A comparative evaluation of overdose prevention programs in New York City and Rhode Island - ABSTRACT More than one million people have died from accidental drug overdose in the United States (US) in the past twenty years. In response to this unabating crisis, New York City implemented the first two publicly recognized overdose prevention centers (OPCs) in the nation in November 2021. Rhode Island became the first state to authorize OPCs through state legislation and they are expected to open in late 2022. OPCs are community- based facilities that permit clients to consume pre-obtained controlled substances under the supervision of personnel who are trained to intervene in the event of an overdose. Staff at OPCs also provide safer drug consumption education, access to sterile drug use supplies, offer health and ancillary services, and provide referrals to other treatment, health, and recovery services. While research from other countries and from an unsanctioned site in the US suggest that OPCs produce individual health and community benefits, no evaluations exist of sanctioned OPCs in the US. The proposed study has extraordinarily high policy significance, as it will evaluate the public health, public safety, and community benefits—and potential unintended effects—of the first sanctioned OPCs in the US. We propose to conduct a rigorous, multi-site, multi-component evaluation of OPCs in New York City and Rhode Island in 2023-2027. At the individual level, we aim to evaluate whether a prospective cohort of 500 persons attending OPCs experience lower rates of overdose, other health problems, and emergency department use, and a higher rate of substance use disorder treatment initiation, compared to a cohort of 500 persons who do not attend OPCs (Aim 1). At the community level, we will examine whether neighborhoods surrounding the OPCs experience a greater change in overdose, measures of drug-related public disorder, and acute economic conditions following the opening of OPCs, compared to neighborhoods unexposed to OPCs (Aim 2). Third, we aim to delve into the role that the operational context, including neighborhood location, program models, and operating procedures, plays in shaping the effectiveness of OPCs using qualitative and ethnographic approaches (Aim 3). Finally, we will estimate additional costs and cost savings to the healthcare and criminal justice systems associated with OPC use, to support future cost-effectiveness analyses of OPCs (Aim 4). To accomplish these aims, we have assembled an internationally renowned investigative team and established strong, community-engaged research partnerships with harm reduction organizations in New York City and Rhode Island. As more jurisdictions throughout the US consider opening OPCs, findings from the proposed research will have critical implications for US drug policy. The study’s results will have powerful, lasting implications for communities that wish to offer OPCs, generate critical data to optimize their effectiveness, and provide models for sustainability and expansion of these interventions.