Part 1. Overview Information

Key Dates

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.

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 How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. 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.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The NIH Helping to End Addiction Long-term (HEAL) Initiative: This notice of funding opportunity (NOFO) encourages applications in support of the NIH's HEAL initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for overdose, opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.

IMPOWR Background

Recent estimates suggest that roughly 60% of people with opioid use disorder (OUD) also have chronic pain (CP), which is associated with substantial illness and death nationwide. Evidence-based treatments exist for both conditions, including behavioral therapies, nonpharmacological treatments, neuromodulation modalities, and medications. Service delivery approaches such as the Collaborative Care Model have also demonstrated effectiveness, particularly for individuals with co-occurring mental illness. Despite the high rate of co-occurrence, evidence remains limited on integrated service delivery packages and multi-component interventions that coordinate these evidence-based elements. Care is often fragmented across providers, health systems, and policy frameworks, creating barriers to access and continuity and leaving only a small fraction of the target population with high-quality care.

The Integrative Management of chronic Pain and OUD for Whole Recovery (IMPOWR) program (FY21) funded 10 clinical trials to evaluate psychosocial interventions, optimize Medications for Opioid Use Disorder (MOUD) dosing strategies, and test innovative care delivery models, informed by collaboration with people living with OUD/CP and practitioners. The IMPOWR network also developed a harmonized dataset capturing key measures across substance use, pain, quality of life, and co-occurring mental health conditions to characterize factors affecting treatment engagement and retention. Since IMPOWR Phase I, regulatory changes have expanded reimbursement pathways, workforce capacity, and service delivery options nationwide. Additionally, observational data suggests GLP-1 agonists and neuromodulation modalities may hold promise for CP and OUD, underscoring the need for data-driven insights to optimize care in this evolving landscape.

Purpose and Scope of Clinical Studies for IMPOWR Phase II 

Implementation determinants across clinical, health system, and contextual domains play a critical role in shaping how quickly evidence-based interventions are integrated into routine care. HEAL IMPOWR Phase II will fund studies that combine clinical intervention research with implementation science. These studies must use hybrid implementation-effectiveness designs that look at both patient outcomes and health system outcomes. The goal is to improve the reach, scalability, and long-term sustainability of integrated, evidence-based treatments for CP and OUD.

IMPOWR Phase II will support a single clinical trial per application that:

• Tests implementation strategies for established treatments for chronic pain when a person also has OUD. Hybrid Type II, III designs or implementation clinical trials are recommended here.
• Provide effectiveness data for new or emerging treatments that were not tested in IMPOWR Phase I and could meaningfully change clinical practice. Hybrid Type 1 or II designs are recommended here.

Areas of special interest include, but are not limited to:

• Implementation strategies, including digital tools, supervised learning, or academic detailing to facilitate collaborative care between pain and addiction specialists. Strategies to restructure workflow to facilitate service integration may be also appropriate.
• Best practices and implementation strategies to expand buprenorphine low dose initiation among providers, patients, and pharmacists for this population.
• Implementation strategies to expand CP and OUD evidenced based practices (EBPs) in relevant health settings among clinical workforce who provide services for this population (e.g., physicians, nurse practitioners, social workers, community health workers, peer navigators).
• Research to test off-label use of FDA approved medications/devices for other indications with foundational efficacy in treating CP or OUD (e.g., GLP1 medications, neuromodulation therapies). These may be tested alone or in combination with other OUD and CP treatments.
• Research to develop and advance adaptive care strategies (e.g., Sequential, Multiple Assignment Randomized Trial or Multiphase Optimization Strategy).

Partner Engagement

Evidence-to-Action Partner (EAP): Individuals at the state and local levels routinely make critical choices affecting access to and the availability, cost, quality, and effectiveness of addiction and pain treatment services. These could be enhanced if they were informed by timely, robust, and actionable health services research findings. Applicants are required to apply user-centered design principles to refine their research process to outline how the EAPs will utilize the data generated by the research study to improve health outcomes for this population.

OUD and Pain Partner (OPP): All projects must include an OUD and Pain Partner (OPP) Engagement Plan that incorporates perspectives from individuals living with CP/OUD to ensure that the study addresses real patient needs and priorities. Applicants will engage with these partners throughout the entire research process, from design through dissemination.

Network Structure and Participation

IMPOWR Phase II will include 6–8 clinical studies to speed adoption of evidence-based treatments in routine care. A single Building Engagement, Assistance, Capacity, and Networks (BEACON) Coordination Center will provide network coordination and administrative support. Applicants are encouraged to review the companion BEACON NOFO (RFA-DA-28-012).

Investigators are expected to:

• Join monthly Steering Committee or workgroup calls
• Attend one annual in-person network meeting (plan for 3–5 staff per Hub). BEACON hosts the first meeting; hosting rotates each year among awardee institutions.
• Work together to choose common measures based on IMPOWR Phase I Common Data Elements (CDEs) and set data sharing policies and processes
• Share de-identified summary statistics and enrollment metrics with BEACON quarterly. BEACON will combine these data to support collaboration and network meta-analyses.

Pre-Application Consultation:

Potential applicants are strongly encouraged to consult with NIDA Program staff early in the application development process. This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope of the project relative to the intent of this NOFO. See Scientific/Program Contacts in Section VII.

Data Harmonization for Substance Use and Addiction via the PhenX Toolkit

 NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit. Please see NOT-DA-12-008 for further details.

For further information on special considerations for NIDA applicants, please see the Resources section on the NIDA Grants and Funding page.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Applications Not Responsive to this NOFO

The following types of applications are not responsive to this NOFO and will not be reviewed:

• Studies that do not include services integrating OUD and CP treatment. CP is defined as pain for at least 90 days. OUD and pain outcomes must be included.
• Research designs that do not include a Hybrid Effectiveness-Implementation Type I, II, III approach or implementation clinical trial design.

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

Section II. Award Information

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

1. Eligible Applicants

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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant Organizations

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 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The Research Strategy must consist of the following sub-sections with the indicated page limits:

• Subsection A: Evidence-to-Action Partner (EAP) Engagement Plan (3 pages): required
• Subsection B: OUD and Pain Partner (OPP) Engagement Plan (3 pages): required 
• Subsection C: Research Project (12 pages): required
• Subsection D: Pilot projects (6 pages): required

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.

SF424(R&R) Cover

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.

• Present data on OUD and CP symptoms, severity, and trends for targeted sites. Data may cover all sites collectively or each site individually.
• Describe the capacity to recruit additional sites, if needed.
• If the study design includes plans to recruit additional sites, include strong justification for feasibility (e.g., letters of support from system overseers) and rationale for this strategy.

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.

• PD/PIs must commit at least 2.0 person-months annually throughout the award period. In multi-PI applications, at least one PD/PI must meet this requirement.
• PD/PIs and key personnel with substantial network commitments must actively participate in activities including but not limited to:
  • Authoring/reviewing network publications
  • Engaging in data harmonization and sharing efforts
  • Executing BEACON Center collaborations (e.g., mentoring, contributing items for the Survey Core). BEACON will track collaborative activities across the network and report as an outcome to NIH.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

• Applicants are encouraged to include support for OPP(s) and EAP(s), including allowable salary support or honorarium, travel, and per diem costs.
• If applications have not pre identified these partners, it is appropriate to set aside a number of slots to fill in after the partner needs have been established based on the research project.
• If appropriate, training courses in research methodology may be provided to ensure meaningful OPP and EAP engagement in the research process.
• Applicants are encouraged to avoid patient tokenism and ensure study-generated data will be utilized by EAP(s) to meaningfully shift clinical practice within health systems.

Requirements for Participating in Network Activities

Budget time and funds for the required network meetings and reporting. Applicants must plan for:

• Annual in-person network meeting (1 PI, 1 EAP, 1 OPP, 3 project staff)
• BEACON will host the first meeting.
• Host sites will rotate each year among awardee institutions. If an applicant is selected to host, budgets should include staff effort and costs to co-organize the meeting  with BEACON (e.g., identifying venue and lodging, meeting logistics)
• One additional in-person kickoff meeting in Year 1 in Rockville, MD to discuss data harmonization policies, network procedures and operations
• Monthly virtual steering committee meetings. Partners may attend every 6 months, when appropriate.
• Participate in additional activities:
• CDE determination and data harmonization
• Network workgroups
• Quarterly summary statistics on CDEs and recruitment/enrollment metrics
• Serving as a mentor and contributing ideas for the annual survey administered by BEACON

Pilot Studies: Pilot studies are limited to $100K direct costs each year of the award.

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: A 1-page Specific Aims is required. Applications must include the following functional and structural units. These units referred to as Sub-sections A-D must be clearly marked and include all information specifically requested for each component. The Research Strategy must consist of the following subsections with the indicated page limits:

Subsection A: Evidence-to-Action Partner (EAP) Engagement Plan (3 pages): required

Subsection B: OUD and Pain Partner (OPP) Engagement Plan (3 pages): required

Subsection C: Research Project (12 pages): required

Subsection D: Pilot projects (6 pages): required

Research Strategy:

Subsection A: EAP Engagement Plan

All projects must include an EAP Engagement Plan. Audience examples include, but are not limited to, individuals responsible for resource allocation, health systems or community-based organizations that monitor or provide treatment services, local health/public health departments, or local services providers leaders. Examples of engagement include, but are not limited to: data collection that would guide intervention implementation in a clinic or community, direct resource allocation, improved efficiencies in integrated care delivery, refinements in insurance coverage and determination, and/or other actions impacting service provision for this population.

This plan should include:

• EAP composition and expertise that complements the goals of the study. There is no minimum or maximum number of EAPs.
• Plans for continued engagement if the primary contact leaves the organization.
• Details on how the EAP will engage in the study and use study data (including economic analyses) to improve health outcomes. Detail engagement frequency, defined roles, shared goals, co-creation, and resource sharing. Include a conflict resolution plan to manage disagreements.
• Justify partnership benefits for advancing care that would not occur otherwise. Include benefits even if findings are null. Discuss how data will translate beyond academia to meaningfully shift clinical practice.
• Provide appropriate resources to partners based on their time and effort, plus mutual benefits and recognition (e.g., authorship, presentations, workgroup roles).
• Methods and metrics to monitor partner engagement efforts, including a description of how data will be collected within the framework of the grant activities
• Commitment to training EAPs in research methodology wherever appropriate to ensure meaningful contributions to the research process.

Letters of Support: Letters of support are required from the EAP(s).

Subsection B: OPP Engagement Plan

This plan should also detail how the proposed intervention and any implementation strategy benefits the patients. Relevant audiences can include: individuals with OUD and CP, members from patient advocacy groups, and/or caregivers. In addition to informing the research design, applicants are strongly encouraged to utilize OPP perspectives to inform intervention selection, subject recruitment, treatment retention, and engagement in follow-up care.

This plan should include:

• Expectations of all partners, including composition, expertise, and research phase(s) of engagement (design, conduct, analysis, interpretation, dissemination). Describe how their input improves research quality and meets patient/community health needs.
• Describe how the plan avoids patient tokenism. No minimum or maximum number of OPP partners required.
• Commit to training OPP(s) in relevant research methods. Identify knowledge gaps and provide training to enable meaningful contributions to study design and execution.
• Provide appropriate resources based on partner time and effort, plus mutual benefits and recognition (e.g., authorship, presentations, workgroup roles).
• Conflict resolution plan to manage disagreements.
• Best practices for co-disseminating findings to audiences beyond researchers.

Letters of Support: Letters of support are strongly encouraged from the OPP(s). If these partners are not pre-identified, include the number of slots and types of expertise sought to complement the research project.

Subsection C: Research Project

HEAL IMPOWR Phase II prioritizes studies that balance clinical intervention innovation with implementation science. Applications must use hybrid implementation-effectiveness designs that address both patient-level and system-level needs to improve reach, scalability, and sustainability of integrated CP and OUD treatments. Multi-site clinical trial designs are strongly encouraged. Implementation emphasis should reflect existing evidence.

IMPOWR Phase II supports two categories of studies:

(a) testing implementation strategies for established interventions that address CP in the presence of comorbid OUD. Applicants are encouraged to use Hybrid Type II, Type III, or implementation clinical trial study designs

(b) providing effectiveness data for novel or emerging treatments not previously tested in IMPOWR Phase I that have the potential to meaningfully shift clinical practice. Applicants are encouraged to use a Hybrid Type I or Type II approach.

Provide a detailed overview of the study design and sample, including:

• A detailed description of the study population. Study participants must have co-occurring CP (pain for at least 90 days) and meet DSM criteria for OUD. The CP condition should be clearly defined rather taking a 'CP agnostic' approach.
• Detailed description of intervention and implementation strategy (when appropriate).
• Study outcomes description. HEAL CDEs are required and IMPOWR Phase I CDEs are strongly encouraged. Select outcomes with OPP and EAP input. Justify follow-up period; 1 year or longer strongly encouraged.
• A brief description of proposed clinical performance sites, including: (1) Detailed plans for ensuring high rates of recruitment and retention; and (2) justification of the selected number of sites including power analyses appropriate to targeted outcomes and study design. Multi-site designs are encouraged. Letters of Support and required details for each research performance site should be provided in the Project/Performance Site Location section.
• Address intervention sustainability and scalability. The project should be high priority to EAP(s) so positive findings can be sustainably incorporated into standard practice after study completion.

Subsection D: Pilot projects

Applicants should plan to support 1-2 pilot projects per year, lasting no more than 2 years. At least 1 pilot project should be planned for the first year, with outyear projects permitted as delayed onset.  Pilot projects may be led by new, early-stage investigators or partners to support:

• Development pilots
• Feasibility studies
• Administrative data analysis
• Acute pain management & OUD

All pilots must align with the grant scope, receive NIH/NIDA approval, and encourage network collaboration, particularly in outyears. Pilot projects cannot be used to supplement ongoing research or serve as bridge funding.

This plan should include:

• Solicitation process: Frequency and methods for recruiting proposals from early career investigators, study partners; outreach to relevant organizations
• Review process: Scientific review procedures and reviewer composition
• Progress monitoring: Evaluation process for ongoing pilots
• Regulatory compliance: Institutional procedures ensuring adherence to Federal human subjects regulations, ethical oversight, and data/safety monitoring for trials
• NIH/NIDA approval: Process and timeline for obtaining authorization

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.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

All applications should provide a plan for sharing data with other research sites within the application, and across awarded research centers, including the BEACON Center.

Applications must comply with Data Management and Sharing (DMS) and Genomic Data policies, methods and standards for scientific data.

HEAL Initiative Expectations

All data from HEAL-funded projects must be shared through a HEAL-compliant data repository so the data can be accessed through the HEAL Data Ecosystem. The HEAL Initiative has additional requirements for awarded applications that must be addressed in the Data Management and Sharing Plan (refer to HEAL Data Sharing Requirements under Section VI.3 for details).

See guidance below for more information:

• Repository selection guidance
• HEAL data sharing policy

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.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Drug Abuse. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

Recipients of both Clinical Trial Required and Clinical Trial Optional awards subject to this term shall report standardized clinical trial activation and enrollment performance data for any interventional clinical trial supported under the award. These metrics are intended to assess trial startup efficiency, site activation, and post-activation performance and to support continuous quality improvement in clinical trial operations (see supplemental guidance). Recipients shall report required data annually at the time of Research Performance Progress Report (RPPR) submission on clinical trial activation and enrollment performance milestone dates as calendar dates; NIH will calculate standardized interval metrics from these dates.

Institutions are expected to maintain capabilities that support efficient clinical trial startup, participant enrollment, and performance monitoring, including streamlined workflows and systems for electronic tracking of milestones.  Recipients are encouraged to implement and evaluate approaches that improve trial efficiency and the participant experience. 

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

Not Applicable

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

HEAL Data Sharing Requirements

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. All HEAL Initiative award recipients, regardless of the amount of direct costs requested for any one year, are required to comply with the HEAL Public Access and Data Sharing Policy. HEAL award recipients must follow all requirements and timelines developed through the HEAL Initiative Data Ecosystem, as described in HEAL's compliance guidance.

1. Study Registration and Metadata (within 1 year of award)

• Register the study with the HEAL platform.
• Provide study information including variable level metadata and any data dictionaries.
• Identify the selected HEAL-compliant data repository.
• Some required study-level metadata will be automatically added during registration.

2. Data and Metadata Submission

Awardees must submit data, metadata, and code (if applicable) to a HEAL-compliant repository.

Before final data submission

• Ensure study registration is complete and updated.

Required data submissions may include:

• Data files
• Data dictionaries (variable level metadata)
• Code (if applicable)

Data dictionaries can be submitted by:

• Following repository-specific submission processes, or
• Using the HEAL Data Ecosystem utility tools to create a HEAL-compliant data dictionary, and then submitting it to the HEAL Platform
• Or sending the data dictionary to: HEALStewards@RENCI.org

Timeline for data sharing (NOT-OD-21-013)

• Share data as soon as possible
• No later than:
  • The time of publication, or
  • The end of the performance period (whichever comes first).

3. Additional Requirements for Human Subjects Research

Studies involving human participants must meet the following:

• Registration at Clinicaltrials.gov
  • Include the term "the HEAL Initiative (https://www.nih.gov/heal)" in the Study Description Section.

Use of Common Data Elements (CDEs)

HEAL funded studies focusing on pain research:

• Are required to use core questionnaires from the HEAL Common Data Elements (CDE) Program
• Encouraged to select supplemental questionnaires
• Report use of CDEs as required

To gain access to the CDEs and questionnaires (NIH box account)

• Email heal_cde@hsc.utah.edu

All other HEAL-funded studies are encouraged to use CDEs when applicable

• NIDA strongly encourages the use of the Core and Specialty collections available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org).
• See NOT-DA-12-008 for further details.

If proposing new questionnaires:

• Consult with the program official and the HEAL CDE team
• Provide justification for inclusion

For copyrighted questionaries

• Obtain licenses before data collection
• Provide licenses to the HEAL CDE team and the program officer

Informed consent

When possible:

• Include language for broad data sharing
• Additional details, resources, and tools are available at https://www.healdatafair.org/.

Data Protection and Confidentiality

All HEAL data are protected under a Certificate of Confidentiality and entitled to the protections thereof.

Awardees and Institutions must:

• Use data only for approved purposes
• Follow all applicable federal and state laws
• Follow informed consent requirements

Comply with NIH policies including:

• NOT-OD-17-109
• 42 U.S.C. 241(d)

Failure to adhere to this criterion may result in enforcement actions.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

Prior to publication, HEAL expects investigators to alert their program officers of upcoming manuscripts to ensure coordination of communication and outreach efforts.

Award recipients and their collaborators are required to acknowledge HEAL Initiative support by referencing in the acknowledgment sections of any relevant publication:

"This research was supported by the National Institutes of Health through the NIH HEAL Initiative (https://heal.nih.gov/)" under award number, [include specific grant/contract/award number; for NIH grant number(s) use full format for the grant number, which includes application type, activity code, institute code, serial number, support year, and other suffixes as defined in Deciphering NIH Application/Grant Numbers. Example: 5R01GM987654-03S]." 

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

Division of Epidemiology, Services, and Prevention Research
National Institute on Drug Abuse (NIDA)
Email: IMPOWR@nih.gov

National Center for Complementary and Integrative Health (NCCIH)
Division of Extramural Research (DER)
Email: NCCIHDERFunding@nih.gov

National Institute on Aging (NIA) 
Email: NIA-NOFO-Scientific@nih.gov

National Institute of Neurological Disorders and Stroke (NINDS) 

NINDS_IMPOWR@ninds.nih.gov

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Division of Neuroscience and Behavior

NIAAA-HEAL@mail.nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Chief Grants Management Officer
National Institute on Drug Abuse (NIDA)
Email: nidagmbemail@nida.nih.gov

National Center for Complementary and Integrative Health (NCCIH)
Office of Grants Management (OGM)
Email: NCCIHDERFunding@nih.gov

National Institute on Aging (NIA) 
Email: NIA-NOFO-Grants@nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Grants Management Contact

Email: NIAAA-GMB@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.