Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist. OBJECTIVE: Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST. METHODS: A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed. RESULTS: Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities. CONCLUSIONS: Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.

Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumours.

BACKGROUND AND OBJECTIVE: Imatinib mesylate is the first effective therapy for advanced unresectable gastrointestinal stromal tumours (GIST). Adoption of this therapy in clinical practice is partly dependent on reimbursement by third-party payers in many countries. The objective of this study was to estimate the cost effectiveness of imatinib mesylate in the treatment of GIST. METHODS: A cost-effectiveness model of GIST treatment was developed. Long- term survival and duration of imatinib mesylate benefit were projected by fitting curves to 52-month follow-up data from a phase II clinical trial of imatinib and projecting weekly probabilities of survival and continued treatment over 10 years. Weekly cost estimates in 2005 US dollars included cost of imatinib mesylate 400 mg/day ($US685), other medical services for imatinib mesylate-treated patients ($US359) and palliative care for patients in the end stage of GIST ($US2575). Utility associated with successful treatment was estimated at 0.935 and that of treatment failure and progressive disease at 0.875. Costs, life-years and quality- adjusted life-years (QALYs) were calculated over the 10-year time horizon and discounted to treatment initiation at an annual rate of 3%. RESULTS: Imatinib mesylate therapy for unresectable GIST was projected to increase life expectancy to 5.8 years, an increase of 2.7 years over the control group. This translated into an increase of 1.9 QALYs at a marginal cost of $US74 369, yielding a cost-effectiveness ratio of $US38 723 per QALY. Cost effectiveness was not very sensitive to model parameters other than the cost of imatinib mesylate itself. CONCLUSION: The cost effectiveness of imatinib mesylate in the treatment of GIST is within the commonly accepted range for life-saving interventions, based on US data.

Impact of rosuvastatin use on costs and outcomes in patients at high risk for cardiovascular disease in US managed care and medicare populations: A data analysis.

BACKGROUND: High blood cholesterol is a major modifiable risk factor for coronary heart disease (CHD) and stroke. OBJECTIVE: The aim of this study was to estimate the economic impact of rosuvastatin calcium use in patients at high risk for CHD and stroke, according to the National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines. METHODS: An economic simulation model was developed that used a Markov process to project the number of cardiovascular events and associated costs in a high-risk population in various treatment scenarios. According to the ATP III, high-risk patients are those with CHD, atherosclerosis of peripheral and/or cerebral arteries, diabetes, and/or multiple other risk factors conferring a risk of at least 20% within 10 years. Data on population characteristics and costs of cardiovascular disease (CVD) were obtained from claims data sets from employer-funded commercial and Medicare health plans in the United States. Treatment of lipid disorders was translated into CVD risk reduction based on results from the Heart Protection Study. The estimated efficacies of individual lipid-lowering drugs were based on data published in package inserts. The model generated costs at the health plan level of lipid-lowering therapy in high-risk patients and the number and total costs of cardiovascular events. Estimates were compared for scenarios representing the mix of treatments used before and after the introduction of rosuvastatin. Estimates were generated separately for commercial and Medicare health plans. RESULTS: For every 1 million members of a commercial health plan, an estimated 44,457 met ATP III criteria for high-risk status. Use of rosuvastatin in place of other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") by 11 % of these patients over a period of 5 years was estimated to result in 36 fewer cardiovascular events and a net savings of US 4.03 million dollars. A Medicare plan of 1 million members with an estimated 433,268 high-risk patients and 7% rosuvastatin use was estimated to avoid 727 events and save US 34.32 million dollars. CONCLUSIONS: The results of this data analysis suggest that increasing the use of rosuvastatin can result in cardiovascular event reduction and cost savings. Because the impact of lipid-modifying therapy on cardiovascular risk has not been thoroughly documented in controlled clinical studies, our model assumed that incremental lipid changes had effects in proportion to the magnitude of change.

A projection of the impact of lipid-lowering therapy on high-risk employee disability and medical costs.

OBJECTIVE: The objective of this study was to examine the impact of introducing rosuvastatin calcium on direct and indirect costs among patients at high risk for coronary heart disease. METHODS: An economic simulation model was developed to project the number of cardiovascular events and associated direct and indirect costs under varying treatment scenarios. RESULTS: In an average-sized commercial health plan with 210,000 covered lives and 9,336 high-risk patients, an uptake of rosuvastatin by 11% of high-risk patients would result in eight fewer cardiovascular events, a net savings of 0.85 million dollars in direct medical costs and a net savings of 36,404 dollars in productivity loss over a period of 5 years. The overall reduction in total costs is equivalent to 1735 dollars per rosuvastatin-treated patient. CONCLUSIONS: At current statin prices, the use of rosuvastatin could lead to fewer cardiovascular events and lower direct and indirect costs.

Patterns of initial pharmacotherapy for Parkinson's disease in the United States.

Data from a mix of employer- and government-funded health plans were used to investigate actual treatment patterns for patients initiating pharmacotherapy for Parkinson's disease in the United States. Treatment patterns evaluated included type of initial therapy and rates and types of adjunctive and substitute therapies. The study confirms that levodopa remains the most often prescribed initial treatment for Parkinson's disease regardless of age or drug benefit coverage. The widespread use of levodopa in young Parkinson's patients (<65 years) with private insurance may indicate that physicians are not overly concerned about or are not fully aware of the association of levodopa with long-term motor complications. It may also indicate that currently available alternatives to levodopa are not sufficiently effective or well tolerated.

Burden of illness in Parkinson's disease.

This study quantifies direct medical care costs for individual patients with Parkinson's disease (PD) and projects total national costs of PD. Anonymous, patient-level data on health care utilization and cost were obtained from Medstat's MarketScan Research Databases. Patients were selected for study if they had either two instances of a diagnosis of PD or one diagnosis and two or more prescriptions for PD-related medication. A control group of persons without PD was selected for comparison. Total annual health care utilization and costs were calculated for both PD patients and controls. A total of 20,016 patients with PD were identified and followed up for an average of 853 days. The mean age of the patients was 73.6 years, and 51.2% were women. Total annual direct costs were 23,101 US Dollars (SD 27,529) per patient with PD versus 11,247 US Dollars (SD 16,486) for controls. The regression-adjusted incremental direct cost of PD versus control was 10,349 US Dollars (95% confidence interval, 9,053, 11,645). Adding 25,326 US Dollars in indirect costs, and multiplying by 645,000 cases of PD in the United States, the total cost to the nation is projected to be 23 billion US Dollars annually. This estimate is higher than most previous studies, with important implications for health care delivery systems worldwide.

Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To estimate the potential effect on cardiovascular event occurrence and treatment costs associated with increases in systolic blood pressure (SBP) among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We used cardiovascular risk prediction models from the Framingham Heart Study and data on risk factors from the Third National Health and Nutrition Examination Survey (NHANES III) to estimate occurrences of ischemic heart disease and stroke over one year among US adults with OA/RA. Separate analyses were conducted for treated hypertensive patients, and untreated hypertensive and normotensive patients, respectively. Published estimates were used to assign costs to these events and to follow care. The effect of incremental increases in SBP on events and costs was then assessed. Monte Carlo simulation was undertaken to assess the range of event occurrence and costs associated with alternative assumptions regarding the distribution of increased SBP in the at-risk population. RESULTS: Of the estimated 30 million adults in the US aged > or = 35 years with OA and RA, roughly 11.8 million (39%) receive pharmacologic treatment for hypertension. Increases in SBP of 1-5 mm Hg were associated with 7,100-35,700 additional ischemic heart disease and stroke events over one year, with corresponding costs (year 2000 USD) of 114-569 million year 2000 USD. A 20 mm Hg increase in SBP experienced by 15% of the at-risk population (equivalent to a population-average 3 mm Hg increase) is associated with about 21,700 additional events (95% CI 19,120, 24,221) and 346 million year 2000 USD (95% CI 305 year 2000 USD, 387 million) in associated costs. CONCLUSION: Relatively small changes in SBP associated with use of common arthritis medications can have a significant effect on the cardiovascular risk profile. It is important that clinicians who treat patients with OA/RA accurately weigh the potential risks of these medications against their benefits.

Impact of leflunomide versus biologic agents on the costs of care for rheumatoid arthritis in a managed care population.

OBJECTIVE: To compare the impact of leflunomide on resource utilization and costs relative to that of etanercept and infliximab among patients with rheumatoid arthritis (RA) in a managed care setting. METHODS: Data were obtained from the PharMetrics Integrated Outcomes Database for all patients newly starting 1 of the 3 medications of interest in 1999 or 2000. Claims were compiled for 180 days prior to the first prescription for study therapy and for a minimum of 90 days thereafter. Measures of interest during follow-up included the incidence of significant interventions (eg, joint injection, synovectomy), 1-year utilization of study therapy, other RA-related medications, inpatient and outpatient services, and total costs of RA-related care. Data were adjusted for variable follow-up using survival techniques. Multivariate analyses were conducted on total costs, controlling for between-group differences in demographic, clinical, and pretreatment characteristics. RESULTS: A total of 4069 patients were included in the study cohort (n = 2217, 1547, and 305 for leflunomide, etanercept, and infliximab, respectively). Three quarters of the cohort were female; etanercept patients were somewhat younger than leflunomide or infliximab recipients. Severity of illness (as measured by the Charlson index) was highest among infliximab patients. The incidence of significant interventions was high in all patients, but did not differ by treatment group. Use of nonsteroidal anti-inflammatory drugs (8.1 versus 8.9 claims) and narcotic analgesics (7.8 versus 8.5) was substantially lower for leflunomide than for etanercept. Costs of RA-related care were 42% to 53% lower among leflunomide patients for biologic medications ($9618 versus $16,534 and $20,263 for etanercept and infliximab, respectively), primarily as a result of lower medication costs. Findings persisted in multivariate analyses of cost. CONCLUSIONS: Leflunomide is associated with reduced costs of medications and other healthcare services relative to biologic medications among managed care patients with RA.

Outpatient treatment of venous thromboembolism with low-molecular-weight heparin: an economic evaluation.

BACKGROUND: The development of low-molecular-weight heparins (LMWHs) has made it possible to shift treatment of deep vein thrombosis (DVT) from inpatient to outpatient settings, thereby saving costs and improving patient quality of life. OBJECTIVE: To quantify the economic benefits of early discharge of patients treated for DVT with LMWH using data pooled from multiple healthcare plans. METHODS: Data sources were integrated medical and pharmacy claims paid by 37 US health plans (the PharMetrics Integrated Outcomes Database, PharMetrics, Inc., Watertown, MA). Hospitalized patients discharged with a diagnosis of DVT were selected and grouped according to the anticoagulation therapy they received after discharge. Outcomes and costs of DVT treatment were assessed over a 1-year period. RESULTS: Patients discharged on the LMWH enoxaparin and warfarin spent 2.6 fewer days in the hospital than those discharged on warfarin alone (P< .0001), resulting in cost savings of $1911 per patient. Mean costs of outpatient management of DVT, including pharmacy and medical services, were $901 higher in the enoxaparin/warfarin cohort, but rate of readmission was lower (6.7% versus 9.0%; P < .05) and hence subsequent inpatient costs were reduced by $140 per patient. Total cost savings in the enoxaparin/warfarin cohort, net of higher outpatient costs, were $1151 per patient. CONCLUSIONS: Outpatient anticoagulation therapy for DVT with enoxaparin and warfarin is associated with earlier hospital discharge, fewer readmissions, and lower total DVT-related costs compared with warfarin monotherapy.

Use of managed care claims data in the risk assessment of venous thromboembolism in outpatients.

BACKGROUND: Deep vein thrombosis (DVT) is a complication of immobilizing illness in both inpatient and outpatient settings and can lead to serious complications such as pulmonary embolism (PE). DVT and PE are collectively referred to as venous thromboembolism. OBJECTIVE: To develop DVT and PE risk assessment models that can be used in office-based practice and for population-based disease management efforts. METHODS: Data were culled from integrated medical and pharmacy claims paid by 37 health plans in the United States (the PharMetrics Integrated Outcomes Database, PharMetrics Inc., Watertown, MA), and included information on adult plan members enrolled during 1998 and 1999. Patients hospitalized for DVT or PE in 1999 were identified, and potential risk factors were assessed by reviewing claims for the entire study population in 1998 to document prior DVT or immobilizing illness. The contribution of each potential risk factor to the probability of the occurrence of DVT or PE was determined by means of multiple logistic regression analysis. A risk-scoring algorithm based on regression coefficients was then developed. RESULTS: Fifty-two percent of the study population of 2.8 million plan members were women. DVT or PE occurred in 1330 of those 2.8 million individuals (47 per 100,000). Logistic regression results confirmed the role of risk factors previously reported in the literature and revealed additional risk factors that have not been reported previously, including diabetes, renal failure, rheumatoid arthritis, cellulitis, use of warfarin, use of systemic corticosteroids, and use of potassium chloride. When risk scores were applied to the study population, the 1% identified as being at highest risk had a probability for the development of venous thromboembolism that was 10 times greater than that of the population average. CONCLUSIONS: This study confirms the feasibility of using managed care claims data to develop a risk assessment tool for venous thromboembolism that can be used in office-based practice and for population-based disease management.