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

Clinically Relevant Genetic Variants Resource: A Unified Approach for Identifying Genetic Variants for Clinical Use (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HG-12-016

Companion Funding Opportunity

Not Applicable.  

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.172 

Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to develop a resource for the identification and dissemination of consensus information on genetic variants relevant for clinical care.

Key Dates
Posted Date

July 10, 2012

Open Date (Earliest Submission Date)

September 21, 2012

Letter of Intent Due Date

September 21, 2012

Application Due Date(s)

October 23, 2012, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

January/February 2013

Advisory Council Review

May, 2013

Earliest Start Date(s)

June, 2013

Expiration Date

October 24, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

Nature of the Research Opportunity

The purpose of this funding opportunity announcement (FOA) is to develop a resource for the identification and dissemination of consensus information on genetic variants relevant for clinical care.  Specific goals are to: 1) identify genetic variants with likely implications for clinical care; 2) incorporate these variants and their supporting evidence into a resource that can serve as the substrate for development of practice guidelines by professional and clinical organizations; 3) establish a process for transferring this information to appropriate organizations for development of these guidelines; and 4) engage, coordinate and build upon existing programs and reduce duplicative efforts to identify such variants across numerous research and clinical organizations.

Background

Genomic studies are increasingly identifying genetic variants with potential implications for clinical care, such as variants increasing risk of disease (e.g., mismatch repair mutations in colorectal cancer) or affecting response to a drug (e.g., CYP2C19*2 in persons receiving clopidogrel).  Dozens of medical centers and research programs nationwide are beginning to explore the use of such variants in clinical care, and many are developing approaches for identifying variants to be assayed and the actions to be recommended when they are detected.  In many cases, there is significant overlap in the evaluation of these assays, the review of the literature, and the assessment of the underlying evidence.  In addition, major efforts to identify variants relevant to drug response have been ongoing through the NIGMS-led Pharmacogenomics Knowledge Base (PharmGKB) and Pharmacogenomics Research Network (PGRN) for some years.

A unified approach to harness and coordinate these often isolated, individual efforts and disseminate their findings would reduce duplication of effort and speed adoption of actionable genetic findings for use in clinical care.  Relevant information could be reviewed and synthesized once (and revisited over time) by appropriate experts, using an agreed-upon consensus framework and incorporated into a user-friendly and accessible resource.  These evidence syntheses and consensus findings could then be handed off to appropriate professional and clinical organizations for development of practice guidelines, to be considered for implementation at the level of a given institution, in the context of local practice and community preference to improve patient care.  A framework for evaluating and recommending variants for implementation, appropriately tailored to the risks and benefits of the clinical action proposed, could be disseminated for consideration by healthcare systems in other countries.  Such decisions, if effectively captured and indexed, could also draw upon and contribute to the extensive research activity in return of genomic research results supported by NHGRI and other NIH Institutes.    

Development of the Clinically Relevant Variants Resource is expected to build on existing extensive work to identify and catalog genotype-phenotype associations with potential clinical implications, such as the nascent ClinVar database of the National Center for Biotechnology Information (NCBI) [www.ncbi.nlm.nih.gov/clinvar/], CDC’s Evaluation of Genomic Applications in Practice and Prevention [www.cdc.gov/genomics/gtesting/EGAPP/recommend/], the International Standards for Cytogenomic Arrays (ISCA) database [www.iscaconsortium.org], the FDA’s Pharmacogenomic Biomarkers in Drug Labels [www.fda.gov/drugs/scienceresearch/ researchareas/pharmacogenetics/ucm083378.htm], and PharmGKB’s Very Important Pharmacogenes [www.pharmgkb.org/search/annotateGene/].   Close integration with these ongoing efforts would position this consensus project at the nexus of variant discovery as captured by these databases, and decision-making for reporting results, as addressed by ongoing research activities and appropriate professional organizations.  Given the large number of groups currently undertaking such efforts, a collaborative approach that engages these ongoing efforts and ensures that diverse perspectives are sought and considered is most likely to yield a widely-embraced and influential resource. 

Maximizing the usefulness of the resource will require engaging the constituencies likely to consult it, including professional and clinical organizations that will develop practice guidelines based on the underlying evidence, regulatory agencies, payers, medical institutions, clinicians, and researchers.  Close consultation with these constituencies and responsiveness to their needs will be essential to the success of the program, along with guidance and facilitation by the NHGRI, other NIH Institutes, and appropriate professional and clinical organizations.  To ensure that the resource is accessed and applied, an effective dissemination strategy is critical.  The framework for developing consensus can also be distributed to other health systems, especially non-US systems, to consider and adapt as desired.

NHGRI recognizes the importance of collaborating with relevant professional organizations on this effort, such as the American College of Medical Genetics (ACMG), the American Society of Human Genetics (ASHG), the Association for Molecular Pathology (AMP), and the College of American Pathologists (CAP), and is engaging other groups and societies involved in similar efforts.

Scientific Knowledge to be Achieved

This funding opportunity will identify a consensus approach for collecting, abstracting, and evaluating the published research regarding clinical relevance of genetic variants associated with clinically important traits and synthesizing these data and their supporting evidence into a user-friendly database that can stimulate further research and serve as the substrate for development of practice guidelines by relevant professional and clinical organizations. Success in this effort will ultimately enable researchers and clinicians to parse the growing number of clinically relevant genetic variants into those that should be added to clinical care and those that require further research before entering the clinical arena.    

Objectives of this Research Program

This FOA will support a multi-faceted strategy for developing a Clinically Relevant Variants Resource (CRVR), including engagement and integration with ongoing efforts, data synthesis and curation, consensus development, and hand-off to professional and clinical organizations for development and dissemination of practice guidelines.  Initial activities of the awardee include, but are not limited to:

Applicants are expected to describe their approaches for defining and prioritizing domains into which variants might be grouped for review and evaluation, sifting the published literature and data resources for genes and variants for consideration, gathering the available evidence regarding their clinical impact and effects of potential interventions, developing consensus, obtaining feedback, and providing the consensus findings in a useful format to appropriate professional organizations for guideline development.

Applicants should describe and justify their approaches for grouping genes or variants into categories such as those likely ready for implementation, those clearly having no clinical implications, and an intermediate group for which more information is needed.  Plans for dealing with a profusion of variants of unknown significance (whether they are to be excluded or included), for focusing on particular types of variants or genes as at least an initial, manageable approach, and for harmonizing across efforts that have already attempted to group variants into meaningful categories should also be described.

Applicants should propose approaches for bringing the deliberations to consensus, for dealing with the inability to do so, and for obtaining input on the draft sets of clinically relevant variants from professional organizations, agencies, and other appropriate experts as needed.  Applicants should describe how they will ensure consistency of domain-specific recommendations with the established framework and with recommendations of other domains. Applicants should also indicate an understanding of the ethical, legal, social, and policy issues regarding results reporting and how these issues might be incorporated into the review framework and possibly influence the operation of the CRVR. 

Applicants should also describe in detail any informatics-based approaches for automating the data synthesis and curation processes.  Plans for maintaining the most up-to-date underlying data used to make recommendations and revisiting the recommendations as new data are generated should be described as well.  Applicants should also describe plans to integrate into other informatics resources, including those for patients/public or other potential constituencies, or assess whether it is desirable to do so. 

Applicants should propose the most cost-effective and scalable approach possible and describe their plans for ensuring minimal costs and maximal efficiency throughout the course of the project.  Applicants should also provide annual milestones with metrics that will allow assessment of progress towards achievement of the goals for the CRVR.  Applications should include plans for critically evaluating and revising these milestones on a regular basis.

Program Formation and Governance

The award funded under this FOA will be a cooperative agreement (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award).  Close interaction among the awardee, the NIH, and other collaborators such as ACMG, AMP, ASHG, and CAP will be required to develop appropriate consensus approaches and dissemination plans for the CRVR.  Willingness to accept guidance and assistance from the NHGRI, in close consultation with participating professional organizations and other relevant stakeholders, and/or potential reasons for the inability to do so, should be described. 

The awardee will also be expected to coordinate productively with related ongoing efforts in the scientific community to identify clinically relevant genomic variants and describe plans for leading and facilitating interaction and coordination of this program with related NIH efforts such as the databases listed above and the Clinical Exploratory Sequencing Centers (RFA-HG-10-017) and Electronic Medical Records and Genomics Network (RFAs: RFA-HG-10-009, RFA-HG-10-010, and RFA-HG-11-022).

The  CRVR’s Steering Committee, which will include the Program Director(s)/Principal Investigator(s), representatives from relevant professional and clinical organizations, the NIH Project Scientist, and other experts as proposed by the grantee, will develop the framework for the review and evaluation process, prioritize domains, review the deliberations of the domain-specific working groups, and advise on strategies for synthesizing the clinically relevant variants and their supporting evidence into a data resource and disseminating these findings to the appropriate communities.   To facilitate interaction with other NIH efforts and adoption across a broader range of interests, a liaison from each interested NIH Institute and Center will be identified and invited to attend all Steering Committee meetings.

Early after funding, the grantee will organize the first Steering Committee meeting to initiate the work of the program on a rapid timeline.  The grantee will work with NHGRI to select Steering Committee members who are leaders in a wide range of domain-specific areas and relevant genomic sciences and who work well interactively.  The grantee will organize Steering Committee meetings three times per year and monthly conference calls as needed.  Key co-investigators, and pre- and postdoctoral trainees, in addition to the PD(s)/PI(s), will be eligible to attend Steering Committee meetings.  The PD(s)/PI(s) is encouraged to include investigators and trainees who are members of under-represented minority groups and those from related disciplines such as bioinformatics, computational biology, public health, social sciences, health services and outcomes research, and translational research where appropriate.

It is expected that the CRVR will have domain-specific working groups as defined by the grantee and NHGRI (in conjunction with the Steering Committee) to apply the agreed-upon review framework, adapted as needed, to each domain to reach consensus on the variants and evidence to be included in the resource.   The cost of organizing and facilitating in-person steering committee and working group meetings including the costs for Steering Committee and Working Group member travel, setting up and facilitating monthly steering committee conference calls and regular working group conference calls, as well as staff needed to facilitate the in-person meetings should be included in the proposed research budget.

Professional Organizations Committee

A committee of representatives from professional and clinical organizations and other relevant stakeholders willing to provide input on the development and use of the resource will be established by NHGRI with assistance from the awardee.  The Committee will be convened to facilitate interactions with and obtain feedback from professional organizations and will meet twice a year by teleconference.  At least once a year, there will be a joint teleconference with the Steering Committee to allow members of both the Professional Organizations Committee and the Steering Committee to interact directly. Representatives will also be invited to attend Steering Committee meetings.  A limited amount of funding may be made available to support their travel; for budgeting purposes applicants should assume 12-15 members attending annually.

Data Sharing under this Initiative

Data from this FOA are expected to be handled so as to increase the value of the significant public investment in incorporating relevant genetic variants into clinical care.  Consistent with achieving the goals of this resource, NHGRI expects that data syntheses, collected evidence, review framework, and consensus outcomes from the CRVR working groups will be widely shared with the clinical and scientific communities for research.  Information such as study protocols, descriptions, bioinformatic tools, and publications are expected to be made available through a user-friendly portion of the resource that provides appropriate caveats on use and limitations of the information. 

Applicants should indicate their willingness to cooperate with NHGRI, professional organizations, and other stakeholders in the development and design of research and consultation methods, procedures, policies and strategies to be applied for this resource. Applicants should also describe prior experience in working as part of a research consortium, developing consensus approaches to address particular research-related topics, or other collaborative activities to meet individual study and collaborative goals.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

NIH intends to fund one award with a total cost not to exceed $2,000,000 for fiscal year 2013. Future year amounts will depend on annual appropriations.

Award Budget

Individual application budgets should not exceed $2,000,000 total costs in FY13 and $4,000,000 per year for years FY14-FY16 and must reflect actual needs of the proposed project.  

Award Project Period

The total award period requested for this FOA may not exceed four years.

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

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

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 eligible to apply.

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

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

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, 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:

The letter of intent should be sent to

Erin M. Ramos, Ph.D., M.P.H.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 3058, MSC 9307
Bethesda, MD 20892-9307
Rockville, MD 20852 (courier/FedEx/UPS)
Email: ramoser@mail.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

PHS 398 Research Plan Component

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

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, with the following modification:

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.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (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 SF 424(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.

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 Central Contractor Registration (CCR). 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, NIH, and for responsiveness by NHGRI.  Applications that are incomplete or unresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at nakamurk@mail.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 NOT-OD-10-115.

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/priority 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 likely is the project to improve the assessment of the clinical relevance of genetic variants associated with clinical phenotypes?

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the investigative team bring complementary and integrated expertise to the project including clinical, genomic, and bioinformatics expertise? Do the PD/PI(s) demonstrate the ability to produce consensus from large groups on complex issues? Have the investigators documented their experience working with clinically relevant genetic variation data?  Are the investigators willing to collaborate with the NIH, and related existing efforts, including other NIH-funded and non-NIH funded programs, consistent with meeting the aims of this program?

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?

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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? 

Does the applicant propose adequate methods for identifying key stakeholders and experts, selecting and convening working groups, and facilitating and monitoring progress of the working groups?  Does the applicant propose state-of-the-art methods for working with content experts and expert groups and for evaluating the clinical significance of genomic variants? Does the applicant propose adequate methods for vetting the design of the CRVR, transferring the information to appropriate professional and clinical organizations for development of practice guidelines, and disseminating the consensus process to appropriate research and clinical communities? Is the bioinformatics infrastructure sufficient to accomplish the goals of the project?  Does the applicant propose adequate plans for managing the informatics requirements of the project? Does the applicant propose a scalable approach that ensures minimal costs and maximal efficiency throughout the course of the project?  Does the applicant provide appropriate annual milestones with metrics that will allow assessment of progress towards achievement of the goals for the CRVR?  

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 institutional resources and infrastructure being committed or leveraged?

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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/priority 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, and 2) Resource Sharing Plan.

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 the NHGRI,,in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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 National Advisory Council on Human Genome Research. The following will be considered in making funding decisions:

Additional criteria for award will include:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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 the CRVR 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:

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 CRVR 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:

Collaborative Responsibilities

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop the CRVR. The awardee and the Project Scientist will meet with the program Steering Committee three times per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results.  Key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, in addition to the PIs, are eligible to attend these meetings.

The Steering Committee will have approximately ten to twelve members and 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 the Principal Investigator, representatives from relevant clinical organizations, the NIH Project Scientist, and other experts as proposed by the grantee.  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.

In addition to the domain-specific working groups, the Steering Committee may establish working groups as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The CRVR SC will have the overall responsibility of assessing and prioritizing the progress of the various domain-specific working groups and other needed subcommittees. Awardee agrees to work collaboratively to:

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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually 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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Erin M. Ramos, Ph.D., M.P.H.
National Human Genome Research Institute
Telephone: 301-451-3706
Email: ramoser@mail.nih.gov

Peer Review Contact(s)

Ken D. Nakamura, Ph.D.
National Human Genome Research Institute
Telephone: (301) 402-8823
Email: nakamurk@mail.nih.gov

Financial/Grants Management Contact(s)

Cheryl Chick
National Human Genome Research Institute
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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