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

Clinical Sequencing Exploratory Research Coordinating Center (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HG-12-008

Companion Funding Opportunity

RFA-HG-12-009, Clinical Sequencing Exploratory Research (U01)

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 is to provide centralized support and coordination for the studies and investigators funded under the the Clinical Sequencing Exploratory Research (CSER) program (RFA-HG-10-017 and RFA-HG-12-009), who will explore, within an active clinical setting, the application of genomic sequence data to the care of patients, as well as the studies and investigators in the Return of Results (RoR) Consortium, which encompasses elements of the CSER program and studies supported under the Ethical, Legal, and Social Implications program RFA-HG-11-003 and RFA-HG-11-004.

Key Dates
Posted Date

April 20, 2012

Open Date (Earliest Submission Date)

June 26, 2012

Letter of Intent Due Date

June 26, 2012

Application Due Date(s)

July 26, 2012, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October/November, 2012

Advisory Council Review

January, 2013  

Earliest Start Date(s)

March, 2013

Expiration Date

July 27, 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

OBJECTIVES

The goal of this FOA is to provide centralized support and coordination for the Consortium of Clinical Sequencing Exploratory Research (CSER) studies and investigators funded under RFA-HG-10-017 and RFA-HG-12-009. That Consortium will explore, within an active clinical setting, the application of genomic sequence data to the care of patients, including the ethical, legal and psychosocial implications relating to the return of results from sequencing data.  The successful awardee also will provide support for the Return of Results (RoR) Consortium, which is supported by NHGRI’s Ethical, Legal, and Social Implications (ELSI) Program and is closely affiliated with the CSER program.  Applications submitted in response to this FOA will propose plans to: 1) facilitate the work of the CSER and RoR Consortia through scientific coordination as well as logistical and administrative activities; 2) accelerate the generation and dissemination of findings and best practices by applying appropriate scientific expertise to the communication of Consortia findings and outputs to the broader genomics research community; and 3) support interactions and potential collaborative activities with research groups conducting investigations related to those of the CSER and RoR Consortia and, as appropriate, promote synergy and consistency among projects of this nature.

BACKGROUND

The CSER Program was launched in late 2011 under RFA-HG-10-017, “Clinical Sequencing Exploratory Research (U01)”.  Six awards were made to investigate the infrastructure, methods and issues that will need to be addressed to make routine interrogation of a patient’s genomic sequence a fundamental aspect of her/his medical care.  See http://www.genome.gov/27546194 for more information on the current awards. The FOA called for grantees to develop and apply methods to integrate sequencing into the clinic, as well as to study relevant ethical, legal and psychosocial issues involved in responsibly applying personal genomic sequence data to medical care. To begin to integrate comprehensive genetic knowledge into clinical care, many steps are necessary.  There are important considerations of societal norms starting with approaches to informed consent.  There also are crucial technical challenges.  For example, annotation of variants with respect to function (e.g., those that disrupt protein structure), unambiguous association with disease susceptibility- clinical validity (e.g., CFH variants and macular degeneration), and clinical utility (e.g., a favorable balance of benefits to risks in terms of implications for health outcomes and personal impact to the patient) must be addressed.  The subset of variants that are determined to be useful for clinical consideration must be identified and presented to the clinician in an intuitive, user-friendly summary report.   A range of approaches may need to be developed with respect to offering to return results (particularly incidental findings) to patients, depending on the nature of the disorder or patient population that is the primary focus of study.  For example, assessments of clinical utility (especially for the return of incidental findings) may be very different for patients (and family members of patients) with advanced stage metastatic cancer than for patients with less acutely life-threatening diseases. Special considerations may also apply to studies with pediatric patients. In addition, approaches to clinical translation are likely to evolve during the next decade in response to changes in healthcare, developments in sequencing and informatics, a greater understanding of disease biology, and a more mature understanding of the associated ethical, legal, and social implications. The collaborative and cooperative nature of this program is designed to facilitate the development and standardization of best practices and common approaches to clinical translation, taking into consideration the different needs of different types of patient populations.   

Reflecting this multidisciplinary endeavor, each of the CSER groups is organized into three interdependent projects:  Project 1, clinical study; Project 2, sequencing, analysis, and interpretation, and Project 3, ethical, legal, and psychosocial research. To leverage opportunities to synergize and build on existing resources, active collaboration across the various CSER groups is also underway. For example, Working Groups formed around sequencing standards, analysis methods, integration into electronic medical records, informed consent, genomic variants of potential clinical relevance, and return of results are working together to compare approaches, identify common challenges and solutions, and develop cross-study resources.  Several of these Working Groups interdigitate with the NHGRI ELSI RoR Consortium, which includes investigators involved in Project 3 of each CSER grant as well as investigators with grants that are exploring related issues in the research context.

The similarities in purpose among the funded grants suggest that facilitating cross-study activities would increase the efficiency and reach of the Consortium as a whole.  In addition, a related FOA, HG-12-009, will expand the CSER Network to include 2-4 additional groups.  To facilitate the work of the expanded Consortium, this FOA will establish a Coordinating Center (CC) to work collaboratively with the CSER investigators, the investigators in the related NHGRI ELSI RoR Consortium and other relevant NHGRI programs, as well as NHGRI staff, to facilitate a robust program of research promoting incorporation of genomic information into clinical care.  The proposed CC will work with all CSER and RoR grantees to determine issues that have broad applicability, within and external to the CSER and RoR Consortia; accelerate the resolution of these issues; and disseminate methods, tools and best practices.  The CC will also be responsible for key logistical and administrative aspects of the program, including meeting planning, generating and distributing documents, and facilitating Consortium-wide communication. Within the context of the 2011 NHGRI Strategic Plan (http://www.genome.gov/SP2011/), the CSER Program will have an important role in defining key challenges and opportunities and exploring approaches to merging genomic sequence data with the complexities underlying the practice of medicine and a complex healthcare system.  Similar efforts are ongoing at other academic medical institutions; the research and insight generated by this Program will benefit the entire field by developing and widely disseminating methods and best practices and, where appropriate, interacting with these other efforts.

Research Plan

The goal of this FOA is to provide centralized support and coordination for the network of CSER Study Investigators funded under RFA-HG-10-017 and RFA-HG-12-009 and investigators in related consortia, such as the NHGRI ELSI RoR Consortium.  To meet this primary goal, the applicant is expected to propose and demonstrate the capability to implement action plans in multiple areas of scientific and administrative coordination. 

Scientific expertise in multiple areas is desired to be able to facilitate and support the Consortia and a diversity of active Working Groups, and to organize the development of best practices in these areas.  The current CSER Working Groups comprise the following topic areas:

The awardees funded under RFA-HG-10-017 and RFA-HG-12-009 are or will be supported to initiate a clinical genomic study emphasizing one or more areas of medical investigation (i.e., disease or therapeutic approach) or a specific approach to the use of genotype-phenotype data within a clinical context (e.g., risk prediction modeling or cancer mutation profiling). Within each clinical study, genome-scale sequencing will be implemented and investigators will develop methods to analyze genomic sequence data for clinically actionable variants, parse the data into manageable components (to be defined by the applicant), and translate findings into a format to ease interpretation by the clinician. Investigations of approaches to return of results to patients, their families, and their medical providers also will be explored, and the empirical data collected by these studies are likely to inform development of guidelines and policy. Among all of these studies, the primary emphasis will be on the application of genomic sequence data to the care of patients; new disease variant discovery is neither required nor encouraged. As studies progress from patient enrollment to sequencing and analysis to return of results, the focus of the consortium will naturally shift and different needs may be anticipated.  Although the primary focus of the CC will be on collaborative activities undertaken by the CSER and RoR Working Groups, where needed, the CC will provide direct assistance to individual Consortia Investigators, help to develop common methods and tools, and facilitate cross-study approaches.   

Applicants for the CC should include expertise to address design and biostatistical issues related to analysis of genomic sequence data, taking into account the many novel genetic variants that will be identified.  Experience in bioinformatics and methods related to incorporation of genomic data into electronic medical records (EMRs) will be beneficial.  Approaches to coordinating and facilitating the development and implementation of methods to accomplish this work should be described.  Approaches should be described for recording and organizing novel clinically relevant genomic information, linking it to appropriate clinical activities, and continually updating it as knowledge accrues, as well as facilitating the development, implementation, and dissemination of clinical decision tools and education efforts for patients and clinicians. Each application should clearly describe approaches for coordinating and facilitating development and dissemination of best practices for incorporation of genomic data into clinical care, including informed consent and relevant approvals for returning of incidental genetic findings and findings of potential clinical relevance for use in clinical care. 

The CC will assist CSER and RoR groups as needed in the release of phenotype and genomic data via NIH data resources, assuring compliance with NIH policies relating to privacy and human subjects protections.  However, the primary responsibility for transmitting individual-level sequence data to NIH data resources will rest with the CSER Study Investigators. The CC will not act as a genomic data repository or data coordination center for individual-level sequence data but will serve as a repository for aggregate genomic findings and summary data derived from the CSER and RoR Consortia.

Applicants should describe their approaches to providing integrative, organizational and logistical support and facilitation of the CSER Steering Committee (SC) and RoR Consortium, subcommittees, and working groups.  Relevant activities may include, but are not limited to:

Applicants should also describe their plans for ensuring the security and integrity of program-wide data and for maintaining the privacy of study participants.

Recognizing that the CSER Consortium is part of a broader scientific effort to integrate sequencing into the clinical context, applicants are asked to describe plans for outreach by which they will engage similar clinical sequencing efforts, many already or likely to be launched at research (and non-research) medical centers during the course of this program.  Consistent with a goal of leveraging existing studies including the RoR Consortium, the awardee under this initiative also will be expected to coordinate productively with related ongoing efforts supported by NIH, as applicable. 

The exact boundaries of the activities of the CC and other CSER and RoR Consortia participants are not possible to delineate in their entirety at this time, and will depend in large degree on the capacities and experience of the Investigators selected.  The full range of responsibilities will be negotiated once the project is funded and underway.  Applicants should describe their willingness to be flexible in assuming or relinquishing responsibilities as program needs arise, and the expertise that makes them uniquely qualified to meet these evolving needs.

No patient recruitment or direct data collection (such as questionnaires, examinations, or laboratory measures), or sample acquisition will be supported by this FOA.  NHGRI will support the sequencing or genotyping activities of the program, if any are needed, separately; no funding should be requested for genotyping or other genomic technologies.

Program Formation and Governance / Cooperative Agreement

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

The Program Director(s)/Principal Investigator(s) from each investigative group and the Coordinating Center and the NIH Project Scientist(s) will meet as a Steering Committee face to face twice per year, and by conference call on an ongoing basis, to identify and address common sequencing, analytic and translational issues, review preliminary results, explore opportunities for synergy among studies, develop best practices, and explore the crucial ethical, legal, and psychosocial issues and findings.  Subcommittees and working groups will be established to facilitate collaborative work and standardize approaches. Working groups may propose new research collaborations with non-network investigators and organizations, as long as the activities are conducted in accordance with the policies and practices of the consortium.  Key co-investigators, and pre- and postdoctoral trainees, in addition to the PIs, will be eligible to attend Steering Committee meetings.  The costs of 5-6 persons to attend these meetings, as well as the costs associated with monthly conference calls, should be included in the proposed research budget.

Other information about application content and form

In addition to the instructions above regarding the Research Plan, the application should include the following.

Data Sharing Plans

The NHGRI has long championed the concept of rapid pre-publication data release.  Data from this FOA are expected to be handled so as to increase the value of the significant public investment in implementing clinical sequencing projects.  Consistent with achieving the goals of this program, NHGRI encourages Project Datasets (including phenotypic, environmental, covariate, process, and other relevant data) and associated genotyping data from the participating projects to be widely shared with the scientific community for research.  Information such as study protocols, descriptions, clinical decision support and bioinformatic tools, 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. 

Applicants should indicate their willingness to cooperate with other awardees in the development and design of research and consultation methods, procedures, policies and strategies to be applied in this program. Applicants should also describe prior experience in working as part of a research consortium or other collaborative activities to meet individual study and collaborative goals.

This initiative will not support studies using animal models.  Applications using animal models will be considered non-responsive and returned to the applicant.

Only applications describing protection of patients’ privacy and confidentiality will be considered.  

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.  

 NHGRI intends to fund one award, with a total cost not to exceed $800,000 for fiscal year 2013.

Award Budget

Individual application budgets should not exceed $800,000 total costs per year and must reflect actual needs of proposed project

Award Project Period

The total award period requested for this RFA 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/Principal Investigator 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:

Lucia Hindorff, 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)
Telephone: 301-496-7531
Email: hindorffl@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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive 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 will the proposed research contribute to the integration of sequencing into clinical practice and help evaluate its impact?  

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?   

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?

Is the proposed approach or methodology dynamic and responsive to likely evolving changes in the research area of clinical sequencing?  Are novel or creative approaches to scientific, administrative, or logistical coordination described?  

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?

Are the plans for assisting with Consortium activities, providing logistical support and fulfilling Coordinating Center functions likely to increase the synergy and productivity of the program? Are the proposed plans for providing operational and analytic coordination and support likely to promote productive collaborations and provide maximal scientific value consistent with meeting the aims of this program? Are the proposals for promoting cross-study analyses and disseminating best practices adequate? 

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?

Have the investigators documented their experience with working with EMR data, genomic sequence data, and ELSI considerations in a highly-effective collaborative relationship?    

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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

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:

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 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:

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:

Collaborative Responsibilities

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to incorporate genomic results into clinical care. The awardees and the Project Scientist will meet as the program Steering Committee twice 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 postdoctoral 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 serve as the main scientific body of the program.  The Steering Committee will be responsible for coordinating the activities being conducted by the program.  The Steering Committee membership will include one NHGRI Project Scientist and the PI from each awarded cooperative agreement.  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.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

To address particular issues, the Steering Committee may establish working groups as needed, which will include representatives from the program and the NIH and possibly other experts.

Sequencing Advisory Panel

A Sequencing Advisory Panel (SAP) will evaluate the progress of the program and provide guidance to NHGRI staff. The SAP also will provide recommendations to the National Advisory Council for Human Genome Research about the progress and scientific direction of all components of the program.

The SAP meets quarterly with NHGRI staff.  At least once a year, with the SAP is invited to meet with the Steering Committee to allow the members of the both the SAP and the Steering Committee to interact directly.

Areas of Joint Responsibility include:

The Steering Committee will:

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)

Lucia A. Hindorff, Ph.D., M.P.H.
National Human Genome Research Institute
Telephone: (301) 496-7531
Email: hindorffl@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
E-mail:  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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