Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden.
The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs.
The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%.
This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.
To estimate the economic implications of introducing dabigatran etexilate ('dabigatran') for anti-coagulation therapy in Danish patients with non-valvular atrial fibrillation based on results of the RE-LY trial.
The lifetime cost and outcomes of dabigatran and warfarin were estimated using a previously published cost-effectiveness model. The model utilizes the data from the RE-LY study to estimate the costs and outcomes of stroke prevention in atrial fibrillation. Cost estimates were based on official Danish tariffs and prices, and published literature on the cost of stroke. In the base-case analysis a conservative approach was adopted applying tariffs from the lowest range for the cost of International Normalized Ratio (INR) monitoring associated with warfarin. The effectiveness measure of the analysis was quality-adjusted life-years (QALY).
The model estimated that the mean cost per patient for the remaining life-time is euro 16,886 treated with warfarin and euro 18,752 treated with dabigatran. This was associated with mean QALYs per patient of 8.32 with warfarin and 8.59 with dabigatran. The resulting incremental cost-effectiveness ratio (ICER) of ~ euro 7000 per QALY gained is regarded as cost-effective by Danish standards. This conclusion was seen to be robust to realistic variations in input parameters, including adjustment for the RE-LY centres achieving the best INR monitoring quality. Threshold analysis revealed that dabigatran would be cost-saving in settings where the cost of warfarin monitoring exceeds euro 744 per year.
The analysis does not include all aspects of Danish clinical practice anti-coagulation that will influence cost-effectiveness of dabigatran, e.g., this study did not attempt to model quality of anticoagulation monitoring and under-utilization in clinical practice.
Based on the outcomes observed in the RE-LY trial, dabigatran represents a cost-effective alternative to warfarin in Denmark for all patients with atrial fibrillation within the licensed indication of dabigatran.
Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients
Sandjar Djalalov, Jaclyn Beca, and Jeffrey S. Hoch, Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital and Cancer Care Ontario; Sandjar Djalalov, Jaclyn Beca, Jeffrey S. Hoch, Murray Krahn, and Natasha B. Leighl, Canadian Centre for Applied Research in Cancer Control; Murray Krahn, Toronto Health Economics and Technology Assessment Collaborative; Ming-Sound Tsao and Natasha B. Leighl, Ontario Cancer Institute and Princess Margaret Cancer Centre, Toronto; and Jean-Claude Cutz, McMaster University, Hamilton, Ontario, Canada.
ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC). We estimated the cost effectiveness of EML4-ALK fusion testing in combination with targeted first-line crizotinib treatment in Ontario.
A cost-effectiveness analysis was conducted using a Markov model from the Canadian Public health (Ontario) perspective and a lifetime horizon in patients with stage IV NSCLC with nonsquamous histology. Transition probabilities and mortality rates were calculated from the Ontario Cancer Registry and Cancer Care Ontario New Drug Funding Program (CCO NDFP). Costs were obtained from the Ontario Case Costing Initiative, CCO NDFP, University Health Network, and literature.
Molecular testing with first-line targeted crizotinib treatment in the population with advanced nonsquamous NSCLC resulted in a gain of 0.011 quality-adjusted life-years (QALYs) compared with standard care. The incremental cost was Canadian $2,725 per patient, and the incremental cost-effectiveness ratio (ICER) was $255,970 per QALY gained. Among patients with known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained. The major driver of cost effectiveness was drug price.
EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.
• To assess the economic value of targeted therapies as first-line metastatic renal cell carcinoma (mRCC) treatment in the US and Sweden by indirect comparison of survival data.
• A Markov model simulated disease progression, adverse events and survival with sunitinib vs sorafenib in the US and bevacizumab plus interferon-a (IFN-a) in both countries. • Results, in life-years (LYs), progression-free LYs (PFLYs), quality-adjusted LYs (QALYs) gained and treatment costs (2008 USD) were obtained through deterministic and probabilistic analyses over the patient's lifetime.
• Sunitinib was more effective and less costly than sorafenib (gains of 0.52 PFLYs, 0.16 LYs and 0.17 QALYs and savings/patient of $13,576 in the US) and bevacizumab plus IFN-a (gains of 0.19 PFLYs, 0.23 LYs and 0.16 QALYs in both countries and savings/patient of $67,798 and $47,264 in the US and Sweden, respectively). • Results were most influenced by hazard ratios for progression-free and overall survival and treatment costs, making results generalizable across other countries if relative costs were to fall within the ranges of those in the US and Sweden.
• The present analyses suggest that first-line mRCC treatment with sunitinib is a cost-effective alternative to sorafenib and bevacizumab plus IFN-a.