Misuse of opioid analgesics is an urgent public health concern. Findings from the 2014 National Survey on Drug Use and Health revealed non-medical use of opioid analgesics is second only to marijuana with respect to illicit substance use [1]. Since the early 90’s, opioid prescribing and dispensing rates have increased, accompanied by an increase in opioid overdose morbidity and mortality rates [2, 3]. As of 2014, 4.3 million individuals within the U.S. reported non-medical use of opioids within the past month [1], and more deaths from drug overdose were recorded than in any previous year. Of the 47,055 overdose deaths that occurred, 61% were caused by prescription opioids [4].

To address the growing problem of opioid misuse and abuse, 49 of 50 states in the U.S. have implemented electronic prescription drug monitoring programs (PDMPs) that track scheduled medications dispensed from pharmacies in an effort to mitigate prescription misuse and diversion, often with financial support from the U.S. Bureau of Justice Assistance [5]. PDMPs require routine, scheduled reporting by pharmacies of prescription-related data for all medications of interest. Typically such information includes medication data for the past year, date medications were dispensed, and information on patient, prescriber, pharmacy, medicine, and dose. Fulfilling both healthcare and legal functions, PDMPs can be used to generate individual-level reports providing a list of all scheduled prescriptions dispensed during a given period of time, or population-level reports identifying broader epidemiologic trends in controlled substance use within and across states. Law enforcement agencies have made use of PDMP data to identify fraudulent prescribing or illegal activity related to diverting controlled substances [6]. Prescribers and pharmacists have access to patients’ medication data and, in some states, unsolicited reports may be delivered if embedded algorithms detect patterns indicating potential misuse, abuse, or diversion [5]. These algorithms vary by state, but may, for example, be triggered when a patient receives scheduled medications from five or more prescribers at five or more pharmacies (“5 × 5″), or three or more early refills within a 3 months period (“3 × 3″) [5].

Although PDMP implementation occurred as early as 1939 in California, and in 1972 in Pennsylvania, many states have initiated PDMPs only within the past decade. In 2001, only 16 had passed legislation regarding the implementation of PDMPs, but by 2012, 49 states had passed similar legislation [5]. Because PDMPs have been adopted at the level of individual states, there is considerable variation in state policy regarding such elements as data reporting, how queries are generated, and the responsibilities of prescribers and law enforcement in prescription monitoring [7]. For example, states such as Delaware, North Dakota, and Utah mandate providers query the PDMP based on subjective “judgment of inappropriate use”, while Oklahoma requires prescribers to check its PDMP only when prescribing, administering, or dispensing methadone [7]. Perhaps as a result of this diversity, relatively little empirical research has examined the impact of PDMPs on opioid-related outcomes of concern, and PDMPs’ effectiveness as an opioid risk mitigation tool remains to be determined. Although selected best practices for PDMPs have been proposed [8], including recommendations that both provider enrollment and utilization be mandated, no standardized model has yet been proposed to facilitate evaluation or comparison of PDMP-related impacts. Defining the desired outcomes of PDMPs and the suspected mechanisms underlying these outcomes is likely to be of value in efforts to improve existing PDMPs and structure those being newly implemented in other systems, particularly in providing a rubric for evaluation that supports valid and reliable assessment of complex PDMP models across diverse settings.

The goals of the current project were therefore to: (1) synthesize the available evidence regarding the impact of PDMP policy and implementation on opioid analgesic misuse within the U.S.; and (2) building upon this literature, to develop a conceptual model in support of future efforts to evaluate PDMP implementation. To these ends, we conducted a scoping review. Scoping reviews are considered preferable to a traditional systematic review when the aim is to “map rapidly the key concepts underpinning a research area and the main sources and types of evidence available” [9]. Scoping reviews are of particular value in enabling synthesis of research that is complex and makes use of a variety of study designs. Because they allow for summary of studies drawing upon diverse outcome measures, as is the case with the emerging literature on PDMPs [10], they can facilitate rapid dissemination of knowledge where the extant research does not yet support systematic review.

A critical finding of this synthesis has been that studies of opioid-related outcomes associated with PDMP implementation typically point to a shared logic for how PDMPs are expected to function, namely that: implementation of PDMPs will increase reporting and monitoring of controlled prescriptions, resulting in reduced opioid prescribing by providers, reduced opportunities for opioid diversion and misuse, and lower frequency of negative consequences such as opioid abuse and mortality [18]. Despite this shared logic, however, there is a marked lack of discussion in the literature to date regarding the scope of PDMP-related outcomes that should be examined and assessed in order to evaluate whether, and under what conditions, their implementation is having the intended impact.

In conducting this review, therefore, we found it useful to identify four domains of opioid-related outcomes frequently examined in original studies evaluating PDMP impacts: opioid prescribing; opioid diversion and supply; opioid misuse; and opioid-related morbidity and mortality. While these domains are subject to debate and may at times overlap, we believe they provide a useful heuristic for identifying areas of relative strength and weakness in the existing evidence for the impact of PDMPs.

While the literature evaluating PDMPs remains relatively nascent, a complex picture is emerging. Studies examining the association between PDMP implementation and opioid-related outcomes do not indicate a consistent pattern of discernible change. Such variation in results is likely due in part to variation in study-related factors, including study design and methods, use of inconsistent measures of impact, and examination of PDMP impacts in a single state vs. across multiple states. Additionally, the characteristics of PDMPs themselves vary considerably across states in both legislated components and strategies for implementation. Use of PDMPs by providers prior to writing a prescription for opioids may be mandatory or optional, and states vary in the responsibility they place upon providers for any negative outcomes associated with misuse or abuse by their patients [5]. PDMPs also vary in the frequency with which data is reported to them by participating pharmacies, the ease of accessing necessary information, the types of providers allowed to register, the information available, the amount of training providers receive in use of PDMPs, and by which state agencies they are administered [5]. As a result, the timeliness and accuracy of PDMP data varies considerably across states, as does the frequency and consistency of use by providers. It was unsurprising to find two studies examining the impact of PDMP implementation on opioid diversion, given the important role played by the Bureau of Justice Assistance in supporting PDMP implementation [8]. However, reviewing the evidence makes it clear that more nuanced investigation of the impact of specific characteristics of PDMP legislation and implementation will be necessary to firmly establish the policy features and strategies associated with PDMPs that are successful in reducing negative outcomes as intended.

Even within the limitations of the current evidence, however, it has already become clear that PDMPs may also be associated with impacts beyond those generally hypothesized, both potential benefits and harms. Studies have reported that many clinicians find PDMPs useful as a tool for communication and interaction with patients [19, 20]. With patient prescription history at their disposal, providers can not only verify the patient’s current prescriptions to avoid doctor shopping or drug abuse, but can also avoid potentially dangerous non-controlled drug interactions. As noted above, an important concern has been raised regarding the “chilling effect” that PDMPs and other opioid control measures may have on providers’ opioid prescribing, leaving patients potentially undertreated for pain or seeking elsewhere for licit or illicit means to manage their pain [11]. What happens when providers re-evaluate their opioid prescribing has proven to be a critical question, although relatively few studies have yet provided data to answer it. Of the studies examined in this review, Rasubula et al. [21] found that dentists reducing their prescriptions of opioid analgesics in a dental urgent care center correspondingly increased their use of non-opioid analgesics, such as acetaminophen, and in this case drew closer to recommended practice guidelines for post-operative management of oral pain. Paulozzi et al. [3]’s findings of increased prescribing of hydrocodone, then a Schedule III drug, in PDMP states may also indicate that some providers have responded to PDMPs and associated shifts in prescribing norms by increasing prescriptions of analgesics from lower schedules. More troublingly, there is also evidence that patients, when faced with reduced ability to access licit opioids, may turn to illicit heroin, morphine, or fentanyl as alternatives, with studies indicating an increase in related mortality in some PDMP states [17, 22, 23].

There are several limitations to this review. Because the PDMP literature remains small and study outcomes and design vary, we were unable to conduct a traditional systematic review or meta-analysis, thus limiting our ability to conduct statistical analysis of the cumulative evidence. Because we described state-administered PDMP programs exclusively, findings may not extend to other prescription monitoring approaches in the U.S. and elsewhere. Nonetheless, this scoping review may inform other monitoring efforts, particularly by underscoring the importance of having clearly defined target outcomes (e.g., reduction in opioid-related morbidity and mortality) and a plan for evaluation. Conclusive evidence regarding impact cannot be determined from observational/cross sectional designs, and data to support causal relationships between PDMP implementation and opioid-related outcomes remain limited as a result. Drawing upon PubMed as the core search database may have resulted in identifying more literature emphasizing healthcare policy rather than law enforcement impacts of PDMPs. In addition, this review was limited to published data; additional analyses may be available in unpublished reports from state or other sources, and should be considered for inclusion in future systematic reviews.

We believe the conceptual framework and synthesis of findings presented here offer valuable tools for evaluating the body of knowledge around PDMPs as policy and research in this area continue to progress. Establishing a conceptual framework for PDMP evaluation is helpful in clarifying areas of relative strength and weakness in the literature. For example, we identified only a single study examining opioid misuse as an outcome of PDMP implementation [15], a concerning gap given the level of national concern about opioid misuse and its potential consequences for leading to abuse and/or overdose. Moreover, evaluating the literature available along each step of the conceptual framework makes it clear how poorly we yet understand the real-time consequences of PDMP implementation, or the nuances of how specific characteristics of PDMP policy or implementation may impact downstream effects. More sophisticated analysis of specific components of PDMPs will be required to fully understand widely varying impacts across states.

Although PDMP implementation has been initiated across the United States, little consistent evidence has yet emerged to demonstrate PDMPs’ impact on outcomes of greatest importance, whether more proximal targets such as prescribing behavior or distal outcomes such as opioid misuse, diversion, morbidity and mortality. We offer a call to action to engage in rigorous examination of PDMP impacts across the range of domains identified here, and particularly with regard to opioid misuse, and to do so with a careful eye to understanding features of PDMP legislation and implementation associated with positive outcomes. This call comes at a time when the field of PDMP evaluation is rapidly maturing and more information is becoming available through data sharing and linking with electronic medical records. The increased analytic capacity enabled by such growth should directly facilitate the examination of algorithms for identifying opioid prescribing, misuse, and abuse that are so much a part of the promise of PDMPs, but which have not yet achieved their full potential in mitigating opioid-related harms for individuals and populations.