Annual cost of hospitalization, inpatient rehabilitation, and sick leave for head and neck cancers in Germany.

BACKGROUND: Data on the economic burden of head and neck cancers (HNCs) in Germany is scarce. About 16%-28% of these cancers are associated with human papillomavirus (HPV) infection. Therefore, the study reported here aimed to assess the annual costs of HPV-related HNCs incurred by hospitalization, inpatient rehabilitation, and sick leave in Germany in 2008. METHODS: A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to HNCs in 2008 were analyzed. Associated numbers of HNC hospitalizations, health care resource use, and costs were identified and extracted using the International Classification of Diseases, tenth revision (ICD-10; World Health Organization, Geneva, 1990) codes C01-C06, C09-C14, and C32 as the main diagnoses. Resources were valued with German official prices in 2008 euros (€). The annual costs of HPV-related HNCs were estimated based on the percentage of HNCs likely to be attributable to HPV infection. RESULTS: In 2008, there were 63,857 hospitalizations, 4898 inpatient rehabilitations, and 17,494 sick leaves due to HNCs, representing costs of €365.78 million. The estimated annual costs associated with HPV-related HNCs were €78.22 million, mainly attributed to males (80%). Direct costs accounted for 84% (80% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 16% of HPV-related HNC costs. CONCLUSION: The economic burden of HPV-related HNCs in Germany in 2008 has been underestimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, as far as we are aware, this study is the first analysis to investigate the economic burden of HNCs in Germany. The estimated annual costs of HPV-related HNCs contribute to a significant economic burden in Germany and should be considered when assessing the health and economic benefits of HPV vaccination in both sexes.

Annual cost of hospitalization, inpatient rehabilitation and sick leave of anal cancer in Germany.

OBJECTIVE: Literature on the economic burden of anal cancer in Germany is scarce. About 84% of these cancers are associated with human papillomavirus infection. This study, therefore, aimed to assess the annual costs of human papillomavirus-related anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in 2008 in Germany. METHODS: A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to anal cancer in 2008 were analyzed. Associated numbers of anal cancer hospitalizations, healthcare resource use, and costs were identified and extracted using the ICD-10 code C21 as the main diagnosis. The annual cost of human papillomavirus-related anal cancer was estimated based on the percentage of anal cancer likely to be attributable to human papillomavirus. RESULTS: In 2008, there were 5774 hospitalizations (39% males, 61% females), 517 inpatient rehabilitations, and 897 sick leaves due to anal cancer representing costs of €34.11 million. The estimated annual costs associated with human papillomavirus-related anal cancer were €28.72 million, mainly attributed to females (62%). Direct costs accounted for 90% (86% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 10% of human papillomavirus-related costs. CONCLUSIONS: The economic burden of human papillomavirus-related anal cancer in 2008 in Germany is under-estimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, this study is the first analysis to investigate the economic burden of anal cancer in Germany. The estimated annual costs of human papillomavirus-related anal cancer contribute to a significant economic burden in Germany and should be considered when assessing health and economic benefits of human papillomavirus vaccination in both genders.

Health economic evaluation of insulin glargine vs NPH insulin in intensified conventional therapy for type 1 diabetes in Germany.

OBJECTIVE: Basal insulin analogs are well established in the treatment of type 1 diabetes in Germany. However, little is known about their economic impact. The aim of this study for an adult population was to compare, from the perspective of the Statutory Health Insurance (SHI), the cost effectiveness of the long-acting insulin analog glargine (GLA) with intermediate-acting neutral protamine Hagedorn (NPH) insulin in basal bolus therapy, considering the interaction between glycemic control and the rate of hypoglycemia. METHODS: A validated discrete event simulation model was adapted to the German setting to project clinical and cost outcomes over 40 years. Resources were valued with German official prices in 2009/2010 Euros. Health-related disutilities were taken from UK sources. Patient characteristics and risk factors were partially extracted from German sources in a sensitivity analysis. RESULTS: In the base-case analysis, GLA was dominant as it increased life expectancy by 0.196 years and improved quality-adjusted life-years (QALYs) by 0.396 units while at the same time leading to savings of €5246 each per patient after 40 years compared to NPH. These results were robust in the sensitivity analyses. Monte Carlo simulation confirmed dominance of GLA in 70% (life-years gained) and 80% (QALYs gained) of the iterations. The price of GLA had the highest impact on savings. In extreme scenarios, incremental cost-effectiveness ratios increased up to €9576 per QALY gained. Limitations of the evaluation included no myocardial re-infarction(s) and no recurrent stroke(s), patient characteristics, risk factors, and disutilities from the UK due to scarce data in Germany, and that not all diabetes-related direct costs were included, namely insulin pens and blood glucose meters. CONCLUSION: GLA appears to be cost effective or even cost saving among type 1 diabetics with basal bolus therapy from the perspective of SHI compared to NPH depending on the scenario chosen.

Association between gout and all-cause as well as cardiovascular mortality: a systematic review.

Gout affects 1% to 2% of the population, and the prevalence is increasing due to changes in diet and the ageing of the population. Its development and risk factors have been explored frequently, and recommendations for the diagnosis and management of gout implemented. Nevertheless, there is a lack of knowledge regarding the long-term impact on gouty patients. This systematic review therefore evaluates the association between gout and all-cause as well as cardiovascular mortality. A systematic literature search was performed, and seven long-term studies were ultimately analyzed. Six of them used multivariate regressions to assess the adjusted mortality ratio in gouty patients with reference to patients without the disorder. Despite differences in study designs, study populations, and definitions of gout, the results were consistent: There was an independent association between gout and all-cause as well as cardiovascular mortality. Knowing that patients with gout are at risk emphasizes the need for adequate care.

Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review.

BACKGROUND: Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. METHODS: A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). RESULTS: A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). CONCLUSIONS: The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses (CUA) included. Thus insulin glargine (GLA) seems to offer good value for money. Comparability between studies is limited because of methodological and country specific aspects. The results of this review underline that evaluation of insulin therapy should use evidence on efficacy of therapy from information synthesis. The concept of relating utility decrements to fear of hypoglycaemia is a plausible approach but needs further investigation. Also future evaluations of basal-bolus insulin therapy should include costs of consumables such as needles for insulin injection as well as test strips and lancets for blood glucose self monitoring.

Economic evaluation of enoxaparin for anticoagulation in early cardioversion of persisting nonvalvular atrial fibrillation: a statutory health insurance perspective from Germany.

OBJECTIVE: To estimate, from the perspective of Statutory Health Insurance (SHI, third-party payer) in Germany, the economic consequences of using the subcutaneous low-molecular-weight heparin (LMWH) enoxaparin instead of intravenous unfractionated heparin followed by oral phenprocoumon (UFH/PPC) for anticoagulation in patients undergoing transesophageal echocardiography (TEE)-guided early electrical cardioversion (ECV) of persisting nonvalvular atrial fibrillation (AF) without intracardiac clot. DESIGN AND SETTING: The incremental cost for the enoxaparin-based regimen versus the UFH/PPC-based regimen was chosen as the target variable. A decision-analytic model considering the in- and outpatient sectors was used to quantify the target variable. Resource use during in- and outpatient treatment was taken from the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial and from expert interviews with cardiologists in Germany in order to reflect the day-to-day conditions of clinical practice. Costs were given by SHI expenses for inpatient treatment and for medical services, drugs, disposables, and laboratory tests during outpatient treatment. These costs were determined by multiplying utilized resource items by the price or tariff of each item based on German healthcare regulations for the reference period of 2003/2004. According to the ACE trial, the evaluation encompassed 28 (26-30) treatment days with two consecutive phases. Phase I with 5 (3-12) days comprised diagnostics, start of anticoagulation, and ECV. Phase II with the remaining days consisted of continued anticoagulation and patient monitoring. The dosage of enoxaparin was 1 mg/kg bodyweight twice daily in treatment phase I followed by 40 mg twice daily with a bodyweight <65 kg or 60 mg twice daily with a BW > or =65 kg in treatment phase II. The daily dosages of UFH by continuous infusion and overlapping PPC were adjusted to an International Normalized Ratio of 2.0-3.0 in treatment phase I followed by 2.25mg PPC once daily in treatment phase II. Patients with any comorbidity and complication level (CCL) and those with low comorbidity and complications expected to occur in rare cases only (low-risk patients) were analyzed separately. In each base-case analysis, exclusively point estimates of all respective model parameters were applied. MAIN OUTCOME MEASURES AND RESULTS: There were savings of 339 euro and 579 euro per patient receiving the enoxaparin-based regimen versus the UFH/PPC-based regimen in the case of patients with any CCL and of low-risk patients, respectively (1 euro approximate, equals $US1.25; first quarter 2004 values). In comprehensive sensitivity analyzes, the robustness of the model and its results was shown. First, the impact of the model parameters on the target variable for each patient group was quantified in a deterministic model. Secondly, the dependency of the target variable on random variables was described for each patient group using Monte Carlo simulation. Irrespective of the patient group, the cost weight and the base rate of hospitals for inpatient ECV in phase I turned out to have the greatest impact on the savings obtained by the enoxaparin-based regimen. In the case of patients with any CCL, this impact was about 1.4-fold of that of the probability of enoxaparin patients undergoing outpatient ECV in phase I. In the case of low-risk patients, the impact of the cost weight and the base rate of hospitals for inpatient ECV in phase I was about 4.1-fold of that of the price of enoxaparin 60 mg prefilled syringes in the outpatient sector. In 79% and 93% of 10,000 simulated comparisons each versus the UFH/PPC-based regimen, there were savings obtained by the enoxaparin-based regimen in patients with any CCL and in low-risk patients, respectively. CONCLUSIONS: Results of this evaluation showed that an enoxaparin-based regimen for TEE-guided ECV of AF in patients without intracardiac clot offers SHI in Germany a considerable saving potential when used instead of an UFH/PPC-based regimen.

Cost effectiveness of enoxaparin as prophylaxis against venous thromboembolic complications in acutely ill medical inpatients: modelling study from the hospital perspective in Germany.

OBJECTIVE: To estimate, from the hospital perspective in Germany, the cost effectiveness of the low-molecular-weight heparin (LMWH) subcutaneous enoxaparin sodium 40 mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and relative to subcutaneous unfractionated heparin (UFH) 5,000 IU three times daily (low-dose UFH [LDUFH]). Each is used in addition to elastic bandages/compression stockings and physiotherapy in the prevention of venous thromboembolic events (VTE) in immobilised acutely ill medical inpatients without impaired renal function or extremes of body weight. METHODS: The incremental cost-effectiveness ratios (ICERs) of the 'additional cost for ENOX per clinical VTE avoided versus NPP' and 'additional cost for ENOX per episode of major bleeding avoided versus LDUFH' were chosen as target variables. The target variables were quantified using a modelling approach based on the decision-tree technique. Resource use during thromboprophylaxis, diagnosis and treatment of VTEs, episode of major bleeding and secondary pneumonia after pulmonary embolism (PE) was collected from a hospital survey. Costs were exclusively those to hospitals incurred by staff expenses, drugs, devices, disposables, laboratory tests and equipment for diagnostic procedures. These costs were determined by multiplying utilised resource items by the price or tariff of each item as of the first quarter of 2003. Safety and efficacy values of the comparators were taken from the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) and the THE-PRINCE (THromboEmbolism-PRevention IN Cardiac or respiratory disease with Enoxaparin) trials and from a meta-analysis. The evaluation encompassed 8 (6-14) days of thromboprophylaxis plus time to treat VTE and episode of major bleeding in hospital. Point estimates of all model parameters were applied exclusively in the base-case analysis. RESULTS: There were incremental costs of euro 1,106 for ENOX per clinical VTE avoided versus NPP (1 euro approximately equals 1.07 US dollars; average of the first quarter of 2003). ENOX dominated LDUFH: cost savings of euro 55,825 were obtained and 7.7 episodes of major bleeding were avoided by ENOX compared with LDUFH, each per 1000 patients. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. CONCLUSIONS: Results of this evaluation suggest that, in immobilised acutely ill medical inpatients, ENOX may offer hospitals in Germany a very cost-effective option for thromboprophylaxis compared with NPP and a cost-saving alternative compared with LDUFH.

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide in rheumatoid arthritis in Germany: I. Selected DMARDs and patient-related costs.

OBJECTIVE: To quantify direct costs of medication and cost of illness (according to functional capacity) for patients with rheumatoid arthritis (RA) in Germany, allowing further use in a health economic evaluation of sequential therapy with disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using a modelling approach, which was based on secondary analysis of existing data and on data from a sample of 583 patients from the German rheumatological database of 1998. Functional capacity was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs were calculated from resources utilised and patients' work capacity. Direct costs consisted of outpatient medical services, inpatient treatment, long-term care and rehabilitation treatment. Indirect costs incurred by sick leave and premature retirement were quantified according to the human-capital approach. MAIN OUTCOME MEASURES AND RESULTS: Average total direct costs (year 1998-2001 values) per patient per year for continuous treatment with the selected DMARDs comprising costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1 approximately equal to $US 0.91; average of the period from 2000 through 2001)] followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for RA-related non-DMARD medication of euro 554 per patient, including management of ADRs. Mean cost of illness (year 1998 values) excluding medication cost amounted to euro 17,868 per RA patient per year. Annual costs increased with increasing disability, i.e. decreasing functional capacity, of RA patients from euro 6029 per patient with more than 94% of functional capacity to euro 28,509 per patient with <20% of functional capacity. In general, there was a predominance of indirect costs in each of the categories of functional capacity, ranging between 74% and 87% of total (direct and indirect) annual costs per RA patient. Annual direct costs increased from euro 811 to euro 7438 per patient with increasing disability. Inpatient treatment was the predominant component of direct costs. Patients in the worst category (<20%) of function experienced hospital costs that were 6.5 times higher than those of patients in the best category (>94%). CONCLUSIONS: On the basis of the data presented it can be concluded that the results of this investigation are typical for patients in rheumatological care in Germany and can therefore be used in a health economic analysis of different DMARD sequences aimed at changing disease progression over time.

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide for rheumatoid arthritis in Germany: II. The contribution of leflunomide to efficiency.

OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND RESULTS: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.

Cost effectiveness of ramipril in patients at high risk for cardiovascular events : economic evaluation of the HOPE (Heart Outcomes Prevention Evaluation) study for Germany from the Statutory Health Insurance perspective.

BACKGROUND: In the HOPE (Heart Outcomes Prevention Evaluation) trial, ramipril (compared with placebo) significantly reduced cardiovascular death and all-cause mortality as well as the incidence of costly cardiovascular events, such as myocardial infarction, revascularisation, stroke, cardiac arrest, hospitalisation due to heart failure and worsening angina pectoris, new-onset diabetes mellitus and microvascular diabetic complications. OBJECTIVE: Data from the HOPE study were used in a cost-effectiveness analysis to determine the additional cost per life-year gained (LYG) when the ACE inhibitor ramipril was added to the current medication of patients at high risk for cardiovascular events. The aim was to establish the incremental cost-effectiveness ratio (ICER) of ramipril versus placebo from the perspective of the Statutory Health Insurance (SHI) provider in Germany, for both the study population as a whole and for the subgroup of patients with diabetes. DESIGN: A modelling approach was used, based on secondary analysis of published data and retrospective application of costs. In the base-case analysis, average case-related expenses of the SHI were applied and LYG were quantified using the average of the difference between the survival rates in the ramipril and placebo groups during the HOPE trial. LYG beyond the trial duration were estimated by the method of declining exponential approximation of life expectancy. RESULTS: After a treatment period of 4.5 years, the ICER of ramipril versus placebo was Euros 4074/LYG and Euros 2486/LYG (discounted at 5% per annum and in 1998-2002 values; Euro 1 approximately USD 0.88; first quarter 2002 values) for the HOPE study population as a whole and the subgroup of patients with diabetes, respectively. To test the model's robustness, the influence of the model variables on the results was quantified using a deterministic model, and a best-case/worst-case scenario analysis. The effect of random variables was investigated in a Monte Carlo simulation. The acquisition cost for ramipril had the greatest impact on the ICER of ramipril (2.2-fold greater than the impact of the number of LYG). In 95% of the 10,000 simulation steps, the ICER of ramipril after 4.5 years of treatment was between Euros 1290 and Euros 9005 per LYG for the entire HOPE study population and between Euros 290 and Euros 6115 per LYG in the diabetic subgroup. CONCLUSIONS: Results of this evaluation suggest that ramipril is likely to be cost effective in secondary prevention of cardiovascular events from the perspective of the SHI (third-party payer) in Germany. The estimated ICER of ramipril compares well with other ICERs of widely accepted treatments used for the management of cardiovascular diseases, such as HMG-CoA reductase inhibitors.

Cost-effectiveness of ramipril in patients at high risk for cardiovascular events: a Swiss perspective.

BACKGROUND: Ramipril may prevent cardiovascular death, myocardial infarction and stroke in patients without evidence of left ventricular dysfunction or heart failure who are at high risk for cardiovascular events. In the present study we assessed the cost-effectiveness of ramipril in patients with an increased risk of cardiovascular events from a third party payer's perspective in Switzerland. In addition, the cost-effectiveness of ramipril in the subgroup of diabetic patients was assessed. METHODS: We developed a decision analytic cost-effectiveness model to estimate the incremental costs (in 2001 in Swiss Francs [CHF]), incremental effects (in terms of life-years gained [LYG]) and incremental cost-effectiveness (CHF per LYG) of ramipril versus placebo. Clinical input parameters were derived from the Heart Outcomes Prevention Evaluation (HOPE) study. Cost data were extracted from the literature. Deterministic sensitivity analysis was used to assess the impact of varying the input parameters on the cost effectiveness of the intervention. In addition, first order Monte Carlo simulation was used to capture patient-to-patient variability, presented as cost-effectiveness acceptability curves. RESULTS: The incremental cost-effectiveness ratio of ramipril versus placebo was CHF 6,005 per life-year gained in the base case analysis. In diabetic patients the cost-effectiveness ratio was CHF 3,790 per life-year gained. Varying the price of ramipril in a deterministic sensitivity analysis only had a moderate impact on the cost-effectiveness ratio in the overall population (range: CHF 3,652-15,418 per LYG) as well as in diabetic patients (range: CHF 2,370-9,468 per LYG). CONCLUSION: Ramipril in patients at high risk for cardiovascular events represents an efficient use of scarce health care resources in Switzerland and is cost-effective under reasonable assumptions. Ramipril is even more cost-effective in the subgroup of diabetic patients.