NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

It is critical that applicants follow the instructions in the Multi-Project Instructions for 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 reviewed.

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

The objective of this FOA is to support the development of a web-based Data Resource Portal for the Gabriella Miller Kids First Pediatric Research Program (Kids First), supported by a Data Coordination Center (DCC) and an Administrative and Outreach Core. The goal of the Data Resource Portal is to accelerate discovery of genetic etiology and shared biologic pathways within and across childhood cancers and structural birth defects by facilitating access to and querying of annotated genomic sequence and phenotypic data from cohorts of patients with these conditions. The Data Resource Portal will serve as an indispensable research resource where genomic data can be aggregated, accessed, analyzed, and shared within and across the childhood cancer and birth defects research communities as well as the broader scientific community. The DCC will work with Kids First investigators and sequencing centers to facilitate data collection and harmonization. The Administrative and Outreach Core will oversee administrative activities and educate the research community on using the Data Resource Portal.

The Gabriella Miller Kids First Pediatric Research Program is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov. The Kids First program will support gene discovery in pediatric cancers and structural birth defects through the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource) Portal. Both childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions.

This FOA solicits applications to create the Kids First Data Resource Portal which will catalog and curate whole-genome sequence (WGS) and phenotypic data from a wide range of childhood cancers and structural birth defects. The Kids First Program has identified cohorts for sequencing via X01 announcements (PAR-15-259 and PAR-16-150) and will continue to do so through future announcements, pending the availability of funds. Kids First supported sequencing center(s), solicited through RFA-RM-16-001, will generate WGS data. Data from these Kids First-supported studies can be accessed by approved researchers through the National Center for Biotechnology Information’s (NCBI) Database for Genotypes and Phenotypes (dbGaP). The datasets themselves are currently (or will be) physically stored as follows: structural birth defects phenotypic data are stored in dbGaP, structural birth defects WGS data are stored in NCBI’s Sequence Read Archive (SRA), and WGS and phenotypic data from childhood cancer cohorts are stored in the National Cancer Institute’s (NCI) Genomic Data Commons (GDC). The goal of the Kids First Data Resource Center is to make these data accessible, alongside analysis tools, through the creation of a portal to promote comprehensive and cross-cutting research and collaboration among researchers studying various types of pediatric disease.

The awardee funded by this FOA will have three broad responsibilities: developing and managing a Data Resource Portal for the Kids First Program, serving as a Data Coordination Center (DCC) for the Program, and developing and managing an Administrative and Outreach Core for the entire Data Resource Center. The Data Resource Portal is the primary focus of this FOA. The DCC will aggregate and harmonize data from researchers and develop and provide tools for the community. The Administrative and Outreach Core will coordinate administrative logistics as well as education on using the Data Resource Portal, and work closely with the Steering Committee (see below under Cooperative Agreement Terms and Conditions of Award for a description of the steering committee) on overall implementation of the program goals.

The activities of the Data Resource Center comprise areas of computer science and informatics but also require effective communication with the experimentally-oriented user community to achieve its goals. This requires that the Data Resource Center have personnel with sufficient knowledge of both worlds to serve as liaisons and translators between experimentalists and bioinformaticists. Centers are therefore expected to be comprised of teams with expertise sufficient to allow them to function in this way. The areas of expertise included should cover both the existing Kids First data and more broadly the fields of structural birth defects/developmental biology and pediatric cancer. Additionally, in an effort to integrate tools and functions amenable to appropriate statistical analyses into the Data Resource Portal, the Center should include statistical genomics expertise within their team. The team should also have experience with phenotype ontology and harmonization.

Data Resource Portal

The selected awardee will develop a single point of entry, web-based, public facing platform to house, organize, index, and display data and analytical tools with links to relevant partners. The goal of the Data Resource Portal is to make whole genome sequence data and associated phenotypic data readily accessible to users with various levels of expertise. To that end, the design of the features and tools are to reflect statistical rigor and valid methods and approaches relevant to the fields of childhood cancer and structural birth defects, serving a range of experts from developmental biologists to clinicians to bioinformaticists. The web portal should be based on open source software and should be developed through an iterative process based on user feedback. The primary whole genome sequence files (BAMs) will be stored and archived in NCBI's dbGaP/SRA and the NCI's GDC. Thus, the Data Resource Center will not be responsible for a primary genomic data repository function. The Data Resource Portal should have the capacity to grow and adapt with the Kids First Program, including being able to incorporate other types of data, such as imaging or other -omics data. To the extent possible, the Data Resource Portal should link to, interact with, and incorporate other relevant genomics datasets and genomic data portals. The Data Resource Portal may initially tap into tools from NCBI as well as other sources readily accessible to the research community. In later stages of the Kids First program, funds and efforts will emphasize and support the development and integration of new tools.

Data Coordination Center (DCC)

The DCC will collect and facilitate the deposition of whole genome sequence and phenotypic data from childhood cancer and structural birth defects cohorts into relevant repositories. To that end, it will be necessary to have a detailed understanding of diverse data types and the ability to manage quality control of the data. Deposition and registration of data from Kids First studies are of top priority; however, Kids First may seek to collect or link to data from other sources with the intention of creating a comprehensive birth defects and childhood cancer catalog. The DCC will work with investigators to harmonize phenotypes, which may require external collaboration or subcontracts. The data included in the Kids First program are expected to increase with the number of participating cohorts, and the DCC will need to be able to adapt to handle different types of data.

Administrative and Outreach Core

The Core will organize, coordinate, and oversee the administrative and outreach activities of the Kids First Program. Administrative activities will include facilitating meetings and communication between the Data Resource Center, NIH, and external key players, and developing procedures and policies for the operation of the Data Resource Center. Outreach activities will include establishing and maintaining a registry of investigators participating in the Kids First program, and educating the research community on how to use the Data Resource Portal through user training utilizing all available methods (e.g., in person, by webinar, through You Tube videos). Equally important will be engaging users for their feedback in order to improve the functionality of the Data Resource Portal.

The Gabriella Miller Kids First Pediatric Research Program (Kids First) staff will hold a Pre-Application Webinar for all interested prospective applicants. Webinar date and other details will be posted on the Kids First website: https://commonfund.nih.gov/kidsfirst.

Questions and answers related to this FOA will be posted and updated at this link: https://commonfund.nih.gov/kidsfirst/faq

See Section VIII. Other Information for award authorities and regulations.

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.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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

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 allowed.

Applicant Organizations

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

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

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

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

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.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the Multi-Project Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

Jonathan Kaltman, MD
Telephone: 301-435-0510
Fax: 301-480-2858
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative and Outreach Core)	6
Data Resource Portal	12
Data Coordination	12

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of 1
• Data Resource Portal: required; maximum of 1
• Data Coordination: required; maximum of 1

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

The Biographic Sketch should address any previous experience in developing data resources that organize and share genomic (in particular genome sequence) and phenotypic data and in coordinating large complex research efforts.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Concisely address the goals of the Data Resource Center and how the work proposed supports the overall objectives of the Gabriella Miller Kids First Pediatric Research Program and the specific objectives of the Kids First Data Resource Portal and associated components as described in Section I. Funding Opportunity Description.

Research Strategy: The Research Strategy should consist of the following subsections, uploaded as a single PDF attachment.

Applicants should address general considerations that will lead to successful development and coordination of the overall Data Resource Center and how the Center will help meet the general objectives of the Kids First Program by providing a general overview of the proposed Center. Describe the overall design and structure of the Data Resource Center including its management structure, integration of components, and any possible subcontracts. Applicants should provide an organizational chart of the tasks and milestones for what they will accomplish, identify the types of staff associated with each task, and describe their respective roles and responsibilities. The applicant should discuss prior experience in developing data resources, experience in coordinating data flow in a multi-component research project, and managing administrative logistics and outreach activities, as described.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plans for all components should be addressed here under the Overall Component. Plans to share open source software, including source code, use cases, and system design documentation, in appropriate repositories should be specified.

The NIH Big Data to Knowledge (BD2K, https://datascience.nih.gov) program is a trans-NIH data science program that is addressing data sharing by working to make biomedical data Findable, Accessible, Interoperable, and Reusable (FAIR; see https://www.force11.org/group/joint-declaration-data-citation-principles-final). Applicants are encouraged to describe their approaches to ensure that the data and analytical resources supported through this FOA will conform to the FAIR principles. Activities that should be discussed in this regard include, but are not limited to, alignment of data and metadata standards, indexing of data and other digital resources, and uses of computing platforms that enable better data access and interoperability.

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.

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

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the administrative and outreach requirements of the Data Resource Center and how the work proposed supports these activities.

Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the Data Resource Center. Applicants are encouraged to describe how their plans in this section will leverage their experience described in the Biographical Sketch. Applicants are encouraged to propose and justify any other coordination activity that would be useful to the Kids First Program, but is not listed explicitly elsewhere in this FOA.

Describe plans for the following administrative activities, which include, but are not limited to:

• Coordinating the functions of the other components of the Kids First Data Resource.
• Coordinating general communications between representatives of the Data Resource Center and the Steering Committee which consists of Kids First Sequencing Center PDs/PIs, representatives of projects solicited through the X01 announcements, and NIH program staff including the Kids First leadership and the Program Officer and Project Scientist designated for this grant.
• Coordinating and leading regular updates with the Kids First NIH staff, which may include scheduling monthly conference calls (especially in the early phases of developing the Center) and/or monthly email reports of milestones.
• Coordinating yearly face-to-face meetings for the Kids First Steering Committee.
• Documenting discussions, decisions, and actions discussed during meetings and conference calls, and following up with relevant players when necessary.
• Archiving and tracking all materials relevant to the development of the Kids First Data Resource.
• Developing and implementing standard operating procedures and policies for the operation of the Data Resource Center and making them readily available to the public.
• Compiling formal progress reports or other reports as directed by the Project Scientist.

Describe plans for the following outreach activities, which include, but are not limited to:

• Developing and implementing an outreach plan to promote the Data Resource Portal to childhood cancer and structural birth defects research communities as well as the broader research community.
• Establishing and maintaining a registry of investigators participating in the Kids First program's activities.
• Creating in-person events and workshops with current or potential users of the Data Resource to provide hands-on tutorials on how to best use the Data Resource Portal and soliciting feedback on the usability of and desired features for the Portal.
• Creating online tutorials and how-to guides to be integrated in the web-based portal site.
• Providing guidance in the appropriate use of the resource for the breadth of user community envisioned for the Kids First Data Resource.

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, with the following modification:

Do not include a Resource Sharing Plan for this Component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

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.

PHS Inclusion Enrollment Report (Administrative and Outreach Core)

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

When preparing your application in ASSIST, use Component Type Data Resource Portal.

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

SF424 (R&R) Cover (Data Resource Portal)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Resource Portal)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Resource Portal)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Resource Portal)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Resource Portal)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Data Resource Portal Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Resource Portal)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Resource Portal)

Specific Aims: Briefly address the Specific Aims for the Data Resource Portal and how they will be accomplished.

Research Strategy: The Data Resource Portal is envisioned as a single point-of-entry, web-based platform for community access to the Kids First genomic and phenotypic data. For this section applicants should address how the Portal will be designed, launched, maintained, and continuously improved. Applicants should provide a detailed timeline of activities with a particular focus on early design and launch milestones to measure progress. Applicants should specify metrics to evaluate usage and usability of the Data Resource.

Describe plans for the following activities to develop the Data Resource Portal, which include, but are not limited to:

• Web Portal Interface: Designing and implementing a web-based portal to make Kids First data accessible to the research community. The web portal should catalog, display, make searchable, and enable summary statistics and basic analyses of all childhood cancer and structural birth defect data stored as part of the Kids First Data Resource. The primary whole genome sequence files (BAMs) will be stored and archived in NCBI's dbGaP/SRA and the NCI's GDC. The portal may serve as a conduit to sequence data through a relationship with or as a Trusted Partner. Basic analyses are defined as anticipated common questions researchers can ask of individual-level data, without having to apply for access to full datasets from NCBI or the GDC.
• Integration of Diverse Data Sets: Retrieving datasets (sequence, and phenotype data including diverse data types) generated as part of the Kids First Program from dbGaP/SRA and GDC, as described below. The Data Resource will develop partnerships with NCBI/dbGaP and NCI’s GDC staff and build avenues of data exchange with these sources. The application should describe how users might integrate Kids First data with diverse data types (gene function, expression, other -omics data, phenotypic data, etc.) to allow those with unique perspectives on human disease to perform data mining and complex data analyses facilitated by the Data Resource Portal. Datasets that will be retrieved include, but are not limited to:

o Kids First X01 projects: Integrating data from Kids First supported X01 projects into the Data Resource is of top priority. Sequence data from structural birth defects cohorts will reside in NCBI's SRA, phenotype and meta-data from structural birth defects cohorts will be accessible through NCBI's dbGaP. Both data types for childhood cancer cohorts will reside in NCI’s Genomic Data Commons (GDC).

o Projects supported by PAR-16-348-(R03): Some grants funded by this FOA may support data analysis of data collected and previously sequenced with non-NIH (e.g. private) funds. Under the condition of the award, grantees will deposit these data in dbGaP/SRA or GDC as part of the Kids First Data Resource.

o Existing birth defect cohorts in dbGaP/SRA and existing childhood cancer cohorts in the GDC (including those collected as part of the Therapeutically Applicable Research To Generate Effective Treatments [TARGET] program or The Cancer Genome Atlas [TCGA]).

o Other external repositories or datasets that may exist in the research or clinical community. Some files may exist in outside domestic and international repositories; the data portal team will be tasked with identifying, cataloging, and creating links to outside datasets, while conforming to the various data sharing policies of the outside repositories.

• Data Storage: Collating and storing datasets of individual level phenotype and sequence variant data of Kids First cohorts. Making these datasets available for query.
• Data Analysis: Developing infrastructure and tools that will enable:

o Viewing, manipulating, and exporting summary analysis of multiple datasets at the same time.

o Identifying cohorts through a "free text" search that accepts a broad range of search terms encompassing standard ontology as well as other common vocabulary relevant to gene variants and phenotypes.

o User-defined queries to identify cases and/or samples sets, based on variants, phenotypes.

o Gene-specific or gene-set-specific queries, returning all data across defined project data sets.

o Case-specific or case-set-specific queries, returning all data across defined project data sets.

o Creating synthetic cohorts by allowing users to specify phenotypes or custom range of data values which will be applied across multiple studies in the Data Resource.

o Grouping and exploring queries by consent group or Data Use Limitations. Specifically, when assembling a cohort filtering out datasets or individuals that cannot be accessed for further analysis.

o Other summary-level queries.

o Making existing data analysis tools (e.g. NCBI's SRA ToolKit, the Genome Workbench, etc.) easily accessible for researchers to use.

o Making available analytic tools that were developed through other Kids First FOAs.

• Data Display: Developing or adapting existing open source or commercially available software utilities to provide online tools for omics data visualization. Providing intuitive and easy to understand display of data and query results.
• Creating a dynamic and cross-referenced index of dataset files relevant to the Kids First program, as described above. Providing links to and access information about these data sources.
• Developing partnerships and links to relevant programs, including but not limited to NCBI, ClinGen, NHLBI's TOPMed program, the Pediatric Cardiac Genomics Consortium Data Hub, FaceBase, the Rare Disease Portal, Matchmaker Exchange, and the Monarch Initiative.
• Creating a system for users to contact cohort recruiting sites for collaboration and collection or sharing of further data, such as more detailed phenotype information. This may involve linking to the PI registry or integrating existing registry systems (e.g. eRA through dbGaP).
• Incorporating new findings, i.e. new annotations, into the stored datasets.
• Working with potential users to refine use cases; design, test, and improve the usability of the interface; and solicit and incorporate ongoing feedback. For example, it is anticipated that users will range from developmental biologists to bioinfomaticists. Therefore, describe several anticipated use cases by different types of users and how the design and implementation of the Data Resource Portal will enable data analysis. Outline how Data Resource Portal user interface will be adaptable for future improvements that might be suggested by the NIH staff as well as the external user community so that the Portal may be improved and refined throughout the project period.
• Developing web-based tutorials for users, including interactive help pages and FAQs.
• Devising and maintaining a system for collecting metrics on website/portal usage and functionality, including a user login/registration system, to inform future decisions about changes and modifications needed for website improvements.
• The web portal should support all major platforms and consider development of mobile apps. The portal should exhibit flexibility to respond to the changing needs of the scientific community in a timely manner.
• Developing and implementing access controls to data in conjunction with dbGaP and GDC consistent with human subjects protections regulations and genomic data sharing r policies.
• The NIH Big Data to Knowledge (BD2K, https://datascience.nih.gov) program is a trans-NIH data science program that is addressing data sharing by working to make biomedical data Findable, Accessible, Interoperable, and Reusable (FAIR; see https://www.force11.org/group/joint-declaration-data-citation-principles-final). Applicants are encouraged to describe their approaches to ensure that the data and analytical resources supported through this FOA will conform to the FAIR principles. Activities that should be discussed in this regard include, but are not limited to, alignment of data and metadata standards, indexing of data and other digital resources, and uses of computing platforms that enable better data access and interoperability

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, with the following modification:

Do not include a Resource Sharing Plan for this Component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

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.

PHS Inclusion Enrollment Report (Data Resource Portal)

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

When preparing your application in ASSIST, use Component Type Data Coordination.

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

SF424 (R&R) Cover (Data Coordination)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Coordination)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Coordination)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Coordination)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Coordination)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Data Coordination Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Coordination)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Coordination)

Specific Aims: Briefly address the Specific Aims for the Data Coordination Center or DCC and how they will be accomplished.

Research Strategy: The applicant should discuss how data coordination tasks will be accomplished, staffed, and managed. Applicants are encouraged to describe how their plans in this section will leverage their experience described in the Biographical Sketch.

Activities of the DCC will include, but may not be limited to:

• Tracking cohort samples through the sequencing pipeline from shipment from cohort investigators to sequencing centers until deposition of data into dbGaP/SRA or NCI's GDC.
• Facilitating, through collaboration with NIH Genomic Program Administrators, dbGaP and/or GDC registration and quality control for data from all Kids First cohorts and external birth defects and childhood cancer cohorts that will be incorporated into the resource.
• Facilitating appropriate data deposition from organizations with previously sequenced data, through the required procedures (dbGaP/SRA or GDC deposition).
• Developing realistic timelines and milestones for generating and depositing Kids First genomic and phenotypic data (including diverse data types) into the Kids First Data Resource.
• Supporting "help desk" functionality for handling questions related to data access, data deposition, etc.
• Developing and implementing a plan for phenotype harmonization that might include:

o Working with PI’s to obtain and clarify/understand source phenotype data

o Working with NIH Kids First Working Group to create standard trait definitions

o Documenting standard operating procedures

o Creating a web-based phenotype inventory

o Leveraging existing efforts where relevant

• Developing and implementing a plan to receive and annotate the results of secondary analyses of Kids First data.

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, with the following modification:

Do not include a Resource Sharing Plan for this Component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

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.

PHS Inclusion Enrollment Report (Data Coordination)

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

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.

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) using ASSIST or other electronic submission systems. 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.

This initiative is not subject to intergovernmental review.

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.

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Data Resource Center 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 Data Resource Center proposed).

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 Data Resource Center that by its nature is not innovative may be essential to advance a field.

Does the Data Resource Center 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 Data Resource Center 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 Data Resource Center? 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? Are the broad areas of expertise necessary for development of the overall Data Resource represented?

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 Data Resource Center? 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?

If the Data Resource Center 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?

As applicable for the Data Resource Center 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 Data Resource Center 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

Not Applicable

Not Applicable

As applicable for the Data Resource Center 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 . Resource sharing for all components of the Resource Center will be considered under the Overall Component.

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.

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 Data Resource Portal that by its nature is not innovative may be essential to advance a field.

Significance

Does the Data Resource Portal 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 Data Resource Portal 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?

Investigator(s)

Are the Lead(s), collaborators, and other researchers well suited to the Data Resource Portal? 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 there is more than one Lead, do the investigators have complementary and integrated expertise; ? Do the investigators demonstrate significant experience with developing web portals and data resources that facilitate data sharing, data queries, and data visualization? Do the investigators have the experience and ability to handle diverse data types and to present an integrated view of these data? Do the investigators demonstrate significant experience with coordinating collaborative basic or clinical research? How strong is the evidence that the investigators have a track record of success in carrying out human genomic research programs?

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? Does the applicant propose innovative strategies for sharing and/or visualizing data or facilitating cross-cutting data analysis?

Approach

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

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

• Are the leadership approach, governance, and organizational structure appropriate for the Data Resource Center?
• Does the application provide a clear plan including milestones for the complex work-flow that will be required, including realistic timelines?
• Do the development plans for the Data Resource Portal include obtaining input from potential end users and usability testing?
• Are all appropriate end users considered?
• Has the applicant demonstrated an understanding of avenues for interfacing with dbGaP, GDC, and other databases containing structural birth defects and childhood cancer data?
• Does the applicant have a plan to ensure that data, consented for different purposes, is used appropriately?
• Will the Portal be flexible and adaptable to the changing needs of the scientific community in a timely manner?
• Will the data resources developed by the Portal conform to FAIR principles?

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 resources available within the scientific environment to support electronic information handling, data systems, web site development, and data security?

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

As applicable for the Data Resource Portal 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

Not Applicable.

Authentication of Key Biological and/or Chemical Resources

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.

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.

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 Data Coordination Center (DCC) that by its nature is not innovative may be essential to advance a field.

Significance

Does the DCC 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 DCC 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?

Investigator(s)

Are the Lead(s), collaborators, and other researchers well suited to the DCC? 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 there is more than one Lead, do the investigators have complementary and integrated expertise? Do the investigators have a track record of success in carrying out human genomic research programs? Do the investigators demonstrate significant experience with coordinating collaborative basic or clinical research? Do the investigators have the experience and ability to handle diverse data types and to present an integrated view of these data?

Innovation

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

Approach

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

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

• Are the leadership approach, governance, and organizational structure appropriate for the DCC?
• Does the application provide a clear plan including milestones for the work-flow that will be required, including realistic timelines, for facilitating deposition of Kids First genomic and phenotypic data into relevant repositories as part of the Kids First Data Resource?
• Does the applicant propose a framework for exploring ontologies and performing phenotype harmonization that builds upon existing efforts?
• Does the applicant describe a plan for helping investigators submit non-NIH sponsored genomic and phenotypic data into the Kids First Data Resource?
• Does the applicant address Data Use Limitations and how they will be incorporated into the Kids First Data Resource?
• Does the applicant provide examples to show experience and ability to accept, handle and integrate diverse data types?

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?

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

As applicable for the DCC 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

Not Applicable.

Authentication of Key Biological and/or Chemical Resources

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.

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.

Reviewers will evaluate the following items while determining the scientific and technical merit, and in providing an Impact Score, but will not give separate scores for these items.

For the Administrative and Outreach Core, the reviewers will evaluate the following:

• Does the Administrative Core Lead have appropriate experience for overseeing the administrative and outreach activities of the Core?
• Are the other Core personnel appropriate?
• Is the management plan sufficient and commensurate with the complexity of the overall Data Resource Center?
• Will the services provided by the Core enable the other components to achieve their goals?
• Are the Core's plans for outreach and community training to enhance the use and utility of the Kids First Data Resource Portal sufficient and likely to be successful?

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

As applicable for the Core 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

Not ApplicableAuthentication of Key Biological and/or Chemical Resources

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

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.

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

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.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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, 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 awardees' 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 responsibilities 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.
• Ensure that all center goals are met.
• Ensure effective interaction and coordination with project/sample PIs, the Kids First Sequencing Center(s), and the NIH staff.
• Adhere to the NIH policies regarding intellectual property, data release and other applicable resource sharing policies that might be established during the funded period as appropriate.
• 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 efforts.
• Inform the Program staff of all major interactions with External Scientific Advisors (ESAs).
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access.

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 Scientist(s) through technical assistance, advice, and coordination. However, the role of the Project Scientist(s) will be to facilitate but not to direct the activities.

Project Scientists' responsibilities are defined as follows:

• Participate (with other Steering Committee members) in the group process of setting project priorities and making decisions on joint activities and standard practices of the Kids First Program. The Project Scientist(s) 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 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 ESAs.
• Serve on subcommittees of the Kids First Steering Committee, as appropriate.
• Assist in promoting the availability of the Data Resource developed 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 Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

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 Kids First Data Resource Center, the PDs/PIs of the Kids First supported Sequencing Center(s), representatives of sample/project PDs/PIs (one from structural birth defects community and one from the pediatric cancer community), and the NIH program staff. The Steering Committee Chair will not be an NIH staff member. Each full member (limited to one person per award) will have one vote except NIH Project Scientist(s), who will have one collective vote. 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 ESAs, who will be appointed by the NIH. The ESAs 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 between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The panel members will be a designee of the Kids First Steering Committee, 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.

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 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.

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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Jonathan Kaltman, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0510
Email:[email protected]

Allen B. Richon, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1024
Email: [email protected]

Tracee Foster
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3843
Email: [email protected]

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.

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.