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

The National Institute on Drug Abuse (NIDA), in partnership with the Substance Abuse and Mental Health Services Administration (SAMHSA) is soliciting cooperative agreement applications with the intention of ultimately funding up to three research sites and one data coordinating center (DCC) (see RFA-DA-19-017) to participate in the: HEALing Communities Study: Developing and Testing an Integrated Approach to Address the Opioid Crisis (HEALing Communities Study). The HEALing Communities Study will test the immediate impact of implementing an integrated set of evidence-based interventions across healthcare, behavioral health, justice, and other community-based settings to prevent and treat opioid misuse and Opioid Use Disorders (OUD) within highly affected communities. Highly affected communities of interest could include counties or cities within states that are burdened with higher than average rates of overdose mortality and opioid-related morbidity, and other complications. Combined, all the communities participating in a single research site application must demonstrate having experienced at least 150 opioid related overdose fatalities (15% of these fatalities must be from rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher in the past year, based on the most recent complete year of data available. States within the top third for age-adjusted drug overdose death rates in 2016, (per the Centers for Disease Control and Prevention) are of special interest. The integrated set of evidence-based prevention and treatment interventions should be designed to achieve the following goals: reduce overdose fatalities (by 40% over a 3-year period), and events; decrease the incidence of OUD; and increase the number of individuals receiving medication for OUD, retained in treatment beyond 6 months, and receiving recovery support services, and the distribution of naloxone compared to baseline.

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.

Communities across the US are dealing with the catastrophic consequences of greater availability of opioids including prescription opioids and illicit opioids, such as heroin and illicitly manufactured fentanyl (and related analogs). Millions of Americans are struggling with inappropriate use of opioids, and OUD. The consequences of this crisis are grave with continued increases in overdose fatalities. In addition, rates of OUD and injection drug use, acute hepatitis C virus (HCV) infections, localized outbreaks of HIV, and other serious health conditions such as endocarditis and neonatal abstinence syndrome continue to rise.

One driver of the opioid crisis is the recognized gap between the number of individuals who could benefit from a prevention or treatment intervention to reduce opioid use and OUD and those engaged in care. Currently, a menu of evidence-based prevention and treatment interventions exist including school and community based primary prevention, prescription drug monitoring programs and other strategies to reduce inappropriate opioid prescribing, medications for addiction treatment, behavioral therapies, and recovery support services. Unfortunately, these evidence-based interventions have largely failed to penetrate community settings including addiction treatment, general medical care, social support services, schools, and the justice system. This failure is in part due to a lack of evidence-based approaches for assisting communities in the development and deployment of a data driven custom-designed response strategy to deliver comprehensive integrated evidence-based interventions.

NIDA, in partnership with SAMHSA, is soliciting applications for research sites to participate in the HEALing Communities Study: Developing and Testing an Integrated Approach to Address the Opioid Crisis. The objectives of this multi-site research cooperative are to support rigorous research to: 1) determine the health impact of implementing a data-driven multi-pronged approach to opioid misuse and OUD by enhancing the systematic delivery of evidence-based prevention and treatment interventions across multiple settings (required settings include healthcare, behavioral health, and justice); 2) identify facilitators and barriers to implementation and sustainability, including relevant payment policy strategies; 3) determine the incremental cost and cost-effectiveness of this multi-pronged approach; and 4) develop an evidenced based model for deploying effective data-driven multi-pronged approach(es) to reduce overdose deaths and prevent and treat opioid misuse and OUD in affected communities across the US.

Highly affected communities of interest could include counties, towns or cities (or a justified aggregate of counties, towns, or cities functioning as one community) within states burdened with higher than average rates of opioid-related overdose morbidity and mortality and other health consequences associated with opioid misuse. For this FOA there is a special interest in states ranking in the top third of age-adjusted drug overdose death rates in 2016, per the Centers for Disease Control. For a particular application, all of the communities participating in the research must be located in the same state and 30% of them must be rural (https://www.ruralhealthinfo.org/am-i-rural/help). For this FOA, the minimum threshold for highly affected" communities is having at least 150 opioid related overdose fatalities (15% of these fatalities must be from rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher, based on most recent complete year of data available. States within the top third for age-adjusted drug overdose death rates in 2016, (per the Centers for Disease Control and Prevention) are of special interest. For this FOA, opioids include prescription opioids and illicit opioids, such as heroin and illicitly made fentanyl (and related analogs). OUD refers to the clinical diagnosis defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Applications must include plans to target multiple communities within a single state. The communities must be highly burdened by mortality, morbidity, and other health and psychosocial complications related to opioid misuse and OUD, and meet the minimum threshold specified above. The integrated set of evidence-based prevention and treatment interventions should be designed to reduce opioid overdose fatalities by at least 40% in three years (See Research Strategy section 2. Content and Form of Application Submission), across the combined communities participating in the cooperative agreement. Secondary aims of interest should be part of a linked pathway to reducing overdose fatalities. Required secondary outcomes to be addressed in communities participating in the research site include: reducing number of overdose events; decreasing the misuse of opioids, decreasing incidence of OUD and progression in severity to OUD or injection drug use; increasing the number of individuals (and percentage of individuals with OUD) receiving medication (methadone, buprenorphine, or naltrexone) and behavioral treatment; increasing the number of individuals and percent of individuals receiving medication and/or behavioral treatment that are retained in treatment beyond 6 months; increasing the number and percent of individuals participating in or completing treatment that are receiving recovery support services; and increasing access to naloxone.

In addition, applications must include structural aims that could decrease overdose fatalities and impact secondary outcomes. Required structural aims include approaches for:

• changing prescribing patterns to reduce the supply of prescription opioids
• increasing the number of specialty treatment programs that provide medications for OUD
• increasing the number of providers (doctors, nurses, nurse practitioners, physician assistants, pharmacists) prescribing and/or monitoring medications for OUD
• increasing the number of providers (physicians, nurse practitioners, physician assistants) with a DATA 2000 waiver to prescribe buprenorphine in the office-based setting
• increasing the availability of naloxone across a community to reduce fatal overdose fatalities
• creating programs that can readily link individuals to treatment following an opioid overdose
• increasing the use of screening to identify opioid misuse and intervention(s) to address misuse within healthcare and other settings
• increasing evidence-based school and community-based opioid prevention services
• increasing number of formal linkages between the justice system and healthcare and behavioral health

Other secondary aims and outcomes would target other health conditions related to opioid misuse and OUD including but not limited to: monitoring the incidence of hepatitis C, HIV, endocarditis associated with injection drug use, neonatal abstinence syndrome, and improving access to prevention and treatment services for these conditions. Optional secondary aims, including structural aims, must be justified in the application.

Applications must include data in each community related to the primary outcome of opioid overdose fatalities and rates. Applicants should include the past two years of data available for communities to characterize opioid specific and other drug related overdose fatalities and rates to begin characterizing the trend. They should also include plans for improving the collection and quality of that data. Applicants must also propose how they will collect other data related to the required individual and structural level secondary outcomes and any optional outcomes included in the application. In addition, they must describe and ensure high quality data for all outcomes proposed in the study.

NIDA and SAMHSA recognize the complexity and heterogeneity of the opioid crisis across the country involving: variations in drug markets, demographics of individuals misusing opioids or with OUD, prevention and treatment infrastructure and capacity, legal and regulatory issues associated with OUD treatment, structure of financing and availability of health insurance, severity of stigma, justice system approaches, and socio-economic and policy differences within communities. This heterogeneity requires research sites to work with highly affected communities to understand the unique aspects of their opioid crisis, available resources, and develop a tailored approach to effectively address local needs.

Research site applicants are therefore required to propose a conceptually driven approach (e.g. the Communities that Care model for integrating evidence-based prevention, https://www.communitiesthatcare.net , or other comprehensive community implementation models) to guide communities through the process of 1) organizing and implementing a local coalition to provide local leadership and context for the interventions; 2) using standardized data to explicate the nature, severity and trends of the local opioid crisis, including prevention and treatment resources and gaps; 3) developing a data-driven strategic plan to implement evidence-based prevention and treatment interventions linked to local needs across multiple systems with goals, milestones, training, and technical support; 4) deploying the strategic plan; 5) measuring the impact; and 6) adjusting interventions based on these assessments of impact.

Specific evidence-based prevention and treatment interventions will vary according to community need and infrastructure but at a minimum must include interventions aligned with the required study aims above in the following areas: prevention efforts related to opioid use, misuse, OUD, and overdose; screening and assessment of opioid misuse and OUD; linkages and engagement in treatment; use of medications and behavioral therapies to treat OUD; and ongoing recovery support services. Applications also must specify plans to deliver these integrated evidence-based interventions across multiple settings and are required to include healthcare, behavioral health, and justice settings. Other community based settings should be included as appropriate to their role in addressing the prevention and treatment of opioid misuse and OUD and the reduction of opioid overdose.

Each research site is required to select at least 15 communities, of which at least 30% must be rural, within a single state to participate in the research. There are a number of geographic classifications for rural . For additional information see: https://www.ruralhealthinfo.org/am-i-rural/help. A community may be a county, a city or town, or a well justified collection of counties, cities, and/or towns that will be treated as a single community. The research plan must include a clear justification for selection of these communities based on overdose mortality, and opioid-related morbidity, and other complications associated with the opioid crisis and the infrastructure and resources leveraged to collect data, provide services, train clinicians, conduct the research, etc. Applicants are also encouraged to include communities with Native American/American Indian populations and work with local tribal leaders to include tribal communities in the study. Also, the research plan must address how variability in population size for the communities will be addressed since this impacts study power (e.g. aggregating communities with a smaller population into a single unit, so that all proposed communities or community aggregates are of similar size).

NIDA and SAMHSA anticipate reaching a total of 40-50 communities through all funded HEALing Communities Study research sites. In considering what communities to include in the study, applicants must demonstrate a strong understanding of the magnitude of the opioid problem in the proposed study communities and ensure that sufficient numbers of individuals and a sufficient rate of individuals per 100,000 are affected by opioid misuse, OUD, and opioid related overdose fatalities to have reliable estimates of impact. This is particularly true for opioid overdose fatalities, a relatively rare outcome. Thus, applicants must document that a total of at least 150 opioid related overdose fatalities (at least 15% of the fatalities occurred in rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher were reported across the combined proposed study communities, based on most recent complete year of available data. Communities within states ranking in the top third of age-adjusted drug overdose death rates in 2016, per the Centers for Disease Control and Prevention are of special interest.

Applicants must provide plans for leveraging toolkits, decision support tools, platforms, infrastructure, data collection initiatives, and prevention, treatment, and recovery support services funded via federal, state, local, foundation, and other entities to address the opioid crisis (e.g. services supported by state, local, and philanthropic initiatives, justice-led initiatives, Centers for Disease Control and Prevention programs, Health Resources and Services Administration funding, etc. These platforms and resources should address both data collection and the delivery of prevention and treatment services.

Applicants should specifically demonstrate how they plan to leverage SAMHSA funding provided to states and local jurisdictions for the provision of evidence-based prevention, treatment, and recovery support services. SAMHSA funding includes grant programs such as the State Opioid Response grants, State Targeted Response Grants, Medication-Assisted Treatment Prescription Drug and Opioid Addiction, CARA First Responders and state-based naloxone programs, drug court and offender re-entry programs, Building Communities of Recovery, and programs for pregnant and postpartum women programs. Information on all of SAMHSA grant programs can be found at https://www.samhsa.gov/grants.

In addition, applicants should demonstrate how they plan to reduce health coverage payment barriers related to medication for OUD and supporting services, such as behavioral health services, including through the state Medicaid program. The Centers for Medicare and Medicaid Services (CMS) has established opportunities for state Medicaid agencies through 1115 demonstration waiver authority to have greater flexibility to tailor their Medicaid programs to address OUD, has issued clarifications on using Medicaid funding to enhance technology systems used to address the opioid epidemic, and has outlined a framework for states to provide Medicaid services related to authorities. States interested in technical assistance related to these activities can review online resources or email: [email protected].

Applicants must propose a cluster study design (e.g. a parallel group- or cluster-randomized trial, or a cluster stepped wedge design) to test effects of the "intervention" in the communities participating in the research. The proposed study, data analyses, and publications must be completed within the funding period for this opportunity announcement. Study designs proposing control communities should propose how all communities would receive some benefit and not be harmed from participating in the research. In addition to the detailed study design, applicants must provide an analysis plan and power calculation for the multi-site study (i.e. for the three research site grantees combined). Sufficient detail should be provided on study design, analysis plan, and power calculations to replicate power calculations and evaluate the assumptions and parameter estimates used in the calculations. Applicants should specify data sources used to determine mortality and morbidity and estimate the magnitude of the population of individuals reporting misuse and those with OUD in research communities, including the number of overdose deaths and rates to ensure sufficient case counts and base rates to detect differences and deploy interventions. Applicants should justify the quality of drug-specific mortality data used and whether it is currently being collected or will need to be collected de novo. Plans for dealing with confounders including time, secular events, contamination, varying intervention effects, treatment and site heterogeneity, etc. must be addressed.

Researchers should partner with multiple communities and organizations within those communities willing to collaborate in delivering an integrated evidence-based prevention and treatment system to meet the needs of their population. These organizations will be expected to adapt, change, and integrate efforts across multiple sectors. Applicants are required to partner with healthcare, behavioral health, and justice settings. They should also partner with other community based organizations necessary to implement the multi-pronged approach (e.g. police, fire department, faith based organizations, schools, affordable housing, social services, business and economic developers, etc.) to meet the needs of the study. Applicants are encouraged to collaborate with one or more members of each community participating in the research with the ability to influence contracting and the type, quality, and support for prevention and treatment services. Documentation of these partnerships is essential and includes an understanding and willingness by community partners to participate in the research. This documentation should be included in letters of support (see Research Plan in Section IV) and also the required attachment detailed in Other Project Information. See Other Project Information Section IV. Application and Submission Information for instructions on providing an attachment detailing this information. Applications must include a list of these partners (with rationale) for each community partner participating in the research. Finally, each research site must convene a Community Advisory Board comprised of representatives from communities involved in the research, consumers of services, and other subject matter experts to provide guidance and recommendations for study design, execution, and dealing with any problems encountered in the conduct of the research.

Each research site must include one highly involved governmental official (e.g., high-level official in the state substance abuse agency) as key personnel. This person must have the documented ability to influence the contracting, type, quality, and integration of multiple systems across all communities involved with the research site to develop a systematic approach to opioid overdose fatalities, opioid misuse, OUD treatment, and prevention and answer research questions described below. This person must be included among the key personnel on the research study and to be involved in all aspects of study design and execution. Applicants should designate a level of effort for this person and as allowable include funding for time and research-related activities for this person in the research site budget. Other areas of expertise for research sites might include epidemiology and modeling, public health and healthcare data systems, data harmonization and integration, health services research, drug abuse prevention, OUD and treatment, systems science, community-based participatory research, implementation science, and health economics.

In addition, if present in the state where the research will take place, applicants are strongly encouraged to take advantage of NIDA's Clinical Trials Network (https://www.drugabuse.gov/about-nida/organization/cctn/ctn) and the Clinical and Translational Science Award Program funded by the National Center for Advancing Translational Sciences (https://ncats.nih.gov/ctsa/about).

This multisite research cooperative will be 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.

On June 18, 2018, NIH held a planning meeting with scientific experts and stakeholders to discuss questions related to the HEALing Communities Study design and outcomes. A summary of this meeting proceedings is available at: https://www.drugabuse.gov/drugs-abuse/opioids/nih-heal-initiative. NIDA also has issued a Request for Information (RFI) (https://grants.nih.gov/grants/guide/notice-files/NOT-DA-18-023.html) to solicit additional input on the study from interested stakeholders. A summary of responses received from the RFI can be found at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/request-information-rfi-healing-communities-study.

A Notice of Intent to Publish a Funding Opportunity Announcement for Research Sites for the HEALing Communities Study: Developing and Testing an Integrated Approach to Address the Opioid Crisis (UM1) can be found at: https://grants.nih.gov/grants/guide/notice-files/NOT-DA-18-026.html. Applicants are encouraged to participate in a future technical assistance webinar related to the FOA by registering at [email protected]. It is anticipated the webinar will take place October 3, 2018.

The cooperative will include up to three research sites, one Data Coordinating Center, a steering committee (SC), a SC chairperson, a Science Officer from NIDA and SAMHSA, and a NIDA Program Officer. Applicants should propose how they will participate in the cooperative agreement activities described in this FOA.

In addition to research sites, NIDA and SAMHSA intend to fund 1 DCC (see the DCC FOA: RFA-DA-19-017). The DCC will support a range of coordination, logistical, and data activities across the cooperative. They will also be responsible for conducting an economic study to determine the incremental costs and cost-effectiveness of a coordinated integrated evidence-based prevention and treatment system compared to standard care in the community with respect to reducing opioid overdose fatalities by at least 40%. Research sites must interface with the DCC to develop the health economics research protocol(s) and collect data needed to address health economic questions. See sub-section F: health economics subsection of the research strategy below.

Special Considerations:

Applications with the following specifics will be considered non-responsive and will not be reviewed:

• Applications proposing studies for developing and testing novel individual-level prevention and treatment interventions
• Applications proposing cohort studies
• Research sites with communities outside the US and its territories
• Research sites involving less than 15 communities for testing the integrated prevention and treatment interventions
• Applications that do not document 150 opioid overdose fatalities (at least 15% of fatalities must be in rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher reported across all proposed study communities in a site based on the most recent complete year of available data
• Applications without state and community-level data related to mortality, morbidity, and other complications associated with the opioid crisis and the infrastructure and resources leveraged to collect data, provide services, train clinicians, conduct the research, etc.
• Applications with communities across more than one state
• Applications with fewer than 30% rural communities as defined: https://www.ruralhealthinfo.org/am-i-rural/help
• Applications including communities that lack a functional infrastructure for delivering evidence-based prevention and treatment interventions to address opioid misuse and OUD
• Applications with study aims that are not consistent with the areas of research identified in this FOA
• Applications that do not include a key personnel, who is a governmental official with the documented ability to influence the type, quality, and integration of multiple systems at a state-wide level to develop a systematic approach to prevent and treat drug overdose, opioid misuse, and OUD
• Research sites that do not include required collaboration(s) with health, behavioral health, and justice systems, and other necessary community-based organizations within each community as evidenced by letters of support and descriptions of collaborative activities in the application
• Applications lacking plans for integration of existing toolkits, decision support tools, platforms, infrastructure, data collection initiatives, and prevention and treatment services funded via federal, state, local, foundation, and other entities to address the opioid crisis (e.g. SAMHSA, Center for Disease Control and Prevention, Department of Justice Bureau of Justice Assistance, Health Resources and Services Administration and Federally Qualified Health Centers, etc.)
• Applications proposing approaches that are not designed to achieve the primary aim of reducing opioid related overdose fatalities by 40% within 3 years
• Applications not providing a PD/PI committing a minimum of 5 person months annually over the life of the grant award

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://ww2.drugabuse.gov/about/organization/nacda/points-to-consider.html) for details.

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 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

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)
• 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 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

The PD/PI of the research site application must commit a minimum of 5 person months annually over the life of the grant award.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. .

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).

Buttons to access the online ASSIST system or to download application forms 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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; name and title of governmental official serving as key personnel
• Participating institution(s); participating communities; participating community-based organizations
• Number and title of this funding opportunity

The letter of intent should be sent to: [email protected].

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. with the following additional requirements:

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

Sub-section A - Research Plan: required - 12 pages

Sub-section B - Infrastructure, Partnerships and Collaborations: required - 6 pages

Sub-section C - Community Engagement and Outreach: required - 6 pages

Sub-section D - Data Collection, Management, and Harmonization: required - 6 pages

Sub-section E - Systems Science, Implementation and Sustainability Research: required - 6 pages

Sub-section F - Health Economics: required - 6 pages

Sub-section G - Research Site Overview, Management, and Operations: required - 6 pages

Sub-section H - Scientific Research Supports: optional - no more than 3 SRS- 6 pages each

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. With the following additional instructions:

Facilities & Other Resources: For each research site, provide details about the infrastructure for the proposed research study and institutional support for the conduct of clinical research under U.S., DHHS, and NIH regulations and policies regarding human subjects.

Other Attachments: Provide the below listed additional materials with the specified names in support of the application. All the listed materials must be provided as a single PDF file, labelled as Organizational Data.

1. Table of contents of the Attachment

2. Research Site Organization: A diagram explaining the overall structure of the research site and how the Subsections of the RFA fit within the overall program must be provided.

3. Community Data Part One: A table listing all the selected highly affected communities (that meet the minimum requirements specified in the FOA), overall numbers of individuals within each community, number of individuals misusing opioids, with OUD, and opioid overdose deaths by year for the most recent 2 years of available data (refer to Sub-section A).

4. Community Data Part Two: A table listing all organizations (including required healthcare, behavioral health, and justice settings) and other community-based organizations (fire departments, faith-based organizations, schools, etc.) delivering prevention and treatment services (at a minimum include prevention efforts related to opioid use, misuse, OUD, and overdose; screening and assessment of opioid misuse and OUD; linkage and engagement in treatment; use of medications to treat OUD; ongoing recovery support services; and distribution of naloxone). Include roles, responsibilities, services delivered, and number of individuals currently served and an estimate of how many will be reached with these services within each community (refer to Sub-section A).

5. Evidence Based Prevention and Treatment Interventions: A table listing anticipated set of evidence-based prevention and treatment interventions to be implemented (refer to Sub-section A).

6. Study Measures, Data Tools, and Resources: A table listing existing measures, datasets, and de novo data collection needed for this study (refer to Sub-section A).

7. Infrastructure, Partnerships, and Collaborations: A table listing resources available such as a list of toolkits, decision support tools, platforms, infrastructure, and funding that will be used for the proposed research study including activities like prevention and treatment services, data collection, physician training, etc. Include how SAMHSA funding provided to states for prevention and treatment services will be utilized and plans to reduce health coverage payment barriers related to medication for OUD and supporting services, such as behavioral health services (see information above related to CMS programs and resources) (refer to Sub-section B).

8. Management and Operations Overview: A Flow chart(s) illustrating the leadership, coordination, and operational processes for the research site (refer to Sub-section G).

9. Communication Plans: A diagram illustrating communication plan(s) across the research site and their partners, the NIH and SAMHSA, other research sites, and the data coordinating center (refer to Sub-section G).

All instructions in the SF424 (R&R) Application Guide must be followed. In addition, the application must include the following information specific to this FOA:

• Each research site must include a highly involved governmental official (e.g., high-level official in the state substance abuse agency) as key personnel in the UM1 application. This person must have the documented ability to influence the contracting, type, quality, and integration of multiple systems across all communities involved with the research site to develop a systematic approach to opioid overdose fatalities, opioid misuse, OUD treatment, and prevention and answer research questions described below. This person must be included among the key personnel on the research study and to be involved in all aspects of study design and execution. This individual will generally have oversight and responsibility for resources, practices, policies, organization, and integration of multiple systems to address opioid misuse and OUD across all communities involved with the research. This individual should be a change leader with the ability to influence the contracting, type, quality, and delivery of evidence-based prevention and treatment interventions. The application should describe the governmental partner s role and experience in directing change within their organization and role in the research site. At a minimum, the governmental partner will: assist in obtaining support for the research across communities at the research site, participate in development of study design and protocols as part of the SC or study workgroups, assist with data collection, provide access to resources to support data collection and the provision of prevention and treatment interventions, provide access to staff as required by the study protocol, maintain records required for the study protocol, adhere to the study protocol and guidelines set by the research site, the SC, NIDA, and SAMHSA, agree not to report data prior to collaborative reporting. Applicants should include allowable support for this individual to participate in research related activities in their budget.
• It is expected that all key personnel with decision-making roles will devote substantial effort to the research program.

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

In the budget justification, provide budget breakout for activities under each sub-section of the research strategy. Include support for the high ranking governmental official listed as key personnel to participate in the research. This might include allowable salary support or reimbursement, support for data related activities to research questions, allowable salary support or reimbursement for some level of effort for staff working in their office to facilitate major research activities. Support for travel of this individual to the kick-off, Steering Committee, and necessary subcommittee meetings should be included. Include support for research site staff to participate in a 3-day face-to-face kickoff meeting (up to 4 staff) and 2 face-to-face Steering Committee meetings in the Bethesda, MD area (up to 3 staff); at least 2 one-two day meetings of the economic evaluation workgroup to facilitate the economics research (up to 2 staff); up to 3 two-day meetings per year for subcommittees of the cooperative to develop specific components of the research (up to 2 staff). Support for communities and community-based organizations participating in the research should be provided. Some support to address gaps in prevention and treatment services may be included in budget requests. However, it is expected that research sites will draw on federal, state, local, other resources to cover prevention and treatment services. The Research Site PD/PI must commit a minimum of 5 person months annually over the life of the grant award.

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 documented in-kind contributions at a rate of not less than 50% of 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:

Specific Aims:

Describe concisely the conceptual framework for the proposed HEALing communities research study. Provide a clear rationale for the study design, the overall approach, and selection of communities in which the study will be implemented. Specific aims should be distinct and outline plans for developing and implementing an evidence-based prevention and treatment response strategy with a focus on the specific primary and secondary outcomes outlined in the RFA. Describe the cluster study design (e.g. stepped wedge study design) used to test the effects of the "intervention" in a sequential manner across all communities participating in the research.

The HEALing Communities Study research sites applications must include the following functional and structural units. These units referred to as Sub-sections A-H must be clearly marked and include all information specifically requested for each of them. (See Other Project Information for instructions about submitting a diagram of organizational structure labeled Research Site Organization )

Sub-section A - Research Plan: required

Sub-section B - Infrastructure, Partnerships and Collaborations: required

Sub-section C - Community Engagement and Outreach: required

Sub-section D - Data Collection, Management, and Harmonization: required

Sub-section E - Systems Science, Implementation and Sustainability Research: required

Sub-section F - Health Economics: required

Sub-section G - Research Site Overview, Management, and Operations: required

Sub-section H - Scientific Research Supports: optional, no more than 3 are allowed

Sub-section A: Research Plan (required)

The research plan must describe the conceptually driven approach to guide communities through: organizing their community; understanding the nature, severity, and trends of the opioid crisis within their community, including prevention and treatment resources and gaps; developing a data-driven plan to implement evidence-based prevention and treatment interventions linked to local needs across multiple systems; deploying the strategic plan; measuring impact; adjusting interventions based on assessments of impact. Each research site is required to select at least 15 communities within a single state, of which at least 30% must be rural (see https://www.ruralhealthinfo.org/am-i-rural/help). The state must demonstrate high burden from morbidity, mortality, and other complications from the opioid crisis. In considering what communities to include in the study, applicants must demonstrate a strong understanding of the magnitude of the opioid problem in proposed study communities and ensure that sufficient numbers of individuals and rates per 100,000 are affected by opioid misuse, opioid use disorder, and opioid related overdose fatalities to achieve reliable estimates of impact. This is particularly true for opioid overdose deaths, a relatively rare outcome. Thus, applicants must document that a total of at least 150 opioid related overdose fatalities (at least 15% of the fatalities occurred in the rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher were reported across the combined study communities for the most recent complete year of available data. The data-driven plan for working with communities must be ready for implementation within 6-12 months of the award depending on study design.

The Research Plan must include:

a) Data sources and use of epidemiological and modeling methodologies to determine the nature, severity, and trends of the opioid crisis in the communities participating in the study; data related to the primary outcome of opioid overdose fatalities and mortality rates for the past two years of data available for communities to characterize opioid specific and other drug related overdose fatalities and mortality rates and plot the current trend; plans to improve the quality of existing data; plans to collect baseline measures and follow-up data for other secondary outcomes linked to reducing opioid overdose fatalities and opioid overdose mortality rate, and plans to track factors outside of the study that could impact the primary outcome and confound results (e.g. changing drug markets or prescribing patterns that could affect the primary outcome); plans for improving the collection and quality of data for opioid related overdose fatalities and mortality rate and other outcomes.

b) A robust model to organize communities and integrate systems across required settings of healthcare, behavioral health, and justice, and other needed settings to address opioid overdose fatalities, misuse and OUD including community collation building;

c) Approach to selecting, developing, and delivering an integrated set of evidence-based prevention and treatment interventions that could be expected to impact the primary outcome of opioid overdose fatalities and other secondary outcomes linked to reducing opioid overdose fatalities;

d) Rigorous stepped wedge, or other group randomized trial study design with a detailed power analysis (with adequate details to allow replication by reviewers and/or NIH program staff). Study designs proposing "control" communities should propose how all communities would receive some benefit and not be harmed from participating in the research;

e) Justification for communities (how they will contribute to having at least 150 opioid overdose fatalities (at least 15% of the fatalities must have occurred in rural communities) and a rate of 25 opioid related overdose fatalities per 100,000 persons or higher across the combined study communities for the most recent year of data available) selected to participate including numbers of individuals within the community overall and the number of individuals affected by opioid misuse, OUD, and opioid overdose deaths and mortality rates by year for the most recent 2 years of available data with indication if trend is stable, escalating, or de-escalating (See Other Project Information for instructions on providing this information in a table labeled Community Data Part One );

f) Justification and commitment for all organizations delivering prevention and treatment services including roles, responsibilities, and services delivered within each community (See Other Project Information for instructions on providing this information in a table labeled Community Data Part Two . Each research site is required to partner with healthcare, behavioral health, and justice settings across communities. In addition, research sites are encouraged to partner with other community-based organizations including schools, faith-based organizations, fire departments, paramedics, pharmacies, social service organizations, etc. delivering prevention and treatment;

g) Anticipated set of evidence-based prevention and treatment interventions to be implemented (including interventions required to: reduce overdose events; decrease the misuse of opioids, decrease incidence of OUD and progression in severity to OUD or injection drug use; increase the number of individuals (and percentage of individuals with OUD) receiving medication (methadone, buprenorphine, or naltrexone) and behavioral treatment; increase the number and percentage of individuals receiving treatment retained in treatment beyond 6 months; increase the number and percent of individuals receiving or completing treatment that are receiving recovery support services; and increasing access to naloxone. Anticipated structural interventions to be implemented to: change prescribing patterns to reduce the supply of prescription opioids; increase the number of specialty treatment programs that provide medications for OUD; increase the number of providers (doctors, nurses, nurse practitioners, physician assistants, pharmacists) who prescribe and/or monitor medications for OUD; increase the number of providers (physicians, nurse practitioners, physician assistants) with a DATA 2000 waiver to prescribe buprenorphine in the office-based setting; increase the availability of naloxone across a community to reduce fatal overdoses; create programs that can readily link individuals to treatment following an opioid overdose; increasing the use of screening to identify opioid misuse and intervention(s) to address misuse within healthcare and other settings; increase evidence-based school and community-based opioid prevention services; and increasing number of formal linkages between the justice system and healthcare and behavioral health) (See Other Project Information for instructions on providing this information in a table labeled Evidence-Based Prevention and Treatment Interventions );

h) Other proposed secondary aims and outcomes related to individual and community impact of the opioid crisis;

i) Measures, use of existing datasets, and de novo data collection needed for this study. When de novo data collection is necessary, a plan to assist participating organizations with the infrastructure necessary to participate in the study, including data management and information systems, staff support, consultation, training, supervision, and other resources as needed. (See Other Project Information for instructions on providing this information in a table labeled Study Measures, Data Tools, and Resources );

j) Approach and timing of baseline and follow-up data collection;

k) Analysis plan including quantitative and qualitative analyses and modeling for change over time;

l) Data harmonization, integration, and sharing across sites.

Sub-section B: Infrastructure, Partnerships and Collaborations (required).

Describe the academic, government, community, and other partnerships needed to achieve the goals of the research and experience in developing and maintaining successful research collaborations. Describe resources available such as a list of toolkits, decision support tools, platforms, infrastructure, funding, etc. to address the opioid crisis including activities like prevention and treatment services, data collection, physician training, etc. Specifically describe how SAMHSA funding provided to states for prevention and treatment services will be utilized and plans to reduce health coverage payment barriers related to medication for OUD and supporting services, such as behavioral health services via healthcare exchanges, CMS programs, other payment initiatives (see information above related to CMS programs and resources). (See Other Project Information for instructions on providing this information in a table labeled Infrastructure, Partnerships, and Collaborations ).

Sub-section C: Community Engagement and Outreach (required).

Describe experience, expertise, and track record of working collaboratively with communities and community-based organizations, an evidence-based approach to community engagement and community coalition building (e.g. Communities that Care Model), a plan to actively engage communities in all aspects of the research, and application of principles from community-based participatory research paradigms. Establishment and regular meetings of a Community Advisory Board that includes customers and family members will be required. Must include plans for developing the Community Advisory Board, structure of the Community Advisory Board, and how they be used, how often they will meet, and how they will meaningfully contribute to the research.

Sub-section D: Data Collection, Management, and Harmonization (required).

Describe the plan for data collection, management, quality control, integration and harmonization across common data elements for your research site and your approach to dealing with these issues between research sites, and collaboration with the data coordinating center including data sharing. Describe plan for collecting high quality data and improving the quality of existing data for the primary outcome of opioid overdose fatalities and fatality rates, including discussion of the medicolegal death investigation system and infrastructure in the study communities, and required secondary outcomes as they relate to reducing overdose fatalities including: number of overdose events, number of people progressing in severity to OUD or injection drug use, number and percent of individuals with OUD receiving medication (methadone, buprenorphine, or naltrexone) and behavioral treatment, number and percent of individuals in treatment that are retained in treatment beyond 6 months, number and percent of individuals in or completing treatment receiving recovery support services, number of individuals accessing naloxone. Describe plan for collecting data for required and other structural outcomes related to reducing opioid related fatalities: prescribing patterns of prescription opioids; number of specialty treatment programs that provide medications for OUD; number of providers (doctors, nurses, nurse practitioners, physician assistants, pharmacists) who prescribe and/or monitor medications for OUD; number of providers (physicians, nurse practitioners, physician assistants) with a DATA 2000 waiver to prescribe buprenorphine in the office-based setting; availability of naloxone across a community to reduce fatal overdoses; number of individuals linked to treatment following an opioid overdose; number of screenings to identify opioid misuse and brief intervention(s) to address misuse within healthcare and other settings; number of evidence-based school and community-based opioid prevention services; number of formal linkages between the justice system and healthcare and behavioral health). Also, describe plan for collecting data on any other opioid-related secondary outcomes of the study.

Sub-section E: Systems Science, Implementation and Sustainability Research (required).

Describe the plan for integrating systems science to create a learning healthcare system for opioid misuse and OUD, how emerging effective prevention and treatment interventions will be incorporated, and how the prevention and treatment interventions will be adapted depending on impact. Describe the plan for implementation and sustainability research to help understand factors that contribute to the successful implementation and sustainability of an integrated evidence-based prevention and treatment system as well as how the research-based model developed through this study to assist communities in dealing with the opioid crisis, including key components of the prevention and treatment integrated services used, can be applied broadly in communities across the U.S.

Sub-section F: Health Economics (required). Describe the approach to interfacing with a data coordinating center (responsible for designing and implementing the health economics study) to develop and collect data needed to address health economics questions related to incremental cost, cost effectiveness, economic modeling, and sustainability.

Sub-section G: Research site Overview, Management, and Operations (required).

Each application must propose a plan for the leadership, coordination, administration, and organization of the research site. An organizational chart explaining overall structure of the research site and how the Subsections of the RFA fit within the overall program must be included as an attachment. (See Other Project Information for instructions on providing this information in a flow chart labeled Management and Operations Overview ) This section should include: a) overall programmatic structure to effectively promote interactions with communities and providers involved with the research, other research sites, the Coordinating Center, NIH and SAMHSA, and other key stakeholders; b) administrative organization with roles, responsibilities, and clear lines of authority for personnel involved in the center; c) project management plans listing study milestones, deliverables, timelines, metrics; d) processes for monitoring, reporting, and meeting milestones; e) quality control to ensure rapid problem identification and resolution, prioritization of resources, high quality data and publications; f) clear communication plan across the research site and their partners, the NIH and SAMHSA, other research sites, and the data coordinating center (See Other Project Information for instructions on providing this information in a diagram labeled as Communication Plans including information related to meetings and teleconferences to facilitate communication).

Sub-section H: Scientific Research Support Unit(s) (optional):

This section includes, up to three, other scientific research support necessary to support the research agenda. A full description with strong justification will be needed.

Letters of support:

The following letters of support are required to demonstrate participation from partners at multiple levels.

1) A letter documenting approval for the high-ranking state official to participate as key personnel in the research.

2) Letters from all community based organizations (healthcare, behavioral health, justice, police, fire departments, faith-based organizations, housing, employment, paramedics, and others) indicating a willingness to adapt, change, expand prevention and treatment services; provide existing data or assist in de novo data collection; and participate in other activities related to the study.

Also encouraged are support letters from state and local government entities to demonstrate strong commitment and support for the applicant to conduct the proposed research study in their communities.

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, should provide a plan for sharing data with other research sites and the data coordinating center.
• Regardless of the amount of direct costs requested for any one year, all applications are expected to include a Data Sharing Plan detailing how data will be made publicly available, as appropriate and consistent with achieving the goals of the program."

Appendix:

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

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

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 NIDA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDA Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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:

In the evaluation of the HEALing Communities Study-Research Site application, reviewers will emphasize overall cohesiveness of the research program with special attention to the demonstration of the capacities to implement an integrated response strategy, collect baseline data, and measure outcomes to achieve the required primary and secondary outcomes of the study outlined above.

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 there a strong scientific premise for the project? 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?

Specific to this FOA: Does the project address overdose deaths in communities that are most affected with the opioid crisis? Does the research scope include a plan for expanding access and utilization of medication to address OUD? Does the research scope include a broad range of other prevention and treatment services, and structural interventions and outcomes that might be expected to decrease opioid overdose fatalities by at least 40% in 3 years and address opioid misuse and OUD?

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?

Specific to this FOA: is the time commitment of the PD/PI (s) and the investigators with decision making authorities appropriate for the stated study goals? Is there clear description of roles for each major key personnel involved in the research site? Does the Government Official identified in the application have the necessary authorities and roles for helping implement the evidence-based prevention and treatment response strategy? Are researchers with expertise in epidemiology and modeling, public health and healthcare data systems, data harmonization and integration, health services research, drug abuse prevention and treatment research, community-based participatory research, and health economics part of the application?

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?

Specific to this FOA: Is there innovation in the approach to developing a tailored response strategy meeting the unique needs of the community and approaches to engaging communities and community partners? Does the application propose novel approaches for implementing and sustaining the response strategy beyond the proposed award period? Are innovative methodologies proposed to broaden the scope of implementation of the treatment and prevention strategies to communities across the US impacted by the opioid crisis? Are there innovative approaches to disseminating findings and best practices to communities and community organizations dealing with the opioid crisis?

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 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?

Specific to this FOA: Is a strong justification provided for selecting the communities based on the metrics specified in the RFA? Is there thorough consideration of the barriers and facilitators for implementing the response strategy at a broader level (state, city or local communities)? Are there plans to leverage existing infrastructure, tools, systems and resources to implement the intervention? Does the study power account for the RFA-specified primary and secondary outcomes? Does the application consider a broad spectrum of secondary outcomes that are directly related to the RFA-specified primary outcome? Is there a thorough approach to participating in the economic research? Is there a clear conceptual framework for working with communities to help them develop a data-driven tailored response to the opioid crisis? Is there a clear plan for communications among the involved key personnel, with research sites, the DCC, NIDA, SAMHSA, the Steering Committee, and other participating entities, e.g. state, local and community organizations? Is there a plan to improve the quality of data related to overdose fatalities and fatality rates if needed? Is there a plan to complete data analysis within the proposed period of the award?

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?

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 children, justified in terms of the scientific goals and research strategy proposed?

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?

Specific to this FOA: Does the application include communities and community organizations with the capacity to participate in the research and implement a systematic integrated response strategy? Does the application describe what existing infrastructure, tools, systems and resources can be leveraged to collect data and implement the intervention(s) and how they will be used? Does the application identify prevention and treatment programs that are currently supported by other federal, state, and local organizational entities, and provide plans to utilize those resources? Does the application demonstrate a track record of collaborating with community-based organizations in research and is there information about the nature and extent of collaborations between the researchers and community partners? Do the communities named in the application have the infrastructure necessary to deliver evidence-based prevention and treatment interventions?

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.

Milestones

Are the proposed milestones quantifiable and appropriate to the proposed work? Will the research be set up for progress after the milestones are met? Are appropriate alternative plans proposed to achieve the primary and secondary outcomes?

Study Timeline

Specific to this FOA: Is the study timeline described in detail milestones for collection of: 1) initial planning for collecting data to understand opioid crisis in communities, activities to organize and mobilize communities and organizations within communities, selection of evidence based prevention activities, selection approach to addressing required structural aims (these activities must be completed in the RFA-specified timeline of 6-12 months depending on study design); 2) collection of baseline data; 3) collection of follow-up data. Are there clear timelines for the anticipated rate of community enrollment, and planned follow-up assessments? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., state and local study related data; infrastructure delivering prevention and treatment services; practice-based research network; electronic medical records administrative databases; 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)?

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 six 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 six 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 children 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.
• Following initial peer review of the applications, the scientific review committee, accompanied by NIDA program and review staff, may conduct site visits as needed to evaluate the strength of infrastructure, partnerships, and resources proposed to support the research.
• Following the site visits, if applicable, all applications will be 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 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 National Advisory Council on Drug Abuse. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Research site infrastructure, community networks and organization.
• Infrastructure and resources available to deliver and support prevention and treatment services
• There is a need to maximize geographic diversity to enhance the understanding of the opioid epidemic across the country. Therefore, NIDA intends to only make one award per state.
• The HEALing Communities Study is designed to examine the impact of a comprehensive set of prevention and treatment interventions in the most highly burden communities in the U.S. Therefore, there is special interest in funding applications from states ranking in the top third of per capita age-adjusted drug overdose death rates in 2016, based on mortality data from the Centers for Disease Control and Prevention.

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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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 and SAMHSA programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH and SAMHSA 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 primary direction, responsibility, or a dominant role in the activities. Consistent with this concept the primary responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees, NIH, and SAMHSA as defined below.

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

• The Program Director/Principal Investigator has primary responsibilities to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies in collaboration with other awardees, and with assistance from the NIDA and SAMHSA Project Scientists.
• Awardees agree to accept coordination, cooperation, and participation of NIDA, SAMHSA, and other federal staff in those aspects of scientific and technical management of the research and to work cooperatively with other awardees to pursue common methods, protocols, and data elements and collection as appropriate.
• Awardees will participate in an initial kick off planning meeting of approximately 3 days and thereafter biannual 2-day meetings per project period year in Bethesda, Maryland. Awardees will cover travel expenses of the contact PD/PI, state-level key personnel, and up to 3 additional project staff or collaborators (as appropriate given agenda topics). The awardees will provide representation to the SC (see below) and will support any other committees, task forces, and advisory panels related to the project, as needed and will participate in regularly scheduled conference calls with the awarding agencies. Project budgets should include travel for participation in these activities.
• Awardees shall participate in the SC and abide by decisions of the SC and the policies and procedures adopted by the SC.
• Awardees agree to work collaboratively with other awardees, NIDA, and SAMHSA to select a single conceptually driven approach to guide communities in the development and implementation of a data-driven strategic plan to prevent and treat opioid misuse and OUD and adapting that strategy based on the availability of new effective interventions, emerging community needs, or other data.
• Awardees will organize their research site with a management and committee structure that invites and ensures participation by health, behavioral health, justice, and other community-based partners participating in the research. Awardees in collaboration with these partners shall develop research plans to develop, implement, and assess the impact of delivering a tailored integrated set of evidence-based prevention and treatment interventions that meet local needs.
• Awardees shall develop research plans and submit them for approval by the SC. Awardees shall take lead responsibility for implementation of selected plans as determined by the SC. Implementation of studies shall be in accord with SC policies and procedures, including policies and procedures pertaining to instrumentation, data collection, data use, data and safety monitoring, and publication. Awardees shall conduct research in partnership with communities and their partnering organizations, assure quality of care, assure that research findings and adverse events are communicated to research partners and to NIH/NIDA, and assure that the study is conducted in accordance with established protocols.
• Awardees shall participate in activities to develop and implement common data elements, instruments, approaches to data collection, outcomes, baseline, and follow-up data collection across all research sites. In addition, awardees will work with the DCC to establish and implement procedures to ensure data are: 1) adequality quality for analyses; b) efficiently collected to encourage participation of community partners and service providers; c) collected in accordance with procedures and requirements established by the steering committee, and d) sufficiently uniform across all sites.
• Awardees will conduct data analyses on data from their own site for primary, secondary, and other study aims and outcomes. Awardees will work collaboratively with the DCC and Steering Committee with conducting cross-site data analyses for primary, secondary aims and outcomes, and the health economic studies.
• Awardees will partner with healthcare, behavioral health, justice system providers, and other community-based organizations capable of delivering evidence-based prevention and treatment interventions for opioid misuse and OUD within communities participating in the research. These service provider organization responsibilities will differ depending on their role in addressing opioid misuse and OUD. General anticipated responsibilities include: obtaining agency support for the research, participating in the development of study design and protocols as part of the SC or study workgroups, participating in a Community Advisory Board, participating in the research study, providing access to agency staff as required by the study protocol, maintaining records required for the study protocol, adhering to the study protocol and to guidelines set by the research site, the SC, NIH/NIDA, and SAMHSA, and agreeing not to report data prior to collaborative reporting.
• Awardees are expected to publish major findings in a timely manner, in accordance with procedures established by the steering committee. Publications or oral presentations of work done under this agreement requires acknowledgment of support from NIDA, SAMHSA, and any other federal agencies as specified. Awardees agree not to report findings prior to collaborative reporting or approval by the steering committee.
• A PD/PI on a UM1 awarded under this RFA will must maintain significant effort with a commitment not smaller than that stated in the application (5 person-months).
• Awardees will designate a representative from a governmental organization (such as a high-level official in the state substance abuse agency) as key personnel. This individual will be a change leader with the ability to influence contracting, type, quality, and delivery of evidence-based prevention and treatment interventions. This governmental partner will: participate in development of study design and protocols as part of the SC or study workgroups, assist with data collection, provide access to resources to support data collection and the provision of prevention and treatment services, provide access to staff as required by study protocol, maintain records required for the study protocol, adhere to the study protocol and guidelines set by the research site and SC, and agree not to report data prior to collaborative reporting. The awardee agrees to provide allowable financial support for this individual to participate in research related activities.
• Awardees shall work with other awardees, NIH/NIDA, SAMHSA, and the DCC to develop, implement, and monitor, and display in a dashboard metrics related to research site. Metrics will at a minimum monitor study progress, data accuracy and timeliness, and compliance with study plans for each research site and use the 4DX framework (see "The 4 Disciplines of Execution" for more information.) Awardees agree to submit metrics data in a timely fashion.
• Awardees will support 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 of the NIDA Program Officer to ensure objectivity of research.
• Awardees will submit semi-annual progress reports to the NIDA program official. Funding is contingent on progress reported in these reports and monthly metrics, including collaborative contributions.
• Awardees will obtain prior written approval of the NIDA Grants Management Specialist in consultation with the NIDA 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 where they made significant contributions 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.
• Award recipients are expected to meet milestones established in the Milestone Study Plan submitted at the time of funding. Failure to achieve minimally acceptable milestones may result in the withholding of future support and/or negotiating an orderly close-out of this study.

Data Coordinating Center (DCC) responsibilities:

One DCC (see RFA-DA-19-017 for details) will oversee the following activities across the cooperative: data management; analyses of cross research site data for the primary aim of reducing overdose fatalities and directly related secondary aims for improved access to evidence-based prevention and treatment interventions at the individual and structural level; and health economics research; cross-site coordination; meeting logistics; communications; development, collection, and reporting of metrics on overall and individual research site progress; and leading health economics research. One SC chairperson, with expertise in community level systems change and implementing evidence-based interventions, will be selected by NIDA and SAMHSA to coordinate the activities of the SC. NIH/NIDA and SAMHSA will have active roles in all activities of the cooperative as voting members of the SC, and through the involvement of appointed project scientists and a program official.

Steering Committee responsibilities:

• The SC will constitute the primary governing body of the cooperative. It will consist of the Principal Investigator (PI) of each research site, the governmental official named in each application as key personnel, and one Community Advisory Board Member from each research site, the NIDA Project Scientist, and the SAMHSA Project Scientist. Each of these individuals will be a voting member. Each research site has a maximum of three SC votes one from the PI regardless of whether the Multiple PI mechanism is used, one from the governmental official, and one from the Community Advisory Board representative. The NIDA and SAMHAS Project Scientists each have one vote. Neither the DCC nor the SC chairperson will be a voting member of the SC.
• The SC will develop the policies and procedures used to govern cross-site research of the cooperative. This includes: planning and coordination, execution of the cross-site research; development and implementation of metrics and monitoring progress of research across all sites, developing plans for and monitor data quality, conducting data analyses, and reviewing results prior to dissemination. All SC members collectively are responsible for the quality of cross-site research protocols, data, findings and publications of studies conducted by the cooperative.
• SC meetings will be held at least twice per project period in the Bethesda, MD area. SC meetings will be led by the Chairperson selected by NIH/NIDA and SAMHSA. This person will have significant scientific expertise in the areas of research conducted by the cooperative, but will not be affiliated with any research site, DCC, or Federal participants. The Chairperson will provide leadership for meetings and activities of the SC but will not be a voting member.
• The SC may establish subcommittees and workgroups to assist it in carrying out its functions, and these groups may comprise individuals affiliated with the research sites or affiliated service provider agencies. The SC will receive feedback from research site Community Advisory Boards related to proposed research concepts and plans, their feasibility and practical importance, and needs related to participating in the research.

NIH, SAMHSA, and other Federal Staff Responsibilities:

• NIH and SAMHSA staff have substantial programmatic involvement that is above and beyond the normal stewardship role.
• NIH/NIDA will name a NIDA program official (PO) responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIDA PO will not participate in the research, publications, or SC, but will be responsible for the oversight of each cooperative agreement. The PO carries primary responsibility for: (1) review and approval of the progress of the research plans in relation to their stated objectives, and (2) making recommendations regarding continuance of the program. The NIDA PO will be responsible for monitoring the conduct of the research and overseeing the individual research sites. The PO will have access to all study metrics, reports, and dashboards to ensure study progress in addition to progress reports. The NIDA PO will work collaboratively with the NIDA Grants Management Specialist to assure high quality business management of the program, including the most effective use of Federal financial assistance provided through this cooperative agreement. The NIDA PO will receive all required progress reports to determine that satisfactory progress is being made.
• NIDA and SAMHSA will designate project scientists (PS) to collaborate with awardees in the development of research including designing studies, monitoring study execution and adapting when necessary, analyzing data, preparing materials to disseminate research findings according to policies governing the cooperative. The NIDA and SAMHSA PSs serve as a resource for specific information on NIDA and SAMHSA’s programmatic intentions and priorities, and will help foster collaborations between researchers, community partners, and service providers to increase the value of the research to these participants. Both the NIDA and SAMHSA PSs will be voting members of the SC, but will not hold the position of chair. They will participate in the development of instrumentation, study plans, quality control, and coordination of projects, but will not participate in activities that directly involve assessment, testing, or treatment of human subjects.
• 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, and will do so with the consultation of other federal partners. NIH support of this study is contingent upon adequate study progress based on the Grantee’s Milestone Study Plan submitted at the time of funding.
• The cooperative will enable cross-institute and cross-agency collaboration of several types. NIH/NIDA and SAMHSA will convene representatives from Federal agencies that provide resources, assistance, expertise, data collection tools and platforms, etc. directly to the research or indirectly to communities and community-based organizations participating in the research. NIH/NIDA and SAMHSA will convene meetings of this panel to ensure Federal agencies are informed of the activities and progress of the cooperative and to provide a venue for receiving their input on research conducted by the cooperative. In addition, members of the panel may be asked for feedback by the SC. The NIDA and SAMHSA PSs will serve on the Federal panel.

Areas of Joint Responsibility include:

• SC: The SC is the primary governing body of the Cooperative. Awardees must participate in the SC. The SC 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 SC.
• Study Plan Development and Implementation: Study plans are mutually acceptable to the research sites and their community partners, the SC, NIH/NIDA, and SAMHSA. Communication throughout all stages of study development and implementation is essential. The NIDA and SAMHSA PSs will contribute to study plan design as appropriate by providing information regarding conceptual models and methods that can be tested within the Cooperative. NIDA and SAMHSA PSs and the NIDA PO will also review the scientific rationale, programmatic relevance, priority, design, statistical requirements, and implementation of proposed studies.
• Data Management, Analysis, and Access. Data generated are the property of the awardee. Research sites must provide data to the DCC for cross research site analyses and the health economic study in a timely fashion in accordance to policies and procedures established in study protocols and by the SC. In addition, the DCC and all research sites must provide NIH/NIDA and SAMHSA with access to all data generated under this award, subject to rules specified in any Certificates of Confidentiality obtained by awardees. Data must be shared upon request with the SC, subcommittees reporting to the SC. As governed by any Certificates of Confidentiality, data may also be available for external monitoring if required by NIH/NIDA's agreements with other Federal agencies.
• As the Cooperative is intended to be a national resource, sites must be prepared to share their data under provisions that safeguard the privacy and confidentiality of respondents. Thus, each proposing research site should include explicit indications of how they will make their data available for broad use and on what timetable. The awardee will provide for data sharing consistent with its data sharing plan, as approved by NIDA.
• The PD(s)/PI(s) provide, in concert with the NIH/NIDA and SAMHSA 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, NIH/NIDA, and SAMHSA will jointly develop appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers and other institutions.
• All awardees, NIH/NIDA, and SAMHSA will cooperate to ensure the timely and broad dissemination of lessons learned, to inform researchers and health care systems engaged in research in health care settings.
• The SC, with the support of the DCC, will facilitate these joint activities and, in particular, provide facilitation 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.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Grantee chosen without NIH staff voting, one NIH designee, and a third designee from CDC with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 on-time submission, 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 processes and NIH grant resources)
Email: [email protected] (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: [email protected]

Redonna Chandler, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-1919
Email: [email protected]

Gerald McLaughlin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5819
Email: [email protected]

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: [email protected]

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.