[Cost of Illness of HIV Patients under Anteretroviral Therapy in Germany - Results of the 48-Week Interim Analysis of the Prospective Multicentre Observational Study 'CORSAR']. / Krankheitskosten von HIV-Patienten unter antiretroviraler Therapie in Deutschland - Ergebnisse einer 48-Wochen-Interimsanalyse im Rahmen der prospektiven multizentrischen Kohortenstudie "CORSAR".

BACKGROUND: With the introduction of highly active combined antiretroviral therapy (c-ART) mortality and morbidity of HIV patients declined substantially. Earlier studies reported that c-ART was able to save health-care costs due to a reduction of other direct medical costs, particularly for inpatient treatments and concomitant medication. To date, analyses of costs and health-related quality of life (HRQOL) of patients under c-ART are lacking in Germany. Hence, this study aims to estimate the current cost of illness and HRQOL of HIV-patients under c-ART in different treatment lines. METHODS: A multicenter, prospective observational study was carried out in 12 specialised German centres for infectious diseases: 8 private practices/outpatient centres and 4 specialised hospitals offering both inpatient and outpatient services. Demographic, clinical and medication data were derived from patient records. Resource utilisation, information on productivity, out of pocket costs and HRQOL (EQ-5D) were collected every 12 weeks via a patient questionnaire. All costs were calculated based on price information from publicly accessible databases. RESULTS: N=1,154 patients were included in the analysis. Mean direct disease-related costs of -patients under c-ART amounted to 22,563 Euro/year. Patients beyond the 3(rd) line of treatment -incurred considerably higher costs 24,654 Euro/year. In the 1(st) treatment line, c-ART accounted for 83.2% of the total direct costs, in the 2(nd)/3(rd) line for 80.8% and in >3(rd) line for 83.4%, respectively. Indirect costs due to impaired productivity were higher in the 2(nd)/3(rd) treatment line (2,843 Euro) compared to the 1(st) (1,604 Euro) and >3(rd) (1,752 Euro) treatment lines, respectively. The average HRQOL (EQ-5D) varied between 0.77 (self-assessment via visual analogue scale) and 0.91 (utility score based on the German time trade-off tariff). CONCLUSIONS: Over the last decade, cost of illness of HIV patients under c-ART decreased slightly with average costs per year still being substantial. Main cost driver of overall costs is c-ART. There have been, however, noticeable shifts between different cost domains.

[Evolution of biologicals in inflammation medicine--biosimilars in gastroenterology, rheumatology and dermatology]. / Evolution der Biologika in der Entzündungsmedizin--Biosimilars in Gastroenterologie, Rheumatologie und Dermatologie.

Biologicals revolutionized the therapy of chronic inflammatory diseases in gastroenterology, rheumatology and dermatology in the last decade. The first generation biologicals mainly targeted against the pro-inflammatory cytokine TNF-α. The evolution of these therapies in the last years led to the development of new antibodies and to the admission of first generation "generic" biologics - the biosimilars. Biosimilars are not a fundamental new pharmacological development for existing substances, however they have the potential to lead to enormous cost savings in healthcare without reducing the level of care for patients. Biosimilars are not identical with the originator, but in an extensive biosimilarity exercise including analytical, preclinical and comparative clinical studies it was shown that the biosimilars could demonstrate comparability in all relevant aspects with the originator.In September 2013, the Infliximab biosimilars (Inflectra(®), Remsina(®)) were the first biosimilars for monoclonal antibodies to be authorized by the EMA for use in the European Union. By demonstrating the therapeutic similarity only in one indication (rheumatoid arthritis) the EMA agreed with an extrapolation also to all approved indications of the originator. This could be a relevant problem in clinical practice. Therefore, comparative studies with the originator are required in all approved indications.After expiration of the national patent protection in beginning of 2015, the infliximab biosimilars will be launched on the market in Germany and will be part of the therapeutic arsenal in gastroenterology, rheumatology and dermatology. Interchangeability (Switching) of biosimilars with the originator will be subject of an important discussion with the health care providers. Regardless of the biosimilars EMA-approval, several potential problems (efficacy, extrapolation, switching, long-term safety) should be the topic of intensive long-term registries in the future.

Clinical status, psychosocial impairments, medical treatment and health care costs for patients with inflammatory bowel disease (IBD) in Germany: an online IBD registry.

BACKGROUND: The aim of this cross-sectional study was to establish an online inflammatory bowel disease (IBD) registry for a first picture of the situation of IBD outpatients' treatment in Germany. METHODS: Between March 2006 and July 2007 IBD outpatients from 24 gastroenterological specialist practices and two hospitals in Germany were enrolled in an Internet-based registry to evaluate the outpatients' clinical status, psychological impairments, provided health care, as well as medical treatment and medication costs. RESULTS: 1032 IBD patients (ulcerative colitis/UC: 519; Crohn's disease/CD: 511; indeterminate colitis: 2) were enrolled in the study (age: 43 ± 14 years/M ± SD). Disease duration of all patients averaged 10 ± 8.5 years. In 519 UC-patients (49% male; 33% pancolitis), 66% were in remission as were 55% of CD patients (37 % male; 41 % active smokers). Associated with higher rates of disease activity (CDAI ≥ 150; CAI>4) were corticosteroids (CD, UC), topical medication (UC), relevant reported depressive symptoms (15%; 6-31%) and impairments in sexuality (21%; 9-42%). Relevant medication groups prescribed were oral aminosalicylates (UC: 70%; CD: 47%); immunosuppressive therapy - mostly azathioprine/6 MP (CD: 47%; UC: 26%), and Infliximab (CD: 8%; UC: 3%). Strongly associated with their clinical disease activity in UC as well as CD patients, 15% (6-31%) reported relevant depressive symptoms and 21% (9-42%) relevant impairments in sexuality. CONCLUSIONS: The registry constitutes a large complemental database for the patient population in Germany. About one third of the IBD patients were not in clinical remission (CDAI ≥150/CAI >4) (CD: 45%; UC: 27%), although high rates of immunosuppressive drugs (CD: 47%; UC 26%) were administered. This study shows a large burden of active disease associated with an unexpectedly high (co)morbidity and high psychosocial impairments, indicating a reduced health state in IBD patients.

[Health economic aspects of a stratified medicine for rheumatoid arthritis]. / Gesundheitsökonomische Aspekte einer stratifizierten Medizin in der rheumatoiden Arthritis.

Up to now stratified therapy concepts have not played an important role in the treatment of patients with rheumatoid arthritis; however, a high heterogeneity regarding the effectiveness of therapies and occurrence of side effects in patients with the same indications provokes research efforts aiming at identifying and developing diagnostic biomarkers. Comprehensive diagnostics could lead to improved patient-oriented therapy algorithms and hence, a higher patient-relevant benefit could be achieved. Furthermore, costs for non-effective therapy options could be reduced, which might improve the cost-effectiveness of single active agents, especially biologicals. For the pharmaceutical industry an enhanced stratification of pharmaceuticals leads to smaller patient target groups and smaller markets on the one hand but on the other hand it may result in higher chances of receiving approval as well as higher reimbursement prices.

Cost-effectiveness of primary HPV screening for cervical cancer in Germany--a decision analysis.

OBJECTIVES: To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. METHODS: A Markov-model for HPV-infection and cervical cancer was developed for the German health care context, and applied to evaluate various screening strategies that differ by screening interval and test algorithms, including HPV-testing alone or in combination with cytology. German clinical, epidemiological, and economic data, and test accuracy data from international meta-analyses were used. Outcomes predicted included the reduction in cervical cancer cases and deaths, life expectancy and discounted incremental cost-effectiveness ratios (ICER). The analysis was performed from the perspective of the healthcare system adopting a 3% annual discount rate for costs and outcomes. Extensive sensitivity analyses were performed. RESULTS: HPV-based screening is more effective than cytology alone. It results in a 71-97% reduction in cervical cancer cases as compared to 53-93% for cytology alone. The ICER range from 2600 Euro/LYG (cytology, 5-year-interval) to 155,500 Euro/LYG (annual HPV-testing starting at age 30 years, cytology age 20-29 years). Annual cytology alone, the current recommended screening strategy in Germany, is dominated by HPV-strategies. Increasing the age at screening initiation from 20 to 25 years does not result in a relevant loss in effectiveness but results in lower costs. CONCLUSIONS: Based on our analyses, HPV-based cervical cancer screening is more effective than cytology alone and could be cost-effective if performed at intervals of two years or longer. In the German context, an optimal screening strategy may be biennial HPV screening starting at age 30 years preceded by biennial cytology for women aged 25-29 years. Longer screening intervals may be considered in low-risk women with good screening adherence and in populations with low HPV-incidence.

[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.

Nutrition economics - characterising the economic and health impact of nutrition.

There is a new merging of health economics and nutrition disciplines to assess the impact of diet on health and disease prevention and to characterise the health and economic aspects of specific changes in nutritional behaviour and nutrition recommendations. A rationale exists for developing the field of nutrition economics which could offer a better understanding of both nutrition, in the context of having a significant influence on health outcomes, and economics, in order to estimate the absolute and relative monetary impact of health measures. For this purpose, an expert meeting assessed questions aimed at clarifying the scope and identifying the key issues that should be taken into consideration in developing nutrition economics as a discipline that could potentially address important questions. We propose a first multidisciplinary outline for understanding the principles and particular characteristics of this emerging field. We summarise here the concepts and the observations of workshop participants and propose a basic setting for nutrition economics and health outcomes research as a novel discipline to support nutrition, health economics and health policy development in an evidence and health-benefit-based manner.

Practical issues in handling data input and uncertainty in a budget impact analysis.

The objective of this paper was to address the importance of dealing systematically and comprehensively with uncertainty in a budget impact analysis (BIA) in more detail. The handling of uncertainty in health economics was used as a point of reference for addressing the uncertainty in a BIA. This overview shows that standard methods of sensitivity analysis, which are used for standard data set in a health economic model (clinical probabilities, treatment patterns, resource utilisation and prices/tariffs), cannot always be used for the input data for the BIA model beyond the health economic data set for various reasons. Whereas in a health economic model, only limited data may come from a Delphi panel, a BIA model often relies on a majority of data taken from a Delphi panel. In addition, the dataset in a BIA model also includes forecasts (e.g. annual growth, uptakes curves, substitution effects, changes in prescription restrictions and guidelines, future distribution of the available treatment modalities, off-label use). As a consequence, the use of standard sensitivity analyses for BIA data set might be limited because of the lack of appropriate distributions as data sources are limited, or because of the need for forecasting. Therefore, scenario analyses might be more appropriate to capture the uncertainty in the BIA data set in the overall BIA model.

Assessment of potential measures in models of progression in Alzheimer disease.

BACKGROUND: In estimating the potential benefits of treatment, it is often necessary to extrapolate beyond clinical trial results using economic modeling. Previous attempts in Alzheimer disease (AD) were primarily based on the Mini-Mental State Examination (MMSE) due to its widespread use. These models were criticized as not accurately reflecting the total impact of the disease, providing untrustworthy estimates of treatment benefit. We compared 3 alternatives to the MMSE with respect to bridging between clinical outcomes needed for regulatory approval and economic and quality of life (QOL) outcomes important to reimbursement agencies. METHODS: The MMSE, Disability Assessment in Dementia (DAD) scale, Clinical Dementia Rating (CDR) scale, and Dependence Scale (DS) were compared in their ability to explain variation in cognitive, functional, and behavioral measures as well as economic and QOL outcomes using univariate (Pearson correlations) and multivariate (linear regression) analyses of data from research sites in the United States and Europe. RESULTS: Subjects with mild to moderate AD (n = 196; mean 75.9 years; 56% female) were evaluated. The DS, DAD, and CDR were moderately correlated with the MMSE (Pearson correlations, range 0.54-0.58) but performed better (higher adjusted R(2)) than the MMSE in explaining variations in subject behavior, QOL, and health status. The DS and DAD performed better in explaining variation in medical costs, caregiver QOL, and caregiver time. CONCLUSIONS: Measures of function (DAD) or dependence on others (DS), or global measures (CDR), appear to be better candidates than the MMSE for modeling AD progression.

[Updated results of a survey on outpatient healthcare structures in rheumatology]. / Aktualisierte ergebnisse einer erhebung zur ambulanten versorgungssituation in der rheumatologie.

AIM: the aim of this study was to give an update on outpatient healthcare structures in rheumatology in Germany. METHODS: a survey among the members of the German Association of Rheumatologists was carried out via a self-developed questionnaire, followed by a detailed descriptive and explorative statistical analysis. Contents of the questionnaire focussed on data concerning the practice, structure of the patients with regard to different indications and therapies, structure and quality of healthcare services provided, quality assurance and the economic situation of the practice as well as a subjective assessment of the outpatient healthcare environment. This approach is similar to the first survey conducted in 2005. RESULTS: compared to the findings from the first survey in 2005 no significant changes could be found in many areas. As this may intuitively sound disappointing it must be stated that high positive levels maintained in some areas, which cannot be taken for granted, can also be counted as success. With respect to the structure of services provided and medical therapies, a further upward trend could be observed. Topics which were assessed for the first time dealt with communication with healthcare insurers and teaching of rheumatology as a discipline in hospitals. CONCLUSIONS: rheumatologists in Germany offer a broad spectrum of different services and actively make use of quality assurance measures in the daily practice. The communication with general practitioners and the training of new rheumatologists in the future remain an area of concern and need to be addressed.

[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.

Evaluation of exenatide vs. insulin glargine in type 2 diabetes: cost-effectiveness analysis in the German setting.

OBJECTIVES: The objective of this analysis was to determine the cost-effectiveness of exenatide vs. insulin glargine in patients with type 2 diabetes failing to achieve glycaemic control with oral antidiabetic agents, in the German setting, from a third-party payer perspective. METHODS: Data from a published randomized controlled trial were used in combination with a published, validated computer simulation model of type 2 diabetes to project clinical and cost outcomes over a time horizon of 10 years. Cost data were obtained from published literature and expert opinion. Clinical and cost outcomes were discounted at 5% per annum. Sensitivity analyses were performed to establish key drivers and parameters. RESULTS: Treatment with exenatide compared with insulin glargine was projected to be associated with improvements in life expectancy of 0.016 years and quality-adjusted life expectancy of 0.280 quality-adjusted life years (QALYs), increased lifetime direct medical costs of euro 3854 (euro 22 095 vs. euro 18 242) and an incremental cost-effectiveness ratio (ICER) of euro 13 746 per QALY. If quality of life was not taken into account, exenatide was associated with an ICER of euro 238 201 per life year gained vs. insulin glargine. Sensitivity analyses revealed that outcomes were most sensitive to changes in assumptions for (dis)utility values relating to weight change and the rate of self-monitored blood glucose testing. CONCLUSIONS: Exenatide was projected to be associated with similar clinical outcomes and increased costs compared with insulin glargine. Analysis of cost-effectiveness from a third-party perspective suggests that exenatide is likely to represent good value for money in the German setting.

[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.

Comparative cost analysis of outpatient and inpatient rehabilitation for musculoskeletal diseases in Germany.

OBJECTIVES: To examine the costs of inpatient and outpatient rehabilitation for musculoskeletal disorders from the perspective of a major statutory health insurance fund in Germany. METHODS: A nation-wide database from a major health insurance fund in Germany was used to evaluate all rehabilitation cases in 2005. In addition, to all direct cost domains of the rehabilitation itself, costs incurred in the preceding and the following year for hospital treatment, drugs and physical therapy were analysed. A cost-cost analysis in different institutional settings was chosen for the cost comparison of inpatient and outpatient rehabilitation. To minimize the influence of possible confounders, a statistical control system was implemented. RESULTS: After a preceding hospital stay, inpatient and outpatient rehabilitation results in mean costs of euro2047 and euro1111, respectively. If the rehabilitation was not preceded by a directly related hospital treatment, mean costs for inpatient (outpatient) rehabilitation were euro2067 (euro1310). No systematic differences could be found between inpatient and outpatient rehabilitation evaluating costs for hospital treatment, drugs or physical therapy in the year preceding and the year directly following the rehabilitation. CONCLUSIONS: Assuming comparable medical outcomes, outpatient rehabilitation seems to be a superior alternative compared with inpatient rehabilitation from an economic perspective. Hence, from the perspective of the statutory health insurance, fostering a higher market share of outpatient rehabilitation may add to a better allocation of overall health care resources. For this, regional differences in rehabilitation infrastructure have to be taken into account.

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.

[Current status of ambulatory rheumatologic health care in Germany. Structure of health care and range of services]. / Bestandsaufnahme der ambulanten rheumatologischen Versorgung in Deutschland. Versorgungsstruktur und Leistungsspektrum.

AIM: To gather information on current organizational structures in rheumatologic ambulatory health care in Germany. Based on the results recommendations on future structures will be discussed. METHODS: This study involved data collection and statistical analysis via a structured 10-page questionnaire among the members of the German Association of Rheumatologists. The questions concerned a variety of topics including information on office structures, patient structure, structure of services offered, co-operation with colleagues and hospitals, quality assurance measures, economic factors, and a subjective assessment of the health care structures in rheumatology by the participants. RESULTS: Data obtained from 197 rheumatologists who participate in health care were analyzed. In this paper results concerning the organizational as well as the medical ambulatory health care structure will be presented. Data on economic factors will be presented in part 2 of this study. CONCLUSIONS: The organization of ambulatory treatment regarding processes and treatment differences between office-based physicians and rheumatologic outpatient departments in hospitals was very homogeneous. However, physicians in the eastern regions treated significantly more patients compared with the western parts of Germany. This difference was also observed between the north and south. Differences in patient groups (e.g. underlying diseases) were reported between different sub-groups of rheumatologists (e.g. internal specialists vs. GP vs. orthopedic rheumatologists). Integrated health care, as promoted by German social law, did not play a major role. Overall there was a high level of self-initiated training of physicians and participation in education of patients and other physicians.