Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality.

Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.

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.