Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Eye Institute (NEI)

Funding Opportunity Title
NEI Regenerative Medicine Clinical Trial Planning Grant (R34 - Clinical Trials Not Allowed)
Activity Code

R34 Planning Grant

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-22-070
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.867
Funding Opportunity Purpose

The National Eye Institute (NEI) supports regenerative medicine clinical trials. Before a research team undertakes a clinical trial, it is critical to have clear delineation and documentation of the trial’s rationale, design, analytic techniques, protocols, and procedures in a Manual of Procedures (MOP).  Additionally, there are other elements essential to the launching of a trial, such as obtaining regulatory authorizations or approvals and establishing agreements with requisite partners including cell manufacturing and production facilities, assay or cell analysis centers, and data coordinating centers. These activities are often costly and time-consuming, and they may involve collection of preliminary data to assess feasibility. The Regenerative Medicine Clinical Trial Planning Grant may be used by applicants to support the preparation of a clinical trial MOP and procedures necessary for implementing a clinical trial to evaluate interventions (or new treatments) that restore vision in humans through regeneration of cells. 

Key Dates

Posted Date
November 15, 2021
Open Date (Earliest Submission Date)
January 16, 2022
Letter of Intent Due Date(s)

Not Applicable

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
February 16, 2022 * March 16, 2022 * Not Applicable July 2022 October 2022 December 2022
June 16, 2022 * July 16, 2022 * Not Applicable November 2022 January 2023 April 2023
October 16, 2022 * November 16, 2022 * Not Applicable March 2023 May 2023 July 2023
February 16, 2023 * March 16, 2023 * Not Applicable July 2023 October 2023 December 2023
June 16, 2023 * July 16, 2023 * Not Applicable November 2023 January 2024 April 2024
October 16, 2023 * November 16, 2023 * Not Applicable March 2024 May 2024 July 2024
February 16, 2024 * March 16, 2024 * Not Applicable July 2024 October 2024 December 2024
June 16, 2024 * July 16, 2024 * Not Applicable November 2024 January 2025 April 2025
October 16, 2024 * November 16, 2024 * Not Applicable March 2025 May 2025 July 2025

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
January 08, 2025
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The National Eye Institute (NEI) Audacious Goal Initiative (AGI) is an effort to push the boundaries of vision science and restore vision through regeneration of cells in the retina. AGI research specifically targets photoreceptors (PRCs) and retinal ganglion cells (RGCs) in the eye. Photoreceptors — often called rods and cones — are cells in the retina that, when stimulated by light, generate signals the brain perceives as images. The retinal ganglion cells carry these signals from the photoreceptors to the brain. Although there has been some success in regenerating retinal neurons and connections in fish, mice, and other systems, the ultimate goal of the AGI is to restore vision in humans.

AGI research has been laying the groundwork for clinical studies of new interventional strategies for reversing vision loss in humans. For example, AGI functional imaging projects developed new methods to noninvasively image cells and tissues of the visual system to evaluate the effects of regenerative therapies; AGI discovery-based projects have identified factors such as genes, proteins, and other cellular messengers that are important for neural regeneration and could serve as interventional targets; and AGI translation-enabling models projects are bridging the gap between basic and clinical research.

Experimental interventions are evaluated in clinical trials. Before a research team undertakes a clinical trial, it is critical to have clear delineation and documentation of the trial’s rationale, design, analytic techniques, protocols, and procedures in a Manual of Procedures (MOP). Additionally, there are other elements essential to the launching of a trial, such as obtaining regulatory authorizations or approvals and establishing agreements with requisite partners including cell manufacturing and production facilities, assay or cell analysis centers, and data coordinating centers. These activities are often costly and time-consuming, and they may involve collection of preliminary data to assess feasibility.

Objectives

This Funding Opportunity Announcement (FOA) provides support for activities central to the refinement and completion of a study protocol and procedures necessary for implementing a clinical trial to evaluate interventions (or new treatments) that restore vision in humans through regeneration of cells. Applicants may use this grant to support the development of a detailed MOP, to collect safety/toxicity data, to conduct preliminary studies evaluating feasibility, or collecting other pre-clinical data of regenerative strategies as part of the planning process.

An important aspect of this grant is that the research team is expected to plan for a treatment trial that addresses loss of vision using an approach that involves regenerating PRCs, RGCs and their connections, and/or regenerating optic nerve fibers. Regenerative strategies may include the use of stem cell-derived precursors and/or progenitor cells as well as adult stem cells and products derived from these cells (e.g., exosomes or conditioned media) and/or employ methods for converting endogenous cells such as glia into PRCs or RGCs. The planned clinical trial and any related preliminary work should use quantitative measures to evaluate survival and integration of the regenerated cells using electrophysiology, functional imaging, behavioral measures or other appropriate technology that would demonstrate circuit integration and restoration of visual function.

If successful, a project funded under this planning grant should lead to its securement of documentation of a United States Food and Drug Administration (FDA) Investigational New Drug (IND) authorization or an Investigational Device Exception (IDE) approval, as applicable; and/or evidence of readiness for an NEI UG1 Clinical Vision Research Grant or equivalent application. The steps towards these goals should be clearly delineated in a series of milestones that support planning of a trial to evaluate a treatment that restores vision through regeneration of cells in the retina.

Applicants should note that funding of this planning grant does not guarantee nor imply funding for any subsequent competitive application for the support of a full-scale study. Although this initiative can be used to support preliminary activities that may involve collection of pilot and feasibility data, it must not be used to conduct a study that meets the NIH definition of a clinical trial (as defined in NOT-OD-15-015).

Scope

This FOA is designed to permit early peer review of the proposed clinical trial in terms of its rationale, design, organizational structure, and implementation plan; to support development of essential elements of a clinical trial (e.g., finalization of the protocol and Manual of Procedures (MOP), development of tools for data management and research oversight); and to lead to an application for support of a full-scale trial, based on elements developed under the planning period.

Applications submitted in response to this FOA are expected to propose planning for a clinical trial that explores and enables the evaluation of the safety and/or efficacy of interventions that restore vision through the regeneration of cells. Activities supported by this FOA may include, but are not limited to, the following examples:

  • Preparing the clinical trial protocol and MOP. Basic elements in the MOP should include identification of the patient population (including stages of disease(s)); inclusion and exclusion criteria; adequate plans for recruitment and retention of participants; experimental design and protocols; clear definition of the research hypothesis, outcome measures, and adverse events; quality control/assurance procedures; data management and analytical techniques; sample size estimates with justification; administrative procedures, including regulatory approvals if necessary; study organization, including an organization chart; duties and responsibilities of the study chairperson, clinical sites, coordinating center, and other central resources such as a reading center; monitoring plans to assure patient protection and data integrity; and plans for addressing Federal gender/minority inclusion and human subjects protection requirements.
    • In addition, the MOP should describe procedures for creating a regenerative environment and for tracking and monitoring stem cell function and integrationin vivo; methods for in-depth stem cell characterization; and plans for sharing data and other resources after the full clinical trial is completed, including a plan to make available representative samples of source stem cell-derived products for in-depth and independent characterization, as appropriate and consistent with achieving the goals of the research.
  • Conducting administrative procedures necessary for obtaining regulatory authorization or approvals (such as pre-IND/IDE meetings with the FDA and other communications).
  • Conducting preliminary studies to refine study procedures, document recruitment potential, and assess feasibility and acceptability of the approaches to be used in a future full-scale clinical trial. For example, applicants may collect information necessary to verify the available study populations and attrition/event/response rates; and to validate or standardize the intervention, outcome measurements, instruments, etc. Preliminary studies may include late-stage IND/IDE-enabling toxicology studies and studies to collect pilot data as required by regulatory agencies such the FDA for IND/IDE applications.
  • Establishing and documenting collaborative arrangements, for example, with extant cell manufacturing or production facilities and with clinical assay or cell analysis centers.
  • Establishing methods for selecting cGMP compliant stem cell production, phase-appropriate GMP, and/or master cell banks; and for utilization of cGMP standards.
  • Developing strategies to detect, prevent, and/or address common challenges related to stem cell therapy, such as differentiation efficiency, possible immune rejection, and other safety concerns.
  • Developing/finalizing data and safety monitoring plans, including defining areas of expertise that will be pertinent in forming these groups.
  • Developing plans for any training that is required to carry out the proposed study. This may include, for example, training of data collectors and individuals who will carry out the planned intervention.
  • Instituting means to assure standardization of procedures across sites and among staff.

Any preliminary study proposed must include clear quantitative benchmarks for measures by which successful (or unsuccessful) feasibility will be evaluated (e.g., 75% of participants in each treatment group will attend 90% of the scheduled clinical visits). These benchmarks must be relevant to the target population and the specific intervention under investigation.

Milestones

The investigative teams are expected to develop milestones for measuring progress at each point in the clinical trial planning process. Milestones should be quantifiable measures that reflect the degree of success of each aspect of the development of the therapeutic or device. Milestones should clearly define the regulatory strategy and transition plan to move the product to the next research phase after successful completion of the award.

Applications Not Responsive to this FOA

The following types of applications will be considered non-responsive to this FOA:

  • Any research conducted as part of the planning process that meets the NIH definition of a clinical trial (i.e., a research study in which one or more human participants are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes).
  • Any research that is not compliant with NIH policy on human embryonic or fetal stem cells (e.g., https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-128.html). Such projects are non-responsive.
  • Any research that does not address loss of vision using an approach that involves regenerating photoreceptors (PRCs) and/or retinal ganglion cells (RGCs) and their connections, and/or stem cell-derived products for regeneration of optic nerve fibers. Such projects are non-responsive.

Non-responsive applications will not be reviewed. Applicants are encouraged to contact the NEI Scientific/Research Contact listed at the end of this FOA to discuss the programmatic priorities of the NEI prior to submission.

Projects will be prioritized on their scientific merit and their collective potential to advance the AGI.

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

The NEI permits direct costs up to $150,000 per year plus applicable F&A for consortia.

Award Project Period

The scope of the proposed project should determine the project period. The maximum period is two years.

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

Eligible Organizations

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)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Required Registrations

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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

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

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).

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.

Instructions for Application Submission

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.

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:

Please clearly address the following:

  1. Explain how the proposed project will significantly advance the field of regenerative medicine by contributing to foundational knowledge while addressing restoration of vision through the regeneration of cells and/or axons in the eye or visual system. 

  2. Provide details on expertise, experience, and ability of the proposed leadership to organize, manage, and implement the proposed clinical trial planning; and to meet milestones. If applicable, show how the study involves collaborations and/or input from community partners and relevant policy makers/regulators in order to inform the research and contribute to ensuring that the results have utility. 

  3. Explain how the design includes innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge. Show how the specific aims will provide results that are both necessary and sufficient to make a final decision about the subsequent trial. 

  4. Show how development of an MOP; proposed strategies to detect, prevent, and address common challenges related to stem cell therapy; and/or information collected through any proposed preliminary activities will be used to inform decisions about the subsequent clinical trial (e.g., study design, primary objective, eligibility criteria, sample size, primary and secondary outcomes, duration of recruitment and follow-up, etc.). 

  5. If proposed, explain benchmarks by which successful (or unsuccessful) feasibility will be evaluated in preliminary studies and the extent that these benchmarks are relevant to the target population and the specific intervention to be investigated. 

  6. If proposed, explain how  collection of pilot data   will further regulatory approvals including from the FDA for IND/IDE applications. 

  7. Explain how the planned analyses and statistical approach(es) are appropriate for the proposed study design and methods. The procedures for data management and quality control must be standardized and applicable and there must be a plan to complete the data analysis within the proposed period of the award. 

  8. Show how the study will utilize existing infrastructure (e.g., eGMP facilities, practice-based research networks, electronic medical records, administrative data bases, patient registries, etc.) or other available resources to increase the efficiency of participant recruitment, data collection, cell standardization and analyses, or other aspects of the proposed project. In the event that such efficiencies cannot be incorporated, a justification can be provided. 

  9. If proposed, explain how the administrative and data coordinating activities are appropriate for the proposed study. Also address the capability and ability to conduct the study at the proposed site. If an international site(s) is/are proposed, show how the application adequately addresses the complexity of executing the study. 

  10. Provide milestones that support planning of a trial to evaluate a treatment that restores vision through regeneration of cells. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

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.

Appendix:

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

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

PHS Human Subjects and Clinical Trials Information

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

In order to expedite review, applicants are requested to notify the {IC} Referral Office by email at libermane@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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).

Scored Review Criteria

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

 

Does the project address an important problem or a critical barrier to progress in the field? Is 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?

How likely is it that the proposed project will significantly advance the field of regenerative medicine by contributing to foundational knowledge while addressing restoration of vision through the regeneration of cells and/or axons in the eye or visual system? 

 

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?

Regarding the proposed leadership for the project, do the PD/PI(s) and key personnel demonstrate adequate expertise, experience, and ability to organize, manage, and implement the proposed clinical trial planning; and to meet milestones?  Where relevant, how adequate are the plans for involving collaborations and/or input from community partners and relevant policymakers/regulators to inform the research and contribute to ensuring that the results have utility? 

 

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge? 

 

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? 
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Will successful conduct of the specific aims of the R34 application provide results that are both necessary and sufficient to make a final decision about the subsequent trial? Is there a clear plan for how development of an MOP; proposed strategies to detect, prevent, and address common challenges related to stem cell therapy; and/or information collected through any proposed preliminary activities will be used to inform decisions about the subsequent clinical trial (e.g., study design, primary objective, eligibility criteria, sample size, primary and secondary outcomes, duration of recruitment and follow-up, etc.).? 

Where relevant (if the application proposes preliminary studies to assess feasibility), does the application provide clear quantifiable benchmarks by which successful (or unsuccessful) feasibility will be evaluated. To what extent are these benchmarks relevant to the target population and the specific intervention under investigation? 

Where relevant (if the application proposes collection of pilot data as part of the planning process, including safety/toxicity data), does the application provide sufficient evidence that collection of pilot data will further regulatory approvals including from the FDA for IND/IDE applications. 

Data Management and Statistical Analysis

Are planned analyses and statistical approach(es) appropriate for the proposed study design and methods? Are the procedures for data management and quality control adequate and standardized, as applicable? Is there a plan to complete data analysis within the proposed period of the award? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed? 

 

 

 

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Does the study utilize existing infrastructure (e.g., eGMP facilities, practice-based research networks, electronic medical records, administrative data bases, patient registries, etc.) or utilize other available resources to increase the efficiency of participant recruitment, data collection, cell standardization and analyses, or other aspects of the proposed project, or provide a justification in the event that such efficiencies cannot be incorporated? 

If proposed, are the administrative and data coordinating activities appropriate for the study proposed? Does the application adequately address the capability and ability to conduct the study at the proposed site? If international site(s) is/are proposed, does the application adequately address the complexity of executing the study? 

 

 

Additional Review Criteria

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.

 

Milestones

Does the application propose appropriate milestones that support planning of a trial to evaluate a treatment that restores vision through regeneration of cells in the retina? How strong are the proposed milestones for measuring progress at each point in the clinical trial planning process? Do milestones clearly define the regulatory strategy and transition plan to move the product to the next research phase after successful completion of the award?

 

For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

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

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

 

Not Applicable

 

Not Applicable

Additional Review Considerations

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.

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

 

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

 

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

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by{ NEI, 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

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.

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

2. Administrative and National Policy Requirements

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

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.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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.

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. 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.

Application Submission Contacts

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: http://grants.nih.gov/support/ (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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Donald Everett, MA 
National Eye Institute (NEI) 
Telephone: 301-435-8181 
Email: everettd@mail.nih.gov 

Maryann Redford, DDS, MPH 
National Eye Institute (NEI) 
Telephone: 301-435-8173 
Email: redfordm@mail.nih.gov 

Sangeeta Bhargava, PhD 
National Eye Institute(NEI) 
Telephone: 301-435-8175 
Email: bhargavas@nei.nih.gov 

Jimmy Le, ScD 
National Eye Institute (NEI) 
Telephone: 301-435-8160 
Email: jimmy.le@nih.gov 

Peer Review Contact(s)

Brian Hoshaw, PhD 
National Eye Institute (NEI) 
Telephone: 301-402-0566 
Email: brian.hoshaw@nih.gov  

Financial/Grants Management Contact(s)

Karen Robinson-Smith 
National Eye Institute (NEI) 
Telephone 301-435-8178
Email: Karen.Robinson.Smith@nei.nih.gov 

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.

Authority and Regulations

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.

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