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 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.

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.



Table of Contents
Part 1. Overview Information
Key Dates
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

Purpose

The goal of this initiative is to support research that can improve public health and respond to the opioid crisis by increasing knowledge pertaining to the delivery and sustainability of prevention services. This notice of funding opportunity (NOFO) solicits applications to address understudied areas of opportunity that, if researched, could create the foundation needed to inform a prevention infrastructure for ongoing delivery and sustainment of interventions to prevent opioid and other substance misuse and use disorders.

This NOFO is a companion to RFA-DA-24-067 which also solicits applications relevant to the focus area. Applicants should note the difference between these NOFOs. This NOFO, RFA-DA-24-066 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 implementation strategies; building necessary infrastructure to support a larger trial; 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 this NOFO may transition to the second (R33) phase to conduct a larger study upon successfully meeting relevant milestones in the R61 phase. In contrast, RFA-DA-24-067 solicits R01 applications that already have relevant preliminary, pilot, or feasibility data.

Background

The NIH HEAL Initiative: This NOFO 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 opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.

The importance of prevention in combating the opioid crisis is clear – identifying and implementing effective strategies to prevent the onset of opioid misuse and use disorder can yield positive individual, societal, and financial benefits and decrease the need for treatment services. In 2020, 9.5 million people aged 12 or older reported misusing opioids in the past year (National Survey on Drug Use and Health, 2021), indicating that there are millions of people whose trajectories could have been changed, had they been exposed to an effective prevention strategy. Recent HEAL-funded research suggests that some risk factors for opioid misuse tend to be similar to risks for using other substances, and initiation of other substance use (e.g., cannabis) may precede initiation of opioid use in some populations. Previous and ongoing studies have developed and are testing innovative prevention approaches to address the range of individual, social, and environmental motivations for using non-prescription opioids, relevant to and effective for diverse populations. 

While there are effective prevention strategies, those strategies may not be widely implemented in practice. One of the biggest barriers to the wide-scale implementation of opioid and other substance use prevention interventions is the lack of infrastructure at the national and state levels to support prevention service delivery. Prevention programs are often embedded in broader systems or settings (e.g., schools, justice settings, social service settings, community behavioral health centers) and, therefore, may be competing with other services for time and resources. In addition to limited resources, the scope and competencies needed for a prevention workforce are not well-defined. Finally, when prevention resources exist, those allocating the funding may not have information regarding evidence-based programs and practices, and therefore they may not require their use. This may result in state agencies distributing the small amount of federal and state funds they receive for prevention to localities with varying guidance on how it can most effectively be used.

Definition of prevention: For this NOFO, the focus is selective or indicated prevention strategies. The scope of this NOFO is services related research to inform the delivery of strategies or programs that reduce risks for substance misuse, prevent initiation, or prevent escalation to substance use disorder (SUD) among individuals who are at-risk or already misusing substances (for additional information on the definition of intervention levels see: https://nap.nationalacademies.org/resource/25552/Prevention%20Models%20-%20FINAL.pdf)

Research Objectives

To ensure existing prevention intervention research efforts have a broad public health impact, research is needed to identify pathways for effective prevention strategies to be adopted and funded for wide-scale delivery. Thus, the goal of this initiative is to support research to address service delivery related questions. Projects submitted in response to this NOFO may define research to inform the establishment of a prevention infrastructure in one of two ways –

1. Research on strategies to implement and sustain evidence-based prevention services, so they are embedded within existing systems and settings (e.g., healthcare, child welfare, justice, education), facilitating the ongoing delivery of prevention services by adapting programs to setting, using natural providers and leveraging existing resources within the system or setting; OR
2. Research to understand how to best develop and maintain an independent prevention workforce and delivery system that the settings/systems noted above can utilize to ‘refer’ individuals or families to for the receipt of preventive services when they may be experiencing risk for opioid or other substance use.

Example areas of research interest include, but are not limited to:   

• Developing and testing approaches to the implementation, sustainability and scale-up of effective interventions to prevent opioid and other substance misuse and use disorder, including the testing of strategies to build infrastructure and capacity to deliver prevention services within diverse systems and settings.
• Research to examine scientific solutions to prevention workforce capacity challenges, including developing and testing new approaches to training and retaining prevention workforce personnel (e.g., prevention practitioners, intervention implementers), task shifting and identifying opportunities to integrate prevention service delivery into a variety of staff positions, and strategies to build centralized, community-based prevention systems and workforces. 
• Developing and testing innovative strategies and models for optimizing key implementation processes: identifying intervention core components, adaptation and customization, implementation fidelity, and organizational or system level strategies to enhance uptake and sustainability of evidence based preventive interventions.
• Research to leverage technology and/or direct to consumer's strategies to facilitate access to preventive care – this may include increased use of smartphone /mobile technology, use of social media for intervention delivery, or other methods as appropriate.
• Research to test the cost benefits/offsets and cost effectiveness of investment in prevention infrastructure and evidence-based interventions, including broad investment and benefits at the community or population level.
• Studies examining the impact of evidence-based practice registries and other decision-making tools on uptake of evidence-based interventions and the longer-term impact on preventing substance use and promoting public health.
• Strategies that seek to improve quality, availability, and utility of data that can be used to track the extent of program implementation and/or receipt of services within or between systems. 

Proposed research under this NOFO must move beyond descriptive studies that simply identify factors that facilitate or impede the delivery of effective preventive services. Rather, applications should seek to develop and test systematic strategies for the implementation and sustainability of effective strategies to prevent opioid and other substance misuse and/or use disorder, and strategies to reduce risk for overdose among individuals who do not meet the criteria for SUD. To ensure sustainability of service delivery strategies tested, applicants should partner with communities and localities who use existing funds (e.g., federal block grant and demonstration grants; settlement funds; private foundations) to support evidence-based prevention programs and leverage those resources as the foundation for building infrastructure. Research should be designed in such a way that there is a high probability that interventions delivered can be scaled and sustained after the study period ends.

Methodology used should accelerate the translation of findings generated by the proposed research into practice. To maximize the acceptability, feasibility, scalability and sustainability of prevention services being studied, applicants must engage relevant end users in study conceptualization, design, execution, and interpretation. For the purpose of this NOFO, end user is broadly defined and may include policymakers, state and local level decision makers, practitioners, intervention implementers, families, youth, and community members. Applications proposing to embed an intervention within a specific setting should consider the potential generalizability of the proposed service delivery model (i.e., is the model specific to the intervention and setting being tested or is it a framework that could generalize to other prevention programs and settings). Attention should be paid to health disparities and inequities and their relevance to the interventions or services being studied.

This NOFO will not accept applications that seek to develop and test the efficacy of novel prevention intervention strategies. However, in most instances an intervention will be delivered in order to evaluate the services related research question. Data on an intervention’s effectiveness may be collected in the context of evaluating the services related research questions. Research that tests adaptations to the delivery platforms of existing interventions may also be submitted through this NOFO. This NOFO will not support overdose prevention or harm reduction strategies for individuals with SUD, but applicants may propose prevention services or infrastructure research that includes consideration for community-level risks of overdose among those at risk for initiation of use or who have initiated substance use but do not meet criteria for SUD.

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 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 trial, (2) stakeholder engagement to ensure support, sustainability, scalability, etc.; (3) testing hypotheses for which preliminary data is not otherwise available; or (4) demonstrating ability to build necessary infrastructure. Applications must delineate milestones that signify the completion of major elements that demonstrate readiness to proceed to 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.). See Part 2. Section IV “Other Project Information” below for instructions on submission of the milestone plan.

For transition to the R33 phase, awardees must submit the transition package at least 75 days prior to the anticipated start date of the R33 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 the intent of this NOFO.

Special Considerations:

National Institute on Drug Abuse (NIDA) applicants are strongly encouraged to review the guidelines and adhere to the requirements applicable to their research listed in the Special Considerations for NIDA Funding Opportunities and Awards. Upon award, these considerations will be included in the Notice of Grant Award.

Applications Not Responsive to this NOFO:

The following applications will be considered non-responsive and will not be reviewed:

• Applications that do not address research questions related to implementation, sustainability or scale-up of prevention services or the development of a prevention infrastructure
• Applications testing novel preventive interventions; studies examining the efficacy of a prevention program
• Applications that do not involve a prevention focus, where prevention is defined as any program or strategy whose purpose is to reduce risks for substance misuse, prevent initiation, or prevent escalation to SUD among individuals who are at-risk or already misusing substances (for additional information on the definition of intervention levels see: https://nap.nationalacademies.org/resource/25552/Prevention%20Models%20-%20FINAL.pdf).
• Studies focused on sustainability and implementation of SUD treatment or treatment adherence related research will not be considered under this NOFO.
• Applications that do not include a plan for the meaningful engagement of end users as partners in the research process.
• Applications that do not include a Milestone Plan (see Part 2. Section IV “Other Project Information” below for instructions on submission of the milestone plan)

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.

Diversity: In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details. 

Engaging People with Lived Experience and Other Collaborators: People with lived experience (e.g., patients, patient advocates, caregivers, families, community leaders) have important insights that can improve meaningful outcomes, uptake of research findings, and health equity across the continuum of research from basic through implementation studies. The perspectives of other relevant collaborators (e.g., health service providers, payors, public health agencies, community-based organizations, biotech, Pharma) can further improve research impact. The NIH HEAL initiative strongly encourages applicants to specify their plan for meaningful engagement of people with lived experience and other collaborators in the research process. Meaningful engagement will vary with the focus of the research but should at minimum ensure that researchers are connecting with relevant collaborators and incorporating their perspectives throughout the conception, implementation, and dissemination of the research. Meaningful engagement should address what the researchers will learn and how the people with lived experience and/or collaborators will benefit from the partnership. To promote health equity, as is relevant for the research proposed, it is recommended that at least two people with lived experience from populations who experience health disparities should be meaningfully engaged in these efforts  . See this resource for more information in engaging people with lived experience: https://aspe.hhs.gov/lived-experience). 

PI 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 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 (if proposed) 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. 

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

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

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

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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 Government

• 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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

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. 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.

Letter of Intent

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: NIDALetterofIntent@mail.nih.gov
 

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

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 should not simply be a restatement of the specific aims for the R61 phase. 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.

Examples of Milestones for the R61 Phase:

• Fully executed 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  
• If preliminary data was not included in original application, preliminary data demonstrating feasibility of R33 phase must be included.

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

• Meetings and Travel:

HEAL Investigators’ Meeting: For budgeting purposes, include travel costs to support the attendance of one PD/PI (one person) at a 2-day, in-person HEAL Investigators meeting in the Washington DC area, annually for the duration of the award.

Additionally, NIH program staff may wish to periodically convene award recipients under this program, both virtually and in person. To plan for potential in-person meetings, budgets should include funds for travel for up to three people to participate in a 2-day meeting in the Washington DC every other year, beginning with the first year of award.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims:

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.

Research Strategy:

The Research Strategy 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 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: 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 dissemination, implementation and sustainability of prevention services and/or inform the development of an infrastructure thought which prevention services could be implemented.

Approach: The application should contain two approach sections, one for each phase 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. 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. 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 the delivery of prevention intervention services.

The approach section must address the following elements in the phase most appropriate to the proposed study:

• Discussion of methodology selected; methods may include implementation science, hybrid implementation/effectiveness studies, and dissemination research designs.
• A strategy for the meaningful engagement of relevant end users (e.g., policymakers, state and local level decision makers, practitioners, intervention implementers, families, youth, and community members) as partners, and plans for utilizing their expertise and perspectives. 
• Discussion of the sustainability of the proposed service delivery model with respect to funding and staffing should it prove to be successful; this may include a plan for how the services may be sustained or scaled after the study period ends.
• Considerations relevant to the potential generalizability of the proposed service delivery model, i.e., discussion of the model’s specificity to the selected intervention/prevention program and setting versus a framework that could be adapted for other programs and settings. 
• Strategies for addressing health disparities and inequities and the relevance to the interventions or services being studied. 

R61 Approach:

 The focus of the R61 phase is the pilot/foundational work needed to inform the larger study proposed in the R33. The R61 Approach section application should detail the strategies that will be taken in order to meet the milestones proposed in order to transition to the R33 phase.

R33 Approach

Although the Research Strategy for the R33 Phase is expected to be broad and flexible due to the nature of the exploratory research in the R61 Phase, the research strategy for the R33 phase of the award should be described in enough detail for reviewers to evaluate the merit of this component of the application, based on anticipated results.

The R33 phase may include a clinical trial if appropriate for the research questions and study design. Applications that propose a clinical trial in the R33 phase should include relevant information for the proposed clinical trial in the clinical trial attachment. As with milestones, the overall design of the R33 may be modified based on findings from the R61 phase, if appropriate. Any such modifications must be discussed in advance with NIH program staff and would be included in the transition application to be submitted towards the end of the R61 phase.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following additional instructions: 

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

The HEAL Initiative has additional requirements that must be addressed in the Data management and Sharing plan. All HEAL-generated data must be shared through the HEAL Initiative Data Ecosystem following HEAL’s compliance guidance (https://heal.nih.gov/data/complying-heal-data-sharing-policy). Specifically, HEAL applicants must include:

• Plans to submit data and metadata (and code, if applicable) to a HEAL-Compliant data repository (https://www.healdatafair.org/resources/guidance/selection) and follow requirements of the selected repository
• Plans to register your study with the HEAL platform within one year of award (https://heal.github.io/platform-documentation/study-registration/) 
• Plans to submit HEAL-defined study-level metadata within one year of award (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) and https://heal.github.io/platform-documentation/slmd_submission/.
• HEAL pain clinical studies must include plan to use HEAL core Common Data Elements (https://heal.nih.gov/data/common-data-elements). HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. 
• To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subject are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research. 
• Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used.
• To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms.  

HEAL has developed additional details and resources to fulfill these requirements (https://www.healdatafair.org/resources/road-map). 

HEAL Public Access and Data Sharing Policy: 

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications (https://heal.nih.gov/about/public-access-data). Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal.nih.gov/data/complying-heal-data-sharing-policy. Resources and tools to assist with data related activities can be found at https://www.healdatafair.org/. For more detail and specific data sharing requirements, see Section 4. Other plans.  

Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication. 

• For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access 
• Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests
•  

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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 SF424 (R&R) 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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. 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

Part I. Overview Information 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 SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 SF424 (R&R) 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.

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.

Overall Impact

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).

Scored Review Criteria

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this NOFO:  

• Are the methods appropriate for the work proposed?
• To what extent does the application include a strategy for the meaningful engagement of relevant end users (e.g., policymakers, state and local level decision makers, practitioners, intervention implementers, families, youth, and community members) as partners, and plans for utilizing their expertise and perspectives? 
• How comprehensive is the discussion of the sustainability of the proposed service delivery model with respect to funding and staffing should it prove to be successful? How extensive and/or realistic is the plan for how the services may be sustained or scaled after the study period ends? 
• How generalizable is the proposed service delivery model, i.e., discussion of the model’s specificity to the selected intervention/prevention program and setting versus a framework that could be adapted for other programs and settings? 
• To what extent does the application include strategies for addressing health disparities and inequities and the relevance to the interventions or services being studied? 
• How appropriate and how well specified are the R61 phase milestones given the work proposed? ? To what extent would they inform a decision of feasibility?
• To what degree does the R33 build logically from the R61?
   

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDA, 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.

Appeals 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 appropriate national Advisory Council or Board. 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.

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

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. 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, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 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.”

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

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 following all requirements and timelines developed through the HEAL Initiative Data Ecosystem (https://heal.nih.gov/about/heal-data-ecosystem), as described in HEAL’s compliance guidance (See “Already Funded” section: https://heal.nih.gov/data/complying-heal-data-sharing-policy):  
 

1. Select a HEAL – Compliant data repository (https://www.healdatafair.org/resources/guidance/selection)  

• Data generated by HEAL Initiative-funded projects must be submitted to study-appropriate, HEAL-compliant, data repositories to ensure the data is accessible via the HEAL Initiative Data Ecosystem.
• Some repositories require use of specific data dictionaries or structured data elements, so knowing your repository’s requirements up front can help reduce the burden of preparing data for submission.
• HEAL-funded awardees must follow requirements for selected repository  

2. Within one year of award, register your study with the HEAL platform (https://heal.github.io/platform-documentation/study-registration/) 

• This process will connect the Platform to information about your study and data, including metadata, and identify the selected repository. HEAL requests initial submission within one year of award, with annual updates, and to be updated in accordance with any release of study data.

3. Within one year of award, submit HEAL-specific study-level metadata. 

• Some of the required study-level metadata (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) will be auto-populated as part of the registration process. 
   

4. Submit data and metadata (and code, if applicable) to HEAL-Compliant repository  

• At the completion of the study and/or when prepared to make the final data deposits in the repositor(ies) of choice, ensure your study registration (https://heal.github.io/platform-documentation/study-registration/) is complete.
• The NIH HEAL Initiative expects data used in publications to be submitted to repositories at the time of or prior to publication, and no later than the end of the project period. 

5. Additional Requirements for HEAL Initiative studies conducting clinical research or research involving human subjects.

These studies must meet the following additional requirements: 

• HEAL Initiative trials that are required to register in clinicaltrials.gov should reference support from and inclusion in the HEAL Initiative by including the standardized terms “the HEAL Initiative (https://heal.nih.gov/)” in the Study Description Section.
• All new HEAL clinical pain studies are required to use core questionnaires required by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements). Outside of the core questionnaires, studies should select questionnaires from among the repository of supplemental questionnaires that are already being used by other HEAL clinical pain studies. The program has created the CDE files containing standardized variable names, responses, coding, and other information for all of these questionnaires The program has also formatted the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C § 794 (d); https://www.govinfo.gov/content/pkg/USCODE-2011-title29/html/USCODE-2011-title29-chap16-subchapV-sec794d.htm) which “require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities.” 
• Studies that wish to use questionnaires not already included in the HEAL CDE repository should consult with their program official and the HEAL CDE team. New questionnaires will be considered for inclusion in the repository on a case-by-case basis and only when appropriate justification is provided.  
• HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program (https://heal.nih.gov/data/common-data-elements). 
• To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subject are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.  
• To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms. 

Additional details, resources, and tools to assist with data related activities can be found at https://www.healdatafair.org/.  

All data collected as part of the NIH HEAL Initiative are so collected under a Certificate of Confidentiality and entitled to the protections thereof. Institutions who receive Data and/or Materials from this award for performance of activities under this award are required to use the Data and/or Materials only as outlined by the NIH HEAL Initiative, in a manner that is consistent with applicable state and federal laws and regulations, including any informed consent requirements and the terms of the institution’s NIH funding, including NOT-OD-17-109 and 42 U.S.C. 241(d). Failure to adhere to this criterion may result in enforcement actions.

Report and ensure immediate public access to HEAL-funded publications 

Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication.  

• For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access  
• Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests   

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

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.

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. 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

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)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Amy B. Goldstein, PhD
National Institute on Drug Abuse (NIDA)
Phone: 301-827-4124
Email: amy.goldstein@nih.gov 

Denise L Stredrick, PhD
Office of Disease Prevention (ODP)
Phone: 301-594-7553
E-mail: stredrid@mail.nih.gov
 

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: (301) 496-9350
E-mail: devon.oskvig@nih.gov

Jennifer N. Baumgartner, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-402-4084 
Email: jennifer.baumgartner@nih.gov

Dharmendar Rathore, PhD
National Institute on Drug Abuse (NIDA)
Phone: 301-402-6965
Email: dharmendar.rathore@nih.gov

Lennin Greenwood 
National Institute on Drug Abuse (NIDA) 
P hone: 301-824-0478 
Email: lennin.greenwood@nih.gov 

Kathleen Moy
National Institute on Aging (NIA)
Phone: 301.827.2856
E-mail: kathleen.moy@nih.gov

Wen G. Chen, M.MSc, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-451-3989
Email: chenw@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 45 CFR Part 75 and 2 CFR Part 200.