Foa_Content_of_RFA-CE-24-013 Modification 1.pdf

Centers for Disease Control and Prevention

NATIONAL CENTER FOR INJURY PREVENTION AND CONTROL

Research Grants to Identify Effective Community-Based Strategies for Overdose Prevention (R01)

RFA-CE-24-013

12/01/2023

Table of Contents 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

Overview Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Components of Participating Organizations:

National Center for Injury Prevention and Control Notice of Funding Opportunity (NOFO) Title Research Grants to Identify Effective Community-Based Strategies for Overdose Prevention (R01) Activity Code Applications in response to this Notice of Funding Opportunity (NOFO) will be funded using the R01 activity code for a research grant.

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-CE-24-013

Assistance Listings Number(s) 93.136 Category of Funding Activity HL - Health NOFO Purpose The Centers for Disease Control and Prevention’s (CDC) National Center for Injury Prevention and Control (NCIPC, Injury Center) is soliciting investigator-initiated research to partner with communities to develop and rigorously evaluate the effectiveness of new, innovative, under-developed, or untested community-based strategies/interventions/programs/practices to reduce overdose. Strategies/interventions/programs/practices may include but are not limited to, those that focus on preventing drug use initiation and drug use, reducing non-infectious harms related to drug use, reducing stigma or other barriers to harm reduction or substance use disorder treatment, and increasing linkage to and retention in care. Research should focus on groups experiencing a disproportionate burden of overdose and/or groups that are at greater risk of experiencing adverse outcomes related to substance use due to social determinants of health.

Research should also involve engaging individuals in the focus population (e.g., people with lived experience with drug use).

The purpose of the Amendment 1 to NOFO RFA-CE-24-013 is to:

• Update the date on the title page of the NOFO to reflect the Application Due Date

Key Dates Publication Date:

To receive notification of any changes to RFA-CE-24-013, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

11/01/2023 Although a letter of intent is not required, is not binding, and does not enter into the review of an application, the information that it contains assists NCIPC with planning for scientific and technical merit peer review.

Application Due Date:

12/01/2023 12/01/2023

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 11:59 PM U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

• E-mail: commons@od.nih.gov

• Phone: 301-402-7469 or (toll-free) 1-866-504-9552

• Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with https://www.grants.gov/ http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

03/01/2024 This is an estimated date.

Secondary Review:

04/01/2024 This is an estimated date

Estimated Start Date:

09/30/2024 This is an estimated date

Expiration Date:

02/01/2024 Required Application Instructions It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note:The Research Strategy component of the Research Plan is limited to 12 pages.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose The Centers for Disease Control and Prevention’s (CDC) National Center for Injury Prevention and Control (NCIPC, Injury Center) is soliciting investigator-initiated research to partner with communities to develop and rigorously evaluate the effectiveness of new, innovative, under-developed, or untested (hereafter referred to as “untested”) community-based strategies/interventions/programs/practices (hereafter referred to as “strategies”) to reduce overdose. Strategies may include, but are not limited to, those that focus on preventing drug use initiation and drug use, reducing non-infectious harms related to drug use, reducing stigma or other barriers to harm reduction or substance use disorder treatment, and increasing linkage to and retention in care. Research should focus on groups experiencing a disproportionate burden of overdose and/or groups that are at greater risk of experiencing adverse outcomes related to substance use due to social determinants of health. Research should also involve engaging individuals in the focus population (e.g., people with lived experience with drug use).

https://grants.nih.gov/grants/how-to-apply-application-guide.html

Mechanism of Support: The funding mechanism for this Notice of Funding Opportunity (NOFO) will be a research grant (R-01).

Funds Available and Anticipated Number of Awards: CDC/NCIPC intends to commit up to $3,750,000 in FY 2024 to fund up to five (5) applications. Awards issued under this NOFO are contingent upon the availability of funds and a sufficient number of meritorious applications.

Budget and Project Period: The maximum award amount will be $750,000 per award for the first 12-month budget period. This includes both direct and indirect costs. Applicants may request a project period of up to five (5) years. The maximum total project funding is $3,750,000 (direct and indirect) per award, over the project period. The project period is expected to be 09/30/2024 to 09/29/2029. The total award will depend upon the project quality, duration, and cost proposed.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. Application and Submission Information of this announcement.

Eligible Institutions/Organizations: Institutions/organizations listed in Section III. Eligibility Information 1. Eligible Applicants are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs):

CDC does not make awards to individuals directly. Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.

Applications in which the contact Eligible PD/PI meets NIH Early Stage Investigator (ESI) status, as verified via the NIH Determination of Investigator Status process, and whose application has a meritorious peer review score, may be considered for prioritization during the second level of review (see Section V. Application Review Information 4. Review and Selection Process). For the contact PD/PI Determination of Investigator Status: Before application submission, PD/PIs are encouraged to verify and/or enter the date of their terminal research degree or the end date of their post-graduate clinical training in their eRA Commons Profile to ensure the correct identification. NIH systems will automatically calculate the status of each investigator and display it within their eRA Commons personal profile. The ESI status of the PD/PIs on any R01 or R01 equivalent application will be flagged at the time of submission.

Investigators should make sure their status is correctly marked in their profile. If your status is incorrect, please contact the NIH eRA Service Desk.

Number of PDs/PIs:

An application may name more than one PD/PI; their names must appear on the face page of the application. However:

• One (1) principal investigator must be designated as the contact PD/PI for all correspondence related to the application.

https://grants.nih.gov/policy/early-investigators/index.htm https://grants.nih.gov/policy/early-investigators/index.htm#dis https://grants.nih.gov/support/index.html

• All PD/PIs must include their eRA Commons Identification in the Credential Field of the Senior/Key Person Profile Component of the SF-424 (R&R) Application Package.

• Institutions/organizations proposing multiple PDs/PIs must visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF-424 (R&R) Application Guide.

Number of Applications: Eligible applicant organizations may submit more than one application to this NOFO, provided that each application is scientifically distinct. However, applicant institutions can submit only one application with the same contact PD/PI. Only one application per contact PD/PI will be funded under this announcement. If two or more applications from the same contact PD/PI are received for this NOFO, the only application that will be submitted for review will be the last application received based on the document’s time and date stamp in Grants.gov (http://www.grants.gov). The applicant must ensure that duplicate applications are withdrawn before the application review date.

Additionally, applicant institutions submitting applications with essentially the same proposed research to two or more CDC/ATSDR NOFOs will not be funded under more than one NOFO.

Applicant institutions submitting multiple applications with essential y the same proposed research to this announcement will not be funded more than once.

Application Type: NEW

Special Date(s) A pre-application teleconference call will be conducted on October 24, 2023 to address questions from prospective applicants regarding NOFO RFA-CE-24-013. The call will begin at 2:00pm Eastern Standard Time (EST) and end at 3:00pm Eastern Standard Time (EST), or sooner if all questions are addressed. Questions and answers from the discussion will be included in an amended NOFO approximately 3 weeks after the call.

Participant Access Information:

• Call Date: October 24, 20203

• Call Start Time: 2:00pm Eastern Standard Time (EST)

• Call End Time: 3:00pm Eastern Standard Time (EST)

• Call Leader: Amanda Garcia-Williams, PhD, Scientific Program Official

• Toll-Free Number: 1-866-600-6035

• Use Passcode 23198543# when prompted

Application Materials See Section IV.1 for application materials.

Hearing Impaired Telecommunications for the hearing impaired are available at: TTY: 1-888-232-6348.

Section I. Funding Opportunity Description http://www.grants.gov

Statutory Authority Section 301 (a) [42 U.S.C. 241(a)] of the Public Health Service Act, and Section 391 (a) [42 U.S.C. 280 b (a)] of the Public Health Service Act, as amended.

1. Background and Purpose Despite efforts to address the overdose crisis, drug overdose deaths are at historic levels, and the U.S. has continued to have year-over-year increases in overdose deaths (1, 2). The proliferation of fentanyl in the illicit drug supply has driven increases in overdose deaths and challenged efforts to address it (3, 4). For example, the Drug Enforcement Agency (DEA) reports of increases in counterfeit prescription medications that contain fentanyl have raised concerns about overdose deaths among those who attempt to obtain prescription medications from illicit sources, including youth (4, 5).

Overdose deaths accelerated during the COVID-19 pandemic, with rapid increases in deaths involving synthetic opioids and increases in overdose deaths involving stimulants such as methamphetamine and cocaine (6). In 2021, 70,601 (66%) of the 106,699 drug overdose deaths involved synthetic opioids such as illicitly manufactured fentanyl, 24,486 (23%) involved cocaine, and 32,537 (30%) involved psychostimulants with abuse potential, such as methamphetamine (2). Deaths involving stimulants often occur in combination with synthetic opioids (7). Moreover, recent increases in overdose deaths have disproportionately affected non- Hispanic Black and American Indian and Alaska Native (AI/AN) persons (8).

Reducing the burden of drug overdose amidst a rapidly evolving overdose epidemic requires addressing drug use from multiple fronts, including preventing initiation or continuation of use and preventing nonfatal and fatal overdose through harm reduction strategies and linkage to evidence-based clinical treatment. Moreover, to improve health equity, prevention strategies need to be tailored for populations at greatest risk of overdose or with least access to care.

State, local, and tribal communities are implementing a variety of innovative strategies to address the crisis, but there is limited knowledge of the effectiveness of many of these strategies.

Furthermore, there is a need to develop and evaluate new strategies in response to the evolving epidemic, including the evolving illicit drug supply.

To address the overdose crisis, additional research is needed to identify effective and scalable community-based strategies to reduce drug use initiation, drug use, and address barriers to care within the context of the evolving drug overdose crisis, and to tailor those strategies to those at greatest risk of overdose or with least access to care.

Purpose:

The Centers for Disease Control and Prevention’s (CDC) National Center for Injury Prevention and Control (NCIPC, Injury Center) is soliciting investigator-initiated research to partner with communities to develop and rigorously evaluate the effectiveness of untested community-based strategies to reduce overdose. Strategies may include, but are not limited to, those that focus on preventing drug use initiation and drug use, reducing non-infectious harms related to drug use, reducing stigma or other barriers to harm reduction or substance use disorder treatment, and increasing linkage to and retention in care. Research should focus on groups experiencing a disproportionate burden of overdose and/or groups that are at greater risk of experiencing adverse outcomes related to drug use. Research should also involve engaging individuals in the focus population (e.g., people with lived experience with drug use).

Of particular interest is research focusing on groups experiencing a disproportionate burden of overdose and/or groups that are at greater risk of experiencing adverse outcomes related to drug use due to social determinants of health.

Research is intended to directly improve the ability of state, tribal, and local health departments or community groups to implement strategies to prevent overdose.

References

1. Ahmad FB, Cisewski JA, Rossen LM, Sutton P. Provisional drug overdose death counts.

National Center for Health Statistics. 2023. Designed by LM Rossen, A Lipphardt, FB Ahmad, JM Keralis, and Y Chong: National Center for Health Statistics.

https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm

2. Spencer MR, Miniño AM, Warner M. Drug overdose deaths in the United States, 2001–2021.

NCHS Data Brief, no 457. Hyattsville, MD: National Center for Health Statistics. 2022. DOI:

https://dx.doi.org/10.15620/cdc:122556.

3. US Department of Justice Drug Enforcement Administration. 2020 National Drug Threat Assessment. March 2021. https://www.dea.gov/documents/2021/03/02/2020-national-drug-threat-assessment

4. Drug Enforcement Administration. DEA Issues Public Safety Alert on Sharp Increase in Fake Prescription Pills Containing Fentanyl and Meth. 2021; September 17.

https://www.dea.gov/press-releases/2021/09/27/dea-issues-public-safety-alert

5. Tanz LJ, Dinwiddie AT, Mattson CL, O’Donnell J, Davis NL. Drug Overdose Deaths Among Persons Aged 10–19 Years — United States, July 2019–December 2021. MMWR Morb Mortal Wkly Rep 2022;71:1576–1582. DOI: http://dx.doi.org/10.15585/mmwr.mm7150a2

6. Centers for Disease Control and Prevention. Increase in fatal drug overdoses across the United States driven by synthetic opioids before and during the COVID-19 pandemic. CDC Health Action Network. 2020; December 17. https://emergency.cdc.gov/han/2020/han00438.asp

7. O’Donnell J, Gladden RM, Mattson CL, Hunter CT, Davis NL. Vital Signs: Characteristics of Drug Overdose Deaths Involving Opioids and Stimulants — 24 States and the District of Columbia, January–June 2019. MMWR Morb Mortal Wkly Rep 2020;69:1189–1197. DOI:

http://dx.doi.org/10.15585/mmwr.mm6935a1external icon.

8. Kariisa M, Davis NL, Kumar S, et al. Vital Signs: Drug Overdose Deaths, by Selected Sociodemographic and Social Determinants of Health Characteristics — 25 States and the District of Columbia, 2019–2020. MMWR Morb Mortal Wkly Rep 2022;71:940–947. DOI:

http://dx.doi.org/10.15585/mmwr.mm7129e2.

9. Guidance for Federal Departments and Agencies on Indigenous Knowledge.

https://www.whitehouse.gov/wp-content/uploads/2022/12/OSTP-CEQ-IK-Guidance.pdf https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm https://dx.doi.org/10.15620/cdc:122556 https://www.dea.gov/documents/2021/03/02/2020-national-drug-threat-assessment https://www.dea.gov/documents/2021/03/02/2020-national-drug-threat-assessment https://www.dea.gov/press-releases/2021/09/27/dea-issues-public-safety-alert http://dx.doi.org/10.15585/mmwr.mm7150a2 https://emergency.cdc.gov/han/2020/han00438.asp http://dx.doi.org/10.15585/mmwr.mm7129e2 https://www.whitehouse.gov/wp-content/uploads/2022/12/OSTP-CEQ-IK-Guidance.pdf

10. Dankwa-Mullan I, Rhee KB, Stoff DM, Pohlhaus JR, Sy FS, Stinson Jr N, Ruffin J. Moving toward paradigm-shifting research in health disparities through translational, transformational, and transdisciplinary approaches. American journal of public health. 2010 Apr;100(S1):S19-24.

Healthy People 2030 and other National Strategic Priorities This research addresses the Healthy People 2030 focus areas of Substance Use and Injury Prevention as described in: https://health.gov/healthypeople. Specifically, this NOFO supports the Healthy People Substance Use (SU) areas of SU-03 Reduce drug overdose deaths, SU-07 Reduce the proportion of adults reporting use of any illicit drugs during the past 30 days, and SU-15 Reduce the proportion of people with illicit drug use disorder in the past year. This research also supports the Healthy People Injury Prevention (IVP) area of IVP-20 Reduce overdose deaths involving opioids, and IVP-03 Reduce unintentional injury deaths. Additionally, this research addresses the Healthy People health equity related goal of SU-01: Increase the proportion of people with a substance use disorder who got treatment in the past year.

Public Health Impact The proposed research is expected to expand the evidence base for the effectiveness of untested community-based strategies to reduce overdose. Strategies evaluated as a result of this NOFO have the potential to prevent drug use initiation and drug use, reduce harms related to drug use, reduce stigma or other barriers to harm reduction or substance use disorder treatment, and increase linkage to and retention in care.

Research is intended to directly improve the ability of state, tribal, and local health departments or community groups to implement strategies to prevent overdose, especially among those most at risk for drug use and overdose, including those impacted by health disparities and social determinants of health. Further, by conducting research that involves partnering with communities and engaging with those who will be affected by the strategies, such as people with lived experience with drug use, the goal is to identify strategies that are effective, tailored, sustainable, scalable, and acceptable and feasible for persons with lived experiences.

Relevant Work The strategic plan for the Division of Overdose Prevention includes the goal: Reduce opioid overdose now. The current concept applies to this goal. The Division of Overdose Prevention research priorities can be found on CDC’s website:

www.cdc.gov/injury/pdfs/researchpriorities/Research-Priorities-Overdose.pdf#page=1

This proposal also aligns with the current research priorities of the Division of Overdose Prevention. This project addresses the following research priority: Develop and evaluate innovative prevention strategies designed to prevent overdose, including among those at greatest risk.

The following publications from Division of Overdose Prevention authors have been recently released and are of relevance for this NOFO:

1. Haegerich T, Jones C, Cote PO, Robinson A, Ross L. Evidence for State, Community and Systems-Level Prevention Strategies to Address the Opioid Crisis. Drug and Alcohol Dependence. 2019; doi:10.1016/j.drugalcdep.2019.107563 https://health.gov/healthypeople http://www.cdc.gov/injury/pdfs/researchpriorities/Research-Priorities-Overdose.pdf#page=1 https://bit.ly/2kAPuUb https://bit.ly/2kAPuUb

2. O’Donnell J, Tanz LJ, Gladden RM, Davis NL, Bitting J. Trends in and Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured Fentanyls— United States, 2019–2020. MMWR Morb Mortal Wkly Rep. ePub: 14 December 2021.

3. Kariisa M, Davis NL, Kumar S, et al. Vital Signs: Drug Overdose Deaths, by Selected Sociodemographic and Social Determinants of Health Characteristics — 25 States and the District of Columbia, 2019–2020. MMWR Morb Mortal Wkly Rep. ePub: 19 July 2022. DOI: http://dx.doi.org/10.15585/mmwr.mm7129e2

4. Kariisa, M., Seth, P., Scholl, L., Wilson, N. O., & Davis, N. L. (2021). Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups – United States, 2004–2019. Drug and Alcohol Dependence, 227, 109001.

https://doi.org/10.1016/j.drugalcdep.2021.109001

CDC funded 66 jurisdictions as part of its Overdose Data to Action (OD2A) Program (https://www.cdc.gov/drugoverdose/od2a/index.html), a cooperative agreement that began in September 2019. The program is focused on the complex and changing nature of the drug overdose epidemic, including stimulant overdoses, and highlights the need for an interdisciplinary, comprehensive, and cohesive public health approach to preventing overdoses.

In 2023, CDC built on this program with two new funding opportunities, one designed for states (Overdose Data to Action in States) and one designed specifically for localities and territories (Overdose Data to Action: Limiting Overdose through Collaborative Actions in Localities), to help ensure broad resources and support to respond to the evolving overdose crisis at all levels of government. Both awards support 5-year cooperative agreements to expand and strengthen overdose surveillance and prevention efforts to reduce nonfatal and fatal overdoses involving opioids and/or stimulants and polysubstance use.

https://www.cdc.gov/drugoverdose/od2a/funding-announcements.html.

In partnership with the Office of National Drug Control Policy (ONDCP), CDC supports more than 700 community coalitions across the country to prevent and reduce substance use among youth through its Drug-Free Communities Support Program (https://www.cdc.gov/drugoverdose/drug-free-communities/about.html).

2. Approach NCIPC intends to fund applications evaluating the effectiveness of untested community-based strategies to reduce overdose. Strategies may include, but are not limited to, those that focus on preventing drug use initiation and drug use, reducing non-infectious harms related to drug use, reducing stigma or other barriers to harm reduction or substance use disorder treatment, and increasing linkage to and retention in care. Applications that do not propose to evaluate the effectiveness of untested (i.e., innovative new, under-developed, or untested) community-based strategies (i.e., intervention, program, practice) to reduce overdose, as evidenced in the Research Strategy section of the application’s research plan, will be considered nonresponsive and will not be forwarded for peer review.

Primary outcomes of interest include, but are not limited to, nonfatal and fatal drug overdose, drug use, drug use initiation, substance use disorders (SUDs) and secondary outcomes of interest include, but are not limited to linkage to SUD care, and retention in SUD care. Process outcomes https://www.cdc.gov/mmwr/volumes/70/wr/mm7050e3.htm https://www.cdc.gov/mmwr/volumes/70/wr/mm7050e3.htm https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e2.htm?s_cid=mm7129e2_w https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e2.htm?s_cid=mm7129e2_w https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e2.htm?s_cid=mm7129e2_w http://dx.doi.org/10.15585/mmwr.mm7129e2 https://doi.org/10.1016/j.drugalcdep.2021.109001 http://www.cdc.gov/drugoverdose/od2a/index.html) https://www.cdc.gov/drugoverdose/od2a/funding-announcements.html https://www.cdc.gov/drugoverdose/drug-free-communities/about.html include stigma or other barriers to SUD care. Care includes harm reduction or evidence-based clinical treatment. Applicants are expected to include at least one primary outcome.

Applications that propose an evaluation of an untested strategy only for its impact related to infectious disease as the main outcomes, without also including a primary outcome that will directly contribute to our understanding of community-based strategies to reduce overdose do not meet the scientific intent of this NOFO. These applications will not be recommended for funding consideration during the NCIPC second-level review (see Section V. Application Review Information).

For this NOFO, the term “substance use” includes prescription drug misuse, illicit drug use, and cannabis/cannabinoid use. For this NOFO this term does NOT apply to nicotine and alcohol.

Applications proposing to evaluate the effectiveness of untested community-based strategies on nicotine and alcohol as the only outcomes of interest do not meet the scientific intent of this NOFO. Measures of nicotine and/or alcohol use can be included as outcomes along with at least one primary outcome of interest including nonfatal and fatal drug overdose, drug use, drug use initiation, and substance use disorders (SUDs). Applications that propose an evaluation of a strategy only for its impact on nicotine/and/or alcohol related outcomes without also including one of the primary outcomes listed above do not meet the scientific intent of this NOFO. These applications will not be recommended for funding consideration during the NCIPC second level review (see Section V. Application Review Information).

For this NOFO, an “untested” strategy is theoretically justified but has not been developed or has not been implemented in the participating community or another community. A “new”, “innovative” or “under-developed”, strategy (i.e., “untested”) has been implemented in the participating community or another community but has not been rigorously evaluated for effectiveness overall or for a specific population, setting, or a primary outcome, and evaluating such a strategy is consistent with the intent of this NOFO. Applicants must demonstrate that the proposed strategy is untested and justify why the proposed research is needed and likely to have substantial implications for addressing the drug overdose epidemic.

This NOFO is intended to support rigorous evaluation of untested community-based strategies to reduce overdose. An application that proposes to develop or implement a strategy (i.e., intervention, program, practice) without also conducting a rigorous evaluation of the strategy (i.e., intervention, program, practice) as evidenced in the Research Strategy section of the application’s research plan, will be considered nonresponsive and will not be forwarded for peer review.

Additionally, for this announcement community-based strategies are defined as strategies that take place in community-based settings.

Examples of community-based settings include, but are not limited to:

• syringe services programs

• public health departments

• social services organizations

• neighborhood groups

• faith-based organizations

• community-based organizations and other places in communities that may serve people at risk of overdose, as well as public places within a community where overdoses can be prevented (e.g., public parks, restrooms, libraries, schools).

The community-based strategies listed above are examples and are not an exhaustive list.

Applicants are encouraged to rigorously evaluate strategies with the potential for population-wide effects. Applicants are expected to examine a range of outcomes from the community-based strategies evaluated, including potential unintended negative effects such as costs or consequences. Applicants should describe how the proposed research is innovative, advances the field of overdose prevention, and adds to the current evidence base.

As a public health agency, CDC focuses on public health responses to overdose prevention.

While overdose prevention strategies may collaborate with law enforcement agencies, applications that propose to focus on law enforcement policies without the inclusion of a strong public health component or focus, as evidenced in the Research Strategy section of the application’s research plan, will be considered nonresponsive and will not be forwarded for peer review.

The proposed research must focus on human subjects. Applications proposing research using non-human species, as evidenced in the Research Strategy section of the application’s research plan, will be considered nonresponsive and will not be forwarded for peer review.

Applicants are asked to indicate in the applications Abstract what NCIPC Research Priority (https://www.cdc.gov/injury/researchpriorities/index.html) the research proposal intends to address.

Research Design

This funding opportunity is intended to support evaluations that are designed to detect whether any measured changes in outcomes can be attributed to the untested strategy. Applicants are expected to use the most objective and rigorous study designs possible to answer the proposed research questions. For this announcement, rigorous evaluation designs include those that utilize experimental (i.e., randomized controlled trials) or quasi-experimental designs (e.g., comparative interrupted time series design, difference-in-differences, instrumental variable methods, regression discontinuity, regression point displacement, stepped wedge, designs using propensity-score matching, designs involving matched comparison groups). Randomized trials are not feasible for some prevention strategies and alternative quasi-experimental designs are appropriate and acceptable. Applicants are expected to justify that the proposed design and data analysis plans (including attention to statistical power and baseline measures) are appropriate for evaluating the impacts of the strategy.

Applications may also include Indigenous knowledge methods and approaches. Indigenous Knowledge is "a body of observations, oral and written knowledge, innovations, practices, and beliefs developed by Tribes and Indigenous Peoples through interaction and experience with the environment, and related practices, if not yet rigorously evaluated, are considered innovative community-based strategies. Indigenous Knowledge is based in ethical foundations often grounded in social, spiritual, cultural, and natural systems that are frequently intertwined and inseparable, offering a holistic perspective" (9) and including an extensive array of activities https://www.cdc.gov/injury/researchpriorities/index.html

(e.g., traditional, healing, and spiritual practices such as ceremonies and rituals, talking circles, and drumming; wellness practices such as learning and speaking a traditional language, engaging in traditional practices, and developing connectedness through community and family activities).

The research proposal should include appropriate outcome measures of primary outcomes of interest (e.g., nonfatal and fatal drug overdose, drug use, drug use initiation, substance use disorders (SUDs)) and any secondary outcomes of interest (e.g., linkage to SUD care, and retention in SUD care). Process outcomes can include stigma or other barriers to SUD care. Care includes harm reduction or evidence-based clinical treatment. Applicants are expected to measure at least one primary outcome. The research proposal should also include data analytic plans that are appropriate to the community-based strategy, research design, and hypotheses, and data collection measures that anticipate and evaluate the effects of threats to the internal and external validity of the specified research design within the project period.

Community-based strategies examined are expected to be theoretically justified and supported with epidemiological and behavioral research. Development of community-based strategies should also be informed by community partners and input from the focus population (e.g., people with lived experience with drug use). Applicants should include the theoretical background or framework, literature support for the strategy including formative research or application in other contexts, or a description of past input from the community and population of focus or plans to collect this information as part of the project.

Examples of outcome and impact data sources include, but are not limited to, vital statistics data, police records, criminal justice data, morbidity data including hospital or emergency department data or emergency medical services (EMS) data, or relevant self-report survey data. The research proposal should appropriately anticipate, conceptualize, and measure the intended benefits and potential unintended negative outcomes relevant to the study proposed. The use of multiple data sources is encouraged to improve the validity and reliability of each outcome or other measure selected. The proposal should also describe appropriate indicators of the strategy implementation process and success.

This NOFO is not intended to support applications that solely evaluate strategies in healthcare settings without also connecting to community resources (e.g., an intervention in a primary care or emergency department setting for youth treated for an overdose). The proposed research may include an evaluation of strategies involving a collaboration between healthcare settings and community-based partners (e.g., a brief intervention in a healthcare setting to treat for overdose that then links patients to community programs). Applications proposing the evaluation of an untested strategy to reduce overdose in healthcare settings without also connecting to community resources do not meet the scientific intent of this NOFO. These applications will not be recommended for funding consideration during the NCIPC second-level review (see Section V. Application Review Information).

Further, research funds are not available to evaluate the effectiveness of medications or a clinical behavioral-based intervention (e.g., contingency management, cognitive behavioral therapy [CBT]). Those that propose to evaluate the effectiveness of a pharmacological intervention approach or propose to evaluate a clinical behavioral-based intervention approach (e.g., contingency management, cognitive behavioral therapy [CBT]) for substance use or substance use disorders as evidenced in the Research Strategy section of the application’s research plan, will be considered nonresponsive and will not be forwarded for peer review.

Applications must be scientifically responsive to NOFO RFA-CE-24-013 to be forwarded for peer review. Additional responsiveness criteria are listed in Section III. Eligibility Information 5.

Responsiveness of this NOFO. It is the applicant’s responsibility to ensure that the submitted research proposal meets all responsiveness criteria listed in Section III. Eligibility Information 5.

Responsiveness.

Data collection, acquisition, and analysis

Applicants must identify and describe appropriate data sources and provide evidence of their ability to acquire and/or collect data of sufficient quantity and quality to conduct the proposed research within the project period. The proposed processes, partnerships, and resources required to accomplish data collection and management should be detailed.

Applications should clearly describe and justify the proposed sampling methods, sample size, power estimates, and data collection methods for the primary outcome(s), at a minimum, and other proposed secondary measures and subgroup analyses. The timeline for data acquisition (requests for extant data and or primary data collection) must be specified. Numerous data sources can be used for the outcome data, including emergency department data, law enforcement data, self-report data, and other sources of data. In addition, administrative data from relevant agencies and survey data collected before or in the context of the evaluation are potential sources.

Applications should include the data analytic plan, timeline, and resources necessary for success.

Protection of Human Subjects and Personally Identifiable Information The Research Strategy section of the application is expected to clearly describe the type, source, access to, and protections of the data and human subjects participating in the study. Access to non-publicly available, previously collected data must be clearly described in the Research Strategy and documented with a signed Data Sharing Agreement or Letter of Support. Access to publicly available, previously collected data must be clearly described in the Research Strategy.

Protection of previously collected data includes but is not limited to, protection of personally identifiable information from loss and/or misuse.

The application is expected to identify each performance site that will be conducting human subjects research and includes the FWA number for the applicant institution and each performance site. Research conducted with more than one institution will be expected to use a single Institutional Review Board (sIRB) to conduct the ethical review required by HHS regulations. See Section IV. Application and Submission Information, 10 Funding Restrictions, Human Subjects for details.

Objectives/Outcomes The primary goal of this research is to determine the effectiveness of untested community-based strategies to reduce overdose. Strategies may include, but are not limited to, those that focus on:

• preventing drug use initiation and drug use

• reducing non-infectious harms related to drug use (i.e., nonfatal or fatal overdose)

• reducing stigma or other barriers to harm reduction or substance use disorder treatment

• increasing linkage to and retention in care

Primary outcomes of interest can include, but are not limited to:

• nonfatal and fatal drug overdose

• drug use

• drug use initiation (e.g., among youth)

• substance use disorders (SUDs)

Primary outcomes to be achieved with funded research should directly contribute to our understanding of community-based strategies to reduce overdose. Applicants are expected to include at least one primary outcome.

Secondary outcomes of interest can include, but are not limited to:

• linkage to SUD care (including harm reduction or evidence-based clinical treatment)

• retention in SUD care (including harm reduction or evidence-based clinical treatment)

• factors that decrease the likelihood of the primary outcomes listed above (i.e., protective factors) such as community cohesion or norm change

• sense of community or social connectedness

• sense of cultural connectedness

Process outcomes of interest can include, but are not limited to:

• Barriers and facilitators to implementation of the strategy, such as stigma

• Extent to which the strategy was implemented as enacted

• Acceptability by the population impacted by the strategy

• Activities (e.g., total number, frequency and duration, content)

• Reach (e.g., number of participants, number of people served in the community)

• Capacity building (e.g., number and types of partnerships such as new or ongoing, number of staff trained)

Outcomes are expected to be measured during the project period and outcome selection should be justified by the theoretical background or framework, literature support for the strategy including formative research or application in other contexts, or description of past input from the community and population of focus or plans to collect this information as part of the project.

Target Population The target population includes those experiencing a disproportionate burden of substance use disorders and overdose, and/or groups are at greater risk of experiencing adverse outcomes related to drug use including people underserved by treatment for substance use disorders or harm reduction services.

This includes those at increased risk of overdose due to the changing illicit drug supply, such as youth or others who may be exposed to counterfeit prescription medications and people who use stimulants that may be adulterated with opioids such as fentanyl. These populations may be harder to reach via syringe services programs, which may be more focused on the injection of opioids.

Other groups experiencing a disproportionate burden of substance use disorders and overdose or that may be at greater risk of experiencing adverse outcomes related to drug use may include but are not limited to people in underserved socio-demographic groups (e.g., non-English speaking populations, tribal populations, rural communities and other geographically underserved areas, racial/ethnic minority groups, and sexual and gender minority groups), people experiencing social determinants of health (e.g., reduced economic stability; limited educational attainment;

limited healthcare access, including those who have been historically underserved or are uninsured; limited health literacy), and people experiencing certain social or physical health conditions or experiences (e.g., recent incarceration, homelessness, a mental health condition, chronic pain, a disability, adverse childhood experiences, a history of suicidal ideation or suicide attempt or a history of substance use disorders and/or overdose).

Research that examines the effectiveness of strategies in high burden areas (e.g., identified through high overdose rates or vulnerability assessments) or that addresses health equity and is tailored for populations at greatest risk or with least access is also encouraged.

Applications must clearly describe how they have identified the target population and how the proposed research will improve health equity among those at greatest risk of overdose or with the least access to care.

Collaboration/Partnerships It is expected that for all applications, the applicant organization and contact PI will provide the scientific and technical leadership necessary to conduct the proposed research throughout the entire project period. It is expected that the proposed research work plan described in the Research Strategy section of the application and the SF-424 Research and Related Budget will demonstrate the applicant organization’s leadership and involvement throughout the entirety of the project period. The applicant organization cannot serve as a “pass-through" to fund another entity to conduct the majority of the research or provide the scientific or technical leadership necessary to complete the proposed research project.

As stated in the Background of this NOFO, NCIPC recognizes the importance of community involvement in research to reduce overdose. Recognizing that the development of partnerships takes time, the timeframe for this NOFO is up to 5 years to support the involvement of communities and the development of community partnerships.

Applicants are encouraged to seek and include the meaningful involvement of communities throughout the development and conduct of the proposed research and in the translation and dissemination of research results, including, but not limited to state, local, and or tribal health departments, local governmental agencies and/or businesses, faith-based organizations, tribal communities, and community-based organizations that serve individuals that are disproportionately burdened by drug use and overdose. This includes engagement and strong partnerships with community members with lived experience who can participate throughout the project (e.g., developing study methods, collecting data, interpreting results, and disseminating findings). By conducting research that involves partnering with communities and engaging with those who will be affected by the strategies, such as people with lived experience with drug use, the goal is to identify strategies that are effective, tailored, sustainable, scalable, and acceptable and feasible for persons with lived experiences.

Research is intended to directly improve the ability of state, tribal, and local health departments or organizations and community groups to implement evidence-based and effective strategies to prevent overdose, and applicants are encouraged to collaborate with state, local, tribal, and community partners, including but not limited to those implementing programmatic work funded by CDC’s Overdose Data to Action in States, Overdose Data to Action: Limiting Overdose through Collaborative Actions in Localities, or Drug-Free Communities (DFC) recipients (see Relevant Work section).

The Research Strategy section of the application is expected to clearly describe the roles and responsibilities of all partnering entities necessary to complete the proposed project. This includes describing how the partnership will allow the applicant to complete the proposed work (e.g., demonstration of the applicant’s access to planned data sources for proposed analyses and study populations). The Research Strategy section of the application must clearly describe the nature and extent of the proposed partnership, including the roles and responsibilities of the PI(s) and of the outside entities or partner agencies, the existing working relationship, the nature and extent of the involvement to be provided by the applicant institution and outside entity, and how the partnership will ensure implementation of the proposed evaluation.

The roles and responsibilities described for each partnering entity must be substantiated with a signed Data Sharing Agreement, Letter of Support (LOS), or Memorandum of Understanding (MOU), and be included in the Letter of Support section of the application. The Data Sharing Agreement, Letter of Support (LOS), or Memorandum of Understanding (MOU) must describe the partner’s commitment of resources, time, and personnel to the proposed research.

Applications that do not include a signed Data Sharing Agreement, Letter of Support, or Memorandum of Understanding from each partnering entity may not be recommended for funding during the second level of review (see Section V. Application Review Information 4.

Review and Selection Process).

Applications will be evaluated during peer review on (under Approach and Environment):

• The extent to which the Research Strategy section clearly describes the roles and responsibilities of each partner involved in data collection and/or the effectiveness evaluation.

• The extent to which the Research Strategy clearly describes the existing working relationships between the applicant institution and all partner organizations.

• The extent to which the Research Strategy clearly describes the involvement and scope of work each partner is willing to complete, including data access for all proposed analyses if applicable, to ensure the success of the proposed research within the proposed project period.

• The extent to which the Research Strategy includes partnering with community-based collaborators, including activities focused on building relationships with community partners.

• The extent to which the Research Strategy involves the engagement of individuals in the focus population (e.g., people with lived experience with drug use).

• The extent to which the relationships and activities of the partnerships described in the Research Strategy, are documented by a signed Data Sharing Agreement, Letter of Support, or Memorandum of Understanding that delineates the intent and capabilities of each partnership.

It is incumbent on the applicant to clearly describe each contribution of each partnership to the proposed research in the Research Strategy and document the intent and capabilities of each partnership with a…