The Cost-effectiveness of Eltrombopag for the Treatment of Immune Thrombocytopenia in the United States.

PURPOSE: Eltrombopag was evaluated as a second-line treatment for adult chronic immune thrombocytopenia (ITP) in the 2006 Phase III RAISE (Eltrombopag for Management of Chronic Immune Thrombocytopenia) randomized, placebo-controlled trial. More than 80% of patients reached satisfactory platelet counts within 2 weeks. However, the economic value of eltrombopag as a second-line treatment for ITP remains to be formally assessed. This study aimed to estimate the cost-effectiveness of treating ITP with a comparable thrombopoietin receptor agonist (eltrombopag vs romiplostim). METHODS: A Markov model was implemented over a lifetime time horizon to estimate the benefits and costs of each treatment. The model featured 3 health states based on current guidelines: (1) on treatment; (2) treatment failure/discontinuation; and (3) mortality. In line with therapeutic goals in ITP, model patients could experience 3 events: no bleeding, mild/moderate bleeding, or severe bleeding. Data on eltrombopag use were obtained from an open-label extension of previous Phase II/III trials, including RAISE. Romiplostim data were obtained from Phase III trials and an extension study. Lifetime overall survival was extrapolated by using treatment-specific mortality rates derived from severe bleeding and natural mortality rates. The costs of drugs, routine care, bleeding episodes, adverse events, and mortality were represented in the model. FINDINGS: Eltrombopag-treated patients gained 17.58 life years and 14.68 quality-adjusted life years, whereas romiplostim-treated patients gained 17.52 life years and 14.67 quality-adjusted life years. The total lifetime cost of eltrombopag treatment was estimated at $1.58 million versus $2.13 million for romiplostim. Sensitivity analyses supported base case findings. Deterministic sensitivity analysis predicted the greatest sensitivity to the rates of severe bleeding, discontinuation, and natural mortality. Probabilistic sensitivity analysis showed that eltrombopag would be an efficient use of resources at a $50,000 threshold in 52.8% of cases. In all probabilistic iterations, the total cost of eltrombopag treatment was lower than with romiplostim, primarily because of lower drug costs. IMPLICATIONS: Clinical data were applied in an economic analysis, and eltrombopag exhibited economic dominance compared with romiplostim, driven largely by the reduced costs of primary therapy. This model was limited by a lack of specific patient-level data and robust data on the duration of secondary therapy, as well as by the fact that utilization values are likely conservative estimates for routine care use.

Healthcare resource use and direct costs in severe aplastic anemia (SAA) patients before and after treatment with eltrombopag.

Purpose: This study evaluated healthcare resource utilization (HCRU), and direct costs among severe aplastic anemia (SAA) patients treated with eltrombopag (EPAG) using US claims data.Methods: This retrospective, real-world claims database study identified SAA patients aged ≥2 years treated with EPAG who initiated any SAA treatment between 1 July 2014 and 31 December 2017 (identification period) using the Truven MarketScan databases. A subset of 82 patients treated with EPAG during the identification period were evaluated for all-cause and SAA-related HCRU and direct costs as well as blood transfusion 1 month before EPAG initiation (baseline) and at Month 6 after EPAG initiation (follow-up period).Results: The average patient age was 50.8 (SD = 20.6) years old, predominantly female (n = 43, 52.4%), and had a mean CCI at baseline of 1.1 (SD = 1.7). Hospitalizations, and ER, office, and outpatient visits were significantly lower at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (p < .05 for all four all-cause HCRU and SAA-related hospitalizations). An almost two-fold decrease in reliance on biweekly blood transfusions was observed: 1.0 at weeks 1-2 to 0.5 at Month 6 after EPAG initiation. Although prescription costs (mean [SD]) were significantly higher at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (difference of $11,045 USD [SD = $18,801]), these increases were offset by savings in direct costs. Overall, a mean reduction in total all-cause costs of $29,391 USD [SD = $137,770] was reported at Month 6 after EPAG initiation due to substantial reductions in hospitalization ($40,060 USD [SD = $123,198]) and outpatient visits ($2,043 USD [SD = $25,264]).Conclusion: All-cause and SAA-related HCRU were reduced following EPAG treatment. Prescription costs were higher following treatment; however, these costs were generally offset by reductions in direct costs. These results provide real-world evidence around the role of EPAG in SAA treatment.

Budget Impact Of Eltrombopag As First-Line Treatment For Severe Aplastic Anemia In The United States.

BACKGROUND: Severe aplastic anemia (SAA) is a rare autoimmune condition resulting in low blood cell counts across lineages. Immunosuppressive therapy (IST) has demonstrated low response, toxicity, and risk of transformation. In a Phase I/II trial, the addition of eltrombopag to first-line IST increased response rates relative to an IST-only historical cohort. METHODS: A model was developed to estimate the budget impact of treating SAA with eltrombopag-based therapy from a US private healthcare system perspective. A simulated cohort of newly diagnosed SAA patients based on the total US population received 6 months of IST ± eltrombopag and were followed for 1 year, with mutually exclusive patient cohorts entering in years 1, 2, and 3. The model assessed the budget impact of first-year treatment for each cohort without considering subsequent years. At 6 months, responders in either arm received maintenance therapy (low-dose cyclosporine), and non-responders received 6 months of second-line eltrombopag monotherapy. Costs considered included first-line, maintenance, and second-line therapy, administration, routine care, mortality, and adverse events (AEs). All cost data were reported in 2018 US dollars. RESULTS: The annual incidence of aplastic anemia was 0.000234%, with 83.8% of cases assumed to be SAA. Based on trial data, 94% of patients receiving eltrombopag and IST responded versus 66% of patients receiving IST, with a 0.3% reduction in the annual risk of mortality for the eltrombopag + IST group. Use of first-line eltrombopag in a model SAA population based on the total US population increased overall costs by $50 million over 3 years. First-line drug costs accounted for an increase of $69 million, while improved response produced $19 million in secondary therapy cost savings. Sensitivity analyses confirmed the robustness of the analysis. CONCLUSION: High response rates combined with reduced rescue medication use and mortality in patients treated with eltrombopag and IST mediated higher medication costs.

Healthcare costs and resource utilization in patients with severe aplastic anemia in the US.

Purpose: This study aimed to evaluate the healthcare resource utilization (HCRU) and costs for patients with severe aplastic anemia (SAA) using US claims data. Methods: This retrospective, observational database study analyzed claims data from the Truven MarketScan databases. SAA patients aged ≥2 years identified between 2014 and 2017 who were continuously enrolled for 6 months before their first SAA treatment or blood transfusion, with a ≥6-month follow-up, were included. Baseline demographics and comorbidities were evaluated. Monthly all-cause and SAA-related HCRU and direct costs in the follow-up period were analyzed and differences were presented for all patients and across age groups. Results: With an average follow-up period of 21.5 months, 939 patients were included in the study. Monthly all-cause and SAA-related HCRU [mean (SD)] were 1.65 days (2.61 days) and 0.18 days (0.70 days) for length of stay, 0.18 (0.23) and 0.01 (0.04) for hospital admissions, 0.25 (0.30) and 0.02 (0.07) for ER visits, 2.24 (1.40) and 0.46 (0.99) for office visits, and 2.90 (2.64) and 0.55 (1.31) for outpatient visits, respectively. On average, SAA patients received 0.15 (0.57) blood transfusions per month. Mean monthly all-cause direct costs were $28,280 USD ($36,127) [US dollars, mean (SD)]. Direct costs related to admissions were $11,433 USD (SD $25,040), followed by $624 USD ($1,703) for ER visits, $528 USD ($694) for office visits, $7,615 USD ($13,273) for outpatient visits, and $5,998 USD ($11,461) for pharmacy expenses. Monthly SAA-related direct costs averaged $7,884 USD (SD $16,254); of these costs, $1,608 USD ($7,774) were from admissions, $47 USD ($257) from ER visits, $127 USD ($374) from office visits, $1,462 USD ($4,994) from outpatient visits, and $4,451 USD ($10,552) from pharmacy expenses. Conclusion: SAA is associated with high economic burden, with costs comparable to blood malignancies, implying that US health plans should consider appropriately managing SAA while constraining the total healthcare costs when making formulary decisions.

Everolimus compliance and persistence among tuberous sclerosis complex patients with renal angiomyolipoma or subependymal giant cell astrocytoma.

OBJECTIVE: Everolimus is the only FDA approved drug to treat renal angiomyolipoma or subependymal giant-cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC). Potential differences exist between patients with commercial and Medicaid insurance on everolimus use; however, there is limited information from the real world. This study compared compliance and persistence of everolimus between commercial and Medicaid patients using US claims data. METHODS: Patients with ≥1 claim of TSC with renal angiomyolipoma or SEGA were selected from the MarketScan commercial (1 January 2009-31 August 2016) and Medicaid (1 January 2009-30 June 2015) databases. Patients were followed from index date (the earliest date of TSC, renal angiomyolipoma or SEGA diagnosis) to death or end of data. Non-persistence, defined as ≥60 day gap without everolimus, and medication possession ratio (MPR) were assessed among the subset of patients with ≥1 year of follow-up from the first everolimus claim. RESULTS: A total of 1497 TSC patients met the study criteria (896 renal angiomyolipoma only, 411 SEGA only and 190 both). Compared to Medicaid patients (N = 513), commercial patients (N = 984) had the same ages (22 years) but a shorter length of follow-up (38 vs. 48 months, p < .001). Medicaid and commercial patients had similar rates of being treated with everolimus (14.4% vs. 13.6%, p = .668), but it took Medicaid patients a longer time to start everolimus (871 vs. 704 days, p < .001). Although the non-persistence rate was not significantly different between commercial and Medicaid patients (42.5% vs. 35.1%, p = .561), the number of days from everolimus initiation to non-persistence was significantly lower for commercial patients (945 vs. 1132, p < .001). During the 1 year post everolimus initiation, commercial patients had a significantly higher MPR (0.81 vs. 0.74, p < .001) and higher percentage of patients with MPR ≥0.80 (67.8% vs. 58.1%, p < .001). CONCLUSIONS: Among TSC patients with renal angiomyolipoma or SEGA and treated with everolimus, everolimus MPR was between 0.74 and 0.81. Medicaid patients had lower MPR than commercial patients but better persistence.

Cost-consequence model comparing eltrombopag versus romiplostim for adult patients with chronic immune thrombocytopenia.

BACKGROUND: Thrombopoietin-receptor agonists eltrombopag (EPAG) and romiplostim (ROMI) are treatment options for adults with chronic immune thrombocytopenia (cITP) who have had an insufficient response to corticosteroids or immunoglobulins. METHODS: A cost-consequence model was developed to evaluate the costs relative to treatment success of EPAG, ROMI, and watch and rescue (W&R) in previously treated patients. The primary endpoint assessed was severe bleeding, derived from all identified phase III registered clinical trials. Health outcomes were compared via indirect treatment comparison. Costs incorporated in the model included drug and administration, routine care, rescue medications, bleeding-related adverse events, other adverse events, and mortality costs. A trial (26-week) time horizon was used, as certain endpoints used in the model were bound to within-trial results. RESULTS: In the intent-to-treat (ITT) population, the overall estimated cost per patient for EPAG was US$66,560 compared to US$91,039 for ROMI and US$30,099 for W&R. Compared to the ITT population, the difference in cost between EPAG and ROMI was slightly greater in splenectomized patients (US$65,998 for EPAG compared to US$91,485 for ROMI) and slightly less in non-splenectomized patients (US$67,151 for EPAG compared to US$91,455 for ROMI), though the overall trend remained the same. When assessing cost per severe bleeding event avoided in the ITT population, EPAG dominated (less expensive, more effective) ROMI. Sensitivity analyses confirmed these results. CONCLUSION: EPAG was preferred over ROMI in the treatment of cITP, largely driven by the reduction in severe bleeding events associated with its use.

Cost-consequence model comparing eltrombopag and romiplostim in pediatric patients with chronic immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an auto-immune disorder characterized by enhanced platelet destruction and, subsequently, the potential for increased bleeding. Thrombopoietin receptor (TPO-R) agonists have recently emerged as promising therapies for ITP patients who are refractory to other treatments. While eltrombopag (EPAG) is the only TPO-R agonist US Food and Drug Administration approved for use in pediatric patients, romiplostin (ROMI) has been used in Phase III clinical studies. METHODS: A cost-consequence model (CCM) was developed to evaluate the costs of EPAG, ROMI, and watch-and-rescue (W&R) in relation to their respective treatment outcomes in previously-treated pediatric chronic ITP (cITP) over a 26-week time horizon. The costs of drugs, administration, routine care, rescue medications, adverse events, and mortality were included. Data on platelet count response rate, bleeding events, and adverse events were derived from all relevant identified Phase III-registered clinical trials, health outcomes were compared via indirect treatment comparison. RESULTS: The overall estimated cost of EPAG per patient was US$66,550, compared to US$101,056 for ROMI and US$32,720 for W&R. EPAG's lower cost compared to ROMI was largely due to lower drug costs (US$62,202 vs US$84,396), administration costs (US$0 vs US$1,955), and significantly lower costs due to severe bleeding (US$354 vs US$10,191). When assessing cost per severe bleeding event avoided, EPAG was dominant over ROMI (less expensive and more effective). EPAG was again dominant over ROMI when assessing the cost per responder and per bleeding event (any grade). Sensitivity analysis was consistent with the base case findings. CONCLUSION: EPAG was the preferred TPO-R agonist to treat cITP when indirectly compared to ROMI, largely driven by its favorable severe bleeding outcomes and lower drug and administration costs.

Economic burden, work, and school productivity in individuals with tuberous sclerosis and their families.

AIMS: Tuberous sclerosis complex (TSC) is a multi-organ autosomal-dominant, genetic disorder with incomplete penetrance. The multiple manifestations of TSC and impacts to numerous organ systems represent significant disease, healthcare, and treatment burden. The economic and employment burden of the disease on individuals and their families is poorly understood. This study assessed the cost of illness and work and school productivity burden associated with TSC in a cross-sectional web-survey sample. MATERIALS AND METHODS: Eligible TSC individuals and caregivers were invited through the Tuberous Sclerosis Alliance advocacy group to complete a web-based survey about illness characteristics, treatment, disease burden, direct and indirect healthcare costs, work and school impairment. RESULTS: Data from 609 TSC adults or caregiver respondents with no cognitive impairments were analyzed. TSC adults (>18 years of age) had significantly higher direct out-of-pocket costs for ER visits, expenses for medical tests and procedures, alternative treatments, medications and lifetime cost of surgeries compared to TSC pediatric individuals. Both TSC adults and TSC caregivers reported work and school absenteeism and presenteeism; however, adults reported significantly higher absenteeism and presenteeism and overall activity impairment due to TSC, as might be expected, compared to TSC caregivers. TSC adults had significantly higher absenteeism and presenteeism rates compared to adults with moderate-to-severe plaque psoriasis and muscular sclerosis. CONCLUSIONS: TSC results in considerable direct out-of-pocket medical costs and impairment to work productivity, especially for adults. Future studies should include the comparator group and examine direct cost burden in the US using electronic medical records and insurance databases.

Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets.

OBJECTIVE: To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]). METHODS: Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar's tests. RESULTS: In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p < .001); 60.9% vs 54.3% of patients had MPR ≥ 0.8 (p = .009); mean 3-month PDC was 0.83 vs 0.71 (p < .001); 64.2% vs 45.4% of patients had 3-month PDC ≥ 0.8 (p < .001); 87.2% vs 63.4% of patients had 3-month persistence with no gap ≥30 days and 96.1% vs 79.9% with no gap ≥60 days (p < .001). Adherence and persistence improved after switching across all diseases, particularly MDS. CONCLUSIONS: Adherence and persistence improved significantly after switching from DFX-DT to DFX-FCT for all diseases, but especially MDS.

Healthcare utilization and costs in patients with tuberous sclerosiscomplex-related renal angiomyolipoma.

OBJECTIVE: To quantify healthcare utilization and costs in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma (AML) in a matched cohort of patients without TSC or AML. METHODS: Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML during January 1, 2000-March 31, 2013 from the Commercial database and January 1, 2000-June 30, 2012 from the Medicaid database. Patients were required to have at least 30 days of follow-up from initiation into the study, and were followed until inpatient death, end of insurance coverage, or the end of study. Age, calendar year, and payer-matched controls that had no TSC and no AML were selected. All-cause annualized healthcare utilization and costs were calculated by service category. RESULTS: A total of 218 patients under 18 years and 377 patients 18 years and older with TSC-renal AML were selected from the Commercial database, and matched to 654 and 1,131 controls, respectively. Thirty-eight patients under 18 years and 110 patients 18 years or older with TSC-renal AML were selected from the Medicaid database, and matched to 54 and 212 controls, respectively. Within the Commercial cohort, and across both age groups, TSC-renal AML patients utilized more healthcare services than their matched controls. Within the Medicaid cohort, in both age groups, utilization was higher in TSC-renal AML patients vs control patients for inpatient admissions, emergency room visits, physician office visits, and hospital-based outpatient visits. Across age groups and in both the Commercial and Medicaid cohorts, the annual average total costs were significantly higher in TSC-renal AML patients compared to control patients (p < 0.05 for all). Healthcare costs ranged from $29,240-$48,499 for TSC-renal AML patients and from $2,082-$10,864 for control patients. CONCLUSIONS: Compared to controls, TSC-renal AML patients incurred substantially higher annual healthcare utilization and costs.

Opioid use in the management of diabetic peripheral neuropathy (DPN) in a large commercially insured population.

OBJECTIVE: To examine the proportion of diabetic peripheral neuropathy (DPN) patients receiving pharmacologic DPN treatments and specifically to identify the rates and factors associated with opioid use and first-line opioid use. METHODS: A 10% sample of IMS-LifeLink claims data from 1998 through 2008 was used. The study population consisted of diabetic patients who met DPN criteria using a validated DPN algorithm. Multivariable logistic regression controlling for demographics, comorbidities, and other clinical characteristics was used to identify factors associated with any DPN pharmacologic treatment, any opioid use, and first-line opioid treatment. Sensitivity analyses were conducted to explore variations in exclusion criteria as well as opioid use definitions. RESULTS: A total of 666 DPN patients met inclusion criteria and pharmacologic treatment was received by 288 patients (43.24%) and of those, 154 (53.47%) had DPN-related opioid use and 96 (33.33%) received opioid as first-line treatment. Persons with diabetic complications were more likely to use opioids (odds ratio=4.53; 95% confidence interval, 1.09-18.92). Food and Drug Administration-approved DPN agents duloxetine 1.04% (n=3) and pregabalin 5.56% (n=16) had much lower rates of use. DPN-related drug use and DPN-related opioid usage increased as we used less restrictive samples in sensitivity analyses. CONCLUSIONS: Opioids were the most frequently prescribed first-line agents for DPN. More than 50% of DPN patients remained untreated with pharmacologic agents 1 year after a DPN diagnosis.

The cost to managed care of managing pulmonary hypertension.

OBJECTIVE: To estimate direct medical costs and resource use for commercially-insured patients within two pulmonary hypertension sub-groups: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, subjects (≥18 years) with ICD-9 code 416.0 (PAH or CTEPH) or 416.8 (CTEPH) were identified during 2004-2009 within the MarketScan database. The date of the first observed claim was the index date. Each PAH and CTEPH patient was matched to one-to-five controls without PAH and CTEPH on age, gender, region, and payer type. Patients and controls were continuously enrolled for at least 12 months pre- and 12 months post-index date. Per-patient-per-month costs and resource use were compared using Wilcoxon rank-sum test. RESULTS: PAH patients (1647) and controls (6352) were identified (mean age 63 years, 73% female). Total monthly costs before PAH diagnosis were: PAH patients $2064 vs controls $1094. After PAH diagnosis, PAH patients had significantly higher monthly costs and resource use vs controls: Total costs $4021 vs $1533, outpatient visits 1.1 vs 0.8, inpatient visits 0.7 vs 0.2, prescriptions 3.6 vs 2.7, all p-values <0.05. One hundred and forty-six CTEPH patients and 558 controls were identified (mean age 64 years, 54.8% female). Total monthly costs in the period before CTEPH diagnosis were higher for CTEPH patients ($3895) than controls ($1177). After CTEPH diagnosis, CTEPH patients had significantly higher monthly costs and resource use vs controls: Total costs $6198 vs $1579, Outpatient visits 1.2 vs 0.8, inpatient visits 2 vs 0.2, prescriptions 4.2 vs 2.8, all p-values <0.05. KEY LIMITATIONS: Identification of PAH is complicated, as there exists no precise ICD-9-CM code for the condition. CTEPH diagnosis was based upon claims data and was not verified clinically. CONCLUSIONS: CTEPH and PAH patients incurred higher costs and used more resources than controls in the baseline and follow-up periods.

Impact of body mass index on the incidence of cardiometabolic risk factors in ambulatory care settings over 5 years or more.

OBJECTIVE: This study was performed to evaluate the association of body mass index (BMI) with the incidence of cardiometabolic risk factors in ambulatory care electronic medical records (EMRs) over 5 years or more. DESIGN: A retrospective cohort of normal versus obese patients. SUBJECTS: Subjects>or=18 years were identified between 1996 and 2005. MEASUREMENTS: Patients were categorized as either normal weight (18 kg/m227 kg/m2) based on baseline BMI (measured 395 days or more after first EMR activity). Outcomes included development, at least 180 days after the first BMI reading date, of four cardiometabolic risk factors (elevated triglycerides, low high-density lipoprotein cholesterol [HDL-C], hypertension, or type 2 diabetes) determined from ICD-9 code, prescribed drug, or biometric reading. Logistic regression estimated the odds of developing cardiometabolic risk factors, alone and combined for normal versus obese patients forward for at least 5 years. RESULTS: Seventy-one percent were female, mean age was 43.5 years, and 37.6% had a baseline BMI>27 kg/m2. Comparing obese versus normal weight patients, adjusted odds ratios for the incidence of elevated triglycerides, hypertension, diabetes, and low HDL-C were 2.1 (95% confidence interval [95% CI] 1.9-2.3), 2.2 (95% CI 2.1-2.4), 2.3 (95% CI 2.0-2.7), and 2.2 (95% CI 2.0-2.4), respectively. Adjusted odds ratios of developing one and all four new risk factors were 1.9 (95% CI 1.8-2.1) and 7.9 (95% CI 5.9-10.5), respectively. CONCLUSION: Obese patients are approximately twice as likely to develop cardiometabolic risk factors compared with those having normal weight over 5 or more years.

Association between cardiometabolic risk factors and body mass index based on diagnosis and treatment codes in an electronic medical record database.

BACKGROUND: Managed care organizations (MCOs) have access to treatment and diagnosis information from administrative claims data but generally have limited or no access to clinical information about laboratory values or biometric values such as body mass index (BMI) or waist circumference. Thus, MCOs are generally unable to identify overweight patients with cardiometabolic risk factors that put them at a high risk of poor outcomes. The National Heart, Lung, and Blood Institute defines normal body weight as a BMI (ratio of weight in kilograms to height in meters squared [kg/m2]) from 18.5 to 24.9 kg/m2, overweight as 25.0 to 29.9 kg/m2, and obesity as a BMI of 30 kg/m2 or greater. Current guidelines for weight-loss pharmacotherapy, including U.S. Food and Drug Administration-approved label indications, specify use in patients with a BMI of 30 kg/m2 or greater, or a BMI > 27 kg/m2 and at least 1 concomitant cardiometabolic risk factor such as controlled hypertension, diabetes, or dyslipidemia. OBJECTIVE: To evaluate the association of cardiometabolic risk factors with BMI as recorded in a database of electronic medical records (EMRs). METHODS: Each patient had a minimum look-back observation period of 2 years from the last date of activity in the EMR. Patients with a BMI of 18 kg/m2 or greater recorded in the EMR at any time during the 10-year period from January 1996 through December 2005 were stratified into groups by the number of cardiometabolic risk factors and by individual cardiometabolic risk for those with just 1 risk factor. Cardiometabolic risk factors were identified from diagnoses and prescription orders in the EMR associated with high triglyceride levels, low high-density lipoprotein cholesterol (HDL-C) levels, type 2 diabetes, or hypertension. Unadjusted and adjusted odds ratios (ORs) of having a BMI >27 kg/m2 were calculated for each risk factor group and for patients with no risk factors. Using logistic regression analysis, ORs were adjusted for age, gender, insurance type, region, medications associated with weight gain or weight loss, and diseases that modify weight. RESULTS: A total of 499,593 patients with a BMI of 18 kg/m2 or greater were identified; 56.4% (n = 281,988) had a BMI > 27 kg/m2, whereas 43.6% (n = 217,605) had a BMI between 18 and 27 kg/m2. Compared with patients with no risk factors (n = 289,960), patients with 1-4 risk factors (n = 209,633) were significantly more likely to have a BMI > 27 kg/m2; 48.4% of patients without cardiometabolic risk factors had a BMI > 27 kg/m2, compared with 63.3%, 79.8%, 84.6%, and 88.5% for patients with 1-4 cardiometabolic risk factors, respectively (all comparisons P < 0.001). Adjusted ORs for having a BMI > 27 kg/m2 were 2.64 (95% confidence interval [CI] = 2.51-2.77) for type 2 diabetes, 2.21 (95% CI = 2.05-2.37) for elevated triglycerides, 1.91 (95% CI = 1.88-1.94) for hypertension, and 1.45 (95% CI = 1.29-1.63) for low HDL-C. Adjusted ORs for having a BMI > 27 kg/m2 were 3.58 (95% CI = 3.47-3.69), 4.24 (95% CI = 3.93-4.59), and 5.07 (95% CI = 3.77-6.81) for patients with any 2, 3, and 4 risk factors respectively, relative to patients with no cardiometabolic risk factors. CONCLUSIONS: For patients with cardiometabolic risk factors, compared with patients with no risk factors, the odds of having a BMI > 27 kg/m2 were multiplied by 1.45-5.07, depending on the type and number of risk factors. Diagnoses and treatment indicators for cardiometabolic risk factors are potential indicators of obesity.

Somnolence effects of antipsychotic medications and the risk of unintentional injury.

PURPOSE: This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). METHODS: The study population included patients of 18-64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients with > or =2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent)--aripiprazole/ziprasidone; medium--risperidone; high--olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. RESULTS: Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03-1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83-1.64) and 1.17 95%CI (0.79-1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15-2.25) and 1.25 95%CI (0.89-1.74), respectively. CONCLUSIONS: High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence.

Problems in studying the association between race and pain in outcomes research.

Variability in the pain experience and treatment among patients of different races or ethnicities has been well studied over the past half century. Despite a large body of evidence describing these differences, the importance of these differences on health and cost outcomes has not be evaluated by pharmacoeconomists and outcomes researchers. We examined the subject to identify potential reasons for the lack of pharmacoeconomics and outcomes research (PE/OR) evaluations by first, defining PE/OR, second, taking the position that race can be an important modifier of disease outcomes by pointing out some identified differences in drug responses due to biology, and third, describing how PE/OR researchers have looked at race in other disease states. Finally, we propose some theories for the lack of such evaluations in pain outcomes research including the limited availability of race and ethnicity data in secondary datasets, a lack of priority for public and private funding organizations to support this type of research, and the potential biases of researchers and funding organizations.

An employer-based cost-benefit analysis of a novel pharmacotherapy agent for smoking cessation.

INTRODUCTION: An employer-based cost-benefit analysis for varenicline versus bupropion was conducted using clinical outcomes from a recently published trial. METHODS: A decision tree model was developed based on the net benefit of treatment to produce a nonsmoker at 1 year. Sensitivity analyses were conducted based on quit rates with placebo and varenicline and the cost of varenicline. RESULTS: Estimated 12-month employer cost savings per non-smoking employee were $540.60 for varenicline, $269.80 for bupropion SR generic, $150.80 for bupropion SR brand, and $81.80 for placebo. Varenicline was more cost beneficial than placebo, which had quit rates of 16.9% or less. The quit rate with varenicline would have to be

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.