Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic

Abstract

Purpose:

The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots.

Methods:

An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables.

Results:

Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates.

Conclusions:

PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.     

Economic analysis of paliperidone long-acting injectable for chronic schizophrenia in Portugal

Objective: Patients with chronic schizophrenia suffer a huge burden, as do their families/caregivers. Treating schizophrenia is costly for health systems. The European Medicines Agency has approved paliperidone palmitate (PP-LAI; Xeplion), an atypical antipsychotic depot; however, its pharmacoeconomic profile in Portugal is unknown. A cost-effectiveness analysis was conducted from the viewpoint of the Portuguese National Health Service.

Methods: PP-LAI was compared with long acting injectables risperidone (RIS-LAI) and haloperidol (HAL-LAI) and oral drugs (olanzapine; oral-OLZ) adapting a 1-year decision tree to Portugal, guided by local experts. Clinical information and costs were obtained from literature sources and published lists. Outcomes included relapses (both requiring and not requiring hospitalization) and quality-adjusted life-years (QALYs). Costs were expressed in 2014 euros. Economic outcomes were incremental cost-effectiveness ratios (ICERs); including cost-utility (outcome?=?QALYs) and cost-effectiveness analyses (outcomes?=?relapse/hospitalization/emergency room (ER) visit avoided).

Results: The base-case cost of oral-OLZ was 4447€ (20% drugs/20% medical/60% hospital); HAL-LAI cost 4474€ (13% drugs/13% medical/74% hospital); PP-LAI cost 5326€ (49% drugs/12% medical/39% hospital); RIS-LAI cost 6223€ (44% drugs/12% medical/44% hospital). Respective QALYs/hospitalizations/ER visits were oral-OLZ: 0.761/0.615/0.242; HAL-LAI: 0.758/0.623/0.250; PP-LAI: 0.823/0.288/0.122; RIS-LAI: 0.799/0.394/0.168. HAL-LAI was dominated by oral-OLZ and RIS-LAI by PP-LAI for all outcomes. The ICER of PP-LAI over oral-OLZ was 14,247€/QALY, well below NICE/Portuguese thresholds (≈24,800€/30,000€/QALY). ICERs were 1973€/relapse avoided and 2697€/hospitalization avoided. Analyses were robust against most variations in input values, as PP-LAI was cost-effective over oral-OLZ in >99% of 10,000 simulations.

Conclusion: In Portugal, PP-LAI dominated HAL-LAI and RIS-LAI and was cost-effective over oral-OLZ with respect to QALYs gained, relapses avoided, and hospitalizations avoided.     

Validation of an economic model of paliperidone palmitate for chronic schizophrenia

Abstract

Objective:

Model validation is important, but seldom applied in chronic schizophrenia. Validation consists of verifying the model itself for face validity (i.e., structure and inputs), cross-validation with other models assessing the same issue, and comparison with real-life outcomes. The primary purpose was to cross-validate a recent pharmacoeconomic model comparing long-acting injectable (LAI) antipsychotics for treating chronic schizophrenia in Sweden. The secondary purpose was to provide external validation.

Methods:

The model of interest was a decision tree analysis with a 1-year time horizon with costs in 2011 Swedish kroner. Drugs analyzed included paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol (HAL-LAI), and oral olanzapine (oral-OLZ). Embase and Medline were searched from 1990–2012 for models examining LAIs. Articles were retrieved, with data extracted for all drugs compared including: expected costs, rates of hospitalization, proportion of time not in relapse, and associated QALYs. Outcomes from the model of interest were compared with those from other articles; costs were projected to 2012 using the consumer price index.

Results:

Twenty-six studies were used for validation; 14 of them provided evidence for cross-validation, 13 for external validation, and four for cost. In cross-validation, cost estimates varied ?1.8% (range: ?12.4–20.1%), hospitalizations 5.2% (?12.1–3.1%), stable disease 2.5% (?5.6–1.5%), QALYs 9.0% (4.3% after removing outliers). All estimates of clinical outcomes were within 15%. In external validation, hospitalization rates varied by 6.3% (?0.7–11.3%). The research was limited by data availability and validity of the original results.

Conclusion:

Other models validated the outputs of our model very well.     

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 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 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.     

Costs of administration,travelling, and productivity losses associated with hospital administration of multiple myeloma drugs in Finland

Aim: To estimate the drug administration, travelling, and productivity costs associated with infusion or subcutaneous proteasome inhibitor (PI) treatments (specifically carfilzomib and bortezomib) for multiple myeloma (MM) patients in Finland.

Materials and methods: Price tariffs of Finnish hospital districts are used as the basis of invoicing sent to healthcare service payers. A review of these price tariff lists was conducted and obtained data analysed to estimate the mean unit cost of PI administration visit. Travelling costs stratified by areas with different population densities were assessed, based on the national travelling reimbursement register data maintained by the Social Insurance Institution of Finland. Productivity costs due to time spent on administration visits and travelling were estimated based on an expert interview and a spatial healthcare accessibility analysis.

Results: Nineteen (95%) of the Finnish hospital districts were included in the review. Relevant unit cost information was found for 15 (75%) of the districts. The mean PI administration cost alone was 270€ (95% CI?=?189€–351€) per administration and increased to 371€ when travelling costs were included. Productivity costs added, the mean PI administration costs totalled 405€ for bortezomib and 437€ for carfilzomib.

Limitations: The costing rationale of price tariffs may vary between hospital districts. Productivity costs were estimated conservatively, due to lack of data.

Conclusions: The administration of intravenous or subcutaneous PIs to treat MM in healthcare facilities causes significant and potentially avoidable healthcare, travelling, and indirect costs, and they should be included in all health economic evaluations (HEEs). As the cost estimates utilized in this study represent most of central hospitals in the country, they provide useful information for future HEEs. A broader conclusion is that novel oral medications, such as the first oral PI, have a significant potential for reducing administration-related costs of subcutaneous or intravenous PIs.     

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 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 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.     

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.     

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.     

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.     

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 of skeletal complications from bone metastases in six European countries

Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]—radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein.

Methods Eligible patients from 49 centers across Austria (n?=?57), the Czech Republic (n?=?59), Finland (n?=?60), Greece (n?=?59), Portugal (n?=?59), and Sweden (n?=?62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and ≥1 index SRE (a SRE preceded by a SRE-free period of ≥?6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros.

Results The mean costs across countries were €7043, €5242, €11,101, and €11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone.

Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here.

Conclusions All SREs were associated with substantial costs. Variation in SRE-associated costs between countries was most likely driven by differences in treatment practices and unit costs.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.     

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.     

Costs of managing severe hypoglycaemia in three European countries

Abstract

Objectives: To assess the costs of severe hypoglycaemic events (SHEs) in diabetes patients in Germany, Spain and the UK.

Methods: Healthcare resource use was measured by surveying 639 patients aged ≥16 years, receiving insulin for type 1 (n=319) or type 2 diabetes (n=320), who experienced ≥1 SHE in the preceding year. Patients were grouped by location of SHE treatment: group 1, community (family/domestic); group 2, community (healthcare professional); group 3, hospital. Costs were calculated from published unit costs applied to estimated resource use. Costs per SHE were derived from patient numbers per subgroup. Weighted average costs were derived using a prevalence database.

Results: Hospital treatment was a major cost in all countries. In Germany and Spain, costs per SHE for type 1 patients differed from those for type 2 patients in each group. Average SHE treatment costs were higher for patients with type 2 diabetes (Germany, €533; Spain, €691; UK, €537) than type 1 diabetes patients (€441, €577 and €236, respectively). Telephone calls, visits to doctors, blood glucose monitoring and patient education contributed substantially to costs for non-hospitalised patients.

Conclusions: Treatment of SHEs adds significantly to healthcare costs. Average costs were lower for type 1 than for insulin-treated type 2 diabetes, in all three countries.     

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.