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s were reviewed by two investigators to identify studies for full-text review. Two investigators then independently reviewed all full-text articles for final inclusion. Inclusion was restricted to English-language articles. Discrepancies were resolved by discussion and consensus. For each study that was determined to meet inclusion criteria, a single investigator abstracted information on study design, year, setting, country, sample size, eligibility criteria, population and clinical characteristics, intervention characteristics (route of administration, dose/ concentration, time to initial and repeat dosing, training/ background of personnel administering drug), source of funding, and results relevant to each Key Question. All data abstractions were reviewed by a second investigator for accuracy. Risk of Bias Assessment of Individual Studies We assessed risk of bias of included studies using predefined criteria. Two investigators independently assessed risk of bias. Disagreements were resolved by consensus. Our approach for assessing risk of bias is based on the Methods Guide for Effectiveness and Comparative Effectiveness Reviews. We adapted criteria for assessing risk of bias from the U.S. Preventive Services Task Force. For RCTs, risk of bias assessment criteria included randomization and allocation concealment methods, comparability of groups at baseline, blinding, attrition, use of intention-to-treat analysis, and prespecification of outcomes. For cohort studies, assessment criteria were based on patient selection methods; comparability of groups at baseline; methods used to ascertain exposures, confounders, and outcomes; blinding of outcomes assessors; attrition and missing data; and statistical analysis of potential confounders. For uncontrolled longitudinal studies, we used the same criteria as for cohort studies, but did not assess comparability of groups at baseline or statistical adjustment for confounders. Studies were rated as “low risk of bias,” “medium risk of bias,” or “high risk of bias” based on the presence and seriousness of methodological shortcomings; uncontrolled studies were rated high risk of bias since they can only address the comparative effectiveness questions addressed in this review indirectly. Assessing Research Applicability Factors important for understanding the applicability of studies were recorded, such as population characteristics (e.g., age, type and dose of opioid involved in overdose, or involvement of other drugs or substances), setting (United States vs. other country, out-of-hospital vs. ED administration of naloxone), and type and level of training of people administering naloxone were recorded and assessed in subgroup and sensitivity analyses to the extent possible. We also recorded the funding source for studies.

Management of Suspected Opioid Overdose With Naloxone by Emergency Medical Services Personnel