Health-related quality of life (HRQoL) in German early benefit assessment: The importance of disease-specific instruments.

INTRODUCTION: Health-Related Quality of Life (HRQoL) data is frequently requested in early benefit assessment in Germany. To test the hypothesis that the importance of HRQoL in general and the significance of disease-specific instruments in particular has increased since the introduction of AMNOG in Germany, we analysed all early benefit assessments between 2011 and 2022. METHODS: All 793 early benefit assessments completed between 01/01/2011 and 03/11/2022 were systematically analysed. The HRQoL instruments featured in the dossier submissions were extracted for all assessments and categorized into generic and specific instruments. All G-BA resolutions were likewise assessed for consideration and acceptance of generic and specific HRQoL instruments. In addition, it was examined whether there was an association between HRQoL data and the extent of additional benefit. RESULTS: Since 2014 HRQoL data have continuously been submitted in 70% to 80% of assessments per year with the exception of 2022 (63%). Generally, disease-specific instruments are favoured, regarding submissions by industry but especially with higher acceptance by the G-BA in the resolution. Subgroup analyses revealed oncology as a major contributor to the submission and acceptance rates of disease-specific instruments. Disease-specific instruments were submitted in 81% of all oncology assessments and accepted in 53% of assessments. Overall, assessments with accepted HRQoL data tend to reach a higher overall benefit. Procedures with accepted HRQoL were most likely to receive a considerable benefit (31%), while for procedures in which HRQoL data were not accepted, a benefit was most often (65%) not proven. DISCUSSION: Industry has followed the request for submission of specific HRQoL instruments early on. Higher submission rates of specific instruments over time which at the same time meet the methodological requirements indicate that industry has learned from early assessments. A potential reason for the high submission- and acceptance rates of specific HRQoL instruments in oncology might be the particularly high relevance of HRQoL in this indication. Possible effects of changes in legislature on the future development of submission and acceptance of HRQoL data need to be monitored. CONCLUSION: In Germany, HRQoL has gained a relevant position in early benefit assessment over time. Overall specific instruments are favoured, regarding submissions by industry but especially through consideration by the G-BA in the resolution. Furthermore, HRQoL data can be supportive for benefit assessments, in particular to show that advantages in morbidity and/or mortality are reflected in HRQoL and not at the expense of HRQoL.

Real-world treatment of German patients with recurrent and advanced endometrial cancer with a post-platinum treatment: a retrospective claims data analysis.

PURPOSE: Endometrial cancer (EC) is the sixth most common malignancy among females worldwide. Due to limited therapeutic options, treatment of advanced or recurrent disease is associated with poor outcomes. The aim of this study was to describe the real-world treatment of patients with advanced or recurrent EC who received a systemic treatment following platinum-based chemotherapy. METHODS: This retrospective cohort study was based on anonymized German claims data covering the period between January 1, 2010, and June 30, 2020. Patients with EC who started an anticancer treatment following platinum-based chemotherapy were observed for a minimum follow-up of 12 months. Available claims data were used to describe patient characteristics, subsequent treatment lines, healthcare resource utilization, and overall survival (OS) of patients. RESULTS: Out of 713 patients with advanced or recurrent EC and who had received a platinum-based treatment, 201 (mean age: 68.9 years) with a post-platinum-based treatment were identified and observed. The median OS in this population was 335.0 days. Of the 201 patients, 79 patients (39.3%) received a second line of treatment (LOT), and 21 patients (10.4%) had 3 or more treatment lines. In the LOTs following platinum-based chemotherapy, more than 70 different treatment regimens were observed. The hospitalization rate was generally high, with 5.2 hospitalizations per patient-year in the follow-up period. CONCLUSION: The wide variety of therapeutic regimens applied in patients in Germany who progressed after platinum-based therapy confirms the lack of therapeutic strategy for these patients, and the poor prognosis highlights the urgent need for new treatment strategies.

Epidemiology, treatment and health care resource use of patients with severe asthma in Germany - a retrospective claims data analysis.

BACKGROUND: Asthma causes various clinical symptoms, including unpredictable severe exacerbations, and even though most patients can achieve a reasonable disease control due to adequate treatment, some patients do not. This study seeks to describe healthcare resource utilization (HCRU) and treatment of asthma and severe asthma patients in Germany. METHOD: A retrospective claims data analysis has been conducted on adult asthma patients and a subset of patients with severe asthma, identified during July 2017 - June 2018. A proxy was used to identify severe asthma patients based on therapy options recommended within the German treatment guideline for treating these patients. These include (i) biologics, (ii) medium/high-dose inhaled corticosteroids (ICS) in conjunction with LABA/montelukast and antibiotics/oral corticosteroids (OCS), and (iii) long-term OCS therapy. HCRU and treatment of patients were observed during a 1-year follow-up period (July 2018 - June 2019). RESULTS: The study included 388 932 adult asthma patients (prevalence: 7.90%), with 2.51%-12.88% affected by severe asthma (depending on the definition). 22.60% of all asthma patients experienced hospitalizations (severe asthma: 36.11%). Furthermore, 13.59% received OCS (severe asthma: 39.91%), but only 0.18% (severe asthma: 1.25%) received biologics. Only 23.95% (severe asthma: 41.17%) visited a pulmonologist. CONCLUSIONS: A considerable proportion of severe asthma patients receive long-term OCS therapy. However, less than 50% have seen a pulmonologist who would typically seek a change in treatment to avoid the long-term consequences of OCS. To optimize the treatment of severe asthma in Germany, better referral of these patients to specialists is needed and considering potential treatment alternatives.

Association between asthma control and healthcare costs: Results from a German linked data study.

Background: This study aimed to evaluate differences in healthcare resource utilization and cost among patients with controlled and uncontrolled asthma.Methods: Claims data from a German sickness fund was linked to patient survey data. Outpatient physicians enrolled patients and assessed asthma control using the ACTTM questionnaire. All-cause and asthma-specific healthcare resource use (HCRU)/costs were compared descriptively and based on multivariable models using a continuous ACTTM score.Results: Overall, 492 asthma patients were included (mean age: 53.8, 73.8% female). The mean/median ACTTM score was 19.9/20.7, with 183 patients (37.2%) classified as having uncontrolled asthma (mean ACTTM score<20) Patients with uncontrolled asthma had significantly more hospitalizations (p = .035) and medication prescriptions (p < .001), which resulted in higher total healthcare costs for asthma-related (€1785 vs. €1615; p = .004) and all-cause care (€4695 vs. €4117; p = .009). While controlling for baseline characteristics, multivariable models confirmed a negative association between asthma control and total all-cause healthcare costs (p = .008), total asthma-related costs (p = .008), and costs of medication prescriptions (p = .001). However, no significant association was found for all-cause (p = .062) and asthma-related hospitalization costs (p = .576).Conclusion: Considering continuous patient care, improving asthma control is not only desirable from a clinical perspective, but could also be an effective approach to reduce asthma-related HCRU and cost burden.

Healthcare Resource Utilization and Cost of Patients with Multiple Myeloma in Germany: A Retrospective Claims Data Analysis.

OBJECTIVE: This study aimed to analyze the healthcare resource use (HCRU) and associated costs of multiple myeloma (MM) using German claims data. METHODS: Anonymized claims data from one of the largest sickness funds in Germany were analyzed. Costs and HCRU were calculated from the perspective of the statutory health insurance. To analyze MM-associated incremental costs in a most recent calendar period for an overall MM population (31 March 2018-31 March 2019), a prevalent cohort of MM patients (continuously insured during 01 January 2010 until 31 March 2019 or death; two or more outpatient and/or one inpatient MM diagnoses [ICD-10: C90.0-] and alive on 31 March 2018) was compared with a control group (not diagnosed with MM) employing propensity-score matching. Additionally, to describe MM-associated HCRU and costs for treated patients per line of treatment (lot), a cohort of newly treated patients was considered (≥ 12 months' pre-index period without MM treatment). Therapy lines were determined based on observed days of medication supply, treatment switches, and treatment discontinuations. RESULTS: Overall, 2523 prevalent MM patients (52.0% female, mean age: 71.3 years) and 1673 newly treated MM patients (50.2% female, mean age: 73.0 years) met the selection criteria and were included in the analyses. After matching, a non-MM counterpart could be identified for 2474 prevalent out of 2523 MM patients. MM-associated incremental HCRU was characterized by an increased number of hospitalizations and a higher number of outpatient specialist visits (per patient-year [ppy] 0.48 additional hospitalizations and 3.80 additional specialist visits; p < 0.001), being also drivers of the associated total incremental add-on costs (15,381.09 € ppy, p < 0.001). Among newly treated patients, total direct costs ppy increased as patients received subsequent treatments (1st lot: 67,681,55 €; 4th lot+: 114,934.01 €), driven by outpatient MM prescriptions (1st lot: 28,692.32 €; 4th lot+: 62,980.72 €). CONCLUSION: The economic burden of MM is driven by outpatient prescriptions, inpatient hospitalizations, and outpatient specialist visits. Treatment and overall costs increase substantially when patients move to later lines of treatment.

Use of Biologic Therapies in the Treatment of Asthma - A Comparative Real World Data Analysis on Healthcare Resource Utilization and Costs Before and After Therapy Initiation.

Background: Asthma is one of the most common chronic diseases in Germany. While many patients achieve asthma control under standard therapies, some patients still experience exacerbations and persistent airway obstructions. Thus, further pharmacological treatment is needed, and biologics could fill this gap, as they have shown clinical benefit in patients with severe asthma. Therefore, this real-world study aimed to compare healthcare resource utilization (HCRU) and associated costs before and after biologic therapy initiation. Methods: A retrospective claims data analysis has been conducted on adult asthma patients who initiated a long-term biologic therapy between January 2015 and June 2018. Patients were therapy-naïve to biologics for at least 12 months. HCRU and cost incurred by patients during 12 months before and after therapy initiation were compared. Results: Overall, 571 asthma patients initiated a biologic therapy during the observational period (316 omalizumab, 232 mepolizumab, 16 benralizumab, and 7 reslizumab). Patients had a mean age of 54.86 (62.70% female), and the majority (93.70%) received at least one follow-up prescription of their index-biologic agent within one year. During baseline, patients received on average 2.75 OCS prescriptions compared to 2.17 during follow-up. Most patients received less or the same amount of OCS after therapy initiation. Moreover, hospitalizations and asthma-related sick leave days decreased significantly. The average total costs per patient were €6618.90 during baseline and €22,832.33 during follow-up. Biologics mainly drove the increase; however, hospitalization costs were reduced significantly (€2443.37 vs €1941.93; p<0.001). Conclusion: Our study demonstrates an improved asthma control due to the initiation of a biologic therapy in terms of decreased hospitalization frequency, OCS consumption, and sick leave days. However, biologics are associated with high costs for healthcare providers during the first year after initiation. Therefore, short- and long-term clinical benefits and financial burden must be considered in the overall context of healthcare.

Extent of non-adherence and non-persistence in asthma patients: analysis of a large claims data set.

OBJECTIVE: The objective of this study was to assess non-adherence (NA) and non-persistence (NP) to long-acting asthma medications in Germany by differentiating between measurement of NA in periods of therapy continuation and measurement of NP in therapy-naïve patients. METHODS: We analyzed treatment adherence to long-acting asthma medication using German claims data for periods of treatment continuation based on the medication possession ratio (MPR) and the proportion of days covered. Persistence was assessed in treatment-naïve patients. Outcomes were observed from the date of the first to the last prescription within a 12-month period. Both NA and NP analyses considered prescription supply, using either defined daily dosages, or prescribed daily dosages derived from a medical chart review. RESULTS: We identified 52,508 asthma patients (mean age: 40.1, 58.4% female) who received at least two long-acting asthma prescriptions within 12 months; 50,660 treatment-naïve patients were included in the NP analysis (mean age: 39.7, 58.8% female). The mean 12-month MPR was 38.5% (89.4% NA according to MPR ≤ 80%) and the average proportion of days covered was 40.4% (85.9% NA). Agent-specific MPR and NA rates varied between 31.8% (91.8% NA) and 56.2% (71.6% NA). The average weighted-MPR increased to 53.1% when using the prescribed daily dosage. Based on a > 90-day gap definition, 86.7% of patients were considered non-persistent after 12 months (>180: 72.3%). When using prescribed daily dosages, NP rates ranged from 66.7 to 78.5%. CONCLUSION: High levels of treatment NA and NP indicate a substantial need to improve adherence and persistence to long-acting asthma medication in Germany.

Identifying the Causes Increasing the Risk of Non-Adherence in Adult Patients with Asthma: An Analysis Combining Patient Survey Data with German Claims Data.

BACKGROUND: There exists a range of treatments in the management of asthma. Non-adherence to these medications has been identified as a factor negatively impacting the effects of treatment. OBJECTIVE: The objective of this study was to identify the potential barriers to medication adherence among adult patients with asthma in Germany. PATIENTS AND METHODS: A multi-center observational study was conducted addressing adult patients with asthma who were prescribed regular maintenance medication between 2014 and 2016. Data were derived from physicians' documentation as well as claims data, which were linked to the above primary observational data, and patient survey data. Adherence barriers were assessed by the validated Adherence Barriers Questionnaire, both descriptively and in a logistic regression framework. Cluster analysis identified distinct patient groups with respect to the relevance of specific adherence barriers. RESULTS: We included 524 patients with asthma (mean age 53.1 years, 74.6% female, 43.1% allergic asthma, 37.6% nonallergic, 19.3% mixed). Most of the participants reported to face at least three barriers (61.1%). Frequently reported barriers were the perception that medications are all harmful (53.6% of the participants), the burden of medication co-payment (44.1%), positive perception about current health status (39.9%), feeling of depression (30.9%), and the fear of side effects (27.5%). Four distinct patient clusters could be identified: cluster 1 with a low number of barriers (28.6% of participants), cluster 2 (11.6%) with a comparably high number of existing barriers, cluster 3 with high importance of depression as a barrier (27.3% of participants), and cluster 4 that was dominated by the perception that medications are all harmful (32.5% of participants). CONCLUSIONS: Results of this study provide important insights for further development of adherence programs, which should focus on distinct patients' clusters that differ substantially in the relevance of specific adherence barriers.

A DELPHI study on aspects of study design to overcome knowledge gaps on the burden of disease caused by serogroup B invasive meningococcal disease.

BACKGROUND: Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. METHODS: We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. RESULTS: Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients' QoL. CONCLUSIONS: Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany.

INTRODUCTION: Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany. METHOD: A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%. RESULTS: The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case. DISCUSSION: The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

Epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany: a systematic review.

OBJECTIVES: Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. The objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany. METHODS: We systematically reviewed studies published since 2000. The literature search was conducted using PubMed and EMBASE. Also, we used German notification data to give an up-to-date overview of the epidemiology of the four diseases under consideration. RESULTS: Thirty-six studies were included in our review. Results suggest that there is still considerable morbidity due to childhood diseases in Germany. Studies providing cost estimates are scarce. Comparative analyses of different data sources (notification data vs. claims data) revealed a potential underestimation of incidence estimates when using notification data. Furthermore, several studies showed regional differences in incidence of some of the diseases under consideration. CONCLUSIONS: Our findings underline the need for improved vaccination and communication strategies targeting all susceptible age and risk groups on a national and local level.

Chlamydia screening is not cost-effective at low participation rates: evidence from a repeated register-based implementation study in The Netherlands.

OBJECTIVE: In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data. METHODS: A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed. RESULTS: In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses. CONCLUSIONS: It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening.

Direct cost analysis of intensive care unit stay in four European countries: applying a standardized costing methodology.

OBJECTIVES: The objective of the present study was to measure and compare the direct costs of intensive care unit (ICU) days at seven ICU departments in Germany, Italy, the Netherlands, and the United Kingdom by means of a standardized costing methodology. METHODS: A retrospective cost analysis of ICU patients was performed from the hospital's perspective. The standardized costing methodology was developed on the basis of the availability of data at the seven ICU departments. It entailed the application of the bottom-up approach for "hotel and nutrition" and the top-down approach for "diagnostics," "consumables," and "labor." RESULTS: Direct costs per ICU day ranged from €1168 to €2025. Even though the distribution of costs varied by cost component, labor was the most important cost driver at all departments. The costs for "labor" amounted to €1629 at department G but were fairly similar at the other departments (€711 ± 115). CONCLUSIONS: Direct costs of ICU days vary widely between the seven departments. Our standardized costing methodology could serve as a valuable instrument to compare actual cost differences, such as those resulting from differences in patient case-mix.

Cost-effectiveness of adjunctive eptifibatide in patients undergoing coronary stenting in Germany.

OBJECTIVE: To determine the cost-effectiveness of adding eptifibatide to the standard treatment for selected high-risk patients undergoing coronary stenting in Germany. Furthermore, to investigate the impact of several extrapolation methods on the results. METHODS: A Markov model was developed to reflect the clinical events in this specific patient population, including target vessel revascularization, myocardial infarction, and death. To extrapolate clinical data beyond 1 year, a linear, an exponential, and a Weibull survival curves were estimated. Patient characteristics and transition probabilities were derived from a high-risk subgroup of the ESPRIT trial; patient-level utility data came from a published Dutch study. Costs were calculated from a hospital and from a third-party payer perspective. RESULTS: For both perspectives, the additional treatment with eptifibatide is the considered dominant alternative. The incremental net benefit of its use exceeds €10,000 for both perspectives. Results proved stable in probabilistic sensitivity analysis as well as under the different extrapolation scenarios. CONCLUSIONS: Eptifibatide is likely to be dominant strategy with 77.7 and 96.7% of the simulations leading to QALYs gained and generating cost savings from both the hospital and the third-party payer perspective. Eptifibatide offsets its additional treatment costs by avoiding costly repeat procedures and leads to positive QALY gains by preventing cardiovascular events lending themselves to transient or permanent lower quality of life. The method used to extrapolate the short-term risks did not impact on results, mainly due to similar clinical risk profiles between the two treatment groups in the long term.

Mortality, morbidity and costs attributable to smoking in Germany: update and a 10-year comparison.

OBJECTIVE: To assess the negative health consequences and associated costs of cigarette smoking in Germany in 2003 and to compare them with the respective results from 1993. METHODS: The number of deaths, years of potential life lost (YPLL), direct medical and indirect costs caused by active cigarette smoking in Germany in 2003 is estimated from a societal perspective. The method is similar to that applied by Welte et al, who estimated the cost of smoking in Germany in 1993. Therefore, a direct comparison of the results was possible. Methodological and data differences between these two publications and their effect on the results are analysed. RESULTS: In 2003, 114,647 deaths and 1.6 million YPLL were attributable to smoking. Total costs were euro21.0 billion, with euro7.5 billion for acute hospital care, inpatient rehabilitation care, ambulatory care and prescribed drugs; euro4.7 billion for the indirect costs of mortality; and euro8.8 billion for costs due to work loss days and early retirement. From 1993 to 2003, the proportionate mortality attributable to smoking remained relatively stable, rising from 13.0% to 13.4%. The smoking-attributable deaths in men is lowered by 13.7% whereas that in women increased by 45.3%. Total real direct costs rose by 35.8%, and total real indirect costs declined by 7.1%, rendering an increase of 4.7% to real total costs. Accountable factors are changes in cigarette smoking prevalence and in disease-specific mortality and morbidity, as well as a rise in general healthcare expenditure. CONCLUSIONS: Despite the growing knowledge about the hazards of smoking, the smoking-attributable costs increased in Germany. Further, female mortality attributable to smoking is much higher than it was in 1993.

Prediction of costs, effectiveness, and disease control of a population-based program using home sampling for diagnosis of urogenital Chlamydia trachomatis Infections.

OBJECTIVE: To estimate the incremental effects and costs of a home sampling screening approach for Chlamydia trachomatis over the current in-office screening practice in Denmark. GOALS: To assess the effect of a new screening strategy. STUDY DESIGN: A dynamic Monte Carlo model estimated prevalence and incidence over 10 years for a home sampling screening program and the current in-office screening. Subsequently, the incremental number of major outcomes averted (MOA) and the related direct and indirect costs were estimated. RESULTS: Infection prevalence after 10 years was 1.0% with a home sampling program and 4.2% with the current in-office screening practice. The total costs per MOA reached 3186 US dollars during the first year of the home sampling strategy, but in year 4, the accumulated indirect costs offset the direct costs, and the program henceforth saved society costs. CONCLUSIONS: Home sampling should be considered a relevant alternative to the current practice of in-office screening.

Combination vaccine against invasive meningococcal B and pneumococcal infections: potential epidemiological and economic impact in the Netherlands.

BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases occur in very young infants. A combination vaccine consisting of 9-valent conjugated pneumococcal and meningococcal B components is currently being developed. The aim of this study was to estimate the potential impact and cost effectiveness from the societal perspective of vaccinating infants in The Netherlands with this combination pneumococcal and meningococcal B vaccine versus no vaccination. METHODS: A Markov cycle model was developed using epidemiological and healthcare resource use data from 1996 to 2001. This model was used to project the annual costs, benefits and health gains associated with vaccinating all newborns. The base year for the costing was 2003 and all costs and health effects were discounted at 4%. The results of the analysis are expressed in costs per QALY and both probabilistic and univariate sensitivity analyses were used to identify the robustness of the results. RESULTS: Annually, an average of 755 cases of invasive pneumococcal and meningococcal B infection occurred in infants aged 0-10 years in The Netherlands. Introduction of the combination vaccine would prevent 201 cases of meningococcal B meningitis and 165 cases of invasive pneumococcal disease per year. Additionally, 3410 cases of pneumococcal pneumonia and 46,350 cases of otitis media would be prevented. Vaccination would save 35 lives per year and prevent 71 cases of severe sequelae. This translates into 860 life-years gained, or 1128 QALYs gained. Alongside these health gains, vaccination would prevent euro 17,681,370 of direct medical and indirect costs attributable to meningococcal and pneumococcal infections in The Netherlands. Depending on vaccine price, cost effectiveness varied from euro 3160 (vaccine price per dose euro 20) to euro 32,170 (vaccine price euro 60 per dose) per QALY. Base-case cost effectiveness (vaccine price euro 40) was euro 17,700 per QALY. The model was most sensitive to changes in incidence, vaccine price and duration of protective efficacy. CONCLUSION: Our results suggest that the introduction of a combination meningococcal B and pneumococcal vaccine into the Dutch infant vaccination programme is potentially cost effective compared with no vaccination.

The role of economic evaluation in vaccine decision making: focus on meningococcal group C conjugate vaccine.

In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic evaluation played in the decision to introduce the conjugate vaccine into either the routine childhood vaccination schedule, as a mass vaccination 'catch-up' campaign or not at all. A literature review was performed and experts from these countries were contacted. For six countries, we identified published economic evaluations for meningococcal C conjugate vaccination. In four of them (Australia, Canada [Quebec], The Netherlands and the UK) the analyses were performed before a decision about the use of the conjugate vaccine was made. In all of these countries, the economic evaluation offered guidance as to the most efficient way to add the conjugate vaccine to the routine infant immunisation schedule and, in three countries, this advice was adopted by decision makers. In Portugal and Switzerland, initial vaccination decisions were made without the economic evaluations that are influencing current decision making. Of the countries without economic evaluations, six implemented vaccination programmes. Overall, there was a positive correlation between the reported incidence of meningococcal C disease and (a) the decision to vaccinate and (b) performing an economic evaluation. All economic evaluations were modelling studies. The reported cost-effectiveness ratios were sensitive to the age of vaccination, the future meningococcal incidence, vaccine price and some methodological characteristics that varied widely between studies making direct comparisons difficult. In conclusion, in almost all countries where economic evaluations for meningococcal C conjugate vaccinations have been conducted, their results had an important role in the decision-making process. However, in most countries with strongly increasing meningococcal incidence, public health considerations took precedence. In order to improve the international comparability of such studies, firmer national and international modelling guidelines and better adherence to such guidelines seem necessary.

Costs and effects of chlamydial screening: dynamic versus static modeling.

OBJECTIVE: The objective of this study was to assess the impact of modeling type on the economic evaluation of screening programs for asymptomatic Chlamydia trachomatis infections. STUDY: We compared a stochastic network simulation model (dynamic model) with a decision analysis model (static model) for estimating the cost-effectiveness of an opportunistic screening program. The influence of the model type on the required data, the computed results, and the sensitivity of model parameters were investigated. RESULTS: When compared with static modeling, dynamic modeling yielded different cost-effectiveness ratios and identified other optimal screening strategies as it considers changes in the force of infection caused by screening. However, it is more complex, data- and time-demanding, and more sensitive to some parameters affecting the force of infection than static modeling. CONCLUSIONS: Dynamic models should be applied for the economic evaluation of prevention measures that have the potential to lower the force of infection such as large-scale chlamydial screening programs.