Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Funding Opportunity Title

The Electronic Medical Records and Genomics (eMERGE) Network, Phase III – Central Genome Sequencing and Genotyping Facility (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

  • August 13, 2014 - See Notice NOT-HG-14-033. Added FAQs for this RFA.
  • Funding Opportunity Announcement (FOA) Number

    RFA-HG-14-027

    Companion Funding Opportunity

    RFA-HG-14-025, U01 Research Project – Cooperative Agreements

    RFA-HG-14-026, U01 Research Project – Cooperative Agreements

    Catalog of Federal Domestic Assistance (CFDA) Number(s)

    93.172

    Funding Opportunity Purpose

    The purpose of this Funding Opportunity Announcement (FOA) is to continue genomic discovery and implementation research in Phase III of the eMERGE Network by providing support for centralized sequencing and genotyping facility(-ies) for the Electronic Medical Records and Genomics (eMERGE) Network.

    Key Dates
    Posted Date

    July 17, 2014

    Open Date (Earliest Submission Date)

    October 12, 2014

    Letter of Intent Due Date(s)

    October 12, 2014

    Application Due Date(s)

    November 12, 2014, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

    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.

    AIDS Application Due Date(s)

    Not Applicable

    Scientific Merit Review

    March 2015

    Advisory Council Review

    May 2015

    Earliest Start Date

    August 1, 2015

    Expiration Date

    November 13, 2014

    Due Dates for E.O. 12372

    Not Applicable

    Required Application Instructions

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


    Table of Contents

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


    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    The purpose of this funding opportunity announcement (FOA), in coordination with RFA-HG-14-025, “The Electronic Medical Records and Genomics (eMERGE) Network, Phase III – Study Investigators” and RFA-HG-14-026,  “The Electronic Medical Records and Genomics (eMERGE) Network, Phase III – Coordinating Center” is to continue genomic discovery and implementation research using large biorepositories linked to electronic medical records (EMRs).  It will do so by providing support to 1-2 Central Sequencing and Genotyping facility(-ies) (CSG) to conduct large-scale, high-throughput genome sequencing of approximately 25,000 DNA samples collected by eMERGE Network study sites for use in genomic discovery and clinical care; these facilities will have to provide CLIA certification for at least some data types.

    NHGRI initiated the eMERGE Network in 2007 to support investigative groups with existing biorepositories to develop necessary methods and procedures, and then to perform genome-wide studies in participants with phenotypes and environmental exposures derived from EMRs.  eMERGE Network Phase II (eMERGE II, 2011-2015) expanded to incorporate current genomic knowledge combined with available genotyping data and state-of-the-art electronic phenotyping and privacy protection methods into clinical research and ongoing clinical care.  eMERGE Network Phase III (eMERGE III) will continue this research, leveraging data from large biorepositories, as well as sequencing data derived from the new eMERGE Network CSG, to build upon the genome sequencing, phenotyping, and implementation methods and knowledge generated in eMERGE II.

    To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity has a goal to further advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community for research use, through community resource databases such as dbGaP and Clinical Genomics Resource (ClinGen). 

    For the purposes of this FOA, a “biorepository” is defined as a resource that collects and stores biospecimens from which DNA sufficient for genome-wide studies can be isolated from individuals, and which are linked to electronic personal health information on these individuals.  The biospecimens may have been collected in the course of clinical care or as part of a research resource.  “Electronic medical records” are defined as computerized data obtained in the course of clinical care or research that can be electronically accessed, manipulated, shared, and analyzed, with appropriate consent and patient protections, for research purposes and ongoing clinical care and quality improvement.  “Large-scale, high-throughput sequencing” is defined as having a state-of-the-art sequencing capacity pipeline to produce at least 8TB of high-quality sequencing data per year or more.  In addition, the pipeline must be able to adapt to ongoing rapid innovations for improving sequencing quality, efficiency, and cost-effectiveness.

    The goals of this initiative are to expand on best practices and knowledge in effective implementation of genomic medicine to pursue a broad-based program sufficiently large to define health outcomes associated with rare (0.5-1.0% MAF) variants in ~100 clinically relevant genes.  Specifically, this initiative proposes to: 1) detect rare variants presumed to affect gene function; 2) assess the phenotypic implications of these variants, singly or in combination, by leveraging well-validated EMR data; 3) report actionable variants to patients and clinicians to improve clinical care and ultimately health outcomes; and 4) assess health impact, cost-effectiveness, and ethical, legal and social implications (ELSI) of reporting these variants on a broader population scale for patients, clinicians, and institutions.  It will also continue efforts to improve electronic phenotyping, discover novel genomic variants associated with these phenotypes, provide electronic clinical decision support, and enable integration of genomic information into EMRs for clinical research and clinical care.

    Background

    eMERGE was initiated in 2007 to develop methods and best practices for conducting genomic research in 5 biorepositories linked to EMRs.  Having demonstrated the robustness of EMR phenotyping for genome-wide studies, defined approaches for enhancing privacy of shared EMR data, and engaged patients and communities in consent and data sharing, eMERGE expanded to include 7 study sites in 2011 and 2 pediatric sites in 2012.  In 2012 eMERGE began a collaboration with the Pharmacogenetics Research Network (PGRN) to perform targeted sequencing of 84 pharmacogenomic genes in 9,000 patients. 

    The large scale of this project has been especially illuminating, not only in the processes for consent, clinical workflow, and institutional approval at 10 diverse institutions, but also in the number of potentially actionable variants found.  Over 2% of the first 2,022 patients studied, for example, carry rare “known or expected pathogenic variants” in two arrhythmia genes, SCN5A and KCNH2; yet we know that familial arrhythmia syndromes are much less prevalent than this.

    Currently, eMERGE II has 328,895 participants with biorepository samples linked to EMRs; 105,524 of these samples have been genotyped.  eMERGE II has expanded its e-phenotyping library to 41 validated phenotypes and has continued genome-wide association study (GWAS) and phenome-wide association studies (PheWAS) for discovery research using common variants.  In 2013 eMERGE was selected to survey ~16,000 patients’ attitudes toward proposed modifications to the Common Rule on broad consent for genomics research, information that is urgently needed NIH-wide for policy development.  Detailed information on the eMERGE network can be found at the eMERGE website (www.gwas.org) and the website of the Division of Genomic Medicine, NHGRI, NIH (https://www.genome.gov/27540473).

    The advent of high-throughput, low-cost sequencing platforms and their initial use in clinical care have revealed genomic variation of an almost unimaginable degree in genes critical to health and disease.  Of particular concern have been variants predicted to disrupt function of these critical genes, which appear to be much more common than the diseases with which they are associated.  Reliable information on the frequency of disease manifestations in carriers of these variants is essential to providing reliable advice to patients, their families, and their clinicians on the actions to be taken (if any) once they are detected.  Biorepositories with extensive EMRs and appropriate consent are uniquely positioned to define the phenotypic correlates of such variants and assess their penetrance through EMR data-mining in large clinical samples.  This information will be critical in moving genome sequencing into wide clinical use.  Without accurate estimates of penetrance and pathogenicity to target feedback only to patients truly at high risk, institutional responsibilities for curating, counseling, and following up these variants will not be sustainable.

    Other obstacles to implementing genomics in clinical care include lack of institutional and clinician acceptance and lack of evidence demonstrating improved patient outcomes or processes of care.  Lack of informatics infrastructure, particularly in integration of genomic results into EMRs and genomic clinical decision support (CDS), are major impediments in providing actionable information to clinicians at the point of care.  Critical issues in genomics and EMRs that eMERGE is well-positioned to address include facilitating confidential, standardized, and efficient genomic data sharing across providers; developing and assessing effectiveness of genomic CDS; harnessing genomic EMR data for quality improvement research around use of genomic tests; and enhancing the usefulness of genomic EMR data for patient education, self-management, and identification of at-risk family members.  Such issues must be addressed if genomic medicine is to be widely implemented and successful in improving outcomes and reducing healthcare costs.

    Objectives of this Research Program

    This FOA will support 1-2 large-scale, high-throughput CSG to generate DNA sequence and genotyping data for the studies supported by RFA-HG-14-025, The Electronic Medical Records and Genomics (eMERGE) Network, Phase III – Study Investigators” and RFA-HG-14-026The Electronic Medical Records and Genomics (eMERGE) Network, Phase III – Coordinating Center.”  The goals of eMERGE III are to: 1) conduct research in both genomic discovery and clinical implementation utilizing large biorepositories linked to EMRs; 2) share resulting best practices, expertise, and experience within and outside eMERGE; and 3) disseminate association findings, tools and best practices to the scientific community.  Specifically, eMERGE III aims to identify, among roughly 25,000 eMERGE III participants, rare variants with presumed major impact on function of a to-be-decided-upon number of clinically relevant genes (currently anticipated for planning purposes to be roughly 100); assess phenotypic implications of these variants by leveraging well-validated EMR data or selective in-depth phenotyping of variant carriers; report actionable variants to patients, potentially their families (as feasible and appropriate), and their clinicians, with appropriate consent and education; and assess health impact, cost-effectiveness, and ethical, legal and social implications (ELSI) of reporting these variants on a broader population scale for patients, clinicians, and healthcare institutions.  In this third phase, eMERGE will also continue to expand and enhance electronic phenotyping; develop and/or refine genomic CDS tools and make them available for clinical use; enable integration of genomic findings into EMRs for clinical research and care; and engage and educate IRBs, health system leaders, EMR vendors, and other stakeholders in implementing genomic medicine in clinical care.

     

    In eMERGE III, DNA samples will be sequenced at the proposed CLIA-certified eMERGE CSG using methods mutually agreed upon by the eMERGE III Steering Committee as providing the optimal balance of cost and breadth and depth of coverage, including relevant non-coding variation as appropriate.  Recognizing the continuing rapid advances in quality and efficiency of genome sequencing technologies, approaches may evolve during the four-year course of phase III to involve exome or genome sequencing.  At present, however, the costs, data management, and interpretative challenges for such broader approaches remain prohibitive, so this FOA will focus on targeted gene sequencing, recognizing that broader approaches may be considered as the field progresses.  

    Within the first year, the eMERGE Steering Committee will agree upon, subject to External Scientific Panel (ESP) review and NHGRI approval, genes to be sequenced and/or types of sequencing to be used (such as targeted genes, exomes, or genomes).  Sequence variants with presumed detrimental impact on gene function and likely to produce disease manifestations in a high proportion of carriers will be analyzed separately and collectively (by gene, pathway, or other logical method of clustering) for associations with clinical and psychosocial outcomes, health behaviors following testing and reporting, and attitudes toward testing.  These analyses will be conducted collaboratively with the other eMERGE funded sites and NHGRI.  The process of defining clinically useful variants and for utilizing and contributing to resources such as ClinGen, the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Clinical Sequencing Exploratory Research (CSER) Network will continue in years 2-4.  As noted above, tools and technology used in genomic research are expected to evolve over the course of the award, and thus eMERGE III study sites will be expected to evolve with them, adopting new technologies as efficiently and cost-effectively as possible and streamlining approaches for variant validation.  Although SNP-based genotyping is not expected to be a major part of eMERGE III, potential roles for it could be envisioned in low-cost typing of very large numbers of participants for variants of particular interest; the CSG will be expected to have this capability and to work with the eMERGE III Steering Committee to develop approaches for genotyping if appropriate. Exploratory functional studies capitalizing on the unique phenotyping strengths of eMERGE, including the potential for re-contact and re-examination, may be supported as funds permit, especially those leveraging consortia such as NHGRI’s Encyclopedia of DNA Elements (ENCODE) and NIH’s Genotype-Tissue Expression (GTEx) project.

    In eMERGE III, biorepositories will be supported to expand and validate the eMERGE library of “electronic phenotyping” algorithms from 41 phenotypes in Phase II to at least 60 and preferably 80 in Phase III, focusing on phenotypes likely to be related to the genes to be sequenced.  Continued enhancements to phenotyping tools, including “modular” phenotypes combinable into multiple complex phenotypes, are expected to increase phenotyping efficiency and transportability.  The network will conduct association analyses using sequencing data and existing genome-wide genotyping data for phenotypes derived from EMRs in previous eMERGE phases and Phase III; incorporate genotyping information into EMRs, where feasible, for improving clinical care; and work within the collaborative infrastructure developed in eMERGE.  Sharing of expertise and experience within and outside eMERGE will continue to be a key goal, with the intent of raising the standards for genomic research in biorepositories and of incorporating robust genomic technologies and genomic approaches into medical care in general.

    eMERGE III will develop and implement institution- or system-wide methods for re-annotation of variants as knowledge accrues, as well as methods for re-contact of clinicians and patients with updated information on actionability.    

    eMERGE III will continue to assess patient and clinician preferences for and reactions to reporting of actionable variants, and will continue to engage and educate IRBs, health system leaders, EMR vendors, and other stakeholders in the challenges involved in genomic medicine implementation.  It will also assess the appropriateness and potential impact of reporting rare sequence variants on family members, and promote and evaluate approaches to consent and education of patients and clinicians for reporting such variants. 

    An eMERGE III CSG will be expected to conduct a rapid release of genomic data and materials to the broader research community.  Therefore, beginning from sample receipt, a four to six week timeline for analysis completion, validation, and return of results to the eMERGE III Coordinating Center and Study Investigators is expected. The CSG is expected to produce, at minimum, standard formats for transmitting information about sequence and variants such as BAM and VCF files.  Participation in more downstream annotations of known or suspected pathogenicity or suspected functional impact in collaboration with other participating eMERGE III sites will be strongly encouraged.

     

    The CSG awardee(s) will work collaboratively with the eMERGE III Study Investigators, Coordinating Center, and NHGRI to conduct a comprehensive program of genomic discovery and clinical implementation research.  Applicants’ capabilities should include, but are not limited to:

    • A state-of-the-art facility to produce high-quality sequencing and genotyping data within a 4-6 week turnaround from sample receipt for use in clinical care.
    • Expertise and ability to participate collaboratively with other eMERGE-funded sites in annotating of variants and identifying potential pathogenic or functional variants in genes critical to health and disease.
    • Innovative plans for generating and utilizing sequencing and genotyping data to identify associated phenotypes in genes critical to health and disease, assessing penetrance of these genetic variants, and improving or standardizing genomic CDS for return of clinical relevant genetic results directly to patients.
    • A proven track record, with respect to cost, throughput, and quality, for producing sequencing and genotyping data.
    • Capabilities for Clinical Laboratory Improvement Amendments (CLIA) validation and submission of data for integration into EMRs and dissemination beyond eMERGE III study sites in a manner consistent with NIH data sharing policies and maintenance of participant confidentiality.
    • A high degree of flexibility and expertise in interacting with other sites participating in eMERGE III.

    Due to regulatory requirements for using research results in clinical care, some sequencing data will be expected to be in compliance with the Clinical Laboratory Improvement Amendments (CLIA).  In addition, a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) may be needed for new sequencing methods used in clinical care, separate to the requirement for the test to have been conducted within a CLIA-certified environment.  The CSG must be prepared to support the Study Investigators in discussing the need for an IDE with their IRBs and documenting the outcome of those discussions, and in engaging in pre-submission discussions with the FDA.  These typically involve submission of actual study protocols, including the entire sequencing pipeline from sample preparation to data analysis; the latter will be prepared in collaboration with the Coordinating Center.

    Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds.

    Program Formation and Governance

    The awards funded under this FOA will be cooperative agreements (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award).  Close interaction among awardees and the NIH will be required to develop appropriate strategies and tools to carry out this program.

    The eMERGE Steering Committee, which will include the PDs/PIs from each Phase III investigative site, Coordinating Center (CC), CSG, and the NIH Project Scientist(s), will determine genes and regions to be sequenced and/or genomic technologies to be used for eMERGE III; continue to define, validate, and disseminate EMR phenotypes; develop informatics tools for enhancing genomic research in biorepositories; examine concerns related to return of genomic data to patients, their physicians, and their EMRs for use in clinical care; address consent, education, and community concerns related to genomic discovery and clinical implementation research; and assess impact to patients, clinicians as well as institutions on patient outcomes and cost of care.

    Early after funding, the eMERGE III Steering Committee will meet to set goals and proposed milestones for Phase III.  The Steering Committee will meet three times per year and monthly on teleconferences to share information on sequencing data production, phenotyping progress, EMR-genomic variant integration and genomic CDS methodologies, analytical tools for genomic discovery, preliminary results, and analyses in progress.  Key collaborators, and pre- and postdoctoral trainees, in addition to the PDs/PIs, will be eligible to attend Steering Committee meetings.  PDs/PIs are encouraged to include investigators and trainees who are members of under-represented minority groups and those from related disciplines such as genomic, bioinformatics, computational/system biology, public health, social sciences, health services, health economics and outcomes research, and translational research where appropriate. 

    eMERGE will continue to have working groups in areas of interest to the awardees and the funding institute(s).  Currently eMERGE has seven such groups, addressing: Consent, Education, Regulation and Community Consultation; Phenotyping; Genomics; Return of Results;Electronic Health Record Integration; Pharmacogenomics; and Pediatrics.  In eMERGE III, these workgroups may be regrouped and new workgroups formed to meet the eMERGE III goals for both genomic discovery and clinical implementation research.  The tasks of the working groups will include, among other responsibilities: identifying common scientific areas and adjusting projects to accommodate shared interests, identifying novel projects that may result from synergy among the awarded groups, and identifying ways to interact with external ongoing networks and initiatives.  Working groups may propose new research collaborations with non-network investigators and organizations, as long as most or all eMERGE sites have the opportunity to participate, according to criteria established by the eMERGE Steering Committee.

    A separate FOA (RFA-HG-14-025) will be issued to support 8-12 Study Investigator Sites.  A second separate FOA (RFA-HG-14-026) will be issued to support a Coordinating Center to be responsible for cross-study functions, such as conducting quality control analyses of sequencing data, harmonizing data across studies, leading any cross-study analyses, establishing and managing the study website, facilitating outside collaborations, and organizing the logistics of the collaborative program.  Early after funding, the CC will organize the first eMERGE III Steering Committee meeting so that goals and milestones can be set for eMERGE III.  The CC will organize Steering Committee meetings three times per year and monthly teleconferences as needed to share information on data resources, methodologies, analytical tools, as well as preliminary results.

    External Input to the Network

    eMERGE will continue to have an External Scientific Panel (ESP).  The ESP will be convened to advise NHGRI and the network on how best to balance genomic discovery and clinical implementation research and accelerate the contributions to the field of EMR and genomic medicine.  The eMERGE Steering Committee members will meet with members of the ESP once a year in-person and once a year through teleconference, will receive and consider a report of the ESP’s comments, and will respond with a written letter each time through NHGRI.

    Data Sharing under this Initiative

    NHGRI recognizes that data sharing is essential in order to advance genomic research and will expect awardees to address and adhere to NIH data sharing policies.  Data from this FOA are expected to be handled so as to advance research and increase the value of the significant public investment in conducting genome-wide studies on samples from the participating biorepositories.  NHGRI intends that Project Datasets (including phenotypic, environmental, covariate and other relevant data) and associated genomic data from the participating biorepositories be widely shared with the scientific community for research uses through NIH-supported databases such as dbGaP, which contains both an open and controlled access section.  Although NHGRI expects all Project Datasets from genomic studies selected as part of this FOA to be available through databases such as dbGaP and ClinGen, the NHGRI does not intend dbGaP, or any single database, to become the exclusive source of this program’s data.  Information such as study protocols, descriptions, and publications are expected to be made available through an open access section of a database such as dbGaP, other public web sites, and/or publication in the scientific literature.

    Phenotypic, exposure and genomic data proposed for use in eMERGE III are expected to be deposited to dbGaP prior to award (aside from newly-defined or refined sequencing variants and phenotypes developed in the course of Phase III).  These data must pass appropriate data quality assessments, conducted in collaboration with NCBI and NHGRI.  Simple, unadjusted genomic- or genotype-phenotype associations (“pre-computes”) may be calculated and made available through these resources.  Data on newly-defined or revised genome sequencing variants, phenotypes or exposures should be deposited in dbGaP as soon as they are available.

    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.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Funds Available and Anticipated Number of Awards

    NHGRI intends to commit $4M in FY 2015 to fund 1-2 awards.  Future year amounts will depend on annual appropriations.

    Award Budget

    The expected direct costs for each individual sequencing facility are not to exceed $2.5M per year for each of the four years and should reflect the actual needs of the proposed project.  If more than one sequencing/genotyping facility is funded, budgets will be reduced accordingly.

    Award Project Period

    The total project period for this FOA is 4 years (FY15 through FY18).

    NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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)

    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)
    • 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 not 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.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) (formerly CCR) – 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. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the 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.  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 NOT-OD-11-101).

    In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

    • To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
    • Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
    • Of an application with a changed grant activity code.
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

    2. Content and Form of Application Submission

    It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    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:

    Kenneth L. Wiley, Jr., Ph.D.
    National Human Genome Research Institute (NHGRI)
    5635 Fishers Lane, Suite 4120, MSC 9305
    Rockville, MD 20852-9305
    Telephone 301-435-5540
    Fax: 301-480-2770
    Email: ken.wiley@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.

    The cost of 1-3 persons to attend meetings should be included in the proposed budget.  Remote participation is also often possible through web-streaming software. No funding should be requested for Central Coordinating Center or Study Investigator initiatives, as these will be supported through separate FOAs.

    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:

    Specific Aims: List each aim for the CSG and how it supports the Objectives of this Research Program as described in Section I. Funding Opportunity Description.

    Research Strategy:

    Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project as well as the following aspects.

    As noted above, the continuing rapid advances in quality and efficiency of genome sequencing technologies may make broader approaches involving exome or genome sequencing feasible during the four-year course of eMERGE III.  To ensure comparability of applications in the evaluation and selection process, applicants should focus their response to this FOA on a plan for targeted sequencing of ~100 genes for discovery of rare variants relevant to health and disease.  A partial list of relevant genes for analysis can be found in the American College of Medical Genetics and Genomics Recommendation for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Applicants should also describe briefly (in less than half a printed application page) how they would adapt their plan as technologies advance, particularly if at the time of award or during its course a more expansive sequencing approach becomes feasible.  Applicants’ research plans should include, but are not limited to, detailed descriptions of the following:

    Genomic Sequencing Plan

    Protocol for sequence and genotype data generation, including the facilities and instrumentation to be utilized for sequence generation, sample processing and tracking, minimum depth of coverage for 90% and 95% of bases sequenced, concordance to array genotypes, and transition/transversion (Ti/Tv) ratio.  CLIA-approved sequencing is not required, but a plan for CLIA variant validation for clinical use must be provided.

    Experience working in a clinical setting related to large-scale, high-throughput data production and analysis at the scale required to achieve eMERGE III goals (an estimated 25,000 patients receiving CLIA results over 4 years), which may include a report on the prior quarter’s sequencing production and quality measures employed.

    Timeline from acquiring purified DNA provided by biorepositories to sequencing patients and disseminating results (BAM and VCF files) within the eMERGE Network, within a 4-6 week period, including components such as sample processing, library preparation, sequence generation, alignment, variant calling, quality control/quality testing, analysis completion, validation, and return of results to the Coordinating Center and/or Study Investigators.

    Genomic Sequencing Analysis

    • Anticipated analysis strategy, including file hierarchy and structure and primary sequence data quality assessments.
    • Genome variant calling strategy, including algorithm development, if any.
    • Proposed approach for participating collaboratively with other eMERGE-funded sites in annotation of variants and identification of potential pathogenic or functional variants in genes critical to health and disease.
    • Bioinformatics infrastructure/capabilities to securely transmit and store genomic data files.
    • Computational and sequencing resources needed to generate large-scale, high-throughput sequencing data with validation, including the type of platform to be utilized and documentation of its quality.
    • CLIA Variant Validation
    • Clinical Laboratory Improvement Amendments (CLIA) variant validation, the facilities and instrumentation to be utilized.
    • College of American Pathologists (CAP) and/or CLIA compliance experience and demonstration of large-scale, high-throughput data production at the scale required to achieve eMERGE III goals (an estimated 25,000 patients receiving CLIA results over 4 years).
    • Sample of a report to be delivered to Clinical Sites, with details on format and the type of information provided.

    Costs: Applicants should provide a “fully loaded” cost with an itemized cost plan for a per person, per genome analysis for sequencing ~100 genes that includes, but is not limited to:

    • Sample receipt and tracking
    • DNA isolation and library preparation
    • Sequencing Cost
    • Variant calling
    • Quality control/quality testing
    • CLIA confirmation and reporting for primary and incidental findings
    • Associated materials, incidentals, equipment
    • Informatics, data storage
    • Labor, fringe
    • Indirect costs
    • Plans for decreasing cost over a four-year period while increasing efficiency and quality

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

    Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    Planned Enrollment Report

    When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

    PHS 398 Cumulative Inclusion Enrollment Report

    When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

    3. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates. 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.

    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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

    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.

    4. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    5. 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.

    6. 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 Applying Electronically.

    Important reminders:
    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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 DUNS number it provides on the application is the same number 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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

    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.

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? 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? How will the proposed research improve current knowledge on  variants presumed to affect gene function?   How does the proposed research improve current knowledge regarding interpretation and dissemination of genomic data for clinical use?

    Investigator(s)   

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? What are their plans for how their research team will interact with the eMERGE consortium?  What are their past experience(s) working in multi-site research networks or consortia?

    Innovation

    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?  Are the investigators’ plans for adapting to evolving technologies innovative and insightful, and demonstrate their ability to be facile and flexible in this rapidly moving field? 

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

    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 children, justified in terms of the scientific goals and research strategy proposed?

    Are the costs per patient for genomic sequencing, primary analysis, and validation appropriate? What are the methods for disseminating results to multiple entities within and outside of the Network? Do the plans presented include a viable method for reducing costs and incorporating new technologies?

    Are they able to produce high-quality genome sequencing data and submit them to the eMERGE database in the volume and timeframe needed to meet the goals of eMERGE III?   

    Environment

    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? Are the bioinformatics infrastructure/capabilities to securely transmit and store genomic data files within the eMERGE network for the research project adequate?

    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.

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the six 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 six 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.

    Inclusion of Women, Minorities, and Children 

    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 children 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.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    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.

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    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.

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

    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).

    Resource Sharing Plans

    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) Genome Wide Association Studies (GWAS)  Reviewers should note that applicants are required to share sequence data within the eMERGE network.

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHGRI, 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:

    • 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.
    • Will receive a written critique.

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

    Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHGRI 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.
    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

    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 grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. 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.

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees 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 share design and analysis techniques and promote comparability across studies wherever possible.
    • Implementing Steering Committee recommendations for selection of genomic technology to identify genomic variants, and annotation of actionable genetic variants.
    • Sharing detailed phenotypic and environmental data derived from EMR systems and collected according to protocols validated within eMERGE or a similar definitive source with databases such as dbGaP.
    • Identifying results most appropriate to report to patients and to extract using clinical decision tools, and appropriate actions to be taken in patients carrying these variants.
    • Identifying concerns unique to underserved populations such as children and minority participants.
    • Collaborating with all eMERGE sites in making eMERGE findings and procedures as widely available and applicable as possible.
    • Sharing results according to the data sharing policy agreed to between the NHGRI and the applicant.
    • Adhering to policies regarding data access, publication, and intellectual property established by NIH and the Steering Committee for this program.
    • Adhering to NIH policies regarding genome-wide association studies, genomic data sharing and other policies that might be established during the course of this activity, as appropriate.
    • Cooperating with other awardees in the development and design of research methods, protocols, tools, and strategies.
    • Abiding by common definitions, protocols, procedures, etc. as chosen by majority vote of the Steering Committee.
    • Accepting and complying with study policies established by NIH, and with additional non-conflicting policies approved by the Steering Committee.
    • Cooperating with other awardees in the publication and dissemination of program results and the eventual release to the scientific community of methods, tools, and results, and other resources.
    • Not disclosing confidential information obtained from other members of the program.
    • Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and External Scientific Panel.

    Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

    The Project Scientist is a scientist of the NHGRI staff who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination.  However, the role of NIH staff will be to facilitate and not to direct the activities.  It is anticipated that decisions in all activities will be reached by consensus of the program and that NIH staff will be given the opportunity to offer input to this process.  The Project Scientist will participate as a member of the Steering Committee and will have one vote.  The Project Scientist 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 awardees, including acting as a liaison to the NIH, and as an information resource for the awardees about genome research activities.  The Project Scientist 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 Project Scientist 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 subcommittees of the Steering Committee and the External Scientific Panel, as appropriate.
    • Assisting awardees in the development, if needed, of policies for dealing with situations that require coordinated action.
    • Providing advice in the management and technical performance of the award.
    • Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
    • Participating in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the program.
    • The Program Official may withhold or reduce support from any awardee that fails to achieve its goals or comply with the Terms and Conditions of Award.
    • Other NHGRI staff may assist the awardees as designated by the Program Official
    • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

    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 medicine discovery and implementation research. The awardees and the Project Scientist will meet as the program Steering Committee three times per year and monthly on conference calls to share information on data resources, methodologies, analytical tools, as well as data analyses and preliminary results.  In addition to the PIs, key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.

    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 P.I. 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.  Awardees agree to work collaboratively to:

    • Share experience and expertise across participating biorepositories and develop guidelines on consent, education, regulation, and consultation for such research, and on collecting, formatting, depositing, and documenting phenotype, genotype, and covariate data for databases such as dbGaP, for dissemination to other biorepositories.
    • Review documentation of existing consent processes, community consultation, and IRB approvals in participating biorepositories to identify best practices for genomic studies, data sharing, results reporting, and incorporation into clinical care.
    • Develop approaches for evaluating concerns among biorepository patients, clinicians, investigators, IRBs, and other relevant groups regarding addition of genomic technologies to the biorepository and widespread data sharing.
    • Establish best practices for IRB interactions, patient consent or assent (as appropriate), and results reporting, and for collecting, formatting, documenting, and sharing data.
    • Develop methods and tools for phenotyping using EMRs and for genomic discovery using genome-wide genotyping data and sequencing data linked to EMRs.
    • Analyze genotype-phenotype associations using network data to increase statistical power for genomic discovery
    • Define optimal approaches for incorporating genomic research into clinical care so as to speed the translation of genomic findings into improved genetic risk assessment, prevention, diagnosis, treatment, cost-efficiency, and, ultimately, improved health and reduced disease.

    External Scientific Panel

    An External Scientific Panel (ESP) will continue to evaluate the progress of the program.  The ESP established in 2007 will continue to provide recommendations to the National Advisory Council for Human Genome Research about the progress and scientific direction of all components of the program.

    The ESP is currently composed of five senior scientists with relevant expertise, although the membership may be enlarged permanently or on an ad hoc basis as needed.  The ESP will meet at least twice a year, once per year in person and once by telephone conference.  At least once per year, there will be a joint meeting with the Steering Committee to allow the members of the ESP and the Steering Committee to interact directly.  Twice a year the ESP will make recommendations regarding progress of the program to the National Advisory Council for Human Genome Research about changes, if any, which may be necessary in the program.

    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 have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee.  This special dispute resolution procedure does not alter the awardee'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, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

    A final progress report, 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.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees 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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

    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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    Finding Help Online: http://grants.nih.gov/support/index.html
    Email: commons@od.nih.gov

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact CenterTelephone: 800-518-4726

    Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
    Email: support@grants.gov

    GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
    Telephone: 301-435-0714
    Email: GrantsInfo@nih.gov

    Scientific/Research Contact(s)

    Kenneth L. Wiley, Jr., Ph.D.
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-435-5540
    Email: ken.wiley@nih.gov

    Peer Review Contact(s)

    Ken Nakamura, PhD
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-402-0838
    Email: nakamurk@mail.nih.gov

    Financial/Grants Management Contact(s)

    Ms. Cheryl Chick
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-435-7858
    Email: ChickC@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 Parts 74 and 92.

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