Using the German HTA guidelines, the ICER is not taken into consideration. Instead, the efficiency frontier was introduced as an alternative, to avoid the use of QALYs and the setting of willingness-to-pay thresholds. • We conducted the first direct comparison of the German efficiency frontier methodology to the conventional ICER, using sacubitril/valsartan, a new treatment for patients with chronic heart failure with a reduced ejection fraction. • Sacubitril/valsartan has a favourable ICER in the German setting, comparable to other European countries. However, using the efficiency frontier, the results would inform decision makers that a considerable discount needs to be negotiated.

While initial extrauterine placement at the time of insertion is the most common mechanism of perforation, delayed transmural migration is another mechanism that can occur.

IntroductionRandomized clinical trials (RCTs) and real-world data (RWD) in patients with atrial fibrillation have shown that—compared to vitamin K antagonists (VKAs)—non-VKA oral anticoagulants (NOACs) are at least as effective in the prevention of ischaemic stroke, while decreasing the risk of bleeding.ObjectiveWe aim to evaluate the cost-effectiveness of the NOAC apixaban versus other NOACs (dabigatran, edoxaban and rivaroxaban) and VKA, for stroke prevention in patients with atrial fibrillation by including the available data both from RCT and real-world analyses of all NOACs into one integrative previously published model.MethodsThe model was updated to the current Dutch healthcare situation. The incremental cost-effectiveness ratio was calculated using either efficacy/effectiveness and safety data derived from a network meta-analysis (NMA) synthesizing NOAC RCTs or RWD. We conducted a systematic literature search to identify eligible publication to best inform the RWD-based analysis. Additional sensitivity and scenario analyses were conducted to test the robustness of the outcomes.ResultsIn the NMA-based analysis, apixaban appeared to be cost-effective compared to VKA (€3,506 per quality adjusted life-year) and dominant (cost-saving and more effective) over dabigatran 110 mg, dabigatran 150 mg, edoxaban and rivaroxaban. In the RWD-based analysis, apixaban was dominant over all other anticoagulants. In the scenario analysis apixaban appeared to be not cost-effective compared to dabigatran 150 mg, when using equal event-unrelated treatment discontinuation rates for each drug. In all other scenarios apixaban is cost-effective or cost-saving compared to VKA and other NOACs.ConclusionBased on RCTs as well as RWD, we conclude that apixaban is generally cost-effective or even cost-saving (less costly and more effective) compared to VKA and other NOACs in the overall population of patients with atrial fibrillation.

Background Adverse drug reactions and medication nonadherence are well-known causes of sub-optimal disease control and worsened disease outcomes in patients who are treated for type 2 diabetes. Metformin sustained release (SR) might reduce these adverse events and improve medication adherence via a simplified treatment regimen for metformin immediate release (IR)-intolerant patients. Objectives The aim of this study is to estimate the budget impact of metformin SR for the treatment of type 2 diabetes in the Netherlands, compared to the current standard of care (SoC) with metformin IR. Methods A budget impact model was built to represent the course of the disease and treatment pathway of type 2 diabetes patients eligible for metformin SR from a healthcare payer's perspective. Patients were considered eligible if they used less than 2000 mg metformin IR per day, but suffered from adverse events that might lead to therapy discontinuation, and if they were newly diagnosed with type 2 diabetes. The costs of type 2 diabetes treatment and related complications over a time horizon of 3 years were calculated. Univariate sensitivity analyses were conducted to show which parameters have the biggest influence on the budget impact. Results The budget impact analysis showed cost-savings of − €1,962,335 over a period of 3 years through implementation of metformin SR as an alternative to SoC with metformin IR. Savings were mostly driven by the delay of other, more expensive type 2 diabetes treatments, such as insulin. In sensitivity analyses, medication adherence and persistence appeared to have the biggest influence on the budget impact. Conclusion Metformin SR could potentially be a cost-saving alternative to metformin IR for the treatment of type 2 diabetes in the Netherlands, especially in patients experiencing adverse events with metformin IR. However, more research is needed to better predict the effect of using once-daily metformin, compared to multiple dosages, on medication adherence and persistence and to evaluate whether metformin SR really decreases the amount of adverse events.

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BackgroundDabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting.MethodsPreviously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER).ResultsIn the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving.ConclusionFrom a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.

ObjectivesIn the ‘Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism’ (SELECT-D) trial, rivaroxaban showed relatively low venous thromboembolism (VTE) recurrence but higher bleeding compared with dalteparin in patients with cancer. We aim to calculate the cost-effectiveness and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent VTE.SettingWe built a Markov model to calculate the cost-effectiveness from a societal perspective over a 5-year time horizon for the Dutch healthcare setting.ParticipantsA hypothetical cohort of 1000 cancer patients with VTE entered the model with baseline characteristics based on the SELECT-D trial.InterventionSix months of treatment with rivaroxaban (15 mg two times per day for first 3 weeks followed by 20 mg once daily) was compared with 6 months of treatment with dalteparin (200 IU/kg daily during month 1 followed by 150 IU/kg daily).Primary and secondary outcome measuresThe primary outcome of the cost-effectiveness analysis was the incremental cost-effectiveness ratio (ICER). The robustness of the model was evaluated in probabilistic and univariate sensitivity analyses. A budget impact analysis was performed to calculate the total annual financial consequences for a societal perspective in the Netherlands.ResultsIn the base case and all scenarios, rivaroxaban were cost-saving while also slightly improving the patient’s health, resulting in economically dominant ICERs. In the probabilistic sensitivity analysis, 77.8% and 98.7% of the simulations showed rivaroxaban to be cost-saving and more effective for a 5-year and 6-month time horizon, respectively. Rivaroxaban can save up to €11 326 763 (CI €5 164 254 to €17 363 231) in approximately 8000 cancer patients with VTE per year compared with dalteparin based on a 1-year time horizon.ConclusionsTreatment with rivaroxaban is economically dominant over dalteparin in patients with cancer at risk for recurrent VTE in the Netherlands. The use of rivaroxaban instead of dalteparin can save over €10 million per year, primarily driven by the difference in drug costs.

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies. Methods: Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device. Results: In the base case, rivaroxaban saved e72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of e20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was e157/QALY. Conclusions: In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands. ARTICLE HISTORY