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Objectives   In the United States, rising rates of overdose deaths and recent outbreaks of hepatitis C virus and HIV infection are associated with injection drug use. We updated a 2014 review of systems-level opioid policy interventions by focusing on evidence published during 2014-2018 and new and expanded opioid policies.Methods   We searched the MEDLINE database, consistent with the 2014 review. We included articles that provided original empirical evidence on the effects of systems-level interventions on opioid use, overdose, or death; were from the United States or Canada; had a clear comparison group; and were published from January 1, 2014, through July 19, 2018. Two raters screened articles and extracted full-text data for qualitative synthesis of consistent or contradictory findings across studies. Given the rapidly evolving field, the review was supplemented with a search of additional articles through November 17, 2019, to assess consistency of more recent findings.Results   The keyword search yielded 535 studies, 66 of which met inclusion criteria. The most studied interventions were prescription drug monitoring programs (PDMPs) (59.1%), and the least studied interventions were clinical guideline changes (7.6%). The most common outcome was opioid use (77.3%). Few articles evaluated combination interventions (18.2%). Study findings included the following: PDMP effectiveness depends on policy design, with robust PDMPs needed for impact; health insurer and pharmacy benefit management strategies, pill-mill laws, pain clinic regulations, and patient/health care provider educational interventions reduced inappropriate prescribing; and marijuana laws led to a decrease in adverse opioid-related outcomes. Naloxone distribution programs were understudied, and evidence of their effectiveness was mixed. In the evidence published after our search’s 4-year window, findings on opioid guidelines and education were consistent and findings for other policies differed.Conclusions   Although robust PDMPs and marijuana laws are promising, they do not target all outcomes, and multipronged interventions are needed. Future research should address marijuana laws, harm-reduction interventions, health insurer policies, patient/health care provider education, and the effects of simultaneous interventions on opioid-related outcomes.

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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