Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed)

Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health. Supports research on cellular and molecular mechanisms underlying complex brain disorders with relevance to health biology.

PAR-25-038: Cellular and Molecular Biology of Complex 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 Cellular and Molecular Biology of Complex 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 Exploratory/Developmental Grants See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) encourages research on the biology of high-confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular, and circuit substrates of neural function.

For the purposes of this NOFO, the term “complex” can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder. Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ or in vitro experimental paradigms, e.g., model organisms or human cell-based assays.

While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular, and circuit mechanisms, these are neither required nor expected.

Studies should not attempt to “model” disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). This can include the fundamental biology of these factors, components, and processes.

The resulting paradigms, component pathways, and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources (e.g., those contributing to the Gene Ontology, Synaptic Gene Ontology, FAIR Data Informatics) in order to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification.

The present NOFO (R01 activity code) can be used for applications to further develop lines of inquiry where feasibility or proof-of-concept has been established. Applicants proposing exploratory research at the early and conceptual stages of project development should apply to the companion R21 NOFO PAR-25-037. 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 Disorders of complex brain function such as schizophrenia, bipolar disorder, major depression, anxiety disorders, tic disorders, and autism exact a very high toll in care and lost productivity in the United States.

However, progress in understanding the causes and developing effective treatments has been slow, in part because these brain disorders currently do not have well-defined biological signatures of pathology that could be utilized in experimental neuroscience paradigms or targeted for intervention.

Recently, there has been substantial progress in identifying statistically significant common and rare disease-associated genetic variants that confer risk for mental illnesses. In parallel, there are now a wide array of novel technologies available to probe brain biology at high resolution and sensitivity and across different molecular, cellular, and circuit scales.

This progress provides leverage for neuroscientists to identify cellular, molecular, and circuit processes that may be differentially affected in these disorders.

Although the questions posed may not be mature from the perspective of hypothesis testing for disease relevance, nurturing the initial stages of discovery and hypothesis generation is critical for advancing our understanding of the factors that contribute to disorders of complex brain functions.

To gain a broader understanding of complex brain disorders, it is important to understand the biology of the multiple factors associated with disease risk and the context in which they act at a molecular, cellular, and circuit level.

For example, filling knowledge gaps in gene ontology (i.e., molecular functions, cell type selectivity and biological processes and relationships) will benefit the study of genetic contributions to disease by increasing the accuracy and reliability of gene and protein network analyses for tissue and cell-specific processes.

Such studies will ultimately facilitate the identification of biological processes/pathways affected by disease risk and targets of therapeutic intervention.

Relevant measures at these biological scales can include intracellular signaling mediated by second messengers, neuromodulators, neurotrophins, and ion channels downstream of receptors; protein synthesis, modification, trafficking, and degradation; membrane and organelle dynamics; bioenergetics; metabolic mechanisms; alterations in cell architecture, polarity and/or synaptic connectivity; synaptic transmission and regulation of the co-release of multiple transmitters from individual neurons, mechanisms of bidirectional signaling between neurons, glia and epithelial cells; homeostatic scaling; gut-brain interactions; changes that target sensitive periods of developmental plasticity or perturbations in circuit dynamics such as excitatory/inhibitory balance and oscillatory activity.

This NOFO encourages research on the biology of high confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular and circuit substrates of neural function. For the purposes of this NOFO, the term “complex” can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder.

Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ or in vitro experimental paradigms, e.g., model organisms or human cell-based assays. While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular and circuit mechanisms, these are neither required nor expected.

Studies should not attempt to “model” disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). This can include the fundamental biology of these factors, components and processes.

The resulting paradigms, component pathways, and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources (e.g., those contributing to the Gene Ontology, Synaptic Gene Ontology, FAIR Data Informatics) in order to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification.

See Section IV, Application and Submission Information, Resource Sharing Plan.

Applicants are strongly encouraged to take advantage of novel technologies (e.g., from the BRAIN Initiative) and other resources (e.g., genetically modified organism repositories, human cell lines from the NIMH Repository and Genomics Resource) that will facilitate the consideration of genetic background/strain differences, sex as a biological variable, sample size and other aspects of experimental/statistical rigor.

Examples of relevant research include, but are not limited to: Analysis of gene(s) where variants have been associated with disease risk at genome-wide significance, but where the basic biology of those genes is poorly understood (e.g., where functional analysis would enrich gene ontology).

Applicants are encouraged to incorporate state-of-the-art methods for testing the functional effects of genes and gene variants (e.g., CRISPR/Cas9-mediated editing or newly emerging temporal / spatial control technologies). Investigations of mechanisms by which high confidence environmental risk factors influence molecular, cellular or circuit-level processes, alone or by interaction with genetic risk factors.

Incorporation of the developmental trajectory of biological processes into experimental designs, including designs that identify developmentally critical / sensitive periods to environmental influence.

Optimization and implementation of novel cell-based experimental systems such as induced pluripotent stem (iPS) cells, including those that are derived from human patients or engineered to carry disease-associated genetic variants, in order to characterize disease-relevant mechanisms.

Applicants are encouraged to request access to the NIMH Repository and Genomics Resource List of Studies or iPS cell collection to determine if source cells for reprogramming or existing iPS cell lines are already available. Applicants proposing to derive new iPS cell lines should refer to instructions in Section IV. Application and Submission Information, Resource Sharing Plan.

Development/optimization of new biological tools or scalable technologies for reporting or manipulating the activity levels and neurobiological functions of brain signaling / effector molecules relevant to complex brain disorders.

Inclusion of computational approaches to analyze large unbiased datasets and identify specific, common or convergent pathways (molecular, cellular, synaptic, circuit) affected by variation associated with disease risk factors; identification of causal linkages across these biological scales; identification of potential therapeutic targets from such analysis.

Evaluation of how data obtained from the chosen paradigm compares by secondary analysis with existing human anatomical, histological or systems-level data, or data from other physiologically relevant paradigms.

Investigators are encouraged to explore data, tools and resources being developed under the NIH BRAIN Initiative and its Cell Census Network , BrainSpan , PsychENCODE Human Brain Development Atlas, Human Connectome Project , or related efforts which, if utilized could further enrich study design and interpretation.

The following research topics are not responsive to this NOFO and will be withdrawn prior to review: Development or use of a ‘model of’ a disease (e.g., based on purported face validity and interpretation of behaviors as symptoms); Research premised on ‘candidate’ risk genes that are not identified by well-powered, statistically significant genome-wide association; Research premised on ‘candidate’ environmental risk factors that are not based on well-powered, statistically significant epidemiological data; A primary focus on phenotyping human subjects or clinical populations, which is more appropriate for other NOFOs (except for those with a strong focus on cell or tissue-based assays, including generation and/or characterization of iPS cells, which is appropriate for this NOFO); A primary or sole focus on behavioral paradigms/measures, pharmacology or drug discovery, and/or immunological challenge paradigms, which are more appropriate for other NOFOs.

Funding Strategy for Research Grants A Hypothesis-Based Approach: The Use of Animals in Mental Health Research NOT-MH-19-053: Notice of NIMHs Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Pre-clinical Studies (nih. gov) NOT-MH-22-010: NIMH Priorities on Research Using Genetically Modified Nonhuman Primates. (nih.

gov) Guidance for Applicants Following the Report of the National Advisory Mental Health Council Workgroup on Genomics The present NOFO (R01 activity code) can be used for applications to further develop lines of inquiry where feasibility or proof-of-concept has been established.

Applicants proposing exploratory research at the early and conceptual stages of project development may instead wish to apply to the companion R21 NOFO ( PAR-25-037 ). 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. Applications that propose the collection and/or processing of human biospecimens, including the derivation of induced pluripotent stem cell (iPSC) lines, should include budgets that comport with NOT-MH-21-265 .

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: The primary focus of applications responding to this announcement is on the biology of high confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular and circuit substrates of neural function.

For the purposes of this NOFO, the term “complex” can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder. Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ or in vitro experimental paradigms, e.g., model organisms or human cell-based assays.

While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular and circuit mechanisms, these are neither required nor expected.

Studies should not attempt to “model” disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). This can include the fundamental biology of these factors, components and processes.

The Research Strategy should: Define the current state of the science as a benchmark against which the new study will be developed and executed; Provide a clear rationalization for studying any risk factors, with a focus only on those supported by rigorous, unbiased, sufficiently powered studies (e.g., genome-wide association or environmental risk epidemiology); Develop or exploit novel tools, technologies, resources and reference datasets (e.g., those developed by the BRAIN Initiative, found in the NIMH Repository and Genomics Resource or in clinical or genomic data archives) to improve the sophistication, robustness, or reproducibility of the design.

As an alternative, describe any proposed unique conceptualization of analytic approaches being applied to the study; Address the contribution of genetic background (e.g., human donor diversity, mouse strain differences) where appropriate to the questions being asked, in order to account for modifiers of the risk factor(s); If proposing a discovery-based, hypothesis-generating approach, focus on designs that will generate unambiguous, highly interpretable data used to generate new hypotheses and broadly advance the field at large; Define key aspects of experimental rigor (as appropriate) and how they will be addressed in the study, including but not limited to: Issues of statistical, computational and/or experimental robustness and reproducibility; Primary and secondary statistical and/or experimental outcomes to be assessed (e.g., gene fold change, variance explained) and clearly state how these relate to proposed objectives; Number of experimental and control groups; The 'experimental unit' in the analysis and the implications thereof (e.g., there is a difference between N samples from one cell line, as distinct from one sample from each of N cell lines, or combining samples from multiple lines); The number of 'experimental units' in each experimental group; The total number of 'experimental units' to be measured; The number of times each 'experimental unit' will be measured; The number of independent replications of each experiment; Steps taken to minimize the effects of bias (e.g., batch effects, blinding, randomization) or an explanation of why this would not be appropriate; Calculated effect sizes and justification regarding how they are biologically relevant ; Demonstration that statistical power calculations are grounded in justifiable and explicit assumptions about both anticipated effect size and variability of the experimental effects; If statistical power calculations cannot reasonably be applied, provide an alternative rationale for the choice of numbers (explanations based solely in terms of 'usual practice' or with reference solely to previously published data will not be considered adequate).

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. Applicants are expected to register resources supported by this NOFO in FAIR Data Informatics ( https://scicrunch. org/ ) and use Research Resource Identifiers (RRID) assigned by ( https://scicrunch.

org/resources ) in any publication supported by this NOFO. NOT-MH-21-265 outlines the expectation that investigators who propose to generate human subject-derived reprogrammed cells in their NIMH-funded research will ensure that both the source biospecimen cells and reprogrammed derivatives (e.g., iPS cells) are made available to the research community through the NIMH Repository and Genomics Resource .

Investigators are expected to discuss plans with Program staff early in the planning stage and prior to submitting an application. Depending on the details of the plan, Program staff may recommend that applicants propose and budget in their application for iPSC derivation to be done as a fee-for-service by the core facility associated with the NIMH Repository.

Sharing plans consistent with this policy will be finalized prior to the release of, and specified in, the Notice of Award.

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. The plan should describe how resulting paradigms, component pathways and biological processes will be disseminated with sufficient detail to enrich common and/or federated data resources. Examples include those contributing to Gene Ontology ( http://geneontology.

org/docs/contributing-to-go/ ) or Synaptic Gene Ontology ( https://syngoportal. org/submit. html ).

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.

NOT-MH-23-100 outlines the expectation that researchers who are funded by NIMH for human subject recruitment studies will deposit all raw and analyzed data (including, but not limited to, clinical, genomic, imaging, and phenotypic data) from experiments involving human subjects into the NDA. Applicants should review NOT-MH-23-100 for additional information when preparing their sharing plan.

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