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

Purpose

The purpose of this FOA is to provide support for planning activities for late phase (phase II and beyond) single-site or multi-site investigator-initiated clinical trials that address critical clinical questions within the mission of the National Heart, Lung, and Blood Institute (NHLBI) and that require non-traditional clinical trial designs with the opportunity for statistical novelty and/or innovation. The FOA will support the development of feasible and well-designed clinical trials utilizing consultative services provided by the Innovative Clinical Trials Resource (ICTR) (N01).

Background and Objectives

Clinical trials are a key strategy used by the NHLBI to improve prevention, diagnosis, and treatment of heart, lung, blood, and sleep disorders. Clinical trials also represent a significant investment of human and material resources. Effective planning, oversight, and high standards for the safe, timely, and efficient conduct of clinical trials are integral to maximizing their scientific impact and return on investment. For a majority of clinical trials, traditional designs adequately power the statistical analysis plan. Some key features of traditional clinical trial designs are participant randomization, blinding (masking) of participants and researchers to the study intervention(s), the use of a control comparison group, and a classic intent-to-treat analysis.

However, as noted in the 2001 IOM Report on Small Clinical Trials, clinical trials conducted in limited populations may not be able to use traditional clinical trial designs to achieve adequate statistical power. The design and planning of trials using innovative approaches to statistical design and analysis plans requires specific expertise that may be difficult to locate and access. Scientific areas identified across NHLBI in which such trials might be required include, but are not limited to, studies of rare diseases and/or therapeutics in which sample size limitations provide a challenge to the statistical power of traditional randomized clinical trial designs; studies in sub-populations of more common diseases, e.g., precision medicine trials; and late-stage implementation research. Other examples could include trials for the study of interventions in a non-randomized study setting and clinical trials in which an optimal treatment control arm may be difficult to implement.

This program is designed to:

1. permit early peer review of the rationale for the proposed clinical trial

2. permit assessment of the design of the proposed trial in its current, early form

3. provide investigators with access (limited to 12 months) to ICTR consultative services in clinical trial optimization through consideration and application of innovative trial design methodology and novel approaches to analytical methods

The ICTR services include assistance in the application of innovative trial design methodology and novel approaches to analytical methods to proposed clinical trials as well as guidance, as required, on regulatory issues related to innovative late phase clinical trials. In addition to specific consultative services, awardees will have access to an on-line education program on the application of non-traditional clinical trial design and analysis to clinical trials.

Supported Research Activities

The planning grant support will allow investigators to accomplish the planning activities that are essential for developing a non-traditional clinical trial. The investigators in this Program will be required to access the consultative services made available through the Innovative Clinical Trials Resource (ICTR) and to develop a timeline for the planning activities. In addition to providing access to the ICTR, the grant will provide the investigator with the support needed to conduct clinical trial planning activities that are not accessible through the ICTR. Examples of such activities could include clinical trial site identification and the development of a participant recruitment strategy, protocol finalization, and clinical trial implementation and project management planning.  

This Program will allow for early identification of non-feasible trial concepts. However, if planning activities can be successfully completed, investigators are expected to have developed a final study protocol with a feasible non-traditional design, an appropriate and potentially novel or innovative statistical analysis plan, and an implementation strategy for the conduct of a late phase single site or multi- site clinical trial.

Those applicants who require access to consultative services for non-traditional trial design and innovative statistical analysis planning, but who do not require support for clinical trial implementation and management planning activities may consider applying for planning assistance through the FOA entitled Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans (X01) (PAR-18-768).

The Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans Program is not designed for the collection of preliminary data or the conduct of pilot studies to support the feasibility of a clinical trial. Applicants should consider PAR-18-463: NHLBI Clinical Trial Pilot Studies (R34) as a potential funding mechanism to support pilot or feasibility studies. Additionally, this Clinical Trial Planning Program is not designed to support the launch and conduct of a full scale clinical trial. Investigators who are seeking support to implement and conduct a full scale clinical trial within NHLBI's mission areas can consider applying through either the single-site (PAR-18-406), or the multi-site (phase II and beyond) clinical trial FOAs - PAR-18-407 (Clinical Coordinating Center) and PAR-18-410 (Data Coordinating Center). Investigators should note that funding of a Clinical Trial Planning Grant does not guarantee or imply funding for a proposed subsequent full-scale trial by NHLBI.

Applications should have developed a draft protocol with a proposed non-traditional clinical trial design and draft statistical analysis plan that warrant further development in collaboration with the ICTR consultative team.  Other aspects of the project should have been planned including coordination and data management plans, and an institutional clinical trials environment that can support the final development, implementation and conduct of a late phase (Phase II and beyond) clinical trial.

This FOA is designed to only support planning activities in preparation for a full-scale late phase single center or multicenter clinical trial. These planning activities are primarily logistical, conceptual, and/or technical in nature. They do not involve the collection of data typical of research-related activities supported by the traditional NIH research project grant. As such, the evaluation of U34 applications will focus on the justification of or need for the proposed non-traditional trial along with the appropriateness of the proposed planning activities.

Applicants are encouraged to contact the NHLBI Scientific Research Contact(s) for this U34 FOA to address questions concerning the U34 application and its responsiveness to the FOA.

Examples of NHLBI Clinical Research Areas of Interest

Selected clinical research areas of interest that may require the use of non-traditional trial designs and application of innovative or novel statistical methods include but are not limited to:

• Determination of the phenotypic, biomarker, and molecular characteristics that predict outcome and, when applied in clinical studies, predict differential responses to therapy in individuals with heart, lung, blood diseases, and sleep disorders
• Integrated analysis of health information from individual patients including genetic, epigenetic, and "omics" data to allow more precise medical management of patients at risk for or afflicted with a heart, lung, blood, or sleep disorder, especially among groups that are understudied or have disparate morbidity and mortality (e.g., minorities, women)
• Evaluation of the efficacy of cell-based approaches to bioengineering of conduits and valves for palliated congenital heart disease
• The step-wise evaluation of multi-drug combinations for severe pediatric pulmonary hypertension
• The study of ongoing stroke risk stratification in children with persistently elevated transcranial Doppler measurements after the initiation of chronic blood transfusion or hydroxyurea.
• Late-stage (T4) research on the optimal implementation of heart failure prevention and treatment with high burden communities of vulnerable populations
• Evaluation of the efficacy of stem cell therapy for single ventricle heart failure, tracheal regeneration, and/or pulmonary alveolar proteinosis
• Biomarker-based targeted anti-factor VIII inhibitor prevention in previously untreated children with severe congenital hemophilia A
• Late-stage (T4) research on the optimal and sustainable implementation of guideline care for Sickle Cell Disease among health care systems where the analysis unit is the health care system
• Evaluation of the efficacy of a multi-component weight loss intervention in children and their families, where participants cannot be masked to the intervention

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organization

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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

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

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

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

• Descriptive title of proposed 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
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.

Applicants are strongly encouraged to name an experienced research team, including a biostatistician, and assemble a diverse team that includes women and minorities. Applicants are also encouraged to include junior faculty or investigators, if appropriate.

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 additional instructions:

Specific Aims:

The goals of the trial and the expected outcome(s) must be stated in the Specific Aims section. The primary and major secondary endpoints of the trial must be specified. The specific objectives of the planning period must be outlined.

Research Strategy:

Applicants should use the Research Strategy section to discuss the rationale for the proposed clinical study, a description of the potential impact, and other key information requested below, but should not duplicate information collected in the PHS Human Subjects and Clinical Trial Information Form. The PHS Human Subjects and Clinical Trial Information Form will capture detailed study information, including eligibility criteria; inclusion of women, minorities, and children; protection and monitoring plans; and statistical design and power.

The Research Strategy section must include the following information:

• Description of rationale for the proposed clinical study, documenting the significance and need to perform the study, and detailing potential risks and benefits.
• Description of the potential impact of the clinical study on health care, policy or practice, and the relevance of the study to heart, lung, blood, or sleep disorders.
• Sufficient background information to enable reviewers to assess the requirement for a non-traditional clinical trial design and appropriate statistical analysis approach within the context of the proposed study population.
• A draft plan for the clinical study, with enough detail to allow assessment of the scientific importance and potential for the proposed innovative trial design to increase the likelihood of feasibility.
• Description of how the study will be organized and managed. This should include information on the leadership of the study, and the ability of the PD/PI to bring together the necessary study team.
• Description of the mechanism for interacting with the Innovative Clinical Trials Resource (ICTR). Description of the research team members participating in the planning process, their roles in the development of the plan, and their experience in related studies.
• Clear timelines for completing the proposed institution- and Innovative Clinical Trials Resource (ICTR)-based activities should be provided.

Investigators are encouraged to discuss the remaining challenges and unanswered questions in the proposed design and draft analytical plan to explain why access to consultative services of the Innovative Clinical Trials Resource is critical to the success of the clinical trial planning.

Applicants including junior faculty or investigators should provide a plan to advise such individuals, if appropriate.

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:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics:

2.5 (Recruitment and Retention Plan) has the following additional instruction:

• Describe and address the availability of the requisite patient population and plans for recruitment outreach and follow-up. Plans for addressing issues and challenges regarding adherence to the proposed intervention protocol must be included.

Section 3 - Protection and Monitoring Plans:

3.5 (Overall Structure of Study Team) has the following additional instructions:

• Provide a description of how the planning period will be used and of the activities to be carried out. Planning activities supported by this FOA should be clearly defined and should not overlap with the milestones for the initial phase of the multi-site and or the single site clinical trial FOAs, UG3 (PAR-18-407) or R61 (PAR-18-406), respectively.

Delayed Onset Study

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

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

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

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

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

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

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

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by 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 the policy. Any instructions provided here are in addition to the instructions in the policy.

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? Is there a strong scientific premise for the project? 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

What is the potential of the proposed project to effectively address all key issues that currently prohibit completion of the trial design? How would the proposed full-scale clinical trial improve public health?

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

Specific to this FOA

Is statistical expertise represented in the proposed investigational team to allow for interaction with the ICTR consultative team of experts?

Are the roles of the research team members participating in the planning process, development of the plan, and their experience in related studies adequately described and justified?

How strong is the application in demonstrating that the PDs/PIs and Key Personnel have the experience and capability to conduct the proposed multi-center trial and meet the milestones and timelines? What evidence is provided to ensure that the clinical centers will employ the appropriate personnel to recruit subjects and design/implement the clinical protocol? How strong is the coordination and project management team at the participating institutions to facilitate the implementation of all aspects of the trial once fully designed? Are roles and responsibilities well-defined?

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? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Specific to this FOA

Is an appropriate timeline provided for the design, implementation and evaluation of the planning phase? How feasible is the plan and how appropriate is the plan for the development and preparation of the non-traditional clinical trial? Have the investigators adequately explained why access to consultative services of the ICTR is critical to the success of the clinical trial planning?

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?

Specific to this FOA

Can the environment appropriately support the final development, implementation and conduct of a late phase (Phase II and beyond) clinical trial?

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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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 (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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.

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Carrying out the activities essential to the planning of the Phase II and beyond single- and multi-site clinical trials.
• Developing the clinical trial protocol, including final non-traditional design and applicable innovative statistical analysis plan as well as all the elements required for trial implementation.  
• Initiating active collaboration with the Innovative Clinical Trials Resource (ICTR) within the first month of the award period.
• Developing and maintaining the communication plan with the ICTR throughout the duration of the study.
• Developing and adhering to the pre-determined timeline for planning activities.
• Participating in scheduled teleconferences with NHLBI and ICTR staff.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

The NHLBI Project Scientist will:

• Assist in the interactions between investigators and the Innovative Clinical Trials Resource (ICTR).
• Review and comment on critical stages of the planning grant development and assess the overall study planning progress based on the established timeline.
• Implement adjustments to the study planning time line as needed.
• Participate in scheduled teleconferences with ICTR staff and U34 investigators.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The Principal Investigator of this award will be required to participate in periodic meetings and telephone conference calls with the NHLBI staff to provide study progress updates and promote sharing of information regarding state of science technologies, data management techniques, analytical strategies and tools, and data sharing. Support or other involvement of industry or any other third party in the study ─ e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources ─ may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.
• Study investigators are encouraged to publish and to release publicly and disseminate results, tools, resources and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely matter to the scientific community. A plan for dissemination of study results will be developed by the awardee and approved by the NIH Project Scientist. Within 3 years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators in accordance with the NHLBI Data Sharing Policy available at https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing-from-clinical-trials-and-epidemiological-studies

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, 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 Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Andrei Kindzelski, MD, PhD
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0050
Email: [email protected]

 
Kristin Burns, MD
Division of Cardiovascular Sciences
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-594-6859
Email: [email protected]

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

Cheryl Boyce, PhD
Center for Translation Research and Implementation Science
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-496-1051
Email: [email protected]

Innovative Clinical Trials Resource (ICTR) (N01) Contact

Erin Smith
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0279
Email: [email protected]

Jayanthi Regunathan (Jay)
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8048
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.