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.

Patient preferences in allergy immunotherapy (AIT) in Germany - a discrete-choice-experiment.

BACKGROUND: Allergic Rhinitis (AR) is a common disorder in Europe with Allergic Asthma (AA) as a frequent comorbidity. Allergy immunotherapy (AIT) is the only causal therapy of AR and AA, and can be administered as subcutaneous injections at the physician or as sublingual drops or tablets at home. The usual treatment duration is 3 years. OBJECTIVE: This study aimed to elicit patient preferences to identify the AIT administration mode preferred by patients. METHODS: A discrete-choice-experiment (DCE) was developed to determine how people weight different treatment options using a paper-based questionnaire from June to September 2014, including 16 study centres. Main inclusion criteria: >18 years, grass, birch and/or house dust mite AR with moderate to severe symptoms, AIT-naïve and AIT-indicated. DCE-attributes were: Administration form, number and duration of physician visits, frequency of life-threatening anaphylactic shocks, local side-effects and co-payments. RESULTS: Two-hundred thirty-nine subjects participated, resulting in analysable 1842 choices. All attributes were significant predictors for the treatment-choice. Ranked by importance, the following first three attributes are most preferred by patients: 1(st) Number and duration of physician visits: Fewer visits with shorter duration preferred (0.658*) 2(nd) Frequency of life-threatening anaphylactic shocks: Lower risk of shocks preferred (0.285*) 3(rd) Local side-effects: Preference for rash/swelling on upper arm over itching/swelling under the tongue (0.210*) (*coefficient-size represents relative importance of the attributes) CONCLUSION: The most important attribute is the number and duration of visits to a physician. A lower risk of life-threatening anaphylactic shocks was ranked as the second whereas co-payments and administration form play a limited role.

Evolution of cost structures in rheumatoid arthritis over the past decade.

OBJECTIVE: To estimate the changes in direct and indirect costs induced by patients with rheumatoid arthritis (RA) in German rheumatology, between 2002 and 2011. To examine the impact of functional status on various cost domains. To compare the direct costs incurred by patients at working age (18-64 years) to patients at an age of retirement (≥65 years). METHODS: We analysed data from the National Database of the German Collaborative Arthritis Centres with about 3400 patients each year. Costs were calculated using fixed prices as well as annually updated cost factors. Indirect costs were calculated using the human capital as well as the friction cost approaches. RESULTS: There was a considerable increase in direct costs: from €4914 to €8206 in patients aged 18-64, and from €4100 to €6221 in those aged ≥65, attributable to increasing prescription of biologic agents (18-64 years from 5.6% to 31.2%, ≥65 years from 2.8% to 19.2%). This was accompanied by decreasing inpatient treatment expenses and indirect costs due to sick leave and work disability. The total growth of cost, on average, was €2437-2981 for patients at working age, and €2121 for patients at retirement age. CONCLUSIONS: The increase in treatment costs for RA over the last decade was associated with lower hospitalisation rates, better functional status and a lower incidence of work disability, offsetting a large proportion of risen drug costs. Since the rise in drug costs has manifested a plateau from 2009 onwards, no relevant further increase in total costs for patients with RA treated in German rheumatology is expected.

Vaccination of children with a live-attenuated, intranasal influenza vaccine - analysis and evaluation through a Health Technology Assessment.

BACKGROUND: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the The German Standing Committee on Vaccination (STIKO) as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV) has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV) for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA) is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view. METHOD: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++), if they met the criteria of European Medicines Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses; 2. one pivotal study. RESULTS: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction - RRR - of laboratory confirmed influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17 years (= 18th year of their lives), LAIV is superior to a vaccination with TIV (RRR 32%). For this age group, no studies that compared LAIV with placebo were identified. It can be concluded that there is high evidence for superior efficacy of LAIV (compared to placebo or TIV) among children aged 6 months to ≤7 years. For children from >7 to 17 years, there is moderate evidence for superiority of LAIV for children with asthma, while direct evidence for children from the general population is lacking for this age group. Due to the efficacy of LAIV in children aged 6 months to ≤7 years (high evidence) and the efficacy of LAIV in children with asthma aged >7 to 17 years (moderate evidence), LAIV is also very likely to be efficacious among children in the general population aged >7 to 17 years (indirect evidence). In the included studies with children aged 2 to 17 years, LAIV was safe and well-tolerated; while in younger children LAIV may increase the risk of obstruction of the airways (e.g. wheezing). In the majority of the evaluated epidemiological studies, LAIV proved to be effective in the prevention of influenza among children aged 2-17 years under everyday conditions (effectiveness). The trend appears to indicate that LAIV is more effective than TIV, although this can only be based on limited evidence for methodological reasons (observational studies). In addition to a direct protective effect for vaccinated children themselves, indirect protective ("herd protection") effects were reported among non-vaccinated elderly population groups, even at relatively low vaccination coverage of children. With regard to safety, LAIV generally can be considered equivalent to TIV. This also applies to the use among children with mild chronically obstructive conditions, from whom LAIV therefore does not have to be withheld. In all included epidemiological studies, there was some risk of bias identified, e.g. due to residual confounding or other methodology-related sources of error. In the evaluated studies, both the vaccination of children with previous illnesses and the routine vaccination of (healthy) children frequently involve cost savings. This is especially the case if one includes indirect costs from a societal perspective. From a payer perspective, a routine vaccination of children is often regarded as a highly cost-effective intervention. However, not all of the studies arrive at consistent results. In isolated cases, relatively high levels of cost-effectiveness are reported that make it difficult to perform a conclusive assessment from an economic perspective. Based on the included studies, it is not possible to make a clear statement about the budget impact of using LAIV. None of the evaluated studies provides results for the context of the German healthcare setting. The efficacy of the vaccine, physicians' recommendations, and a potential reduction in influenza symptoms appear to play a role in the vaccination decision taken by parents/custodians on behalf of their children. Major barriers to the utilization of influenza vaccination services are a low level of perception and an underestimation of the disease risk, reservations concerning the safety and efficacy of the vaccine, and potential side effects of the vaccine. For some of the parents surveyed, the question as to whether the vaccine is administered as an injection or nasal spray might also be important. CONCLUSION: In children aged 2 to 17 years, the use of LAIV can lead to a reduction of the number of influenza cases and the associated burden of disease. In addition, indirect preventive effects may be expected, especially among elderly age groups. Currently there are no data available for the German healthcare setting. Long-term direct and indirect effectiveness and safety should be supported by surveillance programs with a broader use of LAIV. Since there is no general model available for the German healthcare setting, statements concerning the cost-effectiveness can be made only with precaution. Beside this there is a need to conduct health eco-nomic studies to show the impact of influenza vaccination for children in Germany. Such studies should be based on a dynamic transmission model. Only these models are able to include the indirect protective effects of vaccination correctly. With regard to ethical, social and legal aspects, physicians should discuss with parents the motivations for vaccinating their children and upcoming barriers in order to achieve broader vaccination coverage. The present HTA provides an extensive basis for further scientific approaches and pending decisions relating to health policy.

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.

Modeling rheumatoid arthritis using different techniques - a review of model construction and results.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory disease with severe effects on the functional ability of patients. Due to the prevalence of 0.5 to 1.0 percent in western countries, new treatment options are a major concern for decision makers with regard to their budget impact. In this context, cost-effectiveness analyses are a helpful tool to evaluate new treatment options for reimbursement schemes. OBJECTIVES: To analyze and compare decision analytic modeling techniques and to explore their use in RA with regard to their advantages and shortcomings. METHODS: A systematic literature review was conducted in PubMED and 58 studies reporting health economics decision models were analyzed with regard to the modeling technique used. RESULTS: From the 58 reviewed publications, we found 13 reporting decision tree-analysis, 25 (cohort) Markov models, 13 publications on individual sampling methods (ISM) and seven discrete event simulations (DES). Thereby 26 studies were identified as presenting independently developed models and 32 models as adoptions. The modeling techniques used were found to differ in their complexity and in the number of treatment options compared. Methodological features are presented in the article and a comprehensive overview of the cost-effectiveness estimates is given in Additional files 1 and 2. DISCUSSION: When compared to the other modeling techniques, ISM and DES have advantages in the coverage of patient heterogeneity and, additionally, DES is capable to model more complex treatment sequences and competing risks in RA-patients. Nevertheless, the availability of sufficient data is necessary to avoid assumptions in ISM and DES exercises, thereby enabling biased results. Due to the different settings, time frames and interventions in the reviewed publications, no direct comparison of modeling techniques was applicable. The results from other indications suggest that incremental cost-effective ratios (ICERs) do not differ significantly between Markov and DES models, but DES is able to report more outcome parameters. CONCLUSIONS: Given a sufficient data supply, DES is the modeling technique of choice when modeling cost-effectiveness in RA. Otherwise transparency on the data inputs is crucial for valid results and to inform decision makers about possible biases. With regard to ICERs, Markov models might provide similar estimates as more advanced modeling techniques.

Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany.

OBJECTIVE: To obtain detailed real-world data on persistence and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in rheumatoid arthritis (RA) patients treated in Germany. METHODS: In this retrospective observational study claims data of a major German health insurance fund between 2005 and 2008 were analysed. Patients receiving at least one prescription of adalimumab, etanercept or infliximab were identified and categorised as "TNF inhibitor naive" or "TNF inhibitor continuing". For the calculation of TNF inhibitor persistence a survival analysis with the Kaplan-Meier estimator was used. A Cox regression was used to analyse, if any relevant factors were influencing persistence. Dosage increase rates were analysed for adalimumab, etanercept and infliximab. Sensitivity analyses based on variations in gap length were conducted. RESULTS: A total of 2,201 RA patients were identified. 1,468 of these patients were TNF inhibitor naive patients and 733 were defined as TNF inhibitor continuing patients. There were no significant differences in the treatment persistence rates between adalimumab, etanercept and infliximab for TNF inhibitor naive and continuing patients. The persistence rate after three years was 22.47% for adalimumab, 24.27% for etanercept and 21.49% for infliximab naive patients. For continuing patients, the persistence rate after three years was 32.88% for adalimumab, 30.95% for etanercept, and 33.90% for infliximab, respectively. Gender, medication and Charlson Comorbidities Index did not influence the persistence significantly. Dosage increase occurred in 7.3% adalimumab, 1.4% etanercept, and 17.2% infliximab naive patients and 5.8%, 1.1% and 11.9% respectively in the continuing patients. CONCLUSIONS: In this study, there were no significant differences in persistence among adalimumab, etanercept and infliximab treated patients. Consistent with previous research, there was a higher dose escalation for infliximab than for the two subcutaneous treatments, adalimumab or etanercept.

Patient perspective on the management of atrial fibrillation in five European countries.

BACKGROUND: Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS: Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. RESULTS: Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions.

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.

The role of biosimilars in the treatment of rheumatic diseases.

The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.

Biologic TNF inhibiting agents for treatment of inflammatory rheumatic diseases: dosing patterns and related costs in Switzerland from a payers perspective.

BACKGROUND: To obtain detailed real-life data on costs and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in patients treated in Switzerland. METHODS: Administrative claims processed by a major Swiss health insurer between 2005 and 2008 were analysed. Patients with inflammatory rheumatic diseases (IRDs) with at least one prescription for adalimumab, etanercept, or infliximab were identified. All-cause and disease-specific costs, as well as daily costs of treatment, were calculated. Dosing patterns and discontinuation rates were analysed. RESULTS: A total of 555 IRD patients were identified. All-cause costs during the 12 months after the index event were 20,555CHF in the etanercept group, 24,152CHF in the adalimumab group, and 27,614CHF in the infliximab group. The most important cost driver was mean TNF inhibitor drug cost, which was 15,613CHF in the etanercept group, 19,166CHF in the adalimumab group, and 21,313CHF in the infliximab group. Discontinuation rates during the first year after the index event were 46.8% in etanercept, 41.3% in adalimumab, and 51.2% in the infliximab group. Rates of dosage increase were 13.3% in the etanercept group, 13.0% in the adalimumab group, and 14.1% in the infliximab group. When time on treatment was considered, daily costs of treatment were similar for etanercept and adalimumab, but were higher for infliximab. CONCLUSIONS: Marked differences in costs between subcutaneous and intravenous therapies were observed. Among the three groups of patients defined by TNF inhibitor treatment, costs for the infliximab group were highest during the year after the index event.

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.

Why is it so difficult to evaluate nursing interventions in dementia?

Two recent health technology assessment (HTA) reports published in Germany focused on non-pharmacological interventions for patients with dementia. One of the major results was the poor methodological quality of the studies in this field. This paper concisely presents the main quantitative and qualitative findings of the HTA report published by the German Agency for HTA at the Institute of Medical Information and Documentation (dahta@DIMDI), followed by a detailed discussion of the major methodological problems observed for the inclusion criteria, interventions, the setting, number of patients included, duration of observation, comparators, clinical endpoints, health economics, and, most obvious, the impossibility of blinding and eliminating placebo effects for future clinical studies. We conclude with several suggestions addressing these challenges for future research in this field.

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.

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.

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.

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.

Considerations about the effectiveness and cost effectiveness of therapies in the treatment of hyperphosphataemia.

Because of an elevated serum phosphate level, patients who suffer from chronic kidney failure frequently tend to have cardiovascular calcification and are therefore exposed to a higher probability of a fatal event. Phosphate binders are able to reduce these negative effects. Currently, there are primarily two groups of phosphate binders (calcium-containing and calcium-free phosphate binders) which are considered to be almost equally effective in terms of binding of free phosphate. There are, however, a few disadvantages of the two groups. While the calcium-containing binders are associated with an increased risk of hypercalcemia, which is dose dependent, calcium-free binders have been criticized as being too expensive. As the expenditure for patients suffering from chronic kidney failure increases from year to year, as a result of increasing prevalence, there is a growing need for an alternative to existing phosphate binders. The study presented here therefore summarizes available information for the novel combination preparation OsvaRen® (calcium acetate/magnesium carbonate) as an alternative therapy to the calcium-free phosphate binder Renagel® (sevelamer-hydrochloride) and to calcium-containing preparations.The results of this systematic review showed that OsvaRen® is at least equally effective in the regulation of serum phosphate level as Renagel®. In particular, OsvaRen® shows no clinically relevant difference in terms of the control of the serum calcium levels compared to Renagel® and thereby does not increase the risk of a hypercalcaemia, in contrast to pure calcium-based phosphate binders. On the other hand, Renagel® therapy is much more frequently associated with gastrointestinal side-effects, a tendency to result in higher tablet burden for patients and high medication costs. The CALMAG study showed that OsvaRen® was at least as effective and safe in terms of controlling serum phosphate and serum calcium levels as Renagel® while, at the same time, resulting in about 80% lower costs. In addition, OsvaRen® offers a lower risk of hypercalcaemia and associated subsequent costs and is thereby also superior to pure calcium-containing phosphate binders.Because of the effectiveness and tolerability of calcium acetate/magnesium carbonate, OsvaRen® offers a clinically suitable and, at the same time, cost-effective therapeutic option in the therapy of hyperphosphataemia.

Measuring economic consequences of preterm birth - Methodological recommendations for the evaluation of personal burden on children and their caregivers.

This study aims to identify the impact of a preterm birth on financial and emotional burden from the families' perspective. Additionally, a comprehensive schedule of recommendations for a sufficient evaluation of all aspects of burden is developed. Based on the results of a literature search relevant categories and sub-domains for a questionnaire covering multiple aspects of associated financial and emotional burden are identified and converted into a recommendation scheme. Results of the literature search illustrate the large extend of burden of prematurity on parents. This results in substantial out-of-pocket expenditures (OOPE) and emotional distress to the parents besides the medical problems and further financial costs to the health insurance system. According to the results on infants' state of health, OOPE and emotional distress are significantly increased with decreasing gestational age. OOPE for transportation often amounts to the main parental cost dimension. Moreover there is some evidence for a high magnitude of reduced income and missed work days. The family perspective has to be taken into account when calculating the overall costs of preterm births from a societal point of view. However, in recent years economic evaluations were performed rather inhomogeneously in this field. For future studies a) direct medical costs, b) direct non-medical costs, c) indirect costs as well as d) intangible costs (in terms of emotional distress and reduced quality of life for caregivers and children) are the main categories that should be evaluated measuring personal burden of preterm birth on families adequately. A detailed list of specific sub-domains is given. Additionally, the recommendations are not restricted to application in infants born preterm and/or at low birth weight.