Cost-Effectiveness and Budget Impact Analyses of Selective Internal Radiation Therapy versus Atezolizumab Plus Bevacizumab from a German Statutory Health Insurance Perspective.

Purpose: To compare personalized dosimetry with yttrium-90 (90Y)-loaded glass microspheres (SIRT) vs atezolizumab and bevacizumab (A+B) in hepatocellular carcinoma (HCC) treatment in terms of cost-effectiveness and budget impact from a German statutory health insurance (SHI) perspective. Patients and Methods: Cost-effectiveness analysis (CEA) and budget impact analysis (BIA) models were developed in MS Excel. The available key studies (IMbrave150 and DOSISPHERE-01) suggest that both strategies are comparable in terms of progression-free survival and overall survival in HCC, but a difference in severe adverse events (SAE) in favor of SIRT was observed. Accordingly, the CEA model investigates the endpoints "cost per SAE avoided" and "cost per quality-adjusted life year (QALY) gained", whereas the BIA simulates the impact of a stepwise re-allocation of current market share to the option which emerges as more cost-effective from the CEA. Results: The model suite estimated a mean annual total per-patient costs of € 29,984 for SIRT, compared to € 75,725 for A+B. SIRT was associated with a lower number of SAE and a higher number of QALYs compared to A+B. Switching additionally 25% of the eligible patients (≈500) from systemic therapy to SIRT could generate annual savings of approximately € 22.6 million Euros to the SHI. Conclusion: SIRT was identified as dominant treatment strategy. SIRT use not only saves SHI expenditure compared to systemic immunotherapy but also yields extra QALYs. This positions SIRT as the dominant and more cost-effective treatment strategy for patients with HCC. The savings to the SHI system, derived from the BIA conducted, become increasingly significant with rising adoption rates of SIRT.

Budget impact of antimicrobial wound dressings in the treatment of venous leg ulcers in the German outpatient care sector: a budget impact analysis.

Background: Hard-to-heal wounds are associated with high treatment costs and, in Germany, are mostly treated in the outpatient care sector. Wound dressings are the main cost-drivers in venous leg ulcer (VLU) care which prescription is budget-restricted. Objective: To determine to what extent the choice of antimicrobial dressing affects the spending in outpatient care by investigating the budget impact of the bioburden-reducing dressing Cutimed Sorbact. Methods: The budget impact analysis was performed comparing three different scenarios of the intervention mix of antimicrobial dressings. A Markov model was used to estimate the VLU progression during one year. The budget impact was determined by comparing the dressing and medicine resource use and costs of the three scenarios. Results: This analysis confirms the high treatment costs of VLU care. ScenarioA leads to a decreased resource use of antimicrobial dressings and results in 20.86% lower treatment costs after 12 months. The increased use of Cutimed Sorbact has a positive budget impact. Conclusion: This analysis indicates that the treatment of VLU patients may result in an exceedance of the budget per patient that is available to the treating practitioner. The choice of wound dressing, however, may positively affect the prescribers' budget spending in outpatient care.

The role of galenic innovation in improving treatment compliance and persistence: three case studies.

BACKGROUND: The purpose of this study was to explore whether newer galenic formulations with lower treatment burdens are associated with better patient compliance and persistence compared with older more burdensome modalities. METHODS: Data from the IMS Disease Analyzer database were analyzed retrospectively for two pairs of analogs (alendronate sodium once daily vs once weekly and immediate-release vs extended-release methylphenidate) and one pair of drugs with similar indications but important differences in convenience and dosing instructions (desferrioxamine vs deferasirox). Compliance was calculated as the sum of prescription durations for all prescriptions for each patient over 1 year. Persistence was calculated as the time between first and last prescriptions over 2 years (1 year for deferasirox and desferrioxamine). Data from Germany and the UK were available and used for analysis. RESULTS: Incremental improvements in compliance were +30% in the UK and +26% in Germany for alendronate once weekly vs once daily, +14% in the UK and +19% in Germany for extended-release vs immediate-release methylphenidate, and +15% in Germany for desferrioxamine vs deferasirox. Incremental improvements in persistence were +9 months in the UK and +8 months in Germany for alendronate once weekly vs once daily, +4 months in the UK and +3 months in Germany for extended-release vs immediate-release methylphenidate, and +2 months in Germany for deferasirox vs desferrioxamine. CONCLUSION: The new formulations that we evaluated were associated with better compliance and persistence compared with older formulations. Despite the fact that some sources of bias could not be excluded, it is likely that these improvements can be attributed to the lower treatment burdens of the galenic formulations of the drugs considered. Further investigation is required to confirm these findings and to determine whether new galenic formulations can improve health outcomes in routine clinical practice.

Reducing uncertainty in value-based pricing using evidence development agreements: the case of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in Sweden.

BACKGROUND: Value-based pricing (VBP), whereby prices are set according to the perceived benefits offered to the consumer at a time when costs and benefits are characterized by considerable uncertainty and are then reviewed ex post, is a much discussed topic in pharmaceutical reimbursement. It is usually combined with coverage with evidence development (CED), a tool in which manufacturers are granted temporary reimbursement but are required to collect and submit additional health economic data at review. Many countries, including the UK, are signalling shifts in this direction. Several countries, including Sweden, have already adopted this approach and offer good insight into the benefits and pitfalls in actual practice. OBJECTIVE: To describe VBP reimbursement decision making using CED in actual practice in Sweden. METHODS: Decision making by The Dental and Pharmaceutical Benefits Agency (TLV) in Sweden was reviewed using a case study of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in the treatment of advanced Parkinson's disease (PD) with severe motor fluctuations. RESULTS: The manufacturer of Duodopa® applied for reimbursement in late 2003. While the proper economic data were not included in the submission, TLV granted reimbursement until early 2005 to provide time for the manufacturer to submit a formal economic evaluation. The re-submission with economic data was considered inadequate to judge cost effectiveness, so TLV granted an additional extension of reimbursement until August 2007, at which time conclusive data were expected. The manufacturer initiated a 3-year, prospective health economic study and a formal economic model. Data from a pre-planned interim analysis of the data were loaded into the model and the cost-effectiveness ratio was the basis of the next re-submission. TLV concluded that the data were suitable for making a definite decision and that the drug was not cost effective, deciding to discontinue reimbursement for any new patients (current patients were unaffected). The manufacturer continued to collect data and to improve the economic model and re-submitted in 2008. New data and the improved model resulted in reduced uncertainty and a lower cost-effectiveness ratio in the range of Swedish kronor (SEK)430,000 per QALY gained in the base-case analysis, ranging up to SEK900,000 in the most conservative sensitivity analysis, resulting in reimbursement being granted. DISCUSSION: The case of Duodopa® provides excellent insight into VBP reimbursement decision making in combination with CED and ex post review in actual practice. Publicly available decisions document the rigorous, time-consuming process (four iterations were required before a final decision could be reached). The data generated as part of the risk-sharing agreement proved correct the initial decision to grant limited coverage despite lack of economic data. Access was provided to 100 patients while evidence was generated. CONCLUSIONS: Economic appraisal differs from clinical assessment, and decision makers benefit from analysis of naturalistic, actual practice data. Despite reviewing the initial trial-based, 'piggy-back' economic analysis, TLV was uncertain of the cost effectiveness in actual practice and deferred a final decision until observational data from the DAPHNE study became available. Second, acceptance of economic modelling and use of temporary reimbursement conditional on additional evidence development provide a mechanism for risk sharing between TLV and manufacturers, which enabled patient access to a drug with proven clinical benefit while necessary evidence to support claims of cost effectiveness could be generated.

Adjunctive treatment with moxonidine versus nitrendipine for hypertensive patients with advanced renal failure: a cost-effectiveness analysis.

BACKGROUND: Systemic hypertension often accompanies chronic renal failure and can accelerate its progression to end-stage renal disease (ESRD). Adjunctive moxonidine appeared to have benefits versus adjunctive nitrendipine, in a randomised double-blind six-month trial in hypertensive patients with advanced renal failure. To understand the longer term effects and costs of moxonidine, a decision analytic model was developed and a cost-effectiveness analysis performed. METHODS: A Markov model was used to extrapolate results from the trial over three years. All patients started in a non-ESRD state. After each cycle, patients with a glomerular filtration rate below 15 ml/min had progressed to an ESRD state. The cost-effectiveness analysis was based on the Dutch healthcare perspective. The main outcome measure was incremental cost per life-year gained. The percentage of patients progressing to ESRD and cumulative costs were also compared after three years. In the base case analysis, all patients with ESRD received dialysis. RESULTS: The model predicted that after three years, 38.9% (95%CI 31.8-45.8) of patients treated with nitrendipine progressed to ESRD compared to 7.5% (95%CI 3.5-12.7) of patients treated with moxonidine. Treatment with standard antihypertensive therapy and adjunctive moxonidine was predicted to reduce the number of ESRD cases by 81% over three years compared to adjunctive nitrendipine. The cumulative costs per patient were significantly lower in the moxonidine group 9,858 euro (95% CI 5,501-16,174) than in the nitrendipine group 37,472 euro (95% CI 27,957-49,478). The model showed moxonidine to be dominant compared to nitrendipine, increasing life-years lived by 0.044 (95%CI 0.020-0.070) years and at a cost-saving of 27,615 euro (95%CI 16,894-39,583) per patient. Probabilistic analyses confirmed that the moxonidine strategy was dominant over nitrendipine in over 98.9% of cases. The cumulative 3-year costs and LYL continued to favour the moxonidine strategy in all sensitivity analyses performed. CONCLUSION: Treatment with standard antihypertensive therapy and adjunctive moxonidine in hypertensive patients with advanced renal failure was predicted to reduce the number of new ESRD cases over three years compared to adjunctive nitrendipine. The model showed that adjunctive moxonidine could increase life-years lived and provide long term cost savings.

Establishing the health and economic impact of influenza vaccination within the European Union 25 countries.

BACKGROUND: In 2003, the World Health Assembly (WHA) issued a resolution for prevention and control of influenza pandemics and annual epidemics, which urges the European Union 25 (EU-25) Member States to (1) establish and implement strategies to increase vaccination coverage of all people at high risk, including the elderly and people with underlying disease, with the goal of attaining vaccination coverage of the elderly population of at least 50% by 2006 and 75% by 2010; (2) to assess the disease burden and economic impact of annual influenza epidemics as a basis for framing and implementing influenza prevention policies. This resolution was reinforced by the European Union (EU), where Member States agreed to make additional efforts to improve uptake on their territory in accordance with their own recommendations and to achieve the World Health Organisation (WHO) target of 75% in high risk groups before 2010. It was also noted that the changing demographic profile of the EU population would result in an increasing number of elderly people falling within the current target groups. OBJECTIVES: To establish the number of people who may be eligible for influenza vaccination in the EU, and estimate the costs and consequences of not vaccinating this population for five EU Member States, France, Germany, Italy, Spain, and the UK. METHODS: A mathematical model has previously been developed, in which vaccine distribution data are combined with demographic and health economics data to model the public health consequences of influenza and possible intervention strategies. We have extended that model using specific EU-25 demographic data on populations at risk of influenza during the inter-pandemic period. For each country, the total population and age breakdown was calculated to estimate the percentage of the population that falls under the WHA recommendations. Other target groups for influenza vaccination were identified by analysing estimating the proportion of the population with respiratory or cardiovascular related diseases, diabetes, AIDS or transplantation, as well as health care professionals. Target population size and possible vaccination coverage rates across the EU-25 Member States, along with the potential cost and health consequence impact is estimated. RESULTS: For the EU-25, it was estimated that up to 49.1% of the population (or 223.4 million people) should be vaccinated against influenza. This ranged from 41.6% in Cyprus to 56.4% in the UK. There were, on average, 174 vaccine doses distributed per 1000 population within the EU-25, which leads to an average vaccination rate of the target population of 35.4% based on current supply constraints. As a consequence, up to 144.4 million people who could be considered "at risk" may not currently be vaccinated. Implementing a 100% vaccination rate programme for all risk groups across the EU-25 would lead to an estimated reduction of number of influenza cases of 7.22 million, 1.96 million reduced PCP visits for influenza treatment, 796,743 less hospital admissions and 68,537 fewer influenza related deaths for all EU-25 countries. The implementation of a 100% vaccination rate programme for all risk groups in France, Germany, Italy, Spain and UK would require an additional 1.52 billion Euro. This would result in estimated savings of 39.45 million Euro of reduced primary care visits and further savings of 1.59 billion Euro in reduced hospitalisations respectively in these countries. CONCLUSIONS: There is a gap between current vaccination coverage and the EU recommendations. The public health consequences of low vaccination coverage include increased morbidity, hospitalisations and mortality associated with influenza-related complications. This model is a powerful tool to: (1) support EU public health officials in implementing recommendations; (2) to visualize the need for increased vaccination rates for better influenza control; (3) the consequences of low vaccine coverage.

A multi-country health economic evaluation of highly concentrated N-3 polyunsaturated fatty acids in secondary prevention after myocardial infarction.

BACKGROUND: Patients who survive an acute myocardial infarction (MI) are at an increased risk of subsequent major cardiovascular events and (often sudden) cardiac death. The use of highly concentrated and purified omega-3 polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary prevention after MI, results in a significant reduction in the risk of sudden death versus no n-3 PUFAs. This study assessed the cost effectiveness of adding n-3 PUFAs to the current secondary prevention treatment versus standard prevention alone after acute MI in five countries: Australia, Belgium, Canada, Germany and Poland. METHODS: Based on the clinical outcomes of GISSI-P (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico - Prevenzione) [MI, stroke, revascularisation rate and mortality], a decision model was built in DataProtrade mark. The implications of adding n-3 PUFAs to standard treatment in patients aged 59 years with a recent history of MI were analysed from the healthcare payer's perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione) but the effects on life expectancy through avoidance of cardiac events were calculated lifelong. Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were taken from the Saskatchewan database and then adjusted by country. Results are expressed as extra cost (Euro) per life-year gained (LYG). Annual discounting of 5% was applied to health effects and costs. RESULTS: Treatment with highly concentrated n-3 PUFAs yielded between 0.261 (Poland) and 0.284 (Australia) LYG, at an additional cost of 787 Euros(Canada) to 1,439 Euros(Belgium). The ICER varied between 2,788 Euros(Canada) and 5,097 Euros(Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A second-order Monte Carlo simulation based on the 95% confidence intervals obtained from GISSI-P suggests that highly concentrated n-3 PUFAs are cost effective in 93% of simulations in Poland and in >98% of simulations in the other countries, assuming the country-specific societal willingness-to-pay threshold. Total costs were considerably increased by including healthcare costs incurred during the remaining life-years, but this had no impact on the ICER-based treatment recommendation. CONCLUSIONS: Adding highly concentrated n-3 PUFAs to standard treatment in the secondary prevention of MI appears to be cost effective versus standard treatment alone in the five countries studied.

Estimating a preference-based index for a menopause specific health quality of life questionnaire.

BACKGROUND: The aim of the study was to develop a menopause-specific, preference-based health-related quality-of-life (HRQoL) index reflecting both menopausal symptoms and potential side-effects of Hormone Replacement Therapy (HRT). METHODS: The study had three phases: the development of a health state classification, a prospective valuation survey and the estimation of a model to interpolate HRQoL indices for all remaining health states as defined by the classification. A menopausal health state classification was developed with seven dimensions: hot flushes, aching joints/muscles, anxious/frightened feelings, breast tenderness, bleeding, vaginal dryness and undesirable androgenic signs. Each dimension contains between three and five levels and defines a total of 6,075 health states. A sample of 96 health states was selected for the valuation survey. These states were valued by a sample of 229 women aged 45 to 60, randomly selected from 6 general practice lists in Sheffield, UK. Respondents were asked to complete a time trade-off (TTO) task for nine health states, resulting in an average of 16.5 values for each health state. RESULTS: Mean health states valued range from 0.48 to 0.98 (where 1.0 is full health and zero is for states regarded as equivalent to death). Symptoms, as described by the classification system, can be rank-ordered in terms of their impact (from high to low) on menopausal HRQoL as follows: aching joints and muscles, bleeding, breast tenderness, anxious or frightened feelings, vaginal dryness, androgenic signs. Hot flushes did not significantly contribute to model fit. The preferred model produced a mean absolute error of 0.053, but suffered from bias at both ends of the scale. CONCLUSION: This article presents an attempt to directly value a condition specific health state classification. The overall fit was disappointing, but the results demonstrate that menopausal symptoms are perceived by patients to have a significant impact on utility. The overall effect is modest compared to the more generic health state descriptions such as the EQ-5D. The resultant algorithm generates a preference-based index that can be used economic evaluation and that reflects the impact of this condition.

Modeling pandemic preparedness scenarios: health economic implications of enhanced pandemic vaccine supply.

Influenza pandemic planning is a complex, multifactorial process, which involves public health authorities, regulatory authorities, academia and industry. It is further complicated by the unpredictability of the time of emergence and severity of the next pandemic and the effectiveness of influenza epidemic interventions. The complexity and uncertainties surrounding pandemic preparedness have so far kept the various stakeholders from joining forces and tackling the problem from its roots. We developed a mathematical model, which shows the tangible consequences of conceptual plans by linking possible pandemic scenarios to health economic outcomes of possible intervention strategies. This model helps to structure the discussion on pandemic preparedness and facilitates the translation of pandemic planning concepts to concrete plans. The case study for which the model has been used shows the current level of global pandemic preparedness in an assumed pandemic scenario, the health economic implications of enhanced pandemic vaccine supply and the importance of cell culture-based influenza vaccine manufacturing technologies as a tool for pandemic control.