National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Advancing Translational Sciences (NCATS)
R34 Planning Grant
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
RFA-HL-23-019 , U01 Research Project (Cooperative Agreements)
The National Institutes of Health (NIH) participating Institutes and Centers, in coordination with the U.S. Food and Drug Administration (FDA) support the Regenerative Medicine Innovation Project (RMIP), which aims to explore and enable the development of safe and effective regenerative medicine (RM) interventions using adult stem cells. 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. Applicants may use the RMIP Clinical Trial Planning Grant to support the preparation of a clinical trial MOP and procedures necessary for implementing a clinical trial to evaluate interventions (or new treatments) that explore and enable the evaluation of the safety and/or efficacy of RM interventions using adult stem cells that are not of embryonic or fetal origin.
Due to the complex nature of requirements in this FOA (e.g., 1:1 matching funds, resource sharing), applicants are strongly encouraged to communicate with the appropriate NIH Scientific/Research Contact and review online Frequently Asked Questions (FAQs) prior to submitting an application. Staff will be able to advise applicants in determining if their research meets the requirements and objectives of this FOA.
September 2, 2022
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| October 06, 2022 | Not Applicable | Not Applicable | March 2023 | May 2023 | July 2023 |
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.
Not Applicable
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.
Background
The National Institutes of Health (NIH) participating Institutes and Centers, in coordination with the U.S. Food and Drug Administration (FDA) the Regenerative Medicine Innovation Project (RMIP) to explore and enable the development of safe and effective regenerative medicine (RM) interventions using adult stem cells. 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 may also involve collection of preliminary data to assess feasibility and acceptability of the proposed strategies; however, collection of data to support or justify the scientific rationale of the project is not permitted.
Purpose/Research Objectives
- Potential to catalyze sustained and accelerated development of the RM field through contributing to the knowledge critical for clinical testing, stem cell characterization and authentication, cGMP compliant stem cell production or phase-appropriate GMP and utilization of standards, in vivo stem cell tracking and monitoring, data standards development, and data sharing
- Readiness of the RM product for advancement into clinical trials under an IND/IDE application
- Contribution to the significant advancement of the field of RM by addressing well-recognized challenges in clinical development
- Critical issues relevant to clinical research and regulatory submissions, including those related to improved evaluation of product quality
- Provision of preliminary data, clinical and/or non-clinical study data, or information in the literature or citations regarding mechanism of action that support the scientific rationale and need for the clinical trial to test the proposed hypothesis or intervention
- Contribution to the breadth of RM science
- Use of existing research infrastructure such as clinical trial network(s) where possible
- Contribution to an improved and shared understanding of current technical and operational barriers as well as regulatory science issues in the field of RM and how to overcome them
Applicants may use this grant to support the development of a detailed MOP; conduct non-clinical (non- human) work to collect safety/toxicity data; and/or conduct preliminary studies to evaluate feasibility and acceptability of regenerative strategies.
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 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 RM interventions using adult stem cells that are not of embryonic or fetal origin. 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; informed consent procedures; 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 inclusion policies (Women, MInorities and Individuals across the Lifespan) 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 integration in vivo; methods for in-depth stem cell characterization; and plans for sharing data and other resources after the full clinical trial is completed (e.g., plans for making 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, and instruments. Preliminary studies may include late-stage IND/IDE- enabling non-clinical (non-human) toxicology studies and studies to collect pilot data as required by regulatory agencies such as the FDA for IND/IDE applications to assess feasibility and acceptability.
- Establishing and documenting collaborative arrangements, for example, with extant cell manufacturing or production facilities; clinical assay or cell analysis centers; and/or enrollment sites and other research collaborators.
- Establishing methods for selecting cGMP compliant stem cell production, phase- appropriate GMP, and/or master cell banks; and for utilization of cGMP standards.
- Addressing the challenges around scale-up of cell production.
- 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 will attend 90% of the scheduled clinical visits). These benchmarks must be relevant to the target population and the specific intervention under investigation.
Milestones
Matching Requirement
An application funded under this announcement is required to match all federally awarded dollars (total costs: direct costs and indirect costs including facilities and administrative costs) with at least an equal amount (1:1) of non-Federal contributions, as mandated by the 21st Century Cures Act. Qualifying non- Federal contributions may include state and local funding not originating from Federal funds, private- sector investments, in-kind contributions, and donations from foundations. See 45 CFR 75.306, as well as relevant FAQs, for additional details. The applicant will be required to demonstrate that funds and in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source, type, and amount of funds proposed to meet the matching requirement and explain how the value of in-kind contributions was determined. Applications must also include letter(s) of support confirming that the required matching contributions (cash or in-kind contributions such as salary, consultant costs, equipment) are available. See additional details and instructions in Section IV.2 and Section VI.3.
Applications that are incomplete or Not Responsive to this FOA
The following types of applications will be considered non-responsive to this FOA and will not be reviewed
-
- 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). Such projects are non-responsive.
- 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-21-111.html). Such projects are non-responsive.
- Applications that do not include a letter(s) of support confirming that the required matching contributions (cash; in-kind contributions such as salary, consultant costs, equipment) are available. Such applications are incomplete; see additional details and instructions in Section IV.2
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
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.
Not Allowed: Only accepting applications that do not propose clinical trials.
NIH intends to commit total funds of up to $8,000,000 across the project periods of this and the companion FOAs and anticipates issuing up to 10 awards for projects submitted to this FOA. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The total budget (Federal award and non-Federal matching contributions) should reflect the actual needs of the proposed project. While annual project budgets should reflect the actual costs anticipated in each year, the Federal share of this award must not exceed $150,000 in direct costs per year.
The recipient is required to provide at least a 1:1 match of the Federal funds requested (for Direct and Indirect/F&A costs) in the form of non-Federal contributions, as mandated by the 21st Century Cures Act (45 CFR 75.306).
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.
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 Government
- 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 not 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 full SAM and 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.
2. Cost Sharing
This FOA requires cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, 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)
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.
Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute (NHLBI)
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Provide detailed, annual budgets that will enable the trial to meet its milestones. Use budget form pages for Federal funds only. In the budget justification, provide the detailed budget needs (per year and total) of both Federal and non-Federal funds, and an implementation and cost management plan (e.g., capitation).
Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget.
Include budget support for the PD/PI to participate in an NIH-held RM innovation meeting or workshop once each budget year in the Washington, DC/Metropolitan area.
Cost Matching Requirement
Cost matching is required for applicants responding to this FOA. The awardee is required to match (at least 1:1) the total Federally-awarded amount (total Direct and Indirect/F&A costs). Institutions must be able to document their actual contributions, which may include in-kind contributions, to the project and provide assurances that the organization(s) are committed to providing the funds and resources for their share of the project.
Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
- Costs borne by another Federal grant or sub award
- Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds
- Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient)
- Program income
- Patient incentives
Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. Page 2, box 15 of the SF424 should reflect the total Federal funds requested, the total non-Federal funds, and the combined Federal and non-Federal funds.
Budget Justification: A total project budget (i.e., the requested budget plus the cost-matching budget as mandated by the 21st Century Cures Act/45 CFR 75.306) must be provided and must document the cost-matching (non-Federal) component and the Federal (non- cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable. Include a table that shows the annual Federal cost share and the share from matching funds, followed by a description of those costs for each year of the project.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Please clearly address the following:
- Explain how the proposed project will significantly advance the field of regenerative medicine by contributing to foundational knowledge, address well-recognized challenges in clinical development, and evaluate safety and effectiveness RM products
- 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.
- 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.
- 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.).
- 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.
- If proposed, explain how collection of pilot data will further regulatory approvals including from the FDA for IND/IDE applications.
- 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.
- Show how the study will utilize existing infrastructure (e.g., cGMP 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.
- 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.
- Provide milestones that support planning of a trial to evaluate a treatment that address well- recognized challenges in clinical development, and evaluate safety and effectiveness RM products.
- Where relevant (if the application proposes preliminary studies to assess feasibility), provide clear quantifiable benchmarks by which successful (or unsuccessful) feasibility will be evaluated. Explain to what extent these benchmarks are 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), provide sufficient evidence that the collection of pilot data will further regulatory approvals including those from the FDA for IND/IDE applications.
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.
- No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
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.
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
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.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit 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 fieldof 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Amended letter(s) of support indicating whether an applicant successfully competed for non-Federal funds will be accepted as post-submission materials if received no later than 30 days prior to the scheduled peer review meeting.
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.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA:
- How likely is it that the proposed project will significantly advance the field of RM by contributing to foundational knowledge while addressing a well-recognized challenge in clinical development, and evaluation of safe and effective RM products?
- To what extent does the application address critical issues relevant to the fundamental scientific understanding of the safety, quality, and effectiveness of adult stem cell-derived products used in clinical research and regulatory submissions, including those related to RM product development (e.g., improved tools, methods, standards, or applied science that support a better understanding and improved evaluation of in-depth product characterization, manufacturing, potency, identity, quality, safety, in vivo function and integration, or effectiveness)?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?
Specific to this FOA:
Do the investigators have experience or access to expertise in the regulatory science and the regulation of regenerative medicine? This may include but not be limited to experience in the regulatory frameworks for research in areas such as cell or gene therapy.
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?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific to this FOA:
Does the design/research plan include novel elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
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?
Specific to this FOA:
- 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 development of a Manual of Procedures (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.)?
- Does the application provide a comprehensive clinical trial project management plan?
- How sufficient are the details regarding feasibility of trial launch, participant recruitment and retention, performance milestones, conduct and completion of the trial on-time and on-budget, and dissemination of results?
- 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.
- 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?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Specific to this FOA:
- Does the study utilize existing infrastructure (e.g., cGMP facilities, practice-based research networks, electronic medical records, administrative databases, 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.
Protections for Human Subjects
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.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
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.
Vertebrate Animals
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.
Biohazards
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.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
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).
Resource Sharing Plans
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).
Authentication of Key Biological and/or Chemical Resources:
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.
Budget and Period of Support
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 the National Heart, Lung, and Blood Institute , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
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.
- All regulatory requirements have been met.
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.
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.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
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:
- 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.html and https://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. 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, 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: [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]
Martha Lundberg, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0513
Email: [email protected]
Nancy Bridges, MD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3535
Email: [email protected]
Irina Sazonova, Ph.D.
National Institute on Aging (NIA)
Phone: 301-435-3048
Email: [email protected]
PJ Brooks, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-443-0513
E-mail: [email protected]
Aron Marquitz, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: none
E-mail: [email protected]
Tanya Hoodbhoy, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-1310
Email: [email protected]
Ivonne H. Schulman, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-385-5744
E-mail: [email protected]
Thomas Greenwell
National Eye Institute (NEI)
Phone: 301-443-5405
E-mail: [email protected]
Timothy LaVaute, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-3765
Email: [email protected]
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]
Victor M. Henriquez, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0813
E-mail: [email protected]
Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: [email protected]
Regina Kitsoulis
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2946
Email: [email protected]
E.C. Melvin
National Institute on Aging (NIA)
Phone: 301-480-8991
Email: [email protected]
Shannon Oden
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-3028
E-mail: [email protected]
Sarisa Kowl
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-594-1921
E-mail: [email protected]
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]
Tommy Gunter
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-451-3447
E-mail: [email protected]
Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and Section 1001 (b)(4)(D) of the 21st Century Cures Act (P.L. 114-255).
and Human Services (HHS)
