Budget Impact Analysis of Metformin Sustained Release for the Treatment of Type 2 Diabetes in The Netherlands

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

Modelling the Cost-Effectiveness of Implementing a Dietary Intervention in Renal Transplant Recipients

Background: The Dietary Approach to Stop Hypertension (DASH) and potassium supplementation have been shown to reduce the risk of death with a functioning graft (DWFG) and renal graft failure in renal transplant recipients (RTR). Unfortunately, a key problem for patients is the adherence to these diets. The aim of this study is to evaluate the cost-effectiveness and budget impact of higher adherence to either the DASH or potassium supplementation. Methods: A Markov model was used to simulate the life course of 1000 RTR in the Netherlands. A societal perspective with a lifetime time horizon was used. The potential effect of improvement of dietary adherence was modelled in different scenarios. The primary outcomes are the incremental cost-effectiveness ratio (ICER) and the budget impact. Results: In the base case, improved adherence to the DASH diet saved 27,934,786 and gained 1880 quality-adjusted life years (QALYs). Improved adherence to potassium supplementation saved euro1,217,803 and gained 2901 QALYs. Both resulted in dominant ICERs. The budget impact over a five-year period for the entire Dutch RTR population was euro8,144,693. Conclusion: Improving dietary adherence in RTR is likely to be cost-saving and highly likely to be cost-effective compared to the current standard of care in the Netherlands

Comparative Cost-Effectiveness of Drugs in Early versus Late Stages of Cancer:Review of the Literature and a Case Study in Breast Cancer

Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of this study is to identify a possible trend in the cost-effectiveness for the early/adjuvant and late/metastatic stages of oncological drugs through review and case study.We reviewed pairs of cost-effectiveness analyses of the same oncological drug in different stages for Scotland and the Netherlands. The case study in this report was directed at trastuzumab in the Dutch situation. Using a simplified Markov model, the cost-effectiveness in early and late stage of breast cancer was calculated and compared to the findings from the review.Comparable studies were found for cetuximab, bortezomib and bosutinib. Treatments in the late stage were found to be more expensive per QALY by a factor ranging from 1.5 to 12. The case study provided a similar result; late stage treatment was more expensive by a factor 10. Using, for example, a threshold of € 80,000/QALY, the early stage of cetuximab, bosutinib and trastuzumab are deemed cost-effective, while their compared late stage is lifted over the threshold and potentially considered not cost-effective.ICERs of oncological drugs used in different stages are more unfavourable in the late stage than in the early stage. Applying a reasonable threshold may result in early stage treatment being deemed cost-effective while late stage potentially not. Authorities should be aware of this when assessing oncological drugs and interpreting the corresponding ICERs, in the situation where oncological drugs are generally most submitted for reimbursement in the late stage initially

Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands:a real-world data based cost-effectiveness analysis

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 our 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 one-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 subpopulations: 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 €72,350 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 €20,000/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 €157/QALY. CONCLUSIONS: In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and potentially cost-saving alternative to VKA in the Netherlands

Extended Treatment with Apixaban for Venous Thromboembolism Prevention in the Netherlands:Clinical and Economic Effects

Background ?Dutch guidelines advise extended anticoagulant treatment with direct oral anticoagulants or vitamin K antagonists for patients with idiopathic venous thromboembolism (VTE) who do not have high bleeding risk. Objectives ?The aim of this study was to analyze the economic effects of extended treatment of apixaban in the Netherlands, based on an updated and adapted previously published model. Methods ?We performed a cost-effectiveness analysis simulating a population of 1,000 VTE patients. The base-case analysis compared extended apixaban treatment to no treatment after the first 6 months. Five additional scenarios were conducted to evaluate the effect of different bleeding risks and health care payers' perspective. The primary outcome of the model is the incremental cost-effectiveness ratio (ICER) in costs (€) per quality-adjusted life-year (QALY), with one QALY defined as 1 year in perfect health. To account for any influence of the uncertainties in the model, probabilistic and univariate sensitivity analyses were conducted. The treatment was considered cost-effective with an ICER less than €20,000/QALY, which is the most commonly used willingness-to-pay (WTP) threshold for preventive drugs in the Netherlands. Results ?The model showed a reduction in recurrent VTE and no increase in major bleeding events for extended treatment in all scenarios. The base-case analysis showed an ICER of €9,653/QALY. The probability of being cost-effective for apixaban in the base-case was 70.0% and 91.4% at a WTP threshold of €20,000/QALY and €50,000/QALY, respectively. Conclusion ?Extended treatment with apixaban is cost-effective for the prevention of recurrent VTE in Dutch patients

Budget Impact Analysis of a Renal Point-of-Care Test in Dutch Community Pharmacies to Prevent Antibiotic-Related Hospitalizations

OBJECTIVES: Medication errors that lead to adverse drug reactions are a key cause of unintentional patient harm and subsequent economic burden. To prevent this, measurement of renal function could be considered. The aim of this study was to determine the budget impact of obtaining and evaluating renal function in community pharmacies in the Netherlands to prevent antibiotic-related hospitalizations. METHODS: A decision model was built to simulate the process of antibiotic prescriptions in community pharmacies with and without the use of a point-of-care test (PoCT) in patients aged 65 years and older. By using a PoCT, the number of patients with renal function values available increases, leading to the possibility of dose adjustment when necessary. In turn, this might avoid hospitalizations. For this study, real-life patient data were used from 351 community pharmacies. Direct costs of renal function screening, antibiotic treatments, and medical care due to antibiotic-related hospitalization were included. RESULTS: The budget impact analysis showed annual cost-savings of €86 per patient through the availability of renal function values in Dutch community pharmacies. Savings were mostly due to avoided hospitalizations. CONCLUSION: Obtaining and evaluating renal function in community pharmacies by point of care tests is expected to be cost-saving in the Netherlands

A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy

Objective Genotyping for CYP2D6 has the potential to predict differences in metabolism of nortriptyline. This information could optimize pharmacotherapy. We determined the costs and effects of routine genotyping for old aged Dutch depressed inpatients. Methods With a decision-tree, we modelled the first 12 weeks of nortriptyline therapy. Direct costs of genotyping, hospitalization, therapeutic drug monitoring and drugs were included. Based on genotype, patients could be correctly, sub-, or supratherapeutically dosed. Improvement from sub-or supratherapeutically dosed patients to correctly dosed patients was simulated, assuming that genotyping would prevent under-or overdosing of patients. In the base case, this improvement was assumed to be 35%. A probabilistic sensitivity analysis (PSA) was performed to determine uncertainty around the incremental cost-effectiveness ratio (ICER). Results In the base case analysis, costs for genotyping were assumed sic200 per test with a corresponding ICER at sic1 333 000 per QALY. To reach a sic50 000 per QALY cut-off, genotyping costs should be decreased towards sic40 per test. At genotyping test costs <sic35 per test, genotyping was dominant. At test costs of sic17 per test there was a 95% probability that genotyping was cost-effective at sic50 000 per QALY. Conclusions CYP2D6 genotyping was not cost-effective at current genotyping costs at a sic50 000 per QALY threshold, however at test costs below sic40, genotyping could be costs-effective

Budget Impact Analysis of Metformin Sustained Release for the Treatment of Type 2 Diabetes in The Netherlands

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

Model structure for the treatment of major depressive disorder with nortriptyline during the first 12 weeks.

<p>Patients who receive a dosage which led to therapeutic plasma concentrations (i.e. “correct”) did not receive a next dose evaluation. Patients who quit nortriptyline pharmacotherapy entered a wash out period with a disutility of 0.20 for 14 days. After this period, pharmacotherapy with 6 tranylcypromine was initiated for the remaining time in the model. PM = poor metabolizer, IM = intermediate metabolizer, EM = extensive metabolizer, UM = ultrarapid metabolizer.</p