Pulmonary Vascular-Right Ventricular Axis Research Program (R01)

Pulmonary Vascular-Right Ventricular Axis Research Program (R01) is sponsored by National Institutes of Health (NIH). This funding opportunity solicits research grant applications to study right ventricular (RV) function/dysfunction and disease, particularly in the setting of lung vascular disease.

Expired RFA-HL-12-021: Pulmonary Vascular-Right Ventricular Axis Research Program (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating National Heart, Lung, and Blood Institute ( NHLBI ) Funding Opportunity Title Pulmonary Vascular-Right Ventricular Axis Research Program R01 Research Project Grant Funding Opportunity Announcement (FOA) Number Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) This funding opportunity announcement (FOA) solicits research grant applications from organizations proposing to study right ventricular (RV) function/dysfunction and disease.

Utilizing a multidisciplinary and collaborative team approach, this program will foster research which will lead to improved diagnostics and therapeutics for RV disease, particularly in the setting of lung vascular disease. Human subjects research ( http://grants. nih.

gov/grants/policy/hs/ ) must be proposed and applicants are strongly encouraged to use the multiple principal investigator approach to study the right ventricular-pulmonary Open Date (Earliest Submission Date) Letter of Intent Due Date October 13, 2011, by 5:00 PM local time of applicant AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in 424 (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 Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information I.

Funding Opportunity Description Purpose: The purpose of this FOA is to support a novel multidisciplinary and coordinated research effort to acquire critical disease-defining knowledge of the pulmonary vascular-RV axis in human subjects leading to improved and targeted diagnostics and therapeutics for right ventricular failure (RVF).

The pulmonary circulation is intimately coupled with RV function in health and disease and it is clear that patients with lung vascular disease, particularly pulmonary arterial hypertension (PAH), die because of RVF. It is unclear whether RVF and disease occurs only secondary to afterloading effects, or whether the diseased lung vasculature is essential to cause loss of RV compensatory mechanisms during loading.

Furthermore, our understanding of clinical RVF is limited because: 1) current concepts of RVF mechanisms have been shaped largely by inference from investigations of left ventricular failure, despite evidence that the RV and LV may differ in their respective responses to increasing afterload; 2) no detailed knowledge base exists in humans, including genetic/genomic data, regarding the transition from compensatory RV hypertrophy to RVF; and 3) a coordinated effort between pulmonary vascular researchers and cardiac failure investigators has not been specifically fostered to acquire this knowledge.

Therefore, this research program will support meritorious human subjects research (NIH definition) acquiring knowledge of human RVF through studies involving the pulmonary vascular-right ventricular axis. For each individual R01 project, a multidisciplinary approach will be required.

Multidisciplinary "teams" should be constituted by experts in cardiovascular biology, heart failure, and/or clinical cardiology, with expertise in lung vascular biology and disease and/or pulmonology. In addition to the core expertise in cardiac and lung vascular research, expertise may also include imaging, bioengineering, epidemiology, genetics, or any other discipline necessary to produce a robust research project.

Proposals should be hypothesis-driven.

Specific Areas of Research Interest: Examples of studies could include, but are not limited to: defining factors regulating pulmonary circulation-RV dynamics and developing novel measures to assess function/dysfunction; elucidating factors controlling RV growth, injury and repair in conjunction with lung vascular disease development; elucidating biomarkers or other signs indicative of RV reprogramming in the setting of lung vascular disease; discriminating afterload effects from lung vasculopathic-dependent processes of RV dysfunction, compensation, and failure; conducting genetic and epigenetic studies of the lung vascular-right ventricular axis in health and disease; conducting genomic and/or proteomic studies leveraging existing cohorts and/or populations in which RV function can be followed; and testing pilot interventions in well-described lung vascular disease patients in which novel or validated RV indices can be measured and Furthermore, projects proposing to develop new reagents for use in human subjects studies of the pulmonary vascular-right ventricular axis, apply novel imaging approaches or modalities, develop model systems using human subjects research-derived data, or invent tools for advancing mechanistic research into human lung vascular disease and RVF, will also be considered responsive to this Program.

Studies which interrogate RV compensatory mechanisms in the setting of adult congenital heart disease and/or pulmonary thromboembolic disease are also encouraged. Human subjects research ( http://grants. nih.

gov/grants/policy/hs/ ) must be proposed. Projects proposing only animal model studies will not be Principal Investigators who are awarded support under this program will be expected to meet on an annual basis to discuss emerging findings from their respective projects.

Application Types Allowed Glossary and the SF 424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The NHLBI intends to commit $4,050,000 for up to 6 The NHLBI intends to commit an estimated total of $20. 25 Application budgets are limited to $450,000 in direct costs in any year. Funds must also be budgeted for an annual meeting of individual awardees supported by this program.

The project period is 5 years. described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA. Section III.

Eligibility Information 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 Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) 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 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 SF 424 (R&R) Application Guide.

It is expected that key personnel will be constituted by multidisciplinary expertise. Core expertise involving investigators with cardiac and lung vascular expertise is required.

A multiple PD/PI plan is strongly This FOA does not require cost sharing as defined in the NIH Grants Policy Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. IV.

Application and Submission Information 1. Requesting an Application Package 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 .

Form of Application Submission It is critical that applicants follow the instructions in (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 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 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 Name, address, and telephone number of the PD(s)/PI(s) Names of other key personnel Participating institutions 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 National Institutes of Health 6701 Rockledge Drive, Room 7214, MSC 7924 Bethesda, MD 20892-7924 (express/courier zip: 20817) Required and Optional Components The forms package associated with this FOA includes all applicable components, mandatory and optional.

Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components. All page limitations described in the SF424 Application Page Limits must be followed.

PHS 398 Research Plan Component All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 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 Do not use the appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. 3. Submission Dates and Times Part I.

Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission. Organizations must submit applications via 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 are responsible for viewing their application 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. 4. Intergovernmental Review (E.

O. 12372) This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Pre-award costs are allowable only as described in the NIH Grants 6. Other Submission Requirements and Applications must be submitted electronically following the instructions described in the SF 424 (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 All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package .

Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR).

Additional information may be found in the SF424 (R&R) Application Guide. tips for avoiding common errors. Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHLBI , NIH.

Applications that are incomplete and/or nonresponsive will not be reviewed. Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115 . V.

Application Review Information 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 Reviewers will provide an overall impact/priority 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?

Are the PD/PIs, 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? 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 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?

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

Additional Review Criteria As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority 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 Subjects Protection and Inclusion Guidelines .

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 Human Subjects Protection and Inclusion Guidelines .

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 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.

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

Applications from Foreign Organizations Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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) 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 2.

Review and Selection Process Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI , in accordance with NIH peer review policy and procedures , using the stated review criteria . Review assignments will be shown in the eRA Commons. As part of the scientific peer review, all applications: Will receive a written critique.

. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council.

The following will be considered in making funding decisions: Scientific and technical merit of the proposed project as determined by scientific peer review. Relevance of the proposed project to program priorities. 3.

Anticipated Announcement and Award Dates After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) Information regarding the disposition of applications is available in the NIH Grants Section VI.

Award Administration Information If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants 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 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, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website. 2.

Administrative and National Policy All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities .

More information is Conditions and Information for NIH Grants .

Cooperative Agreement Terms and Conditions of Award When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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. Section VII.

Agency Contacts We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Application Submission Contacts Support (Questions regarding Grants.

gov registration and submission, downloading GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources) eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues) Phone: 301-402-7469 or 866-504-9552 (Toll Free) Scientific/Research Contact(s) Timothy M. Moore, M. D.

, Ph. D. Division of Lung Diseases National Heart, Lung, and Blood Institute National Institutes of Health 6701 Rockledge Drive, Room 10182, MSC 7952 Bethesda, MD 20892 (Express/courier zip: 20817) Director, Office of Scientific Review National Heart, Lung, and Blood Institute National Institutes of Health 6701 Rockledge Drive, Room 7214, MSC 7924 Bethesda, MD 20892 (Express/courier zip: 20817) Email: [email protected] .

Financial/Grants Management Contact(s) National Heart, Lung, and Blood Institute National Institutes of Health 6701 Rockledge Drive, Room 7148, MSC 7926 Bethesda, MD 20892 (Express/courier zip: 20817) Section VIII. Other Information Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts .

All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Authority and Regulations Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. Weekly TOC for this Announcement NIH...

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