The Kenevo microprocessor-controlled prosthetic knee compared with non-microprocessor-controlled knees in individuals older than 65 years in Sweden: A cost-effectiveness and budget-impact analysis.

BACKGROUND: Growing evidence suggests that individuals with transfemoral amputation or knee disarticulation using a prosthesis equipped with a microprocessor-controlled knee (MPK) benefit from enhanced mobility and safety, including less falls. In elderly individuals, high mortality rates are assumed to reduce the expected useful life of MPKs, and this raises concerns regarding their economic effectiveness. OBJECTIVE: To investigate the cost-effectiveness and budget impact of the Kenevo/MPK (Ottobock, Germany) compared with non-microprocessor-controlled knees (NMPKs) in people older than 65 years at the time of transfemoral amputation/knee disarticulation, from a Swedish payer's perspective. METHODS: A decision-analytic model was developed to conduct the economic analysis of the Kenevo/MPK. Model parameters were derived from Swedish databases and published literature. Univariate and probabilistic sensitivity analyses were performed to explore parameter uncertainty. RESULTS: Compared with NMPKs, the Kenevo/MPK reduced the frequency of hospitalizations by 137 per 1,000 person years while the frequency of fatal falls was reduced by 19 per 1,000 person-years in the simulation. Over a 25-year time horizon, the incremental cost-effectiveness ratio was EUR11,369 per quality-adjusted life year. The probability of the MPK being cost-effective at a threshold of EUR40,000 per quality-adjusted life year was 99%. The 5-year budget impact model predicted an increase in payer expenditure of EUR1.76 million if all new patients received a Kenevo/MPK, and 50% of current NMPK users switched to the MPK. CONCLUSIONS: Results of the modeling suggest that the Kenevo/MPK is likely to be cost-effective for elderly individuals, primarily because of a reduction in falls.

Healthcare costs associated with breast cancer in Germany: a claims data analysis.

PURPOSE: This study estimates the healthcare costs associated with breast cancer (BC) for different treatment phases (initial, intermediate, terminal) in Germany from the payer's perspective. METHODS: The analysis uses claims data from the AOK Bayern covering 2011-2014 for continuously insured BC patients identified through inpatient and outpatient diagnoses. We calculate the healthcare costs attributable to BC using a control group design comparing the target population to a 1:2 matched control group adjusted for age, gender, and comorbidities. For incident and prevalent BC cases, we calculate age-standardized phase-specific incremental costs stratified by cost domain. RESULTS: The initial, intermediate, and terminal phases comprise 3841, 28,315, and 1767 BC cases, respectively. BC-related incremental costs follow a u-shaped curve, with costs highest near diagnosis and death, and lower in between. With average costs of €33,237 per incident and €28,211 per prevalent case in the remaining 11 months before death, the highest BC-related incremental healthcare costs can be found in the terminal phase. In the initial phase, there were mean incremental costs of €21,455 the first 11 months after diagnosis. In the intermediate phase, incremental costs totaled €2851 per incident and €2387 per prevalent case per year. Healthcare costs decreased with age in most phases. The cost drivers depend on the treatment phase, with cytostatic drugs and inpatient treatment showing the highest economic impact in most phases. CONCLUSION: The study concludes that BC care costs impose a relevant economic burden on statutory health insurance and vary substantially depending on the treatment phase.

Cost-effectiveness and budget impact of the microprocessor-controlled knee C-Leg in transfemoral amputees with and without diabetes mellitus.

BACKGROUND: The safe use of a prosthesis in activities of daily living is key for transfemoral amputees. However, the number of falls varies significantly between different prosthetic device types. This study aims to compare medical and economic consequences of falls in transfemoral amputees who use the microprocessor-controlled knee joint C-Leg with patients who use non-microprocessor-controlled (mechanical) knee joints (NMPK). The main objectives of the analysis are to investigate the cost-effectiveness and budget impact of C-Legs in transfemoral amputees with diabetes mellitus (DM) and without DM in Germany. METHODS: A decision-analytic model was developed that took into account the effects of prosthesis type on the risk of falling and fall-related medical events. Cost-effectiveness and budget impact analyses were performed separately for transfemoral amputees with and without DM. The study took the perspective of the statutory health insurance (SHI). Input parameters were derived from the published literature. Univariate and probabilistic sensitivity analyses (PSA) were performed to investigate the impact of changes in individual input parameter values on model outcomes and to explore parameter uncertainty. RESULTS: C-Legs reduced the rate of fall-related hospitalizations from 134 to 20 per 1000 person years (PY) in amputees without DM and from 146 to 23 per 1000 PY in amputees with DM. In addition, the C-Leg prevented 15 or 14 fall-related death per 1000 PY. Over a time horizon of 25 years, the incremental cost-effectiveness ratio (ICER) was 16,123 Euro per quality-adjusted life years gained (QALY) for amputees without DM and 20,332 Euro per QALY gained for amputees with DM. For the period of 2020-2024, the model predicted an increase in SHI expenditures of 98 Mio Euro (53 Mio Euro in prosthesis users without DM and 45 Mio Euro in prosthesis users with DM) when all new prosthesis users received C-Legs instead of NMPKs and 50% of NMPK user whose prosthesis wore out switched to C-Legs. Results of the PSA showed moderate uncertainty and a probability of 97-99% that C-Legs are cost-effective at an ICER threshold of 40,000 Euro (≈ German GDP per capita in 2018) per QALY gained. CONCLUSION: Results of the study suggest that the C-Leg provides substantial additional health benefits compared with NMPKs and is likely to be cost-effective in transfemoral amputees with DM as well as in amputees without DM at an ICER threshold of 40,000 Euro per QALY gained.

Cost Effectiveness of Elderly Pneumococcal Vaccination in Presence of Higher-Valent Pneumococcal Conjugate Childhood Vaccination: Systematic Literature Review with Focus on Methods and Assumptions.

BACKGROUND: Previous systematic reviews concluded that pneumococcal vaccination in the elderly was cost effective. However, recently published economic evaluations state that it may not be cost effective when children are vaccinated with higher-valent pneumococcal conjugate vaccines. The literature suggests that the outcomes of vaccination in the elderly are strongly influenced by the vaccine effectiveness (VE) against the vaccine-type pneumococcal diseases (PD) and the impact of childhood vaccination on the vaccine-type PD incidence in the elderly, but the extent remains unclear. METHODS: We conducted a systematic literature search of cost-effectiveness studies on vaccination in the elderly in the PubMed database starting from 2006. We included studies that consider the presence of a childhood vaccination with pneumococcal conjugate vaccine (PCV) 10 and PCV13. We focus on methods and assumptions used in modeling VE and epidemiology of PD over time. RESULTS: Twenty-eight economic evaluations underwent full-text review and data extraction. Thirteen were selected for quality assessment. The studies with a higher quality score provide evidence that vaccinating the elderly with PCV13 is not cost effective, when an ongoing rapid decline in the incidence of PCV13-type PD is modeled. A moderate persistence of PCV13 serotypes, in particular due to PCV10 childhood vaccination, makes vaccination of the elderly with PCV13 more attractive. There is no agreement that combining PCV13 with polysaccharide vaccine PPSV23 is cost effective. PPSV23 is attractive when it is effective against non-invasive PD. CONCLUSION: Methodological approaches and assumptions in modeling VE and the indirect effects of childhood vaccination have a major impact on outcomes of decision-analytic models and cost-effectiveness estimates. Considering recently observed trends in the epidemiology of pneumococcal serotypes, there is currently inconclusive evidence regarding the cost effectiveness of pneumococcal vaccination of the elderly due to lack of studies that model key serotypes such as serotype 3 separately from other groups of serotypes.

Trade-off between benefits, harms and economic efficiency of low-dose CT lung cancer screening: a microsimulation analysis of nodule management strategies in a population-based setting.

BACKGROUND: In lung cancer screening, a nodule management protocol describes nodule assessment and thresholds for nodule size and growth rate to identify patients who require immediate diagnostic evaluation or additional imaging exams. The Netherlands-Leuvens Screening Trial and the National Lung Screening Trial used different selection criteria and nodule management protocols. Several modelling studies have reported variations in screening outcomes and cost-effectiveness across selection criteria and screening intervals; however, the effect of variations in the nodule management protocol remains uncertain. This study evaluated the effects of the eligibility criteria and nodule management protocols on the benefits, harms and cost-effectiveness of lung screening scenarios in a population-based setting in Germany. METHODS: We developed a modular microsimulation model: a biological module simulated individual histories of lung cancer development from carcinogenesis onset to death; a screening module simulated patient selection, screening-detection, nodule management protocols, diagnostic evaluation and screening outcomes. Benefits included mortality reduction, life years gained and averted lung cancer deaths. Harms were costs, false positives and overdiagnosis. The comparator was no screening. The evaluated 76 screening scenarios included variations in selection criteria and thresholds for nodule size and growth rate. RESULTS: Five years of annual screening resulted in a 9.7-12.8% lung cancer mortality reduction in the screened population. The efficient scenarios included volumetric assessment of nodule size, a threshold for a volume of 300 mm3 and a threshold for a volume doubling time of 400 days. Assessment of volume doubling time is essential for reducing overdiagnosis and false positives. Incremental cost-effectiveness ratios of the efficient scenarios were 16,754-23,847 euro per life year gained and 155,287-285,630 euro per averted lung cancer death. CONCLUSIONS: Lung cancer screening can be cost-effective in Germany. Along with the eligibility criteria, the nodule management protocol influences screening performance and cost-effectiveness. Definition of the thresholds for nodule size and nodule growth in the nodule management protocol should be considered in detail when defining optimal screening strategies.

Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

BACKGROUND: In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (<2 years old) vaccination with a 13-valent pneumococcal conjugate vaccine (PCV13) in comparison with a 10-valent pneumococcal conjugate vaccine (PCV10) for the prevention of pneumococcal disease in Germany. METHODS: A population-based Markov model was developed to estimate the impact of PCV13 and PCV10 on invasive pneumococcal disease (IPD), non-invasive pneumonia (PNE), and acute otitis media (AOM) over a time horizon of 50 years. The model included the effects of the historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. CONCLUSIONS: Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

Analysis of contemporary HIV/AIDS health care costs in Germany: Driving factors and distribution across antiretroviral therapy lines.

To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics.Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers.Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients.The average annual total costs (SD) per patient are &OV0556;22,231.03 (8786.13) with a maximum of &OV0556;83,970. cART medication is the major cost fraction (83.8%) with a mean of &OV0556;18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs.HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases.

Methods for Health Economic Evaluation of Vaccines and Immunization Decision Frameworks: A Consensus Framework from a European Vaccine Economics Community.

BACKGROUND: Incremental cost-effectiveness and cost-utility analyses [health economic evaluations (HEEs)] of vaccines are routinely considered in decision making on immunization in various industrialized countries. While guidelines advocating more standardization of such HEEs (mainly for curative drugs) exist, several immunization-specific aspects (e.g. indirect effects or discounting approach) are still a subject of debate within the scientific community. OBJECTIVE: The objective of this study was to develop a consensus framework for HEEs of vaccines to support the development of national guidelines in Europe. METHODS: A systematic literature review was conducted to identify prevailing issues related to HEEs of vaccines. Furthermore, European experts in the field of health economics and immunization decision making were nominated and asked to select relevant aspects for discussion. Based on this, a workshop was held with these experts. Aspects on 'mathematical modelling', 'health economics' and 'decision making' were debated in group-work sessions (GWS) to formulate recommendations and/or--if applicable--to state 'pros' and 'contras'. RESULTS: A total of 13 different aspects were identified for modelling and HEE: model selection, time horizon of models, natural disease history, measures of vaccine-induced protection, duration of vaccine-induced protection, indirect effects apart from herd protection, target population, model calibration and validation, handling uncertainty, discounting, health-related quality of life, cost components, and perspectives. For decision making, there were four aspects regarding the purpose and the integration of HEEs of vaccines in decision making as well as the variation of parameters within uncertainty analyses and the reporting of results from HEEs. For each aspect, background information and an expert consensus were formulated. CONCLUSIONS: There was consensus that when HEEs are used to prioritize healthcare funding, this should be done in a consistent way across all interventions, including vaccines. However, proper evaluation of vaccines implies using tools that are not commonly used for therapeutic drugs. Due to the complexity of and uncertainties around vaccination, transparency in the documentation of HEEs and during subsequent decision making is essential.

The Role of decision-analytic modelling in German health technology assessments.

BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in health technology assessments (HTA), but the extent to which modelling is used differs among international HTA institutions. In Germany, the use of DAM is optional within HTAs of the German Institute of Medical Documentation and Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and its effect on the quality of information provided for health policies. METHODS: A review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an economic assessment was performed. All included reports were divided into two groups: HTAs with DAM and HTAs without DAM. In both groups, reports were categorized according to the quality of information provided for healthcare decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used DAM for economic assessment. In the group without DAM, conclusions were limited by the quality of economic information in 51.1% of the reports, whereas we did not find limited conclusions in the group with DAM. Furthermore, 24 reports without DAM (26.7%) stated that using DAM would likely improve the quality of information of the economic assessment. CONCLUSION: The use of DAM techniques can improve the quality of HTAs in Germany. When, after a systematic review of existing literature within a HTA, it is clear that DAM is likely to positively affect the quality of the economic assessment DAM should be used.

Impact of radiofrequency ablation for patients with varicose veins on the budget of the German statutory health insurance system.

OBJECTIVES: In contrast to other countries, surgery still represents the common invasive treatment for varicose veins in Germany. However, radiofrequency ablation, e.g. ClosureFast, becomes more and more popular in other countries due to potential better results and reduced side effects. This treatment option may cause less follow-up costs and is a more convenient procedure for patients, which could justify an introduction in the statutory benefits catalogue. Therefore, we aim at calculating the budget impact of a general reimbursement of ClosureFast in Germany. METHODS: To assess the budget impact of including ClosureFast in the German statutory benefits catalogue, we developed a multi-cohort Markov model and compared the costs of a "World with ClosureFast" with a "World without ClosureFast" over a time horizon of five years. To address the uncertainty of input parameters, we conducted three different types of sensitivity analysis (one-way, scenario, probabilistic). RESULTS: In the Base Case scenario, the introduction of the ClosureFast system for the treatment of varicose veins saves costs of about 19.1 Mio. € over a time horizon of five years in Germany. However, the results scatter in the sensitivity analyses due to limited evidence of some key input parameters. CONCLUSIONS: Results of the budget impact analysis indicate that a general reimbursement of ClosureFast has the potential to be cost-saving in the German Statutory Health Insurance.

Potential cost-effectiveness and benefit-cost ratios of adult pneumococcal vaccination in Germany.

BACKGROUND: Invasive (IPD, defined as detection of pneumococci in sterile body fluids like meningitis or bacteremic pneumonia) and non-invasive Streptococcus pneumoniae infections (i.e. non-bacteremic pneumonia, otitis media) in adults are associated with substantial morbidity, mortality and costs. In Germany, Pneumococcal polysaccharide vaccination (PPV23) is recommended for all persons >60 years and for defined risk groups (age 5-59). The aim of this model was to estimate the potential cost-effectiveness and benefit-cost ratios of the adult vaccination program (18 years and older), considering the launch of the pneumococcal conjugate vaccine for adults (PCV13). METHODS: A cross-sectional steady state Markov model was developed to estimate the outcomes of PCV13, PPV23 vaccination schemes and 'no vaccination'. Conservative assumptions were made if no data were available for PCV13 and PPV23 respectively. The effectiveness of individual pneumococcal vaccination in adults was adjusted for expected indirect effects due to the vaccination in infants. Data on incidences, effectiveness and costs were derived from scientific literature and publicly available databases. All resources used are indicated. Benefit-cost ratios and cost-effectiveness were evaluated from the perspective of the German Statutory Health Insurance as well as from social perspective. RESULTS: Under the assumption that PCV13 has a comparable effectiveness to PCV7, a vaccination program with PCV13 revealed the potential to avoid a greater number of yearly cases and deaths in IPD and pneumonia in Germany compared to PPV23. For PCV13, the costs were shown to be overcompensated by monetary savings resulting from reduction in the use of health care services. These results would render the switch from PPV23 to PCV13 as a dominant strategy compared to PPV23 and 'no vaccination'. Given the correctness of the underlying assumptions every Euro spent on the PCV13 vaccination scheme yields savings of 2.09 € (social perspective: 2.16 €) compared to PPV23 and 1.27 € (social perspective: 1.32 €) compared to 'no vaccination', respectively. CONCLUSIONS: Results of the model indicate that the health economic benefit of immunizing adults with PCV13 can be expected to outperform the sole use of PPV23, if the effectiveness of PCV13 is comparable to the effectiveness of PCV7.

Efficacy and cost-effectiveness of the 13C-urea breath test as the primary diagnostic investigation for the detection of Helicobacter pylori infection compared to invasive and non-invasive diagnostic tests.

BACKGROUND: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans. There is a risk factor for gastric or duodenal ulcers, gastric cancer and MALT (Mucosa Associated Lymphoid Tissue)-Lymphomas. There are several invasive and non-invasive methods available for the diagnosis of H. pylori. The (13)C-urea breath test is a non-invasive method recommended for monitoring H. pylori eradication therapy. However, this test is not yet used for primary assessment of H. pylori in Germany. OBJECTIVES: What are the clinical and health economic benefits of the (13)C-urea breath test in the primary assessment of H. pylori compared to other invasive and non-invasive methods? METHODS: A systematic literature search including a hand search was performed for studies investigating test criteria and cost-effectiveness of the (13)C-urea breath test in comparison to other methods used in the primary assessment of H. pylori. Only studies that directly compared the (13)C-urea breath test to other H. pylori-tests were included. For the medical part, biopsy-based tests were used as the gold standard. RESULTS: 30 medical studies are included. Compared to the immunoglobulin G (IgG) test, the sensitivity of the (13)C-urea breath test is higher in twelve studies, lower in six studies and one study reports no differences. The specificity is higher in 13 studies, lower in three studies and two studies report no differences. Compared to the stool antigen test, the sensitivity of the (13)C-urea breath test is higher in nine studies, lower in three studies and one study reports no difference. The specificity is higher in nine studies, lower in two studies and two studies report no differences. Compared to the urease test, the sensitivity of the (13)C-urea breath test is higher in four studies, lower in three studies and four studies report no differences. The specificity is higher in five studies, lower in five studies and one study reports no difference. Compared to histology, the sensitivity of the (13)C-urea breath test is higher in one study and lower in two studies. The specificity is higher in two studies and lower in one study. One study each compares the (13)C-urea breath test to the (14)C-urea breath test and the polymerase chain reaction (PCR) test, respectively, and reports no difference in sensitivity and specificity with the (14)C-urea breath test, and lower sensitivity and higher specificity compared to PCR. The statistical significance of these differences is described for six of the 30 studies. Nine health economic evaluations are included in the Health Technology Assessment (HTA) report. Among these studies, the test-and-treat strategy using the (13)C-urea breath test is compared to test-and-treat using serology in six analyses and to test and treat using the stool antigen test in three analyses. Thereby, test-and-treat using the breath test is shown to be cost-effective over the serology based strategy in three models and is dominated by a test-and-treat strategy using the stool antigen test in one model. A cost-effectiveness comparison between the urea breath test approach and the empirical antisecretory therapy is carried out in four studies. Of these, two studies report that the strategy using the urea breath test is cost-effective over the empirical antisecretory therapy. In two studies, test-and-treat using the (13)C-urea breath test is compared to the empirical eradication therapy and in five studies to endoscopy-based strategies. The breath test approach dominates endoscopy in two studies and is dominated by this strategy in one study. DISCUSSION: All included medical and economic studies are limited to a greater or lesser extent. Additionally, the results of the studies are heterogeneous regarding medical and economic outcomes respectively. Thus, the majority of the medical studies do not report the statistical significance of the differences in sensitivity and specificity. In direct comparisons the (13)C- urea breath test shows higher sensitivity and specificity than the IgG and stool antigen tests. In comparison to the urease test, results for sensitivity are inconsistent, and the specificity is slightly higher for the (13)C-urea breath test. There are not enough results for comparisons between the (13)C-urea breath test and the (14)C-urea breath test, histology and PCR to describe tendencies. The included economic studies suggest that the test-and-treat strategy using the (13)C-urea breath test is cost-effective compared to test-and-treat using serology as well as empirical antisecretory therapies. Due to a lack of valid studies, it is not possible to assess the breath test approach in comparison to test-and-treat using the stool antigen test and the empirical eradication therapy respectively, regarding the cost-effectiveness. The results of economic analyses comparing test-and-treat using the breath test to endoscopy strategies are too heterogeneous to draw any conclusions. Overall, none of the included economic models is able to completely capture the complexity of managing patients with dyspeptic complaints. CONCLUSIONS/RECOMMENDATIONS: Based on available medical and economic studies, there is no sufficient evidence to recommend test and-treat using (13)C-urea breath testing for the detection of H. pylori infection as the standard procedure for the management of uninvestigated dyspepsia in the German health care system. In addition, it must be considered that the DVGS guidelines of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DVGS) recommend endoscopy based methods for the management of patients with dyspeptic complaints.