Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study.

STUDY OBJECTIVES: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy. METHODS: A retrospective cohort study using IBM MarketScan administrative claims data (2014-2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]). CONCLUSION: Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.

Transferability of real-world data across borders for regulatory and health technology assessment decision-making.

Recently, there has been increased consideration of real-world data (RWD) and real-world evidence (RWE) in regulatory and health technology assessment (HTA) decision-making. Due to challenges in identifying high-quality and relevant RWD sources, researchers and regulatory/HTA bodies may turn to RWD generated in locales outside of the locale of interest (referred to as "transferring RWD"). We therefore performed a review of stakeholder guidance as well as selected case studies to identify themes for researchers to consider when transferring RWD from one jurisdiction to another. Our review highlighted that there is limited consensus on defining decision-grade, transferred RWD; certain stakeholders have issued relevant guidance, but the recommendations are high-level and additional effort is needed to generate comprehensive guidance. Additionally, the case studies revealed that RWD transferability has not been a consistent concern for regulatory/HTA bodies and that more focus has been put on the evaluation of internal validity. To help develop transferability best practices (alongside internal validity best practices), we suggest that researchers address the following considerations in their justification for transferring RWD: treatment pathways, nature of the healthcare system, incidence/prevalence of indication, and patient demographics. We also recommend that RWD transferability should garner more attention as the use of imported RWD could open doors to high-quality data sources and potentially reduce methodological issues that often arise in the use of local RWD; we thus hope this review provides a foundation for further dialogue around the suitability and utility of transferred RWD in the regulatory/HTA decision-making space.

Resource utilization and charges of patients with and without diagnosed venous thromboembolism during primary hospitalization and after elective inpatient surgery: a retrospective study.

AIMS: To assess incremental charges of patients experiencing venous thromboembolisms (VTE) across various types of elective inpatient surgical procedures with administration of general anesthesia in the US. METHODS: The authors performed a retrospective study utilizing data from a nationwide hospital operational records database from July 2014 through June 2015 to compare a group of inpatients experiencing a VTE event post-operatively to a propensity score matched group of inpatients who did not experience a VTE. Patients included in the analysis had a hospital admission for an elective inpatient surgical procedure with the use of general anesthesia. Procedures of the heart, brain, lungs, and obstetrical procedures were excluded, as these procedures often require a scheduled ICU stay post-operatively. Outcomes examined included VTE events during hospitalization, length of stay, unscheduled ICU transfers, number of days spent in the ICU if transferred, 3- and 30-day re-admissions, and total hospital charges incurred. RESULTS: The study included 17,727 patients undergoing elective inpatient surgical procedures. Of these, 36 patients who experienced a VTE event were matched to 108 patients who did not. VTE events occurred in 0.2% of the study population, with most events occurring for patients undergoing total knee replacement. VTE patients had a mean total hospital charge of $60,814 vs $48,325 for non-VTE patients, resulting in a mean incremental charge of $11,979 (p < .05). Compared to non-VTE patients, VTE patients had longer length of stay (5.9 days vs 3.7 days, p < .001), experienced a higher rate of 3-day re-admissions (3 vs 0 patients) and 30-day re-admissions (7 vs 2 patients). CONCLUSIONS: Patients undergoing elective inpatient surgical procedures with general anesthesia who had a VTE event during their primary hospitalization had a significantly longer length of stay and significantly higher total hospital charges than comparable patients without a VTE event.

Use of the SF-36v2 Health Survey as a Screen for Risk of Major Depressive Disorder in a US Population-based Sample and Subgroup With Chronic Pain.

STUDY OBJECTIVES: To assess the feasibility of using the SF-36v2 mental health (MH) and mental component summary (MCS) scores for classification of risk for major depressive disorder (MDD), and to determine cut-off scores based on the sensitivity and specificity in a general US representative sample, and a chronic pain subpopulation. METHODS: Data were analyzed from the 2013 US National Health and Wellness Survey (adults 18 y old and above; N=75,000), and among a chronic pain subpopulation (n=6679). Risk of MDD was a score ≥10 on the Patient Health Questionnaire (PHQ-9). Logistic regression modeling was used to predict at risk for MDD and receiver operating characteristic curves were produced. RESULTS: The total sample had MH scores of 48.8 and MCS scores of 48.9, similar to the normative US population mean. Percent of respondents with a PHQ-9≥10 were 15.0% and 29.1% for the total sample and chronic pain subpopulation, respectively. Cut-off scores (PHQ-9≥10) in the total sample for the MH and MCS were 43.0 and 46.0, respectively. Specificities for the MH and MCS were 77.8% and 76.1%; sensitivities were 84.9% and 88.1%, respectively. Among the subpopulation with chronic pain, cut-off scores for the MH and MCS were 40.4 and 43.1, respectively. Corresponding specificities for the MH and MCS were 77.9% and 73.9%; sensitivities were 78.3% and 83.4%, respectively. CONCLUSIONS: The SF-36v2 was found to have sufficient specificity and sensitivity to categorize participants at risk for MDD. If no depression questionnaire is available, it is feasible to use the SF-36v2 to characterize the MH of populations.

Opioid Treatment Patterns Following Prescription of Immediate-Release Hydrocodone.

BACKGROUND: Immediate-release (IR) hydrocodone is the most widely prescribed opioid in the United States; however, little is known about the utilization patterns and duration of opioid use among patients prescribed IR hydrocodone. A better understanding of the use of IR hydrocodone would result in more appropriate prescribing patterns of extended-release opioids. OBJECTIVE: To assess downstream length of opioid therapy and utilization patterns of extended-release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a better understanding of how IR and ER/LA opioids are used to manage pain. METHODS: Retrospective analysis using health care claims from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline period (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up period (2012) post-index date (January 1, 2012) were selected. Downstream length of therapy, defined as number of days supplied with opioids, and downstream use of ER/LA opioids during follow-up were examined by average pills per month (≤ 60 vs. > 60 pills per month) and days supply (< 60 vs. ≥ 60 days supply) of IR hydrocodone during baseline to mimic intermittent and consistent IR users. RESULTS: At baseline, 1,743,933 commercial, 277,096 Medicare, and 157,922 Medicaid IR hydrocodone patients were identified. During follow-up, 1.7%, 2.9%, and 2.8% of patients initiated (i.e., converted to or newly started) ER/LA opioids for commercial, Medicare, and Medicaid groups, respectively. Approximately 90% of patients were prescribed IR hydrocodone for less than 2 months in the following year, while 10% were high utilizers, averaging nearly 8 months of prescribed opioid use during follow-up. Downstream initiation of ER/LA opioids was significantly higher among commercial patients prescribed IR hydrocodone for > 60 pills per month than with ≤ 60 pills per month (7.8% vs. 1.2%, respectively, P < 0.05) at baseline. For commercial patients initiating ER/LA opioids, length of ER/LA therapy during follow-up was significantly longer among patients with baseline IR hydrocodone > 60 pills per month than with ≤ 60 pills per month. All results were consistent when examined by levels of days supply. CONCLUSIONS: A majority of the population prescribed IR hydrocodone was not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up period. Only a small subset of patients with increased pills per month or days supply of IR hydrocodone in the baseline period continued to be high utilizers in the following year, averaging nearly 8 months of prescribed opioid use. A limited proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This knowledge can assist policymakers and physicians, providing an opportunity to identify small subsets of patients to improve ER/LA opioid prescribing. DISCLOSURES: Funding and support for this study was provided by Purdue Pharma L.P. Consulting fees were paid to Evidera by Purdue Pharma L.P. for this study. Kansal, Chitnis, and Paramore are employees of Evidera and were paid consultants to Purdue Pharma for this research. Holly is an employee for Purdue Pharma, and Bell and Ben-Joseph were full-time employees of Purdue Pharma during the design, planning, and execution of the studies and during the preparation of this manuscript. Burgoyne and Brixner were consultants on this project. Study design was created by Ben-Joseph, Brixner, Paramore, and Burgoyne. Data were collected by Kansal, Chitnis, Bell, Ben-Joseph, and Holly and interpreted by Ben-Joseph, Bell, Kansal, and Holly, with assistance from Brixner, Paramore, Burgoyne, and Chitnis. The manuscript was written by Ben-Joseph, Bell, Paramore, Chitnis, and Holly, with assistance from Kansal, and revised by Bell and Holly, along with Ben-Joseph, Brixner, Kansal, Paramore, Burgoyne, and Chitnis.

Characterizing downstream healthcare resource utilization and costs based on prior utilization patterns of immediate-release hydrocodone.

OBJECTIVE: To assess downstream healthcare resource utilization (HRU) and costs among immediate release (IR) hydrocodone patients by days' supply and average doses/month in the prior 6 months. METHODS: Retrospective analysis using healthcare claims from Truven MarketScan commercial, Medicare supplemental, and Medicaid multistate databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline (July-December 2011), and with continuous enrollment during baseline and the 12-month follow-up (2012) were selected. HRU and per-patient-per-month (PPPM) costs (2014 US dollars) were assessed at follow-up. Descriptive analyses and multivariate regressions were conducted to compare HRU and costs at follow-up by days' supply (<60 vs ≥60 days) and average doses per month (≤60 vs >60 doses/month) of IR hydrocodone at baseline. RESULTS: In total, 1,698,845 commercial, 264,038 Medicare, and 151,063 Medicaid IR hydrocodone patients were identified. During follow-up, commercial patients with prior ≥60 days' supply were more likely to have an inpatient admission (13.2% vs 7.5%), outpatient hospital visit (69.1% vs 57.0%), office visit (97.6% vs 91.0%), emergency room (ER) visit (28.1% vs 21.4%), and had higher PPPM total costs ($1494 vs $842) than the <60 days' supply sub-group (all p < 0.05). Among commercial patients the adjusted odds ratio for prior ≥60 days' supply of IR hydrocodone vs prior <60 days' supply was 1.62 (inpatient), 1.33 (outpatient), 2.58 (office visit) and 1.48 (ER) (all p-values <0.05). Adjusted all-cause total costs were higher ($1245 vs $851, p <0.05) among commercial patients with longer days' supply than those with shorter days' supply. Trends were similar with ≤60 vs >60 doses per month sub-groups and across all plan types. CONCLUSION: Increased days' supply and higher doses/month of IR hydrocodone in the prior 6 months may help to predict levels of HRU and costs in the following year, providing an opportunity to identify patients in order to implement interventions to improve their quality of care.

Characteristics of High-Cost Patients Diagnosed with Opioid Abuse.

BACKGROUND: Prescription opioid abuse is associated with substantial economic burden, with estimates of incremental annual per-patient health care costs of diagnosed opioid abuse exceeding $10,000 in prior literature. A subset of patients diagnosed with opioid abuse has disproportionately high health care costs, but little is known about the characteristics of these patients.  OBJECTIVE: To describe the characteristics of a subset of patients diagnosed with opioid abuse with disproportionately high health care costs to assist physicians and managed care organizations in targeting interventions at the costliest patients. METHODS: This retrospective claims data analysis identified patients aged 12 to 64 years diagnosed with opioid abuse/dependence in the OptumHealth Reporting and Insights medical and pharmacy claims database, Quarter 1 (Q1) 1999-Q1 2012. Inclusion criteria required that patients had a diagnosis of opioid abuse during or after Q1 2006, no prior diagnoses of opioid abuse, and continuous non-HMO coverage over an 18-month study period. The study period comprised a 12-month observation period centered on the date of the first opioid abuse diagnosis (index date) and a 6-month baseline period immediately preceding the observation period. Patients in the top 20% of total health care costs in the observation period were classified as "high-cost patients," and the remaining patients were classified as "lower-cost patients." Patient characteristics, comorbidities, health care resource use, and health care costs were compared between high-cost patients and lower-cost patients using chi-square tests for dichotomous variables and Wilcoxon rank-sum tests for continuous variables. In addition, multivariate regression was used to assess the relationship between patient characteristics in the baseline period and total health care costs in the observation period among all patients diagnosed with opioid abuse.  RESULTS: 9,291 patients diagnosed with opioid abuse met the inclusion criteria. The 20% of patients classified as high-cost patients accounted for approximately two thirds of the total health care costs of patients diagnosed with opioid abuse. Compared with lower-cost patients, high-cost patients were older (42.5 vs. 36.1; P less than 0.001) and more likely to be female (55.9% vs. 42.9%; P less than 0.001). They had a higher comorbidity burden at baseline, as reflected in the Charlson Comorbidity Index (0.8 vs. 0.2; P less than 0.001), and rates of conditions such as chronic pulmonary disease (12.9% vs. 5.6%; P less than 0.001) and mild/moderate diabetes (8.4% vs. 3.4%; P less than 0.001). High-cost patients also had higher rates of nonopioid substance abuse diagnoses (12.4% vs. 8.9%; P less than 0.001) and psychotic disorders (26.5% vs. 13.6%; P less than 0.001). In the observation period, high-cost patients continued to have higher rates of nonopioid substance abuse diagnoses (53.0% vs. 47.2%; P less than 0.001) and psychotic disorders (67.1% vs. 47.5%; P less than 0.001). In addition, they had greater medical resource use across all places of service (i.e., inpatient, emergency department, outpatient, drug/alcohol rehabilitation facility, and other) compared with lower-cost patients. The mean observation period health care costs of high-cost patients was $89,177 compared with $11,653 for lower-cost patients (P less than 0.001). High-cost patients had higher medical costs linked to claims with an opioid abuse diagnosis in absolute terms, but the share of total medical costs attributed to such claims was lower among high-cost patients than among lower-cost patients. While many baseline characteristics were found to have a statistically significant (P less than 0.05) association with observation period health care costs, only 27.3% of the variation in observation period health care costs was explained by patient characteristics in the baseline period. CONCLUSIONS: This study found that the costliest patients diagnosed with opioid abuse had high rates of preexisting and concurrent chronic comorbidities and mental health conditions, suggesting potential indicators for targeted intervention and a need for greater awareness and screening of comorbid conditions. Opioid abuse may exacerbate existing conditions and make it difficult for patients to adhere to treatment plans for those underlying conditions. Baseline patient characteristics explained only a small share of the variation in observation period health care costs, however. Future research should explore the degree to which other factors not captured in administrative claims data (e.g., severity of abuse) can explain the wide variation in health care costs among opioid abusers.

The Burden of Undiagnosed Opioid Abuse Among Commercially Insured Individuals.

OBJECTIVES: Estimate the prevalence and healthcare costs of undiagnosed opioid abuse among commercially insured individuals. STUDY DESIGN: Retrospective analysis of de-identified pharmacy and medical claims data and publicly-available survey data (no IRB approval required). METHODS: This study focused on commercially insured individuals. Rates of prescription pain-reliever abuse/dependence ("abuse") among individuals ages ≥12 were calculated using National Survey on Drug Use and Health (NSDUH) public-use data for 2006-2011 and assumed to capture both diagnosed and undiagnosed opioid abuse. Rates of undiagnosed opioid abuse were calculated as the difference between NSDUH rates and published rates of diagnosed opioid abuse. OptumHealth Reporting and Insights claims data were used to estimate the healthcare costs of undiagnosed abuse. Diagnosed abusers ages 12-64 were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pre-diagnosis costs were assumed to be a proxy for undiagnosed opioid abuse costs. The ratio of undiagnosed to diagnosed abuse costs was calculated as the ratio of annual per-patient healthcare costs between pre-diagnosis and post-diagnosis periods. RESULTS: While rates of diagnosed opioid abuse among commercially insured individuals increased from 0.07% in 2006 to 0.19% in 2011, rates of undiagnosed abuse decreased from 0.42% to 0.38% over the same time period. Annual per-patient healthcare costs of undiagnosed abusers were 69.2% of those of diagnosed abusers. CONCLUSIONS: Per-patient healthcare costs of undiagnosed abusers among the commercially insured are estimated to be lower than those of diagnosed abusers. However, the higher prevalence of undiagnosed opioid abuse implies that undiagnosed abuse represents a substantial burden to commercial payers.

Sources of prescription opioids among diagnosed opioid abusers.

OBJECTIVE: Diversion and abuse of prescription opioids are important public health concerns in the US. This study examined possible sources of prescription opioids among patients diagnosed with opioid abuse. METHODS: Commercially insured patients aged 12-64 diagnosed with opioid abuse/dependence ('abuse') were identified in OptumHealth Reporting and Insights medical and pharmacy claims data, 2006-2012, and required to have continuous eligibility over an 18 month study period surrounding the first abuse diagnosis. We examined whether abusers had access to prescription opioids through their own prescriptions and/or to diverted prescription opioids through family members' prescriptions obtained prior to the abuser's first abuse diagnosis. For comparison, we examined access to prescription opioids of a reference population of non-abusers. Sensitivity analyses focused on patients initially diagnosed with opioid dependence and, separately, abusers not previously treated with buprenorphine. RESULTS: Of the 9291 abusers meeting the selection criteria, 79.9% had an opioid prescription prior to their first abuse diagnosis; 20.1% of abusers did not have an opioid prescription prior to their first abuse diagnosis, of whom approximately half (50.8%) had a family member who had an opioid prescription prior to the abuser's first abuse diagnosis (compared to 42.2% of non-abusers). Similar results were found among patients initially diagnosed with opioid dependence and among abusers not previously treated with buprenorphine. LIMITATIONS: The study relied on the accuracy of claims data to identify abusers, but opioid abuse is often undiagnosed. In addition, only prescription claims that were reimbursed by a health plan were included in the analysis. CONCLUSIONS: While most abusers had access to prescription opioids through their own prescriptions, many abusers without their own opioid prescriptions had access to prescription opioids through family members and may have obtained prescription opioids that way. Given the study design and data source, this is likely a conservative estimate of prescription opioid diversion.

Predicting medication persistence to buprenorphine transdermal system.

OBJECTIVES: Persistence, the duration a patient remains on therapy, in chronic, symptomatic conditions plays an important role in therapy effectiveness. Understanding the duration and patient factors associated with prescribed medication persistence is, therefore, an important step toward better treatment and health outcomes for patients. In the following study, an analysis of such factors associated with buprenorphine transdermal system (BTDS) persistence was conducted utilizing a large US private practitioner and pharmacy claims database and is herein reported. METHODS: Patients aged ≥ 18 years initiating BTDS during January 1, 2011-November 30, 2011 were identified in the IMS Private Practitioner Medical Claims and Pharmacy Claims databases. An index date was defined as the first prescription of BTDS during the studied interval. During the preindex period, Charlson Comorbidity Index (CCI), chronic pain-related conditions, and prior medication use were assessed. Concomitant medications and various treatment patterns (eg, last dose strength and dose adjustments) were assessed in the postindex 6-month period. Persistence was measured as the duration of BTDS from initiation to the 1st >28-day refill gap in the postindex 6-month period. Descriptive statistical and survival analysis was used to assess the predictors of BTDS persistence. RESULTS: During the study period, 10,457 patients newly treated with BTDS were identified. Patients' mean (± SD) age was 54.5 (± 15.2) years; 69.9% were women, and the mean (± SD) CCI was 1 (± 1.4). Utilizing a hierarchical approach, patients were separated into different cohorts based on the initial analgesic prescription identified during postindex period with 91.7%, 34.7%, and 59.0% of the patients using opioids, NSAIDs and adjuvant analgesics, respectively. Multivariate regression analyses showed that patients with prior opioid and adjuvant analgesic use were 21% and 5% less likely to discontinue BTDS (P < 0.05), respectively, as compared to patients not using these agents. Patients with concomitant use of adjuvant analgesics were 15% less likely to discontinue therapy (P < 0.05) as compared to patients without concomitant use of these agents. Long-term BTDS persistence was also observed in patients who had a dose change or a last dose strength >5 mcg/hour. Sensitivity analyses for those with 30-day prior opioid use and patients with ≥ 2 claims of BTDS confirmed these findings. CONCLUSIONS: Prior and concomitant use of adjuvant analgesics, prior use of opioids, and dose adjustments were associated with significantly longer persistence among patients initiating BTDS. The results suggest that patients are less likely to discontinue BTDS early if practitioners account for prior treatment history and dose titration.

Medical resource use and costs among pain patients with potential opioid-tolerability issues.

OBJECTIVE: To estimate excess medical resource use and costs associated with prescription opioid (RxO) tolerability issues. DESIGN: This was an observational, retrospective analysis of deidentified administrative claims data. SETTING: The study included commercially insured patients treated in different healthcare settings captured in the Truven MarketScan claims database. PATIENTS: Patients aged 18-64 years initiating treatment with an RxO (index) and continuously treated with pain relievers over a 6-month period were selected. "Switchers" were patients who discontinued their index RxO and switched to non-RxO pain relievers < 30 days post-index, and whose last pain reliever in the 6-month follow-up period was not an RxO. Such switching was considered a proxy for RxO-tolerability issues. "Continuous RxO users" were patients who remained on the index RxO for the follow-up period. Switchers and continuous RxO users were matched 1:1 on propensity score, baseline medical costs, index RxO days supply, and short-/long-acting index RxO. MAIN OUTCOME MEASURES: Six-month follow-up medical resource use and costs were compared between matched switchers and continuous RxO users. RESULTS: A total of 10,704 pairs of switchers and continuous RxO users were matched. In the 6-month follow-up period, switchers had more outpatient (7.5 vs 6.8; p < 0.001) and inpatient (0.05 vs 0.04; p = 0.002) visits and longer inpatient stays (0.26 days vs 0.19; p = 0.006) compared to continuous RxO users. Switchers also had higher total medical costs ($4,522 vs $3,657; p < 0.001). CONCLUSIONS: Switchers incur greater medical resource use and costs than similar patients continuously treated with their index RxO.

The economic burden of diagnosed opioid abuse among commercially insured individuals.

The abuse of prescription opioids imposes a substantial public health and economic burden. Recent research using administrative claims data has substantiated the prevalence and cost of opioid abuse among commercially insured individuals. Although administrative claims data are readily available and have been used to effectively answer research questions about the burden of illness for many different conditions, an important issue is the reliability, replicability, and generalizability of estimates derived from different databases. Therefore, this study sought to assess whether the findings of a recently published study of opioid abuse in a commercial claims database (original analysis) could be replicated in a different commercial claims database. The original analysis, which analyzed the prevalence and excess health care costs of diagnosed opioid abuse in the OptumHealth Reporting and Insights Database, was replicated by applying the same approach to the Truven MarketScan Commercial Claims and Encounters Database (replication analysis). In the replication analysis, the prevalence of diagnosed opioid abuse increased steadily from 15.8 diagnosed opioid abusers per 10,000 in 2009, to 26.6 diagnosed opioid abusers per 10,000 in 2012. Although the prevalence of diagnosed opioid abuse was higher than reported in the original analysis, the trend of increasing prevalence over time was consistent across analyses. Additionally, diagnosed abusers had excess annual per patient health care costs of $11,376 in the replication analysis, which was consistent with the excess annual per patient health care costs of diagnosed abuse of $10,627 reported in the original analysis. The replication analysis also found an upward trend in the prevalence of diagnosed opioid abuse over time and substantial excess annual per patient health care costs of diagnosed opioid abuse among commercially insured individuals, suggesting that these findings are generalizable to other commercially insured populations.

Impact of middle-of-the-night awakenings on health status, activity impairment, and costs.

STUDY OBJECTIVES: Middle-of-the-night (MOTN) awakenings with difficulty returning to sleep are among the most common symptoms of insomnia. Despite the epidemiological studies that have been conducted, there is a lack of data on the impact of MOTN awakenings on health status and socioeconomic indicators in comparison with other insomnia symptoms. METHODS: Data were analyzed from the 2011 US National Health and Wellness Survey (adults ≥18 years old; N=60,783), which asked respondents whether they had experienced specific symptoms of insomnia (ie, MOTN awakenings, difficulty falling asleep, waking several times, waking up too early, or poor quality of sleep). Respondents who reported only one insomnia symptom were compared among insomnia subgroups and with no insomnia symptom controls with respect to demographics, health history, and health outcomes (Short Form-12v2, Work Productivity and Activity Impairment questionnaire, and costs). Additional analyses compared respondents with only MOTN awakenings and matched controls on health outcomes. RESULTS: MOTN awakenings without other insomnia symptoms were reported by 3.5% of respondents. Poor quality of sleep was associated with the strongest effects on health status compared with other insomnia symptoms even after adjusting for demographic and health characteristics differences. Differences across insomnia symptoms with respect to cost-related outcomes were generally modest, though all were higher (if not significantly so) than respondents without insomnia. Respondents who experienced only waking several times and only MOTN awakenings had the highest direct costs, while respondents who experienced only poor quality of sleep and only difficulty falling asleep had the highest indirect costs. Respondents with only MOTN awakenings reported significantly worse mental and physical health status and worse health utilities relative to insomnia-free matched controls (all P<0.05). Annual per-employee indirect costs were also significantly higher ($4,328 vs $3,000; P<0.05). Among only MOTN awakenings respondents, 74.6% were considered only symptomatic (ie, they did not report having insomnia or having been diagnosed with insomnia). CONCLUSION: These findings collectively highlight the prevalence and socioeconomic impact of specific types of insomnia symptoms, including MOTN awakenings, experienced by adults in the US.

Consequences of patient access restrictions to branded oxycodone hydrochloride extended-release tablets on healthcare utilization and costs in US health plans.

OBJECTIVE: To evaluate the impact of increased access restrictions to branded oxycodone hydrochloride extended-release tablets (oxycodone HCl ER), on healthcare utilization and costs in patients using extended-release and long-acting opioids (ER/LA opioids) from the health plan perspective during the period from 1/1/2009 to 6/30/2012. METHODS: This retrospective cohort study analyzed claims data for adult patients from US plans that increased oxycodone HCl ER access restrictions. Study groups were segmented into commercial and Medicare payers, and by prior authorization (PA) and tier change (TC) restrictions. Six-month outpatient visits and prescription utilization and costs were evaluated during the pre- and post-access restriction periods using a bootstrapped t-test and regression to test the differences. RESULTS: Mean 6-month post-restriction combined pharmacy and outpatient visit costs were $1131 (p < 0.001), $660 (p = 0.009), $699 (p < 0.001), and $564 (p < 0.001) higher than pre-restriction costs in commercial PA, commercial TC, Medicare PA, and Medicare TC groups, respectively. Outpatient visits accounted for the greatest proportion of increased costs in the access restriction groups. CONCLUSIONS: The results of this study suggest that oxycodone HCl ER access restrictions such as PA and TC may increase medical costs without an offsetting savings in pharmacy costs.

Estimating the costs of opioid abuse and dependence from an employer perspective: a retrospective analysis using administrative claims data.

BACKGROUND: Opioid abuse and dependence is problematic across many age groups, including the working-age population and their dependents. Little is known, however, about the economic costs of opioid abuse/dependence imposed on employers, who pay for a substantial portion of healthcare costs through their contributions to employer-sponsored health insurance and are also affected by indirect costs such as those due to disability and workplace absenteeism. OBJECTIVE: To provide a comprehensive, current estimate of the economic burden of prescription opioid abuse/dependence to employers. METHODS: Administrative claims from beneficiaries covered by large self-insured companies throughout the USA were used to identify patients, including employees and dependents, who were diagnosed with opioid abuse and/or dependence ('abusers') between 2006 and 2012. Healthcare and work-loss costs for abusers were assessed over a 12-month period and compared with those for patients not diagnosed with abuse ('comparison patients'), using propensity score matching. RESULTS: 7,658 matched pairs of abusers and comparison patients were analysed. Relative to comparison patients, abusers had significantly higher annual healthcare resource utilization, leading to US$10,627 in per-patient incremental annual healthcare costs. Additionally, abusers had US$1,244 in excess annual work-loss costs. Together, this implies an employer burden for diagnosed abuse of US$1.71 per member per month. CONCLUSION: Opioid abuse/dependence impose a substantial economic burden on employers.

US practitioner prescribing practices and patient characteristics of those newly treated with a buprenorphine transdermal patch system.

OBJECTIVES: Medication prescribing information provides guidance to healthcare providers on how to prescribe a drug properly. Oftentimes patient factors in addition to the prescribing information are considered when selecting medications. Utilizing real-world pharmacy and medical claims data, this study assessed US practitioner prescribing practices of US approved transdermal buprenorphine system (BTDS) in relation to BTDS's full prescribing information (FPI) as well as the relationship between patient factors and initial BTDS dose. RESEARCH DESIGN AND METHODS: Patients aged ≥18 years initiating BTDS between 1 January 2011 and 30 November 2011 were identified in the IMS Pharmacy and Private Practitioner Medical Claims databases. The index date was defined as the first filled BTDS prescription. Demographics, chronic pain-related medical conditions in the 12 months pre-index and prior medication use in the 6 months pre-index were assessed. Initial BTDS dosing strength, receipt of approved initial BTDS dose per the FPI, and concomitant medications were assessed in the post-index 6 month period. RESULTS: The study included 10,457 patients newly treated with BTDS. The majority of patients were female (69.9%) with a mean (±SD) age of 54.5 (±15.2) years. Within the 6 months prior to the index BTDS prescription, 91.7% of the patients used opioids. Overall, 48.9% of patients were prescribed the FPI approved BTDS dose. When stratified, 73.5% of opioid-naïve patients received the FPI approved initial dose compared to 46.0% of those with prior opioid experience of ≤80 mg morphine-equivalent daily dose. Patients on BTDS alone (i.e. monotherapy) had a higher rate of receiving the FPI approved initial BTDS dose compared to patients on BTDS concomitant regimens (p < 0.05). CONCLUSIONS: Practitioners demonstrated that they prescribe in accordance with BTDS's prescribing information in the majority of opioid-naïve patients and in approximately half of opioid-experienced patients. The initial opioid dose is a critical step in treatment, setting the stage for preventing side-effects and improving treatment effectiveness. Understanding practitioner prescribing practices with regard to the initial dose selection of BTDS may provide insight on how to improve outcomes of care and reduce healthcare resource utilization and costs associated with pain management. LIMITATIONS: Data obtained from prescription claims reflect only the activities of prescriptions filled, not medication use or other clinical characteristics observed by physicians when treating patients.

A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States.

Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4 g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to limit and monitor exposure to high-dose acetaminophen. This literature review aims to describe the exposure to and consequences of high-dose acetaminophen among chronic pain patients in the US. Each year in the US, approximately 6% of adults are prescribed acetaminophen doses of more than 4 g/day and 30,000 patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen overdoses are unintentional, largely related to opioid-acetaminophen combinations and attempts to achieve better symptom relief. Liver injury occurs in 17% of adults with unintentional acetaminophen overdose.

Use of prescription opioids with abuse-deterrent technology to address opioid abuse.

OBJECTIVE: The development of new formulations of extended-release (ER) opioids with abuse-deterrent technology attempts to deter prescription opioid abuse while maintaining appropriate access to care for pain patients. This study examined the degree to which some patients may avoid switching to reformulated ER opioids with abuse-deterrent technology and the extent to which those patients are more likely to be abusers. RESEARCH DESIGN AND METHODS: We analyzed Truven MarketScan pharmacy and medical claims data following the introduction of two reformulated ER opioids with abuse-deterrent technology. Adults aged 18-64 who were continuous users of extended-release oxycodone HCl (ER oxycodone) or extended-release oxymorphone HCl (ER oxymorphone) in a 6 month period prior to the introduction of the respective reformulations of those products were identified and categorized based on whether they switched to the reformulation, switched to other ER/long-acting (LA) opioids (without abuse-deterrent technology), or discontinued ER/LA opioid treatment in a 6 month post-reformulation period. Abusers were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pearson's chi-squared tests and Fisher's exact tests were then used to compare rates of abuse between patients who avoided switching to a reformulated ER opioid. Sensitivity analyses examined several definitions used in this analysis. MAIN OUTCOME MEASURES: ER/LA opioid utilization; rates of diagnosed opioid abuse. RESULTS: A total of 31%-50% of patients avoided switching to reformulated ER opioids. Rates of diagnosed opioid abuse were higher among these patients compared to patients who transitioned to the reformulated ER opioids. LIMITATIONS: Due to the observational research design, caution is warranted in causal interpretation of the findings. The study was conducted among commercially insured continuous ER oxycodone or ER oxymorphone users; future research should consider additional patient populations, such as non-continuous users and those without commercial insurance (i.e., Medicare, Medicaid, uninsured). CONCLUSIONS: Some patients switched to other ER/LA opioids without abuse-deterrent technology or discontinued ER/LA opioid treatment when their existing ER treatment was reformulated. Rates of opioid abuse were higher among patients who switched to other ER/LA opioids or discontinued ER/LA opioid treatment, suggesting that abusers may seek more easily abuseable alternatives such as prescription opioids without abuse-deterrent technology.

Medical cost savings associated with an extended-release opioid with abuse-deterrent technology in the US.

OBJECTIVES: In the US, prescription opioids with technology designed to deter abuse have been introduced to deter drug abuse without hindering appropriate access for pain patients. The objective of this study was to estimate changes in medical costs following the introduction of a new formulation of extended-release (ER) oxycodone HCl (oxycodone) with abuse-deterrent technology in the US. METHODS: Health insurance claims data were used to estimate changes in rates of diagnosed opioid abuse among continuous users of extended-release opioids (EROs) following the introduction of reformulated ER oxycodone in August 2010. This study also calculated the excess medical costs of diagnosed opioid abuse using a propensity score matching approach. These findings were integrated with published government reports and literature to extrapolate the findings to the national level. All costs were inflated to 2011 US dollars. RESULTS: The introduction of reformulated ER oxycodone was associated with relative reductions in rates of diagnosed opioid abuse of 22.7% (p < 0.001) and 18.0% (p = 0.034) among commercially-insured and Medicaid patients, respectively. There was no significant change among Medicare-eligible patients. The excess annual per-patient medical costs associated with diagnosed opioid abuse were $9456 (p < 0.001), $10,046 (p < 0.001), and $11,501 (p < 0.001) for commercially-insured, Medicare-eligible, and Medicaid patients, respectively. Overall, reformulated ER oxycodone was associated with annual medical cost savings of ∼$430 million in the US. LIMITATIONS: Because of the observational research design of this study, caution is warranted in any causal interpretation of the findings. Portions of the study relied on prior literature, government reports, and assumptions to extrapolate the national medical cost savings. CONCLUSIONS: This study provides evidence that reformulated ER oxycodone has been associated with reductions in abuse rates and substantial medical cost savings. Payers and policy-makers should consider these benefits as they devise and implement new guidelines and policies in this therapeutic area.