Cost-Effectiveness of Dabigatran Compared to Vitamin-K Antagonists for the Treatment of Deep Venous Thrombosis in the Netherlands Using Real-World Data

Vitamin-K antagonists (VKAs) present an effective anticoagulant treatment in deep venous thrombosis (DVT). However, the use of VKAs is limited because of the risk of bleeding and the necessity of frequent and long-term laboratory monitoring. Therefore, new oral anticoagulant drugs (NOACs) such as dabigatran, with lower rates of (major) intracranial bleeding compared to VKAs and not requiring monitoring, may be considered.To estimate resource utilization and costs of patients treated with the VKAs acenocoumarol and phenprocoumon, for the indication DVT. Furthermore, a formal cost-effectiveness analysis of dabigatran compared to VKAs for DVT treatment was performed, using these estimates.A retrospective observational study design in the thrombotic service of a teaching hospital (Deventer, The Netherlands) was applied to estimate real-world resource utilization and costs of VKA monitoring. A pooled analysis of data from RE-COVER and RE-COVER II on DVT was used to reflect the probabilities for events in the cost-effectiveness model. Dutch costs, utilities and specific data on coagulation monitoring levels were incorporated in the model. Next to the base case analysis, univariate probabilistic sensitivity and scenario analyses were performed.Real-world resource utilization in the thrombotic service of patients treated with VKA for the indication of DVT consisted of 12.3 measurements of the international normalized ratio (INR), with corresponding INR monitoring costs of €138 for a standardized treatment period of 180 days. In the base case, dabigatran treatment compared to VKAs in a cohort of 1,000 DVT patients resulted in savings of €18,900 (95% uncertainty interval (UI) -95,832, 151,162) and 41 (95% UI -18, 97) quality-adjusted life-years (QALYs) gained calculated from societal perspective. The probability that dabigatran is cost-effective at a conservative willingness-to pay threshold of €20,000 per QALY was 99%. Sensitivity and scenario analyses also indicated cost savings or cost-effectiveness below this same threshold.Total INR monitoring costs per patient were estimated at minimally €138. Inserting these real-world data into a cost-effectiveness analysis for patients diagnosed with DVT, dabigatran appeared to be a cost-saving alternative to VKAs in the Netherlands in the base case. Cost savings or favorable cost-effectiveness were robust in sensitivity and scenario analyses. Our results warrant confirmation in other settings and locations

Thromboprophylaxis in total hip-replacement surgery in Europe:Acenocoumarol, fondaparinux, dabigatran and rivaroxban

This paper reviews the clinical and pharmacoeconomic studies that have been conducted within Europe for patients undergoing elective hip-replacement surgery. Additionally, we offer a perspective on the possible future clinical use of new agents in orthopedic surgery, such as dabigatran and BAY 59-7939 (rivaroxban). Low-molecular weight heparins are standard therapy for patients requiring thromboprophylaxis and, therefore, we compare these with the other agents: vitamin K antagonists, fondaparinux and the direct oral inhibitors (thrombin or factor Xa inhibitors). The most evidence on the cost-effectiveness and efficacy is available for the low-molecular weight heparins and fondaparinux. Their major limitation is that they require parenteral administration. Only fondaparinux has undergone an extensive pharmacoeconomic evaluation. The direct thrombin inhibitors and direct factor Xa inhibitors are possibly the drugs of the future, but it must be borne in mind that they are still in Phase III clinical trials and, therefore,their safety and efficacy profile is not completely understood, neither are the pharmacoeconomic aspects

Prospective evaluation of a computerized algorithm for Vitamin K antagonist drug dose calculation

Introduction: In an earlier study, we described and validated a VKA dose-finding algorithm (B2A), based on a novel bidirectional factor (BF). We designed a prospective study to evaluate the B2A in a daily care setting. Methods: In this open-label prospective study, we compared the outcomes of the B2A over the year 2020 with the outcomes of the previous year (2019), using regular algorithms. The outcomes were the duration of Time in the Therapeutic Range (TTR), the percentage of automated dose proposals (PAuP) and the percentage of accepted dose proposals (PAcP). The data were obtained from three anticoagulation centers in the Netherlands, in four locations. The outcomes of this study were based on a non-inferiority level.Results: The TTR over the year 2020 was at least non-inferior compared with the standard of care treatment. The percentage of automated proposals increased in all centers to approximately 96% of all dosages. Conclusion: The B2A performs non-inferior compared with the existing algorithms and in some aspects even better

KNOWLEDGE TRANSFER IN THE CHINESE AUTOMOTIVE INDUSTRY

The automotive industry has been subject to a turbulent shift in the last decades as its markets, production and focus has shifted its center of gravity towards the East, specifically to China. When Western automotive companies seek to establish themselves on the Chinese automotive market they have been forced to engage in joint ventures with Chinese counterparts. As the motivation for the Chinese partners is to accumulate knowledge, experience and competencies from their mature and sophisticated Western partners, the Western partners are faced with the difficult process of transferring competencies and knowledge that have been accumulated over long periods of time and which can be tacit or hard to codify. The question of how to transfer knowledge and competencies successfully to their Chinese joint venture subsidiaries therefore becomes evident. Our aim with this thesis was to identify how Western multinational corporations can upgrade the competencies of their joint venture subsidiaries in China through the transfer of knowledge. We engaged in research of empirical data concerning both the problems faced by the Chinese automotive industry as well as the study of how Western parent firms successfully can transfer knowledge and competencies to their Chinese joint venture subsidiaries. The empirical data consisted of both secondary data as well as primary data collected through interviews. We formulated our hypothesis on the analysis of our empirical data and a theoretical framework on knowledge transfer. Our study shows that the Western automotive parent firms should focus on knowledge transfer associated to the establishment of new organizational structures and managerial principles. Most of the problems faced by the Chinese automotive industry derives from difficulties of retaining skilled personnel, which makes competence building hard, and that the Chinese organizations are not knowledge sharing, accumulating and creating organizations, which deprives them of innovativeness and development. By creating knowledge orientated organizations, not only will the Chinese subsidiaries be able to absorb competencies associated directly to the faced issues but it will also facilitate any future knowledge transfer between the organizations

Intelligent Fuzzy Assessment System for English Academic Writing in Engineering Education

This paper aims to address the objectivity and reliability of academic writing assessment through the rule based fuzzy logic assessment system and to show the feasibility of computer assisted assessment in language learning. In this study, first, a user-friendly and rule based intelligent fuzzy writing assessment software (IFWAS) system was developed. The designed IFWAS is based on the Fuzzy Group Decision Support System (FGDSS), which provides a score and diagnostic feedback to students. The system has a flexible database to form written reinforcing feedback addressed both to students’ weaknesses and strengths in writing. Secondly, to see the efficacy of software in an educational setting, it was implemented to assess the academic English writing skills of 15 engineering students. The focus group interviews conducted with students and teachers after the empirical research underlined the importance of an objective and transparent assessment in learning; thus indicating that the educational use of software had positive pedagogical implications

Events and costs (€, 2013).

<p>Total number of events of symptomatic (recurrent) DVT, symptomatic (recurrent) non-fatal PE, bleeding complications and related costs from societal perspective within a hypothetical patient population of 1,000 subjects receiving dabigatran and VKA for 180 days (base case analysis).</p><p>VKA: vitamin-K antagonist; VTE: venous thromboembolism; DVT: deep venous thrombosis; PE: pulmonary embolism: CRNM: clinically relevant non-major; INR, international normalized ratio.</p><p>¹Until the end of the post-treatment period</p><p>²First occurrence of primary efficacy endpoint</p><p>³During double-dummy period</p><p>⁴Statistically significant differences between VKA and dabigatran</p><p>⁵Productivity losses by those 50% of the patients being 64 years-of-age and younger.</p><p>Events and costs (€, 2013).</p

Cost-effectiveness acceptability curve in the base case analysis.

<p>Cost-effectiveness acceptability curve in the base case analysis.</p

Tornado diagram illustrating the impact on the incremental effects from sensitivity analyses for dabigatran vs. vitamin-K antagonists.

<p>Light grey bars denote influence of the high value of the 95% confidence interval range and dark grey bars denote influence of the low value for parameters investigated. The solid vertical line represents the base case incremental QALYs for dabigatran compared to VKA. Horizontal bars indicate the range of incremental QALYs obtained by setting each variable to the values shown while holding all other values constant. INR, international normalized ratio; PE, pulmonary embolism; rDVT, recurrent deep vein thrombosis; VKA, vitamin K antagonist; CRNM, clinically relevant non-major.</p

Cost-effectiveness plane in the base case analysis.

<p>The graph shows the results of the probabilistic sensitivity analysis of dabigatran treatment compared to VKA treatment in DVT over a period of 180 days from the societal perspective. Points below the diagonal line represent simulations in which dabigatran was a cost-effective alternative at a threshold of €20,000/QALY, below the x-axis, cost-saving points are shown.</p

Decision model for the DVT population.

<p>The model starts with the diagnosis deep venous thrombosis. All patients directly started with the treatment of VKA or dabigatran anticoagulation, probabilities for events differ per arm. VTE: venous thromboembolism; DVT: deep venous thrombosis; PE: pulmonary embolism; CRNM: clinically relevant non-major.</p