Introduction to Helping to End Addiction Long-Term Prevention Cooperative: Overview and Strategies.

This supplemental issue describes the individual studies and collaborative efforts of the Helping to End Addiction Long-term Prevention Cooperative's (HPC's) innovative approaches to rapidly develop evidence-based prevention programs for widespread dissemination. This introduction succinctly reviews (1) the context that demands the rapid development of efficacious prevention programs and their scale-ups, (2) the unique objectives of the individual HPC research projects, and (3) collective efforts to harmonize research across studies to advance the prevention of opioid misuse and gain insight into opioid misuse etiology to inform improvements in preventive interventions. At the conclusion of HPC studies, we anticipate the availability of multiple evidence-based programs to prevent opioid misuse and use disorder for persons who experience particular sources of risk and for delivery in settings where prevention has traditionally been lacking. By harmonizing and coordinating efforts across 10 distinct outcomes studies of prevention programs and making data available for analysis by non-HPC researchers, the HPC's efficacy and etiology evidence will far surpass the additive contributions of 10 individual research projects.

Economic Evaluation Design within the HEAL Prevention Cooperative.

The rapid rise in opioid misuse, disorder, and opioid-involved deaths among older adolescents and young adults is an urgent public health problem. Prevention is a vital part of the nation's response to the opioid crisis, yet preventive interventions for those at risk for opioid misuse and opioid use disorder are scarce. In 2019, the National Institutes of Health (NIH) launched the Preventing Opioid Use Disorder in Older Adolescents and Young Adults cooperative as part of its broader Helping to End Addiction Long-term (HEAL) Initiative ( https://heal.nih.gov/ ). The HEAL Prevention Cooperative (HPC) includes ten research projects funded with the goal of developing effective prevention interventions across various settings (e.g., community, health care, juvenile justice, school) for older adolescent and young adults at risk for opioid misuse and opioid use disorder (OUD). An important component of the HPC is the inclusion of an economic evaluation by nine of these research projects that will provide information on the costs, cost-effectiveness, and sustainability of these interventions. The HPC economic evaluation is integrated into each research project's overall design with start-up costs and ongoing delivery costs collected prospectively using an activity-based costing approach. The primary objectives of the economic evaluation are to estimate the intervention implementation costs to providers, estimate the cost-effectiveness of each intervention for reducing opioid misuse initiation and escalation among youth, and use simulation modeling to estimate the budget impact of broader implementation of the interventions within the various settings over multiple years. The HPC offers an extraordinary opportunity to generate economic evidence for substance use prevention programming, providing policy makers and providers with critical information on the investments needed to start-up prevention interventions, as well as the cost-effectiveness of these interventions relative to alternatives. These data will help demonstrate the valuable role that prevention can play in combating the opioid crisis.

Recruitment and retention for chronic pain clinical trials: a narrative review.

Opioid misuse is at a crisis level. In response to this epidemic, the National Institutes of Health has funded $945 million in research through the Helping to End Addiction Long-term (HEAL) Pain Management Initiative, including funding to the Vanderbilt Recruitment Innovation Center (RIC) to strategize methods to catalyze participant recruitment. The RIC, recognizing the challenges presented to clinical researchers in recruiting individuals experiencing pain, conducted a review of evidence in the literature on successful participant recruitment methods for chronic pain trials, in preparation for supporting the HEAL Pain trials. Study design as it affects recruitment was reviewed, with issues such as sufficient sample size, impact of placebo, pain symptom instability, and cohort characterization being identified as problems. Potential solutions found in the literature include targeted electronic health record phenotyping, use of alternative study designs, and greater clinician education and involvement. For retention, the literature reports successful strategies that include maintaining a supportive staff, allowing virtual study visits, and providing treatment flexibility within the trial. Community input on study design to identify potential obstacles to recruitment and retention was found to help investigators avoid pitfalls and enhance trust, especially when recruiting underrepresented minority populations. Our report concludes with a description of generalizable resources the RIC has developed or adapted to enhance recruitment and retention in the HEAL Pain studies. These resources include, among others, a Recruitment and Retention Plan Template, a Competing Trials Tool, and MyCap, a mobile research application that interfaces with Research Electronic Data Capture (REDCap).

Health economic design for cost, cost-effectiveness and simulation analyses in the HEALing Communities Study.

BACKGROUND: The HEALing Communities Study (HCS) is designed to implement and evaluate the Communities That HEAL (CTH) intervention, a conceptually driven framework to assist communities in selecting and adopting evidence-based practices to reduce opioid overdose deaths. The goal of the HCS is to produce generalizable information for policy makers and community stakeholders seeking to implement CTH or a similar community intervention. To support this objective, one aim of the HCS is a health economics study (HES), the results of which will inform decisions around fiscal feasibility and sustainability relevant to other community settings. METHODS: The HES is integrated into the HCS design: an unblinded, multisite, parallel arm, cluster randomized, wait list-controlled trial of the CTH intervention implemented in 67 communities in four U.S. states: Kentucky, Massachusetts, New York, and Ohio. The objectives of the HES are to estimate the economic costs to communities of implementing and sustaining CTH; estimate broader societal costs associated with CTH; estimate the cost-effectiveness of CTH for overdose deaths avoided; and use simulation modeling to evaluate the short- and long-term health and economic impact of CTH, including future overdose deaths avoided and quality-adjusted life years saved, and to develop a simulation policy tool for communities that seek to implement CTH or a similar community intervention. DISCUSSION: The HCS offers an unprecedented opportunity to conduct health economics research on solutions to the opioid crisis and to increase understanding of the impact and value of complex, community-level interventions.

Health communication campaigns to drive demand for evidence-based practices and reduce stigma in the HEALing communities study.

BACKGROUND: The HEALing Communities Study (HCS) is testing whether the Communities that Heal (CTH) intervention can decrease opioid overdose deaths through the implementation of evidence-based practices (EBPs) in highly impacted communities. One of the CTH intervention components is a series of communications campaigns to promote the implementation of EBPs, increase demand for naloxone and medications for opioid use disorder (MOUD), and decrease stigma toward people with opioid use disorder and the use of EBPs, especially MOUD. This paper describes the approach to developing and executing these campaigns. METHODS: The HCS communication campaigns are developed and implemented through a collaboration between communication experts, research site staff, and community coalitions using a three-stage process. The Prepare phase identifies priority groups to receive campaign messages, develops content for those messages, and identifies a "call to action" that asks people to engage in a specific behavior. In the Plan phase, campaign resources are produced, and community coalitions develop plans to distribute campaign materials. During the Implement stage, these distribution plans guide delivery of content to priority groups. Fidelity measures assess how community coalitions follow their distribution plan as well as barriers and facilitators to implementation. An evaluation of the communication campaigns is planned. CONCLUSIONS: If successful, the Prepare-Plan-Implement process, and the campaign materials, could be adapted and used by other communities to address the opioid crisis. The campaign evaluation will extend the evidence base for how communication campaigns can be developed and implemented through a community-engaged process to effectively address public health crises.

Community dashboards to support data-informed decision-making in the HEALing communities study.

BACKGROUND: With opioid misuse, opioid use disorder (OUD), and opioid overdose deaths persisting at epidemic levels in the U.S., the largest implementation study in addiction research-the HEALing Communities Study (HCS)-is evaluating the impact of the Communities That Heal (CTH) intervention on reducing opioid overdose deaths in 67 disproportionately affected communities from four states (i.e., "sites"). Community-tailored dashboards are central to the CTH intervention's mandate to implement a community-engaged and data-driven process. These dashboards support a participating community's decision-making for selection and monitoring of evidence-based practices to reduce opioid overdose deaths. METHODS/DESIGN: A community-tailored dashboard is a web-based set of interactive data visualizations of community-specific metrics. Metrics include opioid overdose deaths and other OUD-related measures, as well as drivers of change of these outcomes in a community. Each community-tailored dashboard is a product of a co-creation process between HCS researchers and stakeholders from each community. The four research sites used a varied set of technical approaches and solutions to support the scientific design and CTH intervention implementation. Ongoing evaluation of the dashboards involves quantitative and qualitative data on key aspects posited to shape dashboard use combined with website analytics. DISCUSSION: The HCS presents an opportunity to advance how community-tailored dashboards can foster community-driven solutions to address the opioid epidemic. Lessons learned can be applied to inform interventions for public health concerns and issues that have disproportionate impact across communities and populations (e.g., racial/ethnic and sexual/gender minorities and other marginalized individuals). TRIAL REGISTRATION: ClinicalTrials.gov (NCT04111939).

Introduction to the special issue on the HEALing Communities Study.

The severity of the overdose epidemic underscores the urgent need for innovative and high impact interventions that promote the rapid penetration and scale up of evidence-based practices (EBPs) in communities profoundly affected by fatal opioid overdose. This special issue shares scientific advancements in implementation research design and evaluation of a novel data-driven community-based intervention. The HEALing (Helping End Addiction Long-Term) Communities Study (HCS) is a four-year study that is designed to examine the effectiveness of the Communities That HEAL (CTH) intervention. The CTH intervention supports the dissemination of EBPs in 67 communities across four high-burdened states-Kentucky, Massachusetts, New York, and Ohio. The diversity in these communities in terms of rural-urban status, race-ethnicity and other social determinants of health facilitates generalizability of results to other communities across the US. The nine papers in this special issue describe critical elements that constitute the HCS framework and design. This includes the implementation of EBPs that have a substantial impact on fatal and non-fatal opioid overdose, the Opioid-overdose Reduction Continuum of Care Approach, communication campaigns to increase awareness and demand for EBPs and reduce stigma against people with OUD and MOUD interventions, and the process of community engagement. This includes how to form community coalitions and gain their commitment, and steps taken to mobilize coalitions to pursue EBP implementation and ensure EBPs are adapted for community needs. The collective papers in this issue demonstrate that the design of any complex study must adapt to unanticipated temporal events, including the rapidly emerging COVID-19 crisis. Readers will learn about the scientific process of the design and implementation of a community-engaged intervention, its methodologies, guiding conceptual models, and research implementation strategies that can be applied to address other health issues.

Operationalizing and selecting outcome measures for the HEALing Communities Study.

BACKGROUND: The Helping to End Addiction Long-termSM (HEALing) Communities Study (HCS) is a multisite, parallel-group, cluster randomized wait-list controlled trial evaluating the impact of the Communities That HEAL intervention to reduce opioid overdose deaths and associated adverse outcomes. This paper presents the approach used to define and align administrative data across the four research sites to measure key study outcomes. METHODS: Priority was given to using administrative data and established data collection infrastructure to ensure reliable, timely, and sustainable measures and to harmonize study outcomes across the HCS sites. RESULTS: The research teams established multiple data use agreements and developed technical specifications for more than 80 study measures. The primary outcome, number of opioid overdose deaths, will be measured from death certificate data. Three secondary outcome measures will support hypothesis testing for specific evidence-based practices known to decrease opioid overdose deaths: (1) number of naloxone units distributed in HCS communities; (2) number of unique HCS residents receiving Food and Drug Administration-approved buprenorphine products for treatment of opioid use disorder; and (3) number of HCS residents with new incidents of high-risk opioid prescribing. CONCLUSIONS: The HCS has already made an impact on existing data capacity in the four states. In addition to providing data needed to measure study outcomes, the HCS will provide methodology and tools to facilitate data-driven responses to the opioid epidemic, and establish a central repository for community-level longitudinal data to help researchers and public health practitioners study and understand different aspects of the Communities That HEAL framework.

Community engagement to implement evidence-based practices in the HEALing communities study.

BACKGROUND: The implementation of evidence-based practices to reduce opioid overdose deaths within communities remains suboptimal. Community engagement can improve the uptake and sustainability of evidence-based practices. The HEALing Communities Study (HCS) aims to reduce opioid overdose deaths through the Communities That HEAL (CTH) intervention, a community-engaged, data-driven planning process that will be implemented in 67 communities across four states. METHODS: An iterative process was used in the development of the community engagement component of the CTH. The resulting community engagement process uses phased planning steeped in the principles of community based participatory research. Phases include: 0) Preparation, 1) Getting Started, 2) Getting Organized, 3) Community Profiles and Data Dashboards, 4) Community Action Planning, 5) Implementation and Monitoring, and 6) Sustainability Planning. DISCUSSION: The CTH protocol provides a common structure across the four states for the community-engaged intervention and allows for tailored approaches that meet the unique needs or sociocultural context of each community. Challenges inherent to community engagement work emerged early in the process are discussed. CONCLUSION: HCS will show how community engagement can support the implementation of evidence-based practices for addressing the opioid crisis in highly impacted communities. Findings from this study have the potential to provide communities across the country with an evidence-based approach to address their local opioid crisis; advance community engaged research; and contribute to the implementation, sustainability, and adoption of evidence-based practices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04111939).

The Opioid-overdose Reduction Continuum of Care Approach (ORCCA): Evidence-based practices in the HEALing Communities Study.

BACKGROUND: The number of opioid-involved overdose deaths in the United States remains a national crisis. The HEALing Communities Study (HCS) will test whether Communities That HEAL (CTH), a community-engaged intervention, can decrease opioid-involved deaths in intervention communities (n = 33), relative to wait-list communities (n = 34), from four states. The CTH intervention seeks to facilitate widespread implementation of three evidence-based practices (EBPs) with the potential to reduce opioid-involved overdose fatalities: overdose education and naloxone distribution (OEND), effective delivery of medication for opioid use disorder (MOUD), and safer opioid analgesic prescribing. A key challenge was delineating an EBP implementation approach useful for all HCS communities. METHODS: A workgroup composed of EBP experts from HCS research sites used literature reviews and expert consensus to: 1) compile strategies and associated resources for implementing EBPs primarily targeting individuals 18 and older; and 2) determine allowable community flexibility in EBP implementation. The workgroup developed the Opioid-overdose Reduction Continuum of Care Approach (ORCCA) to organize EBP strategies and resources to facilitate EBP implementation. CONCLUSIONS: The ORCCA includes required and recommended EBP strategies, priority populations, and community settings. Each EBP has a "menu" of strategies from which communities can select and implement with a minimum of five strategies required: one for OEND, three for MOUD, and one for prescription opioid safety. Identification and engagement of high-risk populations in OEND and MOUD is an ORCCArequirement. To ensure CTH has community-wide impact, implementation of at least one EBP strategy is required in healthcare, behavioral health, and criminal justice settings, with communities identifying particular organizations to engage in HCS-facilitated EBP implementation.

The HEALing (Helping to End Addiction Long-term SM) Communities Study: Protocol for a cluster randomized trial at the community level to reduce opioid overdose deaths through implementation of an integrated set of evidence-based practices.

BACKGROUND: Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. METHODS: The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) a community engagement strategy with local coalitions to guide and implement the intervention; 2) a compendium of EBPs coupled with technical assistance; and 3) a series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. DISCUSSION: The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

Addressing opioid overdose deaths: The vision for the HEALing communities study.

The United States is facing two devastating public health crises- the opioid epidemic and the COVID-19 pandemic. Within this context, one of the most ambitious implementation studies in addiction research is moving forward. Launched in May 2019, the HEALing Communities Study (HCS) was developed by the National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) as part of the Helping to End Addiction Long-termSM Initiative (National Institutes of Health, 2020). The goal for this research was to reduce opioid overdose deaths by 40 % in three years by enhancing and integrating the delivery of multiple evidence-based practices (EBPs) with proven effectiveness in reducing opioid overdose deaths across health care, justice, and community settings. This paper describes the initial vision, goals, and objectives of this initiative; the impact of COVID-19; and the potential for knowledge to be generated from HCS at the intersection of an unrelenting epidemic of opioid misuse and overdoses and the ravishing COVID-19 pandemic.

Model and approach for assessing implementation context and fidelity in the HEALing Communities Study.

BACKGROUND: In response to the U.S. opioid epidemic, the HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multisite, wait-listed, community-level cluster-randomized trial that aims to test the novel Communities That HEAL (CTH) intervention, in 67 communities. CTH will expand an integrated set of evidence-based practices (EBPs) across health care, behavioral health, justice, and other community-based settings to reduce opioid overdose deaths. We present the rationale for and adaptation of the RE-AIM/PRISM framework and methodological approach used to capture the CTH implementation context and to evaluate implementation fidelity. METHODS: HCS measures key domains of the internal and external CTH implementation context with repeated annual surveys and qualitative interviews with community coalition members and key stakeholders. Core constructs of fidelity include dosage, adherence, quality, and program differentiation-the adaptation of the CTH intervention to fit each community's needs. Fidelity measures include a monthly CTH checklist, collation of artifacts produced during CTH activities, coalition and workgroup attendance, and coalition meeting minutes. Training and technical assistance delivered by the research sites to the communities are tracked monthly. DISCUSSION: To help attenuate the nation's opioid epidemic, the adoption of EBPs must be increased in communities. The HCS represents one of the largest and most complex implementation research experiments yet conducted. Our systematic examination of implementation context and fidelity will significantly advance understanding of how to best evaluate community-level implementation of EBPs and assess relations among implementation context, fidelity, and intervention impact.