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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 US11, 765-US91, 058 per QALY) ; from the societal perspective, all enhanced scenarios were cost-saving (US121 million-US4. 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.
Chhatwal et al. (2026) studied this question.