Application study of the EQ-5D-5L in oncology: linking self-reported quality of life of patients with advanced or metastatic colorectal cancer to clinical data from a German tumor registry.

BACKGROUND: The EQ-5D-5L questionnaire is used in oncology to generate health-related quality of life (HRQoL) weights and corresponding health states. The purpose was to explore the relationship between demographic and clinical characteristics and HRQoL among advanced or metastatic colorectal cancer (CRC) patients by linking clinical data of a German CRC registry to self-reported HRQoL measures from the EQ-5D-5L. METHODS: The study sample included patients with advanced or metastatic CRC currently recruited in the German Tumor Registry Colorectal Cancer. The EQ-5D-5L was administered once to patients who were at the start or at later stages of palliative treatment. Data on comorbidities, disease-specific health states, symptoms, and treatment status were drawn from the registry. Multivariate regression analyses were performed to explore the impact of patient and disease characteristics on HRQoL. RESULTS: In total, n = 433 questionnaires were included in the data analysis. Mean age of patients was 66.3 years and 61.2% were male. The mean EQ-5D-5L utility score was 0.82 and the mean EQ-5D-5L VAS score was 62.05. The regression analyses revealed that none of the demographic characteristics and few of the clinical characteristics, such as fatigue and pain, had a significant impact on the HRQoL. CONCLUSIONS: The study demonstrated a reduced HRQoL of patients with advanced or metastatic CRC when compared to the general population. The symptoms fatigue and pain negatively affected the HRQoL, whereas other characteristics such as age, gender, and comorbidities did not have a significant impact on HRQoL.

Best supportive care from the conservative/non-surgical perspective and its costs in the treatment of patients with advanced medullary thyroid cancer: results of a Delphi panel.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare tumor entity. The contents of best supportive care (BSC) have not been defined in advanced MTC. The objective of this work is to describe the epidemiology, the treatment patterns with respect to symptom management, as well as palliative treatment and associated costs. METHOD: A Delphi panel with 9 clinical experts experienced in treating MTC was conducted to obtain details on the epidemiology of MTC and to gain insights into the therapeutic options considered for BSC in advanced MTC in Germany. Unit costs were applied to the described resources from the perspective of the German National Healthcare System in 2011. RESULTS: The annual incidence of MTC in Germany was estimated at about 220. 32% of all patients were estimated to have aggressive/symptomatic MTC, with an estimated mean survival of 36.7 months (median: 36 months). The core element of BSC is relief of symptoms to maintain quality of life. The total mean cost of BSC per patient/year was estimated at € 9,248, lifetime cost at € 28,283. CONCLUSION: There was consistent agreement within the panel on the epidemiology of MTC and on the structure of the provided therapeutic measures for BSC in advanced MTC, also defining the management of symptoms as a crucial goal of treatment.

Influence of pharmacogenomic profiling prior to pharmaceutical treatment in metastatic colorectal cancer on cost effectiveness : a systematic review.

BACKGROUND: Metastatic colorectal cancer (mCRC) imposes a substantial health burden on individual patients and society. Furthermore, rising costs in oncology cause a growing concern about reimbursement for innovations in this sector. The promise of pharmacogenomic profiling and related stratified therapies in mCRC is to improve treatment efficacy and potentially save costs. Among other examples, the commonly used epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab are only effective in patients with kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type cancers. Hence, the adaptation of predictive biomarker testing might be a valid strategy for healthcare systems worldwide. OBJECTIVE: This study aims to review the clinical and economic evidence supporting pharmacogenomic profiling prior to the administration of pharmaceutical treatment in mCRC. Moreover, key drivers and areas of uncertainty in cost-effectiveness evaluations are analysed. METHODS: A systematic literature review was conducted to identify studies evaluating the cost effectiveness of predictive biomarkers and the result dependent usage of pharmaceutical agents in mCRC. RESULTS: The application of predictive biomarkers to detect KRAS mutations prior to the administration of EGFR antibodies saved treatment costs and was cost effective in all identified evaluations. However, because of the lack of data regarding cost-effectiveness analyses for predictive biomarker testing, e.g. for first-line treatment, definitive conclusions cannot be stated. Key drivers and areas of uncertainty in current cost-effectiveness analyses are, among others, the consideration of predictive biomarker costs, the characteristics of single predictive biomarkers and the availability of clinical data for the respective pharmaceutical intervention. Especially the cost effectiveness of uridine diphosphate-glucuronyl transferase 1A1 (UGT1A1) mutation analysis prior to irinotecan-based chemotherapy remains unclear. CONCLUSION: Pharmacogenomic profiling has the potential to improve the cost effectiveness of pharmaceutical treatment in mCRC. Hence, quantification of the economic impact of stratified medicine as well as cost-effectiveness analyses of pharmacogenomic profiling are becoming more important. Nevertheless, the methods applied in cost-effectiveness evaluations for the usage of predictive biomarkers for patient selection as well as the level of evidence required to determine clinical effectiveness are areas for further research. However, mCRC is one of the first indications in which stratified therapies are used in clinical practice. Thus, clinical and economic experiences could be helpful when adopting pharmacogenomic profiling into clinical practice for other indications.

Cost-effectiveness of TNF-α inhibition in active ankylosing spondylitis: a systematic appraisal of the literature.

Ankylosing spondylitis (AS) is the most frequent prototype of spondyloarthritides. Substantial direct costs and productivity losses often arise in young patients. Currently, tumor necrosis factor (TNF) inhibitors are the only approved therapy escalation when usual care (physiotherapy and NSAIDs) proves to be insufficient. Owing to their high medication costs, TNF inhibitors are a target of cost-effectiveness analyses. There is consistent evidence regarding the use of TNF inhibitors according to recommendations in patients with active AS finding TNF inhibitors to be cost effective from a societal perspective. However, there are relevant uncertainties (discontinuation rate and progression rate) in the long-term estimates of the cost-effectiveness analyses analyzed. Whether TNF inhibitors are cost effective from an insurance perspective in the long run will have to be addressed by models based on observational data.

Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine.

BACKGROUND: The treatment of ulcerative colitis (UC) can place a substantial financial burden on healthcare systems. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA; mesalazine) is the recommended first-line treatment for patients with UC. In this analysis, the incremental cost effectiveness ratio (ICER) of two oral formulations of 5-ASA (Mezavant® and Asacol®) is examined in the treatment of patients with mild-to-moderate, active UC in Germany. METHODS: A Markov cohort model was developed to assess the cost effectiveness of Mezavant compared with Asacol over a 5-year period in the German Statutory Health Insurance (SHI). Drug pricing details for 2009 were applied throughout the model, and overall resource use was determined and also fitted to 2009 from published results of a large cross sectional study of German SHI patients. Cost per quality adjusted life year (QALY) was the primary endpoint for this study. Remission rates were obtained using data from a randomised, phase III trial of Mezavant with an active Asacol reference arm and a long-term, open label, safety and tolerability trial of Mezavant. Uncertainty in the study model was assessed using one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation. RESULTS: Over a 5-year period, healthcare costs for patients receiving Mezavant were 624 Euro lower than for patients receiving Asacol. Additionally, patients receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with Asacol. One-way sensitivity analyses suggest that these results are driven by both differences in the acquisition cost between mesalazine formulations and differences in treatment efficacy. Furthermore, sensitivity analyses suggest a probability of 76% for cost savings and higher QALYs with Mezavant compared with Asacol. If adherence and its influence on the remission rates and the risk of developing colorectal cancer were included in the model, the results might have even been more favorable to Mezavant due to its once daily dosing regimen. CONCLUSIONS: This model suggests that patients treated with Mezavant may achieve increased time in remission and higher QALYs, with lower direct costs to the SHI when compared with Asacol. Mezavant may therefore be a suitable first-line option for the induction and maintenance of remission in UC.

Cost-effectiveness of targeted therapy with cetuximab in patients with K-ras wild-type colorectal cancer presenting with initially unresectable metastases limited to the liver in a German setting.

BACKGROUND: In patients with metastases limited to the liver (liver-limited disease [LLD]), effective therapies such as monoclonal antibodies combined with chemotherapy may facilitate metastasis resection and improve long-term survival. OBJECTIVE: This study assessed the cost-effectiveness of bevacizumab and cetuximab in the treatment of patients with colorectal cancer presenting with initially unresectable liver metastases of the Kirsten rat sarcoma viral oncogene homolog (K-ras) wild type, from the perspective of German statutory health insurance. METHODS: The health-economic modeling approach presented here made indirect comparisons between available data on bevacizumab and cetuximab treatment outcomes using evidence synthesis techniques, extrapolating from the follow-up duration of identified clinical trials to a longer time horizon of up to 10 years and inferring costs and health outcomes based on modeled patient pathways. Expert opinion and Delphi panel methods were used for some assumptions, when evidence was missing. Probabilistic sensitivity analyses and different scenario analyses were applied to test for uncertainty around input parameters and assumptions. RESULTS: For the metastatic colorectal cancer LLD population with K-ras wild-type genotype, mean overall survival estimates were 37.7 months for first-line treatment with cetuximab plus FOLFIRI (irinotecan, leucovorin, fluorouracil) and 30.4 months for bevacizumab plus FOLFOX (oxaliplatin, leucovorin, fluorouracil). Corresponding discounted survival estimates were 2.88 life-years with cetuximab plus FOLFIRI versus 2.38 life-years with bevacizumab plus FOLFOX, an average gain of 0.50 discounted life-years. The incremental cost-effectiveness ratio of cetuximab plus FOLFIRI versus bevacizumab plus FOLFOX was €15,020 (year 2010 €) per life-year gained in the base case (with a 95% CI from the probabilistic sensitivity analysis of €3806-€24,660). Results were robust in different scenario analyses as well as in the probabilistic sensitivity analysis. CONCLUSIONS: First-line treatment with cetuximab plus FOLFIRI offers a cost-effective treatment option versus bevacizumab plus FOLFOX for the metastatic colorectal cancer LLD population with K-ras wild-type genotype in Germany. K-ras testing should be performed on all presenting cases of metastatic colorectal cancer to ensure access to this treatment option.

Health care costs and their predictors of inflammatory bowel diseases in Germany.

OBJECTIVES: Detailed cost studies of inflammatory bowel diseases (IBD) for Germany are limited. Aim of this study was to collect resource-use data related to IBD via a cross-sectional study, to quantify these from the perspective of the Statutory Health Insurance (SHI) and to identify cost-driving factors. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) from 24 gastroenterological specialists' practices and two hospitals were enrolled in an internet-based database between March 2006 and July 2007. Outpatient services, inpatient visits as well as medication usage were recorded and evaluated from the perspective of the SHI for 2007. Disease severity was measured by the Crohn's Disease Activity Index (CDAI) and the Colitis Activity Index (CAI), respectively. Extensive statistical analyses including generalized linear modeling (gamma model with the log link) to identify cost-driving factors were performed. RESULTS: Data from 1,030 patients with IBD (CD: 511; UC: 519) were collected. On average a patient with CD incurs annual costs of EUR 3,767 (± 5,895 (SD)) (among those 68.5% medication; 20.5% inpatient) and an average patient with UC incurs EUR 2,478 (± 4,591) (74% medication; 10% inpatient), whereas 10% of the patient with IBD account for 49% (CD: 50%; UC: 46%) of the costs. The regression analysis showed that especially the use of TNF-alpha-inhibitors, inpatient stays, gender as well as the severity status has a significant influence on costs. Further disease-specific impact factors were identified. CONCLUSIONS: This is the first study to calculate costs due to CD and UC from the perspective of the SHI in Germany and to identify cost-driving factors. It confirms a high economic burden of IBD to payers and society.

Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and cost savings.

OBJECTIVE: Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany. METHODS: Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires. Absolute costs (€/patient/year) are compared and the impact of single-cost domains on overall costing in RA is estimated (relative proportions of cost components within samples). RESULTS: Overall costs are comparable (1997-98: €4280; 2002: €3830; not significant). Differences can be observed in medication (1997-98: €550; 2002: €1580; P < 0.001) and hospitalization costs (1997-98: €1240; 2002: €500; P < 0.001). Productivity costs are significantly lower (€1480 vs €850; P < 0.05) in 2002. The impact of medication costs is outstanding in the 2002 sample (42 vs 12%), the proportion of hospitalization costs is substantially lower (29 vs 13%). Costs for DMARDs in 2002 are mostly driven by TNF blockers (37%). The number of DMARDs per patient is higher in 2002 as are costs for osteoporosis medication and gastroprotective treatment. CONCLUSION: Although overall costs before and after the introduction of TNF blockers are comparable, the decrease in hospitalization and productivity costs is promising in terms of future long-term cost savings. The development of these aspects and of the increasing medication costs will have to be evaluated with longer time frames.

Resource usage in outpatient care and reimbursement for cystic fibrosis in Germany.

OBJECTIVE: Objective of this study is to assess and evaluate resource use in outpatient treatment in Germany and to compare it with remuneration. METHODS: Outpatient treatment was evaluated in seven different centers for pediatric and adult CF patients. Data were recorded during one representative month in 2006. A micro-costing approach was used to value resource use data. RESULTS: For outpatient treatment mean costs (excluding drugs) of 488 € per patient per quarter occurred. Correlation analyses identified significant cost drivers including age and co-morbidities (pancreatic insufficiency, hepatobiliary complications, lung function capacity, or bacterial lung colonization). Remuneration covered only 51% of the total costs (252 € per patient/quarter). CONCLUSIONS: As the human resources available to these centers today are already below the requirements set by the European consensus for standards of CF care it will be important for a high level of patient care to reach a cost-covering remuneration scheme.

[Aspects of outpatient palliative care and assessment of the nursing workload. Survey among care givers in Germany]. / Versorgungssituation von Palliativpatienten und Einschätzung der Arbeitsbelastung der Pflegenden. Befragung unter ambulant tätigen Pflegenden in Deutschland.

INTRODUCTION: The aim of this study is to explore aspects of the health care situation of outpatient palliative patients in Germany as well as effort and workload of care from the viewpoint of involved care givers. Additionally the future development with regard to the cooperation with other health care providers is assessed. METHODS: A detailed questionnaire was developed and sent to 188 outpatient care givers, all members of the German Association for Palliative Medicine, in January 2009. All data was analyzed via SPSS version 16. RESULTS: 69 questionnaires were included into statistical analyses. Care givers estimate the effort of care of palliative patients as very high. 28 per cent of working time is spent on administration. Responders consider general and quantitative workload to be the highest. Most care givers assess the SAPV-directive of the Federal Joint Committee as well as the future health care situation of palliative patients and cooperation with other health care providers as good. DISCUSSION: Further studies should focus on the collection of longitudinal patient data for a more comprehensive insight.

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer's perspective.

No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no study in cost of MDS exists in Germany, the objective of this study was to assess and analyze costs of transfusion-dependent low/intermediate-1-risk MDS in Germany from a payers' perspective. From seven centers, 116 low/intermediate-1-risk transfusion-dependent MDS patients with and without isolated 5q-deletion were identified. Claims data and patient records of the previous 5 years were used to collect health care utilization data retrospectively. Publicly available tariff books and remuneration schemes were applied to evaluate mean costs per year in Euro with 2007 as base year. The annual cost of MDS patients was estimated at 14,883. Subgroup analyses showed differences in patient's characteristics and outcomes among patients treated at a hospital-based vs. an office-based setting. Patients treated at the hospital-based registry show higher cost, whereas the reasons for that still need to be detected. Overall, per annum direct costs range from 12,543 (SD 12,967) to 24,957 (SD 36,399) in different subgroups of patients. In both groups, patients with 5q-deletion use more medication than those without deletion. Mean costs for medication in the office-based setting are 5,902 for patients with isolated 5q-deletion vs. 3,932 for patients with no deletion, respectively. MDS leads to a high health care utilization and resulting costs for the health care system which requires a detailed analysis of underlying services.

[Human papilloma virus (HPV) testing for cervical carcinoma screening]. / Tests auf das Humanpapillomavirus (HPV) in der Zervixkarzinomfrüherkennung.

Cytology-based screening for cervical cancer has been criticised because of its high percentage of false-negative results. Considering HPV testing as an integral part of the screening process has been discussed as a way to address this issue in Germany. The aim of our study was to review trials comparing HPV testing with cytology in cervical cancer screening. Based on a systematic literature review, 14 studies with 85,820 women could be included. Generally HPV testing was more sensitive, but less specific than cytology. Based on the pooled data, sensitivity and specificity for HPV testing were 91% and 90%, respectively, whereas sensitivity and specificity for cytology amounted to 66% and 96%, respectively. Based on these results, including HPV testing in primary cervical cancer screening might lead to a reduction of false-negative results. Due the lower specificity false-positive test results would increase though.

A health-economic evaluation of disease-modifying drugs for the treatment of relapsing-remitting multiple sclerosis from the German societal perspective.

OBJECTIVE: This analysis compared the cost-effectiveness of interferon beta-1a (IFNbeta-1a) 44 microg SC with that of other available first-line treatments for relapsing-remitting multiple sclerosis (RRMS) from the German societal perspective in 2008. METHODS: A decision-analytic model was used to estimate the cost-effectiveness of IFNbeta-1a 44 microg SC given 3 times weekly compared with that of IFNbeta-la 30 microg IM given once weekly, IFNbeta-1b 8 mIU given every other day, and glatiramer acetate 20 mg SC given once daily. Data sources included the published literature, clinical trials, German price/tariff lists, and national population statistics. The time horizon of the model was 4 years, which was the maximum duration of follow-up in published clinical trials. RESULTS: The cost-effectiveness (cost per relapse avoided) of IFNbeta-la 44 microg SC compared with no active treatment was euro51,250, which compared favorably with that of IFNbeta-la 30 microg IM (euro133,770), glatiramer acetate (euro71,416), and IFNbeta-1b (euro54,475). When the cost of disease progression was excluded, the cost per relapse avoided remained favorable for IFNbeta-1a 44 microg SC (euro54,292) compared with the other options (euro143,186, euro72,809, and euro56,816, respectively). Indirect comparison of each available treatment option with the next best alternative indicated that the incremental cost-effectiveness of IFNbeta-la 44 microg SC (euro23,449) was consistent with accepted thresholds. Sensitivity analyses in which the discount rate, frequency of relapse and disease progression, costs of relapse and disease progression, and adherence were varied did not affect the relative outcomes. CONCLUSION: In this analysis from the German societal perspective, IFNbeta-la 44 microg SC had favorable overall cost-effectiveness versus no active treatment compared with other available disease-modifying drugs for the treatment of RRMS.

Outpatient medication costs of patients with cystic fibrosis in Germany.

BACKGROUND: Cystic fibrosis (CF) patients need specialized long-term treatment. In order to support lung function, pharmaceuticals such as bronchodilators, mucolytic agents or anti-inflammatory drugs have to be used. Oral, inhaled or intravenous antibacterial therapy is of special importance for patients who have problems with chronic bacterial colonization of the lung and airways. In case of pancreatic insufficiency, digestive enzymes have to be substituted with every meal. Furthermore, patients often need additional supplements of vitamins as well as high caloric food. All of these aspects lead to high medication use in CF patients. OBJECTIVE: To analyse outpatient medication costs for CF in Germany from a sickness funds perspective (plus some out-of-pocket payments by patients). METHODS: Medication data were evaluated from seven different outpatient CF centres. Data were recorded via medication lists by the physicians, reporting name of medication, dosage and pharmaceutical form. As the medications are mostly used long term, resource use was valued using the largest available package sizes. Prices were taken from the German 'Rote Liste' with year 2006 values. Annual and daily medication costs were analysed for different age groups. In addition, cost-influencing factors were analysed via correlation analyses. RESULTS: A total of 3150 pharmaceutical records from 301 CF patients were collected. Mean annual costs for medication were €21,603 per patient (range €69-104,477). Correlation analyses showed significant correlations between costs of medication and age, co-morbidities (such as pancreatic insufficiency and diabetes mellitus) and clinical parameters such as bacterial colonization of the lung, as well as functional parameters (percent of vital capacity, forced expiratory volume in 1 second, maximal expiratory flow at 25% of forced vital capacity). For example, mean annual costs for medication were €23,815 and €14,884 for patients with and without bacterial colonization of the lung, respectively. Other correlation factors yielded similar cost dispersions between patients with and without the factors. CONCLUSIONS: Costs of outpatient medication for CF patients significantly depend on age, co-morbidities and other clinical parameters. Hence, non-optimal treatment could lead to a significantly higher burden for the healthcare system.

Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany.

BACKGROUND: Persistent infections with high-risk types of human papillomavirus (HPV) are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. RESEARCH QUESTIONS: What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained) of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG) of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? METHODS: A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER). The perspective of the third party payer and 3% annual discount rate were adopted. Extensive sensitivity analyses were performed in order to evaluate the robustness of results and identify areas of future research. RESULTS: In the base case analysis screening resulted in a 53% to 97% risk reduction for cervical cancer with a discounted ICER between 2,600 Euro/LYG (cytology alone every five years) and 155,500 Euro/LYG (Annual cytology age 20 to 29 years, and annual HPV age 30 years and older). Annual cytology, the current recommended screening strategy in Germany, was dominated. In sensitivity analyses variation in the relative increase in the sensitivity of HPV testing as compared to cytology, HPV test costs, screening adherence, HPV incidence, and annual discount rate influenced the ICER results. Variation in the screening start age also influenced the ICER. All cytology strategies were dominated by HPV screening strategies, when relative sensitivity increase by HPV testing compared to cytology was higher (scenario analysis with data for test accuracy from German studies). HPV testing every one, two or three years was more effective than annual cytology. With increased screening adherence a longer screening interval and with low screening adherence a shorter interval would be more cost-effective. With a reduction in HPV incidence of more than 70% triennial HPV screening in women aged 30 years and older (and biennial Pap screening in women aged 20 to 29 years) is cost-effective. The discounted ICER increases with increasing annual discount rate. Increasing screening start age to 25 years had no relevant loss in effectiveness but resulted in lower costs. An optimal strategy may be biennial HPV testing age 30 years and older with biennial cytology at age 25 to 29 years (ICER of 23,400 Euro/LYG). CONCLUSIONS: Based on these results, HPV-based cervical cancer screening is more effective than cytology and could be cost-effective if performed at intervals of two years or greater. Increasing the age at screening start to 25 years causes no relevant loss in effectiveness but saves resources. In the German context an optimal screening strategy could be biennial HPV testing at age 30 years and older with biennial cytology at the age of 25 to 29 years. An extension to a three-yearly screening interval requires substantially improved screening adherence or a higher relative increase in the sensitivity of HPV testing as compared to cytology. The implementation of an organised screening program for quality-controlled introduction of HPV-screening and -vaccination with continued systematic outcome evaluation is recommended.

A structured review and guide through studies on health-related quality of life in kidney cancer, hepatocellular carcinoma, and leukemia.

Aim of this paper is to review and describe Health-Related Quality of Life (HRQoL) measures applied in kidney cancer, hepatocellular carcinoma, and leukemia patients under drug therapy. A comprehensive search in PubMed was conducted to identify studies assessing quality of life (QoL) in these indications. In total 32 studies, including four studies through reference list checking and 21 different HRQoL instruments, were identified. Six generic, five disease-specific, and 10 domain-specific instruments were identified. In conclusion no overall standards in HRQoL measurement could be observed in the respective indications.

Cross-sectional validity of the EQ-5D-Y as a generic health outcome instrument in children and adolescents with cystic fibrosis in Germany.

BACKGROUND: Quality of life is recognized as an important additional outcome measure in clinical trials and health economic evaluations. The EQ-5D is an important generic health outcome instrument often used for economic evaluations as a complement with disease-specific outcome measures. In this study quality of life data was assessed using the EQ-5D-Y (new EQ-5D version for children and adolescents) and the Cystic Fibrosis Questionnaire (CFQ). The objective of the study is to evaluate the cross-sectional validity of the EQ-5D-Y as a generic health outcome instrument in children and adolescents with cystic fibrosis in Germany. METHODS: In 2006 a multi-centre study was conducted in four cystic fibrosis centres in Germany. Quality of life data from 96 patients between eight and seventeen years was collected using the EQ-5D-Y as a generic outcome instrument and the Cystic Fibrosis Questionnaire (CFQ) as a disease-specific instrument. Results of both instruments were compared by statistical analyses using Spearman's rank correlations. RESULTS: 44.6% of the patients stated that they had no problems in any of the EQ-5D-Y dimensions. Several low to high correlations between separate dimensions and the visual analogue scale of the EQ-5D-Y and the different scales of the CFQ for children, their parents and adolescents can be presented in this paper. Looking at the five EQ-5D-Y dimensions the highest correlation (rS = 0.625, p = 0.01) was found between the dimension 'mobility' and the CFQ scale 'physical functioning' in adolescent patients. The overall highest correlation was found between the 'subjective health perception' and the visual analogue scale (rS = 0.744, p = 0.01) in adolescent patients older than 13 years. CONCLUSION: The EQ-5D-Y can be considered a cross-sectional valid generic health outcome instrument which reflects differences in health according to the progression of the life-long chronic disease cystic fibrosis.

[Persistence and frequency of prescriptions of subcutaneous allergen-specific immunotherapy (SCIT) prescribed within the German statutory health insurance]. / Persistenz und Frequenz von Verordnungen im Bereich der subkutanen allergenspezifischen Immuntherapie (SCIT) bei GKV-Patienten in Deutschland.

BACKGROUND AND PURPOSE: In accordance with guidelines subcutaneous allergen-specific immunotherapy (SCIT) should be continued for at least 3 consecutive years, which makes compliance to an issue of special importance. Measuring this compliance poses a methodological challenge. The aim of this study is to analyze persistence (reuptake of SCIT in the following years) and frequency (mean number of prescriptions) with the help of secondary data. METHODS: The sample, which was taken from a regional prescription database, includes all members of the German statutory health insurance, who received at least one prescription of selected allergen extracts between January 1, 2003 and June 30, 2006. In addition to persistence, average prescriptions for each year of therapy were used to compare long-term SCIT and short-term SCIT. Based on mean number of prescriptions per year, it was examined whether persistence is higher in short-term than in long-term SCIT. RESULTS: Mean number of prescriptions is significantly different in the 1st (2nd; 3rd) year of therapy: 1.50 (1.31; 1.28) prescriptions for long-term SCIT, 1.30 (1.42; 1.42) prescriptions for short-term SCIT, and 1.10 (1.12; 1.14) prescriptions for a shortened therapy regimen with an adjuvant-supported allergoid. As presented, persistence is decreasing. Altogether 45% of SCIT patients continue therapy in the 2nd year. In the 3rd year of therapy, there are only 24% of patients remaining. Persistence rates to a certain degree seem to be dependent on the application form. CONCLUSION: The analysis of this secondary dataset has found that nonpersistence may jeopardize the therapy according to guidelines to a greater extent than expected from the literature. Except for one allergen extract the differentiation between long-term and short-term SCIT seems diffuse. Packages for consecutive treatment are used not only in long-term SCIT, but also in short-term SCIT regimens, if they are available. The analysis provides first hints that a shorter therapy regimen supports persistence of SCIT during the 2nd and 3rd year of therapy.

[Cost analysis for ambulatory treatment of cystic fibrosis patients in Germany. Overview of the prospective study results]. / Evaluation von Kosten der ambulanten Behandlung bei Mukoviszidose in Deutschland : Ubersicht über die Ergebnisse einer prospektiven Studie.

PURPOSE: Main objective of this study is to assess and evaluate resource use in outpatient treatment of cystic fibrosis (CF) in Germany and to compare this with current reimbursement. METHODS: Outpatient treatment was evaluated in seven different CF centers.Clinical patient data, resource use, and time consumption were recorded in 2006. A micro-costing approach was used to price resource use data. RESULTS: Mean costs of 488 Euros per patient (n = 326) and quarter occurred. Remuneration (252 Euros per patient/quarter) covered only 52% of the total costs. Furthermore, a considerable time and financial burden for patients as well as decreasing quality of life with increasing age were found. Costs for medication came to 21,604 Euros per patient/year. CONCLUSION: Human resources in German CF centers today already are below the requirements set by the European consensus for standards of CF care. It will be crucial in assuring a high level of patient care to reach a cost-covering reimbursement scheme in Germany.

Cost Effectiveness of Exemestane versus Tamoxifen in Post-Menopausal Women with Early Breast Cancer in Germany.

BACKGROUND: Medical studies have shown that switching to exemestane after 2-3 years of adjuvant treatment with tamoxifen is effective when looking at overall survival. No cost effectiveness study of exemestane has been conducted in the German health care context. PATIENTS AND METHODS: To assess the cost effectiveness of switching to exemestane vs. continued tamoxifen therapy for early-stage breast cancer, a Markov model was developed. The model population was set as postmenopausal women who are in remission from early-stage breast cancer. Upon model entry, either a continuing daily therapy with 20 mg tamoxifen or a switch to 25 mg exemestane for the next 2-3 years takes place. The model takes a German health care perspective. RESULTS: The total incremental costs of exemestane on a lifetime basis are 4,195 Euro, resulting in an incremental cost effectiveness ratio of 17,632 Euro per additional quality-adjusted life year (QALY), or 16,857 Euro per life year gained. Incremental costs per disease-free year of survival are 12,851 Euro. Probabilistic sensitivity analyses proved the robustness of these findings. CONCLUSION: Compared to extended tamoxifen therapy, switching to exemestane after 2-3 years turned out to be a cost-effective strategy in adjuvant therapy for early-stage breast cancer in postmenopausal women within the German health care context.