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.

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.

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.

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.

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.

Agreement between pharmacists for problem identification: an initial quality measurement of cognitive services.

BACKGROUND: Recent changes in national reimbursement policies expand the ability of pharmacists to seek reimbursement for cognitive services. The quality of pharmacist-provided cognitive services has, until now, remained unassessed. Pharmacists should demonstrate the quality and value of their work to ensure the continued and expanded acceptance of reimbursement for their services. A preliminary step in assessing quality is to compare agreement between pharmacists for basic problem identification. OBJECTIVE: To quantify agreement between pharmacist reviewers for problem identification among Utah Medicaid recipients. METHODS: Five pharmacists retrospectively reviewed drug regimens, patient characteristics, diagnosis codes, and procedures for 80 Medicaid patients in September 2008 and identified drug-related problems (DRPs) in 15 predetermined categories. Data for each patient were reviewed twice, and each combination of 2 pharmacists reviewed the same 8 patients' information. We calculated a reliability coefficient to compare the number of DRPs identified and used prevalence and bias adjusted kappa (PABAK) to determine interrater reliability for the presence of a specific DRP. RESULTS: Of the 15 DRPs categorized by pharmacist reviewers, 1 (untreated indications) had a PABAK coefficient of 0.20, indicating a relatively low level of agreement between reviewers. All other DRP categories had good to excellent agreement, with PABAK coefficients ranging between 0.43 and 0.98. CONCLUSIONS: Pharmacist reviewers exhibited less variability in DRP identification or categorization than had been expected for most categories. This work supports the conclusion that pharmacists in our center provide a basic and necessary level of quality for problem assessment. Future work is needed to document the impact of this quality on patient outcomes.

Systematic analysis of outcomes evaluations applied to drug management programs.

OBJECTIVE: To evaluate prior analyses that quantify how drug management programs impact health plans and patients with respect to those analyses' effectiveness in measuring program quality. METHODS: We examined 77 US studies from 1996 to 2007 that evaluated the respective drug management programs of managed care, indemnity insurance, Veterans Health Administration, and Medicaid health plans. Our review included those studies that assessed the ways in which specific drug management tools and the drug management program overall impacted economic, clinical, and/or humanistic outcomes. RESULTS: The 77 studies included in our review used 11 types of outcome end points. A total of 52 studies (68%) incorporated an economic end point; of these, 35 (68%) reported economic data only and did not address clinical or humanistic outcomes. Overall, 33 (43%) evaluated clinical or humanistic end points; of these, 17 (52%) also reported on an economic end point. CONCLUSIONS: Although the number of studies evaluating drug management programs has trended upward, only a handful have integrated economic, clinical, and/or humanistic outcomes when assessing the effects these programs have on health plans and patients. The efforts of these researchers to assess the overall quality of drug management programs have fallen short. To ensure that drug management tools have a desired effect on outcomes and medical costs, measures used to evaluate drug management programs must be improved.

Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay.

BACKGROUND: Opioid analgesics remain a mainstay in the treatment of pain associated with surgical procedures. Such use is associated with adverse drug events (ADEs). OBJECTIVE: To investigate the impact of opioid-related ADEs on total hospital costs and length of stay (LOS) in adult surgical patients. METHODS: This was a retrospective matched cohort study using data from computerized medical records. ADE cases were prospectively detected using computerized surveillance and verified by pharmacists. Surgical patients treated at LDS Hospital in Salt Lake City from January 1, 1998, to December 31, 2003, were included. The primary outcomes were costs and hospital LOS associated with opioid-related ADEs and the relationship of opioid dose to ADE events. RESULTS: Patients experiencing opioid-related ADEs had significantly increased median total hospital costs (7.4% increase; 95% CI 3.83 to 10.96; p < 0.001) and increased median LOS (10.3% increase; 95% CI 6.5 to 14.2; p < 0.001) compared with matched non-ADE controls. The increased costs attributable to ADEs, by surgery type, were general surgery ($676.51; 95% CI 351.50 to 1001.50), orthopedics ($861.50; 95% CI 448.20 to 1274.80), and obstetrics/gynecology ($540.90; 95% CI 281.40 to 800.40). Similarly, increased LOS attributable to ADEs, by surgery type, were general surgery (0.64 days; 95% CI 0.40 to 0.88), orthopedics (0.52 days; 95% CI 0.33 to 0.71), and obstetrics/gynecology (0.53 days; 95% CI 0.33 to 0.72). Higher doses of opioids were associated with increased risk of experiencing ADEs (OR 1.3; 95% CI 1.07 to 1.60; p = 0.01). CONCLUSIONS: Opioid-related ADEs following surgery were associated with significantly increased LOS and hospitalization costs. These ADEs occurred more frequently in patients receiving higher doses of opioids.

Incidence and economic implications of heparin-induced thrombocytopenia in medical patients receiving prophylaxis for venous thromboembolism.

STUDY OBJECTIVES: To determine the incidence of heparin-induced thrombocytopenia (HIT) in patients admitted to a medical service who were given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) to prevent venous thromboembolism, the incremental cost of developing HIT, and the cost consequences of using LMWH to prevent venous thromboembolism in medical patients. DESIGN: Retrospective analysis with a nested case-control. SETTING: University-affiliated tertiary-care hospital. PATIENTS: A total of 10,121 adult medical patients admitted between August 1, 2000, and November 2, 2004, received UFH or LMWH to prevent venous thromboembolism during their admission. From these, patients with immune-mediated HIT were identified and served as case patients, and 3-5 matched control patients were identified for each case patient. MEASUREMENTS AND MAIN RESULTS: The development of HIT was determined for patients who received LMWH and for patients who received UFH. Costs were compared between the patients with HIT and the matched control patients. The cost of using LMWH to prevent venous thromboembolism was compared with the cost of using UFH. In patients receiving UFH and those receiving LMWH, the incidence of HIT was 0.51% (43/8420) and 0.084% (1/1189), respectively (p=0.037), with an overall incidence of 0.43% (44/10,121). Admissions that included development of HIT incurred an average cost of 56,364 dollars compared with 15,231 dollars (p<0.001) for admissions without HIT. Using LMWH to prevent venous thromboembolism in medical patients cost 13.88 dollars less per patient than using UFH. CONCLUSIONS: For the prophylaxis of venous thromboembolism, LMWH was associated with a lower incidence of HIT than UFH in medical patients. An admission during which the patient develops HIT costs significantly more than an admission during which the patient does not develop HIT. Low-molecular-weight heparin is cost-effective for prevention of venous thromboembolism in medical patients.

Gastrointestinal complications of over-the-counter nonsteroidal antiinflammatory drugs.

This study assessed the "real-world" risk of serious gastrointestinal (GI) toxicities, defined as perforations, ulcers and bleeds (PUBs) in a U.S. representative population that was using two commonly available over-the-counter (OTC) non-selective nonsteroidal antiinflammatory drugs (NSAIDs), naproxen or ibuprofen with or without concomitant aspirin usage. A retrospective review of a commercially available electronic medical record (EMR) database containing the ambulatory health record data for over 3.2 million individuals was conducted. Subjects were eligible for inclusion in the study if they received an OTC dosage of naproxen (220 mg) or ibuprofen (200 mg). An index date for each subject was defined as the first mention of an OTC NSAID in the medication list of the EMR dataset. Subjects were excluded from the analysis if they met any criteria, which can lead to GI bleeding complications. The dataset was analyzed for PUBs, as indicated by the ICD-9 diagnosis codes for gastric, duodenal, peptic, or gastrojejunal ulcers, or GI hemorrhage, as well as the concomitant use of aspirin. A pre/post-analysis was conducted using a case-crossover design with subjects as their own controls. The index date was the defining event, in order to determine the odds ratio associated with OTC NSAID usage. A pre-index time period of 365 days was used for prior PUBs. For the post-index time period, only PUBs that occurred within 90 days of the OTC NSAID index date were considered. The data set contained 11,957 subjects on naproxen and 38,507 subjects on ibuprofen. In both cases, OTC NSAID usage was associated with a statistically significant increase in the odds ratio for PUBs. Subjects on ibuprofen had an odds ratio of 1.38 (95% CI 1.07-1.78, P=0.01). Naproxen subjects exhibited an odds of 1.54 (95% CI 1.04-2.28, P=0.03). The concomitant aspirin population consisted of 2,328 naproxen subjects and 4,843 ibuprofen subjects. Concomitant aspirin usage was also associated with a significantly higher risk for PUBs than the corresponding monotherapy. Subjects taking both ibuprofen and aspirin had an odds ratio of 3.36 (2.36-4.80, P<.00001), while those on naproxen and aspirin had an odds ratio of 2.07 (1.23-3.49, P=.005) relative to those subjects on ibuprofen and naproxen monotherapy, respectively. Utilizing a national electronic medical record database representing patients seen predominantly in a primary care setting, this study has documented the "real-world" risk associated with the use of two common OTC NSAIDs, as well as the increased risk associated with concomitant aspirin use in this population.

Economic evaluations in pain management: principles and methods.

This paper describes how investigators may design, conduct, and report economic evaluations of pharmacotherapy for pain and symptom management. Because economic evaluation of therapeutic interventions is becoming increasingly important, there is a need for guidance on how economic evaluations can be optimally conducted. The steps required to conduct an economic evaluation are described to provide this guidance. Economic evaluations require two or more therapeutic interventions to be compared in relation to costs and effects. There are five types of economic evaluations, based on analysis of: (1) cost-effectiveness, (2) cost-utility, (3) cost-minimization, (4) cost-consequence, and (5) cost-benefit analyses. The six required steps are: identify the perspective of the study; identify the alternatives that will be compared; identify the relevant costs and effects; determine how to collect the cost and effect data; determine how to perform calculation for cost and effects data; and determine the manner in which to depict the results and draw comparisons.

Opioid expenditures and utilization in the Medicaid system.

Data from the U.S. Centers for Medicare and Medicaid Services' Medicaid database were analyzed to define recent trends in the use and cost of opioid medications United States as a whole and in seven states between 1998 and 2003. Over this time period, total Medicaid prescriptions for opioids have nearly doubled and, in nominal terms, expenditures have nearly tripled. The morphine derivatives account for the largest share of these increases. By 2003, opioids represented about a four percent share of all Medicaid prescription drugs. Variations among the states in per-enrollee spending on opioids are substantial. The appropriateness of these variations is unknown.

Documentation of chemotherapy infusion preparation costs in academic- and community-based oncology practices.

Significant changes in Medicare reimbursement for outpatient oncology services were proposed as part of the Medicare Modernization Act of 2003. The purpose of this study was to identify the "true cost" associated with drug-related handling for the preparation and delivery of chemotherapy doses to estimate the impact of changing reimbursement schema by Medicare. Two academic medical outpatient infusion centers and 2 community cancer centers provided data used to estimate all costs (excluding drug cost) associated with the preparation of chemotherapy doses. The data included both fixed costs (drug storage, space, equipment, and information resources) and variable costs (insurance management, inventory, waste management, pharmacy staff payroll, supplies, and shipping). The average cost for the preparation of chemotherapy doses across all sites was dollar 34.27 (range, dollar 32.08-dollar 41.23). A time-and-motion study was also performed to determine what tasks were conducted by pharmacy staff and how much time was spent in the preparation of the top 15 chemotherapeutic drugs and regimens used in the 4 sites. Data from the 4 centers was projected to show that if 3,990,495 million chemotherapy infusions were administered to a national Medicare population in 2003, when multiplied by the average cost of preparation for infusions determined by the current study (dollar 34.27), the estimated total annual cost to Medicare for chemotherapy preparation by pharmacists is dollar 136,754,263.65. The pharmacists spent most of their days (90% or more) performing tasks directly related to the preparation of these agents. These data provide scientific support for the consideration of appropriate reimbursement for chemotherapy services provided by pharmacists to Medicare beneficiaries.