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 How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

 Purpose

This Notice of Funding Opportunity (NOFO), RFA-HG-24-023, invites applications to participate as a Sequencing Center (SeqC) in the Genomic Population Screening in Primary Care Network, in collaboration with 4-5 Clinical Groups (CG, RFA-HG-24-021) and a Coordinating Center (CC, RFA-HG-24-022).

This Network will implement a pilot program of population genomic screening for common, actionable genomic conditions in a primary care setting. Specifically, this multi-site program will: 1) evaluate primary care-based screening for roughly 4-7 genomic conditions with the strongest evidence for effectiveness of screening in preventing disease or reducing its severity 2) use established strategies for meaningful community engagement in all phases of design, conduct, and evaluation; and 3) develop effective strategies for connecting patients found to have genomic risk variants to follow-up care.

The intent is to start with conditions that have the strongest available evidence for effectiveness of genomic screening, recognizing that evidence might accrue over time for other conditions that may mature sufficiently for implementation. Conditions to be implemented should include the three Centers for Disease Control and Prevention (CDC) Tier 1 conditions (hereditary breast and ovarian cancer or HBOC, Lynch syndrome or LS, and familial hypercholesterolemia or FH), along with conditions with a strong but perhaps not yet convincing evidence base. Such conditions might include HFE hemochromatosis, ATTR cardiomyopathy and related conditions, APOL1 hypertensive renal disease, or other conditions that investigators might propose in addition to the Tier 1 conditions. Criteria for selecting proposed additional screening conditions may include expected prevalence, penetrance, actionability, and validity of testing and will be decided upon during protocol development.

The Network will assign an Intervention (genomic testing) to human subjects, return the results, and evaluate the preventive strategy of the intervention on patients. Therefore, it meets the 2015 revised NIH definition of a clinical trial as described in NOT-OD-15-015. The ultimate goal of this initiative is to understand the factors shaping the adoption of population genomic screening in primary care in individuals unselected for any disease, not necessarily in any of the high-risk categories for the diseases in the Tier 1 group, and to identify tools and other resources that facilitate, when appropriate, implementation of genomic screening into primary care. The Network is intended to identify and collect outcomes data to better understand the optimal approach to implementation of population genomic screening based on the contextual setting and on what is important to patients, PCPs, and other stakeholders. It will deliver a framework of best practices and lessons learned to ensure equitable and sustainable implementation of Tier 1 conditions in the future as well as creating the foundation for the implementation of additional conditions such as those in the current ACMG 3.2 secondary findings. The Network is not intended to support a large-scale randomized controlled clinical trial of population genomic screening for Tier 1 conditions or conditions with a strong but perhaps not yet convincing evidence base to demonstrate the effectiveness of the screening to detect persons at risk.

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

“Clinical Groups (CGs)” refers collectively to the multi-site recipients to be funded under RFA-HG-24-021.

“Clinical Sites (CSs)” refers collectively to the diverse clinical practice settings, which could include individual primary care practitioners or groups, comprising each Clinical Group (CG).

“Health disparities populations” refers to racial and ethnic minority groups, people with lower socioeconomic status (SES), underserved rural communities, sexual and gender minority (SGM) groups, and people with disabilities (https://www.nimhd.nih.gov/resources/understanding-health-disparities/minority-health-and-health-disparities-definitions.html).

“Diverse clinical practice settings” refers to any settings in which genomic screening could be implemented by primary care providers, including hospitals, clinicians’ offices, community sites, etc.

"Primary care” is defined by the National Academies of Science, Engineering and Medicine (NASEM) as, “the provision of integrated, accessible health care services by clinicians who are accountable for addressing a large majority of personal health care needs, developing a sustained partnership with patients, and practicing in the context of family and community.”

“Primary care providers (PCPs)” are defined by the Centers for Medicare and Medicaid Services (CMS) as including “doctors, nurses, nurse practitioners, and physician assistants” providing primary care. They may include practitioners in family and internal medicine, pediatrics, and obstetrics and gynecology.

“Underserved” refers to populations who are "medically underserved as defined by the Health Resources and Services Administration (HRSA) (https://bhw.hrsa.gov/shortage-designation/muap).

“Clinical Information” refers collectively to a patient’s non-genetic medical information such as personal medical history, family history, physical and laboratory measurements, lifestyle habits, and environmental exposures/social history.

“Outcomes” refers to clinical, behavioral, implementation, process, and economic outcomes.

“Implementation science” is defined by the National Cancer Institute (NCI) as a growing research field that “uses a scientific approach to find the best ways to integrate proven, effective interventions into routine health care.”

“Electronic Health Records (EHRs)” refers to computerized data obtained in the course of clinical care that can be electronically accessed, manipulated, shared, and analyzed, with appropriate consent and patient protections, for research purposes and ongoing clinical care and quality improvement.

“Patients” refers collectively to adults (ages 18 and older) receiving care within one or more Clinical Groups; all participants recruited to this study are expected to be patients with existing and accessible EHRs, hard copy medical records, or other means to access their clinical care records.

“Community engagement” is defined by the National Institutes of Health (NIH) as “the process of working collaboratively with and through groups of people affiliated by geographic proximity, special interest, or similar situations to address issues affecting the well-being of those people.

“Network” refers to the Population Genomic Screening Network comprising the grants to be funded under this NOFO (RFA-HG-24-022), RFA-HG-24-021 and RFA-HG-24-023, unless otherwise indicated.

Background

Screening for genomic variants that substantially increase risk of developing common, complex diseases has been established as a cost-effective strategy for three “Tier 1” genomic conditions identified by the Centers for Disease Control and Prevention (CDC): hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS), and familial hypercholesterolemia (FH). These conditions at present are poorly ascertained by the healthcare system and patients are often unaware of them until they present with late-stage disease. Several other conditions appear “near-ready” for implementation with accumulating but not yet conclusive evidence.

Primary care providers (PCPs) are typically the “first line” for managing preventive care—counseling patients on the need for screening, ordering the tests, and linking patients to appropriate follow-up care. The primary care workforce in general feels poorly prepared to address genomic testing and screening, but approaches are available to improve their readiness. Gaps for this workforce include knowledge, confidence, efficient workflows, and a robust informatics infrastructure to support decision-making. Bridging these gaps is possible by facilitating collaboration between PCPs and expert clinical centers. This partnership would offer PCPs essential resources such as patient educational programs, optimized workflows, established referral processes, access to just-in-time CDS systems, and various other resources and informatics tools. Introducing genomic testing gradually into the primary care space, by picking a few high-value, high-evidence screening tests that are straightforward to implement and understand and creating facile solutions that are not time consuming for the fast pace of primary care practices is likely to be more successful than adopting a very large number (such as the current ACMG 3.2 secondary findings list) all at once. Cost-effectiveness of screening has been shown to increase when multiple conditions are assessed simultaneously, taking advantage of a single genomic screen and results return process. Importantly, effective screening also requires establishing effective referral systems for follow-up care.

Community engagement is critical to conducting successful genomic research and providing effective care, particularly in marginalized communities. This entails proactively seeking out community values, concerns, and aspirations, then incorporating those into decision-making and establishing meaningful, ongoing partnerships. Implementation science provides tools and frameworks to facilitate and evaluate engagement across a number of different stakeholder types, including patients, families, communities, clinicians, health systems, professional societies, and payers.

In November 2023, the Genomic Medicine Working Group of the National Advisory Council on Human Genome Research convened leaders in genomic medicine and related fields in its 15th Genomic Medicine (GMXV) meeting to examine the current state of population genomic screening in the U.S. The group explored obstacles, opportunities, and new directions to inform expanded screening of the general population. A strong recommendation of the GMXV meeting was to support pilot studies of implementing population genomic screening for Tier 1 genomic conditions in primary care as well as near-ready genomic conditions that need that “last mile” of evidence to justify implementation. There was consensus that polygenic risk was not yet ready for population screening and that the current effort should focus on screening for monogenic conditions. GMXV participants recommended the genomics community engage with the prevention research community to co-develop these genomic prevention research projects.

Research Objectives

The Population Genomic Screening Network will consist of 4-5 Clinical Groups (CGs), a Coordinating Center (CC), and a Sequencing Center (SeqC). Each CG will have the necessary expertise and sufficient CSs, including PCPs and patient populations, to accomplish the following objectives:

1) Offer the screening test. The test will be made available to any patient regardless of their health status and other conditions. While patients known to be at increased risk for one or more genomic conditions should not be excluded, they should not be preferentially selected or included at a rate greater than their representation in a routine primary care setting. The Network will agree upon a screening protocol and conduct the same protocol, screening for the same genes using the same sequencing platform, the same return of results procedures, and the same follow-up approaches among all patients across all Clinical Groups. This network-wide population genomic screening will include the three CDC Tier 1 genomic conditions described above, along with conditions with a strong but perhaps not yet convincing evidence base. Such conditions might include HFE hemochromatosis, ATTR cardiomyopathy or related conditions, APOL1 hypertension or other conditions that investigators might propose in addition to the Tier 1 monogenic conditions. For these proposed conditions, the CGs and other participating sites (as appropriate and desired) will provide the evidence supporting their value, workflows for testing and follow-up, education and CDS to be provided, costs, and outcome measures. The network will then compile and review the evidence during the first year to determine which variants are appropriate to identify.

2) Engage the community relevant to the test offered. Community engagement in research is a process of inclusivity of people affiliated with or self-identified by geographic proximity, special interest, or similar situations to address issues affecting the well-being of the community of focus. Community engagement in this study will be a core element of its research effort and will require investigators to become part of the community and community members to become part of the investigative team, creating a unique working and learning environment before, during, and after the research. Members of the community will be engaged throughout the process, from protocol development through analysis, dissemination, and more.

3) Enroll 5,000 patients (per CG) with at least 55% enrollment of patients satisfying the definition of "health disparity populations" and complete enrollment and screening within a 12-month period. Each patient will provide a blood or saliva sample for genomic sequencing performed at the SeqC and the agreed-upon set of screening results will be returned to patients and their PCPs in a Clinical Laboratory Improvement Amendment (CLIA) compliant manner. All recruited patients must be receiving their care at U.S. clinical care settings, including settings with limited resources or those providing care to predominantly underserved populations as defined above. Implementation of population genomic screening in this program will emphasize improving health equity with goals of educating the genomics/precision health workforce, increasing awareness of the power of genomics/precision health, informing policy decisions, improving data infrastructure and the evidence base, and adequately addressing ethical, legal, and social implications and concerns specific to health disparities populations.

4) Perform whole exome sequencing (or alternative technology meeting the aims and time and cost constraints of this NOFO), variant interpretation, quality control and monitoring, generation of clinical reports for PCPs and patients in formats agreed upon by the Steering Committee (SC), and submission of genomic data in computable form to CC and CGs as appropriate.

5) Return genetic testing results to PCPs and patients. PCPs and patients will receive genomic test results along with guideline-based risk management information pertaining to the specific conditions for which they are identified as being at increased genetic risk, as agreed upon within the SC. Results return may occur through electronic clinical decision support (eCDS) incorporated in the electronic health record (EHR), where available, or through other means when not available; electronic approaches should be supported or augmented through genetic counseling when needed. Methods for screening, returning results, counseling, referring, and following up will need to be modified for sites without access to eCDS, EHRs, genetic counseling, and other such resources. Actions taken on these recommendations, such as increased disease screening and surveillance or referral to a specialist, will be assessed through the EHR or other means as necessary. CGs will be expected to share across the Network all the data needed to assess the impact of the implementation on outcomes. Analysis of the implementation process and outcomes during a minimum follow-up of 24 months from return of results for each patient will be conducted on the network-wide population and will be agreed upon during protocol development. Other clinical risk factors at entry and during follow-up (such as hypertension, diabetes, health behaviors) as well as medication use, imaging findings, and other relevant factors, should be available and extractable from EHRs or other clinical information.

6) Implement referral and a minimum 24-month follow-up for outcome data starting from results return to patients. Common, standardized, patient-reported outcomes, implementation outcomes, and other outcomes will be proposed, agreed upon, and adopted by the Network. As the intent of this program is to facilitate implementation of genomic screening in primary care, screening should be easily implemented with minimal disruption in the course of primary care. The network-wide agreed-upon protocols will also emphasize interoperability of processes, standards, referral patterns, best practices, eCDS (where applicable), and data collection methods across sites and with external health systems as feasible. The SC will devise and implement approaches for filling key gaps in identifying patients with at increased genomic risk for the primary care workforce, including appropriate educational materials for PCPs and their patients, efficient workflows, effective referral systems (including guidance for obtaining insurance authorization to cover the cost of genetic testing and follow-up care after the end of the study), and robust informatics infrastructure and CDS needed for a busy primary care practice. Using principles of implementation science, the Network will examine methods for conducting this screening in diverse primary care settings and evaluate them using an implementation framework to be chosen by the program SC, such as the Practical Implementation Sustainability Model (PRISM), Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM), or the Consolidated Framework for Implementation Research (CFIR). In an ongoing manner, the Network will evaluate the need for changes to the screening, reporting, or referral protocols and track those adaptations using agreed-upon tools and metrics. Adaptations may need to be tailored to fit local needs, but the program will emphasize network-wide changes when needed and gather information about them for compiling and disseminating lessons learned in real time and code/analyze at the end for impact. Because evidence supporting the value of implementation may be limited for some of the conditions selected, the program may need to consider an effectiveness-implementation hybrid study.

7) Share lessons learned and successful approaches. Results from this pilot program will be used to refine broader population genomic screening programs that may involve an expanded number of conditions, screening settings, or implementation strategies. Lessons learned, and successful approaches will be gathered and disseminated through outreach efforts such as conferences, publications, websites, etc. It is anticipated that data, including sequencing and clinical information, as well as tools and other resources developed during the 5 years from the Network will be made available through AnVIL or another scalable and interoperable platform approved by NHGRI.

Research topics

NHGRI intends to support a single, network-wide, population genomic screening implementation protocol for 4-7 conditions that can be implemented across a large and diverse patient population, address issues of public health significance, and have a high potential to inform future clinical practice. A single network-wide protocol will be established during the first year after the award by the Network’s Steering Committee (SC) that will identify and collect outcomes important to patients, PCPs, and other stakeholders for successful uptake of screening and referral to follow-up care.

Examples of topics that could be addressed in implementing a population genomic screening program include but are not limited to those listed below:

1) What are the reach, uptake, acceptability, feasibility, and potential sustainability of genomic screening in diverse settings for patients and PCPs?

2) What are the screening conditions that are acceptable or not in different settings/communities?

3) What strategies will be necessary to facilitate equitable offering, uptake of, and action upon population genomic screening?

4) What types of referral preventive strategies and clinical expertise are available in diverse settings, what are the barriers to access, and how often do patients pursue referral?

5) What education/support is needed for PCPs and patients to adopt screening for pathogenic/likely pathogenic variants? What is the impact of education and support on health behavior changes and/or other empowering aspects (e.g., patients better managing their medications)?

6) What adaptations are needed to implement the screening equitably and to connect patients to follow-up care to influence health outcomes equitably across diverse clinical settings, including those with limited resources?

7) What are the potential costs incurred/avoided when implementing a population genomic screening program?

8) What are the unintended consequences of implementing population genomic screening, especially in health disparities populations?

Applicants are not limited to addressing this list of topics and are encouraged to contact NHGRI to discuss their proposed topic(s) to ensure pertinence to the objectives of this NOFO.

Organization of the Network

This NOFO (RFA-HG-24-023), together with RFA-HG-24-021 (CG) and RFA-HG-24-022 (CC), will support a Network to implement a pilot program of population screening for common, actionable genomic conditions in diverse settings. The primary objectives of the Network are outlined above. Here we specifically highlight the roles and responsibilities of each component:

The SeqC (this NOFO) will be primarily responsible for:

1. Providing sequencing of genes selected for population genomic screening for 20,000 adult patients, variant calling, annotation and confirmation, interpretation, and reporting to the CC and CGs.
2. Providing testing kits and paying for costs to ship the samples to the laboratory.
3. Using whole exome sequencing (or alternative technology meeting the aims and time and cost constraints of this NOFO) to produce genomic data from 20,000 biosamples (including saliva, blood or other) and provide the genomic data to the CC for analysis and dissemination.
4. Receiving biosamples from the CGs for data production and providing secure and accessible storage for them for the duration of the program.
5. Contributing to Network-wide protocol development, implementation, monitoring, and data analysis and publication.
6. Working with the CC to standardize and harmonize genomic data such that it can form part of the multi-dimensional data set that will be made accessible to the broader scientific community via a controlled-access data request system hosted by the NHGRI AnVIL or another scalable and interoperable platform approved by NHGRI.

Each CG (RFA-HG-24-021) will be primarily responsible for:

1. Designing a study focused on population screening for genomic variants that substantially increase risk of developing common diseases. Screening will be population-wide among all patients receiving care, not limited to or disproportionately involving those perceived to be at increased risk.
2. Establishing effective outreach, engagement, education, recruitment, and retention strategies to maximize participation among groups most severely impacted by the proposed diseases and understudied in genomic research pertaining to that disease.
3. Engaging PCPs to screen, enroll, and follow approximately 5,000 patients per CG (20,000 total for the 4-5 CGs), with at least 55% enrollment of patients satisfying the definition of “health disparities populations” above, unselected for any disease, and consented for: a) collection of genomic and clinical information; b) future research use; and c) broad data sharing.
4. Submitting biosamples to the SeqC for data production.
5. Returning results, implementing referrals, and collecting follow-up data for a minimum of 24 months after return of results and providing the CC with the data collected.
6. Promoting, encouraging, and ensuring appropriate follow-up care of all screened patients.
7. Contributing to network-wide protocol development, implementation, quality control, and data analysis.
8. Working with the CC to standardize and harmonize participant data to produce a well-documented, de-identified analysis data set that will be made accessible to the broader scientific community via a controlled-access data request system hosted by the NHGRI AnVIL or another scalable and interoperable platform approved by NHGRI.

The CC (RFA-24-022) will be primarily responsible for:

1. Coordinating and contributing to Network-wide protocol development, data collection and analysis plans, and tool and resource development.
2. Serving as the single Institutional Review Board (IRB) and facilitating the submission and review of protocols, consent forms, annual reviews, amendments, and Data Use and Data Sharing Agreements as needed.
3. Monitoring participant accrual, pace of results return, and loss to follow-up; monitoring implementation, coordinating transfer of Network data across sites, and managing and securing network data.
4. Coordinating administrative duties including clinicaltrials.gov registration and maintenance.
5. Coordinating Network logistics and supporting activities related to arranging and conducting meetings of the Network, its Working Groups, and its External Scientific Panel (ESP), and informational conferences and exchanges with the scientific community and other relevant stakeholders.
6. Monitoring data quality and completeness, identifying and implementing corrective actions, tracking adaptations, and coordinating centralized data collection for project outcomes.
7. Registering the study with AnvIL and submitting the well-documented, de-identified analysis data set to the NHGRI AnVIL or another scalable and interoperable platform approved by NHGRI.
8. Coordinating in collaboration with the SeqC and the GCs the development of the data model the SeqC and CGs will follow.
9. Harmonizing the data including sequencing data, clinical data and de-anonymized data in order to conduct the main analysis of results based on the network-wide population.
10. Coordinating outreach and dissemination of findings.

These roles of the participating sites are elaborated further here:

Clinical Groups (CGs)

CGs are responsible for patient recruitment, implementation of all study procedures, and dissemination of research findings in collaboration with the CC, SeqC and NHGRI. In conjunction with the CC, SeqC and NHGRI, CGs will be responsible for finalizing, prioritizing, and implementing the combined, network-wide screening, results return, referral, and follow-up protocols; assessing the implementation; measuring outcomes; and analyzing and interpreting research results. Each CG will participate in a cooperative and interactive manner with all other CGs, the SeqC and the CC in all aspects of the Network, including developing Network procedures and working groups, finalizing protocols, developing a collaborative IRB process for submission to a single, shared IRB as described in NIH’s Single IRB Policy for Multi-site Research, writing template informed consents, delivering recommendations, and assessing clinical uptake and outcomes. As noted above, continued patient involvement and community and stakeholder engagement are key aspects of this project. The CGs will work collaboratively with each other, the SeqC, the CC, and NHGRI to establish a plan for community, stakeholder and patient engagement and patient retention across the Network. The CGs will also work collaboratively with each other, the SeqC and the CC for timely and efficient transmission, in as automated a fashion as possible, of data needed for the CC to monitor recruitment, retention, progress, and study outcomes across the entire Network. CGs are encouraged to engage in outreach efforts to diversify the pool of prospective investigators interested in participating in the program, including those from underrepresented racial and ethnic groups.

Coordinating Center (CC)

The CC will play a major research role in the coordination of the development, finalization, implementation, and distribution of the population genomic screening protocols; quality control of data collection; preparation and distribution of network-wide datasets for distributed secondary analysis; joint primary analyses of network-wide data; analysis of clinical and other outcomes and subgroup effects, and coordination of protocol finalization and implementation. The CC will also collect data on progress of patient recruitment and enrollment and will report progress regularly to the SC, ESP, and NHGRI. These data will be used to inform SC evaluation and recommendation of protocol modifications and recruitment goals as needed. The CC will also be responsible for coordinating all genomic data transfer from the SeqC to their centralized database. The CC will ensure that robust and efficient informatics tools are adopted at the CGs, SeqC and CC to collect, store, transmit, and analyze the data, as well as to obtain consent, educate PCPs and patients, return results, implement follow-up, and monitor data completeness and quality as required by the population screening protocol. The CC will coordinate transfer of deidentified clinical data from each CG to their centralized database and then to an NHGRI-approved data repository for network-wide analysis. The CC will also be responsible for sharing the Network dataset with the broader research community through submission to controlled access databases such as AnVIL, or ClinVar or another scalable and interoperable platform approved by NHGRI.

The CC will perform traditional network coordination and support activities and will promote standardization of terminologies and methodologies to be used. Maintaining patient involvement throughout the study for assessment of outcomes is key to the success of this project. The CC will be responsible for working with the CGs to establish and implement a plan for continued patient involvement and community/stakeholder engagement network-wide. The CC is encouraged to engage in outreach efforts to diversify the pool of prospective investigators interested in participating in the program, including those from underrepresented racial and ethnic groups. In addition, the CC will have primary responsibility for overseeing the drafting, submission, and approval of a single, shared IRB as described in NIH’s Single IRB Policy for Multi-site Research. The CC will also be responsible for registering the Network in, and submitting results information submitted to, ClinicalTrials.gov as described in NOT-OD-16-149, NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.

Sequencing Center (SeqC)

Due to regulatory requirements for using research results in clinical care, genetic testing will be performed in a CLIA environment. CGs will collect and transfer samples in a CLIA-compliant manner and the SeqC will have CLIA-certified genomic testing laboratory capabilities. The SeqC will have the capability to provide test kits with shipping materials to the CGs, extract high-quality DNA, perform cost-efficient clinical exome sequencing (or alternative technology meeting the aims and time and cost constraints of this NOFO), analyze and confirm variants as necessary, generate clinical reports for clinicians and patients in agreed-upon formats, and transmit the genomic data and metadata to the CC data repository in a timely and CLIA-compliant manner. SeqC investigators will also participate in all aspects of protocol development, quality control monitoring, and data analysis.

The SeqC will utilize sequencing rather than genotyping technology to ensure that a broad range of human genomic variation is detectable in the genes and populations to be included in this screening protocol. This should include potential actionable variants in populations underrepresented in human genomic databases but likely to be present in patients included in this Network. At present the most widely available, cost-efficient, and timely approach to detection of such variants appears to be whole exome sequencing using standard, established and validated (“off-the-shelf”) technology. Currently, this approach is highly preferable to developing and validating a network-specific targeted panel, but superior approaches may become available in this rapidly evolving field during the solicitation and conduct of this program. Such technologies may be proposed and considered during protocol development, but any method chosen must be ready for clinical deployment throughout the U.S. by the end of the study’s first year. Consistent with professional society guidelines such as the ACMG SF v3.2 list, all variants deemed clinically actionable (beyond those relevant to the 4-7 conditions included in the initial Network screening protocol) will also be identified by the SeqC and reported back to PCPs and patients, though that reporting may be delayed until the end of the program, after the primary goals of the Network are met. Some unexpected genomic findings may need to be reported more urgently (e.g., HIV, hepatitis C or circulating tumor DNA) as agreed upon by the Network SC.

The SeqC will be actively involved with other Network partners in assessing and improving the approach to population genomic screening in efforts to streamline and simplify the clinical workflow as much as possible to minimize the burden on PCPs and facilitate implementation.

NHGRI

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

Steering Committee (SC)

A SC comprising Program Director(s)/Principal Investigator(s) [PD(s)/PI(s)] of the CGs, SeqC and the CC, and the NHGRI Project Scientist(s), will constitute the main governing body of the Network. All major scientific decisions will be determined by majority vote of the SC. It is anticipated that the SC will meet at least twice per month by conference call and four times per year in person the first year as needed for protocol development, and then monthly by conference call and three times per year in person in years 2-5. The SC will have primary responsibility for the general organization of the Network, finalizing protocols, facilitating the conduct and monitoring of the combined protocol, reporting results in a timely manner, and disseminating the findings. The SC will be responsible for creating a plan for clinical and genomic data sharing consistent with NHGRI policies during the first year of the program. Working groups of the SC will be established to address specific activities, such as recruitment and retention, publications and presentations, genomic testing, risk assessment and management, clinical decision support, and quality control and assurance. Recipients will agree to accept and implement policies approved by the SC.

External Input to the Network

The Network will have an External Scientific Panel (ESP). The ESP will provide input on performance and overall progress of the program. The ESP will consist of experts in genomic medicine, bioethics, biostatistics, outcome measures, implementation science and other areas of expertise as needed. An NHGRI scientist will serve as the Executive Secretary to the ESP. The ESP will meet semi-annually (one conference call and one in-person meeting in conjunction with an in-person SC meeting per year). Following each meeting, the ESP will provide recommendations and will prepare a report for PD(s)/PI(s). The SC members will receive and consider the ESP’s comments and will provide a written response to the recommendations. Applicants should not propose names of potential advisors in their applications; they will be selected after award.

Community Engagement Board

The Network will have a Community Engagement Board which will include a number of different stakeholder types, including patients, families, PCPs, health systems, professional societies, and payers. Community engagement is a process that requires sharing of power, maintenance of equity, and flexibility in pursuing goals, methods, and time frames to fit the priorities, needs, and capacities within the cultural context of communities. The feedback to awardees from this Board will be used to help mobilize resources and influence systems, change relationships among partners, and serve as catalysts for changing policies, programs, and practices as needed. Individual CGs may establish local engagement or stakeholder groups as desired, but applicants should not propose names of potential advisors in their applications.

Program Formation and Governance

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

The SC will evaluate the proposed protocols. In addition to the Tier 1 screening conditions, the additional conditions with a strong but perhaps not yet convincing evidence base to be conducted in the Network will be selected from those proposed by Network members, but a decision to fund a particular CG will not commit the Network to screen for that applicant’s proposed conditions.

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 Plan here, and ensure the Plan is in alignment with NHGRI’s data sharing expectations, which are summarized at genome.gov/data-sharing.

Clinical Trial Registration

The Population Genomic Screening in Primary Care Network meets the 2015 revised NIH definition of a clinical trial as described in NOT-OD-15-015, Notice of Revised NIH Definition of Clinical Trial. It is expected that the Network will be registered in, and results information submitted to, ClinicalTrials.gov by the CC for the Network as a whole as described in NOT-OD-16-149, NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.

Pre-Application Webinar and Program Website

NHGRI will hold a pre-application webinar for potential applicants on Oct 10, 2024, 1:00 PM — 2:00 PM EST. Participation in the webinar is optional and not required to submit an application. Information about the webinar can be found at https://www.genome.gov/event-calendar/population-genomic-screening-NOFO-webinar. The webinar connections will open 15 minutes in advance of the start time. During the webinar, NIH staff will give an overview of the NOFO and application submission process and field questions from potential applicants. Attendees can ask questions during the webinar and are encouraged to email questions in advance to Simona Volpi at [email protected].

For those who cannot attend, a recording of the webinar will be posted on the above website. Questions and answers from the webinar and other frequently asked questions will also be posted.

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 Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

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

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - 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:

Simona Volpi, PhD
Telephone: 301-480-3480
Email: [email protected]

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

SeqC 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 at four in-person SC meetings (2 days, 1-2 nights) in the first year and three in-person meetings per year in years 2-5. CG 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. 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 an appropriate cloud platform such as NHGRI’s AnVIL based on Microsoft Azure Platform pricing. NHGRI will continually assess the utilization of AnVIL.

For budgeting purposes, applicants should assume use of approved and readily available, standard (“off-the-shelf”) exome sequencing technology in a CLIA environment to detect and classify clinically actionable variants in the 20,000 patients expected for the Network. No funding for development of additional approaches/methods should be included in the budget. Development efforts related to potential new methods/approaches will not be supported by this RFA.  Applicants should assume that 4-5% of the 20,000 patients will be identified as being at high risk for at least one condition agreed upon for the screening protocol or reported as secondary findings at the end of the study, in accordance with professional society guidelines. Applicants may assume a maximum of 5 CGs with no more than 10 CSs each.

Applicants should provide an itemized breakdown of direct and indirect costs per patient for sequencing in a CLIA environment, primary analysis, interpretations, reporting, re-analysis, and re-interpretation of sequencing data as needed at a frequency to be determined by the SC protocol.

SeqC budgets should include costs for:

1. Management of biospecimens, including sample receipt, DNA extraction, ensuring sample stability, quality assessments, and quality control.
2. Secure and accessible storage for the duration of the program of the biospecimens submitted by the CGs for variant detection.
3. WES for each of the 20,000 participants and variants analysis of 6 genomic conditions (for budgeting) in total as agreed in the screening protocol: 3 conditions indicated as Tier 1 by CDC and 3 (again for consistent budgeting purposes only) additional conditions with a strong but perhaps not yet convincing evidence base as indicated in the research approach section.
4. Development and generation of readily understood and transmitted clinical reports, preferably in a format that can be transferred and read across multiple EHR systems.
5. Re-analysis of variants after initial report as agreed upon by the Network (for budgeting purposes, re-interpretation should be scheduled once per year after initial report).
6. Clinical reporting of secondary findings not included in the screening protocol at the end of the study as consistent with professional society guidelines.
7. Cost-efficient data transfer to the CC and other data repositories as needed.
8. Supporting sharing of scientific data under this NOFO. NIH provides guidance on allowable costs for data management and sharing here. For projects generating genomic data derived from research participants, investigators should consider costs associated with complying with the NIH and NHGRI GDS Policy expectations (e.g., obtaining samples with explicit informed consent for future research use and broad data sharing, implementing processes to seek new consent from study participants, etc.) 

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Due to regulatory requirements for using research results in clinical care, genetic testing will be performed in a CLIA environment. CGs will collect and transfer samples in a CLIA-compliant manner and the SeqC will have CLIA-certified genomic testing laboratory capabilities. The SeqC will have the capability to extract high-quality DNA, perform cost-efficient clinical exome sequencing (or alternative technology meeting the aims and time and cost constraints of this NOFO), analyze and confirm variants as necessary, generate clinical reports for clinicians and patients in agreed-upon formats, and transmit the genomic data and metadata to the CC data repository in a timely and CLIA-compliant manner. SeqC investigators will also participate in all aspects of protocol development, quality control monitoring, and data analysis.

The SeqC will utilize sequencing rather than genotyping technology to ensure that a broad range of human genomic diversity is detectable in the genes and populations to be included in this screening protocol. This should include potential actionable variants in populations underrepresented in human genomic databases but likely to be present in patients included in this Network. At present the most widely available, cost-efficient, and timely approach to detection of such variants appears to be whole exome sequencing using standard, established, and validated (“off-the-shelf”) technology as the samples are expected to be processed on an ongoing basis. Currently, this approach is highly preferable to developing and validating a Network-specific targeted panel, but superior approaches may become available in this rapidly evolving field during the solicitation and design of this program. Such technologies may be proposed and considered during protocol development, but any method chosen must be ready for clinical deployment throughout the U.S. by the end of the study’s first year. Consistent with professional society guidelines such as the ACMG SF v3.2 list, all variants deemed clinically actionable (beyond those relevant to the 4-7 conditions included in the Network screening protocol) will also be identified by the SeqC and reported back to PCPs and patients, though that reporting may be delayed until the end of the program, after the primary goals of the Network are met.     

Each applicant should offer an approach to accomplishing the primary aims of the pilot program as described below.

Introduction to Application

The pilot study will develop over the course of 5 years. During year 1, protocol development and IRB approval will take place. During year 2, the study will start recruitment and year 3 and 4 will be reserved for follow-up data collection. The SeqC is expected to run the sample pipeline mostly in year 2 and some in year 3 (18-month sample processing timeline). During year 3 and 4 the SeqC will be involved in collecting outcomes related to the SeqC as decided by the SC during protocol development, such as sample quality metrics, turnaround time, need for reanalysis etc. As this is an implementation study, some the outcomes related to the SeqC might be included in the lessons learned at the end of the study. In addition, during these years, the SeqC will also be involved in reanalysis of variants for the 20,000 participants as needed and agreed upon by the Network. Year 5 will focus on study analysis and sharing of results.

Specific Aims

The SeqC will aim to:

1. Design, in collaboration with other Network members, a study focused on population genomic screening for the CDC Tier 1 conditions and 1-4 additional conditions (assuming 3 for budgeting purposes only) in 20,000 patients in a 12-month recruitment period.
2. Perform cost-efficient, CLIA-compliant, clinical exome sequencing (or suitable alternative technology), with analysis, confirmation, and re-analysis as necessary; provide clinical reports for PCPs and patients; and transmit the resulting data to the CC data repository in a timely and CLIA-compliant manner.
3. Create, in collaboration with the CGs, CC and NHGRI, a framework of best practices and lessons learned to ensure equitable and sustainable future implementation of screening for Tier 1 conditions as well as creating the foundation for wider implementation of additional conditions.

Research Strategy

A narrative describing the applicant’s ability to receive, track, store, perform WES, analyze variants and provide clinical reports on 20,000 samples during a 12-month recruitment period in a CLIA-compliant manner should be provided with objective sources of data on the capabilities of the proposed SeqC and demonstration of past experience in the successful conduct of large-scale sequencing and reporting efforts. Flexibility in performing other types of sequencing approaches should be described as well to support possible protocol changes as decided by the SC during the first year Applicants should describe in detail their College of American Pathologists (CAP)-accredited and/or CLIA-certified processes for exome sequence generation, including the facilities and instrumentation to be utilized for sequencing. To enhance the excellence and inclusivity of the research environment, applicants are strongly encouraged to assemble a study team that is richly diverse and provide full opportunity and participation to individuals and groups underrepresented in the genomic workforce.

Applicants should also describe their approach to development of the SC criteria for selecting the 1-4 additional conditions to be screened, the selection of genes/variants to be tested and returned, the referrals to be made (tailored to local settings as needed), the follow-up data to be collected. They should also describe their plans for involvement, if any, in community engagement about the design, conduct, and evaluation of the screening program, distinguishing aspects that may need to be adapted for specific communities from those that can be applied more generally. Applicants should document their willingness to participate actively and collaboratively in protocol development through the SC and its working groups and commit to implementing the approved study protocols.

Applicants should document their ability to support the CGs and CC in designing and managing the logistical aspects of clinical testing such as sample collection, storage, shipping, receipt, tracking, and reporting, as well as participating as needed in development of protocols for sample collection, transmittal, and reporting for the Network. Applicants should also describe how they will meet the 4-week or shorter timeline from sample receipt to clinical reporting to PCPs and patients and document their ability to meet these timelines. They should propose approaches for shortening the turnaround time even further during the course of the study and simplifying the clinical workflow to minimize burden on PCPs and facilitate implementation. If this timeline is deemed unattainable or suboptimal by the applicant, the applicant should propose a feasible timeline that meets the goals of the study based on their sequencing capacity and turnaround time. Applicants should also include in their research strategy their current yearly sequencing capacity and how that would accommodate the timeline and volume of sequencing described in this NOFO. Applicants should also describe and discuss their approach to sample processing and how they plan to run their pipeline to accommodate samples from this study (e.g., batch processing etc.) in the context of the study timeline. Capability for developing, improving, and integrating new variant discovery approaches, methods, and technologies that lead to improved data quality, efficiency, and costs should be described.

Applicants must be prepared to discuss the possible need for an Investigational Device Exemption (IDE) with their current IRB and document the outcome of those discussions, and to subsequently engage in pre-submission discussions with the FDA if the IRB determines they are needed. These typically involve submission of actual study protocols, including the entire genomic testing pipeline from sample preparation to return of results; these aspects will need to be described Network-wide http://www.genome.gov/27561291.

Applicants should describe their plans to support collaborative research and interaction with other Network members and provide evidence of their capability to participate and interact effectively in cooperative, multi-site research. They should document their willingness and ability to adhere to network-wide policies and procedures as well as network-defined timelines for the key SeqC functions described under “Research Strategy” above. Applicants should also describe plans for, and willingness to abide by, Memoranda of Understanding or other sharing agreements potentially needed for data and sample sharing within the Network. Plans to establish and share a framework of best practices and lessons learned from this study should be described to ensure equitable and sustainable implementation of Tier 1 conditions in the future as well as creating the foundation for the implementation of additional conditions.

Multiple PD/PI Leadership Plan, Consortium/Contractual Arrangements

Applicants should explain how the PD(s)/PI(s) and senior/key personnel’s experience and expertise in designing, implementing, analyzing and disseminating research on population screening using genomics; generating, analyzing, and reporting genomic sequence data; and integration of genomic results into the CDS and EHRs, as well as experience with limited resource sites without EHR/CDS), will be used to accomplish the aims of the study. Past experience with genomic medicine implementation in diverse clinical settings should be highlighted, including experience and expertise in developing and implementing population screening using genomics including conducting sample collection and storage in a CLIA-compliant manner and disclosing genomic results in clinical care. Prior experience(s) working in multi-site research networks to meet individual study and collaborative goals should also be highlighted. Applicants should describe their established research program in the scientific areas of interest, appropriate expertise, ability to carry out implementation study protocols, a track record of successful collaborative research, and demonstrated access to appropriate infrastructure and technology to accomplish their portion of the proposed protocol.

Letters of Support: Letters of institutional and departmental support for participation in the Network should be included in the application. The letters of support should demonstrate willingness to participate in the study and in a single IRB for multi-site research.

External Scientific Panel (ESP)

Meetings with the ESP will focus on data related to the progress and quality of study conduct, such as accrual progress, timeliness of data submission, study withdrawals, adherence to assigned treatment, site-specific issues, and any emerging problems related to study conduct. In these meetings, the ESP should be notified of all major changes to the protocol or to study conduct planned or implemented by the Network.

Estimated timeline

During the first year of the program, the SC will work together to develop network-wide protocols for key aspects of the program as described above. Year 2 of the program will be devoted to the recruitment of participants, the collection of baseline data and the collection of biospecimens to be submitted to the SeqC for data generation using the agreed-upon approaches from year 1. Return of results to the PCPs from the SeqC is expected no later than 1 month from collection of the biospecimen, and to the patient by the PCP no later than 1 month after the PCP receives it from the SeqC, with shorter timeframes for both components strongly preferred. Follow-up for outcomes collection will occur during years 3 and 4 during regular clinical care, with all patients to have a minimum of 24 months’ follow-up from their receipt of results and recommendations. During years 2-4, all awardees will also be expected to participate in and contribute intellectually to network-wide data monitoring and analysis plan. Data analysis, publication and dissemination of data and methods will occur in year 5.

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

Other Plan(s): 

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

To assist in improving data sustainability and utility, applicants are encouraged to align the development of their data sets using the Findable, Accessible, Interoperable, Reproducible (FAIR) Guiding Principles (https://www.nature.com/articles/sdata201618). Per NOT-HG-21-022, NHGRI expects applications awarded under this NOFO to share comprehensive metadata and phenotypic, clinical, and environmental exposure data associated with the study; use standardized data collection protocols and survey instruments for capturing data, as appropriate; and use standardized notation for metadata (e.g., controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses.

To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community for research use, through submission of all data to the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL), through submission of variant interpretations to ClinVar, and through publication in the scientific literature. Although NHGRI expects project datasets and human variant information from studies selected through this NOFO to be made available through AnVIL and ClinVar, data can be shared in additional appropriate resources to enhance dissemination.

Applicants are encouraged to get feedback from the communities in which the research will be performed regarding plans for sharing individual level data resulting from the research projects with the scientific community for research purposes. Feedback and recommendations for data access, protection of participant and patient privacy and confidentiality, and management of health information should be integrated into the Data Management and Sharing Plan. Note that any project receiving NIH funding that collects or uses identifiable, sensitive information is automatically deemed issued a Certificate of Confidentiality (CoC).

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

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the NHGRI Scientific Review Branch and responsiveness by NHGRI program at 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 FON and title, PD/PI name, and title of the application.

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

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular NOFO, 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.

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

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group convened by NHGRI, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned 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 NHGRI Advisory Council. 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.
• Flexibility to adapt to the Network’s decision on how to implement sequencing of the 20,000 participants.
• Yearly sequencing capacity sufficient to meet the goals of the study.
• Compliance with data management and sharing policies.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

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 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, designing, and adapting protocols, setting project milestones, and conducting the Network study.
• Participating in group activities, including a study-wide SC.
• Implementing SC recommendations for protocol implementation, data collection, and standardization at the Clinical Sites involved in the relevant protocols.
• Providing protocols, reports and data to the CC, CGs, and NHGRI in a timely fashion as agreed upon by the SC.
• Cooperating with other recipients in the timely publication and dissemination of the results of the study and the eventual release to the scientific community of methods, tools, and results, and other resources.
• Abiding by common definitions, protocols, procedures, etc. as chosen by majority vote of the SC.
• Sharing results according to the Data Management and Sharing Policy as well as the NIH Genomic Data Sharing Policy, and any other data sharing policy agreed to between the NIH and the applicant.
• Adhering to policies regarding data access, publication, and intellectual property established by NIH and the SC for this program.
• Not disclosing confidential information obtained from other members of the program.
• Notifying the Project Scientist(s) of all major interactions with another member of the SC related to the Network.
• Submitting periodic progress reports in a standard format, as agreed upon by the SC and External Scientific Panel.
• Attending and participating in SC meetings and accepting and implementing study protocols, as appropriate.
• Abiding by relevant policies, including, but not limited to:
• Data Management and Sharing Policy: https://sharing.nih.gov/data-management-and-sharing-policy
• NIH Genomic Data Sharing policy:  https://www.genome.gov/about-nhgri/Policies-Guidance/Data-Sharing-Policies-and-Expectations ; https://grants.nih.gov/grants/guide/notice-files/not-od-14-124.html
• Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the NIH Genomic Data Sharing (GDS) Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-086.html )
• Notice on Clarifying NIH Priorities for Health Economics Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-025.html )
• Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-094.html)
• FDA policy on Investigational Device Exemptions (IDE): http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government 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(s) are scientists of the NHGRI who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff 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.  They and/or other NHGRI scientists may serve on additional committees, when appropriate. The NHGRI Project Scientist (and other NHGRI program staff) may work with recipients on issues coming before the SC and, as appropriate, other committees (e.g., recruitment, implementation, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, data completeness and quality control monitoring, data analysis and interpretation, and preparation of publications). NHGRI Program staff, on behalf of the NHGRI, will have the same access, privileges, and responsibilities regarding the collaborative data as the other members of the SC.

The NHGRI reserves the right to phase out this program (or an individual award) in the event of (1) failure to develop or implement mutually agreed upon a collaborative protocol; (2) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (3) major breach of a protocol or substantive changes in the agreed-upon protocol with which NHGRI cannot concur; or (4) human subject ethical issues that may dictate an early phase out of the program.

Annual continuation and level of funding for the CG will be based on NHGRI review of actual recruitment, data completeness and quality, and overall performance, determined as part of the NHGRI review of the annual non-competing continuation grant progress reports submitted by recipients.

The NHGRI reserves the right to modify or phase out the Network based on feasibility of achieving Network goals as determined by recommendations, generated during the periodic reviews, from external experts and NHGRI staff.

In the event of an early phase out of a program, the Network recipients should transfer all project datasets (phenotypic, environmental, covariate, process data, and outcome measures, etc.), associated genomic data, and resources (study protocols, informed consent form templates, results report templates, bioinformatic tools, etc.) collected or developed before the study and/or program was stopped as directed by NHGRI.

The Project Scientist(s) will have the following substantial involvement:

• Participating with the other SC members in the group process of setting research priorities and contributing to the adaptation of research protocols to be implemented Network-wide. 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 and as an information resource for the awardees about genome research activities. The Project Scientist(s) will also coordinate the efforts of the program with other groups conducting similar studies.
• Attending all SC 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.
• Reporting periodically on the progress of the program to the Director of NHGRI, as appropriate, and to the National Advisory Council for Human Genome Research, as appropriate.
• Retaining the option to recommend the withholding or reduction of support from any project that fails to achieve its goals or comply with the Terms and Conditions of award.
• Serving on subcommittees of the SC, as appropriate.
• Serving as a liaison between the SC and the ESP, serving as the Executive Secretary of the ESP, and arranging for timely preparation and distribution of minutes from the closed session.
• Serving as a liaison between the SC and other federal agencies such as the Food and Drug Administration (FDA) or the Centers for Disease Control and Prevention (CDC).
• 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.
• Participating in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the program.
• Other NHGRI staff may assist the recipients, as designated by the Program Official.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.  If the Program Director will dually serve as the Project Scientist, the responsibility for final decision-making will be determined by Institute/Center leadership and may reside with senior management, separate organizational components, and/or oversight committees. Because it is anticipated that the Program Official may participate in activities that rise to a level of involvement (i.e., additional role as Project Scientist) that may result in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NIH Program management staff will provide oversight and manage the conflict accordingly.

Areas of Joint Responsibility include:

• The SC will serve as the main scientific body of the program. The SC will be responsible for coordinating the activities being conducted by the program. The SC membership will include one NHGRI Project Scientist, one Project Scientist from component NIH Institute/Centers (ICs) funding an award, and the PD/PI from each awarded cooperative agreement from this and accompanying NOFOs. The SC may add additional members, and other government staff may attend the SC 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.  The Project Scientist(s) will participate as a member of the Steering Committee and will have one vote.
• Recipients agree to the governance of the study through a SC. The lead investigator(s) from each CG, SeqC and the CC and an NHGRI representative will comprise the SC. All major scientific decisions will be determined by majority vote of the SC. Each CG, the SeqC, and the CC will have one vote. NIH is responsible for organizing and providing overall support and management for the Consortium. 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. Note that each CG, SeqC and the CC will have one vote, even if there are multiple PD(s)/PI(s). If the CGs, the SeqC or CC choose to utilize the multi-PD/PI mechanism, all the PDs/PIs are expected to participate in all SC meetings and teleconferences; however, each CG still has only one vote. It is anticipated that SC meetings will be held up to twice a month by conference call and 4 times per year for the first year in person, shifting to 3 times a year in person for years 2-5.
• An independent External Scientific Panel (ESP) will be appointed by the Director, NHGRI, to provide overall monitoring of study performance, interim data, and safety issues. An NHGRI scientist will serve as Executive Secretary to the ESP.
• Members of the SC will be required to accept and implement policies approved by the SC.
• To address particular issues, the SC may establish Working Groups as needed, which will include representatives from the program and the NIH and possibly other experts.

External Scientific Panel (ESP).

The ESP will be composed of senior scientists with expertise relevant to the study implemented in the program. They will meet at least twice per year, once per year in person and once by telephone conference. At least once per year, there will be a joint meeting with the SC to allow the members of the ESP and the SC to interact directly. Twice per year the ESP will assess the progress and data integrity, of the study and make recommendations to the Network about changes, if any.

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

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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

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

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

Simona Volpi, PhD
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-3480
Email: [email protected]

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

Natalie Linear
National Human Genome Research Institute (NHGRI)
Telephone: 301-827-0611
Email: [email protected]

Section VIII. Other Information

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

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