Pharmacokinetic Parameter Driven Outcomes Model Predicts a Reduction in Bleeding Events Associated with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin- Free Method in a Chinese Healthcare Setting

Background: Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. Methods: Head-to-head PK profile data of BAY 81-8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. Results: Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3%, 9.3% and 19.3%, respectively for BAY 81-8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. BAY 81-8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. Conclusion: Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81-8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81-8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

Cost-effectiveness of thrombectomy in patients with minor stroke and large vessel occlusion: effect of thrombus location on cost-effectiveness and outcomes

BackgroundTo evaluate the cost-effectiveness of endovascular thrombectomy (EVT) to treat large vessel occlusion (LVO) in patients with acute, minor stroke (National Institute of Health Stroke Scale (NIHSS) <6) and impact of occlusion site.MethodsA Markov decision-analytic model was constructed accounting for both costs and outcomes from a societal perspective. Two different management strategies were evaluated: EVT and medical management. Base case analysis was done for three different sites of occlusion: proximal M1, distal M1 and M2 occlusions. One-way, two-way and probabilistic sensitivity analyses were performed.ResultsBase-case calculation showed EVT to be the dominant strategy in 65-year-old patients with proximal M1 occlusion and NIHSS <6, with lower cost (US$37 229 per patient) and higher effectiveness (1.47 quality-adjusted life years (QALYs)), equivalent to 537 days in perfect health or 603 days in modified Rankin score (mRS) 0–2 health state. EVT is the cost-effective strategy in 92.7% of iterations for patients with proximal M1 occlusion using a willingness-to-pay threshold of US$100 000/QALY. EVT was cost-effective if it had better outcomes in 2%–3% more patients than intravenous thrombolysis (IVT) in absolute numbers (base case difference −16%). EVT was cost-effective when the proportion of M2 occlusions was less than 37.1%.ConclusionsEVT is cost-effective in patients with minor stroke and LVO in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with non-reperfusion. Our study emphasizes the need for caution in interpreting previous observational studies which concluded similar results in EVT versus medical management in patients with minor stroke due to a high proportion of patients with M2 occlusions in the two strategies.

Cost-Effectiveness and Value-Based Pricing of Aducanumab for Patients With Early Alzheimer Disease

Introduction:Aducanumab was granted accelerated approval with a conflicting evidence base, near-unanimous FDA Advisory Committee vote to reject approval, and a widely criticized launch price of $56,000 per year. The objective of this analysis was to estimate its cost-effectiveness.Methods:We developed a Markov model to compare aducanumab in addition to supportive care to supportive care alone over a lifetime horizon. Results were presented from both the health system and modified societal perspective. The model tracked the severity of disease and the care setting. Incremental cost-effectiveness ratios were calculated, and a threshold analysis was conducted to estimate at what price aducanumab would meet commonly used cost-effectiveness thresholds.Results:Using estimates of effectiveness based on pooling of data from both pivotal trials, patients treated with aducanumab spent four more months in earlier stages of AD. Over the lifetime time horizon, treating a patient with aducanumab results in 0.154 more QALYs gained per patient and 0.201 evLYGs per patient from the health care system perspective, with additional costs of approximately $204,000 per patient. The incremental outcomes were similar for the modified societal perspective. At the list price of $56,000 per year, the cost-effectiveness ranged from $1.02 million per evLYG to $1.33 million per QALY gained from the health care system perspective; and from $938,000 per evLYG to $1.27 million per QALY gained in the modified societal perspective. The annual price to meet commonly used cost-effectiveness thresholds ranged from $2,950 to $8,360, which represents a discount of 85-95% off from the annual launch price set by the manufacturer. Using estimates of effectiveness based only on the trial that suggested a benefit, the mean incremental cost was greater than $400,000 per QALY gained.Discussion:Patients treated with aducanumab received minimal improvements in health outcomes at considerable cost. This resulted in incremental cost-effectiveness ratios that far exceeded commonly used value thresholds, even under optimistic treatment effectiveness assumptions. These findings are subject to the substantial uncertainty regarding whether aducanumab provides any true net health benefit, but evidence available currently suggests that an annual price of aducanumab of $56,000 is not in reasonable alignment with its clinical benefits.

Cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands in different age groups

Objective We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. Methods A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. Results The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50–60 years, 50–70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50–60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60–70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50–60 years and 50–70 years. Conclusion This study showed that lung cancer screening is cost-effective in the Netherlands.

Cost-Effectiveness Analysis of Camrelizumab Plus Chemotherapy vs. Chemotherapy Alone as the First-Line Treatment in Patients With IIIB–IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Without EGFR and ALK Alteration from a Perspective of Health - Care System in China

Objective: The CAMEL clinical trial (412 patients were randomly assigned to either camrelizumab plus chemotherapy (n = 205) or chemotherapy alone (n = 207)) demonstrated that camrelizumab plus chemotherapy (CC) improved the overall survival time (OS) and progression-free survival time (PFS) of patients with metastatic nonsquamous non-small cell lung cancer (non-sq NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations (EGFRm and ALKm) vs. chemotherapy (C) alone. Our objective was to conduct a cost-effectiveness analysis of CC vs. C from a perspective of health - care system in China with a lifetime horizon to identify whether it will be cost-effective.Materials and Methods: A partitioned survival model (PSM) was applied for patients with IIIB–IV non-sq NSCLC without EGFRm and ALKm. Transition parameters and proportions of three health states were derived from the CAMEL trial. The model was designed using a lifetime horizon, a 21-day cycle, and a 5% discount rate of costs and outcomes. It was deemed cost-effective in China if the incremental cost-effectiveness ratio (ICER) value is less than $32,457 per quality adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses were performed to verify the influence of parameter uncertainty on the results.Results: In the base-case analysis, we found that the ICER of CC compared with C is $-7,382.72/QALY which meant that CC had lower costs and better outcomes. The results of the sensitivity analyses demonstrated that the result was robust for the ICERs never transcending the willingness-to-pay (WTP) threshold.Conclusion: Camrelizumab plus chemotherapy is an obviously cost-effective therapeutic regime for patients of IIIB–IV non-sq NSCLC without EGFRm and ALKm in China at a $32,457 WTP threshold.

The Optimum Allocation of Consumption of the Fisherian Shipwrecked Sailors

The theory of interest of Irving Fisher was designed to explain positive, zero, and negative interest rate. One of the intertemporal equilibria with the zero interest is an economy with a given supply of hardtacks for shipwrecked sailors. Hardtacks can be fully saved for the future, but their stock cannot be enlarged by production. Fisher presented several streams of consumption of hardtacks over time. This paper shows that the Fisherian paths are not consistent with the dynamic optimization model. Different trajectories of the optimum consumption are calculated and sketched. Their shape depends on the value of the subjective discount rate, the intertemporal elasticity of substitution in consumption, and the lifetime horizon of the shipwrecked sailors. None of them resemble the original Fisher examples.

Is single-inhaler triple therapy for COPD cost-effective in the UK? The IMPACT trial

BackgroundThe IMPACT trial demonstrated superior outcomes following 52 weeks of once-daily single-inhaler treatment with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg compared with once-daily FF/VI (100/25 μg) or UMEC/VI (62.5/25 μg). This study evaluates the cost-effectiveness of FF/UMEC/VI compared with FF/VI or UMEC/VI for the treatment of chronic obstructive pulmonary disease (COPD) from a United Kingdom National Health Service perspective.MethodsPatient characteristics and treatment effects from IMPACT were populated into a hybrid decision tree/Markov economic model. Costs (GB£ inflated to 2018 equivalents) and health outcomes were modelled over a lifetime horizon, with a discount rate of 3.5% per annum applied to both. Sensitivity analyses were performed to test the robustness of key assumptions and input parameters.ResultsCompared with FF/VI and UMEC/VI, FF/UMEC/VI provided an additional 0.296 and 0.145 life years (LYs; discounted), and 0.275 and 0.118 quality-adjusted life years (QALYs), at an additional cost of £1129 and £760, respectively. Incremental cost-effectiveness ratios (ICERs) for FF/UMEC/VI were £4104/QALY and £3809/LY gained versus FF/VI and £6418/QALY and £5225/LY gained versus UMEC/VI. At a willingness-to-pay threshold of £20 000/QALY, the probability that FF/UMEC/VI was cost-effective was 96% versus FF/VI and 74% versus UMEC/VI. Results were similar in a subgroup reflecting patients recommended triple therapy in the 2019 National Institute for Health and Care Excellence COPD guideline.ConclusionsFF/UMEC/VI single-inhaler triple therapy improved health outcomes and was a cost-effective option compared with FF/VI or UMEC/VI for patients with symptomatic COPD and a history of exacerbations in the UK at recognised cost-effectiveness threshold levels.

Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors

BackgroundThe INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors.MethodWe used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient’s lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses.ResultsThe base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000.ConclusionAs the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain

Background: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.Methods: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.Results: A target population of 8,755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.Conclusions: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

The cost-effectiveness of B-type natriuretic peptide-guided care in compared to standard clinical assessment in outpatients with heart failure in Tehran, Iran

Background B-type natriuretic peptide (BNP) is commonly used as a diagnostic method for patients with heart failure. This study was designed to evaluate the cost-effectiveness of BNP compared to standard clinical assessment in outpatients with heart failure with reduced ejection fraction (HFrEF) in Tehran, Iran. Methods This study was a cost-effectiveness analysis carried on 400 HFrEF outpatients > 45 years who were admitted to Rasoul Akram General Hospital of Tehran, Iran. A Markov model with a lifetime horizon was developed to evaluate economic and clinical outcomes for BNP and standard clinical assessment. Quality-adjusted life-years (QALYs), direct, and indirect costs collected from the patients. Results The results of this study indicated that mean QALYs and cost were estimated to be 2.18 QALYs and $1835 for BNP and 2.07 and $2376 for standard clinical assessment, respectively. In terms of reducing costs and increasing QALYs, BNP was dominant compared to standard clinical assessment. Also, BNP had an 85% probability of being cost-effective versus standard clinical assessment if the willingness to pay threshold is higher than $20,800/QALY gained. Conclusion Based on the results of the present study, measuring BNP levels represents good value for money, decreasing costs and increasing QALYs compared to standard clinical assessment. It is suggested that the costs of the BNP test be covered by insurance in Iran. The result of the current study has important implications for policymakers in developing clinical guidelines for the diagnosis of heart failure.