Cost-effectiveness of community-based interventions for reducing opioid overdose and non-overdose deaths: simulation modeling of HEALing Communities Study

Background: The opioid overdose crisis remains a public health emergency in the United States. Evidence-based practices—including medications for opioid use disorder (MOUD) and naloxone distribution—can reduce harms, but their community-level cost-effectiveness is uncertain and may vary locally. We aimed to evaluate the cost-effectiveness of enhanced community-level implementation of evidence-based practices for opioid use disorder (OUD). Methods: We used a validated microsimulation model of OUD, calibrated with data from the HEALing Communities Study across 26 highly impacted communities in Massachusetts, New York, and Ohio. Six intervention scenarios for 2025–2030: maintaining 2024 evidence-based practice levels (status quo); improved naloxone distribution; improved MOUD retention; improved MOUD initiation; combined initiation and retention; and combined initiation, retention, and naloxone distribution. Outcomes included opioid overdose deaths (OODs), non-overdose opioid-related deaths, quality-adjusted life years (QALYs), costs (healthcare and societal), and incremental cost-effectiveness ratios (ICERs). Findings: Maintaining 2024 evidence-based practice levels was projected to yield OODs of 39–468 per 100,000 and non-overdose deaths of 238–3018 per 100,000 across communities. Enhancing MOUD initiation, retention, and naloxone distribution reduced OODs by 15–40% and non-overdose deaths by 7–24%, producing the largest QALY gains (1006–38,292). From the healthcare perspective, improved initiation plus retention was cost-effective in all communities (ICER US$11,765–US$91,058 per QALY); from the societal perspective, all enhanced scenarios were cost-saving (US$121 million–US$4.74 billion net savings). Interpretation: Community-level enhancement of MOUD initiation and retention, and for some communities also enhancing naloxone distribution, can substantially reduce opioid-related—overdose and non-overdose—deaths. These strategies are cost-effective from a healthcare perspective and cost-saving from a societal perspective, supporting investment in comprehensive, community-tailored interventions. Funding: NIH HEAL Initiative.