Cost-effectiveness of monitoring endoxifen levels in breast cancer patients adjuvantly treated with tamoxifen.

PURPOSE: Breast cancer is the most common malignancy in women worldwide. Recurrence rates in breast cancer are considered to be dependent on the serum concentration of endoxifen, the active metabolite of tamoxifen. The goal of this study is to investigate the cost-effectiveness of periodically monitoring serum concentrations of endoxifen in adjuvant estrogen receptor alfa (ERα) positive breast cancer patients treated with tamoxifen in the Netherlands. METHODS: A Markov model with disease-free survival (DFS), recurrent disease (RD), and death states was constructed. The benefit of drug monitoring was modeled via a difference in the fraction of patients achieving adequate serum concentrations. Robustness of results to changes in model assumptions were tested through deterministic and probabilistic sensitivity analyses. RESULTS: Monitoring of endoxifen added 0.0115 quality-adjusted life-years (QALYs) and saved € 1564 per patient in the base case scenario. Deterministic sensitivity analysis demonstrated a large effect on the incremental cost-effectiveness ratio (ICER) of the differences in costs and utilities between the DFS and RD states. Probabilistic sensitivity analysis showed that the probability of cost-effectiveness at a willingness to pay of € 0 per quality-adjusted life-year (QALY) was 89.8%. CONCLUSIONS: Based on this model, monitoring of endoxifen in adjuvant ERα + breast cancer patients treated with tamoxifen is likely to add QALYs and save costs from a healthcare payer perspective. We advise clinicians to consider integrating serum endoxifen concentration monitoring into standard adjuvant tamoxifen treatment of ERα + breast cancer patients.

NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands.

BACKGROUND: In 2012, around 400.000 patients in the Netherlands were treated with Vitamin K Antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) are available. NOACs do not require frequent INR monitoring which benefits patients, but also imposes a risk of reduced therapy adherence. The objective of this study is to describe uptake and patient adherence of NOACs in The Netherlands until October 2016. METHODS: Prescription data for 247.927 patients across 560 pharmacies were used to describe patient profiles, uptake of NOACs among new naive patients and switch between VKA and NOACs, and calculate therapy adherence as the Proportion of Days Covered (PDC). RESULTS: During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naive patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated compliance rate for NOAC patients shows that 88% of all users are adherent with a PDC higher than 80%. CONCLUSIONS: NOAC have overtaken VKA as the major treatment prescribed to new oral anticoagulant patients, and the number of starters on VKA is decreasing. Patients are generally adherent to NOACs during the implementation phase, the period that the medication is used. Fear for inadherence by itself does not need to be a reason for not prescribing NOACs instead of VKA.

Does conditional approval for new oncology drugs in Europe lead to differences in health technology assessment decisions?

An early access pathway of conditional approval for potentially beneficial medicines is available within the European regulatory framework. However, marketing authorization does not necessarily result in recommendations for public funding by health technology assessment (HTA) agencies. As conditional approval goes along with less than complete data on benefits and risks of a treatment option for a high medical need, this raises the question how HTA decision-making is affected by these uncertainties.

Real world cost of human epidermal receptor 2-positive metastatic breast cancer patients: a longitudinal incidence-based observational costing study in the Netherlands and Belgium.

Currently, no country-specific metastatic breast cancer (MBC) observational costing data are available for the Netherlands and Belgium. Our aim is to describe country-specific resource use and costs of human epidermal receptor 2 (HER-2)-positive MBC in the Netherlands and Belgium, making use of real-world data. The eligibility period for patient selection was from April 2004 to April 2010. Inclusion and retrospective data collection begins at the time of first diagnosis of HER-2-positive MBC during the eligibility period and ends 24 months post-index diagnosis of MBC or at patient death. We identified 88 eligible patients in the Netherlands and 44 patients in Belgium. The total costs of medical treatment and other resource use utilisation per patient was €48,301 in the Netherlands and €37,431 in Belgium. Majority of costs was related to the use of trastuzumab in both countries, which was 50% of the total costs in the Netherlands and 56% in Belgium respectively. Our study provides estimates of resource use and costs for HER-2-positive MBC in the Netherlands and Belgium. We noticed various differences in resource use patterns between both countries demonstrating caution is needed when transferring cost estimates between countries.

Time-dependent resource use and costs associated with different states of disease in patients diagnosed with HER-2-positive metastatic breast cancer.

Adequate reflection of disease progression and costs over time is essential in cost-effectiveness analyses based on health state-transition models. However, costing studies normally investigate the burden of metastatic breast cancer (MBC) without explicitly examining the impact of specific-disease states on health care costs over time. The objective of this study was to assess time-dependent costs of different health states of human epidermal receptor-2 (HER-2) positive MBC and the factors contributing to these costs. In the Netherlands, HER-2-positive MBC patients were identified in three different hospitals. Resource use was collected during 24 months, which was linked to unit costs and related to time with respect to date of MBC diagnosis, disease progression and death for each individual patient. Subsequently, monthly costs for different health states were calculated. Finally, a nonlinear mixed-effect modelling approach was used to provide a quantitative description of the time course of cumulative progression costs. Costs during stable disease were constant over time with a mean of $4,158. In contrast, monthly costs for progressive disease demonstrated a change over time with the largest costs in the first 2 months after diagnosis (p < 0.005). The developed mixed-effect model adequately described cumulative cost-time course and associated variability. During the last months of life, costs varied over time, with the last month of life as the most expensive one with a mean of $5,811 per patient per month. To reflect costs of HER-2-positive MBC accurately in Markov models, costs for stable disease can be defined time independent, however, costs of progressive disease should be defined time dependent, and costs related to the final months of life should be modelled as such. The mixed-effect model we have developed could now be considered for adequate description of the time-dependent cost of progressive disease.

The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis.

AIM: To compare the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of lymph node metastases in prostate cancer. METHODS: After a comprehensive literature search, studies were included that allowed construction of contingency tables for detection of lymph node metastases using CT or MRI. In addition, a summary receiver-operating characteristic (ROC) analysis was performed. RESULTS: A total of 24 studies were included. For CT, pooled sensitivity was 0.42 (0.26-0.56 95% CI) and pooled specificity was 0.82 (0.8-0.83 95% CI). For MRI, the pooled sensitivity was 0.39 (0.22-0.56 95% CI) and pooled specificity was 0.82 (0.79-0.83 95% CI). The differences in performance of CT and MRI were not statistically significant. CONCLUSION: CT and MRI demonstrate an equally poor performance in the detection of lymph node metastases from prostate cancer. Reliance on either CT or MRI will misrepresent the patient's true status regarding nodal metastases, and thus misdirect the therapeutic strategies offered to the patient.