It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

As part of NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis, NIDA is launching the HEAL Preventing Opioid Misuse and Opioid Use Disorder in Older Adolescents and Young Adults (ages 16-30) initiative. The HEAL prevention initiative will consist of up to ten research projects and one coordinating center. This prevention initiative is designed to solicit research to develop, adapt and test interventions and strategies to prevent initiation of opioid misuse and development of Opioid Use Disorder (OUD) in at-risk older adolescents and young adults (ages 16-30). Of priority are studies that target older adolescents and young adults in health care settings (including emergency departments, surgical, orthopedic and other specialty care, dental care, primary care, urgent care, HIV/STI and reproductive health clinics, prenatal clinics, primary care, federally qualified health centers, school-based health centers, military medicine settings, and occupational health settings); justice settings (including criminal justice, juvenile justice, as well as child welfare and other systems that intersect with the justice system); and, other systems and settings opportune for accessing and engaging at-risk older adolescents and young adults.

An estimated 11.4 million people misused opioids in 2017, of which 11.1 million misused prescription opioid analgesics. Opioid drugs, including opioid analgesics, heroin and illicit synthetics, accounted for more than 60% of overdoses in 2016. There is need to develop preventive strategies that can decrease the incidence and prevalence of opioid misuse and OUD, particularly in at-risk populations. This initiative focuses on older adolescents and young adults (ages 16-30), two of the populations at highest risk for initiation and misuse of opioids, OUD and related consequences, including overdose fatalities.

Currently, evidence-based interventions exist to prevent substance use broadly, that predominantly target children and adolescents. However, there is a gap in the evidence for interventions and strategies to prevent non-medical use of opioids and OUD in the transition from adolescence to young adulthood. The urgency of the opioid crisis calls for research to produce evidence based interventions and strategies to prevent older adolescents and young adults from initiating non-medical use of opioids, escalating from initiation to misuse, and escalating from misuse to OUD.

This funding opportunity is being offered as 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 will bolster 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://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.

Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.

For this FOA, NIDA is seeking applications for research studies to be part of a cooperative agreement that will be comprised of two components: 1) UG3/UH3 research projects solicited under this RFA, and 2) a single coordinating center, which will provide logistical and scientific support related to data collection and management, implementation design and methodology consultation and economic evaluation, to be solicited under a separate FOA. The objectives of this research cooperative are to support rigorous research to: 1) develop strategies to identify, reach, and engage older adolescent and young adult populations at risk for opioid misuse and OUD in prevention interventions and services, 2) develop and adapt interventions and strategies to prevent initiation of opioid misuse, escalation from initiation to misuse, and escalation from misuse to OUD, 3) test the effect of prevention strategies and interventions on initiation of opioid use, opioid misuse, OUD and other opioid related outcomes, 4) develop and test strategies to facilitate implementation and sustainability of prevention interventions and strategies in health care, justice and other systems and settings opportune for accessing and engaging at-risk older adolescents and young adults, and, 5) conduct an economic evaluation (e.g., to quantify programmatic costs and cost-effectiveness of interventions and strategies). Research projects funded under the cooperative are expected to address all five objectives. Of priority are studies that target older adolescents and young adults in health care settings (including emergency departments, surgical, orthopedic and other specialty care, dental care, primary care, urgent care, HIV/STI and reproductive health clinics, prenatal clinics, federally qualified health centers, school-based health centers, military medicine settings, and occupational health settings); justice settings (including criminal justice, juvenile justice, as well as child welfare and other systems that intersect with the justice system); and other systems and settings.

For this FOA, opioids include prescription opioids and illicit opioids, such as heroin and illicitly made fentanyl (and related analogs). For the purpose of this announcement, prevention is defined as interventions that occur prior to the onset of OUD and are intended to prevent or reduce risk for OUD. OUD refers to the clinical diagnosis defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). This FOA seeks research that addresses the appropriate level of risk for the target population and setting (universal, selective, indicated, as defined in the IOM 2009 report). Given the priority on high-risk older adolescents and young adults, selective interventions (targeted to individuals or a subgroup of the population whose risk is significantly higher than average), indicated interventions (targeted to high-risk individuals who are identified as having detectable signs and symptoms but not at the level of a disorder) as well as tiered interventions (that include two or more levels) are of particular interest for this FOA (IOM 2009).

Older adolescence and young adulthood are two distinct and important life stages that can involve significant transitions, change and challenges, particularly for vulnerable and at-risk groups. For some, these periods can involve transition to greater autonomy and independence, which might include participation in the workforce, the military, or entry into college or vocational training. Others might be aging out of the juvenile justice or foster care systems or re-entering the community after being institutionalized. This time of increased decision-making and autonomy is also a period of increased risk for substance use, including opioid misuse and development of OUD, particularly for already vulnerable populations. Identifying, accessing, engaging and retaining at-risk older adolescents and young adults in prevention programs can be particularly challenging, as they may neither be working nor in school/college; they may be disconnected from parents/caregivers, family and other social supports; and/or, they may have an unstable living situation. It is important that prevention programs include strategies to identify, engage and intervene with at-risk, vulnerable groups in an array of settings and with a variety of intervention modalities and strategies.

While the prevention field has made significant progress leading to the identification of effective approaches and strategies to prevent substance use and substance use disorders in children and adolescents, research is needed to develop more effective strategies to prevent opioid misuse and OUD for emerging and young adults. The opioid epidemic presents a potentially unique challenge because of the role that prescription and non-prescription drugs play in treating pain and other medical conditions. This FOA encourages research that takes advantage of existing evidence-based prevention strategies, interventions or models that might be applicable and translatable for preventing opioid misuse and OUD, for example from the drug abuse field broadly, alcohol, suicide, mental health or other fields. Interventions proposed should be theory-based, and the theory and rationale behind the interventions proposed should be clearly described. In addition, interventions proposed should be developmentally appropriate for the target age group of the study, and developmental relevance and tailoring should be clearly explained.

The expectation is that the suite of research studies funded under this FOA will yield efficacious/effective interventions and strategies to prevent initiation of opioid misuse and development of OUD in older adolescents and young adults that will be adopted in health care systems, justice systems and other systems and settings that may be opportune places to reach high risk populations and deliver prevention interventions. Studies proposed under this FOA may span the range of efficacy, effectiveness, and implementation research, and/or propose hybrid study designs relevant to the intervention and research questions proposed. Of interest are research studies designed to test whether an intervention engages a proximal target or specified mechanism presumed to underlie the intervention's effect on a distal outcome. Investigators are encouraged to test hypotheses regarding moderators, mediators and mechanisms of action of interventions. Applications proposing effectiveness trials are encouraged to address the use of scalable and sustainable approaches to improve the uptake of promising interventions. Study designs proposed should be rigorous and appropriate for addressing the research questions proposed within the project timeline. Applicants are encouraged to leverage existing NIDA or NIH-funded networks as platforms for research, to facilitate recruitment and conduct the research.

This FOA encourages, but is not limited to, research applications that address the following areas of interest:

Development of theory-based prevention interventions that can be integrated into health care, justice, or other human service systems and settings for high-risk individuals, including interventions and strategies that address the unique needs of racial/ethnic minority populations and underserved communities. This includes including adaptation of existing evidence-based interventions to address opioids.

Studies to test models of integrating existing substance use prevention and other risk reduction modalities (e.g., motivational interviewing, skill building, enabling of prosocial relationships) into health care, justice or other human service systems.

Implementation of evidence based substance use prevention interventions that incorporate technology, such as mobile health and telehealth delivery or models of consultation, to facilitate linkage and delivery in settings such as primary care and other settings where delivery of prevention interventions is novel.

Research on interventions designed to address known risk factors for risk behaviors such as sensation seeking, impulsivity or others.

Studies to develop and test prevention interventions designed to prevent misuse of opioids and development of OUD in older adolescents and young adults at risk for and who have mental disorders (e.g., depression, anxiety, post-traumatic stress disorder, serious mental illness, suicide ideation and behaviors).

Research that utilizes risk-profiles in dental, orthopedic, surgical, pain, primary care, or other clinical settings to facilitate case identification, active referral and linkage to prevention interventions and or consultation models. For example, using electronic health records and service delivery data collected during routine care to modify opioid prescribing, offer patient education, or provide enhanced pain strategies for people whose alcohol or other drug use may indicate that they are at risk for opioid misuse.

Development and testing of public awareness and communication strategies as part of a broader intervention or strategy targeted to high risk populations in health care, justice, community and other settings, delivered through mobile technology, social media and other novel platforms.

Research on novel funding strategies to implement and sustain prevention interventions, such as Medicaid waivers, reimbursement for telehealth service delivery and consultation.

Research to address system fragmentation and gaps for persons transitioning from pediatric or adolescent medicine practices to adult medicine practices or for persons in specialty settings or social services systems who need linkage to health/behavioral health and prevention services.

Testing of strategies to implement preventive interventions in ways that overcome stigma related to substance use and its consequences, such as discrimination based on substance using behavior. This might include incorporation of content and activities to reduce self-stigma on the part of participant populations, stigma in delivery of basic services to substance users (e.g., discriminatory channels for service; treatment by reception, billing and other non-service provider staff).

This FOA is not focused on research to address general health or global functioning.

Organization of the Cooperative

The cooperative will include up to ten research projects, one Coordinating Center, a Steering Committee (SC), a SC chairperson, one or more Science Officers from NIDA and/or other Institutes, and NIDA and/or other Institute Program Officers.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see (http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding-) for details.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org). Please see NOT-DA-12-008 (https://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

Methodological and Statistical Resources: Applicants are encouraged to employ the strongest prevention study designs and analytic methods. For guidance on state of the art study designs, methods and analytic techniques please visit these resources developed by NIH on Training in Prevention Methods Research, Resources for Researchers and GRTs.

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

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

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

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)
• 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 not 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement. More information on cost matching requirements is in Section IV.2 R&R or Modular Budget

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. 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 NOT-OD-11-101).

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to: NIDALetterofIntent@mail.nih.gov.

Applicants are encouraged to send the letter of intent by email to the email address above but as an alternative, the letter may also be sent to:

Office of Extramural Policy and Review
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

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 FOA.

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.

Other Attachments:

Timelines

Applicants are required to propose well-defined timelines for the entire project, i.e., for both the UG3 and the UH3 phases. Applications must describe timelines that could include, but are not limited to, meeting specified enrollment targets, assessments and data collection, and transition from the UG3 to the UH3. Applications lacking timelines for the UG3 and the UH3 phase will be considered incomplete and will not be reviewed.

Applicants must include clearly identified milestones for successful completion of the UG3 phase at the end of Year 1 or 2 and transition to the UH3 phase for 3 or 4 years of additional funding. A restatement of an application specific aim is not considered an adequate transition milestone. Applications lacking milestones for the transition from the UG3 to the UH3 phase will be considered incomplete and will not be reviewed.

This attachment must not exceed 3 pages.

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

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

Budgets should include funds for travel for the PD(s)/PI(s) and other key personnel (e.g., key project staff, a stakeholder/collaborator from the system/setting where the study will be implemented to participate an in-person Steering Committee meetings one time per year, every year of the award, in Rockville, MD. An additional in-person kickoff meeting to be held in Rockville, MD should be included in the year one budget of the award.

In addition to executing the proposed protocol, applicants will be expected to participate in efforts to harmonize data collection and participate in other trans-cooperative activities. Time should be budgeted to participate in such activities.

Cost Matching Requirement for For-profit Applicants
Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA. The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.
Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
a) Costs borne by another Federal grant or sub award;
b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
(d) Program income; and
(e) Patient incentives.
The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.
Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.

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:

Research Strategy:

The UG3 phase supports a project with specific milestones to be accomplished by the end of the first 1- or 2-year budget period. Phase I UG3 exploratory-developmental activities include scientific and operational planning activities. Scientific planning activities include development, adaptation or refinement of interventions or strategies; feasibility, acceptability and pilot testing of a proposed intervention or strategy; development and testing of engagement and implementation strategies (e.g., fidelity monitoring, training). Operational planning activities, at a minimum, include development of: the intervention, strategy or model protocol; the intervention manual or equivalent (as appropriate); data collection and management safety and operational oversight plans; recruitment, engagement and retention strategies, regulatory approvals (e.g., IRB, DSMP) and other essential documents and procedures.

The UH3 phase is to provide funding for up to 4 additional years (for 3 years if the UG3 phase lasts 2 years) to those projects that successfully complete the milestones set forth in the UG3 phase. UG3 projects that have met the milestones for the first phase (e.g., scientific, operational, feasibility, pilot) will be programmatically considered and prioritized for transition to the UH3 phase. The UH3 phase award will support the conduct of the clinical trial to test efficacy, effectiveness, mechanisms of action (moderators and mediators) of interventions/strategies that demonstrate promise in the UG3 phase, in addition to implementation and economic evaluation relevant to the research proposed. The Coordinating Center will provide consultation to the research projects and cooperative pertaining to implementation design and methodology, as needed, as well as for economic evaluation.

All applications must provide the overall goals and hypotheses for the entire project and indicate separate specific aims to be accomplished in the UG3 phase and the UH3 phase. In addition, projects must include clearly identified transition milestones to be assessed at the end of the UG3 phase. This must include milestones pertaining to recruitment, feasibility, preliminary pilot data, and demonstrated readiness to launch into the second, clinical trial phase. Also, separate sections that describe the research strategy for the UG3 and the UH3 phases are required. Investigators should consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application with regard to specific goals, feasibility, approach, and the transition milestones are critical. It is not necessary to repeat information or details that are described in the UG3 section in the UH3 section.

Funding of the UG3 (Phase 1) does not guarantee support of the UH3 (Phase 2) award. It is anticipated that some funded UG3 projects might not transition to the UH3 phase. Transition to the UH3 phase will be determined by a programmatic evaluation by NIH staff. Continued programmatic priorities and availability of funds also affect the decision to transition to the UH3 award. Appeals of the transition decision will not be accepted.

Applications should clearly detail:

Inclusion and the role of a collaborator or stakeholder (as co-investigator) from the system or setting where the research will be conducted, who will assist with the adoption of the intervention or strategy in that system or setting if it is found to be successful.

A clear description of the theoretical basis for the intervention, strategy or model proposed and the process or steps for development, adaptation, tailoring to the population and system or setting proposed.

Strategies for identifying, reaching, and/or engaging an at-risk population identified for the project, and strategies for linkage to prevention intervention or services.

A clear description of the primary and secondary outcomes that will be evaluated and the proposed measures for both the UG3 and UH3 phases.

A description of the analytic plan for the UG3 and the UH3 phases of the research, including statistical and other methods to be employed should be included.

A description of the team’s experience with developing/testing/implementing prevention interventions, the identified study population (age range/developmental stage and other characteristics), and the systems or settings where the research will be conducted.

A description of previous experience with cooperative agreements or with multi-site studies that include components such as common protocols or data harmonization.

Plans to protect the security of participants personally identifiable information.

A discussion of any impediments that could require an addendum to the research plan, milestone, or timeline with a discussion of alternative approaches.

A strategy to engage and create partnerships with likely end user(s) of the intervention or strategy proposed, and letters of support indicating commitment from end users to implement the intervention or strategies if the outcomes are favorable.

Letters of Support
For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources.

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 modification:

• All applications, regardless of the amount of direct costs requested for any one year, should provide a plan for sharing data with other research sites and the coordinating center.
• All applications, regardless of the amount of direct costs requested for any one year, should provide a plan to make data publicly available.

Projects funded under this FOA are expected to work collaboratively toward core data collection measures and methods, as appropriate, that will enable the construction of data sets that are harmonized and facilitate progressive data sharing models. Consistent with achieving the goals of the program, finished, de-identified datasets are expected to be made available for the research community at the close of the study through deposit at the National Addiction and HIV Data Archive Program: https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/about.html or another site to be determined by the Steering Committee of the cooperative agreement.

Steps also are expected that enable sharing of research findings with the broader research, public health, and health services communities. Applications are, therefore, expected to provide a well-thought-out plan for widely sharing data and resources generated by the research project. After all awards have been made, the Steering Committee, will develop a unified policy for data and resource release, such as harmonized interview instrument(s) and other data collection. During the study the Steering Committee will consider as a group (and usually by consensus) various proposals to analyze aggregate data and will support such efforts. The application is expected to include a statement that the investigators will abide by the Steering Committee’s data and resource policy, consistent with the relevant NIH policies, laws and regulations.

Use of Common Data Elements (CDEs) such as those defined on the on the National Library of Medicine website (https://www.nlm.nih.gov/cde/) is encouraged.

It is anticipated that applicants may propose new approaches for informed consent that improve participant understanding and allow for use of data across a range of health and other electronic platforms.

Appendix:

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

Letters of Support: Provide all appropriate letters of support, including any letters necessary to demonstrate the support of collaborators, stakeholders (e.g., end users), and others.

When involving NIH-defined human subjects research, clinical research, and/or 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.

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 Policy on Late Application Submission.

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.

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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number 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. Any instructions provided here are in addition to the instructions in the policy.

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.

For this particular announcement, note the following: The UG3/UH3 exploratory/developmental phased grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. A UG3/UH3 grant application is not required to have extensive preliminary data, background material or preliminary information, but these may be included if available. Appropriate justification for the proposed work can also be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, the potential to significantly advance knowledge or understanding and have an impact. Reviewers will assign a single impact score for the entire application, which includes the UG3 and UH3 phases.

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

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

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?

Does the application target an at-risk older adolescent and young adult population and/or a setting where at-risk populations can be accessed/engaged for prevention interventions and services? To what degree does the project hold promise for advancing the evidence base for interventions and strategies to identify, reach, engage, and intervene with older adolescents and young adults to prevent initiation of opioid misuse, escalation from initiation to misuse, and OUD? Can the intervention or strategy be expected to be adopted by the system or setting if found to be successful? Can the intervention or strategy be sustained beyond the study, without additional research grant support?

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?

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?

Do the PDs/PIs, co-investigators, and collaborators include key personnel who have demonstrated experience with prevention intervention research, older adolescents and young adults, and high-risk populations? Do the PDs/PIs and collaborators include key personnel who have demonstrated experience doing research in the settings proposed for the projects?

Is a collaborator or stakeholder from the system or setting where the proposed intervention or strategy will be studied included as a co-investigator on the research team? Do the investigators have experience with cooperative agreements or other multi-site or multi-project studies that require collaboration among project sites such as common protocols and data harmonization?

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?

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?

Does the project propose novel, plausible strategies for identifying, reaching, engaging and providing prevention interventions and services to at-risk older adolescents and young adults? Are novel approaches taken to identify and reach at-risk populations and facilitate linkage to prevention interventions and services in health care, justice and other opportune systems and settings?

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?

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?

How well does the research project clearly identify a scientifically justifiable strategy for the UG3 phase of the project? How well does the project's conceptual framework clearly inform the analysis of data and potential pathways for the UH3 phase? How successful is the UH3 phase in proposing novel intervention/service delivery strategies and approaches that have a clear pathway from the UG3 data?

Does the application describe how the project team will work within the cooperative structure taking into account the Coordinating Center s role to provide coordination and communication, data collection and management, implementation design and methodology consultation, and conduct economic evaluation?

Are potential barriers and challenges acknowledged and how adequate are alternative approaches considered? How achievable are the proposed milestones for the UG3 grant?

Are appropriate stakeholders, relevant to the population to be included in the research and the system/setting proposed for the project, included on the research team or the project? Are strong letters included from stakeholders, demonstrating support for the research as well as for implementing the interventions and strategies if the outcomes are favorable?

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?

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?

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?

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?

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

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)?

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.

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.

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 Animal Section.

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.

Not applicable.

Not applicable.

Not Applicable

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.

Not applicable.

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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.

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

Specific to this FOA:
How likely is it that the plans for cost matching will be adequate?

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:

• 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.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 FOA. 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.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee 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).

Special award condition specific to this FOA: A grantee from a for-profit organization funded under this announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018. See 45 CFR 75.306 for additional details. Matching funds must be non-Federal funds set aside for this project and are available from the source(s) identified in the application, as committed to by the recipient. Cost matching will be evaluated by the awarding office to ensure that this requirement is being met. Compliance with the matching requirement must be verified on an annual basis and must be documented in the annual and final FFR.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Prior to the end of the UG3, awardees will submit the transition package, which will include the UG3 progress report delineating progress toward achieving UG3 milestones.

All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators.

The awardee agrees to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the study including those outlined under "NIH Staff Responsibilities" and to work cooperatively with other awardees and the Coordinating Center where it is scientifically advantageous to pursue common methods and protocols.

Awardees will participate in annual meetings of the awardees and will support any committees, task forces, and advisory panels related to the project, as needed and will participate in regularly scheduled conference calls with the awarding agency. Project budgets should include travel for participation in these activities.

Upon implementation of the project, each awardee will follow the procedures required by the protocol regarding study conduct and monitoring and data collection.

Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIH support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur with the concurrence by the NIH Program Officer to ensure objectivity of research.

Obtaining prior written approval of the NIH Grants Management Specialist in consultation with the NIH Program Officer for a change in any of the key personnel identified in the Notice of Award.

Award recipients will own the rights in any tangible work products created under the terms of the cooperative agreement. Work products may include such things as research reports, papers, research, findings, training curricula, data sets, books, patient tools, and other materials. All such products shall be made accessible to the public under NIH’s Public Access Policy https://publicaccess.nih.gov/ and are subject to Government rights of access, as appropriate, in accordance with NIH’s legal directives and authorities.

NIH Staff Responsibilities:

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIH Project Scientists will have access to the data and work with the PD(s)/PI(s) to ensure the objectives of the program are being met. The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the NIH Project Scientists.

NIH staff will act as resources and facilitators for activities of the awardee, and will coordinate activities with federal and non-federal agencies outside of the project awardees.

The NIH, as primary funder and administrator reserves the right to phase out or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting. NIH support of this study is contingent upon adequate participant recruitment based on the Grantee’s Milestone Accrual Plan submitted at the time of funding.

NIH staff will ensure the grantee demonstrates best effort compliance. Failure to achieve minimally acceptable milestone recruitment levels may result in the withholding future support and/or negotiating an orderly close-out of this study.

NIH staff will serve as resources to provide: scientific/programmatic support in the development and modification of study protocols and the design of project activities; advice in the selection of sources or resources; advice in management and technical performance; and assistance in the preparation of publications, as warranted.

NIH staff will participate in the monitoring of issues relating to recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting as needed to the coordinating center.

NIH Scientific Program Officers will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(s) and his/her staff, periodic site visits for discussion with the awardees research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship matters.

Additionally, NIH will appoint Program Officials who will be responsible for the normal scientific and programmatic stewardship of the award, and will be named in the award notice.

Areas of Joint Responsibility include:

The PD(s)/PI(s) provide, in concert with the NIH staff, support necessary to ensure that sites and investigators, and NIH and other research partners fully comply with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.

Awardees and NIH will jointly develop appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data.

All awardees and NIH will cooperate to ensure the timely and broad dissemination of lessons learned, to inform researchers and health care, justice and other systems.

The Steering Committee is the primary governing body of the cooperative. Awardees must participate in the Steering Committee. The Steering Committee reviews and approves the research agenda, develops and monitors policies and procedures guiding the research activities, and oversees communications. Awardees agree to abide by the procedures and policies established by the Steering Committee.

The Steering Committee, with the support of the Coordinating Center, will facilitate these joint activities and, in particular, development of research protocols, human subjects and other regulatory protocols, data harmonization, manuscript and other information dissemination planning, and initial clearance of manuscripts or other dissemination products.

When multiple years are involved, awardees 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 Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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.

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: http://grants.nih.gov/support/ (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: 301-945-7573

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

Dena Fischer, DDS, MSD, MS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: dena.fischer@nih.gov

Jacqueline Lloyd, PhD, MSW
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-8892
Email: lloydj2@mail.nih.gov

Wendy Weber, N.D., Ph.D, M.P.H.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-402-1272
Email: weberwj@mail.nih.gov

Lori Ducharme, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-8507
Email: lori.ducharme@nih.gov

Eve E. Reider, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-827-1496
Email: ereider@mail.nih.gov

Jennifer Alvidrez, PhD
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-9567
Email: jennifer.alvidrez@nih.gov

Gerald McLaughlin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5819
Email: gmclaughlin@nida.nih.gov.

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Edith Davis
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6697
Email: edavis1@mail.nih.gov

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301.594.3788
Email: carows@mail.nih.gov

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA )
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Bryan S. Clark, M.B.A
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Phone: 301-435-6975
Email: clarkb1@mail.nih.gov

Tamara Kees
National Institute on Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mail.nih.gov

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: pg38h@nih.gov

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.