Cost-effectiveness analysis of solifenacin versus oxybutynin immediate-release in the treatment of patients with overactive bladder in the United Kingdom

Abstract

Objective:

To carry out a cost-utility analysis comparing initial treatment with solifenacin 5?mg/day vs oxybutynin immediate-release (IR) 15?mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the UK National Health Service (NHS).

Methods:

A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5?mg to 10?mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a UK database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios.

Results:

Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY.

Conclusion:

Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.     

Solifenacin in the treatment of overactive bladder syndrome in Italian patients: pharmacoeconomic evaluation

Abstract

Objective: To investigate the pharmacoeconomic performance of treatment with solifenacin, a new antimuscarinic with selectivity for the bladder, when compared to tolterodine and placebo, in Italian patients with overactive bladder (OAB).

Methods: The evaluation was performed using a Markov model. The time horizon of the simulation was 52 weeks, with 1-week cycles. The model simulated outcomes and costs of the treatment with solifenacin (5 mg/day), tolterodine ER (4 mg/day) and no treatment in a cohort representative of the Italian population with OAB. The analysis was conducted mainly from the perspective of the patient, since drugs for the treatment of OAB are not included in the Italian reimbursement list. A supplementary scenario explored the consequences of a hypothetical reimbursement decision by the Italian Health Service to reimburse half of the current retail price in incontinent and responding OAB patients only.

Results: Both treatments produced a reduction in symptoms and improvement in patients' quality of life, with an cost increase of about €540–640/patient/year with solifenacin and €680–780/patient/year with tolterodine. In a cost/utility analysis, solifenacin dominated tolterodine as it resulted in both more effective and less costly treatment; the cost/utility ratio with respect to no treatment was in the range €7,600–18,600/Quality-adjusted life year. The overall expenditure of the hypothesised reimbursement decision was estimated to be about 23 million euros, with a cost/utility ratio of about €600–2,400/Quality-adjusted life year, indicating an efficient allocation of health resources.

Conclusions: While both tolterodine and solifenacin appear to be cost/effective in Italy, the latter has proven to be superior.

     

Canadian cost-effectiveness analysis of solifenacin compared to oxybutynin immediate-release in patients with overactive bladder

Abstract

Objective:

To estimate the cost effectiveness of solifenacin 5?mg/day compared to oxybutynin immediate-release (IR) 15?mg/day in patients with overactive bladder, from the perspective of the Canadian healthcare (payer) system.

Research design and methods:

A Markov model was adapted to estimate the incremental cost per quality-adjusted life-year (QALY) of solifenacin and oxybutynin IR over a 1-year time horizon, based on efficacy and discontinuation data from the Canadian VECTOR (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients) study. In the model, patients who discontinued treatment were offered tolterodine extended release 4?mg/day as second-line. Model robustness was tested using various sensitivity analyses. Utility values were derived from published literature; incontinence pads were included in a secondary analysis.

Results:

In the base-case analysis, total costs over 1 year were CAN$695 and CAN$550 in the solifenacin and oxybutynin IR groups, respectively. When including incontinence pad costs, there was an incremental saving of CAN$1,831 per patient with solifenacin. Solifenacin was associated with an incremental QALY gain of 0.01 over 1 year. In the base-case analysis without incontinence pads, the incremental cost-utility ratio for solifenacin was CAN$14,092. Probabilistic analyses showed no overlap in the 95% confidence intervals for total costs or QALYs with or without incontinence pads. Solifenacin was cost effective in >90% of cases, based on a willingness-to-pay threshold of CAN$50,000 per additional QALY, irrespective of whether pad costs were included in the model. The most influential variables were the discontinuation rates and the cost of incontinence pads. Limitations of the analysis relate mainly to the fact that data in the VECTOR study were collected using a direct questioning approach, which might have increased the reporting of dry mouth.

Conclusions:

Solifenacin 5?mg/day was a cost-effective treatment compared with oxybutynin IR 15?mg/day.

Conclusions:

NCT00431041 (of the VECTOR study, upon which the analysis in this paper was based).     

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany

Abstract

Objectives:

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis.

Methods:

The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant’s perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses.

Results:

In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of ?€1142 (95%CI: ?€1255; ?€1038) and ?€54 (95%CI: ?€188; €85) and incremental QALYs of 0.015 (95%CI: ?0.025; 0.056) and 0.027 (95%CI: ?0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects.

Conclusion:

The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.     

Cost-effectiveness analysis of febuxostat in patients with gout in Spain

Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout.

Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80?mg and 120?mg sequentially, used as first line and second line therapy, was compared with allopurinol 300?mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6?mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied. Perspective: National Health System.

Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300?mg ranging from €5268–€9737.

Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000€/QALY).     

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 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 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.     

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban,dabigatran, and rivaroxaban), warfarin,and aspirin

Objectives:

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective.

Methods:

A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections.

Results:

Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110?mg, dabigatran in sequential dosages, dabigatran 150?mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY.

Conclusions:

Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.     

The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland,Norway and the Netherlands

Abstract

Objective:

This study was conducted to assess the cost effectiveness of zoledronic acid 5?mg as a first-line treatment for the secondary prevention of fragility fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.

Methods:

A discrete-event, individual-patient computer-simulation model was used to compare the cost effectiveness of zoledronic acid with that of basic treatment (calcium and vitamin D) and commonly prescribed bisphosphonates in postmenopausal women aged 50–80 years who have experienced one previous fracture and have a bone mineral density T-score of ?2.5.

Results:

The cost per quality-adjusted life-year (QALY) gained with zoledronic acid compared with basic treatment ranged from being cost saving in all age groups in Norway, to costing approximately €19,000 in Finland and €22,300 in the Netherlands. Compared with the other branded bisphosphonates, zoledronic acid was cost saving in many scenarios, including all age groups in Finland. In Norway, zoledronic acid dominated branded risedronate and ibandronate in all age groups and dominated or had incremental cost-effectiveness ratios (ICERs) of up to NOK83,954 per QALY gained compared with branded alendronate. In the Netherlands, zoledronic acid dominated branded intravenous ibandronate in all age groups; compared with branded risedronate and oral ibandronate, zoledronic acid dominated or had ICERs of up to €4832 per QALY gained; compared with branded alendronate, it had ICERs of up to €48,383 per QALY gained. In all three countries, zoledronic acid may be cost effective compared with generic alendronate when patient compliance with drug therapy is taken into account. Sensitivity analyses showed that the model was robust to changes in key values. The main model limitations were the lack of real-life compliance and persistence data, and lack of country-specific data for some parameters.

Conclusions:

Using local or commonly used thresholds, this analysis suggests that zoledronic acid would be a cost-effective first-line option compared with other branded bisphosphonates and, in some scenarios, compared with generic alendronate, for the secondary prevention of fractures in women with postmenopausal osteoporosis in Finland, Norway and 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.     

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium

Abstract

Background and objectivess:

The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer’s perspective of add-on pregabalin in a wider set of NeP conditions.

Methods:

The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were ‘usual care’ or ‘usual care?+?pregabalin’. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care.

Results:

Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion.

Limitations:

The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice.

Conclusion:

Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).     

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.     

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.     

Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron

Abstract

Background:

Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB).

Data:

Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4?mg was included as an active control in one study: (1) placebo, mirabegron 50?mg and 100?mg, and tolterodine 4?mg ER; (2) placebo, mirabegron 50?mg and 100?mg; (3) placebo, and mirabegron 25?mg and 50?mg. Data were collected at baseline, week 4, 8, and 12.

Methods:

Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change.

Results:

In modified ITT analyses, mirabegron 50?mg was superior to tolterodine 4?mg in changes from baseline utilities after 12 weeks (p?<?0.05); similarly, AUC results showed mirabegron 50?mg to be superior to tolterodine (p?<?0.05) and placebo (p?<?0.05) with the benefit already apparent at 4 weeks (p?<?0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms.

Conclusion:

Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4?mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.     

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.     

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing–remitting multiple sclerosis in The Netherlands

Abstract

Objective:

To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing–remitting multiple sclerosis (RRMS) in The Netherlands.

Methods:

A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained.

Results:

Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of ?€2966 (95% CI: ?€4209; ?€1801), ?€6240 (95% CI: ?€8800; ?€3879), ?€15,328 (95% CI: ?€21,539; ?€9692), and ?€28,287 (95% CI: ?€39,661; ?€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165–364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs—including aseptic preparation of the natalizumab solution—needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years.

Limitations:

Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included.

Conclusion:

The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.     

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.     

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 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.