Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed)

Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Encourages innovative drug discovery research for nervous system disorders, excluding clinical trials.

Expired PAR-22-032: Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute on Drug Abuse ( NIDA ) Funding Opportunity Title Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed) R21 Exploratory/Developmental Research Grant Notices of Special Interest associated with this funding opportunity 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 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 242, 93. 866, 93.

273, 93. 279 Funding Opportunity Purpose 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 c andidate 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).

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) 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. Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

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

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of Announcement Section I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Part 2.

Full Text of Announcement Section I. Funding Opportunity Description 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 shou ld 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 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.

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 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.

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

Application Types Allowed 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? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. 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. Section III.

Eligibility Information 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations 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 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2. 3. 7.

4 Submission of Resubmission Application . This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ) Section IV. Application and Submission Information 1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.

gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants. gov Workspace are available in Part 1 of this FOA.

See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission 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.

SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

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

PHS Human Subjects and Clinical Trials Information Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 1.

Section III. 1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4.

Submission Dates and Times Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission. Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement .

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII .

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