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

NIH 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). The NIH HEAL Initiative® aims to accelerate scientific solutions to address the national overdose crisis.

RFA-DA-27-016: HEAL Initiative: Translating Addiction Epidemiology, Prevention, Treatment, and Recovery Research into Practice (R61/R33 - Clinical Trial Optional) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Drug Abuse ( NIDA ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title HEAL Initiative: Translating Addiction Epidemiology, Prevention, Treatment, and Recovery Research into Practice (R61/R33 - Clinical Trial Optional) R61 / R33 Exploratory/Developmental Phased Award Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 93. 279, 93. 273, 93.

866, 93. 213 Funding Opportunity Purpose The goal of this notice of funding opportunity (NOFO) is to address the opioid crisis and/or overdose events by supporting action-oriented research, accelerating the translation of addiction epidemiology, prevention, treatment services, and recovery research to practice. Proposed studies may target the individual, provider, organizational, community, or system level.

This initiative prioritizes replicable and scalable approaches for accelerating the routine use of effective, evidence-based prevention, treatment and recovery interventions and services. The translation of research to practice and research relevant to chronic pain comorbid with substance use is also a priority.

Research may deploy a variety of methods and approaches, including but not limited to identifying and characterizing malleable factors, developing and testing interventions and implementation strategies, deploying and testing collaborative data science approaches, and/or developing and testing approaches that integrate the collaboration of researchers and decision-makers at any levels (e.g., clinical-, health system-, public health- or policy-level).

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 outcome, including HIV/AIDS.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Use Grants. gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Background: HEAL Initiative 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 /. The goal of this initiative is to address the opioid/stimulant crisis and/or overdose events by supporting action-oriented research that accelerates the translation of addiction epidemiology, prevention, treatment, and recovery research to practice.

Research may include the intersection of substance misuse, addiction and pain, however, applications that focus solely on reducing opioid prescribing or that are purely descriptive will not be considered responsive to this NOFO.

This NOFO seeks phased awards, which are most appropriate for projects that require 1-2 years for preparatory work during the R61 phase, leading to a larger scale R33 phase, which may focus on large-scale data collection and/or intervention or implementation trials. Preparatory work in the R61 phase should establish the feasibility of or justification for executing the R33 phase.

Phased awards do not require pilot or feasibility data at the time of submission. Projects must meet relevant milestones outlined in the R61 phase of the project to transition to the R33 phase. Transition to the R33 phase is not guaranteed even if all milestones are met.

Studies should target novel individual, provider, organizational, community, and/or system-level factors relevant to the opioid/stimulant and overdose crises.

Studies may take place across a variety of settings including but not limited to: substance use disorder (SUD) treatment, general and specialty healthcare, criminal justice, social and human services, educational settings, pain clinics, pharmacies, victim service, workplaces, and community settings. Nontraditional service delivery settings are also of interest when they could potentially broaden the reach of evidence-based services.

Intervention studies are not required. Applications are encouraged to use a range of methods and approaches, including multidisciplinary and innovative methods as appropriate to the study questions. For intervention, infrastructure, or services studies, applications should consider acceptability, feasibility, scalability, and sustainability.

Projects are strongly encouraged to engage relevant end users in study conceptualization, design, execution, and interpretation. End user is broadly defined and may include people who experience addiction, youth, families, community members, practitioners, intervention implementers, organizational leaders, prospective funders/payers, and others.

Applications that provide a conceptual and/or pragmatic framework and clear vision for how the research can be sustained beyond the life of the grant will be prioritized.

Specific high priority topics of interest include, but are not limited to: Research resulting in improved methods that enhance meaningful and representative real-time data capture and use to improve public health approaches to reducing substance use, misuse, addiction, and overdose. Research to develop and test strategies to prevent the initiation of substance use, or progression to SUDs.

This may include phased studies to support the rapid translation of epidemiological findings to substance use and addiction preventive interventions.

Of priority is translational research improving the ability to identify and characterize malleable individual, familial, behavioral, developmental, and environmental factors (within the population or precise subgroups) that, if targeted by intervention, could prevent initiation of substance use or progression to misuse or use disorder.

Research on strategies to implement and sustain evidence-based prevention services, that are embedded within or across existing systems and settings (e.g., healthcare, child welfare, justice, education).

This might include research on facilitating the delivery of prevention services by adapting programs to setting or target population, using non-clinical providers, and leveraging existing resources within the system or setting (e.g., data or funding sources).

Additional service delivery-related questions could include implementation, sustainability and scalability, workforce challenges, and economic implications (e.g., cost benefits/offsets and cost-effectiveness). Research to address provider-level challenges in the uptake of effective interventions across diverse care delivery settings (e.g., primary care, mental health, emergency care).

This may include efforts to enhance recruiting, training, and retaining clinicians and other providers and reducing barriers to delivering evidence-based treatment and recovery interventions (e.g., contingency management); efforts to better understand task shifting and other strategies to enhance the efficiency or quality of services ; care models that integrate peers or other lay interventionist (e.g., family) approaches.

Research to enhance our understanding of recovery processes, including understanding mechanisms of recovery, natural recovery trajectories, and influences of services on recovery pathways; whole person approaches that account for dynamic physical, psychological, social, and environmental influences on recovery outcomes; approaches to understanding the role of concerned significant others including dyadic intervention approaches; and testing interventions to support self-management of substance use symptoms, relapse prevention, and treatment re-engagement.

Research on interventions and strategies to better support efficient transitions across care settings or levels of care intensity, for example inpatient to outpatient treatment setting transitions, jail to community settings, hospitalizations and subsequent care, with the goal of increasing retention through a full cascade of care.

Community-Engaged Research Methods in HEAL Research Studies People with lived/living experience (e.g., patients, people in recovery, caregivers, families, community leaders) have important insights that can improve meaningful outcomes and uptake of research findings across the continuum of research from basic through implementation studies.

The NIH HEAL Initiative strongly encourages the use of community-engaged research methods (e.g., the promotion of bi-directional communication between the researchers and the relevant community throughout the research project).

Community-engaged research methods will vary with the focus and approach used in each project but should at minimum ensure that researchers are connecting with people with lived/living experience to incorporate their input throughout the conception, implementation, and dissemination of the research. See this resource for more information on community-engaged research methods: https://heal. nih.

gov/resources/engagement Phases of the Award & Milestones This funding opportunity uses a R61/R33 Exploratory/Developmental Phased Award mechanism. Support will be provided for up to a total of 6 years, which includes initial support of up to 2 years for the R61 phase, followed by up to 5 years of support for the R33 phase, upon successfully meeting R61 milestones. Applicants are not required to provide preliminary data for this NOFO.

The R61 phase is a planning or exploratory phase that can be for up to two years and will support activities that demonstrate feasibility or establish pivotal data infrastructure justification in support of the R33 phase.

Activities during the R61 phase may include: (1) collecting feasibility or pilot data for a clinical trial; (2) stakeholder engagement to ensure buy-in, sustainability, scalability, or other needed components before launching a larger study; (3) testing hypotheses for which preliminary data is not otherwise available; (4) demonstrating ability to access key datasets or build critical infrastructure; (5) primary data collection, secondary analysis of existing data sets (qualitative and/or qualitative); (6) conducting policy analysis/impact studies to establish targets for an intervention; or (7) focus groups or cognitive testing to improve methodology or prepare for larger scale data collection.

Applications must include specific, concrete milestones to be accomplished by the end of the R61 phase (see Section IV, Timeline and Milestone Plan). Milestones should represent findings or successful completion of activities from the R61 phase that would justify transition to the R33 phase of the project.

For example, milestones might be related to demonstrating the feasibility of the approach taken in the R33 phase by including metrics for a successful pilot of an intervention or recruitment approach, timelines for data access, acquisition or management, or establishing Memoranda of Understanding with key stakeholders.

Applications that propose R33 effectiveness or adaptation clinical trials must include successful piloting of the intervention as a R61 milestone. For transition to the R33 phase, recipients must submit the transition package 75 days prior to the anticipated start date of the R33 phase.

The transition package 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.

Approval of the transition to the R33 phase 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 even if all milestones are met.

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 that do not include research related to substance use epidemiology, prevention, or treatment and recovery research or that focus solely on alcohol or tobacco use disorder. Applications focused solely on testing new treatment interventions.

Applications that focus solely on reducing opioid prescribing without addressing/measuring an opioid related harm. Applications proposing an R33 effectiveness clinical trial that do not include a R61 milestone to collect pilot data. 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.

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. 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 The NIH HEAL Initiative intends to commit an estimated total of $6,000,000 to fund 12 awards in FY2027. Awards pursuant to this funding opportunity are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets must reflect the actual needs of the proposed project. The R61 phase is limited to a budget of no more than $350,000 in direct costs per year and the R33 phase is limited to a budget of no more than $750,000 in direct costs per year. 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. Applicants proposing R33 phases that exceed 4 years must provide a very strong justification.

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

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

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Foreign Organizations/International 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 allowed. NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts.

All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16. 8 Collaborative International Research Awards .

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding.

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

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible.

Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications for additional information. System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration.

SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. 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. 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.

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 .

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 (in this NOFO, in a policy notice , or other notice from NIH Guide for Grants and Contracts ). Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

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

Timeline & Milestone Plan (Required - 2 page maximum) Applicants must include an Other Attachment entitled Timeline and Milestone Plan , clearly specifying proposed milestones and when those milestones are expected to be achieved. Milestones should be specific, quantifiable, and scientifically justified; they should establish the feasibility or empirical basis for pursuing the R33 phase of the study.

Milestones must not simply be a restatement of the specific aims for the R61 phase, they should signify the completion of major elements necessary to support the larger scale research project in the second phase of the award.

For applications where there is no preliminary data or where new partnerships are proposed, applicants should be especially attentive to proposing milestones that will help establish the feasibility of their proposed R33 project. The application should include contingency plans to proactively confront potential delays in meeting the milestones.

Examples of potential milestones for the R61 phase include, but are not limited to: Data to be used in the epidemiological study, including how those data represent the population of focus and the targeted outcomes or mechanisms of interest. A report of an epidemiological analysis of risk factors or target consequences to be addressed in a trial.

A summary of planned implementation strategies, including staff selection, staff training, supervision, and fidelity measures. Evidence of having established research partners the community and/or system of relevance, and a plan for collaborating over the course of the research project.

Developed and piloted study elements including measures, the study design, adaptation or refinement of the intervention or delivery strategies, intervention manuals, and/or engagement and implementation strategies (e.g., fidelity monitoring, training).

For prevention or recovery support efficacy studies, a final plan for recruiting, consenting, and retaining participants, describing where recruitment will occur, how many participants are likely to be recruited, and the process for obtaining consent. For effectiveness or adaptation intervention studies, the R61 phase must include piloting the intervention to be tested in the R33 phase.

Tests of data collection and data management systems and processes, including the piloting of survey instruments, cognitive testing, and harmonizing datasets. Data safety and operational oversight plans; regulatory approvals (e.g., IRB, Tribal review, Data and Safety Monitoring Plan [DSMP]) and other essential documents and procedures for safeguarding data and protecting participants.

Updated data sharing protocols and/or plans for data archival, and a timeline for releasing the first set of data or publication of results. SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: Specific Aims: In the single page attachment allowed for the specific aims, applicants must provide 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, 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 will create a significant public health impact by addressing effectiveness, services, or implementation questions relevant to other treatment of and/or recovery from opioid use or stimulant use disorder in the targeted population and/or setting.

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: 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. Given the tight integration of the R61/R33 phases, only one Innovation section is needed Approach: The application should contain separate Approach sections for the R61 and R33 phases, as described below.

It is not necessary to repeat any information or details in the R33 section that are described in the R61 section. Applications must also include a Timeline & Milestone plan as an attachment as described in the SF424(R&R) Other Project Information. The approach sections may reference this attachment and should limit what is repeated from this attachment, except where necessary for clarity.

The approach section must address the following elements in the phase most appropriate to the proposed study: For all studies, approach to engaging relevant practitioners and/or community stakeholders as partners and/or considerations relevant to the perspectives of end-users (i.e., patients, service recipients, payers) of the interventions or infrastructure being studied, where relevant.

For epidemiological studies, considerations relevant to the impact these data would have on translating findings into prevention, services, and/or recovery; For studies of interventions, considerations relevant to the sustainability of the proposed intervention; For studies of interventions or infrastructure, considerations relevant to the potential scalability of the proposed intervention or infrastructure; Preliminary data are 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 milestones for the R61 phase. The R61 phase of the award may be up to 2 years long. The R61 Approach section of the application must include an overview of milestones that are expected to be achieved by the end of the R61 phase.

Milestones should be specific, quantifiable, and scientifically justified; they should establish the feasibility or empirical basis for pursuing the R33 phase of the study. Milestones must not simply be a restatement of the specific aims for the R61 phase. Specific details regarding timelines and other specifics should be included in the Timeline & Milestone Plan in SF424(R&R) Other Project Information.

Examples of Milestones for the R61 Phase: Fully executed Memorandum of Understandings (MOUs), letters of support, and data sharing agreements, as relevant to the goals of the study, from partnering departments, agencies or stakeholders. Demonstration of active engagement and partnership with key entities and stakeholders (e.g., formation of trans-department or trans-agency change teams).

If preliminary data was not included in original application, preliminary data demonstrating feasibility of R33 phase must