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 purpose of this Funding Opportunity Announcement (FOA) is to support studies of the human virome and its role in cardiovascular, pulmonary and hematological health, resilience, and diseases. This FOA seeks applications that aim to identify and evaluate the basic molecular and physiological mechanisms that underlie how the virome may be influencing heart, lung and blood health and disease.

The human microbiome comprises the bacteria, viruses and other microorganisms living in association with the human body. The human virome consists of viruses that infect human cells, virus-derived elements in our chromosomes, and bacteriophages that infect the broad array of bacteria that inhabit the body.

The NIH Human Microbiome Project (HMP) and other studies have allowed us to better understand the importance of bacteria and have led to the realization of the potential importance of the virome for health, resilience, and diseases. For example, gut bacteria play a role in the formation of trimethylamine-N-oxide (TMAO), a metabolite shown to be linked to atherosclerosis, and bacteriophages in the gut which affect the gut flora may affect TMAO formation. A recent study showed higher levels of circulating cell free DNA, in particular, cell-free microbial DNA (microbiome), among cardiovascular disease patients (valvular heart disease, ischemic heart disease and congenital heart disease) compared to healthy individuals. Among a subset of those subjects studied, the circulating virome in cardiovascular disease patients was enriched with bacteriophages containing a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages. Specific expansion of bacteriophages in Crohn’s disease has been associated with decreased bacterial diversity. Research has suggested that respiratory viruses and the consequent response of the innate immune system could also drive the development of asthma and chronic obstructive pulmonary disease. Many viruses can persist in cells such as hematopoietic cells and vascular endothelial cells, and can influence the host in profound ways independent of classical viral disease. The immune system is continuously stimulated by chronic systemic viruses and this aspect of host-microbiome interactions appears specific to the virome. The virome is considered one of the drivers of idiopathic systemic inflammation that has been linked to many severe public health threats, including cardiovascular diseases. Some viruses may be protective; for example, hepatitis G virus (GB virus C or HGV) may have a protective effect against HIV-associated disease. Cytomegalovirus, a highly prevalent virus, appears to promote recipient T-cell immunity following reduced-intensity T-cell-depleted hematopoietic stem cell (HSC) transplantation. While these initial reports highlight the potential role of the virome in health, resilience and disease, the basic molecular and physiological mechanisms underlying these effects are not known. Many human viruses have been understudied so far. There are many viral elements present in blood other than the major known pathogenic viruses. Two examples of this include the recently identified Giant Blood Marseillevirus and the identification of anelloviruses in the majority of individuals. The effect, if any, of these viruses on heart, lung, and blood health and/or disease is not known. Additionally, the effect of transfusing blood products and their "viromes" on the patients who receive these common therapeutics is not known. For example, transfusion of blood to fetuses and infants whose immune system is in development could potentially have a profound impact on their health, whether helpful or harmful. It is well recognized that exposure to viruses early in life could have a very different health impact compared to similar exposure during adulthood. For example, 90% of infants exposed to hepatitis B virus become chronically infected but 95% of infected adults are able to recover completely. In the United States alone as many as 40,000 transfusions are given annually to those younger than 1 year old , but the impact of the infused virome on their health, for example in shaping and regulating immunity and tolerance, is not yet known.

Research that will be supported by this FOA includes but is not limited to the following:

• Blood virome and its effect on transfusion recipients.
• Interactions between the virome and the microbiome, including in the context of HIV infection.
• Fetal origins of adult disease how the virome in utero affects later life.
• Role of the virome in shaping lung mucosal immunity, including the innate immune response to inhaled toxicants and regulation of mucus hyper secretion.
• Role the virome plays in affecting the lung flora and immune system.
• Role of the virome in heart health and diseases such as myocarditis.
• Role of the virome in idiopathic thrombocytopenic purpura (ITP) exacerbation.
• Role of the virome in respiratory bacterial exacerbations.
• Effects of the virome on endothelium, coagulation and thrombus formation, particularly effects on platelets.
• Role of genetic determinants in affecting the interactions between HIV and the virome
• Mechanisms by which interactions between HIV and the virome contribute to heart, lung, and blood co-morbidities as well as HIV pathogenesis and chronic inflammation.
• Role of the virome in heart, lung and blood health in the context of medical and pharmacological interventions such as transfusion, mechanical intubation, hematopoietic stem cell transplantation (HSCT), and treatment of HIV infection with anti-retroviral therapy.

Research supported by this program is expected to be primarily hypothesis-generating in nature. Purely descriptive or correlative studies will not be considered responsive, unless such applications target identification of new virome elements and include study of the molecular and physiological mechanisms by which these newly identified virome elements may impact heart, lung or blood cells. Well known viruses can be included in studies of the molecular and physiological mechanisms because known viruses could inform research on unknown viruses; further, it may be very important to study interactions among all relevant virome elements.

Research applications that can leverage cohorts or populations from other programs including global initiatives such as international sickle cell disease programs as well as global AIDS programs are encouraged. Stored samples, such as those in the NHLBI repository (https://biolincc.nhlbi.nih.gov/home/) may be of interest, but investigators should be aware that stored samples may only be good for certain studies of selected virome elements but not others. How stored samples were collected, handled, and stored should be taken into consideration if their use is proposed.

The R61/R33 mechanism supports bi-phasic innovation awards that include an initial R61 phase and a second R33 phase. This FOA seeks applications that propose research plans for both the R61 and R33 phases and also includes milestones to be achieved during the R61 phase to qualify for the transition to the R33 phase. This funding mechanism is especially suitable for HLB-related virome innovation research in view of the scarcity of knowledge regarding the virome and potential challenges in carrying out such research.

The R61 Phase

This FOA is intended to support innovative applications that propose an exploratory and developmental 1- to 2-year R61 phase with the ultimate goal of advancing knowledge regarding the human virome and its role in cardiovascular, pulmonary and hematological health, resilience, and diseases. Although preliminary data are not required for a R61/R33 application, they may be included. The R61 phase provides time for necessary preliminary work, such as the feasibility of the proposed study, including necessary modification of approaches, methods, or technology.

The R33 Phase

This FOA is intended to support a 3-year R33 phase that expands upon the developmental/exploratory work of the R61 phase with the aim to identify and evaluate the basic molecular and physiological mechanisms that underlie how the virome may be influencing HLB health and disease. Funding for the R33 phase is contingent on successfully meeting the proposed milestones set forth in the R61 phase (see Section VI. Award Administration Information for further information). Not all R61 applications are expected to transition to the R33 phase.

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)
• 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 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).

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, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
6701 Rockledge Drive, Room 7214
Telephone: 301-435-0270
Email: [email protected]

All page limitations 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 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.

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

The R61 phase I budget should include funds for attending a grantees' in-person meeting near Bethesda, Maryland in late 2018 or early 2019.

The R33 phase II budget should include funds for attending a grantees' in-person meeting annually near Bethesda, Maryland.

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, with the following additional instructions:

Specific Aims: Describe and clearly demarcate the specific aims for both the R61 and the R33 phases.

Research Strategy: Describe the research designs, methodologies and milestones for both the R61 and the R33 phases of the award. The R61 and R33 phases must be clearly demarcated.

R61 Phase

Describe the following:

• Background
• Evidence of feasibility of the proposed approach
• Plans for accomplishing the necessary preliminary work (i.e., substantial modification of approaches, methods, or technology during the R61 phase)
• Research strategy and methods for the R61 phase Milestones - Include a clear description of the R61 phase milestones that, if met, will justify taking the proposed intervention into the R33 pilot study. Milestones must be specific, quantifiable, feasible, and scientifically justified with regard to the specific aims. See Milestones heading below for further information.
• Timeline for the completion of the R61 phase. The timeline should include a discussion of the suitability of the milestones for assessing success in the R61 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 phase.

R33 Phase

It is not necessary to repeat background information or methodology details in the R33 research strategy section that were provided in the R61 section.
Describe the following:

• Milestones - Include a clear description of projected specific, measureable and achievable progress throughout the project period, which can be used as an indicator of success.
• Details of the experimental design including plans for the development and expansion of the R33 phase beyond the work accomplished in the R61 Phase. See Milestones heading below for further information.
• The significance and innovation of the proposed work/research with discussion of how the work will be hypothesis-generating and lead to important information regarding the influence of the virome on heart, lung and blood health and resilience.
• How the research proposed for the R33 phase will advance understanding of the role of the virome in heart, lung, and blood health and resilience
• Timeline for the completion of the R33 phase

Milestones:
Adequate identification and evaluation of the basic underlying molecular and physiological mechanisms by which the virome may influence heart, lung, and blood health and resilience must be a key criterion of the decision to move from the R61 to the R33 phase. Milestones for both the R61 and R33 portion of the project must be specific, quantifiable, feasible, and scientifically justified; not simply a restatement of the specific aims. Stating well-defined, measurable milestones is critical to the application. These will vary depending on the nature of the proposed research, and should be tailored to the applicant’s specific research goals. The clarity and completeness of the R61/R33 application with regard to specific goals and feasibility of milestones are critical. Specify conditions under which the project would not proceed to the R33.

Preliminary Data:

The R61 phase will be considered exploratory, so extensive preliminary data from the applicant’s own laboratory is not required. However, the project must be based on a strong rationale, and the applicant should provide evidence that the proposed approach and methods are feasible.

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.

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.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. 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. 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.

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.

Meetings and Webinars:

Funded investigators will be expected to participate in periodic program teleconferences and webinars during the R61 and R33 phases of the award. Additionally, investigators are expected to attend an in-person meeting near Bethesda, Maryland in late 2018 or early 2019 during the R61 phase and an in-person meeting near or in Bethesda, Maryland annually during the R33 phase.

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

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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.

For this particular announcement, note the following:

The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases.

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.

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?

Specific to this FOA: How strong is the likelihood that the proposed R61 phase will be hypothesis-generating and lead to important information regarding the influence of the virome on heart, lung and blood health and resilience? What is the likelihood that the research proposed for the R33 phase will advance understanding of the role of the virome in heart, lung, and blood health and resilience?

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?

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?

Specific to this FOA: Once the R61 milestones are achieved, how clearly are the development and expansion of the R33 phase described?

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?

Specific to this FOA: How strong is the likelihood that the necessary preliminary work, such as, substantial modification of approaches, methods, or technology will be accomplished during the R61 phase? Are the milestones for assessing success in the R61 phase reasonable and are the implications of successful completion of these milestones relevant to the R33 phase research plans? To what extent are the transition milestones adequately described and appropriate for the proposed work?

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

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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.

Milestones

Are quantitative criteria pre-specified and clearly defined to assess milestone achievement and feasibility relevant to advancing from the R61 to the R33 phase? Are R61 milestones feasible, well developed and quantifiable with regard to the specific aims? Are quantitative threshold values specified for the proposed milestones? Specifically, will the milestones help determine if the project succeeded in (a) demonstrating that the basic underlying molecular and physiological mechanisms being studied provides an initial proof of principle, and (b) providing preliminary evidence that the mechanisms proposed in the R61 phase will advance understanding of the manner by which the virome may influence heart, lung, and blood health and resilience. Is the study timeline feasible? Does the application specify conditions under which they would not proceed to the R33 phase?

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

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

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

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

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

Not Applicable

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

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

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 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.

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.

Proposed milestones will be evaluated in the peer review process and any negotiated actions must be mutually agreed upon by the applicant (Authorized Organizational Representative (AOR)), the PD/PI, and the NHLBI program and grants officers prior to the award of the R61 phase. Funded applicants are solely responsible for planning, directing, and executing the proposed project. The approved milestones will be incorporated into the terms and conditions of the award and will be considered in evaluating the progress of the R61 award.

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 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.

PDs/PIs must submit a Non-Competing Continuation Progress Report (PHS 2590) at the end of the R61 project period to inform the decision to move from the R61 to the R33 phase. The PHS 2590 should include:

• A summary of the R61 Specific Aims and importance of the work accomplished
• A section called R33 Transition Milestones, describing in detail the milestones and progress achieved in the R61
• A clear description of how research during the R33 phase will be impacted by attainment of the R61 milestones
• A report which clearly indicates which milestones were or were not completed successfully. In the latter case, an explanation must be provided as to why the milestone was not met.
• Detailed budget pages for current and future years of the R33 phase, and revisions to address reviewers comments from the initial peer review if doing so would provide additional pertinent information about the R33 phase

The AOR will submit the approved R33 transition package to the NHLBI Grants and Program Officer no later than November 30, 2018. Receipt of this progress report will trigger an administrative program review that will determine whether or not the R33 should be awarded. The release of R33 funds will be based on original R61/R33 peer review recommendations, successful completion of mutually agreed upon negotiated scientific milestones, on program priorities, and on the availability of funds. For funded applications, peer review is not anticipated between the two phases of the project, but NHLBI reserves the right to conduct a program review with outside opinions.

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)
Finding Help Online: http://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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Shimian Zou, PhD
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0074
Email: [email protected]

Pothur R Srinivas, PhD
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3712
Email: [email protected]
Lis Caler, PhD

Division of Lung Diseases
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0222
Email: [email protected]

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

Howard Moore
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-5081
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.