National Action Plan for Adverse Drug Event Prevention: Recommendations for Safer Outpatient Opioid Use

Abstract

Introduction. Adverse drug events (ADEs) have been highlighted as a major patient safety and public health challenge by the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion (ODPHP) in August 2014. The ADE Action Plan focuses on surveillance, evidence-based prevention, incentives, and oversights, additional research needs as well as possible measures and metrics to track progress of ADE prevention within three drug classes: anticoagulants, diabetes agents, and opioids.

Objectives and Recommendations. With outpatient opioid prescriptions being a great concern among many healthcare providers, this article focuses on recommendations from the ADE Action Plan to help guide safer opioid use in healthcare delivery settings. Its aim is to discuss current federal methods in place to prevent opioid ADEs while also providing evidence to encourage providers and hospitals to innovate new systems and practices to increase prevention.

Introduction

The National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion (ODPHP) in August 2014, outlines recommendations for three distinct drug classes and the prevention of their associated adverse drug events (ADEs): anticoagulants, diabetes agents, and opioids. The Federal Interagency Workgroup (FIW), consisting of subject matter experts from different federal agencies involved with patient safety in general or specific issues related to medication safety, authored the ADE Action Plan. The FIW’s charge was to marshal the wide array of federal resources and incorporate prior initiatives’ progress in order to create the ADE Action Plan and make opioid prescribing safer. Each section of the ADE Action Plan corresponding to the three drug classes focuses on the following areas: 1) surveillance, 2) evidence-based prevention, 3) incentives and oversights, and 4) additional research needs, as well as possible measures and metrics to track progress of ADE prevention. In the context of growing national concerns about patient safety and public health associated with opioid therapy, especially when prescribed in the outpatient setting for the management of chronic pain, the objective of this article is to adapt, condense, and summarize key points of the ADE Action Plan. These points will help guide recommendations for practitioners and other key stakeholders. The additional aim of this article is to discuss current federal methods in place to prevent opioid ADEs while also providing evidence to encourage providers and hospitals to innovate new systems and practices to increase prevention.

The FIW developed the ADE Action Plan with the understanding that as providers aim to control pain in their patients, they must balance access to safe and adequate pain care with the risk of possible opioid ADEs. The IOM Report Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research focuses on Americans living with pain and the issues they must confront [1]. The Opioids Section of the ADE Action Plan incorporates ideas and recommendations from the IOM Report to help assess the status of pain care in the United States. All recommendations herein as adapted from the ADE Action Plan aim to improve overall patient care through providing the safest and most effective, evidence-based pain care. All existing literature strives to maintain, as its foundation, this balance of effective yet safe pain medicine practices. Therefore, these recommendations recognize the importance of clinician judgment in making these decisions. Because chronic pain accounts for much of the dramatic increase in the use of opioids over the past decades, the outpatient recommendations for safer opioid use will focus on long-term opioid use for chronic pain. However, the ADE Action Plan acknowledges the need for safe opioid prescribing for inpatient acute, postoperative, and procedural pain and recommendations are intended to promote safe use of opioids for any indication. Also, for the purposes of the ADE Action Plan, the recommendations target the prevention of opioid ADEs in patients who are prescribed opioids for pain management, and does not include patients who are injured through aberrant drug behavior. Additionally, the ADE Action plan does not account for patients who are prescribed opioids for addiction treatment, persons who experience adverse outcomes in the context of non-medical use of prescription opioids and who are not prescribed opioids, and persons injured through intentional suicide attempts.

Magnitude of the Problem

Clinicians commonly prescribe opioids to treat acute and malignant pain, and over the last decade opioids have increasingly been used to manage chronic pain, which can have multiple definitions, but typically lasts longer than 6 months after the initial insult or procedure. Chronic pain is a rapidly rising diagnosis and often relates to degenerative joint and other musculoskeletal conditions. Over 100 million Americans report chronic pain annually, with pain affecting more Americans than diabetes, heart disease, and cancer combined [1]. The annual costs of chronic pain, including medical costs of pain care and the economic costs related to disability days, lost wages, and lost productivity, range from $560 billion to $635 billion (in 2010 dollars) [1]. Although opioids are an essential tool for treating and managing acute, postoperative, and procedural pain, as well as chronic pain related to cancer in the palliative care setting [1], using opioids for chronic noncancer pain is more controversial due to the limited evidence surrounding the safety and efficacy of long-term opioid use for this indication [2]. Nonetheless, opioids are recommended for treating chronic pain in clinical practice guidelines when used judiciously in appropriately selected and monitored patients [3].

The use of opioids has increased dramatically over the last decade. Between 1999 and 2010, the number of prescription opioids dispensed has roughly doubled and the sales rate of prescription opioids (in kg/10,000 pop) has increased four-fold [4], with an estimated 201.5 million opioid prescriptions dispensed in 2009 [5]. In 2009, hydrocodone, a prescription opioid, was the single most commonly prescribed medication in the United States and opioid analgesics were the third most commonly prescribed class of medications overall, leading the United States to spend approximately $8.4 billion on opioids in 2010 [6]. However, there is limited evidence on the effectiveness of long-term use of opioids and it is not clear that the dramatic increase in the use of opioids has led to improved treatment of pain overall, especially in chronic pain [7]. This trend has in turn caused several unintended and serious health and social consequences, including ADEs. Although emerging shows evidence of recent declines in incident prescribing of opioids, continued high rates of opioid prescribing, including high dose opioid prescribing, is of considerable concern [8].

Opioids cause a number of ADEs that affect patients in both inpatient and outpatient settings, with the latter being the focus of this article. These ADEs are detrimental to patients’ health and quality of life [9]. Opioid ADEs can include over-sedation and respiratory depression; gastrointestinal adverse events such as nausea, vomiting, and constipation; hyperalgesia; pruritus; and immunological and hormonal dysfunction [10]. While all of these ADEs can significantly affect patients, the FIW decided that ADEs related to unintentional opioid overdoses (i.e., over-sedation, respiratory depression) were the highest priority due to the associated mortality and morbidity. In fact, prescription opioid-related deaths are considered one of the nation’s leading preventable public health problems. In addition, the significant increase in prescription opioid deaths over the last 15 years has mirrored the distinct but interrelated trend in illicit opioid overdose deaths as reported by the Centers for Disease Control and Prevention (CDC) [11]. Opioid overdoses constitute a tremendous public health burden that is potentially amenable to measurable prevention efforts as outlined throughout the ADE Action Plan.

Focus of the ADE Action Plan

To reiterate, the recommendations outlined by the ADE Action Plan do not address misuse or abuse of opioids, which are important and related public health problems in their own right. Determining the cause of opioid-related overdose deaths and ADEs is particularly challenging when considering the differentiation between misuse/abuse and ADEs in the context of therapeutic use of opioids versus misuse/abuse in the context of non-medical use of opioids. This difficulty represents a significant challenge for those invested in reliable public health surveillance. Patients who are appropriately prescribed opioids can gradually drift into the spectrum of misuse/abuse through aberrant drug behaviors, such as increasing the dose or frequency of their opioids without consulting their prescriber [12]. The transition into misuse/abuse is also difficult to track, as healthcare providers rarely know the point at which patients cross the threshold in their private homes. Additionally, the clinical definitions of addiction, dependence, misuse, and abuse continue to be an important topic of discussion within the pain and substance use disorder communities, and this ambiguity makes drawing conclusions from available data difficult [13]. As a result, the ADE Action Plan recommendations seek to reduce harm in the context of clinical care and the therapeutic use of prescription opioids.

The ADE Action Plan recognizes the limitations of the data available and is cautious not to draw conclusions beyond what the data can explain. For example, data from the Drug Abuse Warning Network estimates that over 420,000 emergency department (ED) visits resulted from non-medical use of prescription pain relievers in 2011 [14]. However, limited data are available about the number of ED visits for opioid ADEs during the normal course of care. Due to these limitations, much of the data may include persons who deliberately misuse/abuse opioids. This is noted whenever applicable.

Recommendations

The first of the primary topics on each drug class in the ADE Action Plan is surveillance, which serves as the basis for monitoring trends in opioid injuries and prescribing, especially for monitoring and evaluating the impact of interventions designed to reduce ADEs. Unfortunately, providers responsible for documenting medication-related ADEs might not realize that their accurate reporting and charting of patient data is so important. Clearly, providers need to make their reporting more reliable, although a discussion of these efforts is largely beyond the scope of the ADE Action Plan or this report. In this context, however, the approach to surveillance must be as reliable as possible on multiple levels of aggregated data from provider, to healthcare facility, and to national databases. A number of federal and state-based surveillance systems provide data on opioid ADEs. Broadly, these surveillance systems can be categorized as measuring three types of data: 1) clinical (primary) outcomes (e.g., ED visits, deaths), 2) intermediate (surrogate) outcomes (e.g., clinical or laboratory values that precede or lead to clinical outcomes), and 3) process measures, indicators of actions aimed at mitigating the risk for clinical or intermediate outcomes (e.g., use of urine drug tests or State Prescription Drug Monitoring Program [PDMP] data). Clinical outcomes and process measures are most applicable to opioid ADEs because the utility and role of intermediate outcomes is not clearly established in the context of opioid ADE prevention. Several pre-existing federal systems involved in direct patient care (e.g., Indian Health Service [IHS] and Veterans Health Administration [VHA]) can capture regional- and facility-level information on the quality of opioid management.

However, currently very few validated metrics are available to assess the national- or facility-level burden of opioid ADEs. While there are many opportunities for further research, PDMPs represent one potentially useful surveillance approach focusing on process measures. Continued support and expansion of PDMPs holds great promise for addressing several of the current limitations. These systems can capture the data needed to identify high-risk prescribing patterns and to better understand risk factors for opioid ADEs. As of now, PDMP regulations vary widely across states in terms of which interstate agency controls the PDMP, how the information is collected and shared, along with many other factors. Ideally, PDMPs would be standardized to allow for tracking patients across settings (including across different states), identifying high-risk prescribing practices, and alerting prescribers to aberrant behaviors in patients prescribed opioids, uniformly.

Multiple efforts should be undertaken to improve surveillance approaches. It will be particularly important to establish a standardized set of reliable and valid baseline measures that can serve as the foundation for examining future trends over time and the effectiveness of initiatives to reduce opioid ADEs. A particularly important step in this regard is to improve the reliability of data capture and to validate both process and outcome measures. In this context, efforts to develop and apply reliable measures that discriminate between opioid ADEs in the normal course of care and misuse/abuse should be a priority. Though the current ADE Action Plan recommendations only focus on ADEs in the normal course of care, inevitably, misuse/abuse events will have to be distinguished once standard definitions are established. Also, identifying ADEs that occur during transitions of care will be a priority. A number of potential process measures, such as number and doses of opioids prescribed, number of patients with multiple prescribers, number of patients on high daily doses of opioids, and number of patients co-prescribed opioids and sedatives, are already available through data collection sources, such as electronic healthcare records (EHRs) and PDMPs. Federal agencies should explore the best methods to collect and manage the data to allow for accurate, real-time evaluation of trends in opioid outcomes and validated process measures. Figure 1 summarizes the FIW for Opioids’ recommendations to advance surveillance strategies for opioid ADEs.

Figure 1.

Federal interagency workgroup recommendations for actions that can potentially advance surveillance strategies for opioids ADEs.

Abbreviations: ADE = adverse drug event; CPT = Current Procedural Terminology; EHR = electronic health record; ICD = International Classification of Diseases; NPV = negative predictive value; PDMP = prescription drug monitoring program; PPV = positive predictive value. Adapted from National Action Plan to Prevent Adverse Drug Events.

Evidence-Based Prevention Tools

One of the most important areas of the ADE Action Plan concerns evidence-based prevention tools that providers can employ on a daily basis. Many evidence-based guidelines for opioid prescribing for chronic pain management address the issue of opioid safety [3,15–18]. Specifically, guidelines recommend a patient-centered care approach to shared decision-making that begins with a comprehensive pain assessment, which includes evaluation of patients’ risk for opioid ADEs and establishes treatment goals that balance potential pain management with the risks of harms. There are different risk factors for inpatient and outpatient opioid ADEs. Given the focus on outpatient settings, the authors reiterate the critical importance of safer prescribing and monitoring by providers. Patient-centered interventions are a greater priority in the outpatient setting than the inpatient setting due to the increased risk of inappropriate medication use (e.g., inappropriate dose, issues of adherence, aberrant drug behavior) in a patient’s home [12]. Federal agencies have a number of strategies to promote safe opioid prescribing and reduce opioid ADEs that can serve as a model for private stakeholders. Federal agencies should continue to develop, study, and validate opioid ADE prevention strategies and promote the adoption of validated ADE prevention strategies throughout the health community. Figure 2 summarizes current and future federal assets.

Figure 2.

Current and potential federal assets related to safe management of opioid therapy as identified by national quality strategy priorities.

Reducing Risk of Overdose

Opioid ADEs in outpatient settings are a multifaceted problem. The outpatient setting is complicated by the added complexity of prescription opioid misuse and abuse, which is one of the main drivers of prescription opioid overdoses. Additionally, once the provider writes the prescription, exactly what occurs with the patient outside of the healthcare setting is unknown. Although the ADE Action Plan does not directly address the issue of misuse/abuse, it does advocate for steps to improve prescribing behaviors to prevent patients who are prescribed opioids from engaging in misuse and abuse. While the factors driving opioid overdoses are not completely understood, varying degrees of evidence have associated a number of factors with increased risk of opioid overdose and other harms in outpatient settings and can serve as targets for outpatient opioid overdose prevention. These risk factors include high daily opioid dose [19–23], concomitant use of central nervous system (CNS) depressants (especially benzodiazepines) [12,24], recent initiation of opioid therapy in naïve patients [25,26], multiple opioid prescribers [12,27], mental health disorders [12,24,26,28], medical co-morbidities [3], active or history of substance use disorders [24,26,27], and aberrant drug related behaviors [12,26,29,30]. Federal agencies can play an essential role in promoting evidence-based strategies to address opioid overdose risk factors safe practices. Figure 3 presents opportunities to advance the ADE prevention strategies/tools in outpatient settings. These prevention opportunities are organized around the National Quality Strategy Priorities, established and maintained by the Agency for Healthcare Research and Quality (AHRQ) to improve healthcare quality.

Figure 3.

Opportunities for advancing opioid ADE prevention strategies/tools as identified by the national quality strategy Priorities—Outpatient settings (adapted from National Action Plan to Prevent Adverse Drug Events).

Improving Prevention Strategies

The ADE Action Plan continues with recommendations to foster the uptake of various strategies that promote guideline-concordant safer opioid use. Opioid prescribing guidelines for the treatment of chronic pain recommend the assessment of patients for risk factors prior to initiating opioid therapy and continuing assessment of the therapy goals and outcomes to determine the effectiveness and appropriateness of therapy for the patient. Prescribing guidelines also provide consensus-based strategies on how to reduce the risk for opioid ADEs. Knowledge of these strategies is necessary, though not sufficient, so federal agencies should continue to work to educate clinicians on safe and appropriate opioid prescribing and use available mechanisms to promote clinician education through didactic education, CMEs, and assessments of clinicians’ knowledge of safe opioid prescribing practices. Effective behavior change interventions help ensure these strategies are implemented in clinical practice. Federal agencies should work to develop, evaluate, and disseminate 1) training methods including modeling, practice, expert collaboration, and/or feedback on real-patient cases (such as expert consultation and mentoring); 2) interventions to identify and address high-risk factors for ADEs (e.g., high-risk patient screening); and 3) tools to facilitate and guide clinicians through safe practice in real-time in clinical settings (e.g., computerized decision support systems, clinical reminders, dose determination tools). Of note, ODPHP recently released “Pathways to Safer Opioid Use,” an interactive web-based training designed to reiterate important concepts for safe prescribing to clinicians [31].

Team-Based, Patient-Centered Care

Federal agencies should promote evidence-based practices for all aspects of pain management, including availability of services that identify and properly manage co-morbidities that increase the risk of opioid ADEs. These services include management of behavioral, mental health, and medical risk factors for unintentional and intentional opioid overdose, and opioid abuse, as well as use of non-opioid pharmacological therapies and non-pharmacological therapies as part of an overall pain management plan. Currently, there is limited access to multimodal, evidence-based pain management and treatment of pain co-morbidities. Federal agencies need to promote access to evidence-based therapy for pain and treatment for co-morbidities (e.g., cognitive behavioral therapy (CBT) and multidisciplinary pain clinics for pain, sleep clinics and CBT for insomnia, and substance use disorder (SUD) treatment) while also encouraging the team-based model involving the entire scope of healthcare providers.

The ADE Action Plan also encourages a focus on patient responsibility. Patients should play a major role in increasing the safer use of prescription opioids. To promote safer opioid use at home, patients need to be educated about using opioids for pain management safely and properly, not sharing opioids, storing opioids properly, and safely disposing of any opioids not used as part of therapy. Patient education materials, including materials the prescriber provides, should be developed using principles of health literacy with the aim of improving the patient’s understanding of the messages presented. Patient education should also include how to identify signs of addiction and how to identify and treat an overdose. Federal agencies should help develop, evaluate, and disseminate effective trainings, tools, and programs to provide patients with the skills and resources necessary to safely respond to moderate to severe pain or signs of overdose, and to manage opioid therapy (e.g., medication take-back programs, overdose education and naloxone distribution programs, electronic tracking and reminder tools, suicide hotlines, and relaxation skills training).

Current Federal Initiatives

The Bureau of Prisons (BoP), Department of Defense (DoD), IHS, and VHA, all of whom provide direct patient care, have taken steps to advance the practice of pain management and improve opioid safety. Because the DoD and VHA serve active and veteran military members who often have injuries requiring pain management, these agencies have been at the frontlines of evidence-based pain management and systems to promote opioid safety. Table 1 outlines the initiatives that are currently underway in VHA and DoD systems that can be evaluated, modeled, and expanded to the private sector. DoD and VHA have developed their own opioid prescribing guidelines for chronic pain [13] and have developed system-based methods to measure how the guidelines are followed and to monitor trends associated with the use of practices recommended in opioid prescribing guidelines. For example, the VHA’s evidence-based “Stepped Care Model for Pain Management (SCM-PM)” to encourage guideline-concordant care for opioid therapy showed very positive results such as decreases in opioid prescriptions and increases in non-pharmacologic therapy [32]. Yet the majority of American prescriber adherence to the prescribing guidelines can still improve and requires a system of continuous improvement. Further research and funding for programs like SCM-PM by the VHA and other agencies can allow for their systems to be refined and widely adopted into the private sector to promote evidence-based pain management and opioid ADE prevention strategies for all practitioners [32].

Table 1.

Systematic actions from VHA and DoD facilities for safe and effective opioid use for pain management

System	Action
Systematic Strategy	VHA National Pain Management Strategy—outlines systematic strategies to improve pain management while maintaining opioid safety (includes the Stepped Care Model of Pain Management (SCM-PM)).
	VHA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain —provides evidence-based recommendations on when and how to effectively and safely use opioids for chronic pain
Performance Measurement	Structure Measures—The VHA Health Care Analysis and Information Group created and administered a survey assessing organization, policy, staffing, and availability of pain management services at healthcare facilities in 2010
	Process measures—VHA developed a set of administrative data-based metrics which assess facility-level adherence to key recommendations of the VA/DoD Clinical Practice Guideline for Opioid therapy for Chronic Pain
	Outcome Measures—VHA’s electronic Mental Health Assistant makes validated assessments for patient outcomes, such as the Pain Outcomes Questionnaire (POQ), West Haven Yale Multidisciplinary Pain Inventory (WHYMPI), and the Brief Pain Inventory (BPI) available for use in the EHR
Point of Care Clinical Management and Information Support	VHA ATHENA-Opioid Therapy (OT) CDS—Opioid system is a point of care decision support system to guide opioid management
	VHA inpatient tools for converting between different strengths/formulations of opioids
	VHA’s Academic Detailing program uses clinical pharmacists and computerized panel management dashboards to work with primary care providers to address patient and clinical risk factors within their patient panel.
	VHA’s Opioid Safety Initiative uses performance metric-based review and feedback to identify and assist providers with elevated rates of clinical risk factors within their patient caseload.
	VHA’s Specialty Care Access Network-Extension for Community (SCAN-ECHO) program links a community of primary care providers with pain specialists using telehealth technology to provide co-management, consultation and training on difficult patient cases.
Co-morbidity Management/Individualized Care	Mental Health Assessment and Treatment—VHA requires annual screening for depression using the Patient Health Questionnaire (PHQ-2) and post-traumatic stress disorder (PTSD) using the Primary Care—PTSD (PC-PTSD) screen with referral for additional assessment and treatment of positive cases

Abbreviations: BPI = Brief Pain Inventory; DoD = Department of Defense; EHR = Electronic Health Record; PHQ-2 = Patient Health Questionnaire; POQ = Pain Outcomes Questionnaire; PC-PTSD = Primary Care Post-Traumatic Stress Disorder Screen; PTSD = Post-Traumatic Stress Disorder; SCAN-ECHO= Specialty Care Access Network-Extension for Community Healthcare Outcomes; VHA = Veterans Health Administration; WHYMPI = West Haven Yale Multidisciplinary Pain Inventory. Adapted from National Action Plan to Prevent Adverse Drug Events.

Incentives and Oversight

As the incentives and oversight for preventing opioid-related ADEs is broad, the authors will focus on items that involve healthcare providers and their practices. Current work of federal partners is important for monitoring administrative prescription data to identify high-risk prescribing practices and eliminate fraud, waste, and abuse related to opioids.

Prevention of Opioid Adverse Drug Events in Medicare Part D

A prime example of incentives and oversight affecting many providers concerns a change in Medicare Part D policy. Effective January 1, 2013, Centers for Medicare & Medicaid Services (CMS) implemented a new policy in Medicare Part D requiring plan sponsors to better address potential overutilization of opioids in their prescription drug benefit plans through improved drug utilization controls and case management. The goal of this policy is for Part D sponsors to reduce the overutilization of opioids among their enrollees. The policy, described in the CY 2013 Final Call Letter on April 2, 2012 and supplemental guidance issued on September 6, 2012, includes a medication safety-focused approach while maintaining beneficiary access to needed medications. Implementation of the Part D opioid policy will identify and address overutilization of opioids, thereby reducing adverse drug events.

As part of their opioid overutilization programs, Part D sponsors are expected to use retrospective drug utilization review (DUR) to identify at-risk beneficiaries and engage in case management with their prescribers. The policy permits appropriate claim controls on coverage of opioids for identified enrollees, including safety edits and quantity limits applied at point of sale (POS), with prescriber agreement or when prescribers are not responsive to case management. The suggested retrospective DUR methodology to identify beneficiaries who are at the highest risk of opioid ADEs is based on cumulative daily morphine equivalent dose (MED) across all opioids used by the beneficiary for chronic pain. This methodology accounts for the beneficiary’s use of multiple prescribers and pharmacies. The guidance also addresses data-sharing between Part D plan sponsors when a beneficiary, for whom an individual claim control has been implemented to prevent the unsafe dispensing of opioids, moves from one Part D plan to another.

CMS monitors the implementation of the new opioid policy by Part D sponsors and frequently provides updates and reports on the program. Although not a requirement, in the Final Call Letter for Contract Year 2014, CMS strongly encouraged all sponsors to consider developing the ability to implement drug-level POS audits based upon cumulative MED across the opioid class as soon as possible.

State Medicaid Drug Monitoring for ADE in the Fee for Service Outpatient Pharmacy Program²

Another example of incentives and oversight pertains to the State-level. Pharmacy coverage is an optional benefit under Federal Medicaid law; however, all states currently provide coverage for outpatient prescription drugs to most enrollees within their Medicaid programs. The Medicaid prescription drug programs include the management, development, and administration of systems and data collection necessary to operate the Medicaid Drug Rebate program, the Federal Upper Limit calculation for generic drugs, and the DUR Program.

The Medicaid DUR Program promotes patient safety through state-administered utilization management tools and processes. The state Medicaid agency’s electronic monitoring system screens prescription drug claims to identify problems, such as therapeutic duplication, drug-disease contraindications, incorrect dosage or duration of treatment, drug allergy, and clinical misuse or abuse, to minimize or prevent ADEs. DUR involves ongoing and periodic examination of claims data to identify patterns of medically unnecessary care and implements corrective action when needed.

Future Recommendations and Electronic Healthcare Records

Figure 4 summarizes opportunities to advance the prevention of outpatient opioid ADEs through incentives and oversight-based strategies. The ADE Action Plan recommendations encourage expanding administrative prescription data monitoring to identify high-risk prescribing practices and, in turn, to eliminate fraud, waste, and abuse related to opioids. Incentive and oversight levers that could advance opioid ADE prevention fall into three categories—1) healthcare quality measures utilized in such programs as CMS value-based purchasing incentive programs (e.g., EHR Meaningful Use Incentive Program, Hospital Pay-for-Reporting, Inpatient Prospective Payment System), 2) reimbursement or coverage of services, and 3) identification of inappropriate opioid prescribing, fraud, and abuse through payor data. While the FIW recommendations address the public payor perspective, they also aim to influence private sector advancements in this area allowing for private payors to learn from successful public sector strategies in this regard.

Figure 4.

Federal interagency workgroup recommendations for actions that can potentially advance policy strategies for opioid ADE prevention.

Abbreviations: ADE= Adverse Drug Event; PDMP= Prescription Drug Management Program. Adapted from National Action Plan to Prevent Adverse Drug Events.

EHRs serve an important role in providing the patient-specific information providers need to make appropriate clinical decisions in both the inpatient and outpatient settings. EHRs encourage the use of computerized Clinical Decision Support (CDS) within EHR systems to identify appropriate starting doses and morphine equivalent doses (MED) between different opioid formulations, thereby allowing clinicians to safely transition between opioid formulations and identify high doses. EHRs can also provide clinical reminders and templates to prompt and facilitate recommended clinical practices and to improve assessment, documentation, and collaborative treatment planning for patient risk factors and aberrant behaviors. For example, the VHA CDS system known as “Assessment and Treatment in Healthcare: Evidence-Based Automation (ATHENA)-Opioid Therapy” had very positive usability testing; however, testing also proved that policy initiatives must occur to overcome barriers such as time constraints [33]. Thus, the focus cannot be solely on CDS system innovation.

Healthcare quality measures are important in advancing ADE prevention efforts. In June 2013, the FIW for Opioid ADEs presented recommendations to the HHS Office of the National Coordinator (ONC) for consideration in Stage 3 of the Meaningful Use Incentive Program. These recommendations can potentially support opioid ADE prevention and monitoring and are summarized in Table 2. The recommendations are strictly for data collection purposes to help clinicians and researchers gain a better understanding of the potential risk factors associated with opioid ADEs. When the ADE Action Plan was written, there were no nationally endorsed metrics for opioid ADEs. As a result, the proposed recommendations were developed de novo or based on VHA specific measures and require further development and validation as a tool for reducing opioid ADEs. The outpatient metrics detailed in Table 2 target long-term opioid use for chronic pain and are modeled after measures currently in use by the VHA to measure adherence to the VHA/DoD Clinical Practice Guidelines for the Management of Opioid Therapy for Chronic Pain. The release of Meaningful Use 3 included no specific measures for opioids; however, the broad measure of Clinical Decision Support Interventions was updated from prior Stages, which could help prevent many opioid-related ADEs, endorse guideline-concordant care, and even recommend non-pharmacologic therapy.

Table 2.

EHR (Stage 3) meaningful use requirements that can potentially advance opioid ADE prevention as proposed by the Federal Interagency Workgroup (FIW) for ADEs

Metric	Description/Justification
Outpatient Clinical Quality Measure Concepts
Patients on high daily dose of long-term opioid therapy	There is an association between high daily dose of opioids and opioid ADEs, which requires further study to understand the impact on clinical practice
Patients co-prescribed long-term opioid therapy and CNS depressants	Co-prescribing of opioids with CNS depressants, especially benzodiazepines, is associated with opioid overdose deaths
Patients on long-term opioid therapy given a toxicology screen prior to initiating therapy and at least once a year while on long-term opioid therapy	All guidelines recommend assessment of risk related to substance abuse prior to initiating opioids and while patients are on therapy
Patients on long-term opioid therapy who were checked in the relevant Prescription Drug Monitoring Program prior to initiating therapy and at least every year if on chronic opioid therapy	Guidelines recommend monitoring PDMPs when available
	Early data shows that PDMPs may be effective, though more research will be necessary as PDMPs continue to be developed and used
Patients on long-term opioid therapy who have evidence of a written opioid care management plan	All guidelines recommend that all patients starting on long-term opioid therapy have an opioid care management plan that identifies the goals of therapy and the expectations for the patient
Number of patients on long-term opioid therapy who have evidence of mental health assessment	All guidelines recommend assessment for mental health disorders prior to initiating opioids, and treatment as appropriate
Number of patients in facility or practice prescribed opioids	Based on a VHA measure that is used to compare prescribing rates across facilities
Clinical Decision Support (CDS) Rule Concepts
Clinical Decision Support Rules to support all measures concepts	There should be supporting clinical decision support to promote best practices and improve measured processes Blank

Abbreviations: ADE = Adverse Drug Event; CNS = Central Nervous System; EHR = Electronic Health Record; IV = Intravenous; PCA = Patient Controlled Analgesia; PDMP = Prescription Drug Monitoring Program; UDS= Urine Drug Screen. Adapted from National Action Plan to Prevent Adverse Drug Events.

Research (Unanswered Questions)

A large number of unanswered questions remain about the prevention of opioid ADEs. As a result, there is a great opportunity for impact through research. Opportunities for improvement include the development and validation of clinical outcome and process measures to further establish guidelines, standardized definitions for opioid ADEs as well as aberrant behavior, requirements for reporting, and research into validated metrics that can reliably identify opioid ADEs. Federal resources can play a pivotal role in addressing research questions that can advance opioid safety and improve overall pain management. Within the clinical domain, groups responsible for safe opioid use should perform frequent evaluations of the effectiveness of prevention strategies (e.g., UDS, maximum doses, opioid agreements, single opioid prescriber) that are recommended in opioid prescribing guidelines. Collecting baseline data to evaluate trends and progress will be crucial. Workgroups also must establish and promote adoption of standardized definitions/criteria for ADEs, aberrant behavior, misuse, and abuse to compare results across studies, settings, and health systems. Additionally, stakeholders should require the standardization and coordination of surveillance systems to address opioid ADEs. By doing so, this standardization will permit researchers to study real-world management of patients identified as high-risk for opioid ADEs (e.g., promote the establishment and use of voluntary patient registries), evaluate the clinical outcomes of using PDMPs and the effects on prescribers and patients, and develop strategies to better coordinate care and improve data sharing between settings.

On the biomedical research front, there are several exciting opportunities for advancement that could be incentivized with federal grants and funding. Further research studies on the biochemical and genetic mechanisms for the etiology of chronic pain as well as examining emerging pharmacogenomics related to different responses to opioids could permit more tailored, individualized treatment. At the same time, researchers would benefit from studying the risk factors associated with ADEs to define high risk prescribing practices and identify patients at risk for opioid ADEs would prove to be beneficial. Researchers could potentially impact prescribing guidelines by funding and coordinating a comprehensive evaluation of the safety and efficacy of long-term opioid therapy for chronic pain through high quality randomized controlled clinical trials supplemented by data collected from clinical care. Finally, researchers could greatly decrease the frequency of opioid ADEs by pursuing innovative drug development for abuse resistant opioids and non-opioid drugs for refractory.

Conclusion

Overall, the National Action Plan for Adverse Drug Event Prevention outlines several recommendations to decrease the incidence of ADEs, particularly related to the use of opioids in the outpatient setting. It is a task for both federal and private groups to implement existing programs or develop new ones to decrease the burden that opioid ADEs cause, improving patient care overall. This mission will require collaboration among providers and patients, as well as the integration of existing guidelines, evolving evidence, and technology to help generate better data and outcomes.