Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Heart, Lung, and Blood Institute (NHLBI) National Institute of General Medical Sciences (NIGMS)
Funding Opportunity Title	Blood and Vascular Systems Response to Sepsis (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	November 8, 2013 - See Notice NOT-HL-13-200. Clarification of Number of Applications.
Funding Opportunity Announcement (FOA) Number	RFA-HL-14-028
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.839, 93.859
Funding Opportunity Purpose	The purpose of this FOA is to solicit applications to participate in Blood and Vascular Systems Response to Sepsis (BVSS) Program. The objective of this initiative is to foster multi-disciplinary research projects needed to unravel the cellular and molecular mechanisms underlying the development of severe endothelial dysfunction that contributes to sepsis-related coagulopathy and vascular collapse. To accomplish this goal, the initiative will support research partnerships to conduct multi-disciplinary research needed to dissect the mechanisms of blood and vascular systems in sepsis pathogenesis.

Posted Date	November 1, 2013
Open Date (Earliest Submission Date)	January 6, 2014
Letter of Intent Due Date(s)	January 6, 2014
Application Due Date(s)	February 6, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June 2014
Advisory Council Review	August 2014
Earliest Start Date	September 2014
Expiration Date	February 7, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

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

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 goal of the Blood and Vascular Systems Response to Sepsis (BVSS) Program is to foster the multi-disciplinary research projects needed to unravel the cellular and molecular mechanisms underlying the development of severe endothelial dysfunction that contributes to sepsis-related coagulopathy and vascular collapse. The purpose of this initiative is to develop a new scientific framework for the prevention of sepsis related morbidity and mortality by applying novel approaches to restore vascular integrity through the discovery of new targets for biomarkers and therapy translation in blood and vascular systems. The National Heart, Lung and Blood Institute (NHLBI) and the National Institute of General Medical Sciences (NIGMS) solicit applications to support research partnerships that promote multidisciplinary research required for scientific cross-talk between complementary research disciplines to better understand the barrier functions at the blood and vascular systems tissue interface. This initiative seeks to address this gap by supporting collaborations that pave the way for the identification of new treatment targets, pathways to target validation, and development of innovative anti-sepsis therapeutics.

Sepsis poses a serious public health problem in the United States and globally with an overall mortality rate of 30%. In the US, the estimated cost of ICU care for patients with sepsis exceeds $20 billion annually. A major contributor to sepsis morbidity and mortality is the breakdown in the function of the blood/tissue barrier due to intravascular or extra-vascular infections. This breakdown is caused by a cascade of inflammatory events resulting in severe endothelial dysfunction which leads to systemic vascular leakage and irreversible multi-organ failure. Until recently, recombinant human activated protein C, a coagulation protein, was the only FDA- approved adjunctive therapy for treating sepsis in adults. However, in October 2011, it was withdrawn from the market after failure to demonstrate improved patient survival in clinical applications, suggesting that the mechanisms of blood and vascular systems response to sepsis required further elucidation.

Blood and vascular systems that respond to sepsis-associated microbial virulence factors encompass innate and adaptive immune cells, platelets, and the plasma proteins that represent antibody, complement, coagulation and fibrinolysis networks. These blood systems are enclosed by the enormous surface of the microvascular endothelium forming organ-specific vascular beds. It is vital that the blood/tissue barrier formed by this microvascular endothelium and the adjoining structures maintain their structural and functional integrity in order to support normal physiological functions of key organs. During sepsis-causing infections, the vasculature is profoundly altered by the combination of microbial virulence factors and proinflammatory mediators released from activated blood cells that gain access to surrounding tissue by crossing the leaky endothelial boundary. Severe endothelial dysfunction then results from the loss of homeostatic function of the microvascular endothelium and contributes to hypoxic injury of multiple organs. It is therefore clear that breakdown of the blood/endothelial tissue barrier is one of the major contributors to sepsis morbidity and mortality. By preventing vascular leakage through reinforcement of the endothelial barrier, it is likely that mortality from sepsis can be reduced.

In keeping with the National Heart, Lung, and Blood Institute (NHLBI) Strategic Plan, the Division of Blood Diseases and Resources convened a Working Group of inter-disciplinary scientific investigators on June 2010, in Bethesda, Maryland, to identify scientific priorities for new studies in the field of sepsis. The Working Group noted that the prevailing sepsis paradigm, namely systemic inflammatory responses to infection, also known as cytokine storm, does not explain the mechanism of sepsis pathogenesis since high levels of the same cytokines are recorded in many autoimmune diseases without the evidence of vascular collapse characteristic of septic shock. It was concluded that the current understanding of sepsis should be expanded to the unifying concept of severe endothelial dysfunction syndrome in response to intravascular or extra-vascular microbial agents that cause multi-organ failure. It was also stressed that new strategies requiring cross-talk between scientific disciplines are urgently needed to understand the barrier function at the blood and vascular systems tissue interface (http://www.nhlbi.nih.gov/meetings/workshops/bsrts.htm). This initiative aims to create a program that will bring together investigators from multi-disciplines to address the knowledge gaps in blood and vascular systems response to sepsis.

This initiative will utilize the multi-PD/PI mechanism to ensure a sepsis-focused multidisciplinary research approach. Applicants must propose a single project with at least two multi-disciplinary PDs/PIs. The research partnership could be across disciplines including hematology, cardiology, critical care, infectious diseases, cell biology, molecular biology, vascular biology, physiology, chemistry, biochemistry, microbiology, immunology, genetics and structural biology. Applicants should also include a comprehensive multi-PD/PI leadership plan that addresses strategies for active multi-disciplinary collaborations.

The research project team members do not necessarily have to be located in the same institution or geographical location since desired combinations of expertise and technologies may not reside at a single institution or even a particular region of the country. The inclusion of new and early stage investigators is encouraged.

There will be an annual investigators meeting in Bethesda, Maryland, to present updates on scientific progress, to exchange ideas, and to discuss problems encountered and finding solutions.

Breakdown of the blood/tissue barrier due to infection leads to endothelial dysfunction resulting in tissue injury, vascular leakage, and ultimate lethal outcome when not controlled by antimicrobial therapy and supportive measures. Therefore, a key investigative goal will be to understand the dynamic interplay between pathogen and its host at the blood/tissue interface. Since this interaction results in significant protein remodeling in the blood and has a profound impact on coagulation, inflammation and morbidity in sepsis, it will be important to: (1) understand the mechanism of vascular integrity, and to characterize the elements of an intact endothelial-blood interface; (2) identify pathways that could restore vascular integrity so that vascular leakage and its associated problems can be prevented; (3) elucidate the mechanisms underlying the development of severe endothelial dysfunction and the breakdown of the blood/endothelial barrier and (4) discover endothelial cytoprotective pathways.

It is important to emphasize that scientific topics must be multidisciplinary in scope to explore how sepsis leads to aberrant hemostasis, microvascular thrombosis, and vascular pathobiology, particularly as related to barrier functions at the blood/vascular systems tissue interface. Research projects may address a clinically relevant question from the perspective of the host response and may consist of basic research, preclinical research, or a combination of basic and preclinical research. Investigators are also encouraged to expand the scope of their research programs through partnerships that involve experimental approaches and/or technologies not commonly used in sepsis research. Examples of such research include, but are not limited to the following:

• Understanding the structural and functional biology of blood and vascular cells as well as coagulation and fibrinolysis networks in terms of their responses to microbial virulence factors and proinflammatory mediators.
• Studying mechanisms for vascular integrity and organ specific vascular injury in relevant animal models of sepsis, and innovative approaches to cytoprotection of the vasculature.
• Evaluating the dynamic response of the host following development of sepsis, with specific focus on discovering key turning points where intervention could alter the course of disease.
• Analyzing host factors in human and/or relevant animal models of sepsis uniquely required for the initiation, progression, and resolution of sepsis.
• Developing new biomarkers based on critical host factors in human and/or relevant models to monitor initiation and progression of sepsis.
• Exploring the therapeutic potential of small molecules and novel recombinant protein derivatives that counteract deleterious effects of procoagulant, proinflammatory, and proapoptotic pathways activated at the blood and tissue interface.
• Investigating the role of innate immunity mediated by its cellular effectors, phagocytes, as well as platelet and endothelial cell activation involving innate immunity receptors-initiated pathways.
• Identifying and elucidating the mechanisms and/or ways to moderate the effects of mediators of vascular reactivity implicated in dysfunction such as, but not limited to: impaired endothelial cell signaling via altered/released mediators; increased vascular and microvascular permeability; glycan modulations, impaired vascular and microvascular responses to reoxygenation and resuscitation; and overall impaired vascular functioning in sepsis.
• Investigating the mechanism(s) of the vascular impairment that leads to cardiovascular dysfunction, such as decreased cardiac contractility and depressed endothelium-dependent vascular relaxation.
• Investigating the mechanisms and/or ways to moderate the effects of oxidative stress, autophagy, apoptosis, and other forms of injury that contribute to the vascular impairment and circulatory collapse seen in sepsis.

Projects outside the scope of this FOA and thus non-responsive are:

• Projects that are not related to sepsis with a focus on the blood and vascular systems
• Projects that do not include a multi-disciplinary approach
• Projects that include clinical trials
• Population-based research.

Non-responsive applications will not be reviewed.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NHLBI intends to commit $22 million and the NIGMS intends to commit $13 million over 5 years to fund up to 8 awards. The following NIH components intend to commit the following amounts in FY 2014: NHLBI, $4,400,000, to fund up to 5 awards. NIGMS, $2,600,000, to fund up to 3 awards.
Award Budget	An applicant may request a budget for direct costs up to $500,000 per year, excluding 1st tier subcontractor or consortium facilities and administrative (F&A) costs.
Award Project Period	The total project period may not exceed 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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)
• 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 not 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

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

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 research project
• 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
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 29892-7924 (express mail zip: 20817)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

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

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

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

Scientific partnerships between investigators who have not collaborated in the past are encouraged so that new interdisciplinary research teams can be formed to address BVSS. Investigators with excellent research training, who have not yet achieved established investigator status may participate.

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

Each multi-PD/PI investigator must commit a minimum of 2.4 person months (20 percent) effort to the research project. If there are more than two PD/PIs, the total effort should be at least 4.8 person months (40 percent).

Each applicant should include budget provisions for investigators to attend the investigators's annual meeting in Bethesda, MD.

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

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

Specific Aims: Applicants must propose a single research project with at least two multi-disciplinary PDs/PIs. Target goals and anticipated impact on sepsis research should be clearly outlined. The research partnership could be across disciplines including hematology, cardiology, critical care, infectious diseases, cell biology, molecular biology, vascular biology, biochemistry, chemistry, physiology, microbiology, immunology, genetics and structural biology. Applicants must clearly define the integrating scientific theme and the multidisciplinary approach intended to be used to accomplish the objectives of the proposed research. Contributions of each PD/PI to the research project and the rationale for using a multidisciplinary approach should be outlined. In addition, applicants need to clearly define new research opportunities that the multidisciplinary approach will be used to accomplish.

Research Strategy: The target goals anticipated on completion of the 5-year project period should be outlined carefully with special reference to contributions expected from the multidisciplinary team. Research projects may be basic research, pre-clinical research, or a combination of basic and preclinical research.

Population based research is not acceptable. Applicants proposing clinical trials are not acceptable.

Multiple PD/PI Leadership Plan: Applicants should include a comprehensive multi-PD/PI leadership plan that addresses strategies for active multi-disciplinary collaborations.

Letters of Support: Letters of support are optional and may be included here.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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.

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

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

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

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

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

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

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.

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

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

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

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

See more tips for avoiding common errors.

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 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? 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? Does the application employ multidisciplinary approaches related to sepsis with a focus on the blood and vascular systems?

Investigator(s)

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

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? 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? Does the application include a multi-disciplinary approach?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Heart, Lung, and Blood Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• 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 to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Institute National Advisory Council or the National Institute of General Medical Sciences 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.

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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

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

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

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

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

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

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Rita Sarkar, Ph.D.
National Heart, Lung, and Blood Institute, (NHLBI)
Telephone: 301-435-1324
Email: sarkarr@nhlbi.nih.gov

Sarah E. Dunsmore, Ph.D.
National Institute of General Medical Sciences, (NIGMS)
Telephone: 301-594-3827
Email: dunsmores@nigms.nih.gov

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute, (NHLBI)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Renee Livshin
National Heart, Lung, and Blood Institute, (NHLBI)
Telephone: 301-435-0166
Email: whitesa@nhlbi.nih.gov

Lisa Moeller
National Institute of General Medical Sciences, (NIGMS)
Telephone: 301-594-3914
Email: moellerl@mail.nih.gov

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 Parts 74 and 92.