Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a systematic and qualitative review.

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice represented a major change in the treatment of non-valvular atrial fibrillation (NVAF); drugs as effective as the gold standard were available, rapidly functioning and without major interferences with drugs and foods. However, a huge increase in the economic burden of NVAF was predicted, and many cost-effectiveness analyses were developed to aid policy makers and clinicians in implementing strategies for the prevention of stroke in NVAF. The present systematic review identified 54 studies from 21 different countries, reporting the incremental cost-effectiveness of dabigatran, apixaban, rivaroxaban and edoxaban. A critical appraisal of the studies was conducted in order to highlight consolidated results and biases.

Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis.

Edoxaban, an oral direct factor Xa inhibitor, has been found non-inferior to warfarin for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with a lower rate of intracranial bleeding. The aim of our investigation was to assess the cost-effectiveness of edoxaban versus warfarin from the perspective of the Italian health-care system. A Markov decision model was used to evaluate lifetime cost and quality-adjusted life expectancy of NVAF patients treated with warfarin or edoxaban. Transition probabilities were obtained from the ENGAGE AF-TIMI 48 trial, cost estimates were based on Italian prices and tariffs, utilities were obtained from the literature. One-way and second-order sensitivity analyses were performed. In the base case, lifetime costs were €18,658 for edoxaban and €14,060 for warfarin. Discounted quality-adjusted survival was 9.022 years for edoxaban and 8.425 years for warfarin, leading to an incremental cost-utility ratio of €7,713 per quality-adjusted life year (QALY) gained. Results were sensitive to time horizon, time in therapeutic range of warfarin and to the relative impact of warfarin versus edoxaban therapy onto quality of life. Probabilistic sensitivity analysis showed edoxaban to be cost-effective versus warfarin in 92.3 % of the simulations at a willingness-to-pay threshold of €25,000 per QALY. In conclusion, edoxaban proved to be a cost-effective alternative to warfarin in patients with moderate-to-high-risk NVAF.

Biological therapies in Crohn's disease: are they cost-effective? A critical appraisal of model-based analyses.

In refractory Crohn's disease, anti-TNF and anti-α 4 integrin agents are used for ameliorating disease activity but impose high costs to health-care systems. The authors systematically reviewed cost-effectiveness analyses based on decision models: most of the studies were judged to have a good quality, but a large portion assessed health and costs in a short time horizon, usually disregarding fistulizing disease and not considering safety. Infliximab induction followed by on-demand retreatment consistently proved to have a good cost per quality-adjusted life year, while maintenance treatment never satisfied commonly accepted cost-utility thresholds. Challenges in cost-effectiveness analysis include the lack of a standard model structure, a large variability in the costs of surgery and poor data on indirect costs. As clinical practice is moving to mucosal healing as a robust response marker, personalized schedules of anti-TNF therapies might prove cost-effective even in the perspective of the health-care system in the near future.

Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis.

BACKGROUND AND OBJECTIVE: Non-valvular atrial fibrillation (NVAF) increases the risk of systemic thromboembolic events; therefore, anticoagulant treatment with vitamin K antagonists is widely prescribed. Recently, new oral anticoagulants (NOAs) directly inhibiting thrombin (dabigatran) or factor Xa (rivaroxaban and apixaban) demonstrated their non-inferiority with respect to warfarin in reducing the thromboembolic risk. The aim of this study was to estimate the cost effectiveness of NOAs in an Italian setting. METHODS: A Markov decision model including ten health states and death was developed, and a 3-month Markov cycle and lifetime horizon were adopted. Transition probabilities and quality of life were estimated from three randomized trials and from additional reports in the literature. Analysis was performed in the context of the Italian National Health System. First- and second-order sensitivity analyses were made to test the robustness of the results. The mean European cost of dabigatran (2.58/day) was assigned to each NOA. RESULTS: The incremental cost-utility ratio was below 25,000/quality-adjusted life-year (QALY) gained for each NOA and each CHADS2 level, but differences among drugs were found. This result was sensitive to the time in (warfarin) therapeutic range and time horizon. CONCLUSIONS: Our analysis suggests that NOAs are a cost-effective treatment for the prevention of stroke in patients with NVAF in the Italian healthcare setting.

Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer.

PURPOSE: To evaluate the cost-effectiveness of 12-month adjuvant trastuzumab therapy in women with high-risk human epidermal growth factor receptor 2 (HER2) -positive early breast cancer. METHODS: A Markov model tracked quarterly patients' transitions between five health states: disease free, local relapse, disease free after local relapse, metastatic disease, and death. Patients were allowed to incur symptomatic or asymptomatic transient cardiac dysfunction during trastuzumab administration. Probabilities were derived mainly from the combined report of the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials (95% node positive) and a meta-analysis by the Early Breast Cancer Trialists' Collaborative Group. Costs were estimated from the perspective of the Italian and US health care systems. The analysis was run during a 15-year time horizon. A 3% yearly discount rate was applied to both costs and life-years. Second-order Monte-Carlo and probabilistic sensitivity analyses were performed. RESULTS: Adjuvant trastuzumab increases life expectancy by 1.54 (1.18 discounted) quality-adjusted life-years (QALYs). At a cost of 675 euros and 767 dollars per weekly dose in the Italian and US setting, respectively, trastuzumab achieves its clinical benefit at a cost of 14,861 euros (95% CI, 3,917 euros to 44,028 euros) and 18,970 dollars (95% CI, 6,014 dollars to 45,621 dollars) per QALY saved. The incremental cost effectiveness was higher than 50,000 euros/QALY (or 60,000 dollars/QALY) at time horizons shorter than 7.8 years and for patients older than 76 years or with a 10-year risk of relapse lower than 15%. The results confirmed the cost effectiveness when simulating a Herceptin Adjuvant Trial (HERA) -like scenario at multiway sensitivity analysis. CONCLUSION: In a long-term horizon, adjuvant trastuzumab is a cost-effective therapy for patients with HER2-positive, high-risk, early breast cancer.

Clinical and economic issues in the treatment of advanced breast cancer with bisphosphonates.

An ideal palliative therapy for bone metastases would successfully reduce skeletal complications in several thousands of breast cancer patients. Second- and third-generation bisphosphonates are effective in reducing the overall skeletal complication rate and the time to first skeletal complication. Nevertheless, not enough evidence supports their benefit on quality of life. Furthermore, bisphosphonates are expensive (up to 775 US dollars per month, 2002 value) and cost-effectiveness evaluations have been limited to pamidronate (pamidronic acid). In economic evaluations of pamidronate, resulting incremental dollar per quality-adjusted life year gained ranged from cost savings to 108,000 US dollars per quality-adjusted life year. The data were quite sensitive to quality-of-life estimates and country-specific cost values. Because of the wide range of the cost-effectiveness ratio, it is uncertain whether the universal prescription of bisphosphonates in this setting represents an efficient use of healthcare resources. Probably, country- and drug-specific policies might increase the efficiency of this treatment. Further outcomes research is required to assess these agents more fully.