Economic Evaluation of Atorvastatin for Prevention of Recurrent Stroke Based on the SPARCL Trial

Objectives:  This study evaluated the economic implications of results obtained by the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.
Methods:  To enable long-term projection of the trial results, a discrete event simulation of the course of clinical care after a recent stroke or transient ischemic attack (TIA) was developed. It generates pairs of identical patients; both receive usual care, one receives atorvastatin in addition. Their clinical course is simulated based on their risk of stroke, cardiovascular events, and case fatality rates taken from SPARCL, life expectancy from Saskatchewan Health data, and utility weights from literature. Costs, from a US health-care payer perspective in 2005 US dollars, were estimated for a within-trial 5-year period; survival and quality-adjusted life-years (QALYs) were extrapolated over a patient's lifetime; all discounted at 3%/year.
Results:  The prevention of stroke, coronary, and other cardiovascular events expected with atorvastatin translates to mean gains of 0.155 life-years gained and 0.172 QALYs per patient over their lifetime. Reducing associated medical costs ($8405 vs. $11,237) but increasing drug costs ($13,984 vs. $8752) results in net $2400/patient, or $13,916/QALY gained. Probabilistic sensitivity analysis indicates no simulations yield ratios above $50,000/QALY.
Conclusion:  Prescribing atorvastatin for patients with prior stroke or TIA is expected to provide health benefits at an acceptable cost in the United States.     

A Cost-Effectiveness Analysis of Continuous Subcutaneous Insulin Injection versus Multiple Daily Injections in Type 1 Diabetes Patients: A Third-Party US Payer Perspective

Objective:  To estimate the long-term cost-effectiveness of using continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) of insulin in adult and child/young adult type 1 diabetes mellitus (T1DM) patients from a third-party payer perspective in the United States.
Method:  A previously validated health economic model was used to determine the incremental cost-effectiveness ratio (ICER) of CSII compared with MDI using published clinical and cost data. The primary input variable was change in HbA_1c, and was assumed to be an improvement of −0.9% to −1.2% for CSII compared with MDI for child/young adult and adults, respectively. A series of Markov constructs simulated the progression of diabetes-related complications.
Results:  CSII was associated with an improvement in quality-adjusted life-years (QALYs) gained of 1.061 versus MDI for adults and 0.799 versus MDI for children/young adults. ICERs were $16,992 and $27,195 per QALY gained for CSII versus MDI in adults and children/young adults, respectively. Improved glycemic control from CSII led to a lower incidence of diabetes complications, with the most significant reduction in proliferative diabetic retinopathy (PDR), end stage renal disease (ESRD), and peripheral vascular disease (PVD). The number needed to treat (NNT) for PDR was nine patients, suggesting that only nine patients need to be treated with CSII to avoid one case of PDR. The NNT for ESRD and PVD was 19 and 41, respectively.
Conclusions:  Setting the willingness to pay at $50,000/QALY, the analysis demonstrated that CSII is a cost-effective option for patients with T1DM in the United States.     

A therapeutic HIV vaccine: how good is good enough?

The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources.     

Cost-Effectiveness of Primary versus Secondary Prophylaxis with Pegfilgrastim in Women with Early-Stage Breast Cancer Receiving Chemotherapy

Objective:  Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a ≥20% FN risk.
Methods:  A decision-analytic model was constructed from a health insurer's perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values.
Results:  The incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was $48,000/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of $110,000/life-year gained (LYG) or $116,000/quality-adjusted life-year (QALY) gained. The most influential factors included FN case-fatality, FN relative risk reduction from primary prophylaxis, and age at diagnosis.
Conclusions:  Compared with secondary prophylaxis, the cost-effectiveness of pegfilgrastim as primary prophylaxis may be equivalent or superior to other commonly used supportive care interventions for women with breast cancer. Further assessment of the direct impact of G-CSF on short- and long-term survival is needed to substantiate these findings.     

Cost-Effectiveness of Switching to Exemestane after 2 to 3 Years of Therapy with Tamoxifen in Postmenopausal Women with Early-Stage Breast Cancer

OBJECTIVES: Data from the Intergroup Exemestane Study (IES) suggest that switching to the aromatase inhibitor, exemestane, after 2 to 3 years of tamoxifen therapy prolongs disease-free survival versus continuing on tamoxifen therapy. We sought to evaluate the cost-effectiveness of this management strategy. METHODS: A Markov model was developed to predict patients' transitions across various health states based on treatment strategy (continuing tamoxifen vs. switching to exemestane), breast cancer status (no recurrence, local or distant recurrence, contralateral breast cancer), and other related health events (osteoporosis, endometrial cancer, death). Rates of disease-related events (recurrence and contralateral breast cancer) were estimated using data from the IES. Survival and lifetime medical-care costs by type of disease-related event were estimated using SEER-Medicare data. The model was used to estimate direct costs (in 2004 US dollars), life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. RESULTS: Switching to exemestane versus continuing tamoxifen therapy was associated with increased disease-free survival (181 vs. 172 months), QALYs (12.21 vs. 11.89), and net discounted lifetime costs of cancer care ($12,124 vs. $7724 per patient). The incremental cost-effectiveness ratio of exemestane was $20,100 per QALY gained (95% confidence interval: $12,100, $59,000). Sensitivity analyses showed that results were robust to plausible variations in recurrence rates, costs, and utilities. CONCLUSIONS: Switching postmenopausal early-stage breast cancer patients to exemestane after 2 to 3 years of tamoxifen appears to be a cost-effective treatment strategy versus completing a 5-year course of tamoxifen.     

The Social Distribution of Health: Estimating Quality-Adjusted Life Expectancy in England

ObjectiveTo model the social distribution of quality-adjusted life expectancy (QALE) in England by combining survey data on health-related quality of life with administrative data on mortality.MethodsHealth Survey for England data sets for 2010, 2011, and 2012 were pooled (n = 35,062) and used to model health-related quality of life as a function of sex, age, and socioeconomic status (SES). Office for National Statistics mortality rates were used to construct life tables for age-sex-SES groups. These quality-of-life and length-of-life estimates were then combined to predict QALE as a function of these characteristics. Missing data were imputed, and Monte-Carlo simulation was used to estimate standard errors. Sensitivity analysis was conducted to explore alternative regression models and measures of SES.ResultsSocioeconomic inequality in QALE at birth was estimated at 11.87 quality-adjusted life-years (QALYs), with a sex difference of 1 QALY. When the socioeconomic-sex subgroups are ranked by QALE, a differential of 10.97 QALYs is found between the most and least healthy quintile groups. This differential can be broken down into a life expectancy difference of 7.28 years and a quality-of-life adjustment of 3.69 years.ConclusionsThe methods proposed in this article refine simple binary quality-adjustment measures such as the widely used disability-free life expectancy, providing a more accurate picture of overall health inequality in society than has hitherto been available. The predictions also lend themselves well to the task of evaluating the health inequality impact of interventions in the context of cost-effectiveness analysis.     

The Potential Clinical and Economic Outcomes of Pharmacogenomic Approaches to EGFR-Tyrosine Kinase Inhibitor Therapy in Non–Small-Cell Lung Cancer

Objectives:  Pharmacogenomic applications in oncology offer significant promise, but the clinical and economic implications remain unclear. The objective of this study was to evaluate the potential cost-utility of implementing epidermal growth factor receptor (EGFR) testing before initiating second-line therapy for advanced refractory non–small-cell lung cancer (NSCLC).
Methods:  We developed a decision analytic model to evaluate the cost-utility of EGFR protein expression or gene copy number testing compared to standard care with erlotinib in refractory advanced NSCLC patients. Costs and utilities were obtained from publicly available sources. We performed sensitivity analyses to evaluate uncertainty in the results.
Results:  The quality-adjusted life expectancies for erlotinib, EGFR protein expression testing, and gene copy number testing were: 0.44, 0.48, and 0.50 quality-adjusted life years (QALYs); and the costs were: $57,238, $63,512, and $66,447, respectively. The most cost-effective testing option, EGFR gene copy number testing, produced an incremental cost-effectiveness ratio of $162,018/QALY compared to no testing (erlotinib). The results were most sensitive to the survival estimates, health state utilities, and cost of disease progression. In the probabilistic sensitivity analyses, erlotinib without testing was the optimal treatment strategy until the $150,000/QALY willingness-to-pay threshold, after which gene copy testing was optimal. The discounted expected value of perfect information at a $100,000/QALY threshold in the USA over 5 years was $31.4 million.
Conclusions:  The study results suggest that EGFR pharmacogenomic testing has the potential to improve quality-adjusted life expectancy in the treatment of refractory NSCLC by a clinically meaningful margin at a value commensurate with the approved therapies in this setting. Additional research in this area is warranted.     

Cost-effectiveness of the addition of acarbose to the treatment of patients with type-2 diabetes in Spain

OBJECTIVES: To assess the cost-effectiveness of the addition of acarbose to existing treatment in patients with type 2 diabetes mellitus (DM2) in Spain. METHODS: The CORE Diabetes Model (a published and validated computer simulation model) was used to project long-term clinical and cost outcomes in DM2. Transition probabilities and risk adjustments were derived from published sources. Treatment effects and baseline cohort characteristics were based on a meta-analysis. Direct costs were retrieved from published sources and projected over patient lifetimes from the perspective of the Spanish National Health Service. Costs and clinical benefits were discounted at 3% per year. Sensitivity analyses were performed. RESULTS: Acarbose treatment was associated with improved life expectancy (0.23 years) and quality-adjusted life years (QALY) (0.21 years). Direct costs were on average euro 468 per patient more expensive with acarbose than with placebo. The incremental cost-effectiveness ratios were euro 2,002 per life year gained and euro 2,199 per QALY gained. An acceptability curve showed that with a willingness to pay euro 20,000, which is generally accepted to represent very good value for money, acarbose treatment was associated with a 93.5% probability of being cost-effective. CONCLUSIONS: This long-term economic study showed that the addition of acarbose to existing therapy for DM2 was associated with improvements in life expectancy and QALYs in these patients.     

Cost-Effectiveness of Maraviroc for Antiretroviral Treatment-Experienced HIV-infected Individuals in Mexico

ObjectiveMaraviroc is the first approved drug in a new class of antiretrovirals, the CCR5 antagonists. The objective of this study was to predict the long-term clinical impact and cost-effectiveness of maraviroc in treatment-experienced adults with HIV/AIDS in Mexico.MethodsThe AntiRetroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican context to predict clinical and economic outcomes of treating with optimized background therapy (OBT) versus testing for viral tropism status and treating with OBT ± maraviroc accordingly in treatment-experienced adults in Mexico. Baseline characteristics and efficacy were from the MOTIVATE trials' screening cohort. Costs and population mortality data were specific to Mexico. Results were reported from the perspective of health care payers in 2008 Mexican pesos (converted to 2008 US$ in parentheses).ResultsCompared to treatment with OBT alone, treatment with OBT ± maraviroc contingent on tropism test result increased projected undiscounted life expectancy and discounted quality-adjusted life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429) per QALY gained. The ICER was somewhat lower when maraviroc was modeled in individuals susceptible to ≤2 components of OBT ($407,329; US$38,069), while the ICER was higher in individuals susceptible to ≥3 OBT components ($718,718; US$67,171).ConclusionIn treatment-experienced individuals with HIV/AIDS in Mexico, maraviroc may be cost-effective, particularly in individuals with limited options for active antiretroviral therapy (ART).     

A Cost-Effectiveness Model Comparing Endovascular Repair to Open Surgical Repair of Abdominal Aortic Aneurysms in Canada

Objectives:  The primary risk of abdominal aortic aneurysms (AAAs) is rupture, which is associated with a high mortality rate. Elective surgical options for AAA include open repair (OR) and endovascular aneurysm repair (EVAR). EVAR is less invasive than OR, and therefore may have less surgical risk than OR. However, the graft used for EVAR is much more expensive then the graft used for OR.
Methods:  A decision model with a 10-year time horizon was used to assess the cost-effectiveness of EVAR versus OR. The primary outcome measure was quality-adjusted life-years (QALYs). The model incorporated the costs and benefits of both perioperative outcomes and postoperative outcomes. A systematic review was conducted to derive clinical outcome rates. Cost and utility model variables were based on various literature sources and data from a recent Canadian observational study. Parameter uncertainty was assessed using probabilistic sensitivity analysis.
Results:  In the base-case model, the incremental cost per QALY of EVAR was estimated to be $268,337, whereas the incremental cost per life-year was found to be $444,129. The incremental cost per QALY of EVAR remained above $295,715 under different assumptions of cohort age and model time horizon.
Conclusions:  Based on commonly quoted willingness-to-pay thresholds, EVAR was not found to be cost-effective compared to OR.     

Modeling the Cost-Effectiveness of Galantamine for Mild to Moderately Severe Alzheimer's Disease in Korea

Objective:  The aim of the study was to determine the cost-effectiveness, from the third-party payer viewpoint, of galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease (AD).
Methods:  An existing Markov model was adapted to Korea to predict long-term outcomes over a 5-year time horizon and to estimate the cost-effectiveness of galantamine for the treatment of AD. The model structure is informed by a review of national and international literature on the clinical and cost-effectiveness of galantamine and on the costs and outcomes associated with treatment for AD. The main outcome measure used was the cost per quality-adjusted life year (QALY) gained. All costs were indexed to US$ (2007 value). Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results.
Results:  The study findings indicate that the clinical benefits on AD progression from galantamine treatment resulted in an incremental cost per QALY gained of US$4939 over 5 years (vs. usual care). Probabilistic sensitivity analysis and cost-effectiveness acceptability curve suggest that the probability of galantamine treatment having an incremental cost per QALY over US$6740 is zero. Incremental cost per QALY gained according to scenario analyses ranged from US$2271 to US$8335.
Conclusion:  These findings suggest that the use of galantamine may be a cost-effective use of Korean national health-care resources, considering the gross domestic product per capita of US$21,695 in 2007.     

Cost-effectiveness of diabetes case management for low-income populations

OBJECTIVE: To evaluate the cost-effectiveness of Project Dulce, a culturally specific diabetes case management and self-management training program, in four cohorts defined by insurance status. DATA SOURCES/STUDY SETTING: Clinical and cost data on 3,893 persons with diabetes participating in Project Dulce were used as inputs into a diabetes simulation model. STUDY DESIGN: The Center for Outcomes Research Diabetes Model, a published, peer-reviewed and validated simulation model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy (QALY), cumulative incidence of complications and direct medical costs over patient lifetimes (40-year time horizon) from a third-party payer perspective. Cohort characteristics, treatment effects, and case management costs were derived using a difference in difference design comparing data from the Project Dulce program to a cohort of historical controls. Long-term costs were derived from published U.S. sources. Costs and clinical benefits were discounted at 3.0 percent per annum. Sensitivity analyses were performed. PRINCIPAL FINDINGS: Incremental cost-effectiveness ratios of $10,141, $24,584, $44,941, and $69,587 per QALY gained were estimated for Project Dulce participants versus control in the uninsured, County Medical Services, Medi-Cal, and commercial insurance cohorts, respectively. CONCLUSIONS: The Project Dulce diabetes case management program was associated with cost-effective improvements in quality-adjusted life expectancy and decreased incidence of diabetes-related complications over patient lifetimes. Diabetes case management may be particularly cost effective for low-income populations.     

Cost-Utility Analysis of Rimonabant in the Treatment of Obesity

Objective:  To estimate the incremental cost-utility ratio (ICUR) of rimonabant 20 mg/day in the treatment of obesity from a third-party payer's perspective.
Methods:  Pooled data from three randomized clinical trials were used to develop a decision tree with five treatment alternatives: 1- and 2-year treatment with rimonabant, 2-year placebo, 1-year rimonabant followed by 1-year placebo, and no treatment. All alternatives, except no treatment, were accompanied by lifestyle interventions. Treatment benefits included gains in quality-adjusted life-years (QALYs) and reduced incidence of type-2 diabetes mellitus and coronary heart disease (CHD). Drug acquisition cost was based on the average wholesale price of a comparator drug minus 15%. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the base-case results.
Results:  One-year rimonabant and 1-year rimonabant followed by placebo were extendedly dominated. Rimonabant for 2 years showed an average weight reduction of 8.49 kg, a body mass index reduction of 2.98 kg/m² and reduced waist circumference by 8.24 cm (placebo: 3.55 kg, 1.22 kg/m², 4.18 cm). Two-year rimonabant was associated with a relative reduction in the 5-year incidence of CHD by 7.15% and of diabetes by 9.28%. Incremental benefits (costs) were 0.0984 QALYs ($5209) compared to no treatment and 0.0581 QALYs ($4182) compared to placebo, producing ICURs of $52,936/QALY (95% confidence interval $39K–$69K) and $71,973/QALY ($51K–$98K), respectively.
Conclusions:  Rimonabant combined with lifestyle interventions has the potential to decrease the rate of obesity-related comorbidities and improve health-related quality of life, albeit at considerable cost.     

Cost-effectiveness of screening compared to case-finding approaches to tuberculosis in long-term care facilities for the elderly.

BACKGROUND: To determine if the more interventionist approach of screening with the tuberculin test and chemoprophylaxis for high-risk positive reactors to control tuberculosis in long-term care facilities is cost-effective when compared to the case-finding and treatment approach. METHOD: A decision-analysis model was designed wherein systematic screening with the tuberculin skin test of all elderly patients newly admitted to facilities was compared to public health interventions restricted to investigation of cases and contacts with symptoms of tuberculosis after suspected exposure. Differences in life-years (LY), quality-adjusted life-years (QALY), cost per QALY and LY gained, annual cost per 1000 institutional patients were calculated in a health-care system perspective. RESULTS: In every situation analysed, screening and chemoprophylaxis were more effective. The cost per LY gained was within an acceptable range: $3437 per LY with a 0.6% nosocomial transmission rate and $7552 per LY when no nosocomial transmission was postulated. CONCLUSION: Screening plus chemoprophylaxis for high-risk reactors is more cost-effective than case-finding. This holds even when nosocomial transmission is assumed not to occur in facilities.     

Cost-effectiveness analysis of Helicobacter pylori screening in prevention of gastric cancer in Chinese

OBJECTIVES: The aim of this study was to evaluate the costs and effectiveness associated with no screening, Helicobacter pylori serology screening, and the 13C-urea breath test (UBT) for gastric cancer in the Chinese population. METHODS: A Markov model simulation was carried out in Singaporean Chinese at 40 years of age (n = 478,500) from the perspective of public healthcare providers. The main outcome measures were costs, number of gastric cancer cases prevented, life-years saved, quality-adjusted life-years (QALYs) gained from the screening age to death, and incremental cost-effectiveness ratios (ICERs), which were compared among the three strategies. The uncertainty surrounding ICERs was addressed by scenario analyses and probabilistic sensitivity analysis using Monte Carlo simulation. RESULTS: The ICER of serology screening versus no screening was $25,881 per QALY gained (95 percent confidence interval (95 percent CI), $5,700 to $120,000). The ICER of UBT versus no screening was $53,602 per QALY gained (95 percent CI, $16,000 to $230,000). ICER of UBT versus serology screening was $470,000 per QALY gained, for which almost all random samples of the ICERs distributed above $50,000 per QALY. CONCLUSIONS: It cannot be confidently concluded that either H pylori screening was a cost-effective strategy compared with no screening in all Chinese at the age of 40 years. Nevertheless, serology screening has demonstrated much more potential to be a cost-effective strategy, especially in the population with higher gastric cancer prevalence.     

Cost-effectiveness of a potential vaccine for human papillomavirus

Human papillomavirus (HPV) infection, usually a sexually transmitted disease, is a risk factor for cervical cancer. Given the substantial disease and death associated with HPV and cervical cancer, development of a prophylactic HPV vaccine is a public health priority. We evaluated the cost-effectiveness of vaccinating adolescent girls for high-risk HPV infections relative to current practice. A vaccine with a 75% probability of immunity against high-risk HPV infection resulted in a life-expectancy gain of 2.8 days or 4.0 quality-adjusted life days at a cost of $246 relative to current practice (incremental cost effectiveness of $22,755/quality-adjusted life year [QALY]). If all 12-year-old girls currently living in the United States were vaccinated, >1,300 deaths from cervical cancer would be averted during their lifetimes. Vaccination of girls against high-risk HPV is relatively cost effective even when vaccine efficacy is low. If the vaccine efficacy rate is 35%, the cost effectiveness increases to $52,398/QALY. Although gains in life expectancy may be modest at the individual level, population benefits are substantial.     

Cost-Effectiveness of Sorafenib for Second-Line Treatment of Advanced Renal Cell Carcinoma

Objectives:  To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service.
Methods:  A decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses.
Results:  Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of £75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of £20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of £30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs.
Conclusions:  Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of £70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.     

The implications of using US-specific EQ-5D preference weights for cost-effectiveness evaluation.

OBJECTIVE: The objective of this study is to examine the effect of country-specific EQ-5D preference weights on the cost-effectiveness (CE) of initial pramipexole versus levodopa strategy in patients with Parkinson disease (PD). METHODS: A total of 301 subjects with PD were randomized to initial pramipexole or levodopa and followed every 3 months over a 4-year period. Subjects' health-related quality of life (HRQOL) was measured using EQ-5D, and their health preferences were calculated using both the UK and US sets of weights. The effectiveness of pramipexole was defined as the additional quality-adjusted life-years (QALY) gained compared to levodopa and was estimated as the area between the treatment-specific HRQOL profiles adjusted for baseline difference. RESULTS: Using the original UK weights, the incremental effectiveness was 0.155 QALYs, which resulted in the incremental CE ratio (ICER) of $42,989/QALY and a probability that pramipexole was cost-effective relative to levodopa of 0.57, 0.77, and 0.82 when a QALY was valued at $50,000, $100,000, and $150,000, respectively. Using the US-specific weights resulted in lower incremental effectiveness (0.062 QALYs), higher ICER ($108,498/QALY), and a lower probability that pramipexole was cost-effective compared to levodopa at any valuation of QALY (0.23 for $50,000, 0.48 for $100,000, and 0.58 for $150,000). CONCLUSIONS: Country-specific preference weights in clinical-economic trials might have important effects on estimates of incremental cost-effectiveness. Using US preference weights rather than UK preference weights reduced the probability that pramipexole was cost-effective compared to levodopa.     

Cost-Effectiveness of Testing for Breast Cancer Susceptibility Genes

Objectives:  Genetic mutations in breast cancer susceptibility genes BRCA1/2 are associated with an increased risk of breast/ovarian cancers. Cost-effective preventive measures are available for women who test positive. The objective of this study was to determine at what risk of mutation it is cost-effective to test women for BRCA1/2 mutations.
Methods:  A semi-Markov model accrued costs and quality-adjusted life years (QALYs) annually from the societal perspective. The estimates of health-care costs, life expectancy, likelihood of obtaining a mastectomy or oophorectomy, and patient preferences for treatment and certainty about their BRCA1/2 status were based on the literature.
Results:  At a 10% probability of mutation (the current guideline), the test strategy generated 22.9 QALYs over the lifetime and cost $118k, while the no-test strategy generated 22.7 QALYs and cost $117k. The incremental cost-effectiveness ratio of the test strategy was $9k and the differences between costs and effects were not substantial. The test strategy remained cost-effective to a probability of mutation of 0%, as long as utility gained from a negative test result was 0.006 or greater. These results were sensitive to the frequency of inconclusive test results and utility gain from a negative test result.
Conclusions:  The costs and effectiveness of both the test and no-test strategies are very similar even when there is a small probability of mutation. Current guidelines, which can be used by insurance companies to refuse coverage, could deny some women a cost-effective approach. Further research to decrease the frequency of inconclusive results could improve the cost-effectiveness of this test.     

The Economic Value of Innovative Treatments over the Product Life Cycle: The Case of Targeted Trastuzumab Therapy for Breast Cancer

ObjectivePharmacoeconomic analyses typically project the expected cost-effectiveness of a new product for a specific indication. This analysis develops a dynamic life-cycle model to conduct a multiindication evaluation using the case of trastuzumab licensed in the United States for both early-stage and metastatic (or late-stage) human epidermal growth factor receptor 2 (HER2)-positive breast cancer therapy (early breast cancer [EBC]; metastatic breast cancer [MBC]), approved in 2006 and 1998, respectively.MethodsThis dynamic model combined information on expected incremental cost-utility ratios for specific indications with an epidemiologically based projection of utilization by indication over the product life cycle—from 1998 to 2016. Net economic value was estimated as the cumulative quality-adjusted life years (QALYs) gained over the life cycle multiplied by a societal valuation of health gains ($/QALY) minus cumulative net direct treatment costs. Sensitivity analyses were performed under a range of assumptions.ResultsWe projected that the annual number of EBC patients receiving trastuzumab will be more than three times that of MBC by 2016, in part because adjuvant treatment reduces the future incidence of MBC. Over this life cycle, the estimated overall incremental cost-effectiveness ratio (ICER) was $35,590/QALY with a total of 432,547 discounted QALYs gained. Under sensitivity analyses, the overall ICER varied from $21,000 to $53,000/QALY, and the projected net economic value resulting from trastuzumab treatment ranged from $6.2 billion to $49.5 billion.ConclusionsAverage ICERs for multiindication compounds can increase or decrease over the product life cycle. In this example, the projected overall life-cycle ICER for trastuzumab was less than one half of that in the initial indication. This dynamic perspective—versus the usual static one—highlights the interdependence of drug development decisions and investment incentives, raising important reimbursement policy issues.