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 SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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. 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. Funding Opportunity Description

The rapid evolution and vitality of the biomedical sciences benefit from the contributions and creativity of investigators in the early stages of their careers, and a continuous infusion of new ideas, techniques, and perspectives from other fields. This Trailblazer Award is an opportunity for New and Early Stage Investigators to pursue research programs at the interface of engineering and/or the physical sciences with the biomedical sciences. Applicants are encouraged to contact the appropriate NIBIB Program Director assigned to their specific scientific program area (https://www.nibib.nih.gov/research-funding) to discuss the appropriateness of the project before submission. This Funding Opportunity Announcement (FOA) employs an R21 Exploratory/Developmental Research Grant mechanism enhanced to provide $400,000 in direct costs over three years, allowing expanded time and resources to pursue a new or emerging research program.

To help accomplish the goal of enhancing diversity in the NIH-supported research community, applications from investigators from groups that are underrepresented in the biomedical, behavioral or clinical research workforce (see, Notice of NIH’s Interest in Diversity (NOT-OD-20-031); see also data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering) are encouraged. Such individuals include women, those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds. All applicants to this FOA must meet the NIH definition of New or Early Stage Investigator (https://grants.nih.gov/policy/new_investigators/index.htm).

The application of principles and techniques from engineering and the quantitative sciences, such as physics, mathematics, chemistry, and computer sciences, is providing innovative technologies and novel methods to accelerate the pace of biomedical research, producing new understanding of disease mechanisms and translating these new discoveries to improve human health. The Trailblazer Award seeks to catalyze the development of transdisciplinary research approaches with the potential to open new areas of biomedical investigation.

A Trailblazer project may be exploratory, developmental, proof of concept or have high risk-high impact goals. Importantly, the proposed research for this FOA may be technology design-directed and may or may not be hypothesis-driven. In the context of this FOA, innovation encompasses approaches to address well-defined, unmet biomedical research needs through the development of new methods, ideas, or technologies; early steps along the path toward delivery of a new capability or method; and the integration of existing components in a previously unproven format. High-impact projects should transform our understanding or practice by applying an innovative approach to an important biomedical challenge. For projects supported by a Trailblazer Award, successful results should provide a solid foundation for further research under other funding mechanisms, such as the R01. Applicants will be considered ineligible for this funding opportunity if they have submitted an R01, R15 or any other R21 application, with a participating IC as the primary IC within the same review cycle. An awardee may not hold concurrent Trailblazer awards.

Trailblazer approaches are expected to differ substantially from current thinking or practice, therefore, extensive preliminary data demonstrating feasibility is an indication that the project is beyond the scope of this FOA. Reviewers determinations of merit will rely instead on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding or practice. Applicants can provide appropriate justification for the proposed work through literature citations, data from other publicly available sources, or analytical and computational models. The proposed research will likely involve considerable risk that the work may not be successful, so applicants should clearly explain the significance of the work to allow the reviewers to determine whether the potential impact justifies these risks.

Preliminary Data: Trailblazer applications are meant to be exploratory, novel, and non-incremental. We encourage the submission of high-risk, high-reward projects. A distinct feature for this FOA is that no preliminary data are required, expected, or encouraged. However, if available, some minimal preliminary data is allowed. Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. Such evidence, if provided, should not represent work involving the aims of the Trailblazer application. All preliminary data must be clearly marked and limited to one-half page, which may include one figure. Applications including data more than one-half page or more than one figure will be considered noncompliant with the FOA instructions and not go forward to review. Figures containing published data must include citations within the figure legend. Published data that is included in the research plan, biographical sketch or elsewhere in the application must be cited adjacent to each occurrence. Data that is published must be unambiguously identified as such within the application. References and data from widely available preprints that have a Digital Object Identifier (DOI) are considered published.

Clinical Trials: For applications submitted that propose clinical trials, this FOA will only support applications proposing early-stage clinical trials through Phase I, first-in-human, safety, feasibility, or other small clinical trials that inform the early-stage technology development in the submitted application. This FOA will not support applications proposing Phase II, III, IV or pivotal clinical trials, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern.

Applicants are strongly encouraged to contact the Scientific/Research contact for this FOA for guidance in advance of submitting an application to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial projects that each IC supports.

Not all research endeavors will be suitable for this FOA. Projects from New and Early Stage Investigators that are supported by extensive preliminary data should be submitted to the Parent R01 Clinical Trial Not Allowed FOA (https://grants.nih.gov/grants/guide/pa-files/pa-20-185.html) or the Parent R01 Clinical Trial Required FOA (https://grants.nih.gov/grants/guide/pa-files/pa-20-183.html) or Stephen I. Katz Early Stage Investigator Research Project Grant (R01 Clinical Trial Not Allowed) (https://grants.nih.gov/grants/guide/pa-files/PAR-21-038.html). Established investigators proposing exploratory and developmental projects should consider the Parent R21 Clinical Trial Not Allowed FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-195.html) or the Parent R21 Clinical Trial Required FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-194.html). Projects of limited cost or scope that use widely accepted approaches and methods within well-established fields should be submitted to the Parent R03 FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-200.html). Projects that propose incremental improvements in well-established areas of investigation are not appropriate for this FOA.

Specific Research Objectives and Scope

Each institute has specific areas of research interest.

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

NIBIB interests include the development and integration of advanced engineering, imaging, and computational technologies with life sciences for the improvement of human health and medical care. An application is not within the NIBIB mission and will be withdrawn from consideration if its principal focus is development of technologies whose goal is to understand basic biological function or mechanisms. Additionally, NIBIB only supports projects whose technology would ultimately be applicable to a broad spectrum of disorders and diseases rather than being limited to only a single tissue, organ, or physiological condition. However, applicants may propose research that utilizes only a single tissue, organ or physiological condition as a model system to facilitate the development of what is expected to be a more broadly applicable emerging technology. An application is not within the NIBIB mission and will be withdrawn from consideration if the proposed technology or approach has limited application to a single disease, organ, or physiological condition.

For this Funding Opportunity Announcement, if an application proposes a clinical trial, NIBIB funding of clinical trials will be in accordance with NOT-EB-21-005 "NIBIB Guidance for Support of Clinical Trial Applications." Briefly, NIBIB will only support mission-focused (see NIBIB's program areas) early stage clinical trial applications, i.e., feasibility, Phase I, first-in-human, safety, or other small clinical trials, that inform early stage technology development. NIBIB will not support applications proposing pivotal, Phase II, III, IV, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern. Also, mechanistic trials are not supported unless the primary focus of the project is on technology development.

Applicants are strongly encouraged to contact the NIBIB Scientific Contact listed in this FOA for guidance in advance of submitting an application that includes human subjects research to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial applications that NIBIB supports.

National Eye Institute (NEI)

NEI leads the federal government in conducting and supporting research in vision research. The mission of the National Eye Institute (NEI) is to eliminate vision loss and improve quality of life through vision research. The NEI has framed its current strategic plan around this mission which addresses multiple opportunities as challenges in the vision field.

NEI will support applications that address or seek fundamental knowledge related to vision sciences, including, but not limited to: cellular and molecular neuroscience, imaging, genetics, development, basic/translational research on vision including how the visual system works from the eyes to the brain in health and disease. The overarching goal is to reduce visual impairment and blindness and thus resulting in an improvement in the quality of life for people of all ages. In all these areas and related areas of vision sciences research, NEI encourages an emphasis on understanding and addressing health disparities that are experienced by underserved populations .

For this funding opportunity, only the following trials will be supported by NEI.

• Mechanistic trials defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., HOW an intervention works, but not IF it works or is safe).

Clinical trials that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, biologic, surgical, or device (invasive or non-invasive) interventions, preventive, therapeutic, and services interventions will not be supported under this FOA. Please refer to https://www.nei.nih.gov/grants-and-training/funding-opportunities to find the appropriate NIH or NEI-specific FOA for such clinical trials.

Applications considered for funding by the NEI must fall within the areas of emphasis detailed in the NEI Strategic Plan. (NEI Strategic Plan: Vision for the Future (PDF 22.5 MB)

To determine if your research fits within the NIBIB mission, please contact the appropriate Program Director in your scientific program area of interest (https://www.nibib.nih.gov/research-funding).

National Institute on Aging (NIA)

NIA leads the federal government in conducting and supporting research on aging and the health and well-being of older people. To fulfill its mission, NIA supports technologies which aim to increase the research community's understanding of the aging process, as well as diseases, conditions, and needs associated with growing older, in order to extend the healthy, active years of life. Studies of interest to NIA include, but are not limited to, the following:

• Technology development for imaging modalities and visualization tools as applied to aging
• Applications of artificial intelligence, machine learning, or health monitoring technologies to the study of aging biology or age related diseases
• Bioinformatic, statistical, and computational approaches in aging biology research
• Novel sensors and biomarkers for monitoring age-related changes and diseases
• Less invasive and more ubiquitous ways of collecting biological and diagnostic data
• Systems biology of aging
• Other emerging technologies that may benefit aging research and reflect new directions, such as new imaging technologies or novel biophysical approaches
• Tissues-, organs- and organ systems-on-a-chip technologies
• Imaging of any of the pillars or hallmarks of aging which include protein homeostasis, nuclear and DNA integrity, metabolism and mitochondrial quality control, cellular senescence, autophagy and cell death, and other hallmarks as described in the literature

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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 FOA.

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 Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• 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 his/her 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.

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

This FOA targets New and Early Stage Investigators integrating engineering and physical sciences with the biomedical sciences. Eligible individuals must be a) NIH-defined Early Stage Investigators; or b) NIH-defined New Investigators (https://grants.nih.gov/policy/early-investigators/index.htm). For applications with multiple PDs/PIs, all PDs/PIs must be eligible to apply for this award.

2. Cost Sharing

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

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 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Applicants will be considered ineligible for this funding opportunity if they have submitted an R01, R15 or any other R21 application, with a participating IC as the primary IC within the same review cycle Applicants may not hold concurrent Trailblazer awards.

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

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

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: Trailblazer R21 applications only allow minimal preliminary data. Consequently, determinations of merit and feasibility will rely instead on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Applicants are encouraged to provide justification for the proposed work through literature citations, data from other publicly available sources, analytical and computational models, or when available, from a limited amount of investigator-generated data. Since Trailblazer grant applications could involve considerable risk that the proposed work may not be successful, applicants are encouraged to clearly explain the significance of the proposed work, to allow the reviewers to determine whether the potential impact outweighs these risks.

Trailblazer applications are meant to be exploratory, novel, and non-incremental. We encourage the submission of high-risk, high-reward projects. Applications for Trailblazer R21 awards should describe projects distinct from those supported through the traditional R01 mechanism, which are generally longer-term systematic investigations supported by extensive preliminary data. Projects should have well-defined goals with the potential for future development. Applicants should explain how success in this project could lead to further development under other funding mechanisms, such as the R01.

Preliminary Data:

Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. Such evidence, if provided, should not represent work involving the aims of the Trailblazer application. All preliminary data must be clearly marked and limited to one-half page, which may include one figure.

Applications including data more than one-half page or more than one figure will be considered noncompliant with the FOA instructions and not go forward to review.

Figures containing published data must include citations within the figure legend. Published data that is included in the research plan, biographical sketch or elsewhere in the application must be cited adjacent to each occurrence. Data that is published must be unambiguously identified as such within the application. References and data from widely available preprints that have a Digital Object Identifier (DOI) are considered published.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

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 SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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

PHS Assignment Request Form

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

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’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 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 FOA 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 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described 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.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

For this particular announcement, note the following:

Trailblazer R21 grant applications are required to have minimal or no preliminary data. Reviewers' determination of merit will rely on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding or practice. Appropriate justification for the proposed work can be provided through literature citations, data from publicly available sources, or analytical and computational models. Projects supported under this FOA should not resemble small R01s, i.e., should not propose work using established tools and methods in well-established fields. The proposed research will likely involve considerable risk that the work may not be successful, so applicants should clearly explain the significance of the work to allow the reviewers to determine whether the potential impact justifies these risks

In the context of this FOA, innovation encompasses approaches to address well-defined, unmet needs of the biomedical research community and may include the development of new methods, ideas, or technologies; early steps along the path toward delivery of a new capability or method; and the integration of existing components in an unproven format.

Applicants are strongly encouraged to contact the Scientific/Research contact for this FOA for guidance in advance of submitting an application to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial projects that NIBIB supports.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

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 (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications 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.

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 FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Biomedical Imaging and Bioengineering. 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.

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 VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
  
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws, see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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.

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. NIH FOAs 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

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]

Randy King, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-0707
Email: [email protected]

Leonid V. Tsap, Ph.D.
National Institute on Aging (NIA)
Phone: 301-594-0277
Email: [email protected]

Martha C Flanders
National Eye Institute (NEI)
Phone: 301-827-5191
E-mail: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Katie Ellis
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4791
Email: [email protected]

Jessi Perez
National Institute on Aging (NIA)
Phone: 301-496-1472
Email: [email protected]

Karen Robinson-Smith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: [email protected]

Jessi Perez
National Institute on Aging (NIA)
Phone: (301) 402-7739
E-mail: [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 45 CFR Part 75 and 2 CFR Part 200.