Part 1. Overview Information

Participating Organization(s)
National Institutes of Health (NIH)

Components of Participating Organizations

This FOA is a Common Fund initiative (http://commonfund.nih.gov) through the NIH Office of the Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by a trans-NIH team led by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Funding Opportunity Title
Genome Sequencing Center for the Gabriella Miller Kids First Pediatric Research Program (U24 Clinical Trial Not Allowed)
Activity Code
U24 Resource-Related Research Projects – Cooperative Agreements
Announcement Type
Reissue of RFA-RM-16-001
Related Notices
None
Funding Opportunity Announcement (FOA) Number
RFA-RM-18-030
Companion Funding Opportunity
None
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.310
Funding Opportunity Purpose
The purpose of this Funding Opportunity Announcement (FOA) is to establish one or two centers that can rapidly generate high quality whole genome sequence and variant data from a large number of human specimens representing two types of pediatric conditions - childhood cancers and structural birth defects.  All sequence data generated under this FOA will be re-processed and harmonized by the Gabriella Miller Kids First Pediatric Data Resource Center (Kids First DRC), which is also charged with building a public-facing, web-based portal that will allow researchers to search, access, aggregate, analyze, and share annotated genomic sequence, variant, and phenotypic datasets.  Together these resources will promote comprehensive and cross-cutting research and collaboration within the pediatric research community.

Key Dates

Posted Date
July 23, 2018
Open Date (Earliest Submission Date)
September 30, 2018
Letter of Intent Due Date(s)
September 30, 2018
Application Due Date(s)
October 31, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)
Not Applicable
Scientific Merit Review
February 2019
Advisory Council Review
May 2019
Earliest Start Date
July 2019
Expiration Date
November 1, 2018
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

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

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

Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Introduction

In response to The Gabriella Miller Kids First Act (https://www.govtrack.us/congress/bills/113/hr2019/text), NIH, through the Common Fund, has established the Gabriella Miller Kids First Pediatric Research Program (Kids First). The Kids First program seeks to foster collaborative research to uncover the genetic etiology of childhood cancer and structural birth defects. In pursuit of this goal, the program is intended to support a ten-year effort to develop the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource), which will include a public-facing, web-based portal that will allow researchers to search, access, aggregate, analyze, and share annotated genomic sequence, variant, and phenotypic datasets. This resource will be of high value for the pediatric research community and will facilitate analyses across diverse conditions to uncover shared developmental pathways.  The overall goal is to help researchers understand the underlying mechanisms of these conditions, leading to more refined diagnostic capabilities and ultimately more targeted therapies or interventions. 

The Kids First program seeks X01 proposals for the sequencing of samples collected from childhood cancer and structural birth defects cohorts.   Future calls will be published to continue the identification of similar types of projects and samples for each year of the sequencing center award, pending availability of funds.

This FOA invites applications for Kids First sequencing center(s) that will produce whole genome sequence and variant data from identified cohorts  to contribute to the Kids First Data Resource. Proposals including RNA sequencing, as well as other types of sequencing, are welcome, when justified. This FOA 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.

Goals

The goals of this FOA are as follows:

  • Generation of whole genome sequence data and variant data from childhood cancer and structural birth defects cohorts that the Kids First Program will select through the X01 mechanism described above.
  • Submission of sequence and variant data to the Kids First Data Resource Center, which is serving as the NIH-designated controlled-access public database for this program, and any other databases that may be designated by the Kids First Program, as well as providing the same data to the project/sample Program Directors/Principal Investigators (X01 PDs/PIs), as needed. 
  • Coordination with project/sample PDs/PIs who will submit samples as well as coordination with the Kids First Data Resource Center to fulfill program goals.

The FOA expects high quality sequence and variant data to be generated from the largest number of cases and samples possible with available funds.  It is anticipated that costs will decrease over the course of the award while data quality is maintained or improved, so the number of cases that can be sequenced and analyzed per dollar spent is expected to increase. 

Coordination and Governance 

The center(s) under this FOA will be funded using a cooperative agreement.  The center(s) will be required to closely interact with project/sample PDs/PIs on sample transfer and QC, project design, and data transfer.  If two centers are funded, coordination between the centers will be necessary to assure comparable data quality, standards, and formats, and to avoid unnecessary duplication of efforts.  In addition, the selected center(s) are expected to communicate and closely coordinate with the Kids First Data Resource Center (DRC), which was funded starting in 2017.  Close interactions with the NIH program staff will also be required to assure appropriate and timely project assignments to the funded center(s) and satisfactory progress toward the FOA goals.  The activities to be coordinated include, but are not limited to, establishing data standards and formats, establishing communications for sample tracking, and coordinating data transfer for access by project/sample PDs/PIs and public release of sequence, variant, and phenotypic data by the DRC.

A Steering Committee will be the main governing body of the Kids First Program.  The Steering Committee will be composed of the PIs of the Sequencing Center(s), Kids First Data Resource, representatives of project/sample PDs/PIs, NIH program staff, and an NIH-appointed Chair.  Major scientific and administrative decisions will be determined by majority vote of the Steering Committee.

An independent group of Program Consultants (PC) will be engaged by the NIH to evaluate the progress of the program and to provide advice to the Steering Committee about scientific direction.
See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New
Renewal

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

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH intends to fund one or two awards from this FOA, contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. The total amount of funds available for these awards is anticipated to be $8M per year.

Award Budget
Application budgets for each year should not exceed $8M in total costs.
Award Project Period
The total award period for this FOA is 3 years (FY2019 - FY2021).
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

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

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession
    Other
    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
Foreign Institutions

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

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

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

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

3. Additional Information on Eligibility

 

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

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

 

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

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

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

The letter of intent should be sent to:

Valerie Cotton [C]
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594- 1519
Email: valerie.cotton@nih.gov

Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed
Instructions for Application Submission
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
 

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

Up to 5% of the total budget can be devoted to custom analysis and validation of a selected set of variants in collaboration with X01 project/sample PDs/PIs after the generation of VCF files.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

Applicants should address the following aspects.  Relevant previous experience should be described succinctly.

 A) Genome Sequencing and Variant Identification

  • Sample processing.
    This should include receipt, QC, verification, tracking, and storage of de-identified nucleic acids. Protocols for isolating DNA from tumor (frozen or paraffin embedded) and blood specimens, and DNA quality and yield, should be described.  While project/sample PDs/PIs are expected to extract nucleic acids prior to shipping to the sequencing center, sequencing center staff may be asked to suggest protocols and provide guidance for technically challenging tissue types (e.g., paraffin embedded tumor). 
  • Whole genome sequencing and identification of variants.
    Applicants should describe the facilities, sequencing platform(s), and analytical pipelines that will be used for the proposed activities.  Protocols for 1) generation of libraries, 2) sequence data generation, 3) storage and transfer of BAM and alternative files, 4) generation, storage, and transfer of Variant Call Format (VCF) files, and 5) quality metrics, should be described. 

    This FOA anticipates that the following types of cohorts will be sequenced and analyzed: 1) structural birth defects in families such as “trios”(proband, mother, father) or multiplex/multigenerational pedigrees; 2) childhood cancers in families with or without tumor, such as “quads” (normal from proband, tumor from proband, mother, father). The Kids First program will also accept X01applicationss that include sequencing of affected somatic tissue from structural birth defects cohorts as well as “tumor trios” without family members for childhood cancer cohorts (normal from proband and multiple tumor from proband: pre-treatment, post-treatment, relapse, and/or metastasis), when justified.  In addition, the sample/project PDs/PIs may propose other types of cohorts to be sequenced and analyzed by the funded center(s).  Applicants should propose plans for 1) appropriate whole genome sequence coverages for these types of cohorts and samples, and 2) methods for identifying germline or somatic genomic variants from the sequence data.  Types of variants to be identified should include SNVs, indels, and structural variants.  Applicants should propose timelines from having samples in house through delivering the sequence data and VCF files to project/sample PDs/PIs and the Kids First DRC.  The flexibility of the sequencing and variant calling pipeline to accommodate possible fluctuation of sample availabilities should be described as well.  

    After the delivery of sequence and variant data, the next step may be custom analysis and validation of variants for a subset of cases by the center(s) or between the centers and the project/sample PIs, if both parties are interested in pursuing such collaborations.  The funded center(s) may spend a small portion of the total budget(s) for this type of scientific collaboration (see the instruction for R&R Budget).  Applicants interested in pursuing such collaboration should describe the methods that will be applied and products that will be delivered. 

    Finally, to demonstrate the readiness for performing all of the above activities, applicants should describe relevant examples of previous success. 

 B) Computational and bioinformatics capacity.

Computational and bioinformatics capacity to support sample processing, sequence generation and processing, variant calling, variant validation, data storage, and data transfer to project/samples PIs and the Kids First DRC or other NIH-designated repositories, should be included.

 C) Costs

Applicants should provide the following itemized costs.

  • Cost per genome
    Applicants should estimate the cost for whole genome sequencing and variant identification per sample.  This should factor in, but are not limited to, the following items:

Sample intake and processing

Library preparation

Sequencing

Generation of VCF files

QC

Experimental failures

Equipment

Computational and bioinformatics costs

Labor

Indirect costs

  • Cost reduction. 
    Plans for decreasing all of the above costs over the three funded years while improving efficiency and quality should be proposed.
  • Total number of samples to sequence and analyze. 
    The applicant should estimate the minimum number of samples for which the proposed center can generate whole genome sequence and variant data, with annual breakdowns that factor in the cost reduction plan.  For the sake of the application, assume equal number of samples in each of the two cohort types.  For reference, the Kids First Program so far has identified approximately 6,000 samples per year.  It is anticipated that a similar number of samples will be solicited each year in the next three years.   
     
  • Complementary sequencing approaches.
    While this FOA clearly prefers high throughput and cost-effective whole genome sequencing, complementary approaches may be considered.  For example, some whole exome sequencing may be used for cost effectiveness, or RNA sequencing may be incorporated for tissue-specific analyses.  In addition, applicants are encouraged to consider the role of long-read sequencing technologies in analyzing the sample types discussed above.  Although these technologies are not cost-effective for the main purposes of this FOA currently, it is possible that advances in these technologies will soon make it particularly desirable to apply to some Kids First samples, particularly where complex structural variation is suspected to underlie the phenotype under study. Plans for using complementary sequencing approaches should include a rationale that considers unit costs, scale up costs, and added scientific value for specific sample and variant types.  

D) Management Plan

A management plan for the proposed center should be proposed. The plan should describe the organization, reporting, and communication structure within the proposed center including the roles of key center members and decision-making processes. The plan must assure adequate personnel for 1) the generation and delivery of sequence and variant data; and 2) coordination within the Kids First Program.  Overall, the plan should discuss how the proposed organization and management structure will likely lead to success in attaining the goals of the proposed center and the Kids First program.

 E) Coordination and Communication with the Kids First Data Resource Center

One major component of the Kids First Data Resource Center (DRC) is to serve as a Data Coordinating Center to track, ingest, process, harmonize, store, and distribute genomic data generated by Kids First sequencing centers. Therefore sequencing centers are expected to coordinate and communicate with the DRC on activities that include, but are not limited to:

  • Sample-Level Data Tracking.
    The DRC is tasked with tracking and reporting sample-level status reports for the Kids First program. Sequencing centers are expected to communicate sample-level status updates to the DRC including: date of shipment receipt, initial QC pass/fail results, updates on when sequencing starts and completes, and notifications when data is available.
  • Data Transfer and Delivery.
    Kids First sequencing centers are responsible for submitting sequence and variant data to an NIH-designated data repository such as the Kids First DRC, which is serving as the controlled-access public database for this program and is responsible for distributing Kids First data to the research community. Additionally, sequencing centers are responsible for delivering data to the project/sample PDs/PIs, which can be facilitated by the Kids First DRC.
  • File Formats and Analytical Pipelines.
    For whole genome data, sequencing centers are expected to provide to the DRC, at minimum, 1) individual-level raw data files aligned to the most recent reference genome (e.g., BAM aligned to GRCh38) and/or raw unaligned data files with associated metadata (e.g., FASTQ), and 2) individual-level variant data (e.g., VCF).  Sequencing centers should describe what file formats they intend to provide for whole genome sequence as well as other data types (i.e. exome or RNA). Decisions regarding formats and analysis pipelines of sequence and variant data will be finalized in discussions with the NIH.
Although this list is not exhaustive, such activities require close coordination between sequencing centers and the DRC. Therefore, sequencing center applications should include a plan for how they will communicate and coordinate with the DRC to fulfill the expectations described above.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

  • The Resource Sharing Plan should address how methods, analytical pipelines, tools, and standard practice developed under this FOA will be made publicly available.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by NHGRI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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.

 

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

 

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

Do the PDs/PIs have successful experience in performing large-scale whole genome sequencing and variant identification for human structural birth defects and cancers using state-of-the-art technologies and methods?  Do the PDs/PIs have successful experience in managing multiple collaborative projects simultaneously?

 

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

 

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

Will the proposed approaches lead to large volume and high quality sequence and variant data from Kids First samples in a highly efficient and cost-effective way?  Will the management plan enable the proposed center and the program as a whole to meet the goals of the application? Does the application include a plan for coordinating and communicating with the DRC on activities including sample tracking, data transfer, and data delivery to project/sample PIs/PDs? Is the center willing to share raw and derived data files (e.g., FASTQ, BAM, or CRAM, and VCF or gVCF) with the DRC in order to enable genomic data harmonization?

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

 

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?

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.

 

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.

 

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

 

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

 

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

 

Not Applicable

 

For Renewals, the committee will consider the progress made in the last funding period.

 

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.

 

Not Applicable.

 

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

 

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

 

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

 

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHGRI, NIH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned 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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Advisory Council.. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and 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:

  • Accept close coordination, cooperation, and participation of the NIH staff in the aspects of scientific and technical management of the project as described below.
  • Provide the funded center’s goals as requested by NIH staff, with associated throughput, quality, and cost information. These are usually requested at the outset of the award and annually thereafter, but can also be at other times.
  • Determine the approaches for sequence data generation and variant identification, and carrying out those efforts.
  • Ensure that all center goals are met.
  • Determine ways to establish and disseminate the best practices for sequence data generation and variant identification from Kids First samples.
  • Ensure effective interaction with project/sample PIs, the Kids First Data Resource Center, the NIH staff, and the other sequencing center if two centers are funded.
  • Adhere to the NIH policies regarding intellectual property, data sharing and other applicable resource sharing policies that might be established during the funded period as appropriate.
  • Ensure that the sequence and variant data are deposited into appropriate public databases, and that developed resources, including analytical pipelines, are made publicly available in a manner agreed to by Kids First program staff and/or the Steering Committee.
  • Accept and implement any procedures and guidelines developed and approved for the Kids First Program.
  • Accept and participate in the cooperative nature of the Kids First Program, including
  • Attend the Steering Committee meetings;
  • Coordinate and collaborate within the Kids First Program as described above;
  • Where opportunities are identified, participate in collaborations with other NIH research networks.
  • Submit data for quality assessment in any manner specified by the Steering Committee.
  • Inform the Program staff of all major interactions with of the External Scientific Advisors.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NIH staff will have the role of Project Scientists through technical assistance, advice, and coordination.  However, the role of the Project Scientists will be to facilitate but not to direct the activities.

Project Scientists' responsibilities are defined as follows:

  • Make decisions about assignment of projects, and the final project design, to a sequencing center.
  • Participate (with other Steering Committee members) in the group process of setting project priorities and making decisions on joint activities and standard practice of the Kids First Program. The Project Scientists will assist and facilitate the group process but not direct it.
  • Negotiate goals and timelines with the awardees, as necessary.
  • Serve as liaisons between the awardees and the External Scientific Advisors (ESAs), NIH, and the larger scientific community in helping the Kids First Program to achieve its goals.
  • Coordinate the efforts of the Kids First Program with others engaged in similar and related activities.
  • Attend all Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
  • Periodically report progress to the Director of NIH.
  • Lend relevant expertise and overall knowledge of NIH sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve as External Scientific Advisors.
  • Serve on subcommittees of the Kids First Steering Committee, as appropriate.
  • Assist in promoting the availability of the data generated by the Kids First Program to the scientific community at large.
  • Where warranted, co-author publications about the goals of this FOA, and of results of studies funded under this FOA.

Additionally, an agency program official or institute program will have a major stewardship role in the management of the award(s) and will be named in the award notice(s). This stewardship will include evaluation and monitoring progress with respect to the achievement of specific aims, completion of project milestones, timely transfer of data, conformance to regulatory and policy requirements, fiscal accountability, and adherence to any special terms and conditions of the award. In addition, the Program Official will be responsible for approval of budget adjustments and changes in technical or scientific plans that potentially constitute a change in scope of the project, approval of changes in key personnel or their effort on the project and approval of any carryover or supplemental funding requests. The Program Official will continually assess risk regarding potential issues related to accomplishing the scientific aims of the research and protection of human subjects, taking appropriate actions if serious problems are identified.

Areas of Joint Responsibility include:

A Steering Committee will be the main governing body of the Kids First Program.  The Steering Committee will be composed of the PDs/PIs of the Sequencing Center(s), Kids First Data Resource, representatives of sample/project PDs/PIs (one from structural birth defects community and one from the childhood cancer community), and the NIH program staff.  The Steering Committee Chair will be appointed by the Kids First Working Group and will not be an NIH staff member.  Each full member (limited to one person per award) will have one vote except NIH Project Scientists, who will have one collective vote.  Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions.  Major scientific and administrative decisions will be determined by majority vote of the Steering Committee. 

The Steering Committee will:

  • Establish the milestones under this FOA.
  • Develop uniform procedures and policies necessary to meet the Program goals.
  • Provide information to the Program Consultants, who will be engaged by the NIH as needed.  The PCs will evaluate the progress of the Kids First Program and the Program’s awardees,and provide advice to the NIH about scientific direction. 

An independent group of ESAs will be appointed by the NIH to evaluate the progress of the program and to provide advice to the NIH and the Steering Committee about scientific direction.

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 Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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.

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

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)
James Coulombe, Ph.D.


Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Telephone: 301-451-1390
Email: CoulombeJ@mail.nih.gov
Peer Review Contact(s)

Rudy Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301 402-0838
Email: pozzattr@exchange.nih.gov

Financial/Grants Management Contact(s)
Bryan Clark


Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Authority and Regulations
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.