dates||Review and Award Cycles|
|New||Renewal / Resubmission / Revision (as allowed)||AIDS - New/Renewal/Resubmission/Revision, as allowed||Scientific Merit Review||Advisory Council Review||Earliest Start Date|
|November 07, 2023||Not Applicable||Not Applicable||March 2024||May 2024||July 2024|
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
This Notice of Funding Opportunity (NOFO), RFA-HG-23-042, invites applications for a Coordinating Center (CC) to participate in forming a Genomic-Enabled Learning Health System (gLHS) Network. In collaboration with NHGRI and 4-6 Clinical Sites (CS, RFA-HG-23-041), the CC will work 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:
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 into improved 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, to 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 4-6 CS (RFA-HG-23-041), the CC will work 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-23-041, 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 (RFA HG-23-041) 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 the 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 (this NOFO) will be primarily responsible for:
1. Collecting, compiling, organizing, contributing to, 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.
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 or full-scale 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.
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 their 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, the CC will establish a process and accessible site for each CS to submit a broad suite of strategies, tools, and resources for Network consideration. The CC will work with the CS and NHGRI to organize and finalize the selection, using criteria to be established by the Network, of a subset of 2-4 projects for Network-wide implementation. The CC will facilitate as needed the implementation of these projects within each CSs systems, using 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.
At the end of the first program year, the CC will make submitted tools and resources, whether selected for Network implementation or not, available to the scientific community through a platform and easy-to-navigate portal it will develop and other means as desired. The portal will include tools for data exploration, query, and visualization that are responsive to the needs of the research community and designed with end users in mind (e.g., geneticists, clinicians, and health systems researchers). The CC will ensure that tools and resources that have been selected for Network-wide implementation, evaluation, and refinement are clearly identified on the dissemination platform. Once developmental phases and evaluation are completed for the selected Network-wide tools and resources, the CC will also widely disseminate the revised versions. Refined tools and resources will 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 the best evidence, as reviewed by the Network, that they 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 community. Projects should be designed to demonstrate and enhance the ability to exchange genomic results, recommendations, and workflows across CS. They should also enable a patients genomic information to follow them across multiple providers where appropriate.
The CC will compile proposed intervention protocols and coordinate Network selection of 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.
The CC and each CS 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. The CC will work with NHGRI and the CS to develop and apply evaluation metrics, including outcomes of value to communities and other relevant stakeholders, to be defined in discussions with those groups. The CC will coordinate using the findings 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 future participation in gLHS-delivered genomic medicine.
The CC will manage all aspects of the Networks 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 CC will work with NHGRI and the CS 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.
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.
CC applicants will be expected to have familiarity with LHS approaches, including in underserved communities and settings, and expertise in genomic medicine, management of genomic data, integration with and management of EHRs, and organization of large networks of investigators working toward common scientific goals. They should also have expertise in community and stakeholder engagement, implementation science, change management, and health services research. CC applicants should have experience with and readiness to work with peers in a network setting, and willingness to adopt and implement agreed-upon gLHS approaches Network-wide.
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. 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 programs activities.
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.
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 ESPs 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.
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 NHGRIs data sharing expectations, which are summarized at genome.gov/data-sharing.
The first year will be devoted to sharing of intervention 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. Year 5 will be devoted to evaluation, refinement, re-implementation (as feasible) and dissemination of tools and resources developed by the Network.
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@example.com.
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.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Required: Only accepting applications that propose clinical trial(s).
NHGRI proposes to commit $1.6M per year total costs for five years to support 1 Coordinating Center.
Awards are limited to $900,000 direct costs per year for five years.
The project period for this NOFO is 5 years (FY2024-FY2028).
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations 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 22.214.171.124 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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 126.96.36.199 Submission of Resubmission Application. This means that the NIH will not accept:
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.
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:
The letter of intent should be sent to:
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
The CC budget 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 the CC 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, 2 in person and 1 virtual. The costs of traveling 6 ESP members to one SC meeting per year should also be included. The CC budget should include costs for organizing, managing, and participating in 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, where possible, 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 Networks utilization of AnVIL.
For budgeting purposes, the CC should assume the Network will be conducting 3 Network-wide intervention projects. CC budgets should include support as needed for community engagement and clinical informatics implementation as recommended by the study protocol.
The CC budget should include costs associated with the creation of the portal and platform for disseminating the Networks initial and final revised implementation tools and resources. It should also include the cost to manage and update the Network website, which should be capable of tracking network-wide activities and products for broader distribution.
The CC budget should include the cost to coordinate all activities of the Network that reflects sufficient effort of PIs/MPIs and program coordinators. The CC should also budget for outreach and dissemination activities to both participant and research communities.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 and 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., ensuring samples are collected with explicit informed consent for future research use and broad data sharing by the CS, 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:
The CC will provide critical strategic coordination of all activities of the gLHS Network. Applicants should provide evidence of their successful participation in, and oversight of, networks comprising multiple research sites to achieve common aims. Applicants should describe an operational plan and an organizational strategy to build a collaborative environment across the Network. They should describe their experience in and approach to managing all aspects of the Networks logistics and coordination. They should describe their experience and expertise in LHS approaches, including in underserved communities and settings, and expertise in genomic medicine, management of genomic data, integration with and management of EHRs, and organization of large networks of investigators working toward common scientific goals. They should also describe their expertise in community and stakeholder engagement, implementation science, change management, and health services research.
Applicants should describe their willingness to participate in and lead cross-Network data collection and analysis throughout the five years of the program, describe past experience with such network-wide activities, and budget for them accordingly. They should also describe their familiarity and experience with infrastructure needed for LHS, including constructing user-friendly data and visualization systems. They should describe their expertise in developing informatics that support linkage of EHR and structured genomic data in standard formats, permitting transferability and promoting interoperability and data sharing across multiple LHS. CS data systems will be expected to 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. The CC data system should be capable of receiving and analyzing such data Network-wide. Applicants should also describe their plans to assess and ensure quality of data and resources produced by the Network, and for maintaining security of Network data as needed, as well as their expertise in cloud-based tool development and data management, and in working within the AnVIL ecosystem.
Applicants should articulate a plan to work with the CS and NHGRI to define both the process and the standards for the submissions of Network data, as appropriate, to the AnVIL for public access. Where standards exist for EHR data integration and LHS implementation, CC applicants should describe them and indicate their commitment to using them to promote interoperability and sharing.
Applicants should describe their experience with LHS implementation strategies and give examples of their approaches to using the full cycle of implementation-evaluation-refinement-re-implementation to improve clinical care. They should describe their approaches for compiling, refining, and sharing tools and resources across the Network for consideration for refinement and Network-wide implementation, as well as their approaches to adopting 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 data transfer to other users, as well as their willingness and approaches to sharing tools, resources, and documentation for dissemination to the scientific community.
Applicants should describe their approaches to making submitted tools and resources available to the scientific community through a platform and easy-to-navigate portal and other means as desired, including tools for data exploration, query, and visualization designed with end users in mind. They should describe their plan for identifying, evaluating, and refining tools and resources selected for Network-wide implementation, and disseminating final revised versions designed to maximize interoperability and transferability of genomic information across health systems.
CC applicants may, if they choose, propose one or more 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. The potential for projects to demonstrate and enhance the exchange of genomic results, recommendations, and workflows across CS and adoption by outside groups should be described, as should the potential for a patients genomic information to follow them across multiple providers where appropriate. Approaches for improving interoperability and communication of genomic findings between clinicians and laboratories should also be described. CC applicants should describe their approach to developing criteria for selection of intervention projects and bringing the Network to consensus on these criteria, as well as consensus on selection of intervention projects. They should propose criteria for deciding whether projects should be conducted in pilot or full-scale mode, and for bringing the Network to consensus on these decisions. They should also propose an implementation science framework or frameworks for evaluation of the interventions, and their approach to bringing the Network to consensus on the framework(s) to be applied by the Network.
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 the various stakeholder communities, and their approach to bringing the Network to consensus on the metrics to be applied and outcomes to be assessed. If a CC-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.
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.
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, expectations for the consent process at the CS should be described at a high level in the Research Plan.
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.
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 starting in second year of award.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
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, NIHs 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 188.8.131.52 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.
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 organizations 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 firstname.lastname@example.org 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.
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.
For this particular announcement, note the following:
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.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this NOFO, how well did the applicant provide a scientific rationale, offer methodological advances, cite literature, or provide preliminary data for gLHS approaches? How adequate are the approaches described able to make a significant contribution to understanding how best to establish and utilize gLHS for genomic medicine implementation including how to extend gLHS approaches to underserved settings and populations? How adequate is the applicants plan described for adapting their approaches beyond their institution, including to under-resourced health care environments? How adequate is the applicant's plan described for selecting and including one or more individuals from under-resourced institutions as part of their research team to ensure their unique situations are considered when developing gLHS approaches?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this NOFO, how adequate is investigators experience at their career stage to work in multi-site research networks or consortia, develop network-wide protocols, integrate disparate datasets, and enhance interoperability and transportability of clinical data systems? How adequate do the applicants, based on their career stage, demonstrate the ability to work collaboratively and disseminate findings? How adequate are the applicants experience within LHS (Learning Health Systems) concerning most or all steps of the virtuous cycle of implementation, evaluation, refinement, and re-implementation of interventions to improve clinical care? How adequate do the applicants demonstrate their ability to integrate structured genomic data and genomic-based interventions into their LHS if not already integrated?
Specific to this NOFO, how adequate is the applicants experience and expertise for their career stage to implement genomic medicine interventions and evaluate their outcomes? How adequate is the applicants experience to select and implement data standards, integrate informatic solutions and share research information across collaborating institutions and with NIH-designated databases?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Specific to this NOFO, how adequate are the applicants informatics strategies and data analysis plans to meet the aims of the project? As new technologies and innovations become available, how adequately prepared is the research team to develop and implement these new advances into their research? How significant are the applicants proposed genomic medicine intervention over what is currently implemented in the field?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this NOFO, how adequate are the applicants strategies for community and stakeholder engagement adequate to reach the aims of the project?
Specific to this NOFO, how are adequate are the applicants strategies for outreach, dissemination, and promotion of Network resources likely to engage the broader scientific community?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHGRI Scientific Review Branch, 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:
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.
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:
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 investigators 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.
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 applicants 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:
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:
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:
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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
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Robb Rowley, M.D.
National Human Genome Research Institute (NHGRI)
Rudy, Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
National Human Genome Research Institute (NHGRI)
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.
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