Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting

Objective: Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

Methods: A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed.

Results: An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios.

Limitations: Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients.

Conclusion: Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization’s cost-effectiveness threshold of up to 3-times the gross domestic product.     

Cost-effectiveness of insulin detemir compared with NPH insulin in people with type 2 diabetes in Denmark,Finland, Norway,and Sweden

Abstract

Objective:

To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden.

Methods:

Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir and NPH insulin in insulin naïve people with T2DM, and short-term (1-year) cost effectiveness analyses were performed. As no significant differences in HbA_1c were observed between the two treatment arms, the model was based on significant differences in favour of insulin detemir in frequency of hypoglycaemia (Rate-Ratio?=?0.52; CI?=?0.44–0.61) and weight gain (Δ?=?0.9?kg). Model outcomes were measured in Quality Adjusted Life Years (QALYs) using published utility estimates. Acquisition costs for insulin and direct healthcare costs associated with non-severe hypoglycaemic events were obtained from National Health Service public sources. One-way and probabilistic sensitivity analyses were performed.

Results:

Based on lower incidence of non-severe hypoglycaemic events and less weight gain, the QALY gain from initiating treatment with insulin detemir compared with NPH insulin was 0.01 per patient per year. Incremental cost-effectiveness ratios for the individual countries were: Denmark, Danish Kroner 170,852 (€22,933); Finland, €28,349; Norway, Norwegian Kroner 169,789 (€21,768); and Sweden, Swedish Krona 226,622 (€25,097) per QALY gained. Possible limitations of the study are that data on hypoglycaemia and relative weight benefits from a clinical trial were combined with hypoglycaemia incidence data from observational studies. These populations may have slightly different patient characteristics.

Conclusions:

The lower risk of non-severe hypoglycaemia and less weight gain associated with using insulin detemir compared with NPH insulin when initiating insulin treatment in insulin naïve patients with type 2 diabetes provide economic benefits in the short-term. Based on cost/QALY threshold values, this represents good value for money in the Nordic countries. Using a short-term modelling approach may be conservative, as reduced frequency of hypoglycaemia and less weight gain may also have positive long-term health-related implications.     

Cost-effectiveness of cinacalcet in secondary hyperparathyroidism in the United States

Abstract

Objective:

Cinacalcet has been used in controlling secondary hyperparathyroidism (SHPT) in dialysis patients since 2004, but its full economic evaluation has not been conducted from the US perspective. This study assesses the cost-effectiveness of cinacalcet and low-dose vitamin D for the treatment of SHPT in dialysis patients compared with flexible vitamin D.

Methods:

A lifetime patient-level simulation model was developed using ADVANCE trial data, including biomarker levels: parathyroid hormone, calcium, and phosphorus. The impact of the biomarkers on mortality, cardiovascular events, fractures, and parathyroidectomy were estimated from literature: Block, an observational study; Cunningham, a combined analysis of four randomized trials of cinacalcet; and Danese, a study investigating the effect of duration in recommended targets. Baseline event rates were derived from the large dialysis organizations registries. One-way and probabilistic sensitivity analyses (PSA) were conducted.

Results:

The cost-effectiveness ratio for cinacalcet compared with standard of care (vitamin D and phosphate binders) was $54,560 and $72,456/quality-adjusted-life-year (QALY) gained or an incremental cost of $3155 and $2638 per year alive for the Block and Danese variants, respectively. In the Cunningham variant, cost-effectiveness ratio for cinacalcet was $5064/QALY gained or a cost saving of $1068 per year. The difference in the results of the Cunningham variant vs other variants can be explained by the favorable impact of cinacalcet on outcomes, specifically cardiovascular events observed in the Cunningham study. The PSA showed 98% likelihood for cinacalcet to be cost-effective at $100,000/QALY threshold.

Limitations:

Observational data assessing effects on clinical outcomes, trial restriction to use calcium-containing phosphate binders, no utility data in SHPT dialysis population, and insufficient evidence on long-term impact of cinacalcet and vitamin D on biochemical markers.

Conclusions:

Cinacalcet treatment is cost-effective for treatment of SHPT in the US. Due to cost offsets, cinacalcet can reduce annual costs in some scenarios.     

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands

Abstract

Objectives:

Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands.

Methods:

A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP).

Results:

Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient’s lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000–80,000/QALY).

Conclusion:

RDN is a cost-effective intervention for patients with resistant hypertension 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.     

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 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 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 of benralizumab for severe,uncontrolled oral corticosteroid–dependent asthma in Sweden

Abstract

Aim: We investigated cost effectiveness of benralizumab vs. standard of care (SOC) plus oral corticosteroids (OCS) for patients with severe, eosinophilic OCS-dependent asthma in Sweden.

Materials and methods: A three-state, cohort-based Markov model of data from three Phase III benralizumab clinical trials (ZONDA [NCT02075255], SIROCCO [NCT01928771], and CALIMA [NCT01914757]) was used to assess the incremental cost-effectiveness ratio of benralizumab vs. SOC plus OCS. Health outcomes were estimated in terms of quality-adjusted life-years (QALYs). The model included costs and disutilities associated with extrapolated OCS-related adverse events. Patients with severe asthma were defined as those receiving OCS ≥5?mg/day.

Results: Benralizumab demonstrated a cost-effectiveness ratio vs. SOC plus OCS of 2018 Swedish Kronor (SEK) 366,855 (€34,127) per QALY gained, based on increases of 1.33 QALYs and SEK 488,742 (€45,344) per patient. Benralizumab treatment costs contributed most to incremental costs. The probability of benralizumab’s being cost-effective with willingness-to-pay (WTP) thresholds between SEK 429,972 (€40,000) and SEK 752,452 (€70,000) ranged from 75% to 99%.

Limitations: Potential limitations of these analyses include the use of combined data from three different clinical trials, a one-way sensitivity analysis that did not include mortality and transition estimates, and Observational & Pragmatic Research Institute (OPRI) data from the UK as a proxy of the Swedish health care system.

Conclusions: The results of these analyses demonstrate that benralizumab has a high probability of being cost-effective compared with SOC plus OCS for a subgroup of patients with severe, eosinophilic asthma receiving regular OCS treatment and may support clinicians, payers and patients in making treatment decisions.     

Economic evaluation of anti-epileptic drug therapies with specific focus on teratogenic outcomes

Abstract

Background:

Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy.

Objectives:

To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to estimate the impact of teratogenicity on the costs per quality adjusted life year (QALY).

Methods:

A decision-tree model is used to calculate the costs per QALY, taking into account the malformation risk in offspring due to the exposure to carbamazepine, lamotrigine or valproic acid, based on the European birth cohort of 2007. Probabilistic sensitivity analyses were performed using Monte Carlo simulation.

Results:

Valproic acid is dominated by carbamazepine after rank ordering on costs. The incremental cost-effectiveness of lamotrigine vs carbamazepine was estimated at €175,534 per QALY. Although valproic acid was dominated by carbamazepine in terms of costs and related effects, it is clinically relevant to compare lamotrigine with valproic acid. In particular, treatment options are dependent on several individual and clinical characteristics and these agents are therefore not always considered as interchangeable for all specified populations. The incremental cost-effectiveness for lamotrigine vs valproic acid was estimated at €13,370 per QALY. With assuming a willingness to pay threshold of €50,000 per QALY, results from the probabilistic analysis resulted in an acceptance level for lamotrigine vs carbamazepine and lamotrigine vs valproic acid of 4% and 99%, respectively.

Conclusion:

Based on epidemiological data it is advised to whenever possible avoid valproic acid during pregnancy. Both carbamazepine and lamotrigine are estimated to be cost-effective treatment options vs valproic acid if focused on teratogenicity.     

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 roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD

Abstract

Objective:

To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD.

Methods:

The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY).

Results:

Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963–$32,773.

Limitations:

A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5–30 years, even though the estimates were only observed in trials that spanned less than a year.

Conclusions:

The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.     

Prasugrel vs clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a model-based cost-effectiveness analysis for Germany,Sweden, the Netherlands,and Turkey

Abstract

Objective:

To evaluate the long-term cost-effectiveness of 12-months treatment with prasugrel vs clopidogrel from four European healthcare systems’ perspectives (Germany, Sweden, the Netherlands, and Turkey).

Methods:

In the TRITON-TIMI 38 trial, patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) were treated with prasugrel or clopidogrel. Prasugrel reduced the composite end-point (cardiovascular death, MI, or stroke), but increased TIMI major bleeding. A Markov model was constructed to facilitate a lifetime horizon for the analysis. A series of risk equations constructed using individual patient data from TRITON-TIMI 38 was used to estimate risks of clinical events. Quality-adjusted life-years (QALYs) were derived by weighting survival time by estimates of health-related quality-of-life. Incremental cost-effectiveness is presented based on differences in treatments’ mean costs and QALYs for the licensed population in TRITON-TIMI 38, and the sub-groups of UA-NSTEMI, STEMI, diabetes, and the ‘core clinical cohort’ (<75 years, ≥60?kg, no history of stroke or TIA).

Results:

Mean cost of study drug was €364 (Turkey) to €818 (Germany) higher for prasugrel vs clopidogrel. Rehospitalization costs at 12 months were lower for prasugrel due to reduced rates of revascularization, although hospitalization costs beyond 12 months were higher due to longer life expectancy associated with lower rates of non-fatal MI in the prasugrel group. The incremental cost per QALY saved with prasugrel in the licensed population ranged from €6520 (for Sweden) to €14,350 for (Germany). Prasugrel’s cost per QALY was more favourable still in the STEMI and diabetes sub-groups of the licensed population.

Limitations:

Probabilistic analyses of the whole trial population is impractical due to the number of individual patient profiles over which population level results are calculated.

Conclusion:

Among patients undergoing PCI for ACS, treatment with prasugrel compared with clopidogrel resulted in favourable cost-effectiveness profiles from these healthcare systems’ perspectives.     

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.     

Cost-effectiveness of insulin detemir compared with neutral protamine Hagedorn insulin in patients with type 1 diabetes using a basal-bolus regimen in five European countries

Abstract

Objectives: The aim of this analysis was to evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine Hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Belgian, French, German, Italian and Spanish settings.

Methods: The published and validated IMS CORE Diabetes Model was used to make long-term projections of life expectancy, quality-adjusted life expectancy and direct medical costs. The analysis was based on patient characteristics and treatment effects from a 2-year randomised controlled trial. Events were projected for a time horizon of 50 years. Potential uncertainty using a modelling approach was addressed.

Results: Basal-bolus therapy with insulin detemir was projected to improve quality-adjusted life expectancy by 0.45 years versus NPH in the German setting, with similar improvements in the other countries. Insulin detemir was associated with cost savings in Belgium, Germany and Spain. In France and Italy, lifetime costs were slightly higher in the detemir arm, leading to incremental cost-effectiveness ratios of €519 per QALY gained and €3,256 per QALY gained, respectively.

Conclusions: Compared to NPH, insulin detemir is likely to be a dominant treatment strategy in Belgium, Germany and Spain and highly cost-effective in France and Italy in patients with type 1 diabetes.     

Cost effectiveness of palivizumab in children with congenital heart disease in Germany

Abstract

Objectives: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.

Study design: A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis).

Results: From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting.

Conclusion: This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.     

Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients

Abstract

Objective:

The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNβ-1a, SC IFNβ-1a, SC IFNβ-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain.

Methods:

A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results.

Results:

GA was the less costly strategy (€322,510), followed by IM IFNβ-1a (€329,595), SC IFNβ-1b (€ 333,925), and SC IFNβ-1a (€348,208). IM IFNβ-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNβ-1a (4.158 QALY), SC IFNβ-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNβ-1a were €?1,005,194/QALY, €?223,397/QALY, and €117,914/QALY in comparison to SC IFNβ-1a, SC IFNβ-1b, and GA, respectively.

Conclusions:

First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNβ-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNβ-1a and SC IFNβ-1b. However, IM IFNβ-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNβ-1a exceeds the €30,000 per QALY threshold commonly used in Spain.

Limitations:

The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.     

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 adalimumab,etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis

Abstract

Objective:

The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland.

Research design and methods:

The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab?+?methotrexate, etanercept?+?methotrexate, or tocilizumab?+?methotrexate were used as first biologics followed by rituximab?+?methotrexate and infliximab?+?methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed.

Main outcome measures:

Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI).

Results:

bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab?+?methotrexate was more cost-effective than adalimumab?+?methotrexate or etanercept?+?methotrexate in comparison with methotrexate alone, and adalimumab?+?methotrexate was dominated by etanercept?+?methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab?+?methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab?+?methotrexate should be considered before rituximab?+?methotrexate, infliximab?+?methotrexate, and BSC. Based on the CEAF, tocilizumab?+?methotrexate had a 60–93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230–2182).

Conclusions:

Tocilizumab?+?methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values.

Limitations:

Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.     

Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland

Abstract

Objective:

In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia.

Method:

This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY).

Results:

PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility.

Conclusion:

In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.