Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden.

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives.

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naïve patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use.

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.

The potential impact of monitoring disease activity biomarkers on rheumatoid arthritis outcomes and costs.

Rheumatoid arthritis (RA) management requires monitoring of disease activity to determine course of treatment. Global assessments are used in clinical practice to determine RA disease activity. Monitoring disease activity via biomarkers may also help providers optimize biologic and nonbiologic drug use while decreasing overall drug spend by delaying use of expensive biologic therapies. By testing multiple biologic domains at the same time, a multibiomarker disease activity test may have utility in RA patient management, through improved intra- and inter-rater reliability. This report provides a comprehensive review of studies of objective measures, single biomarkers and multibiomarker disease activity tests as disease activity measures to decrease uncertainty in treatment decisions, and of biomarkers' potential impact on economic and clinical outcomes of treatment choices.

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.

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.

Single- Versus Multiple-Drug Pharmacotherapy in the Management of Diabetic Painful Neuropathy.

This study compared patient characteristics and health care costs between newly treated diabetic painful neuropathy (DPN) patients receiving mono- pharmacotherapy and those receiving combination pharmacotherapy. A retrospective cohort was developed through Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2) database. Patients included were ≥18 years on the date of first DPN prescription: tricyclic antidepressant, opioids, duloxetine, gabapentin, pregabalin, or lidocaine. The authors conducted a simple proportional hazards model comparing times to discontinuation, switch, or addon. Multiple logistic regression was used to identify predictors of combination pharmacotherapy. There were 7145 patients on mono-pharmacotherapy and 421 patients on combination pharmacotherapy. Patients receiving combination pharmacotherapy were 130% more likely to discontinue their medications than patients receiving mono-pharmacotherapy. Female patients and those with > 7 comorbidities were more likely to be started with combination pharmacotherapy. Elderly patients were less likely to be started with combination pharmacotherapy. The total cost of care difference between mono- and combination pharmacotherapy was not statistically significant (P = .66); therefore, newly treated DPN patients should add on another medication sooner than 30 days when considering combination pharmacotherapy. All first-line medications have similar efficacy; for this reason, cost should be considered in the treatment decision.

Long-term cost-effectiveness of initiating treatment for painful diabetic neuropathy with pregabalin, duloxetine, gabapentin, or desipramine.

Painful diabetic neuropathy (PDN) affects nearly half of patients with diabetes. The objective of this study was to compare the cost-effectiveness of starting patients with PDN on pregabalin (PRE), duloxetine (DUL), gabapentin (GABA), or desipramine (DES) over a 10-year time horizon from the perspective of third-party payers in the United States. A Markov model was used to compare the costs (2013 $US) and effectiveness (quality-adjusted life-years [QALYs]) of first-line PDN treatments in 10,000 patients using microsimulation. Costs and QALYs were discounted at 3% annually. Probabilities and utilities were derived from the published literature. Costs were average wholesale price for drugs and national estimates for office visits and hospitalizations. One-way and probabilistic (PSA) sensitivity analyses were used to examine parameter uncertainty. Starting with PRE was dominated by DUL as DUL cost less and was more effective. Starting with GABA was extendedly dominated by a combination of DES and DUL. DES and DUL cost $23,468 and $25,979, while yielding 3.05 and 3.16 QALYs, respectively. The incremental cost-effectiveness ratio for DUL compared with DES was $22,867/QALY gained. One-way sensitivity analysis showed that the model was most sensitive to the adherence threshold and utility for mild pain. PSA showed that, at a willingness-to-pay (WTP) of $50,000/QALY, DUL was the most cost-effective option in 56.3% of the simulations, DES in 29.2%, GABA in 14.4%, and PRE in 0.1%. Starting with DUL is the most cost-effective option for PDN when WTP is greater than $22,867/QALY. Decision makers may consider starting with DUL for PDN patients.

Identifying and Communicating Clinically Meaningful Drug-Drug Interactions.

OBJECTIVE: Providing care to patients with comorbid medical problems may result in complicated, multiple drug therapy regimens, increasing the risk of clinically meaningful drug-drug interactions (DDIs). The purpose of this article is to describe the prevalence of DDIs and provide examples on how to identify and intervene on DDIs. METHODS: We described DDI data from the Utah Drug Regimen Review Center, where adult Medicaid patients were reviewed by pharmacists from 2005 to 2009. Patients were selected by the number of prescriptions filled per month (>7) or having a high RxRisk score. SUMMARY: A total of 8860 patients were reviewed, and 16.6% had at least 1 clinically meaningful DDI. Patients with DDIs were slightly younger (mean age 45.2 vs 48.2), more likely to be female (75.0% vs 68.9%), and had more prescriptions per month (13.4 vs 12.5) compared to patients without (P < .001). Pharmacodynamic DDIs were more prevalent (80.2%) than pharmacokinetic. Pharmacodynamic DDIs mainly occurred with drugs used to treat psychiatric/seizure/sleep disorders (69.4%) and pain/migraine (56.6%). Pharmacokinetic DDIs mainly occurred with drugs used to treat psychiatric/seizure/sleep disorders (53.2%), cardiovascular diseases (46.3%), and infectious diseases (29.6%). CONCLUSIONS: Clinically meaningful DDIs are common in patients with complex medication regimens. A systematic approach for identifying DDIs, determining clinical significance, formulating patient-specific recommendations, and communicating recommendations is important in pharmacy practice.

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.

Effect of i.v. acetaminophen on total hip or knee replacement surgery: a case-matched evaluation of a national patient database.

PURPOSE: The effects of i.v. acetaminophen on adverse events, hospital length of stay (LOS), and overall hospital costs for total hip or knee replacements were evaluated. METHODS: We conducted a matched-pairs analysis of adult inpatients who underwent elective total hip arthroplasty or total knee arthroplasty in hospitals participating in the Premier Healthcare Alliance from January 1, 2011, to November 30, 2012. Each case who received i.v. acetaminophen on the day of surgery was matched to a control who did not receive i.v. acetaminophen within the same hospital. Treatment groups were analyzed for differences in the rate of adverse effects, LOS, and hospital resource utilization. RESULTS: A total of 22,146 cases and controls were similar in terms of age, race, sex, marital status, insurance status, and preoperative comorbidities. Overall adverse events were significantly lower with i.v. acetaminophen (24.3%) than with controls (26.3%, p < 0.001), numerically less frequent in all subgroups, and significantly less frequent for renal, infectious, and miscellaneous adverse events (all p < 0.05). I.V. acetaminophen was also associated with a shorter LOS, with 1 out of 11 patients discharged one day earlier (p < 0.001) and lower average hospital costs: $16,381 for cases compared with $16,927 for controls (p < 0.001). Cost savings estimated by structural equation modeling of $547 per patient were due to $325 from direct effects and $222 from indirect effects, the latter mediated through adverse events and reduced LOS. CONCLUSION: In this retrospective cohort study of case-matched patients who underwent total hip or knee replacement surgery, multimodal analgesia with i.v. acetaminophen was associated with improved clinical outcomes in terms of fewer adverse events, shortened LOS, and reduced total hospital resources compared with patients who did not receive i.v. acetaminophen.

Impact of postsurgical opioid use and ileus on economic outcomes in gastrointestinal surgeries.

OBJECTIVES: To assess the incidence and economic impact of postoperative ileus (POI) following laparotomy (open) and laparoscopic procedures for colectomies and cholecystectomies in patients receiving postoperative pain management with opioids. METHODS: Using the Premier research database, we retrospectively identified adult inpatients discharged between 2008 and 2010 receiving postsurgical opioids following laparotomy and laparoscopic colectomy and cholecystectomy. POI was identified through ICD-9 diagnosis codes and postsurgical morphine equivalent dose (MED) determined. RESULTS: A total of 138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more frequently in colectomy than cholecystectomy and more often when performed by laparotomy. Ileus patients receiving opioids had an increased length of stay (LOS) ranging from 4.8 to 5.7 days, total cost from $9945 to $13,055 and 30 day all-cause readmission rate of 2.3 to 5.3% higher compared to patients without ileus. Patients with ileus received significantly greater MED than those without (median: 285 vs. 95 mg, p < 0.0001) and were twice as likely to have POI. MED above the median in ileus patients was associated with an increase in LOS (3.8 to 7.1 days), total cost ($8458 to $19,562), and readmission in laparoscopic surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients undergoing open procedures regardless of MED. CONCLUSIONS: Use of opioids in patients who develop ileus following abdominal surgeries is associated with prolonged hospitalization, greater costs, and increased readmissions. Furthermore, higher doses of opioids are associated with higher incidence of POI. Limitations are related to the retrospective design and the use of administrative data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore underestimated in our study. Assessment of pre-existing disease and preoperative pain management was not assessed. Despite these limitations, strategies to reduce opioid consumption may improve healthcare outcomes and reduce the associated economic impact.

Physician adherence to ACR gout treatment guidelines: perception versus practice.

BACKGROUND: In October 2012, the American College of Rheumatology (ACR) published recommendations for chronic gout treatment goals and pharmacotherapy. OBJECTIVES: Identify potential gaps between real-world chronic gout treatment, ACR guideline recommendations, and physicians' perceived guideline adherence by evaluating records of patients classified as having "higher" and "lower" guideline adherence as defined by the investigators. METHODS: A comprehensive quantitative survey was administered between February 11 and February 22, 2013, to physicians treating patients with gout; the survey included a patient record chart review informed by prior qualitative interviews. Eight criteria from the ACR gout management guidelines were used to compose the survey. To assess ACR guideline adherence, information from records of patients with chronic gout treated by primary care physicians (PCPs) and rheumatologists was scored from 0 (no adherence) to 8 (total adherence), in accordance with ACR guideline recommendations. Physicians also indicated how closely they believed patient treatment followed current guidelines on a 10-point scale. RESULTS: Of the 350 records of patients with chronic gout, all but 3 PCP patients were adherent on ≥ 1 guideline recommendation, but nearly all patients could be considered nonadherent, considering all potential recommendations. Patients with chronic gout treated by rheumatologists tended to be managed more closely to ACR guidelines than patients treated by PCPs (mean scores: rheumatologists 5.8/8 ± 1.7 vs 4.3/8 ± 1.7 for PCPs). Among patients classified as having "higher adherence" based on adherence scores, there was low adherence on first-line urate lowering therapy dose, acute prophylaxis dosing, and length of prophylaxis treatment. Among PCPs and rheumatologists, there was a disparity between how closely physicians believed patient treatment followed guidelines and actual adherence with ACR guidelines based on adherence scores. For 16.4% of patients treated by PCPs and 18.4% of patients seen by rheumatologists, physicians believed they closely followed ACR guidelines (score of 8-10/10) for each patient; but in actuality, adherence was lower. CONCLUSION: Although adherence with ACR guidelines is higher among rheumatologists than PCPs in treating patients with gout, overall adherence could be improved by both specialties.

Effect of opioid-related adverse events on outcomes in selected surgical patients.

PURPOSE: This retrospective study utilized a large, national hospital database to assess the impact of opioid-related adverse events (ORADE) on patient outcomes following selected surgical procedures known to require postoperative pain control. METHODS: Outcomes of patients with administratively documented ORADE were compared to those without. Multivariate regression determined differences in hospital costs; length of stay (LOS); odds of individuals being an outlier in total cost and LOS; and having a 30-day all-cause readmission. RESULTS: Among 319,898 surgeries of interest, 12.2% of patients experienced an ORADE. Patients had higher adjusted mean costs ($22,077 [95% CI 21,823-22,333] vs. $17,370 [95% CI 17,238-17,503]; p < 0.0001) and greater LOS (7.6 [95% CI 7.5-7.6] vs. 4.2 days [95% CI 4.2-4.2]; p <0.0001). Adjusted odds of being a total cost and LOS outlier were 2.8 (95% CI 2.7-2.8) and 3.2 (95% CI 3.1-3.3) times greater in the ORADE group. These patients were more likely to be readmitted (OR 1.06, 95% CI 1.02-1.09). CONCLUSIONS: Patients exhibiting a documented ORADE had greater overall costs, longer hospitalizations, and increased likelihood for readmission. These results highlight the economic impact associated with opioid use for postsurgical pain management.

Quality assessment of the methods used in published opioid conversion reviews.

The study objective was to assess methodological quality of opioid conversion systematic reviews. The electronic databases PubMed, EMBASE, and Scopus were used to identify the systematic reviews from the earliest available date until April 2012. Studies were not restricted based on type of opioid, country, or languages. Methodological quality was evaluated using the "Assessment of Multiple Systematic Reviews (AMSTAR)." A total of 2772 articles were found from which five met inclusions criteria. No review mentioned about the duplicate study selection and data extraction. Two reviews included a list of studies that were excluded studies. One study did not provided information on the characteristics of primary studies that were included. Of the three reviews that evaluated the quality of primary studies, two used the quality of included studies in formulating conclusions. Only two reviews provided information about conflicts of interest. Of the five included systematic reviews, three reached a moderate score; two had poor quality. Specific recommendations to improve methodological quality would include performing the data selection and extraction in duplicate, listing or showing the flowchart of studies that were included and excluded along with the reasons, including the main studies data illustrating tables, and including an assessment of the quality of the primary included studies.

The association between pain and depression and some determinants of depression for the general population of the United States.

Pain and depression are major reasons for pharmacotherapy, making the relationship between these two complaints important in defining optimal pharmacotherapy for both. Although the association between the two has been documented in the literature, most of the available work only focused on specific disease group or patients with certain type of pain. Whether the association exists for the general population is still an unsettled issue. The goal of this study was to examine the association between pain and depression and explore the some determinants of depression using national representative survey data for the general population in the United States. This work employed data from Medical Expenditure Panel Survey (MEPS) 2009, with people older than 18 were included in the study. Ordered logistic regression and generalized ordered logistic regression were performed while incorporating complex survey features. Estimation results suggested that depression and physical pain were positively associated. In addition, individuals with better perceived health, older age, male gender, higher family income, and employed were less depressed. Divorced or separated marital status was associated with higher depression level. This work fills the gap in the literature by using nationally representative survey data set to examine the association between physical pain and depression. Levels of physical pain and many socioeconomic factors were found significantly associated with depression.

Comparative effectiveness research (CER): a summary of AHRQ's CER on therapies for rheumatoid arthritis.

BACKGROUND: In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. OBJECTIVES: To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ's 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). SUMMARY: As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections.

Costs of opioid abuse and misuse determined from a Medicaid database.

This study determined the associations between opioid abuse, dependence, and poisonings on costs and comorbidities in the Medicaid population. Medicaid patients in the Medicaid Analytic eXtract (MAX) files from 2002 to 2003 with 12 months of continuous eligibility, age >or=12 years, and with an opioid abuse/dependence-related diagnosis, including opioid abuse, dependence, or poisoning, in 2002 (index date) were matched 3:1 to Medicaid patients with no such diagnosis (controls). Medical costs by claim type incurred 12 months post index date were compared as was the prevalence of select comorbidities. The authors conducted a two-step multivariate regression analysis adjusted for patient characteristics that could influence cost outcomes. Opioid abuse/dependence prevalence was 8.7 per 1000 in 2002-2003. A total of 50,162 patients with abuse or dependence-related diagnoses were matched to 150,486 control patients. Total costs were significantly higher for the abuse/dependence patients ($14,537) than matched controls ($8,663) (P < .001). When controlling for baseline characteristics, adjusted costs continued to be higher for abuse/dependence patients ($23,556 versus $8,436; P < .001). A total of 83.7% of abuse/dependence patients and 51.6% of controls had >or=1 of the predefined comorbidities. Other substance abuse (odds ratio [OR] 9.4), hepatitis A, B, or C (OR 8.8), and poisonings (OR 8.5) were highly associated with a diagnoses for opioid abuse or dependence (P < .001). Medicaid opioid abuse/dependence patients had more comorbidities and higher medical costs in 2002-2003 than Medicaid control patients. Successful interventions to prevent opioid abuse and manage comorbidities could help to reduce costs associated with opioid abuse in the Medicaid population.

Economic evaluation of pharmacotherapy of migraine pain: a review of the literature.

This paper reviews the economic evaluation literature on pharmacotherapy for migraine and identifies important trends and gaps in the literature. Given the tremendous economic burden of migraine and the availability of various therapies for migraine treatment, economic evaluation of alternative therapies plays a critical role in identifying the most cost-effective therapy to optimize health care resource allocation and clinical decisions. Particularly, physicians and clinical administrators are expected to take an active role in resource allocation decisions at the clinical level. Thus, it is important for them to be familiar with the economic evaluation in migraine pain management, and most importantly, methodologies of economic analyses and the associated shortcomings of published estimates. In this paper, the methodological characteristics of these studies are examined and their results are compared and interpreted. Alternative treatment and health outcome measures are defined and data sources described while methods for assessing the direct and indirect costs are explored. Directions for future research are identified and discussed.