Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

Catalyze Product Definition: Development of Devices, Diagnostics and Tools

The NHLBI Catalyze program is designed to provide a suite of comprehensive support and services to facilitate the transition of basic science discoveries into new treatments for diseases and disorders that fall under the NHLBI mission. The Catalyze Program initiatives support product development (supporting product definition studies and pre-clinical research and development) and enabling technologies and transformative platforms. Catalyze is coordinated by the Catalyze Coordinating Center, which provides program administration and evaluation, milestone-driven project management, communications and outreach, as well as development guidance for projects in the Catalyze portfolio. The Catalyze program aims to create cultural and systemic changes to more rapidly move breakthrough innovations to products that will have health, economic, and societal impact. Information on the Catalyze programs can be found on the Catalyze website.

This specific Catalyze Product Definition NOFO will provide the early stage translational support needed for the activities required to develop and test device prototypes, identify diagnostic disease targets and develop associated assays, and develop research tools to treat HLBS diseases and disorders. This is a phased initiative for early stage projects. The R61 phase provides support to identify and test initial prototype designs, to identify a disease target and generate experimental design, and to identify, test and pilot research tools. The R33 phase provides support for continued prototype development and testing, in addition to modifying design features and user feedback, diagnostic product generation, exploration of assay components, and characterization of a load design, and research tool improvement, large trial testing and data integration. Following successful completion of the program, it is expected that the potential products will be poised to move forward for in vivo testing (optimization, safety, efficacy) with additional support from NIH and/or other federal and private programs. A companion NOFO (RFA-HL-26-020) is available for more advanced projects that have already completed the activities supported by the R61 phase of this initiative, but need support for continued development of their product. For innovators developing small molecule and biologics, Catalyze has companion initiatives that support therapeutic development (RFA-HL-26-017 and RFA-HL-26-018) and an initiative that supports the development of enabling technologies and transformative platforms for HLBS (RFA-HL-26-016). See website for additional information.

Objectives

1. Novelty: This NOFO seeks applications that propose to apply new knowledge around novel devices, diagnostics and research tools. Projects should aim to develop potential products that are significant improvements over existing solutions for HLBS diseases and disorders. It is expected that proposed projects will provide evidence of the unmet gaps and needs to support proposed activities.
2. Biological rationale and preliminary data: This NOFO will fund projects that have a strong biological rationale for the intended approach, which have preliminary data that reflect well-designed experiments (either from the literature, data from other sources, or, when available, from investigator-generated data).
3. Relevance for development: Projects that propose to develop novel therapeutic agents that can be advanced towards development of NHLBI mission-relevant therapies and cures and fulfill the clinical gaps and needs are of high programmatic interest.

Phased Award Activities

Examples of R61 and R33 activities for the development of devices, diagnostics and tools are listed below:

For devices, the purpose of the R61 phase is to develop and test initial prototype design and the R33 Phase is to allow further prototype development and testing, in addition to modifying design features and incorporate user feedback.

For devices, activities for the R61 and R33 Phases may include, but are not limited to:

R61 activities for Devices:

• Key component testing (electronics, control and feedback system, sensing element, stent deployment, fluid handling, purification/separation efficiency, etc)
• Perform computational modeling to inform design features of the device or diagnostic
• Achieve first prototype or benchtop unit and assess for anatomical fit and ease of implantation
• In-vitro testing
• Acute in-vivo testing
• Small animal model testing
• Limited biocompatibility, hemocompatibility, histopathology testing

R33 activities for Devices

• Complete system integration
• Packaging optimization
• Engineering optimization to reduce size, weight, cost or improve system performance, reliability, repeatability, power consumption, durability
• Design for manufacturing, transition to contract manufacturer
• Parametric investigation for component or system optimization
• Performance comparison against gold standard, competitive devices
• In-vivo evaluation for reduction in procedure time by a panel of independent surgeons
• Verification and validation testing according to ASTM or other appropriate standards
• In-vivo testing
• Demonstrate safety and reliability in chronic in-vivo testing
• Large animal model testing
• Biocompatibility, hemocompatibility, histopathology testing per accepted standards
• Pre-submission meeting with FDA

For diagnostics, the purpose of the R61 phase is to identify a disease target and generate experimental design, and the R33 Phase is to allow product generation, exploration of assay components and characterization of a load design.

For diagnostics, activities for the R61 and R33 Phases may include, but are not limited to:

R61 activities for Diagnostics:

• Preclinical testing or training with limited human samples
• Treat/analyze spiked samples or plasma
• Development of a working prototype
• Optimize or scale-up synthesis of a novel imaging agent
• Perform in-vitro cytotoxicity and mutagenesis assays for a novel imaging agent
• Incorporate a new assay or multiple assays onto an existing sensing platform

R33 activities for Diagnostics:

• Validation in a large panel of human samples or large clinical datasets
• Improvements in sensitivity, repeatability, precision, accuracy, stability
• Identification of misuse modalities
• Performance comparison against gold standard, international standards or competitive devices
• Pre-submission meeting with FDA
• Assessment of pharmacokinetics and biodistribution of a novel imaging agent in an animal model
• Evaluation of multiplex assay, interfering analytes and miniaturized geometry

For research tools, the purpose of the R61 phase is for the identification, design and pilot testing of research tools and the R33 Phase is to allow product improvement, large trial testing and data integration.

For research tools, activities for the R61 and R33 Phases may include, but are not limited to:

R61 activities for Research Tools:

• Design and evaluate algorithms for HLBS disease detection
• Design and build a smartphone user interface and conduct limited user testing
• Conduction of a pilot study to establish feasibility of larger trial to assess tool effectiveness in changing user behavior
• Conduct focus group testing for initial usability
• For tissue-based high-throughput drug screening tools, assess response to reference compounds
• Initial design of a computer-aided system to import patient electronic health record data and prescribe best regimen of medications

R33 activities for Research Tools:

• Improve smartphone user interface based on large population testing
• Large human trial to assess tool usability/comfort, and effectiveness in changing user behavior vs standard medical guidance
• Wireless data integration with electronic health records
• Extend smartphone app and associated systems to iOS or Android platform
• For tissue-based high-throughput drug screening tools, use AI and large numbers/concentrations of compounds to train the prediction system and evaluate its performance
• Multi-site clinical study of a computer-aided system to compare computer-recommended prescriptions vs standard medical therapy

Non-Responsive Projects

Applications considered nonresponsive to the NOFO will not be reviewed. Examples of activities that are not appropriate for this NOFO include, but are not limited to:

• Activities geared toward therapeutic agent development (See companion NOFOs RFA-HL-26-017 and RFA-HL-26-018)
• Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers
• Clinical research and clinical trials

Special Requirements for this NOFO

The NHLBI recognizes that early stage product development requires access to unique expertise, including regulatory, reimbursement, business, legal, partner engagement, and project management. The NHLBI will work with recipients to provide guidance and support in these unique areas of expertise, if needed, to enable advancement of devices, diagnostics and tools towards preclinical testing and development.

Project Management

Each project is expected to use project management processes that guide the studies to successful completion of the established milestones. While it may not be possible to have a full-time project manager, each project is expected to identify a team member who will hold this responsibility as a part of their project management plan. The Catalyze Coordinating Center may support the local project management through resources, educational materials, and regular communications. The project manager will support the development of milestones, timelines, and identification of risks and mitigation strategies and will work closely with the Program Officer and with the support of the Catalyze Coordinating Center to update and refine these upon notice of award and as needed through the project.

Milestones

Applicants are expected to propose activities and milestones, with an associated timeline, to be completed during the proposed duration of award. Recipients will develop specific, measurable, achievable, relevant, and time-bound Specific Aims for their project. Each Specific Aim should have at least one milestone associated with it. Milestones are an event or moment in time in a project that indicate progress toward a Specific Aim has been made or a Specific Aim has been completed. The project Specific Aims and milestones should be laid out as a timeline or GANTT chart as a part of the application. Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals.

To be responsive to this NOFO, applicants must propose two separate groups of clear, quantifiable milestones with timelines (for R61 and R33 phases) to be completed sequentially within a three-year period, but with no more than two years in either stage. Although milestones for the R61 and R33 activities must be submitted at the time of application and will be reviewed simultaneously, funding for the R33 component is contingent on achieving pre-specified milestones during the R61 component. Completion of milestones will ensure sufficient progress during the R61 to provide feasibility and scientific rationale for the goals of the R33 phase. The R61 phase of this program will allow investigators to identify and validate device prototypes, diagnostics and tools and the R33 phase supports progressing the device, diagnostic or tool to a position that enables entry into preclinical programs.

Milestones will be peer-reviewed as well as programmatically reviewed and if needed will be negotiated with the recipients before they are included in the terms of the award. NHLBI staff will monitor program progress against proposed milestones through quarterly meetings and make non-competing award decisions annually based on achieving milestones. NHLBI emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress

R33 Phase Special Requirements

Cost Matching Component

Cost matching is expected for the R33 Phase (Phase II) only. The R33 Phase of this NOFO recommends a minimum of a 0.25:1 non-Federal cash match of the Federal direct costs requested for the R33.  Recipients will be expected to provide evidence of matching funds to NIH in the form of a letter of support prior to the meeting of the NHLBI committee that will make the decisions regarding whether a recipient will transition from the R61 to the R33 award. Proof of matching funds is not required at the time of application. The cash match must be reported annually to the NIH. In-kind contributions are encouraged, but do not apply to the cash matching expectations. Institutions must be able to document their actual contributions to the project and provide assurances that the organization(s) are committed to providing the funds and resources for their share of the project. Federal funds may not be used as a source of matching funds.

Generally, cost matching may not be met from the following sources:

• Costs borne by another Federal grant or sub award
• Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds
• Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient)
• Program income
• Patient incentives

Accelerator Partner(s)

At least one Accelerator Partner is required for the R33 portion of this award. Accelerator Partners are commercialization experts working as development partners with innovators whose projects are funded through the Catalyze program. Accelerator Partners help innovator-researchers achieve the necessary multidisciplinary approach for developing technologies. Accelerator Partners provide skills development and mentoring to enable innovator-researchers to assess the medical and commercial potential of their projects. The support of an Accelerator Partner is expected to help advance the proposed project to a stage suitable to continue product development in the private sector or apply for support through the NHLBI Catalyze Preclinical or other translational programs. Accelerator Partners may do this by connecting innovator-researchers with individuals such as:

• Experienced entrepreneurs and scientists, including those who can facilitate interactions with businesses, industries, sources of private capital, and research-performing institutions
• Experts such as clinicians and biostatisticians who are familiar with how the desired product should look to meet vested shared interests
• Potential partners who have complementary development expertise and resources for successful project development
• Potential licensing and commercialization partners who can offer advice soon after the researcher gets an award
• Ecosystem partners, such as those from biotechnology or pharmaceutical companies, who are knowledgeable about the process for developing therapeutics, devices, and diagnostics

Evidence of an Accelerator Partner is not required at the time of application, however, evidence is necessary for consideration of transition from the R61 to the R33 phase of the award. The Accelerator Partner should catalyze professional development by providing innovators with skills and mentoring to enable them to assess the medical and commercial potential of their research by bringing together experienced entrepreneurs and scientists and by providing connections between the businesses, industries, sources of private capital, and research performing institutions. Accelerator partners are encouraged to provide access to expertise and mentoring related to product development stages, business development and commercialization strategy, market analysis, preparation of regulatory submissions, intellectual property protection, and reimbursement strategy.

It is expected that recipients will search for an Accelerator Partner early in the R61 phase of award. While not required, it is acceptable for an Accelerator partner to provide the matching funds for the R33 stage.  

Transition to the R33 Phase of Award

The following elements will be considered for transition from R61 to R33: (1) acceptable progress and achievement of milestones as described above, (2) ability to secure third party investment by providing evidence of a non-Federal cash match, and (3) securing an Accelerator Partner. Evidence of having secured the third party investment and the Accelerator Partner is not required at the time of application, but will be needed at the time of R61 milestone review to assess transition to the R33 phase of award.

Intellectual Property and Regulatory Considerations

Projects at the stage of development supported through this NOFO may already or will be developed to the point where IP and regulatory strategies should be under consideration or already developed. If projects are too early, applicants should state such in the application with a brief explanation. For more advanced projects, applicants should address their current understanding of regulatory and IP requirements in their application, even if the plans are not fully complete, for their proposed product. Continued development of IP and regulatory strategies will be required for transition from the R61 phase to the R33 phase of the award. See Section IV, Application and Submission Information, SF424(R&R) Other Project Information for details.

Additional Considerations

Applicants are strongly encouraged to contact Scientific/Research Staff listed in Section VII to discuss potential research projects prior to submitting an application.

Prior to funding an application, NHLBI Program staff may contact the applicant to discuss the proposed performance measures, milestones, and any changes suggested by the NHLBI review panel or Program staff. A final set of approved performance measures and milestones will be specified in the Notice of Award.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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).

Federal Governments

• 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 Organizations) 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 How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. 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 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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO has an expectation of cost matching as defined in the NIH Grants Policy Statement. More information on the cost matching expectation is in Section IV.2 R&R or Modular Budget.

3. Additional Information on Eligibility

Number of Applications

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.

Letter of Intent

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
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Other Attachments:

IP and Regulatory Strategies (Required)

Preliminary IP and regulatory plans must be described in an attachment using the filename "IP and Regulatory Strategies.pdf". Applications that do not include this attachment are considered incomplete for this NOFO and will not be peer-reviewed.

NHLBI recognizes that applications submitted in response to this NOFO may detail projects at different stages of development. Applications should include a detailed description of Intellectual property (IP) and regulatory strategies for more advanced projects. If the project is too early for a well-defined strategy, the applicant should indicate so and provide a brief description of the current stage and potential IP and regulatory strategies. For more advanced projects, applicants should address their current understanding of regulatory and IP requirements for the proposed product, even if the plans are not fully complete.

For IP, applicants should describe any known constraints that could impede product development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar products that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program. If any third-party IP is required, identify whether there are any limitations on its use and include a letter from the third-party appended as part of this attachment. If patents pertinent to the product being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable. Describe plans for working closely with institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. Applicants are strongly encouraged to prepare the IP section of this application in consultation with their institution's technology transfer officials.

For the regulatory path, applicants should describe the steps they will take to refine and align their project to align with regulatory requirements either during the currently requested award period or in the future. If a device or diagnostic is being developed, describe the data that will be collected during the project period to support a pre-submission meeting, a 510(k) filing, or an Investigational Device Exemption filing. If the development team has already interacted with their local IRB or FDA regarding regulatory oversight of their proposed product, provide evidence of prior communications (letters/emails) appended as part of this attachment. If there is hypertext in communication with FDA (e.g., hyperlinks and URLs), these should either be removed or disabled by the applicants before submission in accordance with NIH policy on the use of hypertext (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-174.html).

Applicants are also strongly encouraged to contact the appropriate NIH Scientific/Research contact listed in Section VII for questions regarding application expectations for IP and regulatory prior to submission.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R Budget

All instructions in the How to Apply- Application Guide must be followed.

Applicants should include budget support for the PD/PI to participate in a 1.5-day NHLBI-held innovation meeting or workshop once each budget year in the Washington, DC/Metropolitan area

Applicants should budget for an appropriate amount of project management support.

Budget Justification:

The amount, type, and source of funding/contributions from sources other than NIH must be presented in detail in the budget justification. Third Party support of the proposed research activity (if approved) will be incorporated as a Term and Condition of Award. If the Third Party support ceases and the program is no longer tenable without the Third Party support, a close-out plan may be requested.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims 

Within the Specific Aims section, include headers titled R61 Phase Specific Aims and R33 Phase Specific Aims. Under each header, state the specific objectives of the efforts, including the activities to be conducted to meet the goals of each phase to advance development of the proposed product.

Research Strategy 

Describe both the R61 phase and the R33 phases of the proposed project. Include a background section that clearly outlines the biological rationale for the application, including: (1) a description of the relationship between the proposed device, diagnostic, or tool and the disease of interest, (2) evidence for unmet medical need in the disease area, (3) a brief description of any pertinent history for this type of product development in the disease area, (4) evidence supporting the novelty of the design of the proposed approach, and (5) a summary of the project status, including information regarding potential products to be tested in the current application. Provide a carefully developed rationale for the experimental design and a description of how data obtained in the R33 phase will support future product development efforts.

Accelerator Partner

Include a description of how the expertise of a potential Accelerator Partner might fill anticipated gaps in development as related to the project goals.

Milestones

Define milestones for both the R61 and the R33 phases of the grant application. Milestones must be specific, measurable, achievable, relevant, and time-bound. Specific aims or a list of activities are not considered milestones. Transition from the R61 to the R33 phase is contingent upon the successful completion of the proposed R61 milestones, thus, the description of the milestones that need to be met during the R61 phase to allow for successful initiation of the R33 phase must be clear. Describe the milestones that need to be reached in the R33 phase to address the specific aims and ensure the successful completion of the entire project.

Milestones should provide clear indicators of a project's continued success or emergent difficulties.

Timeline

Provide a timeline with specific milestones for progression from the R61 phase to the R33 phase. The timeline, specific goals and feasibility milestones should be clear and complete. Indicate when it is anticipated that essential components of the project will be completed. The proposed timeline with specific milestones should be clearly delineated and should appear as the last element of the Research Strategy section.

Project Management

Describe plans for utilizing project management processes to enable continuous assessment of the progress of the project relative to the established milestones and how the progress assessments will be used to make strategic decisions regarding the proposed project. While it may not be possible to have a full-time project manager, each project is expected to identify a team member who will hold this responsibility as a part of their project management plan. The Catalyze Coordinating Center may support the project management through resources, educational materials, and regular communications. Describe plans for how the selected project management process(es) will support product development studies of the device, diagnostics and/or tools.

Rigor and Reproducitility

High-quality and reproducible product definition studies are an essential cornerstone of the translational research enterprise. Attention to principles of study design and transparency is essential to enable stakeholders to assess the quality of the experimental design and scientific findings. In support of this important goal, investigators must follow instructions to address Rigor and Reproducibility (https://grants.nih.gov/policy/reproducibility/index.htm).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. 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

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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 Section 7.9.1 Selected Items of Cost.

Awards funded under this NOFO will not be provided the authority 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 Grant Award, as outlined in the NIH Standard Award Terms and Conditions. All extensions, including the first extension, will require NIH prior approval.

Applications must be submitted electronically following the instructions described in the How to Apply 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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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 NHLBI. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by a special emphasis panel convened by the National Heart Lung and Blood Institute in accordance with NIH peer review policy and procedures using the stated review criteria.

As part of the scientific peer review, all applications will receive a written critique.

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.
• Compliance with data management and resource sharing policies.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) 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 Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

General Questions
Mike Pieck, Ph.D.
Telephone: 301-827-7986
Email: [email protected]

Division of Blood Diseases and Research
Nitin Agrawal, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-443-9337
Email: [email protected]

Division of Cardiovascular Sciences
Rahul Thakar, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-827-8151
Email: [email protected]

National Center on Sleep Disorders Research
Lawrence Baizer, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0199
Email: [email protected]

Division of Lung Diseases
Sidd Shenoy, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: [email protected] 

Director, Office of Scientific Review
Heart, Lung, and Blood Institute (NHLBI)
Email: [email protected]

Ron Caulder
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8020
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 2 CFR Part 200.