Objectives:

Opioid stewardship interventions promote the appropriate use of prescribed and ordered opioids to reduce the risk of opioid adverse events. Our main objectives were to determine the effectiveness of these interventions in healthcare settings on opioid prescribing and clinical outcomes (e.g., number of opioid prescriptions, opioid dosage, overdose, emergency department visits, and hospitalizations) including unintended consequences (e.g., changes in patient-reported pain intensity), and ways these interventions can be effectively implemented.

Methods:

We followed rapid review processes of the Agency for Healthcare Research and Quality Evidence-based Practice Center Program. We searched PubMed and the Cochrane Library to identify eligible systematic reviews from January 2019 to April 2023 and primary studies published from January 2016 to April 2023, supplemented by targeted gray literature searches. We included systematic reviews and studies that addressed opioid stewardship interventions implemented in healthcare settings in the United States and that reported on opioid prescribing and clinical outcomes.

Findings:

Our search retrieved 6,431 citations, of which 34 articles were eligible (including 1 overview of systematic reviews, 13 additional systematic reviews, 13 randomized controlled trials (RCTs) [reported in 14 articles] and 6 nonrandomized studies). Systematic reviews, mostly summarizing pre-post studies, included a wide variety of opioid stewardship practices that focused on patient and family engagement, healthcare organization policy, or clinician knowledge and behavior interventions, in inpatient, perioperative, emergency department, and ambulatory settings. RCTs addressed multicomponent interventions (typically a combination of prescriber education, care management and facilitated access to resources), and patient education and engagement, mainly in ambulatory chronic pain. Opioid stewardship practices involving clinical decision support or electronic health records, or multicomponent interventions (including for chronic pain) were associated with decreases in opioid prescribing or reduced doses and no increases in pain, emergency department visits, or hospitalizations (low strength of evidence for all outcomes). Patient engagement and education interventions had mixed results for opioid prescribing outcomes (insufficient strength of evidence) and no increases in pain, emergency department visits, or hospitalizations (low strength of evidence). The evidence was insufficient on other types of interventions and on outcomes of opioid refill requests and refills, patient satisfaction, or overdose. Barriers included lack of training, workload, gaps in communication, and inadequate access to nonpharmacological resources. Facilitators included clinician and patient acceptance of intervention components.

Conclusions:

Selected opioid stewardship interventions may be effective for reducing opioid prescribing and dosing without adversely affecting clinical outcomes overall, although strength of evidence was low. Unintended consequences were often not measured or not measured rigorously. Interventions to reduce opioid use should monitor unintended consequences and include access to nonpharmacological pain management resources with appropriate patient education and engagement.

1.1. Overview of the Patient Safety Practice

Opioid stewardship can be defined as promoting the appropriate use of prescribed and ordered opioids while reducing the risk of opioid use disorder, misuse, overdose, and other adverse events.³ The National Quality Forum (NQF) identified fundamental actions to support opioid stewardship in healthcare organizations,⁵ six of which are relevant to this report:

• Promote leadership commitment and culture,
• Implement organizational policies,
• Advance clinical knowledge, expertise, and practice,
• Enhance patient and family caregiver education and engagement,
• Track, monitor, and report performance data, and
• Establish accountability.

The updated 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain provides guidelines for determining whether opioids are appropriate, deciding duration, dosage and followup for prescriptions, and assessing risk and addressing potential harm.³

The MHS III report conducted a targeted search of the literature and summarized one systematic review and 14 original studies on this topic, mainly pre-post studies.⁶ In that limited review, most studies examined multicomponent interventions consisting of clinical interventions and implementation strategies, with a conclusion of moderate strength of evidence for only one outcome—significant reduction in opioid dosages. MHS III did not draw conclusions about clinical outcomes or impact on pain.

1.2. Purpose of the Rapid Review

The overall purpose of this review is to determine the effectiveness of opioid stewardship interventions in healthcare facilities or systems on key opioid prescribing and clinical outcomes (e.g., opioid dosage, opioid prescriptions, overdose, emergency department visits, and hospitalizations) including unintended consequences (e.g., changes in pain intensity), and how these interventions can be effectively implemented.

1.3. Review Questions

1. What are the frequency and severity of harms associated with opioid prescribing and ordering (i.e., outpatient prescribing or inpatient ordering)?
2. What patient safety measures or indicators have been used to examine the harms associated with opioids prescribed or ordered by clinicians?
3. What opioid stewardship PSPs have been used to prevent or mitigate the harms associated with prescribed or ordered opioid, and in what settings have they been used?
4. What is the rationale for the opioid stewardship practices that have been used to prevent or mitigate the harms associated with prescribed or ordered opioids?
5. What are the effectiveness and unintended effects of opioid stewardship practices, and what new evidence has been published since the search was done for the MHS III report in 2019?
6. What are common barriers and facilitators to implementing opioid stewardship practices?
7. What resources (e.g., cost, staff, time) are required for implementation of opioid stewardship practices?
8. What toolkits are available to support implementation of opioid stewardship practices?

2.1. Eligibility Criteria for Studies of Effectiveness

We searched for original studies and systematic reviews on Review Question 5 (the question addressing effectiveness studies) according to the inclusion and exclusion criteria presented in Table 1.

Table 1

Inclusion and exclusion criteria.

2.2. Literature Searches for Studies of Effectiveness

We searched PubMed and the Cochrane Library, supplemented by a narrowly focused search for unpublished reports that are publicly available from governmental agencies, professional societies, or membership organizations with a strong interest in the topic, including the Centers for Disease Control and Prevention (CDC), AHRQ, the National Institutes of Health (NIH), National Quality Forum (NQF), and American Hospital Association (AHA). Given that MHS III used such a limited search, rather than using the end of that report as the start date for our search, we searched for original studies since the release of the CDC guidelines in 2016 that contributed to changes in practice and opioid stewardship interventions, and we searched through April 2023. For details of the search strategy, see Appendix A.

2.3. Data Extraction (Selecting and Coding)

We used the AI feature of DistillerSR (AI Classifier Manager) as a semi-automated screening tool to conduct this review efficiently at the title and abstract screening stage. The title and abstract of each citation were screened by a team member based on predefined eligibility criteria (Table 1). The screening responses by the team members were used to teach the AI Classifier Manager, which served as a second reviewer of each citation. Discrepancies between team members and the AI Classifier Manager were reviewed and resolved by the team members. The full text of each remaining potentially eligible article was reviewed by a single team member to confirm eligibility. A second team member checked a 10 percent sample of the full text reviews to verify that important studies were not excluded.

We prioritized our efforts by extracting detailed information from the highest quality studies. Given the large number of systematic reviews and studies with strong designs, we focused on extracting detailed information from systematic reviews, randomized controlled trials (RCTs), nonrandomized controlled trials (NRCTs), and observational studies with a comparison group. We listed relevant studies having weak pre-post designs with limited information in Appendix C, but we did not synthesize them in the text of the results section.

Reviewers extracted available information and organized it according to the review questions and included author, year, study design, frequency and severity of the harms, measures of harm, characteristics of the PSP, rationale for the PSP, outcomes, implementation barriers and facilitators, resources needed for implementation, and description of toolkits. One reviewer completed the data abstraction, and a second reviewer checked the first reviewer’s abstraction for completeness and accuracy.

2.4. Risk of Bias (Quality) Assessment

For studies that addressed Review Question 5 about the effectiveness of PSPs, we used the Cochrane Collaboration’s tool for assessing the risk of bias of RCTs or the ROBINS-I tool for assessing the Risk Of Bias In Non-randomized Studies – of Interventions.^10,11 We did not assess the risk of bias in the pre-post studies, recognizing that they have a high risk of bias because of the lack of a separate comparison group.

For RCTs, we used the items in the Cochrane Collaboration’s tool that cover the domains of selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.¹⁰ For nonrandomized studies, we used specific items in the ROBINS-I tool that assess bias due to confounding, bias in selection of participants into the study, bias in classification of interventions, bias due to deviations from intended interventions, bias due to missing data, bias in measurement of outcomes, and bias in selection of the reported results. The risk of bias assessments focused on the main outcome of interest in each study.¹¹

For a recent eligible systematic review, the primary reviewer used the criteria developed by the United States Preventive Services Task Force Methods Workgroup for assessing the quality of systematic reviews.¹²

• Good - Recent relevant review with comprehensive sources and search strategies; explicit and relevant selection criteria; standard appraisal of included studies; and valid conclusions.
• Fair - Recent relevant review that is not clearly biased but lacks comprehensive sources and search strategies.
• Poor - Outdated, irrelevant, or biased review without systematic search for studies, explicit selection criteria, or standard appraisal of studies.

2.5. Strategy for Data Synthesis

We narratively summarized findings across systematic reviews and across primary studies. We did not conduct a meta-analysis. For Review Question 5 about the effectiveness of PSPs, we recorded information about the context of each primary study and whether the effectiveness of the PSP differed across patient subgroups. As the systematic reviews generally summarized the literature descriptively and did not grade the strength of evidence, we based our grading on the primary studies. We graded the strength of evidence for PSPs with more than one primary study of effectiveness using the methods outlined in the AHRQ Effective Health Care Program Methods Guide for Effectiveness and Comparative Effectiveness Reviews and focusing on the key clinical outcome for each intervention type such as adverse consequences of changes in pain intensity or healthcare utilization, and the key opioid prescribing outcome such as quantity or doses.¹³

3.1. Benefits and Harms

• PSPs involving clinical decision support or electronic health record interventions, and multicomponent PSPs (including for chronic pain) were associated with decreases in opioid prescribing or doses (low strength of evidence).
• PSPs involving patient engagement and education had mixed results for opioid prescribing outcomes (insufficient strength of evidence).
• PSPs involving clinical decision support or electronic health record interventions, patient engagement and education, and multicomponent PSPs did not show an increase in pain, emergency department visits, or hospitalizations (low strength of evidence for all outcomes).
• The evidence was insufficient on the following intervention types: opioid stewardship committees, protocols or care bundles, clinician education or academic detailing, clinical pharmacist consultation, increased access/emphasis on nonopioid or multimodal analgesia, and/or limits on opioid prescribing/ordering, healthcare organization guidelines, clinical audits, dashboards, prescriber feedback, and peer comparison
• The evidence was insufficient on outcomes of opioid refill requests and refills, patient satisfaction, or overdose.
• Barriers included lack of clinician training, workload, gaps in communication, and inadequate access to non-pharmacological resources. Clinician and patient acceptance of intervention components were facilitators.

3.2. Future Research Needs

• More research is needed on opioid stewardship committees, dashboards and peer comparisons, and care bundle interventions such as urine drug testing, drug use contracts, and prescription drug monitoring program queries, which are commonly used health system interventions and quality indicators.

4.1. Number of Studies

Our search retrieved 6431 unique titles and abstracts from which we reviewed 6431 full text articles for eligibility (Figure 1). We found 34 studies that met our eligibility criteria. A listing of studies excluded during full text review is included in Appendix B, List of Included Studies, and information abstracted from each included study is provided in Appendix C, Evidence Tables.

Pre-post studies do not have a separate comparison group and thus have a high risk of bias, we did not discuss them in the main body of the report, but we summarize them briefly in the appendix.

Figure 1

Results of the search and screening.

4.2. Findings for Review Questions

Figure 2 presents an overview of included evidence by type of opioid stewardship intervention. We did not find any recent systematic reviews or original studies that specifically examined the effectiveness of opioid stewardship committees, dashboards, or prescriber feedback.

Characteristics of the included systematic reviews and primary studies are presented in Tables 2a and 2b.

Figure 2

Overview of included evidence by type of opioid stewardship intervention. SR = systematic review

Table 2a

Characteristics of the included systematic reviews.

Table 2b

Characteristics of the included primary studies (pre-post studies listed in Appendix).

4.2.3. Question 3. What Opioid Stewardship Patient Safety Practices (PSPs) Have Been Used To Prevent or Mitigate the Harms Associated With Prescribed or Ordered Opioids, and in What Settings Have They Been Used?

Table 3 provides an overview of the types of PSPs that have been used to prevent or mitigate the harms associated with prescribed or ordered opioids, and the settings in which they have been used.

Table 3

Overview of opioid stewardship patient safety practices and settings.

4.2.5. Question 5. What Are the Effectiveness and Unintended Effects of Opioid Stewardship Practices, and What New Evidence Has Been Published Since the Search Was Done for the Making Healthcare Safer (MHS) III Report in 2019?

The limited search in the MHS III report included one systematic review and 14 studies, two of which were RCTs, and found that the majority of studies evaluated multicomponent interventions including guideline implementation. Other studies evaluated electronic health record tools such as decision support, alerts and prescription drug monitoring program implementation, dashboards for monitoring and/or feedback, clinician education, opioid committees, and case management. The MHS III report concluded that overall, SOE for significant reductions in opioid dosage was moderate; for clinical outcomes, only two studies evaluated reduction in overdoses, with neither having a significant effect. The systematic review included in the MHS III report (published in 2010) evaluated opioid treatment agreements and urine drug testing in chronic pain and concluded that the strength of evidence was relatively weak for reducing opioid misuse.⁵⁵ Given the limited search in MHS III, we summarize the full literature from our search from 2016 forward instead of relying on a comparison to the MHS III review.

We identified 14 systematic reviews since 2019 (1 overview of systematic reviews and 13 reviews), and 13 RCTs (reported in 14 articles), and 6 nonrandomized studies since 2016 that assessed the effectiveness and unintended effects of opioid stewardship practices. We present the findings by intervention type (Table 4). We first discuss the evidence from systematic reviews, followed by evidence from primary studies (RCTs and nonrandomized studies with a comparison group). A detailed summary of benefits and harms from included systematic reviews and primary studies is provided in Appendix C, Evidence Tables C-2 through C-9.

A list of pre-post studies is in Appendix C (see Evidence Table C-50).

Table 4

Overview of evidence by intervention type for primary studies.

Risk of Bias

Several types of risk of bias were present in the included RCTs based on our assessments using the Cochrane Collaboration’s tool.¹⁰ The most common potential cause of bias was lack of details about allocation and blinding in the majority of studies. Twelve of the 13 RCTs had high risk of bias (Figure 3). For the nonrandomized studies, our assessments using the ROBINS-I tool (Risk Of Bias In Non-randomized Studies – of Interventions) revealed concerns for bias in confounding, patient selection, measurement of outcomes, selection of reported results, and deviations from intended assignments.¹¹ Five of the six nonrandomized studies had critical risk of bias (Figure 4).

Figure 3

Risk of bias assessments for randomized controlled trials included in this review.

Figure 4

Risk of bias assessments for nonrandomized studies included in this review.

4.2.5.1. Interventions Focused on Opioid Stewardship Involving Organizational Leadership and Policies Within a Healthcare Facility or Healthcare System

Intervention categories in this section include opioid stewardship committees, clinical decision support or electronic health record interventions, and protocols or care bundles.

4.2.5.1.1. Opioid Stewardship Committees

No studies met our inclusion criteria for addressing opioid stewardship committees alone.

4.2.5.1.2. Clinical Decision Support or Electronic Health Record Interventions

Five systematic reviews addressed clinical decision support or electronic health record interventions.^{16,21,23,24,26} Clinical decision support at the point of care¹⁶ and reduced default number of prescribed opioid pills in the electronic health record^23,24,26 were associated with reduced opioid prescribing. One systematic review found a significant decrease in opioid prescribing with reduced default electronic health record opioid prescribing quantity, including the finding from interrupted time series studies of a reduced rate of opioid prescription at 6 months (change −11.65; 95% confidence interval (CI): −29.30 to 5.99).²⁴

Providing decision support at the point of care¹⁶ was associated with reduced emergency department (ED) visits. Reducing the default number of opioid pills in the electronic health record²⁶ was not associated with a significant increase in opioid requests. A systematic review addressing computerized order entry in acute care found that its use was associated with lower rates of respiratory depression from opioids.²¹ Neither of these systematic reviews graded the SOE.

We also identified two RCTs^29,30 and one nonrandomized study assessing clinical decision support or electronic health record interventions (Table 5).²⁸ Both RCTs compared the effect of modifying opioid prescribing defaults in the electronic health record to preexisting defaults. One RCT evaluated a default of prescribing a dispense quantity of 10 tablets compared to no change in preexisting defaults in a large health system’s primary care practices and emergency departments.²⁹ The other RCT compared defaults of 10 tablets, 5 tablets, or no change to preexisting defaults within a health system’s dentistry practices.³⁰ Both RCTs evaluated clinical outcomes including outpatient visits, emergency department visits, and hospitalizations during the 30-day period after the index prescription. Neither RCT found statistically significant differences in healthcare utilization.^29–30 The one RCT in dentistry practices found a statistically significant increase in opioid prescription reordering in both the 5 tablet and 10 tablet groups compared to control.³⁰ There was no difference in opioid prescription reorders in the second RCT based in primary care and emergency departments.²⁹

Both RCTs found that the 10 tablet intervention groups (default dispense quantity) were statistically significantly more likely to have prescriptions for 10 tablets or fewer be prescribed fewer tablets at baseline and have a lower total morphine milligram equivalents (MME) per day prescribed at baseline. The RCT in the dentistry practice sustained these statistically significant differences at 30 days while the RCT in primary care and the emergency department found a statistically significant difference at 30 days in total pills prescribed but not in total MME per day. The study comparing 5 tablets to control found no differences in prescriptions for 10 tablets or fewer at baseline, number of tablets prescribed at baseline or at 30 days, nor in MME prescribed at baseline or at 30 days compared to control.

Neither RCT assessed any of the process outcomes defined in our inclusion criteria.

One nonrandomized study evaluated a treatment algorithm for headache in the ED, including diagnostic and treatment planning aids.²⁸ They compared patients in two post algorithm implementation periods (first six months after adoption, and then one year later) to historical controls. Compared to controls, patients in both post-implementation periods were significantly less likely to be treated with opioids or barbiturates in the emergency department or discharged with opioids or barbiturates. There were no significant differences between control and post-implementation time one (i.e., six months after algorithm implementation) groups in post-treatment pain scores, frequency of imaging, consults, or admissions. Findings were similar for post-implementation time two (i.e., one year after algorithm implementation) except for a significant increase in the number of neurology consults and admissions when compared to the control group.

We graded the SOE as low for healthcare utilization and low for opioid prescribing.

Table 5

Overview of clinical outcomes and opioid prescribing/ordering outcomes for clinical decision support or electronic health record interventions reported in the primary studies.

4.2.5.1.3. Protocols or Care Bundles (Which May Address Components Such as Treatment Agreements, Urine Drug Screening, Risk Assessment, and/or Naloxone Prescribing)

One systematic review assessed protocols that used the amount of prescribed opioids used for hospitalized patients to guide discharge prescribing.²³ This review found that the protocols resulted in reduced quantities of opioid prescribed at discharge. We did not identify any systematic reviews or recent primary studies addressing care bundles.

4.2.5.2. Interventions Focused on Clinical Knowledge, Expertise, and Behavior Related to Prescribed or Ordered Opioids

Intervention categories in this section include clinician education or academic detailing, clinical pharmacist consultation, increased access/emphasis on nonopioid or multimodal analgesia and/or limits on opioid prescribing/ordering, and healthcare organization guidelines.

4.2.5.2.1. Clinician Education or Academic Detailing

Four systematic reviews addressed clinician education or academic detailing alone.^16,17,22,23 Three of these reviews reported an association with reduced opioid prescribing after the intervention.^16,17,23 For clinical outcomes, systematic reviews did not find an increase in refill requests,¹⁷ or pain-related complaints,¹⁷ but found an increase in number of patients returning to the emergency department within 30 days for pain control.²³ Only one of the systematic reviews graded the quality of evidence, and determined it to be low for a group of interventions that included this category.¹⁶

4.2.5.2.2. Clinical Pharmacist Consultation

Two systematic reviews addressed clinical pharmacist consultation.^18,26 The interventions addressed clinical pharmacist interventions in outpatient or community pharmacy settings (mostly review of charts)¹⁸ and pharmacist assistance with prescriptions in postsurgical prescribing.²⁶ Both reviews found an overall reduction in overall opioid dose after pharmacist intervention^18,26 and one study included in this review found an increase in nonopioid analgesics.¹⁸

For clinical outcomes, one review found that 5 of 8 studies showed significant reduction in pain intensity¹⁸ and the other review found no increase in post-operative pain,²⁶ and no increases in hospital visits.²⁶

For process outcomes, one study found an increase in physical therapy referrals.¹⁸

Neither of these systematic reviews graded the SOE.

4.2.5.2.3. Increased Access/ Emphasis on Nonopioid or Multimodal Analgesia and/or Limits on Opioid Prescribing/Ordering

We identified three systematic reviews addressing this type of intervention.^14,16,26 These reviews found that opioid replacement treatment (defined as transition to maintenance therapy with a different opioid and then attempting to taper down the opioid) showed no significant difference for opioid dose.¹⁴ The reviews also found that deprescribing methods in ambulatory chronic pain (with or without nonopioid pain management techniques), coordinated recommendations for opioid prescribing, and increasing opioid-free prescribing (often with nonopioid analgesia and related patient counseling) all reduced opioid dose or prescribing.^14,16,26 The review on opioid-free prescribing found results for clinical outcomes, with no differences in pain, requirement for additional prescriptions, or satisfaction.²⁶ One of these reviews graded the SOE and found moderate level certainty for the outcome of opioid dose reduction based on a single study.

4.2.5.2.4. Healthcare Organization Guidelines

Three systematic reviews addressed healthcare organization guidelines for opioids and/or emphasizing nonopioid pain medications in surgical or hospital discharge.^22,23,26 All three found decreases in prescription size and doses.^22,23 For clinical outcomes, there was generally improvement in pain, no difference in patient satisfaction or phone calls for uncontrolled pain, and mixed results for refills or requests.^22,23,26

We identified one primary study of a quality improvement project assessing patient use of post-operative medications; patient satisfaction with their pain management; and standardizing opioid prescribing guidelines for patients undergoing mastectomy with immediate reconstruction.³¹ Across the phases, the overall amount of opioids prescribed per patient was reduced (median of 450 MMEs per day in Phase I, and 98 MMEs per day in Phase IV). The range of the amount of prescribed opioids across patients was reduced from the beginning to end of the project (225 to 925 MMEs per day in Phase I, and 0 to 250 MMEs per day in Phase IV). Across phases, patient satisfaction fluctuated, starting at 93% of patients reporting high satisfaction in Phase I (baseline), 83% in Phase II, 73% in Phase III, and 93% in Phase IV.

We determined that the SOE was insufficient.

4.2.5.3. Interventions Focused on Patient and Family Education or Engagement Related to Use of Prescribed or Ordered Opioids

Six systematic reviews addressed patient and family education or engagement interventions.^{14,16,19,22,26,27} Specific interventions included a variety of counseling and educational interventions in different settings, including perioperative care and chronic pain management, and pain self-management and tapering down opioids.

Four of the five reviews that addressed opioid dose prescribing found significantly reduced doses or discontinued therapy;^14,16,22,26 the other review found no difference in a single study.¹⁹ All of the five systematic reviews addressing pain found reductions in pain intensity^{14,16,19,22,26} and the one review that addressed opioid refill requests found no difference, with low level of certainty.²⁷ One systematic review focusing on long-term management of chronic pain¹⁴ found that patient and family education or engagement interventions that included pain self-management with tapering down opioids moderately reduced opioid dose (mean difference in MME per day −14.31 (95% CI, −21.57 to −7.05) compared to no intervention, with moderate level of certainty. The review found a moderate effect on pain intensity (standardized mean difference −0.59 (95% CI, −1.02 to −0.16), with low level of certainty).

We identified six RCTs that addressed patient and family education or engagement intervention. We report the findings from these six RCTs by outcomes below (Table 6).

4.2.5.3.1. Clinical Outcomes

Six RCTs assessed the effect of patient and family education or engagement on clinical outcomes (Table 6).^32–37 In general, RCTs evaluated education-related interventions (such as pain expectations, use of opioids for pain including risks, and the use of nonopioid analgesics) compared to previously established standard of care perioperative education or counseling. Two studies included a shared decision-making model which incorporated patient expectations of how many opioid tablets they believe they should receive after surgery in subsequent prescribing.^36,37 All studies were conducted in the ambulatory surgery setting. All six RCTs assessed multiple clinical outcomes including pain, patient satisfaction, healthcare utilization, and opioid refill requests (Table 6).

Five of the six RCTs assessed pain as a clinical outcome.^32–35,37 Four of the RCTs found no statistically significant differences in pain between groups.

One RCT compared opioid related postoperative education to standard of care in patients undergoing primary arthroscopic rotator cuff repair.³² They found statistically significantly lower pain scores in the study group compared to the control group at 2 weeks and 6 weeks, with no significant difference at 3 months.

Four of the RCTs evaluated opioid refills.^33,35–37 One RCT in patients undergoing ambulatory hand surgery found statistically significantly higher opioid refills in the control group compared to the intervention group.³⁵ Another RCT in patients undergoing mastectomy with immediate, implant based breast reconstruction did not identify a difference between groups.³³ The two RCTs that included shared decision making around total opioid tablets prescribed found conflicting results.^36,37 One study of patients undergoing minimally invasive hysterectomy reported more refills in the patient directed arm compared to the control group.³⁶ The other study of patients undergoing isolated mid-urethral sling placement found no statistically significant differences in refills between groups.³⁷

Three of the RCTs assessed patient satisfaction.^35–37 Only one RCT found statistically significant differences, with the intervention group being more likely to be satisfied with their pain management.³⁵

Two RCTs evaluated healthcare utilization.^34,36 One RCT evaluated unexpected visits to the emergency department or to the office due to uncontrolled pain and found no differences between groups.³⁶ The other assessed for “serious adverse events” defined as those that led to a call or unplanned return visit to the clinic or hospital setting. There were no differences between groups.³⁴

We determined the SOE to be low for the outcome of pain.

4.2.5.3.2. Opioid Prescribing or Ordering Outcomes

Five of the six RCTs evaluating patient and family education or engagement interventions assessed opioid prescribing or ordering outcomes (Table 6). All five assessed opioids prescribed after surgery, with mixed results. Three of the five had no significant differences between groups in opioids prescribed or dispensed.^33–35 The two studies comparing a shared decision-making model with standard of care did report a statistically significantly lower amount of opioids post-operatively in the intervention arm compared to the control group.^36,37

One RCT also evaluated inpatient MME doses and found no differences between groups.³³

We determined the SOE to be low for the outcome of opioid prescribing.

4.2.5.3.3. Changes in Process Outcomes

None of the RCTs evaluating patient and family education or engagement interventions assessed the process outcomes defined in our inclusion criteria.

Table 6

Overview of clinical outcomes and opioid prescribing/ordering outcomes for patient and family education or engagement interventions reported in the primary studies.

4.2.5.4. Interventions Focused on Tracking, Monitoring, and Reporting Performance Data Related to Prescribed or Ordered Opioids

Intervention categories in this section include clinical audits and dashboards.

4.2.5.4.1. Clinical Audits

One systematic review addressed patient-controlled analgesia safety monitoring in acute care and found a decreased overdose rate in one study.²¹ This review found no change in opioid prescribing. The review did not grade the SOE.

4.2.5.4.2. Dashboards

No studies met our inclusion criteria for addressing dashboards alone.

4.2.5.5. Interventions Focused on Clinical Accountability Related to Prescribed or Ordered Opioids

Intervention categories in this section include prescriber feedback and peer comparison.

4.2.5.5.1. Prescriber Feedback

No studies met our inclusion criteria for addressing prescriber feedback alone.

4.2.5.5.2. Peer Comparison

One systematic review found that in interrupted time series studies there was a reduced rate of opioid prescribing with a change of −28.10 (95% CI, −44.83 to −11.38), and in a combined analysis of pre-post studies, cohort studies and RCTs there was a reduced rate of opioid prescribing, OR 0.46 (95% CI, 0.29 to 0.72).²⁴ The review did not grade the SOE.

We also identified one RCT that assessed an intervention focused on clinical accountability related to prescribed or ordered opioids.³⁸ This study randomized Veterans Health Administration (VHA) facilities to receive a notice describing a new dashboard based on the Stratification Tool for Opioid Risk Mitigation (STORM). It also described the importance of risk mitigation strategies and mandated case review. The intervention arm received the same notice with an extra paragraph stating that facilities which did not meet a target of 97 percent case reviews would receive technical assistance and be required to submit an action plan on improving the review rate. The RCT found no statistically significant difference in serious adverse events or death between groups (hazard ratio (HR) 1 (95% CI, 0.91 to 1.09) for all-cause mortality and 1.03 (95% CI, 0.97 to 1.08) for any serious adverse event). The RCT did not evaluate opioid prescribing or process outcomes.

We determined the SOE to be insufficient for the outcome of serious adverse events.

4.2.5.6. Multicomponent Interventions Focused on Opioid Stewardship

We identified one overview of systematic reviews and three additional systematic reviews that addressed multicomponent interventions.

The overview of systematic reviews²⁰ focused on patient-targeted interventions for opioid prescribing in any setting and included 4 reviews published from 2011 to 2021. These reviews focused on chronic pain in ambulatory settings and (a) multidisciplinary pain programs^57–59 and (b) multicomponent tapering down opioids support interventions, such as dose reduction protocols, opioid replacement, and nonpharmacologic therapies.^57,60 For opioid outcomes, multidisciplinary pain programs were consistently associated with reduced opioid prescribing compared to usual care,^57,58 with low certainty of evidence.²⁰ One review concluded that tapering down opioids support programs were consistently associated with reduced opioid prescribing compared to usual care.⁵⁸ The other review found that patient-focused interventions were not associated with opioid dose reduction in the intermediate term and did not increase the number of individuals able to stop opioids;⁶⁰ the certainty of evidence was low.²⁰ One of the systematic reviews also addressed multicomponent clinician-focused interventions consisting of training plus decision tools, and identified one study that reported a statistically significant difference in opioid dose reduction.⁶⁰

For clinical outcomes, both types of patient-targeted interventions showed improved or unchanged pain,^57–59 with low certainty of evidence.²⁰

Three additional systematic reviews addressed multicomponent interventions.^16,21,23 These interventions often included clinician education as well as system policies or guidelines on opioids and emphasized nonopioid approaches, protocols, audit and feedback, and patient involvement. System policies combined with other interventions were associated with decreased opioid prescribing. These multicomponent interventions included policy limits on number of opioid pills prescribed together with, clinician education,^16,21 discharge prescribing workflow changes,²³ and adverse event monitoring with computerized order entry or opioid safety guidelines. There were mixed results on the effect of multicomponent interventions in acute care on opioid prescribing, but an increase in nonopioid analgesic use. These multicomponent interventions included clinician education emphasizing nonopioid approaches in addition to protocols, audit and feedback or patient involvement.²¹

For clinical outcomes, system policies of number of opioid pills prescribed together with and clinician education¹⁶ was associated with no significant difference in pain intensity. There were mixed results associated with the effects of multicomponent interventions including clinician education (emphasizing nonopioid approaches and protocols), audit and feedback, or patient involvement²¹ on hospital length of stay. The multicomponent interventions were associated with reduced hospital readmissions and increased patient satisfaction with pain treatment. Adverse event monitoring combined with computerized order entry or opioid safety guidelines²¹ had no change in hospital length of stay or mortality.

Eight primary studies (reported in 9 articles) addressed multicomponent interventions (Table 7)]. We report the findings from these primary studies by outcomes below.

4.2.5.6.1. Clinical Outcomes

Four RCTs described in five articles and four nonrandomized studies assessed the effect of multicomponent interventions on clinical outcomes (Table 7). These multicomponent interventions most typically involved a combination of opioid education to prescribers, academic detailing, nurse care management and facilitated access to additional specialists. The majority of RCTs^40–42,45 were conducted on ambulatory care patients on long-term opioid therapy. One RCT was conducted with adult patients who visited an emergency department more than 10 times over a 12-month period, with at least two of those visits attributed to pain or “drug-seeking behaviors.”³⁹ One RCT conducted in the emergency department focused on two components: a case manager and a multidisciplinary collaboration to develop individualized plans for providers to access the next time the patient presented to the emergency department.³⁹

Four RCTs assessed several clinical outcomes including opioid refills, pain, patient satisfaction and healthcare utilization. Two RCTs described in 3 articles reported on opioid refill requests.^40–42 There were no differences in early refill requests between groups in either study.^40,41

One RCT (reported in 2 articles) assessed patient satisfaction.^41,42 There were no differences between groups in high patient satisfaction (defined as a score in the top quartile) or high patient trust in provider (defined as a score in the top quartile).

Two RCTs (reported in 3 articles) reported on pain outcomes with no differences identified between groups in either study.^41,42,45 One RCT³⁹ conducted in emergency departments reported on healthcare utilization and found the intervention group experienced a decrease in the incidence of emergency department visits over the 12-month study period and had a lower average number of emergency department visits over the study period.

One nonrandomized study evaluated the impact of the VHA’s Opioid Safety Initiative (OSI) on opioid prescribing patterns and opioid toxicity.⁴⁴ The OSI comprised five components: (1) prescribing dashboards which aggregated and reported opioid prescribing on the facility-, provider-, and patient-level; (2) clinical practice guidelines for safe prescribing; (3) provider education; (4) a complementary integrative health initiative; and (5) a stepped care model and pain management teams. A second nonrandomized study evaluated the VHA’s Whole Health Primary Care Pain Education and Opioid Monitoring Program (PC-POP) for patients seen in primary care who receive long-term opioid therapy for chronic noncancer-related pain.⁴⁷ PC-POP includes components such as chart review, education, evaluation (patient self-assessments of anxiety, depression, physical functioning, drug use/abuse, and quality of life), prescription and action (e.g., treatment planning and follow up) implemented by a multidisciplinary care team. Two nonrandomized studies evaluated opioid stewardship interventions in surgical services. One study prospectively evaluated the impact of opioid minimizing and opioid eliminating strategies in surgical patients undergoing inguinal hernia repair or cholecystectomy. Patients were grouped into one of three conditions: (1) control in which patients received standard of care with no changes, (2) opioid-sparing in which patients received patient education, perioperative multimodal analgesia, and opioid prescription at discharge, and (3) zero-opioid wherein patients received the same opioid-sparing protocol but were not provided an opioid prescription at discharge.⁴⁶ The second surgical services study reported the results of a quality improvement study evaluating the implementation of an opioid-free discharge protocol in patients undergoing ureteroscopy for urolithiasis.⁴³ The protocol included medication and patient counseling interventions at five stages of perioperative care: pre-operative clinic, preoperative surgical staging, intraoperative, postanesthetic care, and discharge.

Four nonrandomized studies, two conducted in the outpatient setting^44,47 and two in surgical services,^43,46 included patient reported outcomes or emergency department utilization and hospital admission outcomes. A segmented regression of pre-OSI (n = 19,382) and post-OSI (n = 22,682) opioid naïve patients treated for prostate, lung, breast or colorectal cancer at a VHA facility revealed a statistically significant increase in pain-related emergency department visits in post-intervention patients.⁴⁴ There were no significant differences between PC-POP enrollees (n = 423) and non-enrollees (n = 311) in emergency department visits or inpatient hospitalizations.⁴⁷ One study conducted in surgical services found no significant differences in patient-reported pain scores or satisfaction two weeks post-discharge.⁴⁶ The other study found no differences in emergency department visits between groups.⁴³

We determined the SOE to be low for the outcome of pain.

4.2.5.6.2. Opioid Prescribing or Ordering Outcomes

Three RCTs^39,40,45 reported on opioid prescribing or ordering outcomes [Table 7]. Two RCTs found statistically significant decreases in opioid prescribing.^39,40 One RCT, targeting interventions in emergency departments, found a decrease in the odds of receiving an opioid prescription from an emergency department provider as well a smaller average number of opioid prescriptions written over 12 months in the intervention group compared to controls. Another RCT, in primary care, identified an adjusted difference in daily opioid dose of −6.8 MME (p < 0.001). Another third RCT, in primary care, found no difference in prescription opioid dose in MME at final visit.⁴⁵

Three nonrandomized studies reported opioid prescribing or ordering outcomes. The study evaluating the VHA’s OSI program found a statistically significant decrease in the monthly rate of new opioid prescriptions after OSI implementation.⁴⁴ Evaluation of the PC-POP program revealed no significant differences between PC-POP enrollees and non-enrollees in suboxone doses or MME daily dose.⁴⁷ One study in surgical services found enrolled patients were less likely to have an opioid prescription at discharge as well as significantly lower morphine equivalent doses.⁴³

We determined the SOE to be low for the outcome of opioid prescribing.

4.2.5.6.3. Changes in Process Outcomes

Two RCTs reported in 3 articles assessed process outcomes including urine drug testing, presence of an opioid treatment agreement, prescription drug monitoring program reports review, and achievement of guideline concordant care.^40–42 Both RCTs assessed use of urine drug screening and opioid treatment agreements. Both RCTs found that the intervention arm was more likely to undergo urine drug testing (71% versus 20%, adjusted OR 13.38 (95% CI, 5.85 to 30.6) in one study, and 74.6% versus 57.9%, p < 0.001 in the other study) and was more likely to have a signed treatment agreement (adjusted OR 61.5 (95% CI, 15.3 to 247.2) in one study, and 53.8% versus 6%, p < 0.001 in the other study) when compared to controls.

One RCT evaluated achievement of guideline concordant care (defined as urine drug testing and presence of an opioid treatment agreement) and found that the intervention group was more likely to have guideline concordant care than controls (65.9% versus 37.8%, p < 0.001).⁴⁰

Another RCT assessed for use of the prescription drug monitoring program and found no statistically significant differences between groups (adjusted OR 3.85 (95% CI, 0.99 to 14.93).^41,42

One nonrandomized study included process outcomes.⁴⁷ The study evaluating the PC-POP program found rates of naloxone prescriptions, urine drug screens, STORM reports generated, assessments for mental health, substance use, and well-being were significantly more frequent for PC-POP enrollees when compared to non-enrollees (p < 0.001 for all comparisons). No difference in prescription drug monitoring program reports were found between groups (p = 0.428). Enrollees were also more likely to be referred to nonpharmacological treatment (i.e., cognitive behavioral therapy for chronic pain, whole health, living with chronic conditions, and trauma sensitive yoga) than non-enrollees (p < 0.001 for all comparisons) except for mindfulness center referrals which showed no difference in between enrollees and non-enrollees (p = 0.132).

We did not grade the SOE for process outcomes.

Table 7

Overview of clinical outcomes and opioid prescribing/ordering outcomes for multicomponent interventions reported in the primary studies.

4.2.5.7. Systematic Reviews Crossing Different Types of Interventions

We identified three systematic reviews that combined different intervention types: one in urologic surgery¹⁵;one for frequent emergency department visits due to pain²⁵; and part of another systematic review in the ED.²⁴ The interventions (which included hospital or departmental guidelines for opioid prescriptions, analgesic escalation protocols, change in default electronic medical record opioid prescription prescriber instructions, patient education and multicomponent interventions) showed a statistically significant reduction in opioid prescriptions or mean prescribed opioids on discharge,^15,24,25 with no significant worsening of patient-reported satisfaction with analgesia, number of phone calls for inadequate analgesia, or number of patients requiring emergency visits for pain.^15,24

5.1. Summary and Interpretation of Findings

Research on opioid stewardship interventions has expanded significantly in recent years. Included systematic reviews primarily summarized pre-post studies of a wide variety of interventions including patient and family engagement, healthcare organization policy, and clinician education and training. These interventions were evaluated in various healthcare delivery settings including inpatient, perioperative, emergency department, and ambulatory care. Randomized controlled trials (RCTs) mainly addressed multicomponent interventions, most commonly prescriber education, care management and facilitated access to additional resources, and patient education and engagement, mainly studying chronic pain in the ambulatory setting.

Given the heterogeneous intervention types, delivery settings, and outcomes evaluated, we conclude that opioid stewardship patient safety practices evaluated since the release of the 2016 Centers for Disease Control and Prevention (CDC) opioid guidelines were associated with decreases in opioid prescribing or doses (low strength of evidence). With reduced opioid doses, studies did not find increases in unintended consequences of increased pain, or an increase in hospitalizations or emergency department visits (low strength of evidence). Insufficient evidence was available on opioid refills or requests, patient satisfaction or overdose.

Barriers included lack of training, workload, gaps in communication, and inadequate access to nonpharmacological resources. Clinician and patient acceptance were identified as important facilitators. We also noted an emphasis on the important role of patient engagement and education in these interventions, including in nonpharmacological approaches to pain management.

Below we summarize, by intervention category, the broader literature reported in systematic reviews (which generally did not include grading of the strength of evidence) and the high-quality primary studies (Table 8).

No reviews or primary studies were found for dashboards, prescriber feedback, or opioid stewardship committees as standalone interventions.

Table 8

Summary of the evidence by interventions.

5.2. Limitations

We note limitations both of this rapid review and of the literature. Since peaking in 2012, opioid prescribing in the United States has markedly decreased over recent years. This trend might be influenced by a variety of factors including increased recognition of the negative societal impacts of opioid overprescribing, the CDC and other prescribing guidelines, state and federal education, legislative initiatives, and prescribing norms. Thus, it is challenging to interpret the specific impact of interventions evaluated in pre-post studies. We therefore focused on studies with stronger designs, but because these mainly focused on only a few types of interventions, we also descriptively summarized systematic reviews which included pre-post studies to acknowledge the broader lower quality evidence for other kinds of interventions.

We limited our review to systematic reviews and studies that addressed clinical outcomes. Although this ensured that we evaluated the potential patient-centered unintended consequences of reduced opioid prescribing, this excluded some studies of interventions in settings such as the emergency department where followup information on pain outcomes may be limited. However, we included systematic reviews and studies in the emergency department. The studies also included evaluations of unintended consequences of changes in pain, opioid refills, hospitalizations, and emergency department use outcomes for which we found low strength of evidence.

The systematic reviews had important limitations. In particular, systematic reviews generally did not synthesize the literature but summarized the results of individual studies. We also found significant overlap between the studies addressed in the systematic reviews. In addition, some of the reviews included studies that were out of the scope of our review (e.g., studies outside the United States). Because of challenges with the quality of the systematic review methods and their heavy dependence on pre-post studies and lack of evidence grading, we reviewed RCTs and nonrandomized studies dating back to 2016 (the release of the CDC opioid prescribing guidelines) and used these studies as our primary source for drawing conclusions and grading the strength of evidence.

We rated all nonrandomized studies, and all but one of the RCTs, as having a high risk of bias, usually due to lack of blinding for outcome assessments, among other issues. Some earlier systematic reviews often rated the risk of bias of pre-post studies and some of the RCTs as moderate or low risk of bias. We reviewed all RCTs dating back to 2016 and based our grading only on the primary studies. Some of the earlier systematic reviews rated the strength of evidence as low for opioid prescribing outcomes, but other reviews, including Making Healthcare Safer III, rated the strength of evidence for opioid prescribing as moderate. Prior reviews did not consistently provide their methods for assessing risk of bias and strength of evidence, so we noted when our assessments differed from the prior assessments. We included a summary of our assessments of the risk of bias of included primary studies since 2016 (see Figures 3 and 4).

5.3. Implications for Clinical Practice and Future Research

Appendix A. Methods

Appendix B. List of Excluded Studies Upon Full-Text Review

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2. Acquisto NM, Schult RF, Sarnoski-Roberts S, et al. Effect of pharmacist-led task force to reduce opioid prescribing in the emergency department. Am J Health Syst Pharm. 2019 Oct 30;76(22):1853–61. doi: 10.1093/ajhp/zxz204. PMID: 31557284. - Other: Study included in previous systematic reviews [PubMed: 31557284] [CrossRef]
3. Adalbert JR, Ilyas AM. Implementing Prescribing Guidelines for Upper Extremity Orthopedic Procedures: A Prospective Analysis of Postoperative Opioid Consumption and Satisfaction. Hand (N Y). 2021 Jul;16(4):491–7. doi: 10.1177/1558944719867122. PMID: 31441326. - No comparison group [PMC free article: PMC8283100] [PubMed: 31441326] [CrossRef]
4. Agarwal AK, Lee D, Ali Z, et al. Patient-Reported Opioid Consumption and Pain Intensity After Common Orthopedic and Urologic Surgical Procedures With Use of an Automated Text Messaging System. JAMA Netw Open. 2021 Mar 1;4(3):e213243. doi: 10.1001/jamanetworkopen.2021.3243. PMID: 33764425. - Not focused on an intervention of interest [PMC free article: PMC7994954] [PubMed: 33764425] [CrossRef]
5. Ahonle ZJ, Jia H, Mudra SA, et al. Drug Overdose and Suicide Among Veteran Enrollees in the VHA: Comparison Among Local, Regional, and National Data. Fed Pract. 2020 Sep;37(9):420–5. doi: 10.12788/fp.0025. PMID: 33029067. - Does not address an outcome of interest [PMC free article: PMC7535957] [PubMed: 33029067] [CrossRef]
6. Al-Astal AY, Sodhi K, Lakhani HV. Optimization of Prescription Drug Monitoring Program to Overcome Opioid Epidemic in West Virginia. Cureus. 2022 Feb;14(2):e22434. doi: 10.7759/cureus.22434. PMID: 35371719. - Narrative or scoping review [PMC free article: PMC8941824] [PubMed: 35371719] [CrossRef]
7. Alderson SL, Farragher TM, Willis TA, et al. The effects of an evidence- and theory-informed feedback intervention on opioid prescribing for non-cancer pain in primary care: A controlled interrupted time series analysis. PLoS Med. 2021 Oct;18(10):e1003796. doi: 10.1371/journal.pmed.1003796. PMID: 34606504. - Addresses effectiveness review question only but does not report clinical outcomes [PMC free article: PMC8489725] [PubMed: 34606504] [CrossRef]
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12. Andereck JW, Reuter QR, Allen KC, et al. A Quality Improvement Initiative Featuring Peer-Comparison Prescribing Feedback Reduces Emergency Department Opioid Prescribing. Jt Comm J Qual Patient Saf. 2019 Oct;45(10):669–79. doi: 10.1016/j.jcjq.2019.07.008. PMID: 31488343. - Addresses effectiveness review question only but does not report clinical outcomes [PubMed: 31488343] [CrossRef]
13. Anne S, Mims JW, Tunkel DE, et al. Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations Executive Summary. Otolaryngol Head Neck Surg. 2021 Apr;164(4):687–703. doi: 10.1177/0194599821996303. PMID: 33822678. - Qualitative study without any quantitative data [PubMed: 33822678] [CrossRef]
14. Arizmendez NP, Kotovicz F, Kram JJF, et al. Multimodal Local Opioid Prescribing Intervention Outcomes in Chronic Noncancer Pain Management. J Am Board Fam Med. 2019 Jul–Aug;32(4):559–66. doi: 10.3122/jabfm.2019.04.180296. PMID: 31300576. - Addresses effectiveness review question only but does not report clinical outcomes [PubMed: 31300576] [CrossRef]
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17. Aulet RM, Trieu V, Landrigan GP, et al. Changes in Opioid Prescribing Habits for Patients Undergoing Rhinoplasty and Septoplasty. JAMA Facial Plast Surg. 2019 Dec 1;21(6):487–90. doi: 10.1001/jamafacial.2019.0937. PMID: 31600382. - Intervention or policies established by entities other than healthcare providers [PMC free article: PMC6802264] [PubMed: 31600382] [CrossRef]
18. Awadalla R, Gnjidic D, Patanwala A, et al. The Effectiveness of Stewardship Interventions to Reduce the Prescribing of Extended-Release Opioids for Acute Pain: A Systematic Review. Pain Med. 2020 Oct 1;21(10):2401–11. doi: 10.1093/pm/pnaa139. PMID: 32488237. - Addresses effectiveness review question only but does not report clinical outcomes [PubMed: 32488237] [CrossRef]
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21. Baird J, Faul M, Green TC, et al. Evaluation of a Safer Opioid Prescribing Protocol (SOPP) for Patients Being Discharged From a Trauma Service. J Trauma Nurs. 2019 May/Jun;26(3):113–20. doi: 10.1097/jtn.0000000000000435. PMID: 31483766. - Addresses effectiveness review question only but does not report clinical outcomes [PMC free article: PMC6727973] [PubMed: 31483766] [CrossRef]
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Appendix C. Evidence Tables

[Reference list located at the end of the body of the report]

Evidence Table C-1. Characteristics of included systematic reviews addressing harms, effectiveness and unintended effects of opioid stewardship practices (MS Word, 476K)

Evidence Table C-2. Results of included systematic reviews addressing harms, effectiveness and unintended effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 468K)

Evidence Table C-3. Results of included systematic reviews addressing harms, effectiveness and unintended effects of clinical knowledge, expertise, and behavior interventions related to prescribed or ordered opioids (MS Word, 476K)

Evidence Table C-4. Results of included systematic reviews addressing harms, effectiveness and unintended effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 447K)

Evidence Table C-5. Results of included systematic reviews addressing harms, effectiveness and unintended effects of tracking, monitoring, and reporting performance data (MS Word, 447K)

Evidence Table C-6. Results of included systematic reviews addressing harms, effectiveness and unintended effects of clinical accountability interventions (MS Word, 449K)

Evidence Table C-7. Results of included systematic reviews addressing harms, effectiveness and unintended effects of multicomponent interventions (MS Word, 460K)

Evidence Table C-8. Results of included systematic reviews addressing harms, effectiveness and unintended effects of a combination of interventions (MS Word, 459K)

Evidence Table C-9. Results of included systematic reviews addressing harms, effectiveness and unintended effects of other types of interventions (MS Word, 471K)

Evidence Table C-10. Characteristics of included primary studies addressing effects of opioid stewardship practices (MS Word, 489K)

Evidence Table C-11. Intervention characteristics of primary studies addressing effects of opioid stewardship practices (MS Word, 489K)

Evidence Table C-12. Patient characteristics of primary studies addressing effects of opioid stewardship practices (MS Word, 525K)

Evidence Table C-13. Healthcare utilization outcome (categorical data) of primary studies addressing effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 487K)

Evidence Table C-14. Opioid refill request (categorical data) of primary studies addressing effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 459K)

Evidence Table C-15. Rates of opioid prescribing (categorical data) of studies addressing harms, effectiveness and unintended effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 467K)

Evidence Table C-16. Pain intensity or distress outcome (continuous data) of included studies addressing effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 453K)

Evidence Table C-17. Number of pills per prescription (continuous data) of primary studies addressing effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 503K)

Evidence Table C-18. Total morphine milligram equivalents per prescription (continuous data) of primary studies addressing effects of organizational leadership and policies within a healthcare facility or healthcare system (MS Word, 478K)

Evidence Table C-19. Opioid refill request (categorical data) of primary studies addressing effects of clinical knowledge, expertise, and behavior interventions related to prescribed or ordered opioids (MS Word, 450K)

Evidence Table C-20. Patient satisfaction (categorical data) of primary studies addressing effects of clinical knowledge, expertise, and behavior interventions related to prescribed or ordered opioids (MS Word, 449K)

Evidence Table C-21. Number of pills per prescription (continuous data) of primary studies addressing effects of clinical knowledge, expertise, and behavior interventions related to prescribed or ordered opioids (MS Word, 453K)

Evidence Table C-22. Total morphine milligram equivalents per prescription (continuous data) of primary studies addressing effects of clinical knowledge, expertise, and behavior interventions related to prescribed or ordered opioids (MS Word, 451K)

Evidence Table C-23. Healthcare utilization outcome (categorical data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 453K)

Evidence Table C-24. Opioid refill request (categorical data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 456K)

Evidence Table C-25. Opioid refill request (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 455K)

Evidence Table C-26. Patient satisfaction (categorical data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 455K)

Evidence Table C-27. Patient satisfaction (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 447K)

Evidence Table C-28. Rates of opioid prescribing (categorical data) of studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 449K)

Evidence Table C-29. Rates of opioid prescribing (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 452K)

Evidence Table C-30. Pain intensity or distress outcome (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 468K)

Evidence Table C-31. Number of pills per prescription (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 453K)

Evidence Table C-32. Total morphine milligram equivalents per prescription (continuous data) of primary studies addressing effects of patient and family education or engagement related to use of prescribed or ordered opioids (MS Word, 449K)

Evidence Table C-33. Overdose rates (categorical data) of primary studies addressing effects of clinical accountability interventions related to prescribed or ordered opioids (MS Word, 451K)

Evidence Table C-34. Healthcare utilization outcome (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 459K)

Evidence Table C-35. Healthcare utilization outcome (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 459K)

Evidence Table C-36. Opioid refill request (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 460K)

Evidence Table C-37. Opioid refill request (continuous data) of studies addressing effects of multicomponent interventions (MS Word, 457K)

Evidence Table C-38. Pain intensity or distress outcome (categorical data) of studies addressing effects of multicomponent interventions (MS Word, 447K)

Evidence Table C-39. Pain intensity or distress outcome (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 474K)

Evidence Table C-40. Patient satisfaction outcome (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 456K)

Evidence Table C-41. Patient satisfaction outcome (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 447K)

Evidence Table C-42. Rates of opioid prescribing outcome (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 454K)

Evidence Table C-43. Rates of opioid prescribing outcome (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 459K)

Evidence Table C-44. Other referrals relevant to paint management outcomes (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 455K)

Evidence Table C-45. Risk assessment outcomes (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 455K)

Evidence Table C-46. Total morphine milligram equivalents per prescription (continuous data) of primary studies addressing effects of multicomponent interventions (MS Word, 464K)

Evidence Table C-47. Treatment agreement use (categorical data) of studies addressing effects of multicomponent interventions (MS Word, 470K)

Evidence Table C-48. Urine drug screen ordering or administration (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 460K)

Evidence Table C-49. Urine drug screen ordering or administration (categorical data) of primary studies addressing effects of multicomponent interventions (MS Word, 449K)

Evidence Table C-50. Characteristics and reported outcomes of identified pre-post studies addressing harms, effectiveness and unintended effects of opioid stewardship practices (MS Word, 595K)

Evidence Table C-51. Strength of evidence from included primary studies (MS Word, 447K)