Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. 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 initiative will provide the early stage translational support needed for prototype testing/design modification, assay development for diagnostic disease targets, and development of research tools for use in the treatment of HLBS diseases and disorders. 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 FOA (RFA-HL-20-024) is available for earlier stage projects (initial prototype design/testing). For innovators developing small molecule and biologics, Catalyze has companion initiatives that support therapeutic development (RFA-HL-20-023 and RFA-HL-20-027). See website for additional information.

Objectives

1. Novelty: This FOA 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 FOA 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..

Applicants will be expected to meet the following:

• For Devices:
  • Tested key components testing (electronics, control and feedback system, sensing element, stent deployment, fluid handling, purification/separation efficiency, etc)
  • Performed computational modeling to inform design features of the device or diagnostic
  • Achieved first prototype or bench-top unit and assess for anatomical fit and ease of implantation
  • Conducted In-vitro testing
  • Conducted acute in-vivo testing
  • Conducted small animal model testing
  • Conducted limited biocompatibility, hemocompatibility, histopathology testing

• For Diagnostics:
  • Completed preclinical testing or training with limited human samples
  • Treated/analyzed spiked samples
  • Generated experimental design, have a working prototype and preclinical testing and have a working prototype
  • Optimized r scaled-up synthesis of a novel imaging agent
  • Performed in-vitro cytotoxicity and mutagenesis assays for a novel imaging agent
  • Incorporated a new assay or multiple assays onto an existing sensing platform
  • Identified a disease target

• For Research Tools:
  • Designed and evaluated algorithms for HLBS disease detection
  • Designed and built a smartphone user interface and conduct limited user testing
  • Conducted pilot studies to establish feasibility of larger trial to assess tool effectiveness in changing user behavior
  • Conducted focus group studies for initial usability testing
  • Assessed response to reference compounds, for tissue-based high-throughput drug screening tools
  • Have an initial design f a computer-aided system to import patient electronic health record data and prescribe best regimen of medications

All projects funded through this FOA will be expected to provide preliminary or advanced intellectual property and regulatory plans (depending on project stage), evidence of a secured cash match equivalent or greater than 25% of the direct federal costs of the award, and identified a committed Accelerator Partner to support project development.

Award Activities

For Devices, the R33 allows prototype development and testing, in addition to modifying design features and user feedback.

Examples of activities for the R33 phase may include, but are not limited to:

• For Devices:
  • Complete system integration
  • Packaging optimization
  • Engineering optimization to reduce size, weight, cost or improve system performance, reliability, repeatability, power consumption, durability
  • Design fr 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 standards
  • In-vivo testing
  • Demonstrate safety and reliability in chronic in-vivo testing
  • Large animal model testing
  • Bicompatibility, hemocompatibility, histopathology testing per accepted standards
  • Pre-submission meeting with FDA

For Diagnostics, the R33 award allows product generation, exploration of assay components and characterization of a load design.

Examples of activities for the R33 phase may include, but are not limited to:

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

For Research Tools, the R33 will allow product improvement, large trial testing and data integration.

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

• For Tools:
  • Improve smartphone user interface based on large population testing
  • Large human trial t 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
  • Use AI and large numbers/concentrations of compounds to train the prediction system and evaluate its performance, for tissue-based high-throughput drug screening tools
  • Multi-site clinical study o a computer-aided system to compare computer-recommended prescriptions vs standard medical therapy

• Examples of activities that are not appropriate for this FOA include, but are not limited to:

  • Activities geared toward therapeutic agent development (See companion FOAs RFA-HL-20-023 and RFA-HL-20-027)
  • Early stage device and diagnostic development activities, including initial prototype and diagnostic disease target identification (See companion FOA RFA-HL-20-024)
  • Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers
  • Clinical research and clinical trials

Special Requirements for this FOA

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 awardees 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 enable continuous assessment of the progress of the studies relative to established milestones. Project management may be at the local level, or in some instances provided through NIH support.

Matching Component

Cost matching is required for applicants responding to this FOA. The awardee is required to provide a minimum of a 0.25:1 non-Federal cash match of the Federal direct costs requested. 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. To be considered responsive to this FOA, applicants are expected to include a description in the Budget Justification of how the matching funds will be used.Generally, cost matching requirements 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

The application must include a letter of support from the non-Federal source(s) of cost matching. Applications that do not include the letter of support from the non-Federal source(s) of cost matching are incomplete for this FOA and will not be peer reviewed.

Accelerator Partner(s)

At least one accelerator partner is required for this award. Developing device prototypes, diagnostics and research tools requires a multidisciplinary approach, and applicants should consider how they will identify and foster relationships with potential licensing and commercialization partners early in the product development process once an award is made. Collaborative relationships with ecosystem partners knowledgeable in device, diagnostics and tools development processes, as well as those familiar with what the desired end product should look like (such as clinicians and biostatisticians), results in vested shared interests, and access to complementary development expertise and resources for successful development. The Accelerator Partner should help advance the 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.

Evidence of an Accelerator Partner is required and applicants must include a letter of support from the Accelerator Partner in their application. Applications that do not in clude the letter of support from the Accelerator Partner are incomplete for this FOA and will not be peer reviewed. 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, business development and commercial strategy, entrepreneurship, regulatory submission, evaluation, and review, market and commercial evaluation, intellectual property protection, and reimbursement strategy. Career development through accelerator partners is highly encouraged to achieve the goal of exposing innovators to the myriad processes required to translate discoveries into useful products.

Milestones

This Catalyze Product Definition initiative targeting advancement of device prototypes, diagnostics and research tools is an R33 innovation award. This program will allows investigators to perform the product definition studies required for prototype design and testing, and development of diagnostics and tools for future preclinical testing and development. Applicants must meet the entry criteria to be eligible for the award, and propose activities and milestones to be completed during the proposed duration of award.

These milestones will ensure that projects are sufficiently progressing to be in a position to enter preclinical programs following completion of the award. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision making and should have timelines and quantitative criteria associated with them. All milestones should be useful as a measure of progress toward the overall goal of the project. Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals. Milestones must be identified in the application, and these may be negotiated by the NHLBI team pre-award, based on comments of the peer review panel. NHLBI staff will meet annually to monitor program progress against proposed milestones and make non-competing award decisions. NHLBI emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress. This award should result in prototype development and in vitro efficacy testing, preliminary diagnostic assay and tool development, and advance projects towards preclinical product characterization and optimization activities.

Intellectual Property and Regulatory Considerations

Projects at the stage of development supported through this FOA are expected to be developed to the point where initial IP and regulatory strategies are being developed. This FOA requires that applicants submit their IP and regulatory strategies in their applications, even if the plans are not yet fully developed. 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 milestones and any changes suggested by the NHLBI review panel or Program staff. A final set of approved milestones will be specified in the Notice of Award.

Section II. Award Information

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)

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

• 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

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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but 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 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.

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.

2. Cost Sharing

This FOA requires cost matching as defined in the NIH Grants Policy Statement. More information on the cost matching requirement is in Section IV.2 R&R or Modular Budget.

3. Additional Information on Eligibility

Number of Applications

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)

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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]

Other Attachments:

IP and Regulatory Strategies (Required)

The filename "IP and Regulatory Strategies.pdf" must be used and attached.

Projects funded through this program should be at the stage where investigators should be considering IP and regulatory strategies, although the strategies may be in the early development stages. Applicants must include preliminary IP and regulatory plans in their applications. If the project is at the appropriate stage, please include the following for IP and regulatory plans:

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.

Applicants are also strongly encouraged to contact the appropriate NIH Scientific/Research contact listed in Section VII or NHLBI’s Office of Translational Alliances and Coordination for questions regarding application expectations for IP and regulatory prior to submission.

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

Applicants must 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.

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.

Budget Justification: A total project budget (i.e., the requested budget plus the cost-matching budget) must be provided and must document the cost-matching (non-Federal) component and the Federal (non-cost matching) component. All costs and contributions used to satisfy the matching requirement must be documented by the recipient prior to release of the award, and are subject to audit.

Specific Aims: Include Specific Aims that state the specific objectives of the efforts, including the activities to be conducted to meet the goals of developing the proposed product.

Research Strategy:

Provide 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 approach, and (5) a summary of the project status, including information regarding potential products to be tested in the current application. An important component of the strategy should be a carefully developed rationale for the experimental design and a description of how data obtained through this grant will provide a path for optimization of preliminary products and how knowledge gained from this work 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: Milestones must be relevant, measurable, feasible, scientifically justified, results-focused and time-bound. Specific aims or a list of activities are not considered milestones. 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.

Timeline: Provide a timeline with specific milestones for the work proposed in each year of the award. 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. Project management may be at the local level, or in some instances provided through NIH support. Describe plans for how the selected project management process(es) will support product development studies of the device, diagnostics and/or tools.

Rigor and Reproducibility

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).

Letter of Support:

The application must include a letter of support from the non-Federal source(s) of cost matching that documents their actual contributions to the project and demonstrates assurances that they are committed to providing the cost matching funds and/or resources for their share of the project. Applications that do not include the letter of support from the non-Federal source(s) of cost matching are incomplete for this FOA and will not be peer reviewed

The application must include a Letter of Support from the Accelerator Partner. A?pplications that do not include the letter of support from the Accelerator Partner are incomplete for this FOA and will not be peer reviewed.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

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 SF424 (R&R) Application Guide must be followed.

Not Applicable

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

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

4. Submission Dates and Times

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&##8217;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.

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.

7. Other Submission Requirements and Information

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 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 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 NHLBI. Applications that are incomplete, non-compliant and/or non-responsive will not be reviewed.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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:

To what extent does the application describe how the project will provide significant improvement over the existing technology? To what extent is the project relevant for device, diagnostic or tool development, and is there a strong rationale for the proposed activities? How will the project, if successful, bring the investigators closer to products that will be a significant improvement over existing products to treat HLBS disorders?

Investigator(s)

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:

What makes the investigators knowledgeable and experienced about the prototype development for devices, diagnostics and research? To what extent does the researcher have experience with target identification and validation, and lead selection, or include collaborators with the appropriate expertise to support the proposed experimental design and implementation activities and overall project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:

To what extent is the project novel for device, diagnostic or tool development?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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:

To what extent has the innovator identified clear, well-defined, measurable goals to pursue to advance development of the proposed products?

To what extent is the project feasible? How will the project, if successful, support development of future products for HLBS diseases and disorders? To what extent is the process for prototype development and testing, and diagnostic and tool development appropriate? How will completion of activities yield potential products that meet the entry criteria for Catalyze Preclinical or other federal or private further development mechanisms?