Foa_Content_of_RFA-CE-24-012 Modification 2.pdf

Centers for Disease Control and Prevention

NATIONAL CENTER FOR INJURY PREVENTION AND CONTROL

Rigorous Evaluation of Policy-Level Interventions to Prevent Overdose (R01)

RFA-CE-24-012

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 Rigorous Evaluation of Policy-Level Interventions to Prevent Overdose (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-24-012

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 rigorously evaluate the effectiveness of policies for reducing drug use and overdose as well as the effect of these strategies on disparities in medical care and health outcomes. Equally important to quantifying the impacts of these policies on health outcomes is understanding their implementation and how implementation affects achieving the intended outcomes of the policy among 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.

The proposed research should evaluate the impact of a selected local, state, tribal, federal, or organizational policy (e.g., school or health systems) aimed at reducing or regulating substance use or reducing drug overdose, on rates of at least two overdose outcomes (i.e., nonfatal overdose, fatal overdose, substance use disorders, substance use, initiation of substance use among youth).

The purpose of the Amendment 2 to NOFO RFA-CE-24-012 is to:

• Update the maximum total project funding per award over the project period.

The purpose of the Amendment 1 to NOFO RFA-CE-24-012 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-24-012, 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 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 https://www.grants.gov/ http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov

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 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:

05/01/2024 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 rigorously evaluate the effectiveness of policies for reducing drug use and overdose as well as the effect of these strategies on disparities in medical care and health outcomes. Equally important to quantifying the impacts of these policies on health outcomes is understanding their implementation and how implementation affects achieving the intended outcomes of the policy among 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.

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

The proposed research should evaluate the impact of a selected local, state, tribal, federal, or organizational policy (e.g., school or health systems) aimed at reducing or regulating substance use or reducing drug overdose, on rates of at least two overdose outcomes (i.e., nonfatal overdose, fatal overdose, substance use disorders, substance use, initiation of substance use among youth). The inclusion of social and structural determinants in outcome evaluations and implementation assessments can help to account for and better understand potential differential outcomes across population groups.

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 $700,000 in FY 2023 to fund up to two (2) 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 $350,000 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 three (3) years. The maximum total project funding is $1,050,000 (direct and indirect) per award, over the project period. The project period is expected to be 09/30/2024 to 09/29/2027. The total award will depend upon the project quality, duration, and cost proposed.

Application Research Strategy Length: Page limits for the Research Strategy are 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 https://grants.nih.gov/policy/early-investigators/index.htm https://grants.nih.gov/policy/early-investigators/index.htm#dis 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.

• 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 in response to two or more CDC/ATSDR NOFOs may only be selected for funding under one NOFO.

Application Type: NEW

Special Date(s) A pre-application teleconference call will be conducted on October 17, 2023 to address questions from prospective applicants regarding NOFO RFA-CE-24-012. 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 17, 2023

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

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

• Call Leader: Joyce Dieterly, MPH, Scientific Program Official

• Toll-Free Number: 1-866-600-6035

• Use Passcode 23198543# when prompted https://grants.nih.gov/support/index.html

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 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 The opioid crisis was first declared a public health emergency in 2017, due in part to increasing rates of opioid-involved overdoses, by the U.S. Department of Health and Human Services (U.S.

Government Accountability Office, 2018), and the drug overdose epidemic is also now characterized by stimulant-involved overdoses.1 Studies have evaluated the impact of policy-level interventions on overdose-related outcomes, some of which include state-level laws and policies such as those governing prescription drug monitoring programs (PDMPs), Good Samaritan Laws (GSLs), pain clinic regulations, insurance strategies, and naloxone standing order and prescribing laws.2,3,4 For example, pain clinic regulations combined with mandatory PDMP review are associated with decreased prescribing and prescription opioid-involved overdose deaths, and mandatory PDMPs alone are associated with a reduction in opioid-involved mortality2,5 . Studies examining the impact of naloxone access laws (NALs) and GSLs found that NALs were associated with reductions in opioid-involved deaths using National Vital Statistics System (NVSS) data from 1999-2014 and 2000-2014 and neither policy was associated with increases in prescription opioid misuse.3,4

Though some policies have been evaluated, more evidence is needed to understand policies that are most effective at reducing drug use and overdose as well as the effect of these strategies on reducing or worsening existing disparities in medical care and health outcomes. For example, other policies are less studied and continue to evolve. Medical marijuana laws show associations with reductions in opioid-involved deaths5; however, more recent work suggests previous findings may not hold over time.6 Additionally, some have found that non-medical marijuana laws are not associated with overdose.5,6 Policies related to marijuana are not the only laws that continue to evolve. Policies expanding access to and increasing the provision of medications for opioid use disorder were implemented during the COVID-19 pandemic, but there was variation in combinations of policies within state approaches, and the effects of interactions between those policies may not be well understood.7 More recently, the federal requirement for practitioners to have a waiver to prescribe medications such as buprenorphine for the treatment of opioid use disorder was removed8. However, studies showing that previous increases in the number of waivered clinicians did not correspond to increases in buprenorphine uptake suggest that future evaluations of the impact of the removal of the waiver can benefit from rigorous evaluation9.

Unintended consequences of policy interventions are also important to explore. For example, there is some evidence that states with active PDMPs show greater heroin use compared to states without active PDMPs or show increased treatment admissions for heroin after PDMPs were put in place.6 Some studies may also reflect both intended and unintended outcomes. For example, a Medicaid prior authorization policy study using data from Oklahoma suggested that while extended-release/long-acting opioid prescriptions were reduced among opioid-naïve patients, short-acting opioid prescriptions increased.10 Given the recency of many policies aimed at reducing drug-related harms and the possibility of changes over time and potential unintended consequences, rigorous research evaluating the effect of policy interventions is needed. It is important to assess the potential unintended consequences of such policies, including whether these policies worsen existing health disparities and systemic inequities.

Key to understanding policy impact and unintended consequences is assessing implementation.

For example, a statute enabling first responders to carry and administer naloxone has limited practical implementation without training response agencies and equipping responders with naloxone.11 Legislation requiring licensing for pain clinics that results in the revocation of licenses for doctors may serve to reduce opioids prescribed but may also create the unintended need to reassess pain and treatment for patients of those doctors.12 In both of these examples, the specific import was ascribed to considerations for people in rural areas given gaps in dissemination of naloxone training and availability in rural areas and rural residents potentially having to travel greater distances should their doctor become unavailable.10,11 Therefore, these instances also illuminate how understanding implementation is important to understand whether the intended outcomes of the policy are achieved equitably, in particular among 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.

The drug overdose epidemic is evolving rapidly, and policies are created at multiple levels of the social ecology to prevent or mitigate overdose-related outcomes. Many policies are promising or with underdetermined evidence of impact, creating a need for rigorous evaluation to inform the implementation of current policies and the development of new ones. Rigorous policy impact evaluation can help ascertain whether changes in outcomes can be attributed to a policy and builds the evidence base for policy-level strategies by creating new knowledge about the impact of policies aimed at reducing or regulating substance use or drug overdose. To support comprehensive prevention efforts, research is needed on policy approaches that have not undergone rigorous evaluations of their impact on overdose-related outcomes (i.e., nonfatal overdose, fatal overdose, substance use disorders, substance use, initiation of substance use among youth).

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 rigorously evaluate the effectiveness of policies for reducing drug use and overdose as well as the effect of these strategies on disparities in medical care and health outcomes. Equally important to quantifying the impacts of these policies on health outcomes is understanding their implementation and how implementation affects achieving the intended outcomes of the policy among 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.

The proposed research should evaluate the impact of a selected local, state, tribal, federal, or organizational policy (e.g., school or health systems) aimed at reducing or regulating substance use or reducing drug overdose, on rates of at least two overdose-related outcomes (i.e., nonfatal overdose, fatal overdose, substance use disorders, substance use, initiation of substance use among youth). The inclusion of social and structural determinants in outcome evaluations and implementation assessments can help to account for and better understand potential differential outcomes across population groups.

References

1. 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.

2. Haegerich, T. M., Jones, C. M., Cote, P.-O., Robinson, A., & Ross, L. (2019). Evidence for state, community and systems-level prevention strategies to address the opioid crisis.

Drug and alcohol dependence, 204, 107563.

3. McClellan, C., Lambdin, B. H., Ali, M. M., Mutter, R., Davis, C. S., Wheeler, E., Pemberton, M., & Kral, A. H. (2018). Opioid-overdose laws association with opioid use and overdose mortality. Addictive behaviors, 86, 90-95.

4. Rees, D. I., Sabia, J. J., Argys, L. M., Dave, D., & Latshaw, J. (2019). With a little help from my friends: the effects of Good Samaritan and naloxone access laws on opioid-related deaths. The Journal of Law and Economics, 62(1), 1-27.

5. Ansari, B., Tote, K. M., Rosenberg, E. S., & Martin, E. G. (2020). A rapid review of the impact of systems-level policies and interventions on population-level outcomes related to the opioid epidemic, United States and Canada, 2014-2018. Public Health Reports, 135(1_suppl), 100S-127S.

6. Shover, C. L., Davis, C. S., Gordon, S. C., & Humphreys, K. (2019). Association between medical cannabis laws and opioid overdose mortality has reversed over time.

Proceedings of the National Academy of Sciences, 116(26), 12624-12626.

7. Pessar, S. C., Boustead, A., Ge, Y., Smart, R., & Pacula, R. L. (2021, November).

Assessment of state and federal health policies for opioid use disorder treatment during the COVID-19 pandemic and beyond. In JAMA health forum (Vol. 2, No. 11, pp.

e213833-e213833). American Medical Association.

8. Waiver Elimination (MAT Act) | SAMHSA (https://www.samhsa.gov/medications-substance-use-disorders/waiver-elimination-mat-act#:~:text=Removal%20of%20DATA%20Waiver%20%28X- Waiver%29%20Requirement%20Section%201262,for%20the%20treatment%20of%20o pioid%20use%20disorder%20%28OUD%29.)

9. Luo, Q., & Erikson, C. E. (2023). Changes in Waivered Clinicians Prescribing Buprenorphine and Prescription Volume by Patient Limit. JAMA, 329(20), 1792-1794.

10. Heins, S. E., Frey, K. P., Alexander, G. C., & Castillo, R. C. (2020). Reducing high-dose opioid prescribing: state-level morphine equivalent daily dose policies, 2007–2017. Pain Medicine, 21(2), 308-316.

https://www.samhsa.gov/medications-substance-use-disorders/waiver-elimination-mat-act#:~:text=Removal%20of%20DATA%20Waiver%20%28X-Waiver%29%20Requirement%20Section%201262,for%20the%20treatment%20of%20opioid%20use%20disorder%20%28OUD%29.

11. Wood, C. A., Duello, A., Horn, P., Winograd, R., Jackson, L., Mayen, S., & Wallace, K.

(2021). Overdose response training and naloxone distribution among rural first responders. Journal of rural mental health, 45(3), 207.

12. Penm, J., MacKinnon, N. J., Boone, J. M., Ciaccia, A., McNamee, C., & Winstanley, E.

L. (2017). Strategies and policies to address the opioid epidemic: a case study of Ohio.

Journal of the American Pharmacists Association, 57(2), S148-S153.

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-01 Increase the proportion of people with a substance use disorder who got treatment in the past year, 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.

Public Health Impact The drug overdose epidemic is evolving rapidly, and policies are created at multiple levels of the social ecology to prevent or mitigate overdose-related outcomes. Policy approaches have the potential to reach a large number of individuals. Many policies are promising or with underdetermined evidence of impact, creating a need for rigorous evaluation and assessment of implementation to inform how current policies are implemented and the development of new ones. The inclusion of social and structural determinants in outcome evaluations and implementation assessments can help to account for and better understand potential differential outcomes across population groups. Rigorous policy impact evaluation can help ascertain whether changes in outcomes can be attributed to a policy and builds the evidence base for policy-level strategies by creating new knowledge about the impact of policies aimed at reducing or regulating substance use or drug overdose, especially among those most at risk for substance use and overdose, and related harms, including those impacted by health disparities and social determinants of health.

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 here.

This proposal also aligns with the current research priorities of the Division of Overdose Prevention. This project addresses the following research priority: Evaluate federal, state, tribal and local laws, regulations, and policies with the potential to address risk factors for and prevent prescription opioid and other prescription drug misuse, illicit drug use, overdose, and related harms.

The following publications from Division of Overdose Prevention authors have been recently released:

• 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 https://health.gov/healthypeople https://www.cdc.gov/injury/pdfs/researchpriorities/Research-Priorities-Overdose.pdf#page=1 https://www.cdc.gov/injury/pdfs/researchpriorities/Research-Priorities-Overdose.pdf#page=1 http://dx.doi.org/10.15585/mmwr.mm7150a2

Morb Mortal Wkly Rep 2022;71:1576–1582. DOI:

• Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1–95. DOI: http://dx.doi.org/10.15585/mmwr.rr7103a1

• Scholl L, Liu S, Pickens C. Suspected Nonfatal Cocaine-Involved Overdoses Overall and With Co-involvement of Opioids. Journal of Public Health Management and Practice.

2023 March 03. DOI: 10.1097/PHH.0000000000001719

• Corry B, Underwood N, Cremer LJ, Rooks-Peck CR, Jones C. County-level sociodemographic differences in availability of two medications for opioid use disorder:

United States, 2019. Drug Alcohol Depend. 2022 May 13;236:109495. doi:

10.1016/j.drugalcdep.2022.109495. Epub ahead of print.

• Cremer LJ, Underwood N, Robinson A, Guy GP Rooks-Peck CR. Association between county-level sociodemographic characteristics and county-level differences in opioid dispensing. Preventive Medicine Reports. (2021); 24, 101612. doi:

10.1016/j.pmedr.2021.101612.

• Kariisa M, Seth P, Scholl L, Wilson N, Davis NL. Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups– United States, 2004–2019. Drug and alcohol dependence. 2021 Oct 1;227:109001.

• 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

• Mital, S., Wolff, J., & Carroll, J. J. (2020). The relationship between incarceration history and overdose in North America: a scoping review of the evidence. Drug and alcohol dependence, 213, 108088. https://doi.org/10.1016/j.drugalcdep.2020.108088

• 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

CDC currently funds 66 jurisdictions as part of its Overdose Data to Action 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 fatal and non-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 http://dx.doi.org/10.15585/mmwr.mm7150a2 https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm http://dx.doi.org/10.15585/mmwr.rr7103a1 https://journals.lww.com/jphmp/Abstract/9900/Suspected_Nonfatal_Cocaine_Involved_Overdoses.116.aspx https://journals.lww.com/jphmp/Abstract/9900/Suspected_Nonfatal_Cocaine_Involved_Overdoses.116.aspx https://journals.lww.com/jphmp/Abstract/9900/Suspected_Nonfatal_Cocaine_Involved_Overdoses.116.aspx https://www.sciencedirect.com/science/article/pii/S0376871622002320 https://www.sciencedirect.com/science/article/pii/S0376871622002320 https://www.sciencedirect.com/science/article/pii/S0376871622002320 https://pubmed.ncbi.nlm.nih.gov/35605533/ https://pubmed.ncbi.nlm.nih.gov/35605533/ https://www.sciencedirect.com/science/article/pii/S221133552100303X https://www.sciencedirect.com/science/article/pii/S221133552100303X https://www.sciencedirect.com/science/article/pii/S221133552100303X https://doi.org/10.1016/j.pmedr.2021.101612 https://doi.org/10.1016/j.pmedr.2021.101612 http://dx.doi.org/10.15585/mmwr.mm7129e2 https://doi.org/10.1016/j.drugalcdep.2020.108088 https://www.cdc.gov/drugoverdose/od2a/index.html https://www.cdc.gov/drugoverdose/od2a/funding-announcements.html youth through its Drug-Free Communities Support Program (https://www.cdc.gov/drugoverdose/drug-free-communities/about.html).

2. Approach The proposed research should evaluate the impact of a selected local, state, tribal, federal, or organizational policy (e.g., school or health systems) aimed at reducing or regulating substance use or drug overdose, on reducing rates of at least two primary overdose-related outcomes (i.e., nonfatal overdose, fatal overdose, substance use disorders, substance use, initiation of substance use among youth). Applicants are encouraged to assess the impact of the policy on as many primary overdose-related outcomes as feasible. Applications that do not propose to evaluate the impact of a selected local, state, tribal, federal, or organizational policy aimed at reducing or regulating substance use or drug 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.

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 impact of policies on nicotine and alcohol as the only primary outcomes of interest do not meet the scientific intent of this NOFO. Measures of nicotine and/or alcohol use can be included with overdose-related outcomes such as nonfatal overdose, fatal overdose, substance use disorders, substance use, and initiation of substance use among youth. Applications that propose evaluation of a policy only for its impact on nicotine and/or alcohol-related outcomes as overdose-related outcomes 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 “primary overdose-related outcomes” are defined as measures of overdose-related morbidity and mortality. This could include, but is not limited to nonfatal overdose, fatal overdose, substance use disorders, substance use, and initiation of substance use among youth.

For the purposes of this NOFO “secondary overdose-related outcomes” are defined as correlates of overdose morbidity and mortality that may function as mediators of the impact of the policy on the primary outcomes or modifiers of the association between the policy and the primary outcomes (i.e., moderators). This could include but is not limited to substance use disorder treatment initiation, changes in opioid prescribing practices, fentanyl test strip distribution, naloxone distribution, other potential mediators of the association between the policy and the outcome, and moderators of the association between the policy and the outcomes. Applications that propose an evaluation of a policy for its impact only on the secondary outcomes without also evaluating the policy’s impact on at least two primary overdose-related outcomes 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).

Policy Selection

The proposed research should focus on creating new knowledge about the impact of policies aimed at reducing or regulating substance use or drug overdose. Therefore, policies https://www.cdc.gov/drugoverdose/drug-free-communities/about.html with demonstrated impacts on primary overdose-related outcomes in the scientific literature such as mandatory PDMP review and NALs, etc., are less of a priority for this funding opportunity.

This NOFO is not intended to support policy implementation. This NOFO intends to evaluate the impact of a selected local, state, tribal, federal, or organizational policy aimed at reducing or regulating substance use or drug overdose, on reducing rates of at least two primary overdose-related outcomes. The policy selected for evaluation must have been implemented before the proposed period of evaluation and may or may not be ongoing. Applications proposing to rigorously evaluate policies that have not been enacted and implemented at the time the application is submitted, as evidenced by a lack of inclusion of the dates of the enactment and implementation of the policy in the SF-424 Research Strategy, will not be recommended for funding consideration during the NCIPC second-level review (see Section V. Application Review Information).

This NOFO intends to evaluate policies that have the potential to affect social and structural conditions to reduce inequities in rates of overdose across population groups. This means the policy applies broadly to the level at which it is enacted (i.e., local, state, tribal, federal, or organizational policy [e.g., school or health systems]) and included in the evaluation are primary overdose-related outcomes at the same level. Policy evaluations that incorporate social and structural determinants in outcome evaluations and implementation assessments are strongly encouraged and could be considered new knowledge about policy impact for policies that have been previously evaluated. This NOFO will not support applications that propose to evaluate strategies (e.g., media campaigns or educational interventions) that only address individual-, peer-, or other proximal relationship and family-level factors (e.g., parenting skills, personal attitudes, knowledge about substance use, and overdose prevention).

Applications that propose only to evaluate a strategy that addresses change in individual-, peer-, or family-level factors, rather than change in social or structural community conditions (i.e., without also evaluating the policy’s impact on at least two primary overdose-related outcomes at the level of the policy) 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).

Applicants are encouraged to propose rigorous evaluations of policies that do not already have demonstrated impacts on primary overdose-related outcomes in the scientific literature. These include previously or currently implemented policy strategies with promising or undetermined evidence of impact on primary overdose-related outcomes. Promising policies include those with demonstrated impacts on risk and protective factors for primary overdose-related outcomes, but not on these specific outcomes. Policy strategies that have not been evaluated with an experimental or quasi-experimental design are considered to have undetermined effectiveness (Puddy RW, Wilkins N. Understanding evidence part 1: Best available research evidence. Accessed at:

https://www.cdc.gov/violenceprevention/pdf/understanding_evidence-a.pdf).

Examples of strategies that could be evaluated include, but are not limited to:

1. Policies to improve prescribing practices

2. Policies to expand access to and increase the provision of medications for opioid use disorder

3. Mandatory reporting of overdose data policies https://www.cdc.gov/violenceprevention/pdf/understanding_evidence-a.pdf

4. Policies related to cannabis availability and/or use

5. Polices that facilitate harm reduction strategies (e.g., distribution of fentanyl test strips, syringe service programs)

6. School-based policies related to preventing initiation of substance use or decreasing current use

The policies listed above are examples and are not an exhaustive list.

Applications proposing to engage in advocacy efforts designed to enact laws, regulations, administrative actions, or incentives will not be recommended for funding consideration during the NCIPC second-level review (see Section V. Application Review Information).

Additional information about anti-lobbying restrictions for CDC recipients is available at:

https://www.cdc.gov/grants/additional-requirements/ar-12.html.

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 polices without a 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 application’s Abstract what NCIPC Research Priority (https://www.cdc.gov/injury/researchpriorities/index.html) the research proposal intends to address.

Logic Model or Theory of Change

All applicants should provide a logic model or theory of change that links how the policy is expected to influence at least two primary overdose-related outcomes. The logic model or theory of change should include, as appropriate, process or implementation measures as well as any risk and protective factors for overdose at multiple levels of the social ecology that may serve as mediators of the association between the policy and the outcomes as well as factors that may function as moderators of the association between the policy and the outcomes (Baron and Kenney, 1986). Inclusion of such variables can facilitate our understanding of how implementation and contextual factors affect achieving the intended outcomes of the policy, in particular among 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. Additionally, implementation measures such as barriers and facilitators to implementation of the policy, the extent to which the policy was implemented as enacted, and acceptability by the population impacted by the policy can aid the understanding of the differential impacts of policies.

Specifically, the narrative describing the logic model or theory of change should:

• Describe the federal, state, local, tribal, or organizational policy to be evaluated, including details about when the policy was enacted and implemented, and justification https://www.cdc.gov/grants/additional-requirements/ar-12.html https://www.cdc.gov/injury/researchpriorities/index.html that the timeframe of the policy’s implementation allows for rigorous evaluation of impact on at least two primary overdose-related outcomes.

• Describe the level of policy implementation and intended reach (e.g., population(s), geographic region) and level of evaluation that is appropriate. For example, a local policy should be evaluated at the local level only. A state policy could be evaluated at the state or local levels. A federal policy could be evaluated at the national, state, or local levels.

• If the policy has already been or is currently being evaluated for impacts on primary overdose-related outcomes, discuss the gaps being addressed in the proposed research, and how the proposed research is not duplicative with previously conducted or current research.

• Demonstrate, through the logic model or theory of change:

o How the policy could affect rates of two or more primary overdose-related outcomes, o How the proposed measures of the primary outcomes (as well as secondary outcomes such as potential mediators and moderators and process or implementation measures if also proposed for measurement) would validly and reliably demonstrate the hypothesized changes¸ and o How the policy has the potential to reduce inequities in rates of overdose across the population in the study.

Please note that if a logic model is used, the narrative does not need to describe each element of the logic model, but rather broadly explain the proposed mechanism.

As part of demonstrating how the policy has the potential to reduce inequities in rates of overdose across the population in the study, applicants are also strongly encouraged to further examine differences in outcomes by one or more social or structural measures and provide information on the importance of the selected measure(s) in the context of overdose.

Disproportionate experiences by race, ethnicity, gender, age, geography, socioeconomic status, and other relevant dimensions should be considered at the level of the selected policy. Applicants must include literature to support their proposed research or describe an innovative approach based on knowledge of the topic in the community. Applicants must also be able to disaggregate data for analysis such that the selected measure can be examined. If applicable data are available at the selected policy level (e.g., county, school district, health system, state), as stated above, applicants are encouraged to include the measure(s) as part of the logic model or theory of change.

Research Design

This funding opportunity is intended to support evaluations that are designed to detect whether any measured changes in primary overdose-related outcomes can be attributed to the selected policy. To this end, applicants are expected to employ the most rigorous research design feasible to examine the impact of federal, state, local, tribal, or organizational policies on primary overdose-related outcomes and inequities in rates of overdose. 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). Because a policy must have been previously or is currently implemented and may have been implemented outside the control of the investigators, applicants must propose to utilize an appropriately matched comparison group or other design that would maximize the ability to make causal inferences from the findings. 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.

While it can be difficult to distinguish the impact of a policy when more than one is implemented simultaneously (Haegerich et al., 2019), applicants are also encouraged to consider designs that allow comparing changes in outcomes across polices if more than one is selected, in particular those with different aims, where data will allow. If an applicant proposes to evaluate more than one policy, each policy must be evaluated for its impact on at least two primary overdose-related outcomes and inequities across populations of interest (the latter if the data allow it).

Applicants are expected to include samples with sufficient power to assess changes following the enactment and implementation of the policy. Additionally, there should be sufficient power to assess reductions in health inequities (i.e., sample sizes among groups defined by race, ethnicity, gender, age, geography, socioeconomic status, and other relevant dimensions at the level of the selected policy).

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 three-year project period. 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 outcomes 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 hospital and emergency department data, emergency medical services (EMS) 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. Appropriate data sources will vary by the proposed research approach and outcome measures.

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 evaluate the impact of a selected local, state, tribal, federal, or organizational policy (e.g., school or health systems) aimed at reducing or regulating substance use or drug overdose, on reducing rates of at least two primary overdose-related outcomes. Primary outcomes of interest (i.e., primary overdose-related outcomes) can include, but are not limited to:

• Fatal and nonfatal drug overdose

• Substance use disorders

• Substance use

• Initiation of substance use among youth

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

• Substance use disorder treatment initiation

• Fentanyl test strip distribution

• Naloxone distribution

• Other mediators of the association between the policy and the primary outcomes

• Moderators of the association between the policy and the primary outcomes, including measures of social determinants of health

Process or implementation measures can include, but are not limited to:

• Barriers and facilitators to implementation of the policy

• Extent to which the policy was implemented as enacted

• Acceptability by the population impacted by the policy

Innovation is encouraged in the identification of data sources for measuring outcomes included in the proposed evaluation when applicable. Selection of appropriate data sources will be informed by the selected policy approach(es), primary overdose-related outcomes, and evaluation design.