Economic evaluation of adverse events of dabrafenib plus trametinib versus nivolumab in patients with advanced BRAF-mutant cutaneous melanoma for adjuvant therapy in Germany.

Background: Adjuvant treatment options have become the standard therapy for stage III and IV resectable cutaneous melanoma. Two recent studies led to the registration of dabrafenib and trametinib as targeted therapies for BRAF-mutated melanoma, and of immunotherapy with nivolumab irrespective of BRAF-mutation status. Both therapies have different spectrums of adverse events. Objective: To estimate the financial impact of side effects from the perspective of the German statutory sick funds to compare both therapeutic options and to relate the burden to the overall costs of the treatment. STUDY DESIGN AND SETTING: Thirty-six adverse event categories for the combination of dabrafenib and trametinib ('combi treatment') and for nivolumab were extracted from the original publications of the studies named COMBI-AD and CheckMate 238. PATIENTS AND INTERVENTION: For all event categories a diagnosis and therapy recommendation were determined according to current national or international guidelines or from leading German textbooks. MAIN OUTCOME MEASURE: The resulting diagnostic steps, treatments, and therapies were evaluated with unit costs based on the German fee schedule for ambulatory physicians, the German G-DRG scheme, and the German drug price list. RESULTS: The number of events with nivolumab per one hundred treatments amounted to 3.8 mandatory hospitalizations, 3.5 emergency care events and 0.8 life-threatening events. For the combi treatment, the respective number of events per one hundred treatments was 2.7, 1.8, and 0.5. The overall cost burden was calculated as €899 for nivolumab and €861 for combi-treatment. CONCLUSION: The treatment of adverse events resulting from adjuvant melanoma therapy showed comparable costs for both therapies.

Guidelines versus reality: is coronary stent application in three-vessel disease standard or the exception?

The national guidelines for treatment of chronic coronary heart disease (CHD) recommend surgical coronary aortic bypass grafting (CABG) rather than percutaneous coronary intervention (PCI) for patients with a coronary three-vessel disease. The epidemiology of three-vessel CHD and data about the application of different revascularisation strategies raise suspicion of deviation from the guidelines in the treatment of those patients. Claims data containing records of almost 10 million patients of the largest German statutory health insurance fund (Techniker Krankenkasse) were utilised to measure adherence to the guidelines for treatment of groups of patients with one-, two-, and three-vessel CHD, respectively. The impact of age, sex, and comorbidity on each patient's revascularisation procedure was investigated as well. There was no significant difference in the rate of PCI between the groups. In conclusion, the hypothesis that patients with a coronary three-vessel disease are not always treated according to the recommendations of the national guidelines could not be disproved by this study. Finally, the results of this study suggest that the best revascularisation strategy for each patient with two- and three-vessel disease should be decided upon by an interdisciplinary discussion between both cardiologists and cardiac surgeons.

[Cost-Effectiveness of Pharmacological Smoking Cessation Therapies - A Systematic Literature Review]. / Kosteneffektivität von pharmakologischen Raucherentwöhnungsmaßnahmen ­ ein systematisches Literaturreview.

Aim of the Study: Through the promotion of smoking cessation premature mortality can be prevented. Therefore it is necessary to provide effective and cost-effective smoking cessation interventions. In Germany the cost of pharmacological smoking cessation measures are not yet reimbursed by the statutory health insurance. The aim of this study is to present the evidence on the cost-effectiveness of already approved pharmacological smoking cessation therapies and to evaluate their quality. Method: A systematic literature research was conducted in the databases by DIMDI (Medline, Embase, etc.) in April 2013 (update April 2014). The study research was focused on studies for cost effectiveness of nicotine replacement therapy (NRT), varenicline and bupropion. The assessment of study quality was performed using the "Quality of Health Economic Studies" (QHES) instrument. Results: 33 Of the original 10 340 identified studies were finally included. The majority of the studies show that an additional prescription of NRT or bupropion to a medical consultation is a cost-effective strategy. In addition, in most studies varenicline is a dominant strategy compared to bupropion. Overall, the study quality was found to be very heterogeneous between 45 and 80 points (Ø 63.7 points). Conclusion: The studies show that treatment with varenicline is the most cost effective strategy followed by bupropion and the NRT. However, the studies can only be compared inadequately due to different levels of age and country-specific intervention costs.

Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with juvenile idiopathic arthritis (JIA) in Europe. METHODS: We conducted a cross-sectional study of patients with JIA from Germany, Italy, Spain, France, the United Kingdom, Bulgaria, and Sweden. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D-5L) questionnaire. RESULTS: A total of 162 patients (67 Germany, 34 Sweden, 33 Italy, 23 United Kingdom, 4 France, and 1 Bulgaria) completed the questionnaire. Excluding Bulgarian results, due to small sample size, country-specific annual health care costs ranged from €18,913 to €36,396 (reference year: 2012). Estimated direct healthcare costs ranged from €11,068 to €22,138; direct non-healthcare costs ranged from €7837 to €14,155 and labor productivity losses ranged from €0 to €8715. Costs are also shown to differ between children and adults. The mean EQ-5D index score for JIA patients was estimated at between 0.44 and 0.88, and the mean EQ-5D visual analogue scale score was estimated at between 62 and 79. CONCLUSIONS: JIA patients incur considerable societal costs and experience substantial deterioration in HRQOL in some countries. Compared with previous studies, our results show a remarkable increase in annual healthcare costs for JIA patients. Reasons for the increase are the inclusion of non-professional caregiver costs, a wider use of biologics, and longer hospital stays.

Analysis of Driving Factors of Willingness to Use and Willingness to Pay for Existing Pharmacological Smoking Cessation Aids Among Young and Middle-Aged Adults in Germany.

BACKGROUND: Smoking cessation is a challenging task with a high risk of relapse. Depending on the choice of medication and duration of therapy, the costs of using a smoking cessation aid can be high. Additionally, these costs are not covered by health insurance in Germany. Information on willingness to use (WTU) and willingness to pay (WTP) for smoking cessation aids is valuable for developing different smoking cessation strategies. OBJECTIVES: The study analyses WTU and WTP for three pharmacological smoking cessation aids (nicotine replacement therapy (NRT), bupropion and varenicline) among young and middle-aged adults in Germany and attempts to determine their major driving factors. METHODS: Two cross-sectional internet-based surveys of smokers over 18 years of age were conducted in 2014 and 2015 in Germany. Respondents were asked about smoking-related issues and WTU and WTP for each therapy. The contingent valuation method with payment cards was used to measure WTP. Descriptive statistics, logistical regression and accelerated failure-time regression models were performed. RESULTS: The total sample size is 505. Half of the respondents are willing to use NRT and one-third are willing to use bupropion and/or varenicline. WTU induces positive WTP; however, the magnitude of WTP is beneath the market price. WTU significantly increases with a higher addiction level and if smokers have previously heard about the therapy. CONCLUSION: This study indicates different points to be considered for policy development. Promotion information and improving awareness about medication aids might increase WTU, and development of monetary incentives for young smokers could create a better chance for successful smoking cessation.

[Age- and Gender-specific Costs as Well as Drug Therapies of ADHD Patients]. / Alters- und geschlechtsspezifische Kosten sowie die Versorgung mit medikamentösen Therapien von ADHS-Patienten.

UNLABELLED: Backround and Objectives: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed mental disorders in children and adolescents. The rate of persistence into adulthood varies up to 60% and shows the importance of the disease. Here we present age-stratified cost information on adult patients, as well as data on occupational therapy, medication and multimodal treatment. Furthermore, we also investigated retrospectively if methylphenidate was prescribed for adults already before its approval in 2011. METHODS: Claims data of a major German insurance fund (Techniker Krankenkasse) was available. Inclusion criteria were patients with ADHD diagnosis, either hospitalized or treated on an outpatient basis in 2006, 2007 and 2008 and insured over this period. This enabled identifying this disease as chronic. The data were analyzed as part of a control group design (1:3). Cost differences were examined as also the odds ratios for the burden of comorbidities and use of atomoxetine and methylphenidate. RESULTS: 77.9% of the identified ADHD patients were male (mean age: 16.5 years ±11.1). The mean total costs of patient treatment were € 2,032 (±4,112). The odds ratio was highest for the indication developmental disorders of scholastic skills (15.4) and differed between the sexes (female: 24.0 vs. male: 14.2). Drug prescription was higher in male than in female patients (atomoxetine: 7.2 vs. 5.9% and methylphenidate 59.1 vs. 48.4%). CONCLUSIONS: This study provides important insights into the importance of the adult ADHD collective. There were increasing resource consumption identified in adult ADHD patients. In addition, methylphenidate was used off-label for treating adults already before 2011 and its approval in 2011 provided increased certainty for physicians regarding prescription of this drug.

Cost of poor adherence to anti-hypertensive therapy in five European countries.

The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This study is the first attempt to estimate the economic impact of non-adherence amongst patients with diagnosed hypertension in Europe, using data from five European countries (Italy, France, Germany, Spain and England).

A systematic review of cost-effectiveness of monoclonal antibodies for metastatic colorectal cancer.

UNLABELLED: Metastatic colorectal cancer (mCRC) imposes a substantial health burden on patients and society. In recent years, advances in the treatment of mCRC have mainly resulted from the introduction of monoclonal antibodies (MoAbs). However, the application of these MoAbs considerably increases treatment costs. The objective of this article is to review and assess the economic evidence of MoAB treatment in mCRC. A systematic literature review was conducted and cost-effectiveness (CE) as well as cost-utility-studies were identified. For this, Medline, Embase, SciSearch, Cochrane, and nine other databases were searched from 2000 through February 2013 for full-text publications. The quality of the studies was assessed via a validated assessment tool (Quality of Health Economic Studies (QHES)). A total of 843 publications were screened. Of those, 15 studies involving the MoAbs bevacizumab, cetuximab and panitumumab met all inclusion criteria. Four studies analysed the CE of first-line treatment with bevacizumab and nine the CE of cetuximab in subsequent treatment lines. Two studies dealt with the CE of panitumumab. The analysis of sequential regimes and the direct comparison of two MoABs were analysed by only one study each. The quality of the included studies was high with the exception of one study. CONCLUSIONS: The treatment with bevacizumab, cetuximab and panitumumab is mainly considered to be not cost-effective in patients with mCRC. However, testing for Kirsten ras oncogene (KRAS) mutation prior to the treatment with cetuximab or panitumumab is found to be clearly cost-effective compared to no testing. Future research should focus on the CE of first-line treatment with cetuximab or panitumumab and studies on upcoming agents like regorafenib and aflibercept.

[Calculation of disease-related costs in claims data analyses with the example of attention-deficit hyperactivity disorder. Comparison of methods]. / Die Berechnung indikationsspezifischer Kosten bei GKV-Routinedatenanalysen am Beispiel von ADHS. Ein Methodenvergleich.

Claims data have proven useful for carrying out cost-of-illness studies. To avoid overestimating disease-related costs, only those costs that are related to a specific disease should be considered. The present study demonstrates two basic approaches for identifying disease-related costs. Using the example of attention-deficit hyperactivity disorder (ADHD), the advantages and drawbacks of expert-based approaches and those based on control groups are compared. Anonymized data from the "Techniker Krankenkasse" for 2008 were available for the study. The study population encompassed all ADHD patients and a control group that was five times bigger. Additionally, a systematic literature review was carried out on 65 relevant studies. Compared with the control group, disease-related costs were EUR 2,902 per ADHD patient on average. However, using the expert-based approach, costs were established to be EUR 923 lower. This is mainly because a comparison with an appropriate control group incorporates all costs for possible comorbidities and concomitant diseases. Both approaches have specific advantages and drawbacks, and when planning studies the respective limitations need to be considered.

[Therapy of rheumatoid arthritis with methotrexate. Claims data analysis of treatment patterns]. / Therapie der rheumatoiden Arthritis mit Methotrexat. Analyse von Versorgungsaspekten anhand von GKV-Routinedaten.

Methotrexate (MTX) is the most important disease-modifying antirheumatic drug (DMARD) and is recommended by national and international guidelines as the first choice for treatment of rheumatoid arthritis (RA). Recent studies reporting prescription data of MTX captured only patients who were treated by rheumatologists. Therefore, the aim of the present study was to analyse several aspects of the prescription of MTX based on claims data. Outpatient and inpatient diagnoses as well as prescription data was available for 9579 RA patients for the years 2005-2008. Of the patients 45% were treated exclusively with parenteral MTX, 8% were treated exclusively with oral MTX and 48% switched between both forms of application. The average weekly dosage presribed in 70% of the patients was between 10 and 25 mg. The most common DMARD combination was MTX plus leflunomide with 16%. In 16% RA patients were treated with a combination of MTX and TNF-α inhibitors. Glucocorticoids were prescribed temporarily in 81% together with MTX and supplementation with folic acid was given only in 65%. The results of this study provide important insights into the drug supply of MTX to RA patients in the German statutory health care sector. In particular, the high frequency of prescriptions of parenteral MTX and the inadequate prescription of folic acid are different from the recently published multinational recommendations of the 3E initiative for the use of MTX.

[Decision support through economic evaluation from the perspective of science in Germany]. / Entscheidungsunterstützung durch gesundheitsökonomische Evaluation in Deutschland aus Perspektive der Wissenschaft.

For decades, economic evaluation studies, or cost-benefit analyses (CBA), have been a tool for decision support in the use of public funds. Despite this, in the last few years, debates on the inclusion of CBAs in the German health care system have paid little attention to the findings and practical experiences of scientific research. CBAs - especially the QALY - were instead represented a priori as "unfair" and "discriminatory." Today they have virtually no meaning when it comes to allocation and pricing decisions about publicly funded health services. Of course, CBAs are based on value judgments, which have to be communicated. They can lead to allocations that violate the minimum standards of justice. Here, distributive requirements and criteria are needed and must be developed in an interdisciplinary discourse. However, a general waiver of CBA does not make decisions about the allocation of resources easier, especially since its involvement can contribute to more openness and transparency in the system. Accordingly, for Germany a dual approach is recommended: an interdisciplinary exploration of the methodological foundations of economic evaluation and a consistent application of these in healthcare decision-making.

[Implementation of the new German job role code and its application in claims data analysis. Possibilities and limitations]. / Einführung des neuen Tätigkeitsschlüssels und seine Anwendung in GKV-Routinedatenauswertungen. Möglichkeiten und Limitationen.

In recent years, claims data analyses have become of increasing importance in several scientific disciplines in Germany. In specific research projects, it can be necessary to refine and to standardize the results by socioeconomic data. Information about graduation, social status, and occupation are provided by the German job role code for all people insured by statutory health insurance. During recent years, the working scheme has changed and new professions have appeared. Therefore, there has been a discussion about actualization and modification of the job role code. Since December 2011, an actualized job role code with an extensive set of new information is available. In addition, a new classification of professions is available in Germany which was considered in the design of the new job role code. The aim of this overview is to describe the structure of the new job role code as well as to discuss possible uses and limitations.

[Costs of illness and health-related quality of life for community-acquired pneumonia--a systematic review]. / Krankheitskosten sowie gesundheitsbezogene Lebensqualität (hrQoL) bei ambulant erworbener Pneumonie (CAP)--ein systematisches Review.

AIM: There are only very limited data available on the costs and health-related quality of life (hrQoL) of patients with community-acquired pneumonia (CAP) in Germany. The aim of this review was to identify studies in the international literature regarding the costs and hrQoL of CAP. METHOD: In March 2010, a systematic literature search was performed. The acquired literature was evaluated separately for costs of illness and/or hrQoL analyses followed by a structured discussion of the findings. RESULTS: A total of 172 references was identified. Sixteen publications on the cost of illness for CAP and five publications on hrQoL met the selection criteria and were included in the present review. CONCLUSION: There are only very limited and, furthermore, outdated data available on the costs and quality of life impacts of CAP. Hence, further research is urgently needed to fill this lack of evidence.

[Economic valuation of physician contacts in German outpatient care of COPD. Results from a survey of general practitioners and respiratory specialists]. / Ökonomische Bewertung ambulanter Arztkontakte von COPD-Patienten in Deutschland. Ergebnisse einer Befragung von Allgemeinmedizinern und Pneumologen.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with considerable morbidity and mortality and features a substantial economic burden. METHODS: This article analyses the frequency of physician contacts and commonly provided services in the outpatient care of patients with COPD in Germany. Information on characteristic health care delivery in case of patients with COPD has been further used to construct basic scenarios of outpatient resource use. RESULTS: Altogether, 34 out of 150 respiratory specialists and 55 out of 350 general practitioners participated in the survey (response rates of 22.7 and 15.7%, respectively). Results point out, that the number of commonly provided services (a) is limited to a very basic set, (b) does not differ substantially according to severity of COPD, and (c) does not substantially vary between the stable phase of the disease and the presence of exacerbations. CONCLUSIONS: Despite its low level of evidence, the use of expert opinion can serve as a valuable and legitimate tool; especially when the literature does not provide any or only outdated information.

[Costs of ulcerative colitis within the German Statutory Health Insurance]. / Kosten der Colitis ulcerosa--eine Kalkulation aus der Perspektive der Gesetzlichen Krankenversicherung.

BACKGROUND AND OBJECTIVES: Studies estimating the costs of ulcerative colitis (UC) within the German setting are limited. The aim of this cross-sectional study was to collect data on the overall costs arising from the care of patients with UC and to quantify this expenditure as incurred by the German Statutory Health Insurance (SHI). METHODS: Between March 2006 and July 2007 patients from 24 ambulatory gastroenterologist practices and two hospitals were enrolled in an internet-based database. Outpatient and inpatient visits, all procedures as well as drug usage were obtained from the collected data and evaluated from the perspective of the SHI, taking also into account statutory discounts and patients' co-payments. The year 2007 was selected as the pricing period. RESULTS: Data from 519 patients with UC were collected (gender ratio 1:1; average age 46 years). The average annual cost per UC patient to the SHI is 2,477.72 Euro, 74 % of this amount results from drug usage, 10 % from inpatient care and another 10 % from ambulatory procedures. Costs increase with the severity of the disease. CONCLUSION: This is the first study to calculate the costs caused by UC and payed by the SHI in Germany. Future research should focus on collecting longitudinal data and also on comparing the resources used in the care of patients with other inflammatory bowel diseases, such as Crohn's disease.

[Costs of Crohn's disease in Germany from the perspective of the Statutory Health Insurance]. / Die direkten Kosten der Versorgung von Patienten mit Morbus Crohn aus der Perspektive der Gesetzlichen Krankenversicherung.

INTRODUCTION: Data concerning treatment reality in patients with Crohn's disease (CD) are limited in Germany. The aim of this cross-sectional study was to collect resource use data due to CD and quantify these from the perspective of the Statutory Health Insurance in Germany. METHODS: Between March 2006 and July 2007 the patients from 24 ambulatory gastroenterological specialist practices and 2 hospitals were enrolled in an internet-based online database. Based on the collected data, the outpatient and inpatient visits, all procedures as well as medication usage were determined and evaluated from the perspective of the Statutory Health Insurance taking also into consideration patient co-payments, company and pharmacy discounts. 2007 was selected as the price year. RESULTS: Data from 511 CD patients were collected, with 37 % being male. Patients were on average 41 years old. According to the calculations, an average CD patient in Germany causes costs of 3767.26 euro from the perspective of the Statutory Health Insurance. 68.5 % are medication costs, 20.5 % result from inpatient care. The costs increase with the severity of the disease. DISCUSSION: This is the first study to calculate costs due to CD (3767 euro/year) from the perspective of the Statutory Health Insurance in Germany. To illustrate the costs from the societal perspective, indirect costs need to be included in the calculation in future studies.

[Appraisal of resource use in the German health-care system from the perspective of the statutory health insurance]. / Bewertung von Ressourcenverbräuchen im deutschen Gesundheitswesen aus Sicht der Gesetzlichen Krankenversicherung.

This paper gives a systematic overview of resource use that is relevant within the German health-care system from the perspective of the statutory health insurance and how these resource uses should be priced in economic analyses. This includes all relevant cost domains from ambulatory and inpatient care as well as a detailed description of relevant data resulting from drug usage. For prescriptions the legal framework (e.g., reference pricing) is applied to list all relevant co-payments or discounts (e.g., for pharmaceutical companies) which have to be considered in patented as well as off-patent drugs. The same method is applied for ambulatory services [taking the universal remuneration scheme (EBM) into account] as well as for inpatient stays (discussing certain characteristics of the German DRG system). As a result, for the first time, a pragmatic as well as a practical approach is presented to value resource usage within the German health care system in future studies from the perspective of the statutory health insurance or, in other words, the sickness funds.

Personal and economic burden of late-stage rheumatoid arthritis among patients treated with adalimumab: an evaluation from a patient's perspective.

OBJECTIVES: This study evaluated the patients' perspective of burden of disease among 505 patients with severe, long-standing rheumatoid arthritis receiving adalimumab. METHODS: Health-related quality-of-life and resource use data were collected during a 144-week open-label study. RESULTS: Adalimumab maintained pain control and reduced the duration of morning stiffness. Work impairment decreased and work productivity was maintained over the duration of the study. Costs were estimated at approximately 2100 euros over the course of the study, and personal help and transportation costs comprised a large percentage of total costs. CONCLUSIONS: These results suggest that adalimumab could improve many aspects of a patient's burden of disease.

[Modelling of the costs of productivity losses due to smoking in Germany for the year 2005]. / Modellierung der Produktivitätsausfallkosten als Folge des Rauchens in Deutschland für das Jahr 2005.

PURPOSE: The aim of this study was to estimate disease-related productivity costs attributable to smoking in the year 2005 in Germany. METHODS: The calculation was based on the updated relative smoking-related disease risk found in the US Cancer Prevention Study II combined with data on smoking prevalence for Germany. With this, smoking-attributable cases resulting in premature mortality, invalidity, and temporal disability to work could be estimated. Neoplasms, diseases of the circulatory and the respiratory systems as well as health problems in children younger than one year were considered in the analysis. The human capital approach was applied to calculate years of potential work loss and productivity costs as a result of smoking. Various sensitivity analyses were conducted to test for robustness of the underlying model. RESULTS: Based on the assumptions within the model, 107,389 deaths, 14,112 invalidity cases, and 1.19 million cases of temporary disability to work were found to be due to smoking in 2005 in Germany, respectively. As a result, productivity costs of 9.6 billion were caused by smoking. CONCLUSIONS: The model showed that smoking has a high financial effect. Even so, further analyses are necessary to estimate an overall impact of smoking on the German society.