National Institutes of Health (NIH)
R21 Exploratory/Developmental Research Grant
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
- October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
- September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
- August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
- August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
- April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
This Funding Opportunity Announcement (FOA) supports the discovery of novel compounds for the prevention and treatment of nervous system disorders. Through this FOA NIMH, NIA, NIAAA and NIDA wish to stimulate research in: 1) Identification, design, synthesis, and preclinical testing of small molecules for their potential as candidate therapeutics; 2) Initial hit-to-lead chemistry to improve activity of compounds against the target of interest; 3) Later stage lead optimization to improve efficacy and pharmacokinetics; and 4) Initial drug metabolism and pharmacokinetic properties (DMPK). Emphasis will be placed on projects that provide novel approaches for identifying potential therapeutic agents.
This FOA will also support applications proposing preclinical discovery of biotechnology products and biologics with potential as candidate therapeutics including, but not limited to, large biologic macromolecules, (e.g., proteins, antibodies, and peptides), gene-based therapies (i.e., oligonucleotide- and viral-based), cell therapies, and novel emerging therapies (e.g., microbial and microbiome therapies).
Not Applicable
| 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.
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.
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.
- Use the NIH ASSIST system to prepare, submit and track your application online.
- 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.
- Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
Purpose and Research Objectives
Significant advances in neuroscience, genetics, and basic behavioral science, together with technological developments, have provided a rich knowledge base for identifying new molecular targets for drug discovery, and developing rational pharmacotherapies for the treatment of a wide variety of nervous system disorders. With the wealth of potential new drug targets, the opportunity exists to accelerate the process of drug discovery and development to make quantum leaps toward novel and effective treatments for mental disorders and nervous system disorders associated with Substance Use Disorder (SUD), Alcohol Use Disorder (AUD) or aging.
Through this Funding Opportunity Announcement (FOA) the National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute on Aging (NIA) encourage the submission of research grant applications that aim to translate this wealth of basic science findings into the conceptualization, discovery, and preclinical evaluation of innovative therapeutics for mental illnesses and nervous system disorders associated with Substance Use Disorder (SUD), Alcohol Use Disorder (AUD) or aging, with the goal of accelerating the development of new treatments for these diseases.
The objective of this FOA is to stimulate research in the discovery, design, and preclinical testing of innovative and effective therapeutics aimed at prevention or treatment of nervous system disorders of primary interest to the NIMH, NIDA, NIAAA, and NIA. Projects focused on novel approaches and targets are highly encouraged. Projects designed for target identification or elucidation of disease mechanisms are not covered under this announcement.
Specific Areas of Research Interest
Applications aimed at the discovery of novel agents for ameliorating, modifying, or correcting potential aberrations in brain signaling are encouraged. These agents should be designed to affect fundamental processes associated with disease, such as neuronal dysfunction, abnormalities in cell growth, migration, plasticity, connectivity, and cell death, by targeting molecules and cellular mechanisms such as neurotransmitters, bioactive lipids, neuromodulators, and neurotrophins; receptors and ion channels; second and third messenger systems; protein synthesis, aggregation, and degradation; brain energy utilization; gene expression; neural-glial communication; and oxidative, immunological, and inflammatory mechanisms.
Research projects may include any activities required to identify, optimize, and validate potential therapeutic candidates and may propose studies focused on all stages of the early drug discovery pipeline, from screening to candidate selection.
Examples of these activities may include, but are not limited to:
- Preliminary identification of candidate therapeutics, using in silico, in vitro, ex vivo, or in vivo assays. This may include:
- Application of machine learning (ML), including human-in-the-loop ML (an ML model that requires researcher interaction), at each step of the drug discovery stage, spanning from hit/lead identification to lead optimization
- Use of generative ML models in de-novo design of drug chemical structures with desired properties
- Ligand-based virtual screening and computational hit expansion following high-throughput screening (HTS) campaigns
- Use of ML in the design of new molecules employing phenotypic and high content screening data and assessing their potency, selectivity, and binding affinity
- Use of ML models for predicting bioactivity and ADMET parameters of compounds
- Use of predictive and generative ML approaches in the design and development of potential therapeutic Biotechnology Products and Biologics to aid in biomolecule design, optimization, and formulation development.
- High, medium, or low-throughput assays, as well as counter-screening to assess the activity and selectivity of small molecules and biotechnology products and biologics with potential as candidate therapeutics.
- Ligand-based virtual screening and computational hit expansion following high-throughput screening (HTS) campaigns.
- The isolation, identification, characterization and synthesis of promising naturally occurring products.
- Design, synthesis, and preclinical testing of therapeutic approaches directed toward altering, modifying, or regulating aspects of disease processes, as well as disease initiation or progression. This may include:
- Initial medicinal chemistry to improve activity and selectivity of validated hit compounds against the target of interest.
- Initial in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) and in vitro toxicity studies of candidate therapeutics. IND-directed toxicology and safety pharmacology studies are outside the scope of this announcement.
- Later stage lead optimization to improve efficacy and pharmacokinetics.
- Development of ligands to serve as research tools in support of proof-of-principle preclinical studies and the validation of novel therapeutic targets.
- Initial DMPK and toxicity studies of candidate therapeutics. This may include in vitro and/or in vivo testing.
- Development of novel delivery systems to target therapeutics to the brain.
Use of innovative assays for the evaluation of the potential efficacy or toxicity of candidate therapeutics, such as cell-based or in vivo model systems that recapitulate critical molecular, cellular, or circuit/systems level features of a specific nervous system disorder, are encouraged. Preclinical assays should be directed toward assessing CNS effects rather than elucidating disease mechanisms. The choice of assays should be well-justified and appropriate for the stage of therapeutic development. While non-selective behavioral assays of CNS effects may be appropriate for initial in vivo preclinical screening to establish pharmacodynamics, later stage in vivo assays used for candidate prioritization should incorporate measures of circuits and brain processes linked to disorders.
The above-mentioned areas of investigation are representative and not meant to be exhaustive.
Investigators are highly encouraged to explore novel approaches for identifying potential therapeutic agents. While such projects involve higher risk, they also offer the potential for high impact. It is anticipated that investigators will balance risk, innovation, and impact and that applications that involve higher risk may focus on a shorter term, proof of concept effort.
This FOA uses the R21 grant mechanism while PAR-22-031 uses the R01 mechanism. High risk/high payoff projects that lack preliminary data may be most appropriate for the R21 mechanism, while applicants with preliminary data may wish to apply using the R01 mechanism.
Points to consider relevant to this announcement:
- Applications should be relevant to mental illnesses and/or nervous system disorders relevant to Substance Use Disorder (SUD), Alcohol Use Disorder (AUD) or aging.
- The main emphasis of projects submitted under this FOA should be on therapeutic discovery rather than target identification or elucidation of disease mechanisms.
Applications Not Responsive to this FOA
Applications on the following research topics are not responsive to this FOA and will be withdrawn prior to review:
-
Research involving human subjects
-
Projects seeking extensive studies required for the clinical development of candidate therapeutics, such as:
- IND-enabling studies (e.g. lead compound directed absorption, distribution, metabolism, and excretion [ADME])
- IND-directed toxicology and safety pharmacology studies
- Good Manufacturing Practices (GMP) synthesis
Data Sharing
A goal of the program is to further research advancements across the scientific community as rapidly as possible. In order to reap the maximum benefit from this program, assay data, assay protocols, and chemical structures of compounds tested are expected to be made publicly available, consistent with achieving the goals of the program.
Institute Interests
Projects proposing to develop compounds for targets that have significant prior or current investment may be of lower programmatic interest to participating ICs, unless applicants provide a compelling case that there are significant advantages to their approach.
Applicants are strongly advised to contact the Scientific/Research contacts listed in this announcement for NIMH, NIDA, NIAAA, and NIA prior to submission of an application.
NIMH
NIMH supports neuroscience research to discover the causes of mental illness and to develop more effective and safer treatments. Specifically, the NIMH is interested in the discovery of novel molecules to explore innovative targets for treatment development to address key deficits within and across mental illnesses, especially schizophrenia (cognitive and affective components), autism spectrum disorder (ASD), treatment-resistant depression, bipolar disorder, post-traumatic stress disorder (PTSD), and HIV-induced CNS dysfunction (see From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses). Therapeutic approaches aimed at addressing brain defects downstream of genomic mutations must be based on adequately powered clinical studies as detailed by the NIMH Report of the National Advisory Mental Health Council Workgroup on Genomics.
NIMH is also interested in the discovery of novel pre-clinical drug targets that can ameliorate the neuronal dysfunction targeting molecules and mechanisms that alter the neuron-glia interactions, immune dysfunction and/ or chronic inflammation in the periphery and CNS caused by Human Immunodeficiency Virus (HIV) and antiretroviral therapy ART.
NIMH is particularly interested in applications that address specific go/no-go criteria based on reliable and quantitative assay measures that assess whether the therapeutic approaches have: 1) sufficient activity at the appropriate molecular target or brain region, and 2) effects on specific neurophysiological systems or functional domains that are potentially impacted in mental disorders (see Research Domains Criteria (RDoC).
Projects aimed at the Discovery of Cell-based Chemical Probes for Novel Brain Targets should consider applying to PAR-21-028, projects aimed at the Discovery of in vivo Chemical Probes for the Nervous System should consider applying to PAR-21-029. Projects spanning broader goals including development and testing of novel assays or biomarkers of drug effects, initial GLP (Good Laboratory Practice) and GMP, to first in human studies should consider the National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction PAR-20-118 (U01) and PAR-20-119 (U19). Projects at the development stage proposed by small businesses should consider applying to the NIMH SBIR/STTR Programs.
Scientific rigor and transparency in conducting biomedical research are key to the successful application of knowledge toward improving health outcomes. In support of this important goal, investigators must follow NIH Guidance on addressing rigor and reproducibility in grant applications (http://grants.nih.gov/reproducibility/index.htm).
Applicants considering animal neurobehavioral approaches in research relevant to mental illnesses should follow the guidance NOT-MH-19-053 NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Pre-clinical Studies.
Further information on NIMH research priorities can be found on the NIH/NIMH Therapeutics Discovery Research website and in the NIMH Strategic Plan and Strategic Research Priorities. Applicants are strongly encouraged to discuss applications with NIMH staff listed in Section VII - Agency Contact(s) Scientific/Research Contacts.
NIDA
NIDA is interested in the discovery of novel therapeutics including small molecules and biologics to treat substance use disorders or the adverse effects of addictive substances (e.g., overdose, withdrawal). The focus of the research projects could encompass screening, discovery, and synthesis of novel small molecules and evaluation of their efficacy in validated preclinical models. The identification and pursuit of agents to modulate previously unrecognized or understudied targets for the treatment of mono- and polysubstance use disorders are especially encouraged.
NIAAA
NIAAA promotes discovery, synthesis and screening of novel small molecules for innovative priority targets, and supports evaluation of their efficacy in validated preclinical models to assess their therapeutic potential for treating alcohol misuse and alcohol use disorder (AUD). The focus of proposed research projects should follow that described above and be relevant to the mission of NIAAA. The identification and pursuit of agents towards novel targets previously un-recognized or understudied for the treatment of alcohol misuse and AUD are especially encouraged. NIAAA encourages applications focusing on agents that alleviate symptoms of protracted abstinence, including craving and dysphoria, and agents effective in patients who have co-morbid psychiatric illnesses (e.g., posttraumatic stress disorder).
NIA
NIA is interested in the discovery of novel therapeutics including small molecules and biologics aimed at modifying the behavioral symptoms in Alzheimer's disease (AD), delaying the onset or slowing the progression of AD, mild cognitive impairment (MCI), other dementias of aging and age-related cognitive decline. NIA is not interested in projects aimed at repurposing therapeutics or developing combination therapies.
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.
Resubmission
Revision
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.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Direct costs are limited to $275,000 over a two-year period, with no more than $200,000 in direct costs allowed in any single year.
The maximum project period is 2 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)
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.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
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.All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: Applications should clearly describe how the proposed plan for discovery and testing of novel therapeutics addresses unmet needs relevant to the target disease. Applications should address the competitive landscape for the proposed targets, discussing other efforts in academia and industry relevant to the target, and highlight the innovation or improvements offered by their proposed approach. Innovation in the therapeutic targets, mechanism, and/or measures to assess target biology should be addressed.
Applications should detail the current status of lead compounds or biotechnology products or biologics (e.g., potency, efficacy, pharmacokinetic parameters, etc.) and key lead optimization goals for a development program as well as go-no-go criteria for each assay/test proposed in the testing funnel for advancing compounds across stages.
There is increasing awareness among neuroscience disease communities that to assess the predictive value of preclinical research, sufficient information must be available about study design, execution, analysis, and interpretation. Applicants are urged to consider key elements of a well-designed study (e.g., justification for the sample size, randomization, blinding, selection of appropriate statistical methods, etc.) when describing supporting data and designing the proposed studies. Sufficient information should be provided in the application to assess whether definitive go/no-go studies are appropriately powered and whether proposed statistical analyses are robust.
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.
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Not Applicable
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.
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
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 field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.
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.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
For this particular announcement, note the following:
The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
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?
To what degree does the proposed plan for discovery and testing of novel therapeutic candidates, research tools, and/or preclinical models support an unmet need for the targeted disease?
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?
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?
Are the therapeutic targets, mechanisms, or measures to assess target biology considered to be novel? Has the competitive landscape for the proposed targets been addressed? Does the application make a convincing case for the need for therapeutic candidates for the proposed target?
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?
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?
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
Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.
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
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.
Renewals
Not Applicable.
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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
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.
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 Center for Scientific Review in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- 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.
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.
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.
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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please 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 further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
- Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please 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. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. 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.
- Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please 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
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
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]
Enrique Michelotti, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-443-5415
Email: [email protected]
Qiying Liu
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: 301-443-2678
E-mail: [email protected]
Subramaniam Ananthan
National Institute On Drug Abuse (NIDA)
Phone: 301-435-2199
E-mail: [email protected]
National Institute on Aging (NIA)
Telephone: 301-594-7576
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: [email protected]
Judy Fox
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: [email protected]
Pamela G Fleming
National Institute On Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: [email protected]
National Institute on Aging (NIA)
Phone: 301-402-7974
Email: [email protected]v
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 Human Services (HHS)
