Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

National Institute of Environmental Health Sciences (NIEHS)

National Cancer Institute (NCI)

Funding Opportunity Title
Multi-Omics for Health and Disease - Disease Study Sites (U01 Clinical Trial Optional)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

October 18, 2022 - Notice of Frequently Asked Questions (FAQs) for Multi-Omics for Health and Disease RFA-HG-22-008, RFA-HG-22-009, RFA-HG-22-010. See Notice NOT-HG-23-011.

October 12, 2022 - Notice of Change in the Number of Disease Study Sites (DSSs) in RFA-HG-22-010 Multi-Omics for Health and Disease - Data Analysis and Coordination Center (U01 Clinical Trial Not Allowed). See Notice NOT-HG-23-008.

October 12, 2022 - Notice of Change in the Number of Disease Study Sites (DSSs) in RFA-HG-22-009 “Multi-Omics for Health and Disease - 'Omics Production Centers (U01 Clinical Trial Not Allowed)” . See Notice NOT-HG-23-007.

October 12, 2022 - Notice of Change in the Number of Disease Study Sites (DSSs) in RFA-HG-22-008 “Multi-Omics for Health and Disease - Disease Study Sites (U01 Clinical Trial Optional)” . See Notice NOT-HG-23-006.

September 12, 2022 - Notice of Pre-Application Webinar for Multi-Omics for Health and Disease (RFA-HG-22-008; RFA-HG-22-009; and RFA-HG-22-010). See Notice NOT-HG-22-034.
RFA-HG-22-009 - Multi-Omics for Health and Disease - 'Omics Production Centers (U01 Clinical Trial Not Allowed)

RFA-HG-22-010 - Multi-Omics for Health and Disease - Data Analysis and Coordination Center (U01 Clinical Trial Not Allowed)

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-HG-22-008
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.172, 93.396, 93.399, 93.113
Funding Opportunity Purpose

The goal of this Funding Opportunity Announcement (FOA) is to establish Disease Study Sites (DSS) that will be part of a collaborative initiative to advance the application of multi-omic technologies to study health and disease in ancestrally diverse populations.. Together with the ‘Omics Production Centers (RFA-HG-22-009) and the Data Analysis and Coordination Center (RFA-HG-22-010), the Disease Study Sites will leverage clinical conditions where multi-omic approaches are expected to be most informative to:

1) explore the use of multi-omics, integrated with phenotypic and environmental exposure data, including social determinants of health (SDOH), to detect and assess molecular “profiles” associated with healthy and disease states;

2) develop generalizable data harmonization, integration, and analysis methods, as well as best practices and standards for the optimal application of multi-omics; and

3) create a multi-dimensional dataset that is available to the research community.

Each DSS will be primarily responsible for proposing a study design focused on a disease area for which integrative multi-omics could be used to define associations with healthy and disease states and to detect changes to associations and molecular profiles over time. Each DSS will also be responsible for utilizing effective strategies to enroll and consent participants (of which a minimum of 75% should be from self-identified racial and ethnic communities expected to have genetic ancestries currently underrepresented in genomic research) collecting phenotypic and environmental exposure data, collecting samples and measures at a minimum of three time points, and contributing to consortium-wide protocol development, data analysis, methods development, and the production of the multi-dimensional dataset.

While this program may provide some insights into disease etiology, its primary goal is to validate and enhance generalizable multi-omic approaches to identify meaningful biological changes related to health and disease.

Key Dates

Posted Date
September 07, 2022
Open Date (Earliest Submission Date)
October 18, 2022
Letter of Intent Due Date(s)

October 18, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 18, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

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.

Expiration Date
November 19, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

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

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

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA), RFA-HG-22-008, invites applications to participate as Disease Study Sites (DSS) in the Multi-Omics for Health and Disease Consortium. In collaboration with up to 2 ‘Omics Production Centers (OPC, RFA-HG-22-009) and a Data Analysis and Coordination Center (DACC, RFA-HG-22-010), the Consortium will aim to advance the application of multi-omic technologies to study health and disease in ancestrally diverse populations. By leveraging clinical conditions where multi-omic approaches are expected to be most informative, this Consortium will:

1) explore the use of multi-omics, integrated with phenotypic and environmental exposure data, including social determinants of health (SDOH), to detect and assess molecular “profiles” associated with healthy and disease states;

2) leverage these association studies to develop generalizable data harmonization, integration, and analysis methods, as well as best practices and standards for the optimal application of multi-omics; and

3) create a multi-dimensional dataset that is available to the research community.

While this program may provide some insights into disease etiology, its primary goal is to validate and enhance generalizable multi-omic approaches to identify meaningful biological changes related to health or disease.

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

  • “Ancestrally diverse populations” refers to study populations with a diversity of genetic ancestries, with a focus on individuals expected to have genetic ancestries currently understudied in genomic research.
  • “Community engagement”, as defined by the National Institutes of Health Director’s Council of Public Representatives, refers to a process of inclusive participation that supports mutual respect of values, strategies, and actions.
  • “Consortium” refers to the Multi-Omics in Health and Disease Consortium comprising the grants to be funded under this FOA and RFA-HG-22-009 and RFA-HG-22-010, unless otherwise indicated.
  • “Environmental exposure data” refers to any information collected or used in the project related to a person’s exposures to chemical, biological, or physical substances found in air, water, food, or soil, and the SDOH relevant to the understanding and promotion of an individual’s health.
  • “Genetic Ancestry”, as noted by as noted by Peterson et al. 2019, refers to estimates from DNA that provide information about shared demographic history at the population level.
  • “High throughput technologies” refers to technologies, often involving large-scale assays and automation, that allow the accurate and simultaneous analysis of large quantities of molecules, such as genes, proteins, and metabolites.
  • “Molecular profile” refers to a characteristic pattern of multi-omic data associated with a healthy or disease state or condition.
  • “Multi-omics” refers to a systems biology investigative approach involving multiple ‘omics data types, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics.
  • “Phenotypic information” refers to a participant's non-genetic information such as demographic information, personal medical history, family health history, and physical and laboratory measurements.
  • “Social determinants of health (SDOH)” refers to the conditions in the environments where people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks.

Background and Objectives

Expansions in high-throughput technologies have increased access to molecular (or ‘omic) data generated from distinct components of a biological network, such as genomic, epigenomic, transcriptomic, proteomic, and metabolomic measures. While single ‘omic analyses have produced valuable insights, recent studies have shown that integrative (or multi-omic) analysis approaches can improve the classification of disease into clinically relevant subgroups and potentially identify biomarkers of health or predictors of disease progression. Multi-omic analyses can also help define relationships among ‘omic data types to unravel biological networks regulating transitions from health to disease.

Despite some successes by NIH-funded programs in producing large multi-omics datasets, critical gaps prevent the routine application of multi-omics to disease studies. Production and standardization of multiple data types from the same sample remain key challenges, including inter- and intra- ‘ome variability, non-uniform content across platforms and assays, and lack of consensus regarding quality assessment approaches and practices to account for missing data (e.g., imputation). Computational methods remain underdeveloped to integrate, analyze, and interpret 1) multiple ‘omes from the same sample, 2) multi-omic data combined with phenotypic and environmental exposure data, and 3) multi-modal data across ancestrally diverse populations. Importantly, lack of prospective data collections adhering to agreed-upon data standards has limited the number of widely available multi-omic datasets that have both well-described and harmonized metadata and multiple types of ‘omic data.

In June 2021, the NHGRI virtually hosted a workshop entitled “Multi-omics in Health and Disease: Current Applications, Challenges and Future Directions” to understand the state of the field of multi-omics and to gather recommendations on a research strategy using multi-omics that is in line with the objectives in the NHGRI 2020 Strategic Vision and reflected in this FOA.

This FOA, together with RFA-HG-22-009 and RFA-HG-22-010, will support a Consortium to implement multi-omics technologies to study health and disease in ancestrally diverse populations. The primary objectives of the Consortium are:

  1. Examine the use of multiple ‘omics data, combined with phenotypic and environmental exposure data, to detect and assess molecular “profiles” associated with healthy and diseased states as well as transitions from health to disease or vice versa. Through the establishment of working groups, all sites and centers are expected to work collaboratively to perform data integration and analysis deploying computational modeling and machine learning, interpret molecular “profile” associations, explore gene networks, and assess potential causal relationships.
  2. Leverage this collaborative analysis to develop generalizable data harmonization, integration, and analysis methods, as well as best practices and standards for the optimal application of multi-omics technologies across clinical conditions.
  3. Make use of the data generated by the Consortium to create a standardized and harmonized multi-dimensional data set that is widely available to the broader research community, is interoperable with existing resources, and upholds data sharing and privacy principles. This rich data set will include 1) persons from ancestrally diverse populations; 2) persons with and without specific diseases; 3) harmonized and standardized phenotypic and environmental exposure data; 4) harmonized and standardized data for all or most ‘omes for each biosample; 5) data from multiple time points; and 6) associated meta-data to facilitate links across data types.

This FOA solicits applications to establish 6 DSSs. RFA-HG-22-009 and RFA-HG-22-010 will establish the OPC(s) and the DACC, respectively.

Each DSS (this FOA) will be primarily responsible for:

  1. Designing a study focused on a clinical condition for which integrative multi-omics could be useful in defining associations with healthy and disease states and in detecting changes to associations and molecular profiles over time.
  2. Establishing effective outreach, engagement, education, recruitment, and retention strategies to maximize participation among groups most severely impacted by the proposed disease and understudied in genomic research pertaining to that disease.
  3. Enrolling 300 participants, approximately 200 with disease and 100 without disease, consented for: a) collection of multiple ‘omic, phenotypic, and environmental exposure measures at multiple time points; b) future research use; and c) broad data sharing.
  4. Enrolling a minimum of 75% individuals from self-identified racial and ethnic communities expected to have genetic ancestries currently underrepresented in genomic research, consented as noted above.
  5. Collecting phenotypic and environmental exposure data (as defined above).
  6. Collecting samples and measures at a minimum of three time points; for example, at baseline (study entry) and during exacerbation, remission, subsequent disease stages, or treatment.
  7. Submitting biosamples to the OPCs for data production.
  8. Contributing to Consortium-wide protocol development, data analysis, and methods development efforts.
  9. Working with the DACC to standardize and harmonize participant 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.

The OPC(s) (RFA-HG-22-009) will be primarily responsible for:

  1. Using high-throughput molecular assays to produce ‘omics data from biosamples (including tissues and cells, as needed) provided by participants enrolled and collected by the DSSs.
  2. Producing a minimum of three data types from the following: 1) genomics (WGS); 2) epigenomics (methylation arrays, ATAC-Seq, or ChIP-Seq); 3) transcriptomics (bulk RNA-Seq); 4) proteomics (targeted or untargeted, mass-spectrometry (MS), SOMAmer); and 5) metabolomics (targeted or untargeted, NMR spectroscopy, GC-MS, LC-MS). If producing fewer than five ‘omic data types, at least one should be genomics and one should be non-nucleic acid-based (proteomics, metabolomics, etc.).
  3. Receiving biosamples from the DSSs for data production and providing secure and accessible storage for them for the duration of the program.
  4. Contributing to Consortium-wide protocol development, data analysis and methods development efforts.
  5. Working with the DACC to standardize and harmonize ‘omic 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.

The DACC (RFA-HG-22-010) will be primarily responsible for:

  1. Coordinating, and contributing to, Consortium-wide protocol development, data analysis, and methods development.
  2. Managing and securing Consortium data.
  3. Creating a multi-dimensional dataset that is available to the broader research community and a portal for visualization.
  4. Coordinating Consortium logistics.
  5. Coordinating outreach and dissemination of findings.

Research Approach

Through a prospective study design and collaborative collection and analysis of multiple ‘omic, phenotypic, and environmental exposure data in conditions where distinct stages, transitions, or responses to treatment can be defined and evaluated, the Multi-Omics for Health and Disease Consortium is expected to produce consensus approaches, best practices, and standards that can be generalized across diseases and populations. It will also generate a standardized and harmonized dataset for general research use available through controlled-access processes and a portal for visualization.

Each DSS funded under this FOA will focus on a clinical condition for which integrative multi-omics could be useful in defining associations with healthy and disease states and in detecting changes to associations and molecular profiles over time; for example, relapsing diseases with difficult-to-predict exacerbations and remissions, or diseases with distinct stages, transitions, or responses to treatment.

This FOA is intended to support ‘omics research across a broad range of dissimilar conditions, enabling a focus on ‘omic methods, standards, and practices in common amongst them and potentially most generalizable to other conditions.To ensure programmatic balance,only one scientifically meritorious application in a particular disease area is likely to be considered for funding. In addition, due to significant research already in progress on ‘omics of tumors, DSS proposing investigations of tumor samples only will be considered non-responsive under this FOA. DSS examining conditions with substantial ongoing work on multi-omics approaches supported by NIH Institutes and Centers, or other publicly available resources will be considered a low priority for funding from NHGRI under this FOA. DSS proposing diseases with the highest likelihood of providing new insights into ‘omic associations will be given highest priority for funding under this FOA.

Each site will work collaboratively with the OPC(s) and the DACC to: 1) integrate multiple data types including ‘omic, phenotypic, and environmental exposure data; 2) define molecular profiles; 3) assess associations with healthy or disease states; 4) detect patterns of change in profiles and associations; 5) identify genetic variants, genes, and gene networks involved in disease transitions, and determine how those networks are impacted by phenotypic and environmental information; and 6) explore potentially causal relationships that lead to changes in health status.

While this this collaborative analytical effort may provide some insights into disease etiology, the primary goal is to validate and enhance generalizable multi-omics-based approaches, not to define the pathobiology or predict the course of a particular disease. This FOA, therefore, expects each DSS, together with the other Consortium components, to leverage the study design to develop methods, best practices, and standards to integrate and analyze ‘omics, phenotypic, and environmental exposure data to identify meaningful biological changes related to health and disease.

Each DSS will propose technological and computational analytical protocols for their study, as noted above; however, data analysis will be a cross-Consortium activity. Biosamples to be collected and ‘omic technologies to be applied must thus be developed iteratively and collaboratively across the DSSs and OPC(s), considering, where possible, the unique characteristics of each disease and the capabilities and budget constraints of the OPC(s). Similarly, computational and statistical analyses will be developed iteratively across the DSSs, the OPC(s), and the DACC to maximize applicability to each disease and ‘omic technology under study.

Consortium-wide data analyses will be performed using the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL) cloud-based ecosystem. The AnVIL is a scalable and interoperable platform established by NHGRI to reduce barriers for collaboration by leveraging a cloud-based infrastructure for democratizing genomic data access and sharing, and for securely computing across large genomic related datasets. Using the AnVIL platform will facilitate the collaborative development and optimization of methods and the establishment, by consensus, of best practices and standards for the application of multi-omics to study health and disease in ancestrally diverse populations. Demonstration of the generalizability of these methods across different diseases and populations is expected.

To facilitate this collaborative analysis approach, the Consortium will devote the first year to developing network-wide protocols for the following key aspects of the work of the Consortium: 1) the community engagement plan, 2) the recruitment strategy including the characteristics of participants and the consent language, 3) the plan for defining, measuring, and collecting core phenotypic and environmental exposure measures and ensuring appropriate quality assurance and quality control, 4) the biospecimen procurement and processing approaches, 5) the types of ‘omics assays, 6) the data analysis methods, 7) common data models, and 8) the plan for utilizing the AnVIL platform to share data and tools among the Consortium and broader research community including through open and controlled access processes.

Each DSS will be responsible for the enrollment of 200 participants with disease. In addition, each DSS will enroll 100 generally healthy participants free of that disease or condition to be contributed to a pooled, Consortium-wide healthy comparator group. Participants free of that disease should be similar in key demographics and exposures to the participants with disease. The comparator group will facilitate the assessment of the generalizability of each DSS’s proposed analyses, provide opportunities for standardization and quality control, produce a unique dataset of participants free of disease for analysis, and allow for comparisons with individual disease groups.

To facilitate analysis and data sharing, participant phenotypes and environmental exposures, as relevant to the disease under study, will be clearly defined and collected using standard measures when available (e.g., PhenX Toolkit). All phenotypic and environmental exposure data, as defined above, will be collected by the DSSs. With assistance from the DACC, all data will be standardized and harmonized according to agreed-upon data standards and submitted to the AnVIL to be cataloged, maintained, and made accessible as controlled-access data. The DSSs will work with the DACC and the OPC(s) to define both the process and the standards for these submissions, utilizing widely available protocols such those validated within the Electronic Medical Records and Genomics (eMERGE) Network (i.e. PheKB), the PhenX Toolkit, and the AnVIL data model, when appropriate. These standards will enable submissions and integration with processes and pipelines employed at the sites and center(s). The biosamples collected by the DSS will be submitted to the OPC(s) for processing, production of ‘omics data types, and storage for the duration of the program.

Each proposed study should be well-suited to detect aspects of disease progression within the 5-year period of this program; for example, change in status from healthy to disease or transitions across stages of a disease. As such, recurring assessments of all participants will be conducted, with measures collected at a minimum of three timepoints; for example, at baseline (study entry) and during exacerbation, remission, subsequent disease stages, or treatment. If suitable for the disease under study, collection of tissue and/or biopsy samples may be appropriate, in addition to sample sources obtained by less invasive methods such as blood, urine, or saliva.

As highlighted by Popejoy et al., racial and ethnic minority populations have been massively understudied in genomic research to date. A robust body of research has identified the scientific, ethical, and social challenges presented by the overrepresentation of European ancestry groups in genomic research, some of which include undiscovered genetic variation, inaccurate risk prediction tools, and inequity in the distribution of benefits from research. Understanding and applying the vastness of human genetic variation for clinical diagnosis, prevention, and treatment requires capturing this variation and its disease consequences across multiple racial and ethnic groups, which will improve genomic interpretation and application across all population subgroups, even those not previously understudied in research.

The Multi-Omics for Health and Disease Consortium will solicit DSSs (RFA HG-22-008) enrolling a minimum of 75% of individuals from self-identified racial and/or ethnic communities expected to have genetic ancestries currently understudied in genomic research. This 3:1 proportion of racial and ethnic minority populations to non-minority populations provides greater statistical power and allows for exploratory subgroup analyses. It will also provide stable frequency and effect size estimates by site among adequately represented racial and ethnic participants for comparison to understudied participants.

Based on experience with other NHGRI-funded initiatives, such as eMERGE and the Clinical Sequencing Evidence-Generating Research (CSER) Consortium, the 75% threshold is achievable, should not place undue constraints on the ability of the DSSs to recruit participants for their studies, and helps ensure adequate statistical power for comparative analyses at the population level.

This program will utilize recruitment, retention, and meaningful community engagement strategies emphasizing outreach to racial and ethnic minority communities in the United States. This will maximize benefits from participation by enhancing the relevance of research findings to these communities, creating space for community input throughout the program, potentially increasing trust in the research enterprise, and ensuring that research findings are translated and disseminated, as appropriate, to participant communities. Informed consent for broad data sharing and for the collection of multiple ‘omic, phenotypic, and environmental exposure measures at multiple time points will be needed for each 'omics study participant. Re-consent of individuals participating in existing longitudinal studies for prospective data collection and sharing may be considered with a clear description of how they meet the requirements for this program, particularly the need for collection of new samples conforming to Consortium-wide protocols that are yet to be developed.

The 2020 NHGRI strategic vision  emphasizes that the promise of genomics can’t be fully realized without a diverse genomics workforce; diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. As noted in NIH’s Noice of Interest in Diversity (NOT-OD-20-031), scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Therefore, applicants should strive to compose teams richly diverse in backgrounds and academic disciplines, and provide full opportunity and participation to individuals and groups underrepresented in the genomic workforce.

National Institute of Environmental Health Sciences (NIEHS) Interests:

  • NIEHS is interested in the incorporation of multi-dimensional exposure data with other omics data to inform mechanistic understanding of diseases and health outcomes particularly where exacerbation or progression of disease is impacted by environmental exposures. Examples of exposures of interest include, but are not limited to, air pollution, extreme weather/climate, pesticides, metals, and other chemical stressors and biologically derived toxins. NIEHS will prioritize applications with innovative methods and approaches for integrating various types of environmental data (including location-based data, personal monitoring, biomonitoring, and validated questionnaires, etc.) with other omics data. Applications that will inform how the dynamic interactions between environmental exposures and molecular networks drive health and disease outcomes (particularly in preexisting disease conditions, in underserved populations, and during potential windows of susceptibility) is strongly desired.
  • NIEHS is interested in establishing effective and authentic outreach and engagement with communities adversely affected by environmental exposures. Additionally, applications should discuss retention strategies to maximize involvement of study participants from understudied and underserved groups disproportionately affected by environmental exposures. NIEHS encourages applications that explore environmental health disparities and environmental justice issues by incorporating measures of social determinants of health into the analysis of study populations.
  • Applicant research and study teams are encouraged to be diverse to include individuals from a wide range of underrepresented groups in science, geographic locations, scientific expertise areas, as well as stage of career growth.
  • NIEHS is interested in applications that promote harmonization and integration of complex environmental health data with other multi-omics and phenotypic data. NIEHS will prioritize applications that facilitate cross-platform interoperability through activities that extend existing omics data models, data platforms, workflows, and community-based data standards to include environmental health data and concepts.

 

National Cancer Institute (NCI) Interests:

  • NCI is interested in supporting a disease study site focused on cancer. Studies collecting both tumor and normal tissues from cancer cases are strongly encouraged and will be prioritized for funding.

Program Formation and Governance

This FOA uses the Cooperative Agreement mechanism. Successful applicants will become members of the Multi-Omics for Health and Disease Consortium composed of investigators who have been funded in response to one of the three related FOAs. Recipients are expected to work collaboratively with all members of the Consortium towards meeting Consortium goals, in addition to the research goals outlined in their individual applications. Close interaction among recipients and the NIH will be required to develop appropriate strategies and tools to carry out this program. A kickoff meeting for the Consortium will take place soon after awards are made to officially start the program’s activities and to establish the Steering Committee. As noted above, a major focus of the first year will be to set network-wide goals, including 1) the community engagement plan, 2) the recruitment strategy including the characteristics of participants and the consent language, 3) the plan for defining, measuring, and collecting core phenotypic and environmental exposure measures and ensuring appropriate quality assurance and quality control, 4) the biospecimen procurement and processing approaches, 5) the types of ‘omics assays, 6) the data analysis methods, 7) common data models, and 8) the plan for utilizing the AnVIL platform to share data and tools among the Consortium and broader research community including through open and controlled access processes.

NIH

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.

Steering Committee

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

External Input to the Network

The Multi-Omics for Health and Disease Consortium will have an External Scientific Panel (ESP). The ESP will provide input on performance, priorities, and overall progress. The ESP will consist of experts in a broad range of subjects, including biostatistics, clinical coordination, community engagement (in particular with populations understudied in genomic research), data science, environmental exposures, epidemiology, multi-omic technologies, population genetics, and other areas as needed. An NHGRI Project Scientist will serve as the Executive Secretary to the ESP. The ESP will meet semi-annually (one conference call and one in-person meeting per year), in conjunction with Steering Committee meetings, as appropriate. Following each meeting, the ESP will submit recommendations for a report for PD(s)/PI(s). The Consortium SC members will receive and consider the ESP’s comments and will provide a written response to the recommendations.

Data Sharing

NHGRI recognizes that data sharing is essential to advance genomic research and will expect recipients to comply with the NIH Genomic Data Sharing Policy. NHGRI supports the broadest appropriate genomic, phenotypic, and metadata data sharing with timely data release through widely accessible data repositories. Per NOT-HG-21-022, NHGRI expects applications awarded under this FOA 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. For more information on NHGRI’s genomic data sharing expectations, see the NHGRI’s Genomic Data Sharing Policy FAQs webpage.

NHGRI expects studies involving human data to use data generated from sources that can document explicit consent for future research use and broad data sharing. Consent language should avoid restrictions on the types of users who may access the data. Additional guidance on informed consent can be found in the NHGRI Informed Consent Resource.

To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community for research use, through submission of all data to the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL), through submission of variant interpretations to ClinVar, and through publication in the scientific literature. Data submitted to the AnVIL will be accessible by the scientific community upon review and approval of a data access request by the NHGRI Data Access Committee.

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

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 NIH Genomic Data Sharing (GDS) Policy allows investigators to perform genomic analyses on a cloud platform. The NIH security best practices and provisions 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 for managing and mediating any loss of data or compromise of data confidentiality.

Raw and processed data and metadata, protocols, software code and algorithms, tools, analyses, and methods derived from them, publications, and other products of the consortium are expected to be made available through the AnVIL; other public web sites, as relevant; and/or publication in the scientific literature.

After the initial review, NHGRI program staff will conduct an additional administrative review of the plan for sharing data and may negotiate modifications of the resource sharing plan with the prospective recipient. The final negotiated version of the resource sharing plan will become a term and condition of the award of the cooperative agreement and will be reviewed over the years of funding.

Estimated timeline

During the first year of the program, the DSSs, OPCs, and DACC will work together to develop network-wide protocols for key aspects of the work of the Consortium, such as 1) the community engagement plan, 2) the recruitment strategy including the characteristics of participants and the consent language, 3) the plan for defining, measuring, and collecting core phenotypic and environmental exposure measures and ensuring appropriate quality assurance and quality control, 4) the biospecimen procurement and processing approaches, 5) the types of ‘omics assays, 6) the data analysis methods, 7) common data models, and 8) the plan for utilizing the AnVIL platform to share data and tools among the Consortium and broader research community including through open and controlled access processes.

Year 2 of the program will be devoted to the recruitment of participants, the collection of baseline measures, including phenotypic and environmental exposure measures, and the collection of biosamples to be submitted to the OPCs for ‘omic data production using the agreed-upon approaches from year 1. Subsequent measures and biosamples will be collected during years 3 and 4, or as needed based on the disease under study, but no later than the end of year 4. During years 2-4, all recipients will also be expected to participate in and contribute intellectually to Consortium-wide data analysis, such as applying novel computational modeling and machine learning approaches, interpreting molecular “profile” associations, exploring gene networks, and assessing potentially causal relationships. During this time, the Consortium will work to develop generalizable methods, best practices, and standards that address data harmonization, integration, and analysis challenges and gaps. The Consortium will use the resulting data to create a standardized and harmonized multi-dimensional data set that is available to the research community and adheres to NIH genomic data sharing expectations. During year 5, the Consortium will finalize the analyses, methods development, and production of the final data set, and will focus on data and methods dissemination and publications.

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

Funding Instrument

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

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Funds Available and Anticipated Number of Awards

NHGRI intends to commit up to $3.2M in Total Costs, NIEHS intends to commit up to $900K in Total Costs, and NCI intends to commit up to $1.6M in Total Costs in FY2023 to fund up to 6 awards.

Award Budget

Future year awards will be limited to $500,000 Direct Costs per year in FYs 2024-2027.

Award Project Period

The project period for this FOA is 5 years (FY2023-FY2027).

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

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

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

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her 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 Notice of NIH’s Interest in Diversity, NOT-OD-20-031, see also, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. However, only one application from each applicant organization will be funded.

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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Joannella Morales, Ph.D.
Telephone: 301-480-3517
Email: joannella.morales@nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

Effective management of this center requires a significant commitment by the Program Director(s)/Principal Investigator(s). For an application proposing a single PD/PI, the PD/PI is expected to devote at least 2.4 person months annually to the project. If multi-PDs/PIs are proposed, the aggregate level of effort required is a minimum of 2.4 person months. In the MPI model, one PD/PI is expected to commit a minimum of 1.2 person months annually and the other(s) should devote sufficient time to serve his/her proposed role while maintaining the aggregate required level of effort.

DSS budgets should include the costs required for active Consortium participation, including regular teleconferences and meetings of the SC and its working groups. For budgeting purposes, applicants should budget for attendance of 4-5 investigators from each DSS at up to four SC meetings per year during year 1, 2 in person (2 days, 1-2 nights) and 2 virtual. In years 2-5, applicants should budget for up to 3 SC meetings per year, 1 in person and 2 virtual. DSS budgets should include personnel costs for twice monthly SC conference calls in the first year, and monthly conference calls in years 2-5.

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

For budgeting purposes, each DSS should assume it will be recruiting 300 participants. DSS budgets should include community engagement and patient-related clinical research costs (clinical costs that are not covered as part of a patient’s existing insurance coverage) such as additional tests, sample and data collection, supplies, etc. recommended by the study protocol.

Each DSS should budget for the management of biosamples, including ensuring sample stability, quality assessments, and quality control. Each DSS should also budget for costs associated with submitting the biosamples to the OPCs for ‘omics data production.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Applicants should describe and justify the proposed study design, clearly noting the value of, and rationale for, utilizing an integrative multi-omics approach for their disease of interest. Diseases proposed for the study should be characterized by frequent (1-2X/year) exacerbations or remissions, or distinct stages, transitions, or responses to treatment characterized by documented changes in one or more ‘omic measures; preference will be given to diseases affecting multiple and accessible ‘omic measures. Applicants should describe how and why their disease area has a high likelihood of providing new insights and demonstrate that substantial work on multi-omics approaches is not currently being funded by the NIH or other major research funders. Proposed diseases should be expected to be informative for ‘omic measures, methods, or approaches that are generalizable to other common conditions, but conditions proposed for study should be specific enough to produce an interpretable signal on multi-omic testing of a relatively small group of affected participants.

Applicants should describe how they will explore and address challenges related to data harmonization approaches, quality control, batch effects, computational and statistical methods to integrate and analyze multiple modalities, and the selection and analysis of multiple ‘omic data measures from the same sample. Applicants should describe approaches to integrate molecular and non-molecular data, such as environmental exposure data and social determinants of health. Applicants should demonstrate that the methods and approaches proposed are generalizable to ancestrally diverse populations. .

Applicants are expected to submit a comprehensive study design for a study aimed at: 1) integrating multiple data types including ‘omic, phenotypic, and environmental exposure data; 2) defining molecular profiles; 3) assessing associations with healthy or disease states; 4) detecting patterns of change in profiles and associations; 5) identifying genetic variants, genes, and gene networks involved in disease transitions; and 6) exploring potentially causal relationships that lead to changes in health status.

While each DSS will propose technological and computational analytical protocols for their study, as noted above, data analyses and methods development will be cross-Consortium activities. Applicants should describe how they propose to develop a cross-Consortium approach for biosamples to be collected and ‘omic technologies to be applied, considering, where possible, the unique characteristics of each disease and the capabilities and budget constraints of the OPC(s). They should also describe how they will develop a cross-Consortium approach to computational and statistical analyses with the OPC(s) and DCC to maximize applicability to each disease and ‘omic technology under study. It is expected that applicants will aim to innovate, refine, and utilize novel theoretical concepts, approaches, or instrumentation, as appropriate.

To facilitate this collaborative analysis approach, applicants should plan to focus their first year on developing network-wide protocols for the following key aspects of the work of the Consortium: 1) the community engagement plan, 2) the recruitment strategy including the characteristics of participants and the consent language, 3) the plan for defining, measuring, and collecting core phenotypic and environmental exposure measures and ensuring appropriate quality assurance and quality control, 4) the biospecimen procurement and processing approaches, 5) the types of ‘omics assays, 6) the data analysis methods, 7) common data models, and 8) the plan for sharing data and tools sharing across the Consortium on the AnVIL platform.

Applicants should develop a plan for collection of phenotypic, clinical, environmental exposure, including SDOH, from the participants enrolled in the program. Applicants should describe the measures they will use and provide the relevant rationale for their selection, including their relevance to the disease being studied. Applicants should utilize standard measures when available (e.g., PhenX Toolkit). Applicants should describe steps they will take to perform quality assessments and ensure quality control, as well as to ensure all the data conform to the agreed-upon data model. Applicants should describe data security measures and protection of patients' privacy and confidentiality consistent with requirements of the Health Insurance Portability and Accountability Act (HIPAA) and other applicable regulations. This should include precautions taken to ensure removal of personally identifying information (PII), prevention of inadvertent release of data, or identification of participating individuals or groups.

Applicants should describe their ability to recruit a cohort with the following characteristics:

  • Composed of 300 participants; approximately 200 participants with disease and 100 participants free of disease to be contributed to a pooled, Consortium-wide comparator group. Participants without disease should be similar in key demographics and exposures as the participants with disease.
  • Composed of a minimum of 75% individuals from self-identified racial and ethnic communities with genetic ancestries currently underrepresented in genomic research.
  • Recruited within year 2 of the program, to allow baseline analyses to begin and for follow-up measures to be completed in years 3 and 4. See “Estimated Timeline” mentioned above.
  • Consented for the prospective collection of broad and standardized phenotype and environmental exposure data (multiple measures per participant collected using standards, such as the PhenX Toolkit). If standard measures for the data of interest have yet to be defined, applicants should provide justification for such data and describe measures that will be implemented for its collection.
  • Consented for broad data sharing for ‘General Research Use’ as defined by NIH at https://osp.od.nih.gov/wp-content/uploads/standard_data_use_limitations.pdf.
  • Consented for follow-up and recurring assessments, with measures collected at a minimum of three time points, for example at baseline (study entry) and during exacerbation, remission, disease progression, or treatment. Clear description and scientific justification for the time points or events proposed to elicit repeated sampling, including their likelihood of capturing changes in ‘omic measures, should be provided.
  • If suitable for the disease under study, consented for tissue and/or biopsy sample collection, in addition to sample sources obtained by less invasive methods, such as blood, urine, or saliva.

Applicants should provide power calculations and justification for the number of participants with and without disease (while estimating the comparator group pooled, where appropriate, which would be up to 600 participants without disease across 6 DSSs), the range of effect sizes, the extent of multiple testing, the models to be tested, and the significance levels for testing, allowing for a justifiable rate of loss to follow-up. If the study design requires separate analysis of subject groups (e.g., phenotypic classes or ancestry groups) power analyses for each category should be provided.

All applicants are expected to establish recruitment, retention, and meaningful community engagement strategies, including outreach to racial and ethnic minority communities in the United States. A plan should be clearly articulated. Each DSS should describe plans and document its expertise in community engagement and recruitment strategies and methods and its ability to obtain informed consent for broad data sharing and for the collection of multiple ‘omic, phenotypic, and environmental exposure measures at multiple time points. Applicants proposing re-consent of individuals participating in existing longitudinal studies for prospective data collection and sharing should describe how they meet the requirements for this program, particularly the need for collection of new samples conforming to Consortium-wide protocols that are yet to be developed.

Applicants should develop a plan (and proposed costs) for the collection and management of biosamples, including protocols to ensure sample stability and quality control, and for the submission of biosamples to the OPCs for data production. Similarly, applicants are expected to develop a plan to standardize, harmonize, and conform phenotypic and environmental exposure data to the agreed-upon data models and standards, and for regular submissions to the AnVIL for inclusion in the multi-dimensional data set that will be created and made available to the wider scientific community via controlled access processes.

Applicants should articulate the analytical tools and methods, including technological and computational (including artificial Intelligence), that will be developed and optimized to achieve the goals of this program. As applicants are expected to perform data analyses within the AnVIL ecosystem, they should provide a comprehensive plan (including proposed costs) for cloud-based data analysis approaches. The plan should include analytical approaches to be used and their justification, plans for quality control analyses, methods to control for possible confounding (including batch effects) and imputation, and how false positive rates will be controlled in light of multiple testing. Demonstration of the generalizability of these methods across different diseases and populations is expected. It is expected that applicants will aim to innovate, refine, and utilize novel theoretical concepts, approaches, or instrumentation, as appropriate. ‘Omics approaches result in large amounts of complex data and associated metadata. A proposed data analysis plan must be included in the application, recognizing that it may be modified in Steering Committee discussions during protocol development and the subsequent course of the project.

Without duplicating information contained in the biosketches, relevant previous experience should be described succinctly. All applicants are expected to describe their past experience and willingness to actively participate in a Consortium-wide activities. Applicants should demonstrate strong expertise in multi-omics high throughput assays and in the use of multiple types of ‘omic assays to identify profiles from human samples. Applicants should describe experience in computational and statistical data integration and data analysis methods, in cloud-based tool development and data wrangling, and in working within the AnVIL ecosystem or similar cloud-based platform. Expertise in participant recruitment approaches and community engagement is also expected. 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.

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

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • A plan for sharing project datasets (phenotypic, environmental, covariate, process data, outcome measures, etc.) and associated ‘omic data should be provided. Recipients are expected to comply with the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and the NHGRI implementation of this policy. The plan should also describe how informed consent will be designed and obtained to allow broad data sharing of project datasets for unrestricted access or for ‘General Research Use’ under controlled access, as defined by NIH at https://osp.od.nih.gov/wp-content/uploads/standard_data_use_limitations.pdf. Broad data sharing for general research use is expected for Consortium datasets. A plan to share computerized resources such as study protocols, consent form templates, results report templates, and bioinformatic tools should also be provided.
  • All controlled access data generated are expected to be deposited into the AnVIL.
  • Rapid deposition of data into repositories is expected. Depending on the type of data, the duration of data production, as well as the quantity of the samples assayed in a given period, the frequency of data deposition might vary.
  • Applicants should provide a specific proposal for preparing and submitting biosamples to the OPC(s) and participant data and associated meta-data to the DACC. Applicants are encouraged to address the issue of frequency of submissions, based on practical considerations or previous experience and the recommendations above. The reasonableness of the proposed data sharing plan will be assessed by the reviewers.
  • Applicants should describe their plans to broadly disseminate methods and tools, including statistical and computational, developed as part of this program.

Appendix:

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

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, 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 Policy on Late Application Submission.

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, 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 grahambj@exchange.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

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

Overall Impact

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).

Scored Review Criteria

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

 

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

For this particular announcement

Are the scientific rationale and need for multi-omics approaches well supported by preliminary data, methodological advances, or information in the literature or knowledge? Will the proposed approaches make a significant contribution to understanding how multi-omics, integrated with phenotypic and environmental exposure data, can be used to study ‘omics profiles associated with healthy and disease status, evaluate aspects of disease progression, define relevant pathways and assess causal relationships?

 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

For this particular announcement

Do the investigators have experience appropriate for their career stage in working in multi-site research networks or consortia, developing methods, harmonizing phenotypes, integrating disparate datasets, and analyzing large-scale data to ensure the results are high quality and are produced in a timely way? Do the PD(s)/PI(s) and research team have a track record of working collaboratively and disseminating findings that is appropriate for their career stage?

Do the PD(s)/PI(s) and research team have experience and expertise appropriate for their career stage in working on multi-omics approaches and analyses? Have they demonstrated the ability to select and implement data standards, integrate informatic solutions and share research information across collaborating institutions and with NIH-designated databases?

Do the PD(s)/PI(s) and research team have experience appropriate to their career stage in successfully recruiting and retaining patients from understudied

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

For this particular announcement

Are data analysis plans sufficiently innovative to meet the goals of the project? As new technologies become available, is the research team poised to develop and implement them to do further research analyses?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

For this particular announcement

Have the sources and diversity of the study population(s) been clearly described? Are the strategies for recruitment and community engagement adequate? Has the applicant demonstrated the ability to enroll 300 participants of whom 75% are from population currently underrepresented in genomics studies? Will the phenotype and environmental exposure measures be of sufficient quality and completeness to provide maximal scientific value, or do they have the potential to be such within the project period? Is the plan to perform recurrent biosample collections adequate?

Are the strategies for outreach, dissemination, and promotion of Consortium resources likely to engage the broader research community?

 

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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.

 

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

 

For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

Not Applicable

 

Not Applicable

 

Not Applicable

Additional Review Considerations

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

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

 

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

 

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

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

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

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
  • Public health importance of the condition proposed for study.
  • Potential for broader application or generalization of findings from proposed condition to other conditions.
  • Emphasis on genetic ancestries underrepresented in genomic databases.
  • Programmatic balance among conditions to be studied, healthcare settings, and approaches to be implemented.
  • Ability of investigative group to work effectively in large collaborative efforts or consortia.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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

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

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

Cooperative Agreement Terms and Conditions of Award

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 (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award 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 the NIH as defined below.

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

  • Determining research approaches, designing protocols, setting project milestones, and conducting research.
  • Participating in group activities, including a study-wide Steering Committee to develop 1) the community engagement plan, 2) the recruitment strategy including the characteristics of participants and the consent language, 3) the plan for defining, measuring, and collecting core phenotypic and environmental exposure measures and ensuring appropriate quality assurance and quality control, 4) the biospecimen procurement and processing approaches, 5) the types of ‘omics assays, 6) the data analysis methods, 7) common data models, and 8) the plan for utilizing the AnVIL platform to share data and tools among the Consortium and broader research community including through open and controlled access processes.
  • Abiding by common definitions, protocols, procedures, etc. as chosen by majority vote of the Steering Committee.
  • Collaborating with all Consortium sites in making Consortium findings and procedures as widely available and applicable as possible.
  • Sharing research resources, tools, and data of interest with members of the consortium consistent with achieving the goals of the project.
  • Ensuring that the data, software, resources, materials, etc. produced as part of this project are released appropriately according to the Resource Sharing Plan.
  • Sharing results according to the NIH data sharing policy.
  • Adhering to policies regarding sharing of genomic and other types of data, data access, and standardized formats; timely publication; and intellectual property established by the NIH, NHGRI, and the Steering Committee (SC) for this program.
  • Sharing detailed genomic, phenotypic, family history, clinical, and related data derived from EMR systems and collected according to standard and widely available protocols such as those validated within eMERGE (i.e. PheKB) or the PhenX Toolkit through a definitive source such as AnVIL or ClinVar.
  • Cooperating with other recipients in the development and design of research methods, protocols, tools, and strategies.Working productively with NHGRI and with program staff from other NIH Institutes who may be providing co-funding for projects.
  • Accepting and complying with study policies established by NIH, and with additional non-conflicting policies approved by the Steering Committee.
  • Cooperating with other recipients in the publication and dissemination of program results and the eventual release to the scientific community of methods, tools, and results, and other resources.
  • Preparing abstracts, presentations and publications in a timely manner.
  • Assessing and disseminating data, protocols, consent materials, and methods developed within and outside the Consortium.
  • Not disclosing confidential information.
  • Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee, External Scientific Panel, and NIH.
  • Attending and participating in Steering Committee and other working group meetings and accepting and implementing the decisions, guidelines, and procedures adopted by the Steering Committee, External Scientific Panel, and NIH, as appropriate.
  • Interacting with other relevant NHGRI and NIH activities, as needed, to promote synergy and consistency among similar or related projects.
  • Collaborating with the Data Analysis and Coordinating Center (DACC) tasked with a variety of roles, such as: ensuring that consortium products are the highest quality; developing standards; disseminating information; providing logistics, outreach and training, etc.
  • For the collaboration to be effective, PDs/PIs are responsible for:
    • Ensuring that therecipient receives the appropriate approvals for sharing data with data repositories such as, AnVIL, dbGaP, and ClinVar and other appropriate public databases.
    • Working with the DACC to ensure thatdetailed phenotypic, environmental, clinical, and related data and metadatais standardized using agreed-upon formats and processes, submitted to the AnVIL to be cataloged, maintained, and made accessible as controlled-access data, and disseminated more broadly throughdbGaP or ClinVar or other appropriate databases.
    • Submitting datasets generated from the Consortium directly to public data repositories such as AnVIL, dbGaP, and ClinVar, as appropriate and agreed upon with the DACC, Steering Committee, and NIH.
    • Providing reports, summary statistics, and data, as appropriate, in a timely fashion as agreed upon by the Steering Committee and NIH.
    • Collaborating with the DACC to establish data formats and standards, to track and document collaborations and incoming samples, report findings, etc.
  • The clinical trial(s) supported by this award are subject to the plan in the application submitted to NIH and the NIH policy on Dissemination of NIH-Funded Clinical Trial Information (Public Law 110-85 and NOT-OD-16-149). Consistent with 45 C.F.R. 75.322, the recipient will own the data and software developed under this award and be able to continue to use these data and software upon expiration or termination of the award.
  • Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

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

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

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

Areas of Joint Responsibility include:

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

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

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

  • Meet at frequency specified in RFA or otherwise agreed to with NIH to share information, experience and expertise across participating sites and centers on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.; and to develop consensus approaches to: recruiting study participants and informed consent; integrating, harmonizing, analyzing data; developing methods, best practices, and standards; and disseminating data to other Consortium members, the broader scientific community, and NIH-designated databases.
  • Set research priorities, decide optimal research approaches and protocol designs, and contribute to the adjustment of research protocols or approaches as warranted.
  • Inventory, assess and control quality, harmonize, and catalog Consortium data.
  • Develop methods and tools for the integration and analysis of multi-omics, combined with phenotypic and environmental exposure, to study health and disease.
  • Establish best practices and standards for data integration and collaborative analyses, as appropriate.
  • Generate responses to ESP recommendations.
  • Generate a multidimensional data set that is available to the research community and is interoperable with existing resources.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will be composed of three members: a designee of the SC 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 disagreement for one award, 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 DHHS regulation 45 CFR Part 16.

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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: http://grants.nih.gov/support/ (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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Joannella Morales, Ph.D.

National Human Genome Research Institute (NHGRI)

Telephone: 301-480-3517

Email: joannella.morales@nih.gov

Kimberly A. McAllister, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3287
Email: mcallis2@niehs.nih.gov

Leah E. Mechanic, PhD, MPH
National Cancer Institute (NCI)
Phone:  240-276-6847
Telephone: mechanil@mail.nih.gov

Peer Review Contact(s)

Rudy Pozzatti, Ph.D.

National Human Genome Research Institute (NHGRI)

Telephone: 301-219-6235

Email: pozzattr@exchange.nih.gov

Financial/Grants Management Contact(s)

Donna Morris

National Human Genome Research Institute (NHGRI)

Telephone: 301-827-2745

Email: donna.morris@nih.gov

Lisa Archer Edwards, MBA
National Institute of Environmental Health Science (NIEHS)
Phone:  984-287-3258 
Email:  archer@niehs.nih.gov

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email:  wolfreyc@mail.nih.gov

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.

Authority and Regulations

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

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