Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/).  The FOA will be administered by the National Human Genome Research Institute (NHGRI/NIH), (http://genome.gov) on behalf of the NIH.  

Funding Opportunity Title

DNA Sequencing Core for an Undiagnosed Diseases Network (UDN) (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

RFA-RM-13-018

Companion Funding Opportunity

RFA-RM-12-020, U01 Research Project – Cooperative Agreements
RFA-RM-13-004, U01 Research Project – Cooperative Agreements

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.310

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to establish a centralized DNA Sequencing Core for Undiagnosed Diseases Network (UDN) patients. 

Key Dates
Posted Date

August 7, 2013

Open Date (Earliest Submission Date)

October 19, 2013

Letter of Intent Due Date(s)

October 19, 2013

Application Due Date(s)

November 19, 2013, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March 2014

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

November 20, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Nature of the Research Opportunity

The purpose of this funding opportunity announcement (FOA) is to establish a DNA Sequencing Core for patients seen through the NIH Undiagnosed Diseases Network (UDN).

Background

Rare and yet-to-be-described disorders are a difficult problem for patients, their families and their physicians.  The NIH Office of Rare Diseases Research notes that about 6% of patients seeking their assistance have an undiagnosed disease.  For those who were ultimately diagnosed, as many as 15% had persistent symptoms without diagnosis for at least 5 years, a difficult and costly delay for patient, family (including other afflicted family members), and physicians who struggle to identify and treat these disorders.  This diagnostic odyssey is usually expensive with repeated, sequential diagnostic efforts involving a series of physicians pursuing similar duplicative imaging (with related increased X-ray exposure and other risks) and biomarker investigations.

In addition, these patients present compelling research questions since clarification of the underlying genetics, biochemistry and physiology of these disorders will lead to a better understanding of their disease processes and those of related disorders.  Advances in the science of genetics and genomics in medicine have made it possible to understand the causes and potential targets for treatment of some of these diseases.  Furthermore, as the cost of genotyping and sequencing continues to fall and the accuracy of these methods increases, these approaches become more attractive as potentially standard means to diagnose these disorders.

The Intramural Research Program – Undiagnosed Diseases Program (IRP-UDP) began in May 2008 and from modest initial recruitment numbers, has over a four-year period received approximately 6,300 inquiries. Despite the resource limitations of a new pilot program, NIH investigators over the four years since program initiation have responded each year to an average 1,575 inquiries, evaluated 575 medical records for potential participation and admitted 113 patients for evaluation.  As these data reveal, even without a systematic approach to advertising the program, there is a substantial unmet demand for these capabilities. This justifies the creation of a Network that will be able to address more inquiries, and potentially be more accessible to patients throughout the country who require these services.

Scientific Knowledge to be Achieved

The applicant(s) funded by this FOA will join the NIH Undiagnosed Diseases Network, consisting of the grantees from the related FOAs (RFA-RM-12-020, “Coordinating Center for an Undiagnosed Diseases Network” and RFA-RM-13-004, "Clinical Sites for an Undiagnosed Diseases Network"), together with the ongoing IRP-UDP and NIH program staff.  This funding opportunity is designed to provide centralized DNA sequencing services to UDN patients network-wide.  The Network will increase the availability of diagnostic services, expand the geographic distribution of patient access sites, foster opportunities for collaboration between laboratory and clinical investigators, and provide resulting data and protocols to the broader community.  These efforts will lead to new knowledge regarding the biochemistry, physiology, and mechanisms of these diseases and improve diagnostic and management options for patients afflicted with them.

Objectives of this Research Program

The objectives of this program are to:

1.  Provide DNA sequencing (exome and genome) and CLIA variant validation to facilitate research into the etiology of undiagnosed diseases by collecting and sharing standardized, high-quality sequence data;

2.  Provide raw (unassembled) sequence results as quickly as possible within at most a two-week turnaround time.  Approximately 3,300 UDN patients and their family members are anticipated over 4 years; and

3.  Participate in an integrated and collaborative research community across multiple clinical sites and core laboratories with laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases and share this understanding to identify improved options for optimal patient management.

It is the intent of the NIH to establish a Network Coordinating Center (CC) several months prior to the selection of the new Clinical Sites (CS) and DNA Sequencing Core in the fall of 2013.  All CS (including the IRP-UDP) will be expected to utilize common investigative and data collection protocols to the degree possible in order to facilitate pooling of data to enhance the scientific and diagnostic value of the resulting information.  The UDN DNA Sequencing Core will similarly be expected to adopt a standard protocol for sequencing UDN patients network-wide.  All data from UDN patients will be submitted to the CC as soon as they are collected for cleaning, quality control, and compilation in a Network-wide dataset to be distributed periodically to all CS (including the IRP-UDP) as agreed upon by the Network Steering Committee. 

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 interactions amongst the awardee and NIH will be required to develop this complex Network.  Shortly after the award, the DNA Sequencing Core Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) and key personnelwill meet with CC representatives, CS PD(s)/PI(s), IRP-UDP investigators and NIH program staff to plan approaches, identify barriers, and propose solutions for creating and maintaining a centralized DNA Sequencing Core for the UDN. 

The UDN governance will rest with the Network Steering Committee in collaboration with NIH program officials, with advice from an External Scientific Panel, and subject to oversight by a UDP Working Group of the NIH Common Fund.  The Steering Committee may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific Network functions such as patient recruitment, patient selection and assignment to specific CS, clinical evaluation, final diagnosis, and access to Core Laboratories (including the DNA Sequencing Core), as needed.

A Steering Committee composed of PD(s)/PI(s) from all sites (including the DNA Sequencing Core, CS, CC and the IRP-UDP) and the NIH Project Scientist(s) will be responsible for the scientific direction of the Network.  The Steering Committee will meet quarterly during the first year and three times per year or as needed subsequently.

The UDN Steering Committee will be the operational group through which the NIH UDP Working Group interacts with the UDN.  It will also ensure dissemination of program data such as sequence data and other materials to the wider scientific community.

An External Scientific Panel (ESP) will be named by NIH program officials and will be responsible for monitoring Network activities and making recommendations to the UDP Working Group and NIH regarding processes and substantive issues that arise during Network operations.

Core Laboratories for specialized technologies will be established by the UDN, including the DNA Sequencing Core and other Core Laboratories.  To facilitate data sharing and pooled analyses, these Core Laboratories will provide these services Network-wide, but depending on capabilities at the individual CS, such testing could be conducted locally according to agreed-upon standards, with resulting data submitted for Network-wide analyses and data deposition.  A competition for providers of other Core Laboratory functions, to which the new CS may apply, will be conducted once the new CS are established and running smoothly. 

The Network SC will be tasked with developing an equitable process for prioritizing access to these resources, whether at the IRP-UDP, the new CS, or their contractors or collaborators, to be reviewed and approved by the Network’s External Scientific Panel and the NIH Working Group.  This process will likely involve a subcommittee or working group to define priorities for access, formats for requests, and expectations for turnaround and follow-up as needed.

Data Sharing under this Initiative

Data from the UDN are expected to be handled so as to increase the value of the significant public investment in the creation and operation of the Network. Consistent with achieving the goals of the program, NIH expects that the project datasets (phenotypic, environmental, covariate, process, and other relevant data) and associated genotyping/sequencing data from the Network will be widely shared with the scientific community for research, while carefully observing standards of patient privacy, confidentiality, and management of health information.  Information such as sequencing data is expected to be made available through an open access section of a database such as dbGaP, other public web sites, and publication in the scientific literature.  The UDN Steering Committee will also develop and implement network-wide approaches for data deposition.

Mid-Course Review (July 2017)

Applicants should describe their plans to participate with the CC in preparing yearly reports for the Network leadership, the External Scientific Panel, and the NIH UDP Working Group. The yearly report for FY17 will include a more detailed report which an external group will use to make recommendations on the continuation or shut-down of the UDN effort.

This review group will also be asked to make recommendations for orderly close-out of this project either in FY18/FY19 if the mid-year review determines that close-out is warranted, or for issuing a renewal FOA to continue the project through final closeout in FY22.

The Network can be envisioned as beginning with a phase of network design prior to the UDN DNA Sequencing Core award; this Design phase will involve only the CC, IRP-UDP, and NIH program staff and not the new CS or the DNA Sequencing Core.  Once the new CS and DNA Sequencing Core are awarded, subsequent phases involving them will include: 1) start-up; 2) full network operation; and 3) mid-course review.  Should the mid-course review be successful, a repeat solicitation for Network continuation and eventual close-out will be released; if unsuccessful, modest close-out funding may be provided.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

One award is anticipated from this FOA, contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.  The total amount of funds available for this award is approximately $800K total costs for FY2014.  In FY2015-FY2017, $1.4M total costs per year is anticipated though future year amounts will depend on annual appropriations.

Award Budget

Application budgets should not exceed $800K total costs in FY14 and $1.4M total costs per year in FY15-FY17. The budget must reflect the actual needs of the proposed project.  

Award Project Period

The total award period for this FOA is 4 years (FY14 through FY17).

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 not eligible to apply.

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

Required Registrations

Applicant Organizations

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

Applications for the DNA Sequencing Core may be submitted by individuals located at the same institution as an applicant for the CC submitted under FOA RFA-RM-12-020 or a CS submitted under RFA-RM-13-004, but an individual may not be the PD/PI of RFA-RM-12-020 or RFA-RM-13-004 and the DNA Sequencing Core grant.

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 that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

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:

Anastasia L. Wise, PhD
National Human Genome Research Institute
Telephone: 301-443-0585
Email: anastasia.wise@nih.gov

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required 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.

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities and Other Resources: Applicants should describe the relevant institutional environments which would facilitate the effective implementation of the proposed DNA Sequencing Core.  Applicants should also describe existing or planned resources that would be available to the DNA Sequencing Core, such as clinical and research sequencing facilities, participating and affiliated institutions and units, geographic distribution of space and personnel, and consultative and statistical resources.

Other Attachments: The Responsibilities of the UDN DNA Sequencing Core are described in Section VI.2, “Administrative and National Policy Requirements.”  Applicants should indicate their willingness to cooperate with other UDN awardees in the development and design of research approaches, procedures, policies and strategies to be applied to this program.

Applicants should describe how they will work with the other members of the Network Steering Committee (SC) to define a mode of operation that best matches the sequencing needs of the selected sites and the IRP-UDP, within broad guidelines of parity, openness, cost-effectiveness, timeliness, and optimal patient care, as defined by the SC, the NIH, and its advisors.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: List each aim for the DNA Sequencing Core and how it supports the Objectives of this Research Program.

Research Strategy: In this FOA, as in all FOAs related to the UDN, applicants are encouraged to creatively engage the scientific and operational problems that need to be addressed for the Network to be a success.  NIH recognizes that the approach developed by the IRP-UDP is only one model, albeit a successful one, that may be challenging to adapt outside the unique setting of the NIH Clinical Center.  Within the framework of this FOA, there are a variety of approaches to Network creation and subsequent function that may ultimately be adopted by the Steering Committee and NIH.  DNA Sequencing Core applicants should discuss sequencing plans, defend the approaches they favor, and describe their willingness to implement sequencing protocols agreed upon by the Network as a whole.

A) Genomic Sequencing Plan

B) Genomic Sequence Analysis

C) CLIA Variant Validation

D) Costs

An itemized breakdown of costs per patient for sequencing (exome and genome), primary analysis, and CLIA validation.  

Letters of Support: Institutional commitments made to the UDN DNA Sequencing Core should be clearly documented.

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 modifications:

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

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

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-13-030.

Section V. Application Review Information


1. Criteria

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

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  How will this project improve the approach to sequencing patients who suffer from rare diseases or yet to be described diseases?  

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Have the PD(s)/PI(s) participated in any collaborative, multi-center networks?  Do the PD(s)/PI(s) have experience collecting, analyzing, and publishing genomic sequence data?  Does the proposed research team have adequate genome sequencing experience?  

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? Will this research advance the use of genomics, sequencing, related technologies and the use of common data elements/protocols in clinical care of patients with rare or as-yet-undescribed diseases?    

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?

Is the genomic sequencing strategy adequate?  Is the proposed research plan likely to yield high quality unassembled sequence data as quickly as possible within at most a two-week turnaround time?  Is the analysis strategy appropriate for the UDN?  Are the costs per patient for genomic sequencing, primary analysis, and CLIA variant validation appropriate?

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?  Are the plans for sustaining the DNA Sequencing Core once Common Fund support ends presented and substantiated by clear institutional commitments?  Are the bioinformatics infrastructure/capabilities to securely transmit and store genomic data files for the research project adequate?  Are the computational and analysis resources adequate? 

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves 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 Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

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 National Human Genome Research Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for 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/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

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

Section VI. Award Administration Information


1. Award Notices

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

Any application awarded in response to this FOA will be subject to the DUNS, SAM 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 UDN 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(s) 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 UDN and that NIH staff will be given the opportunity to offer input to this process.  The Project Scientist(s) will participate as members of the Steering Committee and will have one vote.  The Project Scientist(s) will have the following substantial involvement:

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop the UDN. The awardee and the Project Scientist(s) will meet in person with the program Steering Committee on a quarterly schedule during the first year of Network operation and subsequently 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. PDs/PIs, 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, 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 the PD(s)/PI(s) of the DNA Sequencing Core, PD(s)/PI(s) of each CS and the CC award, other staff as needed (ex-officio) and the NIH Project Scientist(s).  The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired.  Each CS (including the IRP-UDP), the CC, and the DNA Sequencing Core will have one vote and the NIH Program Scientist(s) together will have one vote. 

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 UDN SC will have the overall responsibility of assessing and prioritizing the progress of the various working groups and other needed subcommittees.

The DNA Sequencing Core 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 annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

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

Application Submission Contacts

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

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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

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

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

Scientific/Research Contact(s)

Anastasia L. Wise, Ph.D.
National Human Genome Research Institute
Telephone: 301-443-0585
Email: anastasia.wise@nih.gov

Peer Review Contact(s)

Rudy O. Pozzatti, Ph. D.
National Human Genome Research Institute
Telephone: 301-402-8739
Email: pozzattr@mail.nih.gov

Financial/Grants Management Contact(s)

Lisa Oken
National Human Genome Research Institute
Telephone: 301-594-5250
Email: loken@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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