Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) is sponsored by NIH (National Institutes of Health), National Institute on Drug Abuse (NIDA). This funding opportunity supports research on the discovery and development of interventions to prevent and/or treat substance use disorders (SUDs) and overdose, including medications and medical devices to treat co-morbid SUDs.

PAR-25-446: Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Drug Abuse ( NIDA ) Funding Opportunity Title Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement November 24, 2025 - Notice to Expire PAR-25-023, "Device Based Treatments for Substance Use Disorders (UG3/UH3 Clinical Trial Optional)".

See Notice NOT-DA-25-042 . 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 purpose of this notice of funding opportunity (NOFO) is to seek grant applications to support research on the discovery and development of interventions to prevent and/or treat substance use disorders (SUDs) and overdose, including interventions to treat co-morbid SUDs.

This includes preclinical and clinical research studies that will have high impact and quickly yield the necessary results to advance candidate interventions closer to regulatory approval or clinical adoption. This NOFO will utilize the UG3/UH3 activity code. Funding Opportunity Goal(s) To support basic, clinical, translational, and implementation research in the field of substance use.

To develop new knowledge and approaches for the prevention, diagnosis, and treatment of drug use, misuse, and addiction, drug overdose, and related health outcomes, including HIV/AIDS. Open Date (Earliest Submission Date) 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 Over 40 million people in the United States have a substance use disorder (SUD).

Drug overdose is the leading cause of accidental death, with an estimated 105,000 deaths in 2023. Deaths involving synthetic opioids other than methadone (primarily fentanyl), amphetamine-type psychostimulants (primarily methamphetamine), and cocaine were estimated to be 71%, 33%, and 27%, respectively.

Furthermore, 48% of the 2022 overdose deaths were attributed to a synthetic opioid and another non-opioid substance (i.e., polysubstance overdose). Thus, there is an urgent need to develop safe and effective interventions to prevent and treat SUDs and overdose. These needed interventions include medications, digital therapeutics (DTx), device-based treatments, and behavioral interventions.

The National Institute on Drug Abuse (NIDA) seeks preclinical and clinical research studies that will have high impact and quickly yield the necessary results to advance candidate interventions to prevent or treat SUDs and overdose closer to the Food and Drug Administration (FDA) approval/authorization/clearance and/or implementation into clinical practice and community care.

There is particular interest in the development of therapeutic interventions for: Prevention of initiation of SUDs Prevention of progression of the severity of SUDs Reduction of the dose of opioids analgesics Improvement of SUD treatment adherence Facilitation of substance use discontinuation Treatment of drug withdrawal signs and symptoms Treatment of neonatal drug withdrawal Treatment of co-morbid SUDs Reduction of lethality of overdose Reduction of overdose relapse Reduction of the risk of substance-induced respiratory depression Any other behavioral and medical manifestations or consequences of SUDs or overdose Single or multiple comorbid SUDs Populations at high risk for SUDs Because the development of SUD interventions is likely to be high risk, UG3/UH3 grant applications must provide clear milestones to be accomplished at the end of the UG3 phase.

Objective milestones of success and go/no-go rules for medications development progression are required, and both must have quantitative criteria associated with them. Advances in the understanding of SUDs and overdose provide new opportunities to improve the treatment and prevention of these disorders and may ultimately contribute to reducing the current SUD and overdose crises.

Some of these advances include the new findings of receptors, neurotransmitters, neuromodulators, and brain circuits associated with these disorders. These advances have led to a greater understanding of endogenous systems and well as risk/protective factors for the onset and progression of SUDs. Application of these findings has led to new targets, formulations, and delivery systems to be evaluated.

Therefore, multiple therapeutic approaches may be poised for the next step in the FDA approval process and concerted efforts are needed to advance these potential pharmacotherapies to approval. Applications may focus on studying new chemical entities (NCEs), medications already marketed for other indications, biologics, natural products, or combinations of medications.

Topics that are considered to be within the scope of this NOFO include, but are not limited to: Evaluation of NCEs at a preclinical or late preclinical IND-enabling stage; Early clinical evaluation of drug candidate at early clinical development stages: first-in-human, single ascending dose/multiple ascending dose, pharmacokinetics/pharmacodynamics, drug-drug interaction studies, translational clinical studies in patient populations, testing the target for safety and early evidence of efficacy to de-risk further clinical development; Repurposing of marketed medications that are used for a non-SUD indication can include: preclinical and clinical safety evaluation (drug-drug interaction studies with the target SUD drug of use/misuse); clinical translational studies in early phase of clinical development, and/or proof-of-concept study assessing the pharmacologically best dose/dosing strategy, efficacy, and safety endpoints for the drug in preparation for phase III; Phase II and Phase III clinical stage drug candidates can include clinical development plans with the preparations for an end of phase II meeting with the FDA and phase III development program studies layout, where, if needed, the FDA feedback could be incorporated.

With the approval of neuromodulatory devices for treatment of depression, obsessive-compulsive disorder and tobacco smoking cessation, interest has rapidly grown around applying these and related technologies to all SUDs. These technologies include, but are not limited to, transcranial magnetic stimulation (TMS), transcranial direct current stimulation, vagal stimulation, deep-brain stimulation, focused ultrasound, and others.

Also of interest are technologies that may not directly modify neuronal function but report on or alter neurophysiology that affect outcomes. This NOFO strongly encourages the testing of device-based interventions for SUDs. The main goal is to advance the development of neuromodulatory devices in the FDA approval pathway.

Studies are strongly encouraged, when appropriate, to include evaluation of circuit-directed target engagement, using on-line (e.g., TMS/fMRI interleaving, EEG, PET) or off-line (e.g., PET, fMRI/rsfcMRI, MRS) approaches, depending on the nature of the spatial anatomical and/or neural oscillatory targets. Careful attention should be paid to the time-course of action.

For rapidly acting interventions, where changes in circuit-based targets occur acutely during administration, it may be most appropriate to use pharmacodynamic outcome measures (e.g. neurocognitive task performance, craving). Sham/placebo stimulus comparators should be included when appropriate.

If a sham is used, demonstration must be provided not only of adequate masking procedures but also lack of biological action that would exert central nervous system effects. For studies requiring an Investigational Device Exemption (IDE), applicants are expected to provide confirmation of an existing IDE, or describe the status of any such pending regulatory submissions.

If an IDE application is not submitted by the time of the grant application submission, the applicant is expected to describe the plan and timeline for submitting the request and obtaining the IDE prior to the initiation of a grant award. If the device is exempt from the IDE, the grant application is expected to include the justification and documentation for why the device would be exempt.

Digital Therapeutics (DTx) DTx are mobile, web, or other software-based platforms designed to make diagnostic or therapeutic claims (i.e., prevent, manage, or treat medical conditions or diseases). These therapeutic interventions do not include wellness apps or telehealth which provides remote access to a clinician.

Instead, DTx can deliver new behavioral interventions or those that have previously only been available for delivery through direct, face-to-face interactions with a clinician. DTx can provide therapeutic opportunities beyond those that are available under current standard of SUD care. For example, the delivery of a behavioral intervention by DTx ensures it is provided in a highly reproducible manner.

Access is not affected by transportation challenges to a clinician, or by when a patient might have the time available to visit a clinician. Privacy can be ensured by providing discreet and confidential care, avoiding the challenges of stigma around the potential for public exposure of receiving treatment. DTx can be highly scalable, increasing access at low cost.

Over the last several years, the FDA has provided a pathway for authorization of DTx and there already has been approval of DTx for SUD. However, more work is needed to expand on the types of treatments delivered, the technologies used for delivery, that target special populations or specific SUDs, or other aspects that can increase the efficacy and reach of treatment using DTx.

Investigators are strongly encouraged to reach out to the appropriate FDA Center for Devices and Radiological Health (CDRH) office via the Pre-Submission process to discuss the proposed development pathway and clinical validation data requirements. Guidance on this process can be found here: Q Submission Process .

Questions for discussion in a Pre-Submission could include: whether a DTx would meet the definition of a medical device and require FDA oversight; the most appropriate regulatory pathway for a DTx if it does meet the definition of a medical device; whether a clinical trial investigating the safety and effectiveness of an investigational DTx would represent a significant risk study and require prior IDE approval.

Additional discussions can include clinical study design considerations (including feedback on the proposed patient population, study endpoints and assessments, statistical analysis plan, study comparator, and others) to support the safety and effectiveness of the DTx for a particular use indication. Sham comparators or validated active comparators should be included when appropriate.

If applicable, investigators should design studies to evaluate potential sex differences. Methods to evaluate subjects' compliance with the study treatments should be included when possible. Monitoring adherence to the treatment would be especially appropriate for DTx that are integrated with FDA-approved SUD interventions.

Behavioral treatments play a critical role in most evidence-based SUD interventions and often constitute the entire treatment. This UG3/UH3 is intended to support behavioral and integrative intervention research with the goal to advance science, including treatments that are intended to be more efficient, better tailored to individuals, or more readily transported to the community.

The objective of this announcement is to ensure sufficient emphasis and support for Stages I through III of behavioral and integrative treatment research. Studies will support translation of scientific knowledge into more efficient behavioral, combined behavioral and pharmacological, combined behavioral and neuromodulatory, integrative, and complementary treatments so that they ultimately can be effectively scaled.

The NIH Stage Model describes behavioral intervention development in six stages: basic science (Stage 0); intervention generation, refinement, modification, and adaptation and pilot testing (Stage I); traditional efficacy testing (Stage II); efficacy testing with real-world providers (Stage III); effectiveness research (Stage IV); dissemination and implementation research (Stage V).

Under this NOFO, only stages I, II and III are supported. Intervention development within each stage should be viewed as iterative, recursive, and bidirectional.

Stage I: Stage I research is iterative and may involve: 1) identifying promising basic or clinical scientific findings relevant to the development or refinement of an intervention; 2) generating/ formulating theories relevant to intervention development and putative change mechanisms; 3) operationally defining, and standardizing new or modified principle-driven interventions; 4) initial or pilot testing of the intervention; 5) experimentally testing the mechanisms and principles of behavior change of the intervention; and 6) as necessary, further refining the intervention.

The Stage Model presumes that intervention development is incomplete if no materials and methods are available to ensure faithful administration of an intervention. Therefore, therapist/provider training and fidelity assessment and enhancement methods are an integral part of behavioral intervention development.

Stage II: Stage II research consists of testing promising behavioral interventions in research settings, with research therapists/providers while maintaining a high level of control necessary to establish internal validity. This treatment stage also involves examining mechanisms of behavior change. Stage II does not specify a particular research design.

Testing of interventions may be done in randomized clinical trials, but may also be conducted using other methodologies as appropriate (e.g., adaptive designs, multiple baseline single-case designs, A-B-A designs, etc.). Stage II studies may include exploration of intervention components, dose-response, and theory-derived moderators. Information obtained from Stage II studies may be used to inform future Stage I studies.

For example, if it is shown that an intervention works for some people, but not for others, especially if such a moderator effect makes conceptual sense, a Stage II study may lay the groundwork for a Stage I application aimed at developing an intervention (or modifying the intervention) for people who were unresponsive to the initial intervention.

Stage III: Stage III research determines efficacy in community settings and with community therapists/providers. Although Stage III occurs in real-world settings, investigators should maintain a high level of control to establish internal validity.

Proceeding directly from Stage I to Stage III requires Stage I research to be promising and requires the existence of methods to ensure fidelity of delivery of an intervention, along with therapist training materials (as required by the intervention).

Applications Not Responsive to this NOFO The following types of studies are not responsive to this NOFO and will not be reviewed: Applications focusing solely on novel target identification/validation, generation of new animal models, development/testing of new human laboratory models Applications focusing on mechanistic studies of the neurobiology of addiction Applications that address alcohol as the only substance of use Applications related to behavioral interventions in stages IV, V, or VI Applications focusing on effectiveness research Applicants should consult with NIDA staff when developing plans for an application (see Agency Contacts, Section VII).

This early contact will provide an opportunity to clarify NIDA policies and guidelines, identify whether the proposed project is consistent with NIDA program priorities, and discuss how to develop an appropriate project timeline, which is subject to peer review. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations. Section II.

Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this NOFO. 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.

Optional: Accepting applications that either propose or do not propose clinical trial(s). 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 limited to $3 million per year for direct costs. The maximum period of support is 5 years. The maximum period of support for the UG3 Phase is 2 years, and the maximum period of support for the UH3 Phase is 3 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 - Includes all types 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) Foreign Organizations/ International Collaborations NIH will no longer issue awards (new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts.

All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025. Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding.

This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components , funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors. 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.

Target Product Profile (Optional): Applicants may include a target product profile for therapeutic candidates. This may not exceed one page in length. Interactions with FDA (Optional): Applications may include a summary of interactions with FDA, which may not to exceed two pages in length.

Applications exceeding the above page limitations or including other information in these attachments, will be withdrawn without review. 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: Without duplicating the information provided in Section 2.

7 Study Timeline from PHS Human Subjects and Clinical Trials Information Form of the How to Apply - Application Guide , include a study timeline that relates to the anticipated completion of Aims and/or milestones. Applications must provide a decision tree for the compound testing, with appropriate go/no-go decision points.

They must also provide the entry and exit points of the proposed compound in the FDA's medications development continuum, if applicable. All clinical trial applications must include methods to evaluate subjects' compliance with the study medications. If applicable, investigators must include male and female samples and data analysis to evaluate potential sex differences.

When samples or analysis are not proposed, scientific justification must be provided. For studies requiring an IDE, applicants are expected to provide confirmation of an existing IDE, or describe the status of any such pending regulatory submissions.

If an IDE application is not submitted by the time of the grant application submission, the applicant is expected to describe the plan and timeline for submitting the request and obtaining the IDE prior to the initiation of a grant award. If the device is exempt from the IDE, the grant application is expected to include the justification and documentation for why the device would be exempt.

Milestones and UG3/UH3 Transition : Applicants must plan and submit the application for both a UG3 and a UH3 phases. The section describing the research to be conducted under the UG3 must include a description of an entry point and the milestone(s) that will be reached at the end of this phase. To successfully transition to the UH3 phase, the project must reach the milestones outlined in the application.

The application must provide quantifiable metrics to determine success of the UG3. Additional milestone(s) may be negotiated before or after funding decisions have been made. 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. 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