Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive,non-small cell lung cancer in China

Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China.

Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model.

Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1?mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY.

Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.     

Cost-effective analysis of clopidogrel versus aspirin for high risk patients with established peripheral arterial disease in China

Abstract

Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.

Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.

Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.

Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.     

Cost utility of allogeneic stem cell transplantation with matched unrelated donor versus treatment with imatinib for adult patients with newly diagnosed chronic myeloid leukaemia

Objective: To estimate, from the perspective of the German statutory health insurance, the cost utility of allogeneic stem cell transplantation with matched unrelated donor (MUD-SCT) in newly diagnosed, chronic-phase chronic myeloid leukaemia (CML) patients aged 40 years or younger, relative to the treatment with imatinib.

Methods: The incremental cost-effectiveness ratio (ICER) of the additional cost of imatinib versus MUD-SCT per quality-adjusted life year (QALY) gained was chosen as a target assessment. ICER was quantified using a Markov cohort modelling approach. The evaluation encompassed 5 years of treatment with either approach, and only direct medical costs (in €, year 2005) were considered.

Results: There were incremental costs of €77,410 for imatinib therapy per QALY gained versus MUD-SCT. No strategy was clearly dominant; on average, during 5 years, cost savings of €63,433 were obtained and 0.82 QALY lost by SCT compared to treatment with imatinib. QALYs gained in CML patients with either treatment resulted in considerable cost to the third-party payer in Germany. The results were particularly sensitive to the price of imatinib.

Conclusions: The analysis finds that imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of €77,410 per QALY is higher than commonly cited thresholds. The cost utility of MUD-SCT to treat CML in patients with a European Group for Blood and Marrow Transplantation score ≤ to 2 compares with that of the imatinib strategy.     

Cost-effectiveness analysis of tissue plasminogen activator in acute ischemic stroke in Iran

Aims: Tissue plasminogen activator (tPA) is used to treat acute ischemic stroke up to 4.5?h after symptom onset. Its cost-effectiveness in developing countries is not specified yet. This study aimed to study cost-effectiveness of tPA in Iran.

Methods: This is a cost-effectiveness analysis from the perspective of the third party payer to compare IV tPA with no tPA of ischemic stroke. A Markov model with a lifetime horizon was used to analyze the costs and outcomes. Cost data were extracted from the 94 patients admitted in two hospitals in Iran. All costs were calculated based on US dollars in 2016. Quality-adjusted life years (QALY) were extracted from previously published literature. Cost-effectiveness was determined by calculating ICER by TreeAge Pro 2011 software.

Results: Lifetime costs of no tPA strategy were higher than tPA ($10,718 in the no tPA group compared with $8,796 in the tPA group). The tPA arm gained 0.20 QALY compared with no tPA. ICER was $8,471 per QALY. ICER value suggests that tPA is cost-effective compared with no tPA.

Limitations: The limitations of the present study are the reliance on calculated QALY value of other countries and difficulty in accessing patients treated with tPA.

Conclusions: The balance of hospitalization and rehabilitation costs and QALYs support the conclusion that treatment with intravenous tPA in the 4.5-h time window is cost-effective from the perspectives of the third party payer and inclusion of tPA in the insurance benefit package being reasonable.     

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States

Abstract

Objective:

Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations.

Methods:

Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained.

Results:

Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations.

Limitations:

Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study.

Conclusions:

This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.     

Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective

Objective: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph?) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective.

Methods: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC. Response rates, event-free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year.

Results: The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab vs SOC was estimated to be $110,108/QALY gained in the base case. Cost-effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the sub-group of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost-effective was estimated to be 74%.

Limitations: The study does not explicitly consider the impact of adverse events of the treatment; no adjustments for long-term transplant rates were made.

Conclusions: Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph???B-precursor ALL from the US healthcare perspective at an ICER threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality-of-life (HRQoL) benefit over SOC.     

Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml

Abstract

Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400?ng/ml in the United States.

Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.

Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.

Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400?ng/ml, it is not a cost-effective treatment from a United States payer perspective.     

Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective

Abstract

Objective:

In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4?mg 3–4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600?mg daily, in 1970 patients with newly-diagnosed multiple myeloma (MM).

Methods:

An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources.

Results:

Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of £1653, yielding an ICER of £5443 per QALY gained. If the threshold ICER is £20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%.

Limitations:

The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years.

Conclusions:

Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.     

Cost-effectiveness of risk stratification for preventing type 2 diabetes using a multi-marker diabetes risk score

Abstract

Background:

Personalized medicine requires diagnostic tests that stratify patients into distinct groups that may differentially benefit from targeted treatment approaches. This study compared the costs and benefits of two approaches for identifying those at high risk of developing type 2 diabetes for entry into a diabetes prevention program. The first approach identified high risk patients using impaired fasting glucose (IFG). The second approach used the PreDx Diabetes Risk Score (DRS) to further stratify IFG patients into high-risk and moderate-risk groups.

Methods:

A Markov model was developed to simulate the incidence and disease progression of diabetes and consequent costs and quality-adjusted life expectancy (QALY), comparing alternative approaches for identifying high-risk patients. We modeled direct medical costs, including the costs of the stratification testing, over a 10-year time horizon from a US payer perspective.

Results:

Stratification of IFG patients by the DRS method leads to improved identification and prevention among those at highest risk. At 5 years, the number needed to treat (NNT) in the IFG-only approach was 39 patients to prevent one case of diabetes compared to an NNT of 15 in the IFG?+?DRS approach. When compared to IFG alone, the IFG?+?DRS approach results in an incremental cost-effectiveness ratio (ICER) of $17,100/QALY gained at 5 years and would become cost saving in 10 years. In contrast and as compared to no stratification, the IFG-only approach would produce an ICER of $235,500/QALY gained at 5 years and $94,600/QALY gained at 10 years. The study findings are limited by the generalizability of the DRS validation study and uncertainty regarding the long-term effectiveness of diabetes prevention.

Conclusions:

The analysis indicates that the cost-effectiveness of diabetes prevention can be improved by better identification of patients at highest risk for diabetes using the DRS.     

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium

Abstract

Objective:

To assess the cost-effectiveness of dabigatran etexilate (‘dabigatran’) vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF).

Research design and methods:

A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses.

Results:

In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses.

Limitations:

The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium.

Conclusion:

This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.     

Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis

Abstract

Objective:

To determine whether Medicare’s decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time.

Methods:

The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses.

Results:

Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses.

Limitations:

This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature.

Conclusions:

This study indicates that Medicare’s coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.     

Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer

Background: Nab-paclitaxel plus gemcitabine (NAB-P?+?GEM) and FOLFIRINOX have shown superior efficacy over gemcitabine (GEM) in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDA). Although the incremental clinical benefits are modest, both treatments represent significant advances in the treatment of a high-mortality cancer. In this independent economic evaluation for the US, the aim was to estimate the comparative cost-utility and cost-effectiveness of these three regimens from the payer perspective.

Methods: In the absence of a direct treatment comparison in a single clinical trial, the Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. A Markov model evaluated life years (LY) and quality-adjusted life years (QALY) gained with NAB-P?+?GEM and FOLFIRINOX over GEM, expressed as incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). All costs and outcomes were discounted at 3%/year. The impact of parameter uncertainty on the model was assessed by probabilistic sensitivity analyses.

Results: NAB-P?+?GEM was associated with differentials of +0.180 LY and +0.127 QALY gained over GEM at an incremental total cost of $25,965; yielding an ICER of $144,096/LY and ICUR of $204,369/QALY gained. FOLFIRINOX was associated with differentials of +0.368 LY and +0.249 QALY gained over GEM at an incremental total cost of $93,045; yielding an ICER of $253,162/LY and ICUR of $372,813/QALY gained. In indirect comparison, the overall survival hazard ratio (OS HR) for NAB-P?+?GEM vs FOLFIRINOX was 0.79 (95%CI?=?0.59–1.05), indicating no superiority in OS of either regimen. FOLFIRINOX had an ICER of $358,067/LY and an ICUR of $547,480/QALY gained over NAB-P?+?GEM. Tornado diagrams identified variation in the OS HR, but no other parameters, to impact the NAB-P?+?GEM and FOLFIRINOX ICURs.

Conclusions: In the absence of a statistically significant difference in OS between NAB-P?+?GEM and FOLFIRINOX, this US analysis indicates that the greater economic benefit in terms of cost-savings and incremental cost-effectiveness and cost-utility ratios favors NAB-P?+?GEM over FOLFIRINOX.     

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States

Abstract

Objective:

To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV?+?r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy.

Methods:

A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts.

Limitations:

The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV?+?r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained <$50,000/QALY when these values were varied in sensitivity analyses.

Results:

ATV?+?r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs ($275,986 vs. 269,160). ATR?+?r patients had lower rates of AIDS (19.08 vs. 20.05 cases/1,000 patient-years), OIs (0.44 vs. 0.52), diarrhea (1.27 vs. 6.26), and CHD events (5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25). ATV?+?r added 0.26 QALYs at a cost of $6826, for $26,421/QALY.

Conclusions:

By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV?+?r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (<$50,000/QALY) compared with LPV/r.     

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia

Aim:

A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US.

Methods:

A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs.

Results:

In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs?=?0.2–2.0), QALYs (ΔQALYs?=?0.2–1.9), and accrue highest CML-related costs (ΔCosts?=?$64,000–$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population.

Conclusions:

This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.     

Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands

Aims: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. Methods: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. Results: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ～50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. Conclusions: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.     

The cost effectiveness of palivizumab in term Inuit infants in the Eastern Canadian Arctic

Abstract

Introduction: Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation.

Methods: Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD$) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU.

Results: For all of Baffin Island infants (<1 year), the ICER was $39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of $152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of $24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time.

Conclusions: The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit.     

Cost effectiveness of rosuvastatin in patients at risk of cardiovascular disease based on findings from the JUPITER trial

Abstract

Objective:

This study assessed the long-term cost effectiveness of rosuvastatin therapy compared with placebo in reducing the incidence of major cardiovascular (CVD) events and mortality.

Methods:

A probabilistic Monte Carlo simulation model estimated long-term cost effectiveness of rosuvastatin therapy (20?mg daily) for the prevention of CVD mortality and morbidity. The model included three stages: (1) CVD prevention simulating the 4 years of the JUPITER trial, (2) initial CVD prevention beyond the trial, and (3) subsequent CVD event prevention. A US payer perspective was assessed reflecting direct medical costs, and up to a lifetime horizon. Sensitivity analyses tested the robustness of the model estimates.

Results:

For a hypothetical cohort of 100,000 patients at moderate and high risk of CVD events based on Framingham risk of ≥10%, estimated quality-adjusted life-years (QALYs) gained with rosuvastatin therapy compared with placebo was 33,480 over a lifetime horizon, and 25,380 and 9916 over 20-year and 10-year horizons, respectively. Approximately 12,073 events were avoided over the lifetime; 6,146 non-fatal MIs, 2905 non-fatal strokes, and 4030 CVD deaths avoided. Estimated incremental cost-effectiveness ratio (ICER) for cost per QALY was $7062 (lifetime), $10,743 (20-year horizon), and $44,466 (10-year horizon). For a hypothetical cohort similar to the overall JUPITER population, the cost per QALY ICER was $11,025 for the lifetime and $60,112 for a 10-year horizon.

Limitations:

The cost-effectiveness comparison of rosuvastatin 20?mg was against no active treatment (as opposed to an alternative statin) due to lack of comparative cardiovascular morbidity and mortality risk reduction data for other statins in a population similar to the JUPITER trial population. The analysis was conducted from the payer perspective and lack of inclusion of indirect costs limit interpretability of results from a societal perspective.

Conclusions:

Treatment with rosuvastatin 20?mg daily, is a cost-effective treatment alternative to no treatment in patients at a higher risk (Framingham risk ≥10%) of CVD.     

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma

Objective: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A?+?AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A?+?AVD from a US healthcare payer perspective.

Methods: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1.

Results: The ICER for A?+?AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure.

Conclusion: The ICER for A?+?AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A?+?AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Trial registration: ClinicalTrials.gov identifier: NCT01712490.     

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Abstract

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective.

Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018?US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness.

Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations.

Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15?months.

Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.     

Economic analysis of bevacizumab,cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC)

Abstract

Objective:

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients.

Methods:

A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources.

Results:

Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab?+?FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab?+?FBC, panitumumab?+?FBC is dominated and cetuximab?+?FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab?+?FBC had ～100%, ～100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively.

Conclusion:

For first-line treatment of KRAS-WT mCRC, bevacizumab?+?FBC is associated with substantially lower costs as compared to panitumumab?+?FBC or cetuximab?+?FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.