Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01) is a grant from the National Institutes of Health (NIH/NIDA) that funds assay development, high-throughput screening, and drug discovery research targeting brain disorders including neurological and psychiatric conditions.

Supported by NIMH and NIDA, the program seeks to identify and validate small molecule chemical hits that may serve as leads for new therapeutics. Eligible applicants include public and private institutions of higher education, nonprofit organizations, and small businesses engaged in drug discovery research. Awards vary based on the scope of the proposed research.

The application deadline is May 7, 2026. Clinical trials are not allowed under this funding opportunity.

PAR-25-063: Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 ) Funding Opportunity Title Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01 Clinical Trial Not Allowed) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The overarching goal of this Notice of Funding Opportunity (NOFO) is to support the development and validation of screening assays for the discovery of validated hits that can be used in future drug discovery/development efforts for identifying potential drug candidates for the treatment of mental illness.

For purposes of this initiative, a “hit” is defined as a compound that has the desired activity in a compound screen and whose activity is confirmed upon retesting in orthogonal assays.

Stages of discovery research covered by this NOFO include 1) assay development; 2) primary screen implementation to identify initial screening hits (high throughput target-focused screens, or moderate throughput screens); and 3) hit validation using a series of assays and initial medicinal chemistry inspection to prioritize the hit set.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of 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. Notice of Funding Opportunity Description Through this Notice of Funding Opportunity, (NOFO), NIMH wishes to stimulate research in the discovery and development of novel screening assays for the discovery of validated hits that can be used in future drug discovery/development efforts for identifying potential drug candidates for the treatment of mental illness.

For purposes of this initiative, a “hit” is defined as a compound that has the desired activity in a compound screen and whose activity is confirmed upon retesting in orthogonal assays.

Stages of discovery research covered by this NOFO include 1) assay development; 2) primary screen implementation to identify initial screening hits (high throughput target-focused screens, or moderate throughput screens); and 3) hit validation using a series of assays and initial medicinal chemistry inspection to prioritize the hit set.

Assessment of the reasons for failures of small molecule therapeutic agents in the clinic points to several areas for improvement of the drug discovery and development process that are pertinent to this NOFO: First, increased rigor in target identification is necessary. For instance, whether prior studies of the selected target were adequately controlled and powered are important considerations.

Were cell lines verified, plasmids sequenced, and protein reagents tested for contaminants? Second, reproducibility of the proposed primary assay should be carefully considered because this assay is often the basis for assessing not only initial hits but also for iteratively assessing optimized hits during structure-activity relationship (SAR) studies.

Development of primary screening assays that test a key biological function of the target of interest are likely to yield hits of increased relevance. In this respect, phenotypic screens have had a resurgence.

Third, a hit validation scheme or “critical path” that includes orthogonal assay(s) to eliminate false positives, as well as a series of assays in diverse biological systems with diverse read-outs, particularly including assays that model human disease, is likely to yield hits of increased relevance.

Fourth, the inclusion of skilled synthetic and/or medicinal chemists to assess the validity of the hit chemotypes to eliminate PAINS (pan-assay interference compounds) or other undesirable chemotypes.

Projects covered by the NOFO should focus on the following stages of the discovery research: 2) Primary screen implementation Areas to be considered for each stage are described below and given in greater detail in Section IV (Application and Submission Information, PHS 398 Research Plan).

This NOFO supports implementation of innovative biological, biophysical or cell-based assays for novel biological targets or processes relevant to mental disorders. Projects for assay development should emphasize the design and validation of creative approaches to assess biological and disease processes that have the potential to be used as starting points for chemical probes or drug development.

Proposed primary screening assays must be relevant to neuroscience research aimed at discovering pathological processes of psychiatric disorders and developing safer and more effective treatments.

The NIMH is interested in applications proposing the development of therapies aimed at novel molecular targets for the treatment of psychiatric disorders, such as treatment-resistant depression, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), panic disorder, and autism spectrum disorders. Primary screening assays may be target-, pathway-, or phenotype-based .

Some examples include: Target-based biochemical or cellular assays that measure receptor-ligand binding, protein-protein interactions, activities of enzymes, ion channels, transporters, nuclear receptors, and other transcription factors, and other novel targets emerging from genetic, epigenomic, transcriptomic, proteomic, and metabolomic research in model systems and in human diseases Cell- or organism-based assays that detect phenotypic changes linked to the biological or disease process of interest Assays may utilize any preparation which enables high throughput screening (HTS) or moderate throughput screening (MTS), including cell-free systems, cultured cells, induced pluripotent stem cells (iPSCs), organoids, organotypic brain slices, or model organisms (e.g., zebrafish, Caenorhabditis elegans (C.

elegans) and Drosophila melanogaster), which adequately recapitulate important aspects of neuronal or glial function.

Phenotypes of interest may include, but are not limited to, dendritic morphology; axonal outgrowth; neuronal activity and plasticity; synaptic maturation or synaptic function; neuronal and/or glial signaling pathways; receptor function, trafficking, and/or localization; protein synthesis, sorting, interactions, and turnover; cell fate specification; or chromatin remodeling.

Assay detection methods may include, but are not limited to: Fluorescence, luminescence, absorbance Fluorescence resonance energy transfer (FRET) Time-resolved fluorescence resonance energy transfer (TR-FRET) Fluorescence polarization Flow cytometric measurements Bioluminescence resonance energy transfer (BRET) AlphaScreen, scintillation proximity assay (SPA) In general, assays should adopt an adequate detection principle that results in the sensitive detection of even weak binders with expected low rates of false positives and false negatives.

Complementary research, for example virtual screening, may also be conducted to improve the likelihood of success and cost-effectiveness. Instructions for the design and testing of a primary assay may be found in Section IV (Application and Submission Information, PHS 398 Research Plan). 2.

Primary Screen Implementation This NOFO seeks to make use of large, publicly available databases of 3D protein structures, genomic, metabolomic, and proteomic data, and virtual small molecule libraries, combined with computational approaches to accelerate the discovery of novel and potential drug candidates based on specific molecular targets.

Projects proposing the use of VS, either ligand-based screening or receptor-based screening, must collaborate with hit assay validation and medicinal chemistry experts for experimental testing of the proposed in silico hits.

VS techniques may involve computational approaches that include, but are not limited to: Machine learning based QSAR (particularly deep learning methods) Innovative protein-ligand docking algorithms (e.g., evolutionary search methods) Similarity search methods Pharmacophore mapping methods Moderate throughput screening (MTS) and high throughput screening (HTS) Applicants are encouraged to collaborate with an experienced MTS or HTS facility.

The screening facility may provide advice such as identification and selection of commercial MTS/HTS assay reagents, and suitable MTH/HTS assay format and readout. In addition, the screening facility may be able to aid in adapting assays to an HTS format (e.g.,1536-well or 384-well microplate) and performing a pilot screen of a small library of compounds.

Further, the applicants are expected to seek advice from the screening laboratory about orthogonal assays to validate the screening hits. Projects focusing on screen implementation are required to provide preliminary data demonstrating that a primary screen has been developed, fully characterized, and tested in a pilot format. See Section IV for further details on expected information prior to the Primary Screen Implementation stage.

Phenotypic and model organisms screening In vivo whole organism assays (e.g., zebrafish, Caenorhabditis elegans (C. elegans) and Drosophila melanogaster) should only be proposed if they adequately recapitulate important aspects of neuronal or glial function and are needed to demonstrate the biological or physiological effects of validated hit compound(s).

Phenotypic screening should only be proposed if a target deconvolution is included in the application or there is a strong association between the mechanisms that drive the phenotypic assay, the preclinical disease model and the human disease. For purposes of this initiative, a “hit” is defined as a compound that has the desired activity in a compound screen and whose activity is confirmed upon retesting in orthogonal assays.

Hits from a primary screen may be systematically assessed using a cascade of follow-up assays to remove false positives efficiently and effectively. Primary HTS assays typically generate hundreds to thousands of hits, many of which are false positives or are chemically intractable. Hits from smaller scale primary screens are also likely to generate false positives or chemically intractable molecules that require additional screens.

Post-primary screening assays may include, but are not limited to: An assay that is essentially identical to the primary assay but with an orthogonal detection scheme (e.g., switching light detection mode or wavelength to avoid intrinsic compound interference); A target-minus assay (e.g., coupling enzymes in the absence of the assay target enzyme, parental cell line without the assay target protein, etc.); An assay that is different in biological context and process (e.g., protein functional assay vs. protein binding assay; RT-PCR or Western blot vs. reporter gene assay; cell-based assay vs. biochemical assay); Target selectivity assay(s); Specificity assays to distinguish biological activities of chemical entities among orthologous targets across organism species through kingdoms (e.g., yeast vs. mammalian cell targets; parasite vs. host targets); Mode of action assays (e.g., allosteric vs. orthosteric; competitive vs. noncompetitive or uncompetitive); or Target identification assays.

Downstream assays may also include cellular and/or tissue models pertaining to the relevant physiology or pathophysiology, or to the mode and mechanism of action of the validated hits. In vivo whole organism assays (e.g., zebrafish, Caenorhabditis elegans (C. elegans) and Drosophila melanogaster) should only be proposed if they are needed to demonstrate the biological or physiological effects of validated hit compound(s).

In addition, applicants are expected to conduct advanced cheminformatics analysis and medicinal chemistry inspection to prioritize the hit set. It is expected that the applicants will test powder samples of hit compounds and commercially available analog compounds during the hit validation stage.

Applicants must verify the chemical structures of hit compounds using a combination of analytical methods and, if possible, re-synthesis of select hits.

The NIMH encourages applications proposing novel, clinically relevant targets with the goal of transforming target discovery into the therapeutic treatment of psychiatric disorders such as depression, bipolar disorder, schizophrenia, anxiety, panic disorder, autism spectrum disorders, etc. (see From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses ).

Proposed projects should be relevant to NIMH's mission of supporting basic science discoveries and translating these discoveries into new therapeutic interventions that will relieve the suffering of people with psychiatric disorders. Projects aimed at the discovery of in vivo chemical probes should consider applying to PAR-21-029 . Projects aimed at the discovery of cell-based chemical probes should consider applying to PAR-21-028 .

Projects aimed at early stages of drug discovery and development should consider the Drug Discovery for Nervous System Disorders PAR-22-031 (R01) and PAR-22-032 (R21) or the National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction PAR-22-144 (U19) and PAR-22-143 (U01) Small businesses should consider applications through the Small Business Innovation Research Program .

Applications Nonresponsive to This NOFO The following studies will be considered non-responsive for this announcement and will not be reviewed: Assays focusing on targets or/and approaches that have been extensively studied Implementation of structure-activity relationship (SAR) assays In vitro Absorption, Distribution, Metabolism, and Excretion (ADME) assays Proposing in silico hits without experimental validation In vivo rodent activity assays Lack of verification of the chemical structures of hit compounds using a combination of analytical methods See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A financial assistance 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 How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. 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. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum project period is 5 years NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 their organization to develop an application for 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 How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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 How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Address the following topics as they pertain to the research project proposed: Factor 1.

Importance of the Research Significance : Address whether the hit(s) will provide new insight into important disease targets and processes. Any existing modulators for the target should be mentioned, and a rationale for additional discovery and/or development of small molecules that address the target should be delineated.

Innovation : Innovative aspects of studying the proposed target or pathway and of the proposed assay(s) and screening scheme should be highlighted. Factor 2. Rigor and Feasibility Approach : Define the scope of the proposed research project via the three drug discovery research stages outlined in Section I.

Include a flow diagram outlining all critical steps in sequential and/or parallel manners with appropriate benchmarks and timelines for the stage(s) of discovery research proposed.

The application should include the following topics in the research plan: 1) Assay Development : An explanation of the scale of the proposed assay campaign (i.e., low-, moderate- or high-throughput), reproducibility of the primary screening assay, and reproducibility and robustness of the primary screening assay in a low-to-moderate throughput setting.

2) Primary Screen Implementation : A discussion of the following parameters: anticipated number of hits; feasibility of assessing hits (particularly in large numbers); test concentrations; cut-off concentration; reagent availability; equipment used in configuring the assay; a strategy to characterize initial active compounds, and a rationale for the size and selection of the library of compounds to be screened regardless of the scale of the screen.

3) Hit Validation: a rationale for the chosen hit validation scheme, considering the number of hits from the primary screen, anticipated false positives inherent in the primary assay format, and/or necessary assays to test the biology or physiology of the target, availability and suitability of secondary and counter-screen assays as appropriate for the scale of the screening campaign or plans to develop and characterize them, a definition of the specific criteria that a compound must meet to be considered a validated hit, a plan to conduct advanced cheminformatic analysis and medicinal chemistry inspection to prioritize the hit set, confirmation of hit compound structures by testing powder samples and commercially available analog compounds and resynthesis of selected hits.

Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this Notice of Funding Opportunity (NOFO) are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100 ).

Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission.

The NDA website provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page .

Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission.

Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied.

For more guidance on submitting data to NDA, refer to the NDA Data Sharing Plan on the NDA website . NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary . Appendix: Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the How to Apply- Application Guide. No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 2.

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. 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 Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications . 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 How to Apply-Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. 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