The health and economic burden of osteoporotic fractures in Singapore and the potential impact of increasing treatment rates through more pharmacological options.

PURPOSE: This study aims to estimate the health and economic burden of osteoporosis in Singapore from 2017 to 2035, and to quantify the impact of increasing the treatment rate of osteoporosis. METHODS: Population forecast data of women and men aged 50 and above in Singapore from 2017 to 2035 was used along with prevalence rates of osteoporosis to project the osteoporosis population over time. The population projections by sex and age group were used along with osteoporotic fracture incidence rates by fracture type (hip, vertebral, other), and average direct and indirect costs per case to forecast the number of fractures, the total direct health care costs, and the total indirect costs due to fractures in Singapore. Data on treatment rates and effects were used to model the health and economic impact of increasing treatment rate of osteoporosis, using different hypothetical levels. RESULTS: Between 2017 and 2035, the incidence of osteoporotic fractures is projected to increase from 15,267 to 24,104 (a 57.9% increase) F 10,717 to 17,225 (a 60.7% increase) and M 4550 to 6878 (a 51.2% increase). The total economic burden (including direct costs and indirect costs to society) associated with these fractures is estimated at S$183.5 million in 2017 and is forecasted to grow to S$289.6 million by 2035. However, increasing the treatment rate for osteoporosis could avert up to 29,096 fractures over the forecast period (2017-2035), generating cumulative total cost savings of up to S$330.6 million. CONCLUSION: Efforts to improve the detection, diagnosis, and treatment of osteoporosis are necessary to reduce the growing clinical, economic, and societal burden of fractures in Singapore.

Estimating Years of Life Lost Due to Cardiovascular Disease in Japan.

BACKGROUND: In Japan, the burden associated with myocardial infarction (MI) and ischemic stroke as well as atherosclerotic cardiovascular disease (ASCVD) generally is high. One key element in measuring disease burden is years of life lost (YLL). The aim of this study was to understand the burden of these diseases by estimating YLL at an overall disease level and average person-YLL (PYLL), a measure of disease burden also used in prior studies. Methods and Results: Because calculation of YLL and PYLL involves inputs such as disease prevalence, disease-related mortality by age, and general population mortality by age and sex, we searched public databases of disease surveillance to identify comprehensive Japanese-specific inputs. For our reference analysis, disease-specific prevalence and mortality were taken from the Institute for Health Metrics and Evaluation Global Disease Burden study, and background mortality data were from the Japanese life tables published by the Ministry of Health, Labour and Welfare. The average age of patients with MI or stroke was 74 and 70 years, respectively. On average, men comprised 59% and 54% of the MI and stroke population, respectively. The disease-level burden of ASCVD (inclusive of MI, stroke, and peripheral artery disease) was 2,703,711 YLL in 2017. The patient-level burden was 11.99 PYLL for MI and 9.39 PYLL for stroke. CONCLUSIONS: The burden of ASCVD, MI, and stroke in terms of premature mortality is substantial in Japan, both on a population disease level and an individual patient level.

Autoimmune comorbidities in patients with metastatic melanoma: a retrospective analysis of us claims data.

BACKGROUND: Immunotherapies have advanced the treatment of metastatic melanoma; however, they are associated with immune-related toxicities. Patients with pre-existing autoimmune comorbidities are commonly excluded from clinical trials investigating immunotherapies in metastatic melanoma. Since information on pre-existing autoimmune comorbidities in "real-world" patients with newly diagnosed metastatic melanoma is limited, we sought to estimate the prevalence of autoimmune comorbidities and its change over time. METHODS: Data were obtained from a large US claims database, MarketScan®, from 2004 to 2014. Records of patients with newly diagnosed metastatic or non-metastatic melanoma and of general population were analyzed. Autoimmune comorbidities were defined as presence of autoimmune disorders, which were obtained from the list of diseases at the American Autoimmune-Related Diseases Association web portal ( www.aarda.org ). The prevalence of pre-existing autoimmune comorbidities and its change over the 11-year period were calculated. Logistic regression analyses were performed to evaluate the relationship between clinical and demographic factors and pre-existing autoimmune comorbidities in patients with metastatic melanoma. RESULTS: This study assessed the prevalence and change of prevalence over a period of 11 years of 147 autoimmune comorbidities. Among 12,028 patients with newly diagnosed metastatic melanoma, the prevalence rate of pre-existing autoimmune comorbidities increased from 17.1% in 2004 to 28.3% in 2014 (P < 0.001). The prevalence rates of autoimmune comorbidities increased from 11.7% in 2004 to 19.8% in 2014 in patients with non-metastatic melanoma and 7.9% in 2004 to 9.2% in 2014 in the general population. In addition, patients with bone or gastrointestinal melanoma metastases, those with more comorbid diseases, or female patients, were found to have a higher risk of autoimmune comorbidities. CONCLUSIONS: The prevalence of pre-existing autoimmune comorbidities in patients with newly diagnosed metastatic melanoma was high, and increased over 11 years. In comparison, a lower prevalence of autoimmune comorbidities was seen in patients with newly diagnosed non-metastatic melanoma and in the general population. Increases in prevalence for these population groups were also observed over 11 years. Impact of autoimmune comorbidities on treatment decisions in patients with metastatic melanoma should be explored.

Patterns of use of systemic therapies among patients with metastatic melanoma: a retrospective claims database analysis in the United States.

OBJECTIVES: This retrospective analysis of the IMS PharMetrics Plus claims database aimed to describe the current real-world treatment patterns for metastatic melanoma in the USA. METHODS: Included patients (aged ≥18 years) had ≥1 prescription for ipilimumab, vemurafenib, temozolomide or dacarbazine between 1 January 2011 and 31 August 2013; diagnosis of melanoma and metastasis before first use (index date); no index drug use prior to the index date; continuous health plan enrollment for ≥6 months before and ≥3 months after index date. Proportion of days covered (PDC) was defined as days exposed to index therapy divided by continuously enrolled days between index date and last prescription date. RESULTS: Overall, 1043 patients were included (median age 57 years, 63% male), of whom 39% received the index drug ipilimumab, 35% vemurafenib, 19% temozolomide and 7% dacarbazine. Mean treatment duration (days) was 174 (vemurafenib), 100 (temozolomide) and 64 (dacarbazine). Mean PDC was 81% (vemurafenib), 67% (temozolomide) and 51% (dacarbazine). For patients receiving ipilimumab, 58% had the full 4 doses, 20% 3 doses, 14% 2 doses and 9% 1 dose only for the first induction course; 4% received re-induction, and none had a second re-induction. CONCLUSIONS: This study provides insights into the treatment patterns for metastatic melanoma, including newer agents, in real-world clinical practice.

Economic burden of toxicities associated with treating metastatic melanoma in eight countries.

BACKGROUND: Information on costs of managing adverse events (AEs) associated with current treatments in metastatic melanoma is limited. This study estimates costs of AEs in eight countries: Australia (AU), Canada (CA), France (FR), Germany (GE), Italy (IT), the Netherlands (NL), Spain (ES), and the UK. METHODS: A literature search was conducted to identify grade 3/4 AEs from product label, published trials, conference abstracts, and treatment guidelines. Resource utilization for the management of each type of AE was determined via interviews with 5 melanoma clinicians in each country. Outpatient and inpatient costs were estimated for each type of AE using country-specific tariffs or government/published sources. RESULTS: In outpatient settings, the most costly AEs per incident included cutaneous squamous cell carcinoma (CSCC) (€1063, £720; NL/UK), anemia (€1443, €1329, €1285; ES/IT/FR), peripheral neuropathy (€1289; ES), and immune-related diarrhea (AUS$1,121; AU). In inpatient settings, the most costly AEs per hospitalization included hypophysitis (€10,265; €5316; CAN$9735; AUS$7231: ES/FR/CA/AU), dyspnea (€9077; GE), elevated liver enzymes (€6913, CAN$8030, AUS$6594; FR/CA/AU), CSCC (CAN$8934; CA), peripheral neuropathy (€6977, €4144, CAN$9472; NL/ES/CA), and diarrhea (£4284, €4113; UK/ES). CONCLUSIONS: Costs of managing AEs can be significant, and thus effective treatments with lower rates of severe AEs would be valuable.

Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.

BACKGROUND: Little has been reported on the costs of managing the adverse events (AEs) associated with current therapies for patients with regional or distant metastatic melanoma. OBJECTIVES: To identify treatment-related AEs in patients with metastatic melanoma and to estimate the associated costs of treating these AEs in the United States. METHODS: A cost-estimation study for AEs associated with treatment of metastatic melanoma was conducted from 2012 to 2013 by identifying grades 3 and 4 AEs through the use of a comprehensive search of drug labels and English-language, published phase 2/3 studies in PubMed, conference abstracts, and the National Comprehensive Cancer Network guidelines. Resource utilization for the management of each type of AE in the outpatient setting was obtained via interviews with 5 melanoma specialists in the United States. Unit costs for an AE associated with melanoma treatment in the outpatient setting were assigned using Medicare reimbursement rates to obtain these costs. Hospitalization and length-of-stay costs were estimated for each associated AE using the large national claims database Optum Clinformatics Data Mart for the period of July 1, 2004, to November 30, 2012. RESULTS: The most common AEs associated with chemotherapies used for melanoma were neutropenia, vomiting, and anemia. The most common AEs associated with vemurafenib were cutaneous squamous-cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and pyrexia. Trametinib was most often associated with hypertension and rash. The most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea, anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4 AE with talimogene laherparepvec was cellulitis. The highest treatment costs for an AE in the outpatient setting were for neutropenia ($2092), headache ($609), and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma, thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and elevated liver enzymes were associated with mean costs for hospitalization ranging from $19,122 to $26,861. CONCLUSION: The costs of managing treatment-related AEs in patients with metastatic melanoma are substantial. Effective treatments with improved safety profiles may help to reduce these costs. Until real-world evidence for the costs associated with treatment toxicity is available in the outpatient and inpatient settings, the costs estimated in this study can help inform decision makers about the cost-effectiveness of managing patients with metastatic melanoma.

Estimating healthcare resource use associated with the treatment of metastatic melanoma in eight countries.

Objectives Studies reporting healthcare resourse use (HRU) for melanoma, one of the most costly cancers to treat, are limited. Using consistent, robust methodology, this study estimated HRU associated with the treatment of metastatic melanoma in eight countries. Methods Using published literature and clinician input, treatment phases were identified: active systemic treatment (pre-progression); disease progression; best supportive care (BSC)/palliative care; and terminal care. HRU elements were identified for each phase and estimates of the magnitude and frequency of use in clinical practice were obtained through country-specific Delphi panels, comprising healthcare professionals with experience in oncology (n = 8). Results Medical oncologists are the key care providers for patients with metastatic melanoma, although in Germany dermato-oncologists also lead care. During the active systemic treatment phase, each patient was estimated to require 0.83-2 consultations with a medical oncologist/month across countries; the median number of such assessments in 3 months was highest in Canada (range = 3.5-5) and lowest in France, the Netherlands and Spain (1). Resource use during the disease progression phase was intensive and similar across countries: all patients were estimated to consult with medical oncologists and 10-40% with a radiation oncologist; up to 40% were estimated to require a brain MRI scan. During the BSC/palliative care phase, all patients were estimated to consult with medical oncologists, and most to consult with a primary care physician (40-100%). Limitations Panelists were from centers of excellence, thus results may not reflect care within smaller hospitals; data obtained from experts may be less variable than data from broader clinical practice. Treatments for metastatic melanoma are continually emerging, thus some elements of our work could be superseded. Conclusions HRU estimates were substantial and varied across countries for some resources. These data could be used with country-specific costs to elucidate costs for the management of metastatic melanoma.

Use Patterns and Costs of Isolated Limb Perfusion and Infusion in the Treatment of Regional Metastatic Melanoma: A Retrospective Database Analysis.

INTRODUCTION: Isolated limb perfusion and infusion (ILP/ILI) are therapies for regional metastatic melanoma that allow high doses of anticancer drugs to be delivered directly into the circulation of an affected limb, thereby minimizing systemic drug toxicity. This procedure can lead to high response rates and is recommended in patients with Stage III unresectable metastatic melanoma. However, limited information is available on patterns of use and costs. This study examined patterns of ILP/ILI use and associated costs in patients with melanoma in the United States (US). METHODS: Retrospective, observational study, using administrative claims data from the MarketScan(®) databases, was performed in patients with a diagnosis of melanoma (ICD-9-CM: 172.xx, V10.82) who underwent ILP/ILI (CPT-4: 36823) between January 1, 2002 and March 31, 2013. Patient characteristics, use patterns, length of hospital stay, and costs (per 2014 US $) of ILP/ILI were assessed. RESULTS: One hundred and thirteen patients met the study criteria and were included in the analysis. Mean age was 61.4 years (standard deviation [SD] 13.8) and 38.9% of patients were male; the mean baseline Charlson Comorbidity Index was 0.19; 34.5% of patients were Medicare beneficiaries. The majority of patients (87.6%) had melanoma of the lower limb, 11.5% of the upper limb, and 0.9% of both limbs; 60.2% had lymph node metastasis and 56.6% had skin metastasis. Four patients (3.5%) underwent multiple ILP/ILI. The mean (± SD) length of hospital stay was 5.6 (± 3.5) days and the mean (± SD) cost was US$36,758 (± 27,124) per ILP/ILI procedure. CONCLUSIONS: Isolated limb perfusion and infusion in patients with melanoma were associated with long hospital stays and high costs. These results provide useful source data for the economic evaluation of treatment options for regional metastatic melanoma. FUNDING: This study was funded by Amgen, Inc.

Systematic review on infusion reactions associated with chemotherapies and monoclonal antibodies for metastatic colorectal cancer.

OBJECTIVE: The objective of this systematic review is to summarize the literature to date on the rates of infusion reactions (IR) associated with chemotherapies and monoclonal antibody (mAb) drug therapies used for the treatment of metastatic colorectal cancer (mCRC) and the associated clinical and economic impact. METHODS: This study searched Medline, Medline (R) In-Process, Embase and Cochrane Library databases for studies on IRs associated with chemotherapy and mAbs in mCRC patients from 2000-2011. RESULTS: For chemotherapy, the incidence of IRs ranged from 0-71% for all grades and 0-15% for grade 3-4. Rates of all grade IRs associated with cetuximab ranged from 7.6-33% and grade 3-4 IR rates were 0-22%. Rates of all grade IRs associated with panitumumab ranged from 0-4% and rates of grade 3-4 IRs ranged from 0-1%. The overall rate of IRs associated with bevacizumab ranged from 1.6-11%, with a rate of 0-4% for grade 3-4 IRs. A range of 50-100% of patients with grade 3-4 IRs terminated chemotherapy, and 34-100% of cetuximab patients with grade 3-4 IRs discontinued cetuximab therapy. No data were reported for bevacizumab or panitumumab. Only one study evaluated the economic impact of IRs. The study compared cetuximab administrations without an IR to those with an IR requiring resource utilization and found that mean costs were $9308 and $1725 higher for those with an IR requiring an emergency room visit or hospitalization and for those with an IR requiring outpatient treatment, respectively. CONCLUSIONS: The incidence of IRs varies among different mAbs; and IRs may cause treatment disruption and require costly medical interventions.

Economic burden of toxicities associated with metastatic colorectal cancer treatment regimens containing monoclonal antibodies.

OBJECTIVES: Little is known about toxicity-related costs of monoclonal antibody treatments in metastatic colorectal cancer. This study aimed to identify toxicities associated with bevacizumab, cetuximab, and panitumumab and estimate the direct costs of these toxicities. METHODS: Grade 3 and 4 toxicities were identified by a comprehensive literature search. Inpatient costs were estimated using ICD-9 codes and 2007 Medicare payments from the Healthcare Cost and Utilization Project database; costs were converted to 2010 dollars. Outpatient costs were estimated by applying 2010 Medicare reimbursement rates to resource use assumptions (based on in-depth clinical interviews). RESULTS: Toxicities associated with bevacizumab included hypertension, arterial thrombosis, hemorrhage, gastrointestinal (GI) perforation, fistula, and wound-healing complications; toxicities associated with cetuximab and panitumumab included skin rash, hypomagnesemia, and infusion reactions. The inpatient cost per event was highest for GI perforation (USD 32,443), followed by fistula (USD 29,062), arterial thrombosis (USD 20,346), and wound-healing complications (USD 13,240), while inpatient costs per event for hypomagnesemia and skin rash were among the lowest. The cost per event of toxicities treated in the outpatient setting included USD 185 for skin rash up to USD 585 for wound-healing complications. LIMITATIONS: Treatment costs of toxicities for the outpatient setting were determined using assumptions validated by clinicians, and unit costs were based on Medicare reimbursement rates, which are often lower than the reimbursement rates for commercial health insurance plans. Toxicities included were only grades 3 and 4 adverse events and might be limited by differences between clinical studies. CONCLUSIONS: Monoclonal antibodies have different toxicity profiles and the costs associated with managing these toxicities vary greatly.

Costs of hospital events in patients with metastatic colorectal cancer.

BACKGROUND: In the last decade, the number of new agents, including monoclonal antibodies, being developed to treat metastatic colorectal cancer (mCRC) increased rapidly. While improving outcomes, these new treatments also have distinct and known safety profiles with toxicities that may require hospitalizations. However, patterns and costs of hospitalizations of toxicities of these new 'targeted' drugs are often unknown. OBJECTIVE: This study aimed to estimate the costs of hospital events associated with adverse events specified in the 'Special Warnings and Precautions for Use' section of the European Medicinal Agency Summary of Product Characteristics for bevacizumab, cetuximab, and panitumumab, in patients with mCRC. METHODS: From the PHARMO Record Linkage System (RLS), patients with a primary or secondary hospital discharge code for CRC and distant metastasis between 2000-2008 were selected and defined as patients with mCRC. The first discharge diagnosis defining metastases served as the index date. Patients were followed from index date until end of data collection, death, or end of study period, whichever occurred first. Hospital events during follow-up were identified through primary hospital discharge codes. Main outcomes for each event were length of stay and costs per hospital admission. RESULTS: Among 2964 mCRC patients, 271 hospital events occurred in 210 patients (mean [SD] duration of follow-up: 34 [31] months). The longest mean (SD) length of stay per hospital admission were for stroke (16 [33] days), arterial thromboembolism (ATE) (14 [21] days), wound-healing complications (WHC), acute myocardial infarction (AMI), congestive heart failure (CHF), and neutropenia (all 9 days; SD 5-15). Highest mean (SD) costs per admission were for stroke (€13,500 [€28,800]), ATE (€13,300 [€18,800]), WHC (€10,800 [€20,500]). LIMITATIONS: Although no causal link could be identified between any specific event and any specific treatment, data from this study are valuable for pharmacoeconomic evaluations of newer treatments in mCRC patients. CONCLUSIONS: Inpatient costs for events in mCRC patients are considerable and vary greatly.

Characterizing medical care by disease phase in metastatic colorectal cancer.

OBJECTIVE: To characterize patterns of medical care by disease phase in patients with newly diagnosed metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC newly diagnosed between 2004 and 2008 were selected from a large US national commercially insured claims database and were observed from initial mCRC diagnosis to death, disenrollment, or end of study period (July 31, 2009), whichever occurred first. The observation period was divided into 3 distinct phases of disease: diagnostic, treatment, and death. Within each phase, patterns of medical care were examined by the mutually exclusive service categories of inpatient, emergency department (ED), outpatient office and facility, outpatient pharmacy, chemotherapy, and biologic therapy, as measured by estimation of aggregate and category costs per patient per month. RESULTS: A total of 6675 patients with newly diagnosed mCRC were analyzed. Mean age was 64.1 years; 55.5% were males. Mean costs per patient per month for diagnostic, treatment, and death phases were $16,895, $8891, and $27,554, respectively. Inpatient care was the primary driver of medical care for both the diagnostic (41.7% of costs) and death (71.4% of costs) phases. The largest category of medical care for the treatment phase was outpatient care (45.0% of costs). Chemotherapy and biologic therapy accounted for 15.6% and 17.6% of costs in the treatment phase, respectively. CONCLUSION: Substantial differences in patterns of medical care were found between mCRC disease phases. Inpatient care was the key driver of medical care in the diagnostic and death phases compared with outpatient care in the treatment phase.

Cost of illness in patients with metastatic colorectal cancer.

OBJECTIVES: To estimate total costs and metastatic colorectal cancer (mCRC)-related costs and assess primary cost drivers of treating newly diagnosed mCRC patients after the introduction of biologic therapies. METHODS: Using a large national claims database, costs of mCRC patients were estimated in 2004-2009 by examining (1) the cost difference between mCRC patient and their matched non-cancer cohorts, and (2) mCRC-related costs. Costs were further assessed by phase of disease (diagnostic, treatment, and death). The survival analysis technique was used to estimate cost of handling variable length of follow-up and data censoring. RESULTS: A total of 6,746 mCRC patients met all eligibility criteria, 6,675 of them were matched to patients without cancer. Among the three phases of disease, the treatment phase was the longest (16.4 months). Compared with matched patients with no cancer, total monthly costs were $14,585 higher for mCRC patients, which was driven by higher inpatient ($7,546) and outpatient ($6,749) care (p < 0.001 for all comparisons). During the study period, cost share of biologics increased from 4.8% among patients diagnosed in 2004 to 9.4% for those diagnosed in 2008. CONCLUSIONS: The costs associated with treating mCRC are substantial. Inpatient and outpatient care remain key cost drivers in the medical management of mCRC. Cost chare of biologics was low, but increased between 2004 and 2009. The study sample only included patients with commercial and Medicare supplemental insurance in the US thus may not be generalizable to patients with other insurance or in other countries. Indirect costs associated with mCRC were not examined.

The cost of comorbid depression and pain for individuals diagnosed with generalized anxiety disorder.

Patients with generalized anxiety disorder (GAD) often have comorbid medical and psychiatric disorders and may incur higher costs. In this study, a total of 36,435 GAD patients aged 18 to 64 were identified from a claims database. Patient's total health care and component costs were compared between GAD patients with and without comorbid depression and pain using general linear models. The average total annual cost for all the GAD patients in the study was $7451. Compared with patients with GAD-only, the estimated total cost was $762 higher for GAD with depression (p < 0.001), $2989 higher for GAD with pain (p < 0.001), and $6073 higher for GAD with both depression and pain (p < 0.001). Comorbid depression and pain had significant impact on costs, especially those with pain or with both depression and pain. This suggests that an optimal strategy for GAD should take into account comorbid pain and depression.

Urban employee health insurance reform and the impact on out-of-pocket payment in China.

Since the middle of the 1990s, China has undertaken a significant reform in urban employee health insurance programs. Using data from the pilot experiment conducted in Zhenjiang, this study examines changes in the pre- and post-reform distributions of out-of-pocket (OOP) expenditures across four representative groups by chronic disease, income, education, and job status. Major findings suggested increased OOP expenditures for all groups after the reform. However, the redistributions in OOP appear to be in favor of the disadvantaged groups, suggesting a more equitable change led by the reform. This study concludes that the post-reform insurance model did not compromise equity in cost-sharing while containing cost inflation and increasing insurance coverage for the urban population.

Service utilization and costs of olanzapine versus divalproex treatment for acute mania: results from a randomized, 47-week clinical trial.

OBJECTIVE: This study examined direct treatment costs based on medication and service use data collected in a 47-week multi-center, double-blind, randomized clinical trial of olanzapine versus divalproex for patients with bipolar disorder and and experiencing acute mania. RESEARCH DESIGN AND METHODS: Patients who completed the 3-week acute phase and entered into the 44-week maintenance phase (n = 147) of the trial were included. Service use data were collected at weeks 3, 7, 15, 23, 31, 39 and 47 of the maintenance phase. Analyses were conducted to address potential biases from discontinuation patterns and use of this patient sub-sample. RESULTS: Overall, per patient yearly costs were similar for olanzapine- and divalproex-treated patients ($14 967 vs. $15 801). Psychiatric-related costs accounted for 95.4% and 93.6% of the total costs for olanzapine- and divalproextreated patients, respectively. Study medication costs were significantly higher for olanzapine than for divalproex ($4662 vs. $1755, p < 0.01). However, this was offset by the combined effects of numerically lower costs for several other services with olanzapine treatment. Some of the savings associated with olanzapine treatment compared with divalproex treatment resulted from differences in costs associated with emergency room services ($432 vs. $1346, p < 0.05). CONCLUSIONS: Overall per-patient treatment costs were similar for olanzapine and divalproex. Recognizing challenges in analyzing and generalizing cost outcomes from a clinical trial setting, results provide some much-needed comparative economic information regarding these two medication options for treating mania in bipolar disorder.

Economic outcomes associated with olanzapine versus risperidone in the treatment of uncontrolled schizophrenia.

OBJECTIVE: This study, based upon a database analysis, compares a one-year drug treatment course (duration of therapy, concomitant use of typical antipsychotics, anxiolytics/antidepressants or anti-Parkinsonians) and direct health care costs of uncontrolled schizophrenia patients initiated on olanzapine versus risperidone. METHODS: The integrated medical and pharmacy claims of a large, geographically diverse, commercially insured population of 1.6 million employees, retirees and dependents were used to conduct this analysis. Patients who initiated outpatient treatment with either olanzapine or risperidone (no prescription for olanzapine or risperidone during a 1-year period prior to the initiation) and with uncontrolled schizophrenia were included. Drug treatment course and associated health care costs (calculated based on charges) during the subsequent 12-month period were examined using univariate and multivariate methods. RESULTS: 431 patients initiated on risperidone and 142 initiated on olanzapine met the inclusion criteria. The mean dose was 4.34 and 11.00 mg/day for risperidone and olanzapine, respectively. Olanzapine was associated with more favorable drug treatment course than risperidone. Although pharmaceutical costs were significantly higher, medical costs were significantly lower for patients on olanzapine compared to those on risperidone. Univariate and multivariate analyses (controlling for potential confounding factors including demographic and clinical characteristics) consistently demonstrated that olanzapine patients had significantly lower schizophrenia related costs (2839 US dollars less, p < 0.011), lower mental health care costs (3744 US dollars less, p < 0.004) and lower total health care costs (4674 US dollars less, p < 0.001) than those patients initiated on risperidone. CONCLUSIONS: The findings revealed significant differences between olanzapine and risperidone in the treatment of uncontrolled schizophrenia patients in clinical practice. Olanzapine patients experienced a favorable drug treatment course and incurred lower overall costs. The lower costs were hospital-treatment driven. Further studies are needed to examine if these results hold for different patient populations.

Economic outcomes associated with switching individuals with schizophrenia between risperidone and olanzapine: findings from a large US claims database.

OBJECTIVES: To assess the impact of switching atypical antipsychotic treatment [from (i) risperidone to olanzapine or (ii) olanzapine to risperidone] on medication use patterns and treatment costs for individuals with schizophrenia. METHODS: Using a large, integrated medical service and pharmacy claims database, 244 individuals diagnosed with schizophrenia (International Classification of Diseases [9th revision]: 295.xx) who switched treatment from risperidone to olanzapine (n = 202) or from olanzapine to risperidone (n = 42) were identified. Changes in medication use patterns and treatment costs (1999 values) per patient from the pre- to the post-switch period were evaluated. McNemar's tests were used to compare changes in use of antiparkinsonian, antidiabetic and antihyperlipidaemic agents and typical antipsychotics, while the Wilcoxon signed rank tests were applied to examine changes in treatment costs. RESULTS: After switching from risperidone to olanzapine, the percentage of patients using concomitant antiparkinsonian agents and typical antipsychotics decreased significantly from 30.20% to 21.29% (p = 0.0094) and from 30.69% to 18.32% (p = 0.0006), respectively. There was no significant change in the use of antidiabetic or antihyperlipidaemic drugs. For mental health-related treatment, annualised pharmaceutical costs increased by $US1761 (from $US1829 to $US3590, p < 0.0001) but medical service costs decreased by $US3511 (from $US11 292 to $US7781, p = 0.0036), driven primarily by significantly lower emergency room care and hospital outpatient costs. This resulted in no significant change in overall mental healthcare costs. Similar results were observed with total healthcare costs. In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs. CONCLUSIONS: Switching from risperidone to olanzapine was associated with improved medication use patterns for antiparkinsonian and typical antipsychotic agents. While both mental health and total healthcare pharmaceutical costs increased significantly, this was not associated with a significant increase in overall mental health and total healthcare costs. These outcomes, however, were not evidenced in patients switched from olanzapine to risperidone.

Antipsychotic medication use patterns and associated costs of care for individuals with schizophrenia.

BACKGROUND: Schizophrenia is a costly and complicated disorder to treat. A variety of schizophrenia treatment guidelines have been developed to provide valuable expert advice to practicing psychiatrists on various treatment options that are presumed to result in the best outcomes. However, examination of antipsychotic medication use patterns has suggested that current prescribing practices do not mirror recommended treatment guidelines and may have adverse economic consequences. AIM OF THE STUDY: This study seeks to describe antipsychotic medication treatment patterns and estimate the total costs of care associated with treatment patterns for individuals diagnosed with schizophrenia in usual care settings. METHODS: Use of outpatient antipsychotic medications and other health services during 1997 was obtained for 2,082 individuals with a diagnosis of schizophrenia in the IMS Health LifeLink employer claims database. We describe outpatient antipsychotic treatment patterns, estimated the costs of schizophrenia care by treatment pattern, and compared costs by treatment pattern using regression models. RESULTS: During 1997, 26% (n=536) of individuals diagnosed with schizophrenia received no antipsychotic medication in the outpatient setting, while 52% (n=1,088) were treated with only one antipsychotic (Monotherapy). For individuals who received more than one antipsychotic medication during 1997 (n=458), 13% (n=262) switched antipsychotic medications (Switch), 7% (n=154) augmented their original antipsychotic therapy with an additional antipsychotic (Augment), and 2% (n=42) of individuals were on more than one antipsychotic therapy at the start of the year. After adjusting for covariates, Switch and Augment patterns were associated with significant increases in total costs (an increase of 4,706 dollars (p<0.0001) and 4,244 dollars (p=0.0002), respectively) relative to Monotherapy. DISCUSSION: These results indicate that a substantial proportion of individuals with a diagnosis of schizophrenia were not treated with or had low exposure to antipsychotic therapy. Individuals treated with antipsychotic monotherapy experienced nearly half the annual costs as individuals who were treated with antipsychotic polytherapy or who switched antipsychotic medications. These observations should be interpreted in the context of the study limitations. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This analysis indicates that there may be considerable room for improvement in the treatment for individuals diagnosed with schizophrenia. IMPLICATIONS FOR HEALTH POLICIES: Though schizophrenia affects a very small portion of the population, the individual and societal burden associated with the disorder is quite high. This paper suggests that antipsychotic monotherapy and continuous therapy, commonly recommended by published treatment guidelines, may be associated with economic savings. IMPLICATIONS FOR FURTHER RESEARCH: Future research should evaluate the impact of newer antipsychotic medications on patterns of care and economic outcomes. More information is also needed on which individual patient characteristics are likely to predict success or failure on specific treatments. Finally, more detailed information on the reasons or rationale for switching or augmenting original pharmacotherapy would be valuable in improving medication management in these complex and often difficult to treat patients.