Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands

Abstract

Background: Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.

Objective: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.

Methods: A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. 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 in the Netherlands.

Results: The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in the in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. 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 Dutch healthcare setting.

Conclusion: Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.     

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 analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States

Abstract

Objective:

Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population.

Methods:

A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤6 months chronologic age (CA); (2) 32–34 wGA, ≤3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32–35 wGA, ≤6 months CA with 2006 AAP RF; and (4) 32–35 wGA, ≤6 months CA with ≤1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted.

Results:

Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32–34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32–35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32–35 wGA with ≤1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab.

Key limitations:

These results are not generalizable to commercially insured infants or infants outside of the US.

Conclusions:

This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32–35 wGA infants with ≤1 RF.     

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 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.     

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.     

Changing costs and the impact on RSV prophylaxis

Abstract

Objective:

Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks’ gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.

Methods:

New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.

Results:

Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.

Conclusions:

Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks’ GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.

Limitations:

There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.     

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 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 utility of palivizumab prophylaxis among pre-term infants in the United States: a national policy perspective

Abstract

Objective:

The cost-effectiveness of palivizumab has previously been reported among certain guideline-eligible, high-risk premature infants in Medicaid. Because guideline authorities base decisions on a national perspective, the economic model of palivizumab was adapted to include all infants, that is, public and privately insured patients (60% of palivizumab use is public, 40% is private).

Methods:

This study examined four groups of premature infants without chronic lung disease of prematurity or congenital heart disease: (1) <32 weeks gestational age (wGA) and ≤6 months chronologic age (CA); (2) 32–34 wGA, ≤3 months CA, with 2009 American Academy of Pediatrics (AAP) risk factors (RFs); (3) 32–35 wGA, ≤6 months CA, with 2006 AAP RFs; and (4) 32–35 wGA, ≤6 months CA, with ≤1 RF. An average estimate was used between public and private payors for (1) background rates of respiratory syncytial virus hospitalization (RSV-H), (2) direct medical costs associated with RSV-H, and (3) cost of palivizumab. Incremental cost-effectiveness ratios (ICERs) are reported in cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed.

Results:

Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32–34 wGA with 2009 AAP RFs ($44,774 per QALY) and in infants 32–35 wGA with 2006 AAP RFs ($79,477 per QALY). The ICER for infants 32–35 wGA with ≤1 RF was $464,476 per QALY. Influential variables in the sensitivity analysis included background rate of RSV-H and cost and efficacy of palivizumab.

Limitations:

The results are not generalizable to populations outside of the US. The model did not examine all RFs. The wholesale acquisition cost was used as a payment benchmark; actual price paid by end providers varies.

Conclusions:

From a national policy perspective, palivizumab remained cost-effective for publically and commercially insured, guideline-eligible, high-risk premature infants. Palivizumab was not cost-effective in infants of 32–35 wGA with ≤1 RF.     

Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise

Objectives: the study aims to estimate the clinical-impact and cost-effectiveness value of adding human papillomavirus 16/18 vaccination against cervical cancer among women currently undergoing organised screening in Finland.

Methods: A Markov cohort model evaluating high-risk HPV infections and cervical cancer (CC) cases combined with screening has been customised to the Finnish setting. The model outcome for a cohort of 30,000 girls aged 10 years was calibrated to age-specific annual number of Pap smears, CC incidence and mortality.

Results: The observed age-specific incidence and mortality rates of CC closely match the data replicated by the model. The model predicts that with a 90% vaccine coverage rate, CC cases and mortality would be reduced by 70%. In the base-case analysis with a discount rate of 3% the incremental cost per quality-adjusted life-years (QALY) gained, from a healthcare perspective, was €17,294. Without discounting this value is €2,591/QALY gained.

Conclusions: The analysis suggests that implementing prophylactic CC vaccination within the current screening system would substantially reduce CC cases and deaths, as well as the overall disease burden expressed in pre-cancer lesions averted. Vaccination could be a cost-effective intervention in Finland despite the fact that the number of CC cases and deaths are currently relatively low. Conservative estimates of the cost effectiveness of the vaccination were provided since it was not possible to assess herd protection induced by vaccination using this Markov model.     

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 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.     

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.     

The cost-effectiveness of solifenacin vs. trospium in the treatment of patients with overactive bladder in the German National Health Service

Objective:

To carry out a cost–utility analysis comparing initial treatment of patients with overactive bladder (OAB) with solifenacin 5?mg/day versus either trospium 20?mg twice a day or trospium 60?mg/day from the perspective of the German National Health Service.

Methods:

A decision analytic model with a 3 month cycle was developed to follow a cohort of OAB patients treated with either solifenacin or trospium during a 1 year period. Costs and utilities were accumulated as patients transitioned through the four cycles in the model. Some of the solifenacin patients were titrated from 5?mg to 10?mg/day at 3 months. Utility values were obtained from the published literature and pad use was based on a US resource utilization study. Adherence rates for individual treatments were derived from a United Kingdom general practitioner database review. The change in the mean number of urgency urinary incontinence episodes/day from after 12 weeks was the main outcome measure. Baseline effectiveness values for solifenacin and trospium were calculated using the Poisson distribution. Patients who failed second-line therapy were referred to a specialist visit. Results were expressed in terms of incremental cost–utility ratios.

Results:

Total annual costs for solifenacin, trospium 20?mg and trospium 60?mg were €970.01, €860.05 and €875.05 respectively. Drug use represented 43%, 28% and 29% of total costs and pad use varied between 45% and 57%. Differences between cumulative utilities were small but favored solifenacin (0.6857 vs. 0.6802 to 0.6800). The baseline incremental cost–effectiveness ratio ranged from €16,657 to €19,893 per QALY.

Limitations:

The difference in cumulative utility favoring solifenacin was small (0.0055–0.0057 QALYs). A small absolute change in the cumulative utilities can have a marked impact on the overall incremental cost-effectiveness ratios (ICERs) and care should be taken when interpreting the results.

Conclusion:

Solifenacin would appear to be cost-effective with an ICER of no more than €20,000/QALY. However, small differences in utility between the alternatives means that the results are sensitive to adjustments in the values of the assigned utilities, effectiveness and discontinuation rates.     

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.     

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.     

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.     

A cost-utility study of the use of pregabalin added to usual care in refractory neuropathic pain patients in a Swedish setting

Abstract

Objectives:

Patients refractory to older therapies for neuropathic pain (NeP) have few remaining therapeutic options. This study evaluates the cost-utility of pregabalin in the treatment of patients with refractory neuropathic pain in Sweden, from a healthcare and a societal perspective.

Study limitations:

The use of non-randomized (observational) data to determine the effectiveness of treatments for NeP. The use of non-Swedish data for some input parameters in the model.

Methods:

A previously constructed discrete event simulation model was adapted to compare pregabalin combined with usual care to usual care alone in a Swedish setting. Pain profiles were generated using clinical data from five non-randomized pregabalin studies in refractory NeP patients. Utility data were generated from a UK survey of patients with NeP. Cost data were generated from the Swedish Dental and Pharmaceutical Benefits Board (TLV’s) product price database, a national NeP register, and a regional registry study. Indirect costs were estimated from published sources. One-way and probabilistic sensitivity analyses evaluated uncertainty in the model’s output.

Results:

The incremental cost-effectiveness ratio (ICER) for pregabalin plus usual care treatment compared to usual care was 51,616 SEK/€5364 and 123,993 SEK/€12,886 with and without indirect costs, respectively. One-way sensitivity analyses confirmed the clinical input data as the main driver of the model; even considerable changes to all other input parameters had only a modest effect on the ICER. The ICER remained well below a conservative threshold of 347,495 SEK /€36,113/£30,000 in all scenarios modelled.

Conclusions:

This study found pregabalin combined with usual care to be cost-effective compared to usual care in patients with refractory NeP from a Swedish Health Care perspective. Moreover, sensitivity analysis showed pregabalin’s cost-effectiveness to be robust in all scenarios modelled.     

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.