It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

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

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

Program Overview:

The Bench to Bassinet Program (B2B) was launched by the NHLBI as a novel approach to address the major barriers of research translation from identifying the causes of human congenital heart disease to ultimately improving outcomes for individuals with congenital heart disease. The B2B strategy is to accelerate the translation of scientific discovery into clinical practice through collaborations of basic, translational, and clinical researchers. Recognizing that many research institutions excel in one or two of these areas, but not necessarily all three, the B2B is structured into three consortia. The Pediatric Cardiac Genomics Consortium (PCGC) comprises human genetics and genomics researchers; the Cardiovascular Development Consortium (CvDC) basic scientists; and the Pediatric Heart Network (PHN) clinical trial and observational study experts. Although each component is free-standing, the close communication among the groups means that the findings of one consortium are readily shared with and acted on by the others, thereby driving the science forward in a more comprehensive, translational manner.

Since 2009, the CvDC component of the Bench to Bassinet Program has generated and publicly distributed a variety of datasets related to cardiac morphogenesis; including whole-tissue and single-cell RNAseq, ChIP-seq, ATAC-seq, and chromatin conformation capture using tissue from mice and zebrafish embryos and differentiated pluripotent stem cells. This data, and similar datasets deposited in other public data repositories, have high value toward the interpretation of genomic variants identified through the PCGC or understanding the mechanism of normal and abnormal cardiac development, NHLBI Trans-Omics Precision Medicine (TOPMed) Program, and other genomics studies.

However, a gap remains in the integration of multiple existing computational tools and approaches to bridge the current knowledge of cardiovascular developmental biology with genomics data. Specifically, a computational model is needed in which candidate genes and variants could be entered to predict their impact on developmental processes. Computational modeling is hampered by the lack of a centralized resource to access community-wide datasets and lack of flexibility in common pipelines for data analysis tailored to specific research questions. To address this gap, the CvDC will transition from a data-generating consortium to a Cardiovascular Developmental Biology Data Resource Center (CDDRC).

Research Objectives:

The CDDRC will facilitate analysis of candidate genes and variants associated with CHD by assembling the data output from previous funding cycles of the CvDC, plus external datasets, into a queryable data repository complete with computational tools. The goals of the CDDRC will be to:

• standardize/harmonize basic science developmental datasets;

• develop tools to enable integration and analysis of these datasets;

• facilitate integrative cross-omics analyses across multiple datasets and data types, and

• apply use cases driven by variants identified by the PCGC to validate the data harmonization and tools developed.

The product of the CDDRC would, by the end of the project period, be a coordinated and interoperable suite of harmonized datasets, computational tools, and links to model organism databases that could be inserted as a functional module into the NHLBI DataStage platform.

A second function of a CCDRC will be to expand the cadre of data scientists using data generated by the B2B Program. In conjunction with the B2B Administrative Coordinating Center, this could be stimulated through Challenge Prizes and an educational program. Challenge Prizes offer cash awards to any individual or group that provides a creative solution to a specifically defined problem. Such challenges might include:

• use of machine learning approaches to integrate gene expression, epigenetics, and chromatin conformation datasets from a variety of model organisms or cell culture systems and developmental stages to identify novel developmental pathways or novel disease/gene associations, or
• integration of multiple omics datasets from PCGC and the CvDC (and other sources) to identify novel genes/pathways involved in the pathogenesis of CHD.

Educational programs might involve short-courses (e.g., less than 2 weeks) provided at the CDDRC or remotely to introduce potential users to the data repository; long-term (e.g., 3 months to < 1 year) courses to enable postdoctoral fellows or graduate students to spend time in residence at the CDDRC and to develop a computational model; or summer research fellowships for undergraduates.

Selected Research Examples

Examples of research activities that could be supported by this FOA include, but are not limited to, the following:

• Develop a comprehensive computational model to estimate morphological impact of PCGC variants
• Map how signaling pathways direct cells down the cell state landscape
• Identify how extracellular signals integrate with cardiovascular development intracellular gene regulatory networks
• Link alterations in developmental cell lineages to CHD
• Link chromatin modifications to critical developmental timepoints
• Develop/adopt cutting edge methods of data manipulation and display to allow users to better probe and visualize developmental biology and CHD datasets and enable users to create phenotype-specific metadata to conform to community standard ontologies
• Develop a means of matching phenotypes/pathways between species, for example human and model organisms
• Develop computational methods that integrate multiple functional genomics data to predict noncoding regulatory sequence variants to further decipher mechanisms of gene regulation in CHD

These topics are examples only. Applicants should not feel limited to the topics mentioned above and are encouraged to submit other topics pertinent to the objectives of the FOA.

Applications that focus on the following topics would NOT be responsive to this FOA:

• Mechanistic studies of cardiovascular development. Applicants are encouraged to submit applications for mechanistic studies in response to the R01 parent program announcement.
• Development of novel model organisms
• Data generation, such as RNAseq, ChIP-seq, or chromatin conformation
• Construction of a human genomics data repository

Consortium Organization

The B2B Program is a consortium that includes the CDDRC, cooperative PCGC Research Centers, an Administrative Coordinating Center (ACC), the PHN, and NHLBI Project Scientists.

The CDDRC will be responsible for assembling data relevant to cardiovascular developmental biology into a queryable data repository complete with computational tools. The CDDRC will establish an educational program and collaborate with the ACC to stimulate use of the data through Challenge prizes. The CDDRC will collaborate with the PCGC Steering Committee to use the CDDRC data resource to relate genes and variants identified by the PCGC to cardiovascular developmental biology and gene regulatory networks. The CDDRC will collaborate with the PCGC Data Hub to assure interoperability between the CDDRC data resource and human genomics data collected by the PCGC.

PCGC Research Centers are responsible for proposing and developing human genomics studies, recruiting study subjects, entering data into the web-based data collection system, performing other aspects related to conducting the research, providing skills development for junior investigators, and disseminating research findings.

The Administrative Coordinating Center (ACC) issues subcontracts to core facilities that support the scientific work of the consortium, organizes meetings, and coordinates activities of the External Advisory Committee (EAC). The ACC also provides a PCGC Data Hub that serves as PCGC data repository and internal data portal, supports the PCGC’s clinical protocols, and performs administrative tasks for the entire B2B program. Cores necessary to support the science and to provide resources and services to multiple Research Centers are established by the ACC. The NHLBI will determine the Core configuration with input from the Steering Committee and the EAC (see below). Cores can be located at Research Centers or at institutions outside of the PCGC, depending upon expertise, performance, and cost. The ACC and NHLBI will oversee the process of Core selection, and the ACC will administer the budget for the Cores. Cores may be phased in and out based on scientific need during the course of the funding cycle.

The NHLBI is responsible for organizing and providing overall support for the B2B Program. The NHLBI Program Office and Office of Grants Management are responsible for the overall management. In addition to regular grant stewardship, the NHLBI Project Scientists will be involved substantially with the awardees as a scientific partner, consistent with the Cooperative Agreement mechanism.

An independent External Advisory Committee (EAC), appointed by the NIH and funded through the ACC, reviews the progress of the program every 6 - 12 months and provides advice to the PCGC and CDDRC grantees about scientific direction. Members of the EAC and ad hoc external experts review all applications for potential cores and provide advice to the ACC about core selection.

Data sharing

A critical mission and goal of the B2B Program is to expand resources to the broader scientific community to advance research. The B2B Program strives to meet or exceed expectations in NIH data sharing policies. Data generated by the B2B Program are expected to be made available to the broader research community through open, shared databases consistent with achieving the goals of the program.

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

• 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

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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. 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.

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Letter of Intent

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

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

• 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:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Telephone: 301-435-0270
Email: [email protected]

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

• Direct costs for CDDRC personnel and the data resource are allowed up to a maximum of $750,000 direct costs per year.
• Direct costs for an educational program and Challenge prizes are allowed up to a maximum of $250,000 direct costs per year. The applicant is allowed to request funds to support participants in the educational program,
• Include travel costs for 2-3 members of the CDDRC to attend an annual meeting of the B2B Program in Bethesda, MD.

Specific Aims: Applicants should list the overall Specific Aims of the proposed CDDRC.

Research Strategy: The Research Strategy must consist of the following subsections uploaded as a single attachment:

A. Current state of the science

Applications should summarize the current state of the science by identifying existing public datasets of high value toward developing a comprehensive cardiovascular development/CHD resource, discussing the significance of the existing datasets toward interpretation of CHD candidate genes and variants, and identifying gaps in the existing data.

B. Use Cases

Applications should describe several use cases that will drive dataset harmonization and development of tools and models. A use case is a narrative of how an end user might use and interact with a system or computational tool. It includes a description of the type of user, the goal of the interaction (scientific output), and the requirements needed to achieve that goal (datasets, tools, etc.). Based on the use cases, applicants should identify the requirements and resources needed to prepare the relevant datasets and develop the tools and models. They will also identify barriers that will need to be overcome to harmonize cardiovascular development/CHD datasets and enable the computational models required for the use cases.

C. CDDRC structure and development

Applications should describe a data strategy which addresses data storage, data identification, data access, data sharing, data processing, data provenance and data governance. Applications should also describe the structure of the proposed data resource and address how it will be capable of supporting the use cases and providing computational tools needed to fulfill the goals of the data resource. Describe the personnel involved and their experience with similar activities. Describe the proposed approach to software tool development including the proposed project management method for delivering milestones on time. Applications should also describe how the proposed CDDRC will overcome the barriers identified in the use cases.

Applications may propose to participate as a CDDRC made up of two or more sites. If two or more sites are proposed, plans for collaboration and interaction among sites should be clearly documented in the application, and the responsible investigator(s) at the collaborating site(s) should be named.

Applications should propose a data structure that has potential for integration within the NHLBI DataSTAGE platform. Applications need not propose a cloud contract, but should propose a data structure as if cloud support is provided through the NHLBI.

D. Interaction with B2B components and DataSTAGE

Describe opportunities for interaction with other components of the B2B Program. At a minimum, interactions should include monthly conference calls with NHLBI and ACC personnel; attendance at the annual meeting of the B2B Program of key members of the CDDRC team, including PD/PIs; and participation as needed on conference calls with members of the PCGC. Applicants are encouraged to contact members of DataSTAGE Project Teams to maximize leveraging of the DataSTAGE cloud-based platform.

E. Outreach and Skills Development

A critical component of software development is user engagement. Applications should describe the proposed plan to engage users throughout the development process. The plan should also include a process for selecting topics for Challenge prizes, administering a Challenge competition, and awarding prizes. An education program should be described to provide short- or long-term plans for skills development that use the CDDRC data resource or to develop new computational tools.

F. Milestones

Identify key milestones for development of the CDDRC and propose a timeline to achieve the milestones.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The overall goal of the CDDRC is to produce a data resource that makes cardiovascular development datasets broadly usable by the research community to help researchers conduct mechanistic research in cardiovascular development and to effectively interpret candidate genes and variants identified from human studies. Therefore, the Data Sharing Plan should address ease of access and usability of the CDDRC for investigators who may or may not be familiar with the Bench to Bassinet Program.

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

How well do the example use cases described in the application represent the primary needs of the cardiovascular developmental biology community?

Investigator(s)

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

Specific to this FOA:

Does the applicant demonstrate a thorough understanding of the breadth and depth of existing cardiovascular developmental biology datasets?

Innovation

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

Approach

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

Specific to this FOA:

How well does the proposed structure for the data resource demonstrate its capability of providing the community access to data and tools necessary to advance the field of cardiovascular developmental biology? How likely is it that the proposed approach to software tool development will generate tools of value to the community? How well-designed is the plan for user engagement and how likely is it to stimulate broad use of the data? Does the educational program target skills development toward gaps in the field and how likely is the strategy to be effective? Are the key milestones identified and appropriate, and is the timeline for achieving the milestones realistic? How well does the plan to interact with B2B and leverage DataSTAGE demonstrate that it is likely to be realistic and effective?

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

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?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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 Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) 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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group, convened by the NHLBI, 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.

• 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.

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

1. Award Notices

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

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

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

2. Administrative and National Policy Requirements

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Accept close coordination, cooperation, and participation of the NIH staff in the aspects of scientific and technical management of the project as described below.
• Ensure that all CDDRC goals are met.
• 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 participate in the cooperative nature of the B2B, including participation on regular teleconference calls with NHLBI Project Scientists and ACC personnel, and with PCGC members as necessary.
• Attend B2B Program annual meetings.
• Where opportunities are identified, participate in collaborations with other NIH research efforts.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• The NHLBI is responsible for organizing and providing overall support for the B2B Program. The NHLBI Program Office and Office of Grants Management are responsible for the overall management.
• The NHBLI Project Scientists will serve as NHLBI representatives on any B2B committees, when appropriate.
• The NHLBI Project Scientists, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.
• The NHLBI will appoint members of the External Advisory Committee (EAC), and serve as liaisons between the awardee and the EAC.
• Support or other involvement of industry or any other third party in the study - e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources - may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
• Additionally, an agency program official or IC 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:

• Establish the milestones under this FOA.
• Develop uniform procedures and policies necessary to meet the B2B Program goals.
• Promote the availability of the data resource developed by the CDDRC to the scientific community at large.
• Report periodically to the EAC.

3. Reporting

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Charlene Schramm, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3793
Email: [email protected]

Office of Scientific Review
National Heart, Lung, and Blood Institute
Telephone: 301-435-0270
Email: [email protected]

Lynn Rundhaugen
National Heart, Lung, and Blood Institute (NHLBI)
Telephone:301-480-4546
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.