Adapting a global cost-effectiveness model to local country requirements: posaconazole case study

Abstract

Background:

Many countries have various requirements for local economic analyses to assess the value of a new health technology and/or to secure reimbursement. This study presents a case study of an economic model developed to assess the cost-effectiveness of posaconazole vs standard azole therapy (fluconazole/itraconazole) to prevent invasive fungal infections (IFIs), which was adapted by at least 11 countries.

Methods:

Modeling techniques were used to assess the cost-effectiveness of posaconazole vs fluconazole/itraconazole as IFI prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndromes and chemotherapy-induced neutropenia. For the core model, the probabilities of experiencing an IFI, IFI-related death, and death from other causes were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. Locally changed parameters were probabilities of long-term death and survival, currency, drug costs, health utility, IFI treatment costs, and discount rate.

Results:

Locally adapted cost-effective modeling studies indicate that prophylaxis with posaconazole, compared with fluconazole/itraconazole, prolongs survival, and, in most countries, is cost-saving. In all countries, the model predicted that prophylaxis with posaconazole would be associated with an increase in life-years, with increases ranging from 0.016–0.1 life-year saved. In all countries, use of the model led to posaconazole being approved by the appropriate reimbursement authority.

Limitations:

The study did not have power to detect differences between posaconazole and fluconazole or itraconazole separately. The risk of death after 100 days was assumed to be equal for those who did and did not develop an IFI, and equal probabilities of IFI-related and other death during the trial period were used for both groups.

Conclusions:

A core economic model was successfully adapted locally by several countries. The model showed that posaconazole was cost-saving or cost-effective vs fluconazole/itraconazole and led to positive reimbursement listings.     

Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

Cost effectiveness of posaconazole in the prophylaxis of invasive fungal infections in acute leukaemia patients for the French healthcare system

Abstract

Background:

Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population.

The authors estimated the cost effectiveness of posaconazole versus SAA in France.

Methods:

A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design.

Results:

IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior.

Conclusion:

The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.     

Cost-effectiveness of rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation in the Japanese healthcare setting

Abstract

Aims: This article aimed to examine the cost-effectiveness of rivaroxaban in comparison to warfarin for stroke prevention in Japanese patients with non-valvular atrial fibrillation (NVAF), from a public healthcare payer’s perspective.

Materials and methods: Baseline event risks were obtained from the J-ROCKET AF trial and the treatment effect data were taken from a network meta-analysis. The other model inputs were extracted from the literature and official Japanese sources. The outcomes included the number of ischaemic strokes, myocardial infarctions, systemic embolisms and bleedings avoided, life-years, quality-adjusted life-years (QALYs), incremental costs and incremental cost-effectiveness ratio (ICER). The scenario analysis considered treatment effect data from the same network meta-analysis.

Results: In comparison with warfarin, rivaroxaban was estimated to avoid 0.284 ischaemic strokes per patient, to increase the number of QALYs by 0.535 per patient and to decrease the total costs by ¥118,892 (€1,011.11) per patient (1 JPY = 0.00850638 EUR; XE.com, 7 October 2019). Consequently, rivaroxaban treatment was found to be dominant compared to warfarin. In the scenario analysis, the ICER of rivaroxaban versus warfarin was ¥2,873,499 (€24,446.42) per QALY.

Limitations: The various sources of data used resulted in the heterogeneity of the cost-effectiveness analysis results. Although, rivaroxaban was cost-effective in the majority of cases.

Conclusion: Rivaroxaban is cost-effective against warfarin for stroke prevention in Japanese patients with NVAF, giving the payer WTP of 5,000,000 JPY.     

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.     

A short-term cost-effectiveness study comparing robot-assisted laparoscopic and open retropubic radical prostatectomy

Abstract

Objective:

To evaluate cost effectiveness and cost utility comparing robot-assisted laparoscopic prostatectomy (RALP) versus retropubic radical prostatectomy (RRP).

Methods:

In a retrospective cohort study a total of 231 men between the age of 50 and 69 years and with clinically localised prostate cancer underwent radical prostatectomy (RP) at the Department of Urology, Aarhus University Hospital, Skejby from 1 January 2004 to 31 December 2007, were included.

The RALP and RRP patients were matched 1:2 on the basis of age and the D’Amico Risk Classification of Prostate Cancer; 77 RALP and 154 RRP.

An economic evaluation was made to estimate direct costs of the first postoperative year and an incremental cost-effectiveness ratio (ICER) per successful surgical treatment and per quality-adjusted life-year (QALY). A successful RP was defined as: no residual cancer (PSA <0.2?ng/ml, preserved urinary continence and erectile function. A one-way sensitivity analysis was made to investigate the impact of changing one variable at a time.

Results:

The ICER per extra successful treatment was €64,343 using RALP. For indirect costs, the ICER per extra successful treatment was €13,514 using RALP. The difference in effectiveness between RALP and RRP procedures was 7% in favour of RALP. In the present study no QALY was gained 1 year after RALP, however this result is uncertain due to a high degree of missing data. The sensitivity analysis did not change the results noticeably.

Limitations:

The study was limited by the design resulting in a low percentage of information on the effect of medication for erectile dysfunction and only short-term quality of life was measured at 1 year postoperatively.

Conclusion:

RALP was more effective and more costly. A way to improve the cost effectiveness may be to perform RALP at fewer high volume urology centres and utilise the full potential of each robot.     

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.     

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial

Abstract

Background:

Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands.

Methods:

A multistate Markov model was developed to simulate how patients’ clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion.

Results:

The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained.

Limitations:

A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results.

Conclusions:

Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.     

Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Abstract

Objective:

To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium.

Methods:

A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained.

Results:

Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold.

Discussion:

Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published.

Conclusions:

HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.     

Evaluation of the long-term cost-effectiveness of liraglutide therapy for patients with type 2 diabetes in France

Objectives:

The present study aimed to compare the projected long-term clinical and cost implications associated with liraglutide, sitagliptin and glimepiride in patients with type 2 diabetes mellitus failing to achieve glycemic control on metformin monotherapy in France.

Methods:

Clinical input data for the modeling analysis were taken from two randomized, controlled trials (LIRA-DPP4 and LEAD-2). Long-term (patient lifetime) projections of clinical outcomes and direct costs (2013 Euros; €) were made using a validated computer simulation model of type 2 diabetes. Costs were taken from published France-specific sources. Future costs and clinical benefits were discounted at 3% annually. Sensitivity analyses were performed.

Results:

Liraglutide was associated with an increase in quality-adjusted life expectancy of 0.25 quality-adjusted life years (QALYs) and an increase in mean direct healthcare costs of €2558 per patient compared with sitagliptin. In the comparison with glimepiride, liraglutide was associated with an increase in quality-adjusted life expectancy of 0.23 QALYs and an increase in direct costs of €4695. Based on these estimates, liraglutide was associated with an incremental cost-effectiveness ratio (ICER) of €10,275 per QALY gained vs sitagliptin and €20,709 per QALY gained vs glimepiride in France.

Conclusion:

Calculated ICERs for both comparisons fell below the commonly quoted willingness-to-pay threshold of €30,000 per QALY gained. Therefore, liraglutide is likely to be cost-effective vs sitagliptin and glimepiride from a healthcare payer perspective in France.     

Cost-effectiveness of continuous subcutaneous apomorphine in the treatment of Parkinson’s disease in the UK and Germany

Abstract

Background:

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting ～5.2 million people worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option for advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC).

Methods:

A multi-country Markov-Model to simulate the long-term consequences, disease progression (Hoehn & Yahr stages 3–5, percentage of waking-time in the OFF-state), complications, and adverse events was developed. Monte-Carlo simulation accounted for uncertainty. Probabilities were derived from RCT and open-label studies. Costs were estimated from the UK and German healthcare provider’s perspective. QALYs, life-years (LYs), and costs were projected over a life-time horizon.

Results:

UK lifetime costs associated with CSAI amounts to £78,251.49 and generates 2.85 QALYs and 6.28 LYs (€104,500.08, 2.92 QALYs and 6.49 LYs for Germany). Costs associated with LCIG are £130,011.34, achieves 3.06 QALYs and 6.93 LYs (€175,004.43, 3.18 QALYs and 7.18 LYs for Germany). The incremental-cost per QALY gained (ICER) was £244,684.69 (€272,914.58). Costs for DBS are £87,730.22, associated with 2.75 QALYs and 6.38 LYs (€105,737.08, 2.85 QALYs and 6.61 LYs for Germany). CSAI dominates DBS. SOC associated UK costs are £76,793.49; 2.62 QALYs and 5.76 LYs were reached (€90,011.91, 2.73 QALYs and 6 LYs for Germany).

Conclusions:

From a health economic perspective, CSAI is a cost-effective therapy and could be seen as an alternative treatment to LCIG or DBS for patients with advanced PD.     

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France,Germany, Portugal,and the Netherlands

Abstract

Objective:

Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients.

Methods:

This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n?=?214) or placebo (n?=?208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses.

Results:

ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (?€2396 [€1284] in France, ?€2606 [€841] in Germany, ?€3326 [€309] in Portugal and ?€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France).

Conclusions:

This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.     

Cost-effectiveness analysis of bariatric surgery for morbid obesity in Belgium

Aims: This study presents the cost-effectiveness analysis of bariatric surgery in Belgium from a third-party payer perspective for a lifetime and 10-year horizon.

Materials and methods: A decision analytic model incorporating Markov process was developed to compare the cost-effectiveness of gastric bypass, sleeve gastrectomy, and adjustable gastric banding against conventional medical management (CMM). In the model, patients could undergo surgery, or experience post-surgery complications, type 2 diabetes, cardiovascular diseases, or die. Transition probabilities, costs, and utilities were derived from the literature. The impact of different surgical methods on body mass index (BMI) level in the base-case analysis was informed by the Scandinavian Obesity Surgery Registry and the Swedish Obese Subject (SOS) study. Healthcare resource use and costs were obtained from Belgian sources. A base-case analysis was performed for the population, the characteristics of which were obtained from surgery candidates in Belgium.

Results: In the base-case analysis over a 10-year time horizon, the increment in quality-adjusted life-years (QALYs) gained from bariatric surgery vs CMM was 1.4 per patient, whereas the incremental cost was €3,788, leading to an incremental cost-effectiveness ratio (ICER) of €2,809 per QALY. Over a lifetime, bariatric surgery produced savings of €9,332, an additional 1.1 life years and 5.0 QALYs. Bariatric surgery was cost-effective at 10 years post-surgery and dominant over conventional management over a lifetime horizon.

Limitations: The model did not include the whole scope of obesity-related complications, and also did not account for variation in surgery outcomes for different populations of diabetic patients. Also, the data about management of patients after surgery was based on assumptions and the opinion of a clinical expert.

Conclusions: It was demonstrated that a current mix of bariatric surgery methods was cost-effective at 10 years post-surgery and cost-saving over the lifetime of the Belgian patient cohort considered in this analysis.     

A review of international pharmacoeconomic models assessing the use of aspirin in primary prevention

Abstract

Purpose:

The aim of this narrative review was to summarise the cost analyses and supporting trial data for aspirin prophylaxis in primary prevention.

Methods:

A PubMed search using the term ‘aspirin and cost-effective and primary prevention’ was performed. Professional meetings (2009) were also searched for any relevant abstracts contacting the terms ‘aspirin’ and ‘cost effectiveness’. Where possible, outcomes were discussed in terms of cost implications (expressed as quality-adjusted life-year [QALY], disability-adjusted life-year or incremental cost-effectiveness ratio) in relation to the annual risk of cardiovascular disease. Aspirin was included in cost-effectiveness models that determined direct cost savings.

Results:

A total of 67 papers were identified using PubMed, and 17 cost-effectiveness studies, which assessed aspirin in primary prevention (largely based on the key primary prevention studies), and two abstracts were included in the review. These analyses showed that low-dose aspirin was cost effective in a variety of scenarios. In the UK, Germany, Spain, Italy and Japan, the mean 10-year direct cost saving (including follow-up costs and aspirin costs) per patient was €201, €281, €797, €427 and €889 with aspirin use in patients with an annual coronary heart disease risk of 1.5%. Cost-effectiveness analyses were affected by age, risk level for stroke and myocardial infarction (MI), risk of bleeds and adherence to aspirin. Underutilisation is a major limiting factor, as the appropriate use of aspirin in an eligible population (n?=?301,658) based on the NHANES database would prevent 1273 MIs, 2184 angina episodes and 565 ischaemic strokes in patients without previous events; this would result in a direct cost saving of $79.6?million (€54.7?million; 2010 values), which includes aspirin costs.

Conclusions:

Most analyses in primary prevention have shown that low-dose aspirin is a cost-effective option, and is likely to meet the willingness of a healthcare system to pay for any additional QALY gained in the majority of healthcare systems.     

Cost-effectiveness of switching to insulin degludec from other basal insulins in real-world clinical practice in Italy

Abstract

Aims: The costs associated with insulin therapy and diabetes-related complications represent a significant and growing economic burden for healthcare systems. The aim of this study was to evaluate the cost-effectiveness of switching to insulin degludec (degludec) vs continuing previous basal insulin, in Italian patients with type 1 (T1D) or type 2 (T2D) diabetes, using a long-term economic model.

Materials and methods: Data were retrieved from a real-world population of patients from clinical practice in Italy. Clinical parameters included in the base-case model were change from baseline in HbA_1c, rates of hypoglycemia, and basal and bolus insulin dose, at 6?months following switch to degludec. Costs of treatments were taken from official Italian pharmaceutical list prices and costs of hypoglycemia were based on the literature. The data were used to populate a long-term (lifetime) IQVIA CORE Diabetes Model to evaluate the incremental cost-effectiveness ratio (ICER) – cost per quality-adjusted life-year (QALY). The robustness of these results was tested with extensive sensitivity analyses by varying the time horizons and abolishing each of the treatment differences and previous basal insulins.

Results: The total incremental cost for degludec vs previous basal insulin was €–6,310 and €–2,682 for patients with T1D and T2D, respectively; the switch to degludec resulted in a QALY gain of 0.781 and 0.628. The long-term ICER for degludec vs continuing the previous basal insulin regimen showed that degludec was dominant for both T1D and T2D, meaning that patient health was improved in terms of QALYs with lower healthcare costs. Sensitivity analyses showed that degludec remained dominant in most scenarios including after elimination of any benefit in non-severe hypoglycemia and insulin dose, in both T1D and T2D.

Conclusions: Under routine care, switching to degludec is dominant, compared with continuing previous basal insulin, in Italian patients with T1D or T2D.     

Cost-effectiveness of everolimus plus reduced tacrolimus in de novo liver-recipients in the Italian setting

Introduction: Long-term exposure to calcineurin inhibitor-based immunosuppressant (IS) therapy in liver transplant (LT) recipients is associated with renal complications. In the randomized trial H2304, everolimus?+?reduced-dose tacrolimus (EVR?+?rTAC) demonstrated equivalent efficacy and superior renal function compared to standard-dose tacrolimus.

Methods: To evaluate the cost-effectiveness of EVR?+?rTAC vs TAC, in de novo LT patients, a Markov model simulating both liver and kidney function was developed and estimated the long-term outcomes of IS following LT. The analysis used the Italian healthcare payer perspective.

Results: Patients treated with EVR?+?rTAC gained on average 1.92 years and 1.62 quality-adjusted life years (QALYs). The incremental cost-effectiveness ratios (ICER) were €35,851 and €42,567 for LY gained and QALY gained, respectively. For the hepatitis-c sub-population, the ICERs decreased to €22,519 and €30,658, respectively.

Conclusion: EVR?+?rTAC improves survival and quality-of-life and is a cost-effective alternative to calcineurin-inhibitor monotherapy for patients requiring LT.     

Cost-effectiveness analysis of a sealing hemostat patch (HEMOPATCH) vs standard of care in cardiac surgery

Background: A recent randomized controlled trial showed that patients undergoing ascending aorta surgery treated with HEMOPATCH to control bleeding had a significantly better hemostasis success rate than with dry or wet gauze compression or similar standard of care (SOC).

Objective: To compare the cost-effectiveness using two different agents for hemostasis (HEMOPATCH vs dry or wet gauze compression or similar SOC) in cardiac surgery from the European hospital perspective.

Methods: A literature-based cost-effectiveness model estimating average cost per successful hemostasis event was developed based on the hemostasis efficacy difference (HEMOPATCH?=?97.6%, SOC?=?65.8%, p?<?.001). Additional clinically significant end-points studied in the trial (blood transfusions and surgical revisions) were also analyzed. It was assumed that each surgery utilized two units of HEMOPATCH (dimensions of 4.5?×?9?cm) and two units of SOC. Product acquisition costs for HEMOPATCH and SOC were included along with outcome-related costs derived from the literature and inflation-adjusted to 2017 EUR and GBP. Results are presented for an average hospital with an annual case load of 574 cardiac surgeries. One-way and probabilistic sensitivity analyses were performed.

Results: Considering only product acquisition cost, HEMOPATCH had an incremental cost-effectiveness ratio (ICER) of €1,659, €1,519, €1,623, and £1,725 per hemostasis success when compared to SOC for Italy, Spain, France, and the UK, respectively. However, when considering the cost and potential difference in the frequency of transfusions and revisions compared to SOC, the use of HEMOPATCH was associated with an annual reduction of six revisions and 60 transfusions, improving the ICER to €1,440, €1,222, €1,461, and £1,592, respectively. Sensitivity analysis demonstrated model robustness.

Conclusions: This analysis supports the use of HEMOPATCH over SOC in cardiac surgery in European hospitals to improve hemostasis success rates and potential cost offsets from reduced transfusions, complications, and surgical revisions.     

Cost-effectiveness of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with type 1 diabetes mellitus in the UK

Abstract

Objective:

The aim of this study was to evaluate the cost-effectiveness of insulin degludec (IDeg) vs insulin glargine (IGlar) as part of a basal-bolus treatment regimen in adults with T1DM, using a short-term economic model.

Methods:

Data from two phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg vs IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. The main outcome measure, the incremental cost-effectiveness ratio (ICER), was the cost per quality-adjusted life-year (QALY).

Results:

IDeg is a cost-effective treatment option vs IGlar in patients with T1DM on a basal-bolus regimen. The base case ICER was estimated at £16,895/QALY, which is below commonly accepted thresholds for cost-effectiveness in the UK. Sensitivity analyses demonstrated that the ICER was stable to variations in the majority of input parameters. The parameters that exerted the most influence on the ICER were hypoglycemia event rates, daily insulin dose, and disutility associated with non-severe nocturnal hypoglycemic events. However, even under extreme assumptions in the majority of analyses the ICERs remained below the commonly accepted threshold of £20,000–£30,000 per QALY gained.

Conclusions:

This short-term modeling approach accommodates the treat-to-target trial design required by regulatory bodies, and focuses on the impact of important aspects of insulin therapy such as hypoglycemia and dosing. For patients with T1DM who are treated with a basal-bolus insulin regimen, IDeg is a cost-effective treatment option compared with IGlar. IDeg may be particularly cost-effective for sub-groups of patients, such as those suffering from recurrent nocturnal hypoglycemia and those with impaired awareness of hypoglycemia.     

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.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in four European countries: Austria,Belgium, Greece,and Italy

Aim: The approved indication for denosumab (120?mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy.

Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study (“20090482”) in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included.

Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1–3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69–94%, 84–96%, 79–96%, and 50–92% likely to be cost-effective vs ZA, respectively.

Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data.

Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.