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 National Heart, Lung, and Blood Institute (NHLBI) invites applications to participate in the NHLBI Progenitor Cell Translational Consortium (PCTC). The goal of the Consortium is to translate advances in progenitor cell biology towards application to heart, lung, and blood diseases. The initiative will focus on the use of progenitor cell-based disease models to understand disease mechanisms and to develop novel therapies, and the application of progenitor cell-based therapies for the treatment of heart, lung, and blood diseases.

Stem cell research promises major new insights and therapeutic approaches for human disease of the heart, lungs, and blood, but critical barriers to effective translation exist, many of which entail shared challenges among these distinct organ systems. The NHLBI has provided significant support for the development of the progenitor cell biology field through the NHLBI Progenitor Cell Biology Consortium (PCBC) and the Lung Repair and Regeneration Consortium (LRRC). This initiative will establish a new consortium, the NHLBI Progenitor Cell Translational Consortium (PCTC), to leverage the advances in progenitor cell biology made by the PCBC and LRRC and the broader scientific community. Scientists have made significant progress in applying bioengineering to heart, lung and blood diseases, developing organs-on-a-chip and developing decellularized scaffolds for tissue replacement. The use of patient-specific induced pluripotent stem cells (iPSCs) in combination with bioengineering advances and genome editing offers unique opportunities for developing personalized disease models and tissues for regenerative medicine. Coupling multiple organ chips together may offer unique opportunities in drug discovery. Advances in 3D printing also offer exciting new opportunities for regenerative medicine, including incorporation of vascular scaffolds into bioengineered tissues and organs.

The goal of the PCTC will be to leverage these scientific advances and tools to develop new treatments for heart, lung, and blood diseases. This FOA solicits multidisciplinary applications to translate advances in progenitor cell biology to develop treatment strategies for specific cardiovascular, pulmonary, or hematologic diseases. In some cases the selected disease area may involve more than one organ system, e.g. pulmonary arterial hypertension. The investigational group will be expected to include expertise in the selected disease area as well as expertise in progenitor cell biology. Other areas of expertise should address the needs of the specific project, (e.g. large animal expertise, bioengineering, genome editing, transplant immunology, systems biology, bioreactor expertise for scale-up of cell production, product development, and other areas as needed).

Focus areas include the continued development of patient-specific disease models using progenitor cells and genome editing; the use of progenitor cells (including gene modified progenitors) and their differentiated progeny for cell therapy and tissue engineering; the development of strategies to promote the reparative potentials of endogenous progenitor cells; and expansion of efforts to employ direct reprogramming of cells in vivo to treat disease. When needed to inform translational potential and strategies, applications may propose studies that further elucidate disease mechanisms, e.g. obtaining a better understanding of the principles governing how terminally differentiated cells re-enter the cell cycle to proliferate. Applications addressing modeling and therapeutic development for rare diseases are encouraged.

It is recognized that for different diseases the starting point on the translational continuum varies, and this will influence how far towards clinical implementation investigators can anticipate to progress during the seven year funding period. Projects may vary substantially in their objectives and scope of research. The feasibility of the investigators projections and the linked milestones will be important review considerations.

Collaborations: The consortium will leverage shared expertise in tools and technologies, as well as intellectual insights. The requirement for collaboration will be an integral part of the Notice of Award. The program may leverage regulatory support from the new Production Assistance for Cellular Therapies (PACT) program so that investigators are well informed about the specific long term needs for their project to be translatable, e.g., advice on standard operating procedures, Good Laboratory Practices, and interactions with the FDA to develop IND and IDE applications; investigators will be expected to obtain regulatory advice early in the project, consult frequently with their advisors to ensure that unforeseen regulatory barriers do not arise, and report on them to NHLBI.

Research examples appropriate for this FOA include, but are not limited to, those listed below:

• Transplantation of genome-edited iPSC-derived hematopoietic progenitor cells for treatment of sickle cell disease and other monogenic hematologic diseases
• Genome editing of cystic fibrosis lung stem/progenitor cells to ameliorate lung disease and promote regeneration
• Derivation of mature, functional cardiomyocytes from progenitor cells and transplantation of tissue-engineered cardiac patches into large animal models of heart failure
• Engineering durable effective organ replacement therapies for patients with advanced lung disease
• Direct differentiation of cardiac fibroblasts into cardiomyocytes in situ to improve function in pre-clinical models of heart failure
• Determining mechanisms of phenotypic reprograming induced by severe viral infection and development of progenitor-based therapies for lung injury repair
• Development of strategies to promote reparative activities of progenitor cells in acute lung injury and in pulmonary fibrosis
• Derivation of patient-specific mature endothelial and smooth muscle cells and transplantation to revascularize ischemic myocardium or limbs
• High level transgene expression in iPSC-derived megakaryocytes for correction of Glanzmann’s thrombasthenia and Wiskott-Aldrich syndrome
• Developing methods and strategies for studying the biology of specific progenitor cells, strategies to genome-edit the target cells, and establishing novel approaches for cell delivery, replacement or engraftment in rare, congenital lung diseases
• Applying regenerative strategies to reverse the degenerative process in chronic lung diseases including COPD
• Generation of functional neutrophils and macrophages from iPSCs for chronic granulomatous diseases

Areas of interest that will not be considered responsive to this FOA include:

• Cancer or communicable diseases
• Projects focused on the empirical application of poorly-characterized cell types for cell therapy

The goal of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data and resources to advance translation of progenitor cell biology. Thus, in addition to interactions within a Research Hub, extensive collaboration among Research Hubs is expected and may include collaborations between investigators at multiple institutions. The Consortium will consist of Research Hubs funded through this FOA, and an Administrative Coordinating Center (ACC) that will be responsible for enabling collaboration across the consortium through logistical support and a variety of tasks. The ACC will also administer funds to support pilot studies, ancillary and collaborative research studies, and skills development activities. The ACC is funded through a separate FOA, RFA-HL-16-022. Applicants to this Consortium FOA are strongly encouraged to read the ACC FOA.

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 not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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
Division of Extramural Research Activities
6701 Rockledge Dr.
Room 7214, MSC 7924
Bethesda, MD 20892-7924
Bethesda, MD 20817 (Express/courier service)
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, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

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, with the following additions.

The PD/PI (of a single PD/PI application) or contact PD/PI (of a multi PD/PI application) must commit at least 3 months.

For this FOA, applicants are expected to have appropriate collaborators or consultants with expertise in regulatory affairs and intellectual property.

All instructions in the SF424 (R&R) Application Guide must be followed. In the application, research project budget requests must include costs for travel for the PD/PI and key collaborators of the individual project to attend both the initial in-person PCTC meeting and the annual PCTC Investigator's Meeting. Key collaborators will be identified following funding of the PCTC; by applying to this FOA applicants agree to attend if identified. Funds should be budgeted for administering the scientific oversight committee and activities noted in the management plan. The PD/PI (of a single PD/PI application) or contact PD/PI (of a multi PD/PI application) must commit at least 3 months.

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:

Research Strategy:

It is expected that over the funding period a broad range of methodologies, technologies and expertise will be needed to carry out the broad scope of the projects, moving from basic hypothesis-driven experiments to inform strategies to translational work to move the projects toward clinical application. Thus, the Research Strategy should:

• Outline a strategy leading to treatment of the disease; the strategy should be based on well-defined knowledge of progenitor cell biology, rigorous scientific rationale and relevant pathobiologic processes of the selected disease;
• Describe how the science proposed represents an advance in stem cell therapy toward human implementation.
• Identify barriers that need to be overcome to implement the strategy.
• Propose a plan to overcome the identified barriers.
• Identify barriers where the proposed solutions are viewed as high risk, as well as identify alternate strategies to be taken if the proposed solution fails.
• When needed to inform translational potential and strategies, applications may propose studies that further elucidate disease mechanisms.
• Provide the preliminary data evidence to support feasibility of the translational project
• Provide feasible projected milestones for achieving the predicted endpoint(s).

The Research Strategy should also clearly describe the management plan for the proposed collaborative research. In particular, outline plans and mechanisms to keep the project focused and progressing:

• Set realistic and quantifiable intermediate milestones on a timeline to allow for the evaluation of progress towards the project's goal. Progress towards these milestones will be assessed by NHLBI project staff on a regular basis; consistent failure to achieve milestones may result in termination of the award.
• Explain how collaborators can be added or removed as the expertise, knowledge, and skills necessary to advance the project evolve.
• Describe how intellectual property issues will be handled.
• Identify an internal scientific oversight committee

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.
• Applicants should discuss the following:
  • Availability of biological resources utilized and/or developed (mouse models, cell lines, reporter systems, vectors, molecules, antibodies, biomarkers, etc.);
  • Availability of technologies and protocols developed with funds from this award.

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.

As noted in the Terms and Conditions:

• Grants funded under this FOA will not be awarded with the Streamlined Noncompeting Award Process (SNAP) authorities (NIH Grants Policy Statement 8.4.1.2 Streamlined Non-Competing Award Process).
• Grantees will not be able to submit a modified progress report.
• Grantees will not be provided the authority outlined in the NIH Standard Terms of Award to extend the final budget period of the previously approved project period one time for up to 12 months beyond the original expiration date shown in the Notice of Award. All extensions, including the first extension, will require NIH prior approval.
• Grantees will not have authority to automatically carryover funds. All carryover actions require NIH prior approval.
• Grantees must submit annual Federal Financial Reports (FFRs).
• This award is subject to the audit requirements 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.

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.

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 for this FOA: Considering the state of the art for the chosen disease, how strongly does the science proposed represent an advance in stem cell therapy toward human implementation?

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?

Specific for this FOA: Considering the start of the art for the chosen disease, to what extent have appropriate collaborators or consultants with expertise in regulatory affairs and intellectual property been included?

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 managed?

Specific for this FOA: To what extent is the proposed strategy based on well-defined knowledge of progenitor cell biology and relevant pathobiologic processes of the chosen disease? How well is the scientific rationale for the proposed strategy clearly stated? To what extent are the proposed milestones realistic and quantifiable to permit assessment of progress?

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.

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 Wide Association Studies (GWAS) /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.

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75 and other HHS PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the Awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the Awardees' activities by involvement in and otherwise working jointly with the Awardees in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the Awardees for the project as a whole, although specific tasks and activities may be shared among the Awardees and the NIH as defined below.

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

• The Awardee will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• The Principal Investigator/Program Director will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• The Awardee will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH policies.
• All staff of the Awardee will maintain the confidentiality of the information developed by the investigations, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.
• Awardees must analyze, publish and/or publicly release and disseminate results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the FOA.
• All staff of the Awardee will be required to participate in a cooperative and interactive manner with NIH staff, one another and with the PCTC.
• Awardees are expected to share data, materials, models, methods, information and unique research resources that are generated by the projects in accordance with PCTC policies in order to facilitate progress and consistent with achieving the goals of the program. When appropriate, and in accordance with NIH policies, Awardees will be expected to collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities of other PCTC members.
• PCTC Awardees agree to establish agreements amongst themselves that address the following issues: (1) Procedures for data sharing among consortium members and data sharing with industry partners as appropriate; (2) Procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) Procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) Procedures for sharing biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner as appropriate and consistent with achieving the goals of the program; and (5) Procedures for reviewing publications, determining authorship, and industry access to publications.
• Awardees agree that industry collaborations should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures and any policies and procedures developed by the PCTC.
• Awardees must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• Upon completion or termination of the research project(s), the Awardees are responsible for making all study materials and procedures broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research. The data sharing plan should include a plan to accomplish this at the end of the study.
• Awardees may be asked by NIH staff to scientifically review applications for special opportunity pool funds, as deemed appropriate.

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

• The NHLBI will designate program staff, including a Program Officer to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer will be named in the Notice of Award.
• The NIH will invite experts with relevant scientific expertise to provide feedback to the NIH on PCTC activities. The EAC will give feedback to NIH staff on scientific developments and opportunities that may enhance the achievement of the study goals.
• An NHLBI Project Scientist will be named in the award notice and substantially involved in this project as follows:
  • The NHLBI Project Scientist will coordinate and facilitate the activities of the PCTC-ACC, attend and participate in all meetings of the PCTC-ACC, and act as a liaison between the Awardee and the EAC.
  • The NHLBI Project Scientist and Program Officer will review the scientific progress and administrative accomplishments of the PCTC-ACC, and review the project for compliance with operating policies developed by the PCTC Steering Committee. Based on this review, the Program Officer may recommend to the NIH to continue funding, or make recommendations for corrective action to improve progress, or failure to adhere to PCTC or NIH policies. Review of progress may include regular communications between the Principal Investigator and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• The NHLBI reserves the right to curtail or phase out any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or PCTC policy and procedure, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or (3) concerns related to human subject safety that prompt the need for premature termination.
• The NHLBI Project Scientist will have substantial scientific programmatic involvement in research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the awardee, however, specific tasks and activities in carrying out the studies will be shared among the Awardees and the NHLBI Project Scientist.
• The NHLBI Project Scientist serves as a resource with respect to other ongoing NIH activities that may be relevant to PCTC studies to facilitate compatibility and avoid unnecessary duplication of effort.
• The NHLBI Project Scientist or designee may coordinate activities among Awardees by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.
• The NHLBI Project Scientist may review procedures for assessing data quality and monitor study performance.
• The NHLBI Project Scientist may be a co-author on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

Areas of Joint Responsibility include:

• Through the Awardee(s) and NIH staff, PCTC will cooperatively develop and implement processes to submit information and data to the PCTC, determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the Funding Opportunity Announcement.
• There will be an initial face-to-face meeting of PCTC and a minimum of 2 PCTC meetings (teleconferences or face-to face meetings) annually. PCTC Awardees, key collaborators, and the PCTC Project Scientist are expected to attend these meetings. One of these bi-annual meetings could be combined with the annual PCTC Investigator Scientific Retreat.

Steering Committee

By applying to this FOA, PCTC Awardees agree to the governance of the PCTC through a Steering Committee that is responsible for joint governance of the PCTC.

• On an annual basis, and following input from the PCTC Steering Committee members, NHLBI staff will appoint a Steering Committee Chair who will be in charge of facilitating the PCTC Steering Committee meetings and teleconferences. In collaboration with the PCTC ACC and the NHLBI Project Scientist, the Chairperson is responsible for coordinating the Steering Committee activities, for preparing meeting agendas and for chairing meetings.
• The Steering Committee, including the Project Scientist, is responsible for establishing and implementing processes and criteria for recommending special projects for consideration for special opportunity funds by NIH staff.
• The NHLBI Project Scientist may work with Awardees on issues coming before the Steering Committee and, as appropriate, other committees.
• The Steering Committee will be composed of the Principal Investigators/Program Directors for each U01, or by U01 representatives (one per U01 grant) chosen by the Principal Investigators/Program Directors in the cases of multi-PI grants, and the NHLBI Project Scientist. Only the U01 PI/PD or multi-PI U01 representatives and the NHLBI Project Scientist will be voting members of the Steering Committee and will attend all meetings of the Steering Committee. Each full member will have one vote. Other designated NIH program staff attending the steering committee meetings will be ex officio (non-voting) members. The PCTC Steering Committee will meet at least twice times a year.
• All major scientific and policy decisions will be determined by voting policies as established by the Steering Committee at the initial meeting. This committee will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools developed within each individual project. Steering Committee activities and decisions will consider the advice of the External Experts.
• The NHLBI Project Scientist will help the Steering Committee develop and draft operating policies.
• NHLBI staff, in concert with the Steering Committee, will have the option to redirect research activities being pursued within the U01 grants if it is considered beneficial to the overall program.
• The Awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees. Awardees must serve on PCTC subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.

External Advisory Committee: An External Advisory Committee (EAC) composed of five to seven members will provide feedback to grantees and the ACC on Consortium activities. This Committee will consist of non-Consortium affiliated scientists and other experts appointed by the NHLBI, to provide feedback to grantees on progress and scientific direction, and to give feedback to the ACC on the quality of applications for pilot studies, ancillary and collaborative studies, and cores, as needed.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Denis Buxton, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Division of Cardiovascular Sciences
Telephone: 301-435-0515
Email: buxtond@nhlbi.nih.gov

John Thomas, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Division of Blood Diseases
Telephone: 301-435-0065
Email: thomasj@nhlbi.nih.gov

Sara Lin, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)\
Division of Lung Diseases
Telephone: 301-443-8797
Email: sara.lin@nih.gov

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

Ms. Beckie Chamberlin
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0183
Email: chamberr@nhlbi.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 Part 75.