Association Between Prescription Drug Monitoring Programs and Nonfatal and Fatal Drug Overdoses

The overuse of prescription opioids during the past 2 decades has evolved into a major public health issue in the United States. Opioid prescribing increased 350% between 1999 and 2015, from 180 to 640 morphine milligram equivalents per capita (1), with parallel increases in nonmedical use (2, 3), neonatal abstinence syndrome (4), and deaths due to both prescription opioid and heroin overdose (5, 6). The age-adjusted rate of prescription opioidrelated deaths rose from 1.0 to 4.4 deaths per 100000 population between 1999 and 2016, whereas heroin-related deaths increased nearly 5-fold since 2010, rising from 1.0 to 4.9 deaths per 100000 population between 2010 and 2016 (7). State prescription drug monitoring programs (PDMPs) have been advanced as a critical tool to better inform clinical care, identify illegal prescribing, and reduce prescription opioidrelated morbidity and mortality (8, 9). By 2017, all 50 states and the District of Columbia had an operational PDMP or passed legislation to operate a PDMP. Although PDMPs in the United States have commonalities in terms of centralized statewide data systems that electronically transmit prescription data, the administrative features of PDMPs have varied substantially among states and over time. Programs operate under different regulatory agencies, collect different types of data, require data to be updated at different intervals, and allow access to different groups of people. Despite this variability in PDMP administrative features, previous studies found implementation of these programs to be associated with reductions in the supply (10), diversion (11), and misuse of prescription opioids (12). As such, PDMPs are increasingly promoted as valuable, user-friendly, accurate, and real-time digital resources for providers and law enforcement alike (13, 14). However, evidence for the effect of PDMPs on drug-induced overdoses remains unclear. The objective of our review was to systematically search and review the literature to assess whether PDMPs are associated with changes in nonfatal or fatal overdoses; to evaluate whether specific administrative features of PDMPs are differentially associated with these outcomes and, if so, which features are most influential; and to investigate any potential unintended consequences associated with PDMPs. Methods Data Sources and Searches We followed a predefined protocol developed in November 2016 (Supplement 1 and structured reporting of the review according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines (15). We searched 5 online databases (MEDLINE, Current Contents Connect [Clarivate Analytics], Science Citation Index [Clarivate Analytics], Social Sciences Citation Index [Clarivate Analytics], and ProQuest Dissertations) for titles and abstracts of articles that examined an association between PDMP implementation and nonfatal or fatal drug overdoses. We did not impose a time or language restriction on searches (that is, queries surveyed the entire history of each online database). We included dissertations and peer-reviewed articles, as well as both published and in-process texts. We also examined references from the selected materials to identify additional articles and searched ClinicalTrials.gov. The search was first conducted in November 2016 and repeated in December 2017. All the resulting study titles and abstracts were exported to Covidence, a Web interface developed by Cochrane to systematize the review process (16). For the search terms and algorithm used in the literature search, see Appendix Table 1. Supplement. Supplementary Material Appendix Table 1. Search Strategy Study Selection All titles and abstracts were independently screened by 1 of 3 investigators (D.S.F., J.P.S., or K.K.G.) for eligibility, and those considered relevant by any investigator advanced to the full-text review. We included observational studies published in English if they estimated the before-and-after change in rates of nonfatal or fatal drug overdoses after a PDMP was implemented within a single U.S. state or in a set of states. No restrictions were placed on sample size or population age. A PDMP was considered implemented when a state operationalized its program and began to collect and distribute data or to make the data available to authorized users. Data Extraction and Quality Assessment Two researchers (J.P.S. and K.K.G.) independently read selected articles. Using a standardized article assessment form, they captured data on the specific policy studied; outcome data sources; study design; and results, including point estimates and CIs or P values. After the data were abstracted independently from each study, the 2 researchers reviewed the data for each article to ensure consistency and resolve differences. Disagreements between the researchers were reconciled by the first author (D.S.F.). Finally, 2 investigators independently assessed risk of bias (ROB) for the overdose outcomes reported in each study by using the Cochrane Risk Of Bias In Non-randomized Studiesof Interventions (ROBINS-I) assessment tool (17). By answering questions provided by ROBINS-I, the investigators assessed ROB within 8 specific bias domains (confounding, selection of participants, classification, deviations from intended interventions, missing data, measurement of outcomes, selection of the reported results, and overall bias), grading each domain as low, moderate, serious, or critical. Disagreements were resolved by consensus. Data Synthesis and Analysis Because of substantial heterogeneity in the policies examined and the analytic methods applied, we did not do a meta-analysis. Instead, we performed a qualitative assessment and synthesis using methods outlined by the Agency for Healthcare Research and Quality (18). We categorized studies into 5 groups: PDMP implementation only, specific administrative features only, both PDMP implementation and specific administrative features, PDMP implementation with other opioid policies, and PDMP robustness. Studies examining only PDMP implementation treated all PDMPs as homogenous programs without considering how their administrative features have varied among states and over time. Studies investigating specific administrative features compared states with a PDMP having a specific feature (such as mandatory registration or use, frequency of reporting, or proactive reporting) with states that either had no PDMP or had a PDMP without the specific feature. Studies of PDMPs implemented with other, associated opioid policies examined the contribution of PDMP features to those policies. Finally, studies examining PDMP robustness presented quantitative ratings of PDMP features according to their potential effectiveness in reducing diversion and overdose. We also examined 3 outcomes: nonfatal overdoses, fatal overdoses, and unintended consequences. The investigators assessed the overall strength of evidence (SOE), considering 5 domains: study limitations (determined by using ROBINS-I), directness (whether evidence linked interventions directly to a key question in the review), consistency (degree to which studies found the same direction of effect estimates), precision (degree of certainty surrounding an effect estimate), and reporting bias (selective publishing or reporting of findings on the basis of favorability of the direction or magnitude of effect estimates). On the basis of grades from the 5 specific domains, we rated the overall SOE for each intervention and outcome as insufficient, low, moderate, or high. Role of the Funding Source The National Institute on Drug Abuse (NIDA) and Bureau of Justice Assistance (BJA) had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. Results Figure 1 depicts the literature search and selection process. Seventeen articles met the inclusion criteria; 4 reported nonfatal drug overdoses, and 13 reported fatal drug overdoses. All were published between 2011 and 2018. Three were doctoral dissertations (1921), and 14 were published in peer-reviewed journals (2235). Of note, outcome data from 1 study were extracted from 2 publications (29, 36). Supplement 2 presents the characteristics and Appendix Table 2 the ROB assessments of the studies. Figure 1. Evidence search and selection. PDMP= prescription drug monitoring program. Appendix Table 2. ROB Assessment in Studies That Reported on the Association Between PDMPs and Nonfatal and Fatal Drug Overdoses The Table shows the various PDMP configurations evaluated in the 17 studies. Of these studies, 8 examined PDMP implementation in general (21, 29, 3035), 2 looked at program features alone (23, 24), 5 analyzed both PDMP implementation and program features (19, 20, 22, 27, 28), 1 investigated PDMP implementation with mandated provider review combined with pain clinic laws (25), and 1 assessed PDMP robustness (26). The study that examined robustness generated a score of PDMP administrative strength or robustness by assigning weights to specific administrative features on the basis of extant evidence, or expert judgment if evidence was lacking, regarding the expected effect of the characteristic on prescribing or overdose, then summing the weights for a PDMP in a given state for a particular year (26). Among the 7 studies that examined program features, whether alone (22, 24) or in addition to PDMPs in general (19, 20, 22, 27, 28), mandatory provider use of or registration for the PDMP was the most frequently evaluated administrative feature, with 1 study examining the association with nonfatal overdoses (28), 4 studies investigating the association with fatal overdoses (20, 22, 24, 27), and 1 study looking at the association with both nonfatal and fatal overdoses (23). In addition, 2 studies examined state authorization for providers to access PDMP data (20, 22), 2 focused on proactive repo