Exploratory cost-effectiveness analysis of cardiac resynchronization therapy with systematic device optimization vs. standard (non-systematic) optimization: a multinational economic evaluation.

BACKGROUND: Recent studies provide evidence of improved clinical benefits associated with cardiac resynchronization therapy (CRT) optimization. Our analysis explores the cost-effectiveness of systematically optimized (SO, 3 times a year) vs. non-systematically optimized (NSO, less than 3 times a year) CRT, whatever the echo optimization method used (manual or SonR® automatic). A longitudinal cohort model was developed to predict clinical and economic outcomes for SO vs. NSO strategies over 5 years. The analysis was performed from the payer perspective. Data from CLEAR study post-hoc analysis was used with 199 pts with CRT pacemaker (CRT-P). The main economic outcome measure was incremental cost-effectiveness (ICER) expressed as cost per Quality Adjusted Life Years (QALY) gained. To assess the impact of data uncertainty, a sensitivity analysis was performed. The model also predicts outcomes for the two optimization strategies for CRT-D therapy vs. optimal medical treatment (OPT). RESULTS: At 1 year, ICERs for SO CRT vs. NSO CRT-P range between 22,226 (Spain) and 26,977 (Italy). Therefore, on the basis of a Willingness-To-Pay of 30,000 per QALY, the SO method develops into a cost effective strategy from 1 year, onwards. These favorable outcomes are supported by the sensitivity analysis. Systematic optimization of CRT-D might also improve the cost-effectiveness of this device therapy by 27 % to 30 % dependent on the country analyzed, at 5 years. CONCLUSIONS: Our economic evaluation shows promising health economic benefits associated with SO CRT. These preliminary findings need further confirmation.

Evaluation of a possible predictor for Federal Joint Committee decisions on early benefit assessments according to the German act on the reform of the market for medicinal products.

OBJECTIVES: As of 1st January 2011 the German drug market is regulated by the act on the reform of the market for medicinal products (AMNOG). Since then the normal procedure for reimbursement of a new pharmaceutical is a benefit assessment by the joint federal committee (G-BA) which determines one of six additional benefit levels. METHODS: In order to evaluate a possible predictor of G-BA decisions, the 'evaluation of pharmaceutical innovations (EVITA)' score was calculated for 40 out of 63 dossiers and compared with published G-BA appraisals. RESULTS: Univariate ordinary least squares (p<0.001) and ordered logit regression (p=0.008) analyses show statistically significant correlations between EVITA scores and the G-BA additional benefit levels. Moreover, for the prediction of an additional benefit level of at least 'minor', an EVITA score cutpoint of ≥3 is associated with a sensitivity of 100% and a specificity of 80%. For the prediction of an additional benefit level of at least 'considerable', an EVITA score cutpoint of ≥7.5 is associated with a sensitivity of 100% and a specificity of 93.1%. CONCLUSION: The present investigation indicates that the EVITA score may have some potential to act as a possible predictor of G-BA decisions related to AMNOG early benefit assessments.

Cost effectiveness of transcatheter aortic valve replacement compared to medical management in inoperable patients with severe aortic stenosis: Canadian analysis based on the PARTNER Trial Cohort B findings.

OBJECTIVE: The only effective treatment for severe aortic stenosis (AS) is valve replacement. However, many patients with co-existing conditions are ineligible for surgical valve replacement, historically leaving medical management (MM) as the only option which has a poor prognosis. Transcatheter Aortic Valve Replacement (TAVR) is a less invasive replacement method. The objective was to estimate cost-effectiveness of TAVR via transfemoral access vs MM in surgically inoperable patients with severe AS from the Canadian public healthcare system perspective. METHODS: A cost-effectiveness analysis of TAVR vs MM was conducted using a deterministic decision analytic model over a 3-year time horizon. The PARTNER randomized controlled trial results were used to estimate survival, utilities, and some resource utilization. Costs included the valve replacement procedure, complications, hospitalization, outpatient visits/tests, and home/nursing care. Resources were valued (2009 Canadian dollars) using costs from the Ontario Case Costing Initiative (OCCI), Ontario Ministry of Health and Long-Term Care and Ontario Drug Benefits Formulary, or were estimated using relative costs from a French economic evaluation or clinical experts. Costs and outcomes were discounted 5% annually. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analysis. RESULTS: The incremental cost-effectiveness ratio (ICER) was $32,170 per quality-adjusted life year (QALY) gained for TAVR vs MM. When the time horizon was shortened to 24 and 12 months, the ICER increased to $52,848 and $157,429, respectively. All other sensitivity analysis returned an ICER of less than $50,000/QALY gained. LIMITATIONS: A limitation was lack of availability of Canadian-specific resource and cost data for all resources, leaving one to rely on clinical experts and data from France to inform certain parameters. CONCLUSIONS: Based on the results of this analysis, it can be concluded that TAVR is cost-effective compared to MM for the treatment of severe AS in surgically inoperable patients.

Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain.

Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain. Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed. Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates. Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile.

Economic evaluation of varicella vaccination in Swiss children and adolescents.

This study explores the effects of three different 2-dose varicella zoster virus (VZV) vaccination strategies in Switzerland. The EVITA model was used to assess clinical benefits and costs of strategies (1) vaccination of 11-15 year old adolescents with a negative or uncertain history for chickenpox, (2) universal vaccination of toddlers at age 1 to 2 years, and (3) strategy 2 plus catch-up vaccination of 11-15 year old susceptible adolescents. The cost-effectiveness analysis compares strategies 2 and 3 versus strategy 1 (current vaccination policy in Switzerland). Probabilities for clinical outcomes and medical resource utilization were derived from a real-world survey among Swiss pediatricians and general practitioners including 236 individuals with VZV infection, published information on varicella complications, and expert opinion. Costs of medical resource utilization represent official Swiss medical tariffs. The model predicts both universal childhood vaccination strategies to be more effective in reducing varicella disease burden compared to strategy 1. Economically, both universal childhood vaccination strategies with or without catch-up result in net savings from the societal perspective reflected by a benefit cost ratio (BCR) of 1.22 or 1.29, respectively. In contrast, the model predicts net costs from the payer perspective (BCR of 0.27 and 0.30, respectively). These economic findings are comparable to those reported from other similar evaluations. However, due to the recent recommendation for using a 2-dose varicella vaccination schedule, our economic results for Switzerland are somewhat less favorable than those for other country analyses in which a less expensive 1-dose vaccination regimen for toddlers has been studied.

Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland.

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94 % primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0 - 47 years with a median of 5 years. The great majority of patients (179 = 76 %) were

Economic evaluation of varicella vaccination in Italian children and adolescents according to different intervention strategies: the burden of uncomplicated hospitalised cases.

An economic evaluation of universal varicella vaccination in Italy was performed to assess the potential clinical and economic effects of three different strategies versus no vaccination. By means of the EVITA model, vaccination with two doses in toddlers only (1-1.5 years), adolescents only (13 years) and toddlers with adolescents catch-up programmes were simulated. All universal varicella vaccination strategies including toddlers (with or without an adolescent catch-up programme) turned out to be highly effective in reducing the burden of disease due to varicella. In addition, they lead to significant net savings from the societal perspective but to higher costs compared to return of investment from National Health Service perspective. The huge economic burden of hospitalised uncomplicated varicella cases registered in Italy can partially explain these highly beneficial findings for the societal perspective. Overall, our analysis confirmed the favourable clinical and economic impact of routine varicella vaccination with two doses of vaccine in Italy.

Cardiac resynchronization therapy (CRT) in heart failure--a model to assess the economic value of this new medical technology.

OBJECTIVES: This article describes the framework of a comprehensive European model developed to assess clinical and economic outcomes of cardiac resynchronization therapy (CRT) versus optimal pharmacological therapy (OPT) alone in patients with heart failure. METHODS: The model structure is based on information obtained from the literature, expert opinion, and a European CRT Steering Committee. The decision-analysis tool allows a consideration of direct medical and indirect costs, and computes outcomes for distinctive periods of time up to 5 years. Qualitative data can also be entered for cost-utility analysis. Model input data for a preliminary economic appraisal of the economic value of CRT in Germany were obtained from clinical trials, experts, health statistics, and medical tariff lists. RESULTS: The model offers comprehensive analysis capabilities and high flexibility so that it can easily be adapted to any European country or special setting. The illustrative analysis for Germany indicates that CRT is a cost-effective intervention. Although CRT is associated with average direct medical net costs of Euro 5880 per patient, this finding means that 22% of its upfront implantation cost is recouped already within 1 year because of significantly decreased hospitalizations. With 36,600 Euros the incremental cost per quality-adjusted life-year (QALY) gained is below the euro equivalent (41,300 Euros, 1 Euro = US1.21 dollars) of the commonly used threshold level of US50,000 dollars considered to represent cost-effectiveness. The sensitivity analysis showed these preliminary results to be fairly robust towards changes in key assumptions. CONCLUSIONS: The European CRT model is an important tool to assess the economic value of CRT in patients with moderate to severe heart failure. In the light of the planned introduction of Diagnosis Related Group (DRG) based reimbursement in various European countries, the economic data generated by the model can play an important role in the decision-making process.

The burden of varicella in Germany. Potential risks and economic impact.

Varicella (chickenpox) has traditionally been regarded as a benign, inevitable disease of childhood. In Germany information on the clinical and economic impact of varicella is limited. This study assessed the health risks and economic burden of varicella with a special focus on the relevance of complications as a cost driver. We used an age-structured, dynamic infectious disease model for the spread of infection in the German population combined with a module modeling the course of disease and medical management in the case of infection. Model input data were derived mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. This survey included detailed information on outpatient care, complications, inpatient treatment, and sick leave. In the base case analysis the model predicted approx. 740,000 varicella cases per year. Some 40,000 experienced complications, of which 5,700 required inpatient care. Total annual costs for payers, i.e., sickness funds, was 78 million euro, the largest portion of which was due to the significant coverage of work loss costs incurred by parents caring for their sick children ("Kinderpflegekrankengeld"). For the society total annual costs were 187.5 million euro, 82% of which was indirect. Complications account for disproportionate 32% (25%) of cost from the payers' (societal) perspective. However, the vast majority of costs are due to uncomplicated cases. The burden of varicella in Germany is thus significant, not only in terms of morbidity but also from an economic viewpoint. Vaccination strategies targeting groups with high risk of complications might fail to reduce the considerable burden of varicella substantially. Routine vaccination against varicella would be a meaningful measure to reduce the burden of VZV infection in Germany.

Validation of health economic models: the example of EVITA.

OBJECTIVES: The credibility of models rests on their validity. An age-structured decision analytic model, Economic Varicella Vaccination Tool for Analysis (EVITA), has been developed to examine the epidemiologic and economic effects of universal varicella (chicken pox) vaccination in Germany. EVITA combines a varicella transmission module describing the spread of infection in a population over time with a second module describing the course of disease in case of an infection. Any vaccination strategy can be assessed dependent on coverage levels and targeted age group. Model input data include epidemiologic, clinical, and economic information, which were mainly derived from actual varicella cases (retrospective survey). The objective of this study was to illustrate the efforts undertaken to validate the EVITA model. METHODS: We assess the descriptive validity, i.e., whether the model provides an adequate picture of the reality and covers all relevant aspects of the spread of varicella and the course of disease. Analyzing the consistency of the model results with observable data does technical verification. Face validity, i.e., the consistency with the underlying theoretical basis of the spread of varicella, is analyzed with respect to results on possible age shifts and elimination of varicella. Tests of corroboration, or convergent validity, are performed by comparisons with other models. RESULTS: Without vaccination, the EVITA model predicts undiscounted, indirect costs of 154 million euros, nearly 40,000 complications and 5,700 hospitalizations per year owing to varicella. These results, especially the distribution of complications and hospitalizations, fit well with population-based survey data. The development of the EVITA model is based on an established epidemiologic model and on real-life data from the survey, ensuring descriptive validity. Results on age shifts and elimination show face validity. Although other models differ considerably with respect to methods applied, the economic results of EVITA, i.e., a benefit-cost ratio of 4.12 when vaccinating young children, lies in the range found in other studies. This underscores its convergent validity. Comparable with other studies, discount rates and price of vaccine proved to be most sensitive variables. CONCLUSIONS: EVITA provides a powerful tool to simulate the highly complex processes associated with varicella infections and the impact of vaccination. The results of EVITA provide a reliable tool for informed decision making and should enhance the acceptance of such models.

Can varicella be eliminated by vaccination? Potential clinical and economic effects of universal childhood varicella immunisation in Germany.

Varicella is a potentially serious infection not only in immunocompromised individuals but also in otherwise healthy adults and children. Vaccination plays an important role in preventing the disease and its sequelae. A universal vaccination in childhood is expected to reduce substantially the number of uncomplicated cases of varicella and decrease the number of complicated cases requiring hospitalisation. To generate data as basis for decisions of the health authorities concerning prevention of varicella, epidemiological and health-economic data were collected in two studies. Using an age-structured decision analytic model the benefits, costs and cost effectiveness of a varicella immunisation program for a period of 30 years were assessed. It was shown that after the first year of life seroprevalence rates increased steadily and reached 62% among the 4- to 5-year olds and 94% among the 10- to 11-year olds, respectively; 90% of varicella patients were younger than 12 years. A severe course was assessed for 16.3% of the cases. Overall incidence of complications was estimated to be 5.7%. A routine varicella vaccination program targeting healthy children could prevent 82.7% of varicella cases and over 4,700 major complications per year provided the coverage level was 85%. Under these conditions the elimination of varicella is predicted to be achievable within 18 years. It is expected that a combined measles, mumps, rubella and varicella vaccine could provide the required coverage. Average yearly discounted net cost savings of universal childhood vaccination are 51 million Euro with a benefit-cost ratio of 4.12. Childhood vaccination with catch-up of adolescents provides additional clinical benefits. The break-even point indicating first net savings could be achieved already 3 years after the implementation of the vaccination program. In summary, routine childhood varicella vaccination appears to be a highly efficient strategy to significantly reduce the sizeable burden of varicella and would lead to net savings from both the societal but also the payer perspective.

Economic value of thrombolysis with adjunctive abciximab in patients with subacute peripheral arterial occlusion.

BACKGROUND AND OBJECTIVE: Glycoprotein (GP) IIb/IIIa receptor inhibitors enhance thrombolysis in patients with acute coronary syndromes. This analysis evaluates the economic impact of abciximab, a GP IIb/IIIa inhibitor, as an adjunct to urokinase in peripheral artery occlusions of less than 6 weeks duration. STUDY DESIGN: A post-hoc economic analysis was performed using clinical data and inpatient resource utilisation derived from the prospective comparative phase II Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis (PROMPT) pilot study. Study endpoints were amputation-free survival and survival without open surgery or major amputation after 90 days, and the rate of major complications at 30 days. PERSPECTIVE: Third-party payer and the societal perspective. PATIENTS AND METHODS: Seventy patients with lower extremity thrombi were randomised (2 : 5 ratio) to urokinase plus placebo or to urokinase plus abciximab. Economically relevant data were retrospectively derived from the clinical study database from a specific evaluation of patient records and from expert opinion. RESULTS: From the viewpoint of the society, average total per-patient direct and indirect costs accruing over 3 months were more favourable for treatment with abciximab plus urokinase than for urokinase alone [9723 euros (EUR) vs EUR10 322; 2000 values], despite higher initial hospitalisation costs of the combination therapy. Abciximab plus urokinase was the dominant strategy at 3 months due to a clinically higher rate of survival without amputation or bypass surgery coupled with a lower average per-patient cost. From the perspective of the third-party payer, treatment with abciximab plus urokinase was economically also superior to urokinase alone (EUR8773 vs EUR9663). CONCLUSIONS: Based on the preliminary findings of the PROMPT trial, the use of abciximab as an adjunct to urokinase in patients with subacute peripheral artery occlusions may be the favourable strategy compared with urokinase alone, in terms of clinical and economic outcomes. Further trials are needed to confirm these clinical and economic findings. The preliminary clinical benefits experienced by patients treated with abciximab plus urokinase in the PROMPT trial translated into cost savings in terms of reduced direct medical costs at 3 months. These cost savings more than offset the cost of abciximab. The use of abciximab as an adjunct to urokinase in patients with subacute peripheral artery occlusions may be the favourable strategy compared with urokinase-alone in terms of clinical and economic outcomes, but further trials are needed to confirm the these clinical and economic findings.