HEAL Initiative: Translating Addiction Epidemiology, Prevention, Treatment, and Recovery Research into Practice (R61/R33 - Clinical Trial Optional)

HEAL Initiative: Translating Addiction Epidemiology, Prevention, Treatment, and Recovery Research into Practice (R61/R33 - Clinical Trial Optional) is sponsored by National Institutes of Health (NIH) - HEAL Initiative. This grant supports research to accelerate scientific solutions to address the national opioid overdose crisis and improve pain management.

Expired RFA-DA-25-078: HEAL Initiative: Translating Research to Practice to End the Overdose Crisis (R61/R33 Clinical Trial Optional) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

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

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Drug Abuse ( NIDA ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Mental Health ( NIMH ) National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title HEAL Initiative: Translating Research to Practice to End the Overdose Crisis (R61/R33 Clinical Trial Optional) R61 / R33 Exploratory/Developmental Phased Award Notices of Special Interest associated with this funding opportunity April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Exploratory/Developmental Grants Phase II See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) 93.

279, 93. 213, 93. 865, 93.

273, 93. 866, 93. 242 Funding Opportunity Purpose The goal of this initiative is to support action-oriented research that accelerates the translation of research to practice to address the overdose crisis.

There remains an urgent need for research that advances the design of stigma-free patient-centered systems of care such that people who experience addiction can recover and sustain their recovery over the long-term.

This notice of funding opportunity (NOFO) solicits applications that address understudied areas of opportunity, particularly those that focus on fundamental barriers or facilitators to reducing overdose deaths at the individual, provider, organizational, community, or system levels.

Projects should be in alignment with the overall goals of the HEAL Initiative, and should focus on replicable, scalable, effective approaches for accelerating the movement of evidence-based and promising treatments into routine use. This NOFO invites phased applications to support projects for which preliminary or feasibility data is not available at the time of submission.

This NOFO is a companion to RFA-DA-25-077 , which solicits applications for which pilot data is available. 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) Letter of Intent Due Date(s) 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.

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 Background: HEAL Initiative The NIH HEAL Initiative: This study is part of the NIH’s Helping to End Addiction Long-term (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/ .

The goal of this notice of funding opportunity (NOFO) is to support action-oriented research that accelerates the translation of research to practice to address the overdose crisis. There remains an urgent need for research to address understudied areas of opportunity, particularly addressing the fundamental barriers or facilitators to reducing overdose deaths at the individual, provider, organizational, community, or system levels.

High priority areas are those that advance the goal of creating stigma-free patient-centered systems of care such that people who experience addiction can recover and sustain their recovery over the long-term. This NOFO is a companion to RFA-DA-25-077 which also solicits applications relevant to the focus area.

Applicants should note the difference between these NOFOs: RFA-DA-25-078 (this NOFO) solicits phased awards, which are most appropriate for projects that require 1-2 years for preparatory work such as collecting pilot data; obtaining and integrating existing data sets; building stakeholder engagement; developing, adapting, and testing the feasibility of key components of interventions or implementation strategies; building necessary infrastructure to support a larger trial (e.g., clinical alerts; recordkeeping systems); or similar activities upon which the subsequent phase would be dependent.

Phased awards do not require pilot or feasibility data at the time of submission. Awards made under RFA-DA-25-078 (this NOFO) may transition to the second (R33) phase to conduct a larger study upon successfully meeting relevant milestones in the R61 phase of the project.

In contrast, RFA-DA-25-077 solicits applications that already have relevant preliminary, pilot, or feasibility data and are prepared to launch a larger study immediately upon award. Proposed research under this NOFO must move beyond descriptive studies that enumerate factors that facilitate or impede the delivery of high-quality, effective addiction treatment services.

Rather, applications should seek to develop and test systematic strategies for improving the quality of care for all people who experience addiction. Applications should attend to methods to accelerate the translation of insights generated by the proposed research into practice.

Methods such as implementation science, hybrid implementation/effectiveness trials, and dissemination research are critical tools for achieving this acceleration. Applications must be innovative and should not focus on replicating previous findings.

Key elements that must be considered in all applications include: Meaningful engagement of relevant practitioners and community stakeholders in study conceptualization, design, execution, and interpretation. Potential scalability of the proposed intervention, including perspectives of prospective payers should the proposed intervention prove to be successful. Sustainability of the proposed intervention should it prove to be successful.

Health disparities and the relevance to the interventions or services being studied. Perspectives of patients or recipients of the services or interventions being studied. Proposed projects must address services related to the treatment of and/or recovery from opioid use or stimulant use disorder.

Applications may also propose to explore issues relevant to the intersection of opioid or stimulant misuse/use disorders and pain. Applications that focus solely on primary prevention or opioid prescribing will not be considered responsive to this NOFO. Applicants interested in primary prevention and opioid prescribing should respond to other relevant HEAL NOFOs.

Studies may take place in a variety of settings including those in substance use disorder (SUD) treatment, general and specialty healthcare, criminal justice, social and human services, pain clinics, pharmacies, workplaces, and community settings.

Applicants are encouraged to consider nontraditional service delivery settings when these could potentially broaden the reach of evidence-based services to populations and other groups that have historically experienced challenges in access to addiction services. This NOFO is a companion to RFA-DA-25-077 .

These NOFOs solicit applications relevant to translating research to practice for the prevention of overdose and the treatment of and recovery from opioid and stimulant addiction. Periodically, additional Notices of Special Interest (NOSIs) may be released by the NIH and published in the NIH guide identifying specific high priority areas of interest relevant to these NOFOs.

In addition to areas of interest specified by such NOSIs, effectiveness, services, or implementation questions relevant to treatment of opioid use or stimulant use disorder and recovery support are of general interest.

Examples of specific areas of interest include, but are not limited to: Provider, organizational, community, or system-level interventions that seek to enhance uptake of evidence based practices; Studies that test novel and efficient service delivery models for opioid use disorder (OUD) and other comorbid medical and mental conditions; Studies that seek to identify, develop, test, evaluate, and/or refine strategies to disseminate and implement evidence-based practices (e.g. behavioral interventions; prevention, early detection, diagnostic, treatment and disease management interventions; quality improvement programs) into public health, clinical practice, and community (e.g., workplace, school, place of worship) settings to address opioid or stimulant use and comorbid medical and mental conditions, including pain; Approaches that enhance the quality, effectiveness, affordability, or utilization of existing treatments for OUD and comorbid medical or mental conditions, including pain; Studies that address novel research questions that would otherwise not be addressed by programs or infrastructure supported through other funders (e.g., Substance Abuse and Mental Health Services Administration (SAMHSA), Health Resources & Services Administration (HRSA), Bureau of Justice Assistance (BJA), settlement funds, private funders, etc.); Studies that seek to understand major changes or variations in the service delivery environment that may facilitate or impede the delivery of effective, high-quality, patient-centered services; Projects that seek to understand circumstances and test strategies to stop or reduce (i.e., “de-implement”) the use of interventions that are ineffective, unproven, low-value, or harmful in efforts to demonstrably free up resources and then implement a high-value evidence-based practice Strategies that seek to improve quality, timeliness, and utility of data to inform and support real-time proactive responses within systems and in cross-system collaborations; Multi-level intervention designs that tackle multiple barriers to or facilitators of access to evidence-based services.

Additional high priority topics may periodically be solicited under this NOFO through one or more NOSIs, published in the NIH Guide . This NOFO will not support applications that seek to develop and test the efficacy of novel addiction treatments or similar clinical interventions or new prevention interventions. Phases of the Award & Milestones This funding opportunity uses a R61/R33 Exploratory/Developmental Phased Award mechanism.

Support will be provided for up to 6 years, which includes initial support of up to 2 years of the R61 phase, followed by up to 5 years of support for the R33 phase upon successfully meeting R61 milestones. This mechanism is provided to facilitate research for which preliminary data is not available, including high risk/high reward research.

However, even for high risk/high reward research, applicants must provide a clear vision for how the research would progress if successful. The R61 phase is a planning phase that can be for up to two years and will support activities that demonstrate feasibility.

It is expected that work during this phase will largely focus on issues related to (1) collecting feasibility or pilot data for a clinical trials, (2) stakeholder engagement to ensure buy-in, sustainability, scalability, etc; (3) testing hypotheses for which preliminary data is not otherwise available; or (4) demonstrating ability to access key datasets or build critical infrastructure.

Applications must delineate milestones that signify the completion of major elements necessary to support a larger scale project in the second phase (e.g., successful piloting of an intervention or intervention component; accessing or improving timeliness of a specific dataset; establishing Memoranda of Understanding [MOU] with key stakeholders, etc.).

For transition to the R33 phase, recipients must submit the transition package no less than 75 days before the completion of the R61 phase. The transition plan should include the R61 progress report describing in detail the progress towards the R61 milestones and a description of how research proposed for the R33 phase will be supported by the completion of the R61 phase milestones.

These materials will be evaluated by NIH program staff to determine if the milestones were met. Transition to the R33 phases requires administrative review by NIH staff and is not guaranteed. R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, any proposed changes to the R33 research based on R61 findings, program priorities, and availability of funds.

It is not expected that all applications will continue to the R33 phase. Pre-Application Consultation Potential applicants are strongly encouraged to consult with appropriate NIH 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 HEAL initiative mission and intent of this NOFO.

Non-responsive Applications The following applications will be considered non-responsive and will not be reviewed: Applications testing new clinical interventions to prevent or treat opioid addiction (i.e., drugs, devices, behavioral therapies).

(Note applications may test adaptations of existing interventions, health services interventions, new recovery support interventions, etc.) Applications that do not address effectiveness, services, or implementation questions relevant to the treatment of and/or recovery from opioid use or stimulant use disorder. There are also opportunities to harmonize data within the broader NIH HEAL Initiative.

Applicants selected for funding should expect to have a conversation with NIH program staff early in their project regarding high priority areas for potential harmonization. NIH HEAL Requirements: The NIH HEAL Initiative will require a high level of coordination and sharing between investigators.

It is expected that NIH HEAL Initiative award recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual NIH HEAL Investigators Meeting, as well as other activities. HEAL Scientific Meeting Attendance: The NIH HEAL Initiative will require a high level of coordination and sharing between investigators.

It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Scientific Meeting, as well as other activities.

Clinical Trial Accrual: This NOFO will support applications that include a series of milestones for completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of the HEAL Initiative.

If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIH will consider ending support and negotiating an orderly phase-out of the award. NIH retains the option of periodic external peer review of progress. NIH program staff will closely monitor progress at all stages for milestones, accrual, and safety.

Please refer to the HEAL Policy for the Enrollment of Participants in Clinical Trials for additional information.

National Institute of Mental Health (NIMH) Areas of Specific Interest and NIMH-Specific Instructions NOT-DA-23-008 Notice of Special Interest (NOSI) HEAL Initiative: Workforce Interventions to Improve Addiction Care Quality and Patient Outcomes NOT-DA-23-007 Notice of Special Interest (NOSI): HEAL Initiative: Opioid Use Disorder Care Pathways for Individuals with Histories of Exposure to Violence For assignment to and funding consideration at NIMH, applicants should include “NOT-DA-23-007" or “NOT-DA-23-008” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form.

Applications that do not include this information will not be assigned to NIMH. All applications that propose clinical trials and that seek funding consideration at NIMH should follow the NIMH’s experimental therapeutics approach to intervention development and testing (see https://www. nimh.

nih. gov/funding/opportunities-announcements/clinical-trials-foas/index. shtml ).

That is, the scope of work must include specification of targets/mechanisms and assessment of intervention induced changes in the presumed targets/mechanisms that are hypothesized to account for the intervention’s outcomes.

In this manner, the results of the trial will advance knowledge regarding therapeutic change mechanisms and be informative regardless of trial outcomes (e.g., in the event of negative results, information about whether the intervention was successful at engaging its targets can facilitate interpretation). NIMH is committed to supporting research that reduces disparities in mental health interventions, services, and outcomes.

Accordingly, this NOFO encourages research studies that seek to reduce disparities for racial and ethnic minority groups, individuals limited by language or cultural barriers, individuals living in rural areas, socioeconomically disadvantaged persons and other underserved groups.

NIMH encourages a deployment-focused model of intervention and services design and evaluation that takes into account the perspective of relevant stakeholders (e.g., service users, providers, administrators, payers) and the key characteristics of the settings (e.g., resources, including workforce capacity; existing clinical workflows) that are intended to implement optimized mental health interventions.

This attention to end-user perspectives and characteristics of intended clinical and/or community practice settings is intended to ensure the resultant interventions and service delivery strategies are acceptable to consumers and providers, the approaches are feasible and scalable in the settings where individuals are served, and the research results will have utility for end users.

NIMH encourages research on potentially scalable preventive, therapeutic, and services interventions that focuses on practice-relevant questions. Accordingly, collaborations between academic researchers and clinical or community practice partners or networks are encouraged.

When possible, studies should capitalize on existing infrastructure (e.g., practice-based research networks such as the NIMH-sponsored Mental Health Research Network (MHRN), electronic medical records, administrative databases, patient registries, institutions with Clinical and Translational Science Awards) to increase the efficiency of participant recruitment (i.e., more rapid identification and enrollment) and to facilitate the collection of moderator data (e.g., clinical characteristics, biomarkers), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, value and efficiency of intervention approaches).

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 Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. 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 NIH intends to commit up to $10 million in FY2026 to fund up to 12 awards for both this NOFO and the companion NOFO, RFA-DA-25-077 . Awards pursuant to this funding opportunity are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project.

Unless well-justified, it is strongly recommended that applicants not request a budget of more than $300,000 in direct costs per year for the R61 phase and $750,000 in direct costs per year for the R33 phase of the project. The scope of the project should determine the project period for each phase.

The maximum period of the combined R61 and R33 phases is 6 years, with a maximum of 2 years for the R61 phase and maximum of 5 years for the R33 phase of the project. Applicants are encouraged to streamline the project period to complete the research as efficiently as possible. It is recommended that the R33 phase not exceed 4 years unless exceptionally well justified.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 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 .

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 registration; 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. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: [email protected] 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. Applications without the following documents will be considered incomplete and will be withdrawal without review. Timeline & Milestone Plan (Required - 2 page maximum) Applicants must include a Timeline and Milestone Plan, clearly specifying proposed milestones and when those milestones are expected to be achieved.

Milestones for both phases must be specified, though it is expected that R33 milestones may change based on results from the R61 phase for awards that transition to the R33 phase. Applications without the required Timeline & Milestone Plan will be considered incomplete and will not be reviewed.

Stakeholder Engagement Plan (Required– 2 page maximum) Applications must include detailed plans for engaging key stakeholders, including patients, families, providers, payers, and community leaders, as appropriate to the specific goals of their study. Applications without the required Stakeholder Engagement Plan will be considered incomplete and will not be reviewed.

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. Meetings and Travel: Applicants should assume that all meetings referenced throughout this NOFO will be held virtually unless otherwise specified.

NIH program staff may wish to periodically convene award recipients under this program, both virtually and in person. To plan for potential in-person convenings, budgets should include funds for travel for up to 3 people to participate in a 2-day meeting in the Washington DC area in each year of the award.

HEAL Scientific Meeting: For budgeting purposes, include travel costs to support the attendance of one PD/PI (one person) at a 2-day, in-person HEAL Scientific Meeting in the Washington DC area, annually for the duration of the award. 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: In the single page attachment allowed for the specific aims, applicants should provide an overview of the overarching research question of interest as well as include clearly marked headers for “R61 Specific Aims” and “R33 Specific Aims” with brief descriptions of the aims specific to each phase of the study.

The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application should present an overview of the state of the science, current status and relevance of the proposed activities, and consideration of long-term sustainability and scalability of the proposed efforts.

The research strategy must clearly specify how the proposed project addresses effectiveness, services, or implementation questions relevant to other treatment of and/or recovery from opioid use or stimulant use disorder.

The following criteria should be addressed: Significance: The R61 and R33 should coherently address a single set of research questions and goals, with the R61 phase establishing feasibility and necessary data to support transition to the R33 phase. Given this tight integration, only one Significance section is needed. Innovation: Given this tight integration of the R61/R33 phases, only one Innovation section is needed.

The Innovation section should explain how the proposed project, if successful, would lead to innovations that could help accelerate the translation of research findings to practice that would address the overdose crisis. Preliminary data is not required nor is it required that teams have worked together previously. The phased award approach allows for earlier stage high risk/high reward projects.

However, applications without preliminary data should have a strong scientific premise and establish a strong rationale for how solving the challenges outlined in the application would improve outcomes relevant to overdoses and/or opioid-related morbidity and mortality.

NOTE: For early stage research involving new partnerships or where preliminary data is needed to support the premise of the larger study, these aspects of feasibility must be explicitly included as