Experience of switching from a daily to a less frequent administration of injection treatments.

BACKGROUND: Daily injections of recombinant human growth hormone are the standard of care to treat growth failure due to pediatric growth hormone deficiency (GHD). While effective, daily injections are burdensome and can compromise adherence. In recent years, novel injection treatments requiring less frequent administration for growth hormone deficiency (GHD) have been developed. A targeted, pragmatic literature review was conducted to summarize and document the patient experience of moving from daily to less frequent injections, with a specific focus on changing from daily to weekly injection treatments in pediatric GHD (pGHD). OBJECTIVE: Explore and describe the patient experience when switching from a daily to a less frequent injection schedule for GHD. METHODS: Targeted literature searches were conducted to identify literature describing the patient experience of moving from a daily to weekly injection in GHD. Supplementary searches were conducted to identify literature describing the patient experience of moving from daily to less frequent injection regimens in other medical conditions. RESULTS: Across searches, 1,691 abstracts were reviewed and 13 articles were included in the final analysis. These publications reported that patients moving to less frequent injections across a variety of conditions, including GHD, experienced increased convenience and satisfaction, higher adherence rates, fewer adverse events, and improved quality of life. Less frequent injections were also reported to be at least as efficacious as daily treatments. CONCLUSIONS: Less frequent injections in GHD and as other conditions are less burdensome, positively benefit patients, and result in improved adherence that may lead to improved clinical outcomes. Clinicians may consider weekly regimens as an effective alternative for patients, in particular in pGHD, especially when missed injections can negatively impact treatment outcomes. More research is needed to better understand the real-world benefits of injectable therapies that require less frequent administration (e.g., weekly versus daily).

Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study.

CONTEXT: Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). OBJECTIVE: We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. METHODS: In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. RESULTS: HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: -0.24, 0.89). The lower bound of the 2-sided 95% CI was higher than the prespecified noninferiority margin (-1.8 cm/year), demonstrating noninferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height standard deviation score at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon: 78.9%, somatropin: 79.1%). CONCLUSION: The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles. (ClinicalTrials.gov no. NCT02968004).

Modeling the potential impact of abuse-deterrent opioids on medical resource utilization.

Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abuse-deterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies. Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids. Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by ∼13-31% (e.g. 78,000-186,000 emergency department visits) and lower annual medical costs by ∼$640 M-$1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events. Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.

Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients.

OBJECTIVE: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients. METHODS: Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years. RESULTS: There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort. CONCLUSION: Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

The Prevalence and Cost of Medicare Beneficiaries Diagnosed and At Risk for Opioid Abuse, Dependence, and Poisoning.

BACKGROUND: Reliance on prescription opioids to manage pain has been associated with increases in diversion, overdose, and addiction. Prevalence of misuse and abuse has been shown to be higher among government-insured populations than commercially insured populations. However, the prevalence and costs of misuse/abuse among the Medicare fee-for-service (FFS) population has not been studied. OBJECTIVES: To (a) determine the prevalence and costs of prescription opioid misuse/abuse and (b) evaluate the prevalence and costs associated with those identified as at risk for opioid misuse/abuse in Medicare FFS beneficiaries. METHODS: This retrospective case-control study used Medicare claims data for the calendar years of 2010 and 2011 and included Medicare beneficiaries aged at least 18 years. The index date was the date of first diagnosed misuse/abuse or at risk for abuse and had to occur between July 1, 2010, and June 30, 2011, and beneficiaries had to have at least 6 months continuous eligibility before and after the index date. Matching (1:1) was used for comparing opioid misusers/abusers with nonabuser controls, as well as comparing patients at risk for opioid abuse with controls not at risk for abuse. Controls were matched to cases by gender, age, disability, and geographic region. The index date of the control patient was set equal to the index date of the matched case. RESULTS: Prevalence of misuse/abuse in the Medicare FFS population was 13.1 per 1,000 persons, with the majority among patients receiving Medicare based on disability (76.2%). The prevalence of at risk for misuse/abuse was 117.4 per 1,000 persons. Approximately half of the Medicare FFS patients used an opioid. Overall total annual unadjusted mean costs of health care resources were significantly greater for abusers than for matched controls ($46,194 vs. $21,964; P < 0.0001), with a mean annual excess cost of $24,230. The overall total adjusted 6-month post-index mean costs of health care resources for abusers was significantly greater than that of matched controls ($33,942 vs. $10,754; P < 0.0001), with a mean excess cost of $23,188. CONCLUSIONS: The prevalence of diagnosed abuse among Medicare FFS population (13.1 per 1,000 persons) was higher than other payer groups studied using similar ICD-9-CM codes, and the majority of abuse was among those receiving Medicare based on disability (76.2%). The prevalence of at-risk abuse was 9 times higher than the prevalence of diagnosed abuse. As with other studies, health care resource utilization and costs were significantly greater for diagnosed abuse than matched controls. DISCLOSURES: This study was sponsored by Pfizer. Roland is a Pfizer employee and stockholder and was involved in all aspects of the study as part of a mid-career fellowship in pharmacoeconomics with the University of Utah. Ye and Stevens are employees of University of Utah, and Oderda was an employee of University of Utah, which received financial support from Pfizer in connection with the development of this manuscript. Oderda also reports consulting fees from Pfizer, Trevena, and Pacira, unrelated to this study. The results of this study were presented at the Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, FL, and the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2016; April 19-22, 2016; San Francisco, CA.

Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients.

OBJECTIVES: To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population. DESIGN: A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/or abuse-related events, opioid discontinuation, and switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated. RESULTS: Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223-1,410 and associated costs ranged from $20-$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions. CONCLUSIONS: A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.

Educational intervention for physicians to address the risk of opioid abuse.

OBJECTIVE: To evaluate the impact of a pilot intervention for physicians to support their treatment of patients at risk for opioid abuse. SETTING, DESIGN AND PATIENTS, PARTICIPANTS: Patients at risk for opioid abuse enrolled in Medicare plans were identified from July 1, 2012 to April 30, 2014 (N = 2,391), based on a published predictive model, and linked to 4,353 opioid-prescribing physicians. Patient-physician clusters were randomly assigned to one of four interventions using factorial design. INTERVENTIONS: Physicians received one of the following: Arm 1, patient information; Arm 2, links to educational materials for diagnosis and management of pain; Arm 3, both patient information and links to educational materials; or Arm 4, no communication. MAIN OUTCOME MEASURES: Difference-in-difference analyses compared opioid and pain prescriptions, chronic high-dose opioid use, uncoordinated opioid use, and opioid-related emergency department (ED) visits. Logistic regression compared diagnosis of opioid abuse between cases and controls postindex. RESULTS: Mailings had no significant impact on numbers of opioid or pain medications filled, chronic high-dose opioid use, uncoordinated opioid use, ED visits, or rate of diagnosed opioid abuse. Relative to Arm 4, odds ratios (95% CI) for diagnosed opioid abuse were Arm 1, 0.95(0.63-1.42); Arm 2, 0.83(0.55-1.27); Arm 3, 0.72(0.46-1.13). While 84.7 percent had ≥1 psychiatric diagnoses during preindex (p = 0.89 between arms), only 9.5 percent had ≥1 visit with mental health specialists (p = 0.53 between arms). CONCLUSIONS: Although this intervention did not affect pain-related outcomes, future interventions involving care coordination across primary care and mental health may impact opioid abuse and improve quality of life of patients with pain.

Prevalence of and Comorbid Health Conditions Associated With Pediatric Prescription Opioid Use in the US.

Prescription opioids are among the most effective analgesics to treat moderate to severe pain; however, little is known about the use of prescription opioids in children, particularly those receiving an extended-release formulation for the treatment of chronic pain. In this retrospective study, the authors determined the prevalence of prescription opioid use among 7-17-year-old children and associated comorbid health conditions from 2010 to 2013 using Truven Health MarketScan (MarketScan) and Optum Clinformatics DataMart (Optum). The primary end points were prevalence of using any prescription opioids, using only prescription short-acting opioids (SAOs), and at least one prescription of a long-acting opioid (LAO). The prevalence of prescription opioid use among children is non-negligible and has been trending downwards: 6.90% in 2010 and 5.93% in 2013 using MarketScan and a similar trend using Optum: 5.47% in 2010 and 4.51% in 2013. Very few children had claims for LAOs, with only 0.04% (4979 children) in MarketScan and 0.03% (1117 children) in Optum. Given the very small number of children, primarily in the 12-17 age group, who are prescribed LAOs, there is a need to focus on a better understanding of the patterns of SAO use in children.

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. PERSPECTIVE: Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation.

Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration.

BACKGROUND: Prescription opioid abuse and misuse is a serious and growing public health issue. While the most common form of abuse is swallowing intact tablets/capsules, some abusers manipulate, or tamper with, these medications by altering the dosage form to allow for non-oral routes of administration (e.g., injection, inhalation) in order to achieve more rapid or enhanced psychoactive effects. Because administration of opioids via non-oral routes results in greater systemic availability and more rapid central nervous system penetration, we hypothesized that death and major medical outcomes occur more frequently with non-oral routes compared to oral route alone. METHODS: This retrospective cohort study analyzed data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program to investigate relative risk of prescription opioid abuse via oral and non-oral routes. RESULTS: While the oral route was the most commonly reported route of abuse (64.0%), non-oral routes were reported in 14.6% exposures and unknown routes in 21.4% exposures. The relative risk of an exposure resulting in death or major effect was 2.43 (95% CI 1.97, 2.99) if non-oral routes were reported compared to exposures involving oral route only. CONCLUSION: Analysis of acute health events recorded by poison centers indicates that death or major effects are twice as likely to occur with intentional abuse of prescription opioids via non-oral routes of administration than ingestion alone. Effective interventions to prevent abuse via non-oral routes of solid dosage forms of prescription opioids, such as abuse-deterrent formulations could have a significant public health impact.

The content validation of the Self-Reported Misuse, Abuse and Diversion of Prescription Opioids (SR-MAD) instrument for use in patients with acute or chronic pain.

BACKGROUND: Establishing content validity is an essential component of instrument development. OBJECTIVE: To assess the content validity and patient interpretation of the Self-Reported Misuse, Abuse and Diversion of Prescription Opioids (SR-MAD) instrument. METHODS: A cross-sectional, qualitative study was conducted in patients with chronic or acute pain. Patients were recruited from three patient groups (opioid naïve, known opioid abusers, and chronic opioid non-abusers). After patients completed the SR-MAD, they participated in an in-person cognitive interview to assess the patient's understanding of the instrument. Descriptive statistics and content analysis were performed. RESULTS: Fifty-seven patients (Wave 1: 20; Wave 2: 37) were enrolled and completed the SR-MAD and cognitive interview. Mean age was 54.5 ± 13.7 years (range 25-84) with 12.5 years of living with pain. The most common chronic pain conditions were back pain (68%), neck pain (32%), and osteoarthritis (25%). Overall, most patients understood the meaning of each question and were able to describe each item using their own words. Many patients reported that some questions were not applicable to them but understood the meaning of the questions as well as the need to ask questions about misuse, abuse, and diversion of opioid medications. Minor revisions to the SR-MAD wording, response options, recall period, and the definition of "opioid", were recommended by the patients in both waves. LIMITATIONS: Given its qualitative design, this study has a small sample size. Additionally, quantitative validation of the SR-MAD is needed. CONCLUSION: The SR-MAD, developed based on expert consensus and revised with patient input, is a 15-item self-report instrument that can be used to identify and monitor prescription opioid abuse, misuse, and diversion.

Evaluating the abuse potential of opioids and abuse-deterrent -opioid formulations: A review of clinical study methodology.

With the development of opioid abuse-deterrent formulations (ADFs), there is a need to conduct well-designed human abuse potential studies to evaluate the effectiveness of their deterrent properties. Although these types of studies have been conducted for many years, largely to evaluate inherent abuse potential of a molecule and inform drug scheduling, methodological approaches have varied across studies. The focus of this review is to describe current "best practices" and methodological adaptations required to assess abuse-deterrent opioid formulations for regulatory submissions. A literature search was conducted in PubMed® to review methodological approaches (study conduct and analysis) used in opioid human abuse potential studies. Search terms included a combination of "opioid," "opiate," "abuse potential," "abuse liability," "liking," AND "pharmacodynamic," and only studies that evaluated single doses of opioids in healthy, nondependent individuals with or without prior opioid experience were included. Seventy-one human abuse potential studies meeting the prespecified criteria were identified, of which 21 studies evaluated a purported opioid ADF. Based on these studies, key methodological considerations were reviewed and summarized according to participant demographics, study prequalification, comparator and dose selection, route of administration and drug manipulation, study blinding, outcome measures and training, safety, and statistical analyses. The authors recommend careful consideration of key elements (eg, a standardized definition of a "nondependent recreational user"), as applicable, and offer key principles and "best practices" when conducting human abuse potential studies for opioid ADFs. Careful selection of appropriate study conditions is dependent on the type of ADF technology being evaluated.

Assessing the impact of abuse-deterrent opioids (ADOs): identifying epidemiologic factors related to new entrants with low population exposure.

OBJECTIVE: Prescription opioid misuse and abuse is a serious public health concern that can lead to overdose, addiction, and death. The development of opioid formulations designed to deter misuse and abuse is considered an important step towards addressing the problem, but the extent to which abuse-deterrent opioids (ADOs) actually deter abuse in the community requires confirmation through epidemiologic studies. Epidemiologic evaluations of misuse and abuse present several unique challenges related to study design, sources of data, and methodology, particularly for new entrant ADOs with low population exposure. The purpose of this article is to review the critical methodologic issues that must be considered when designing an epidemiologic evaluation of prescription opioid misuse and abuse, and deterrence for new entrant ADOs. METHODS: A systematic feasibility assessment was conducted by critically evaluating and applying epidemiologic principles to combinations of epidemiology study design, study directionality, population, data source, clinical and patient-reported endpoints, type of comparator, effect size, and the ability to control for confounding variables. RESULTS: Ten epidemiologic factors were identified that are considered key to an epidemiologic evaluation, and the issues associated with each are summarized. CONCLUSION: Given the low population exposure of new entrant ADOs, there is limited feasibility in conducting the epidemiologic studies necessary to evaluate the effectiveness of these products in deterring abuse. Clear regulatory guidance is needed.

Prescription opioid abuse and misuse: gap between primary-care investigator assessment and actual extent of these behaviors among patients with chronic pain.

OBJECTIVES: To compare the results of two open-label primary care-based studies that examined investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion relative to patient self-reports and urine drug tests (UDTs). METHODS: Risk assessment data from two open-label, multicenter, primary care-based US studies in patients with chronic pain were compared. RESULTS: In one study (n = 1487), 54.4% of patients were at moderate, 24.8% at high, and 20.8% at low risk based on patients' self-reports at baseline on the Screener and Opioid Assessment for Patients with Pain®-Revised questionnaire. Investigators assigned 1.3% of patients as high risk despite 5.0% self-reporting prior illicit drug use and 15.3% with positive UDT(s) for an illicit drug at baseline. In the second study (n = 684), few patients were considered by investigators to be at high risk for misuse (1.6%), abuse (1.8%), or diversion (1.0%). However, 10.4% of patients reported prior illicit drug use; 23.4% had at least one abnormal baseline UDT; 60% of 537 patients reported on the Self-Reported Misuse, Abuse, and Diversion questionnaire they took more opioids than prescribed; and 10.9% reported chewing/crushing opioids in the past. Of patients completing the Current Opioid Misuse Measure, 40.6% were classified as having aberrant behaviors. CONCLUSION: A comparison of risk assessment across two studies indicates a tendency for investigators to assess patients as lower risk for opioid-related aberrant behaviors despite a significant proportion self-reporting aberrant behavior and/or presenting with illicit UDTs. These consistent findings underline the importance of appropriate implementation of objective measures and self-reporting tools when evaluating risk in patients. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers: NCT00640042 and NCT01179191.

Measurement of Drug Liking in Abuse Potential Studies: A Comparison of Unipolar and Bipolar Visual Analog Scales.

Abuse liability studies usually measure drug liking using 100-mm visual analog scales (VAS), presented as unipolar (liking measured on entire scale) or bipolar (liking and disliking measured with a neutral midpoint). These 2 types of VAS were compared using drug liking ratings from a randomized double-blind crossover study of immediate-release and controlled-release oxycodone in 2 cohorts of nondependent recreational opioid users. Cohort 1 (n = 19) received intact oxycodone 40 mg, intact OxyContin® 40 and 80 mg, crushed OxyContin® 40 mg, and placebo, while cohort 2 (n = 16) received intact oxycodone 20, 40, and 80 mg and placebo. In general, bipolar and unipolar ratings were positively correlated (r = 0.72) for all values (n = 2,477). Emax for both scales generally had higher correlation than individual responses for active drug or placebo. The correlation for individual scores after placebo treatment for the 2 scales was poor in both cohorts (r = -0.11, cohort 1 and r = 0.17, cohort 2). Both scales performed similarly within the context of the study, but bipolar scales can also assess disliking, which may be a consideration depending on anticipated drug effects. Appropriate participant training on the use of these scales is also necessary to reduce variability.

Prevalence of Prescription Opioid Misuse/Abuse as Determined by International Classification of Diseases Codes: A Systematic Review.

We conducted a systematic review to evaluate worldwide human English published literature from 2009 to 2014 on prevalence of opioid misuse/abuse in retrospective databases where International Classification of Diseases (ICD) codes were used. Inclusion criteria for the studies were use of a retrospective database, measured abuse, dependence, and/or poisoning using ICD codes, stated prevalence or it could be derived, and documented time frame. A meta-analysis was not performed. A qualitative narrative synthesis was used, and 16 studies were included for data abstraction. ICD code use varies; 10 studies used ICD codes that encompassed all three terms: abuse, dependence, or poisoning. Eight studies limited determination of misuse/abuse to an opioid user population. Abuse prevalence among opioid users in commercial databases using all three terms of ICD codes varied depending on the opioid; 21 per 1000 persons (reformulated extended-release oxymorphone; 2011-2012) to 113 per 1000 persons (immediate-release opioids; 2010-2011). Abuse prevalence in general populations using all three ICD code terms ranged from 1.15 per 1000 persons (commercial; 6 months 2010) to 8.7 per 1000 persons (Medicaid; 2002-2003). Prevalence increased over time. When similar ICD codes are used, the highest prevalence is in US government-insured populations. Limiting population to continuous opioid users increases prevalence. Prevalence varies depending on ICD codes used, population, time frame, and years studied. Researchers using ICD codes to determine opioid abuse prevalence need to be aware of cautions and limitations.

Prescription pain reliever misuse and levels of pain impairment: 3-year course in a nationally representative outpatient sample of US adults.

BACKGROUND: The primary aim of this work was to present the prevalence data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a representative 3-year longitudinal survey (ages 18+ years) that captured information on patterns of self-reported pain interference and prescription pain reliever misuse. A second aim was to assess the degree to which the risk of various types of opioid misuse (onset, desistance, and incidence of dependence) was related to the longitudinal course of self-reported pain interference over the 3-year period. METHODS: We used a two-wave, nationally representative sample of adults (aged 18+ years) in which the baseline data were collected during 2001-2002 and a single follow-up was obtained ~3 years later (2004-2005 with 34,332 respondents with complete data on study variables for both waves). RESULTS: Our findings indicated that ~10% reported high pain interference in the past month at each wave. There was tremendous stability in levels of pain, with ~5% reporting consistent levels of high impairment over the 3-year study, a proxy for chronic pain. Levels of pain were more strongly associated with prescription pain reliever misuse concurrently rather than prospectively, and the association was largely linear, with the likelihood of misuse increasing with levels of pain. Finally, health service factors were also prominent predictors of onset, but not the outcomes, of desistance or transitions to problem use. CONCLUSION: This study is the first to use a nationally representative sample with measures of pain and drug use history collected over an extended period. These results may help provide clinicians with an understanding that the risk of misuse is greatest when pain is active and may help guide the selection of appropriate intervention materials and monitor strategies for those at greatest risk.

Economic Burden of Prescription Opioid Misuse and Abuse: A Systematic Review.

A 2009 systematic review found that the total cost of prescription opioid abuse in 2001 in the United States was approximately $8.6 billion and medical expenses were estimated to be $15,884 for opioid abusers and $1,830 for nonabusers. A search was conducted for English publications on the cost of prescription opioid abuse and misuse from 2009 to 2014. The initial literature search identified 5,412 citations. Title and abstract review selected 59 for further review. The final review process resulted in 16 publications for inclusion that examined cost from the payer perspective. Mean costs to the payer for abusers were $23,000-$25,000 per year and excess costs approximately $15,000 per patient. Three papers were identified that presented societal costs, including direct and indirect costs such as criminal justice costs and costs associated with lost productivity. The strongest evidence suggests that societal cost is in excess of $50 billion per year in the United States. Prescription opioid abuse and misuse is a common and important problem throughout the world that has significant associated societal costs and excess medical costs.

A multicenter, primary care-based, open-label study to identify behaviors related to prescription opioid misuse, abuse, and diversion in opioid-experienced patients with chronic moderate-to-severe pain.

OBJECTIVE: To compare the investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion with patient self-reports of these activities in a population with chronic pain. METHODS: As a secondary objective of an open-label, multicenter, primary care-based clinical study to evaluate the success of converting opioid-experienced patients with chronic pain to morphine sulfate with sequestered naltrexone hydrochloride, risk for misuse, abuse, and diversion was assessed using two nonvalidated questionnaires: one was completed by the investigator and another by the patient (Self-Reported Misuse, Abuse, and Diversion [SR-MAD]). In addition, the validated Current Opioid Misuse Measure (COMM) test and urine drug test were used. RESULTS: Of the 684 patients assessed by the investigators, 537 returned the self-assessment, SR-MAD. Most patients were assigned by the investigator as low risk for misuse (84.2%), abuse (89.3%), and diversion (94.3%). Of the patients who returned SR-MAD, 60% indicated having taken more opioids than prescribed and 10.9% reported chewing or crushing their opioids in the past. Of the patients who completed COMM, 40.6% were deemed as having aberrant behaviors. COMM results correlated with the risk levels from the investigator assessment. One-third of patients (33.8%) had at least one abnormal urine drug test result. CONCLUSION: More research is needed to better understand the gap between the investigator assessment of potential risk for misuse, abuse, and diversion and the actual extent of these behaviors among patients with chronic pain.

A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.

OBJECTIVE: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. METHODS: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. RESULTS: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. CONCLUSION: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.