Cost-effectiveness of clopidogrel treatment in percutaneous coronary intervention: a European model based on a meta-analysis of the PCI-CURE,CREDO and PCI-CLARITY trials*

ABSTRACT

Objective: Our objective was to conduct a comprehensive cost-effectiveness analysis of pre-treatment and long-term treatment with clopidogrel in percutaneous coronary intervention (PCI) in three European countries based on a meta-analysis of the PCI-Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO) and PCI-Clopidogrel as Adjunctive Therapy (CLARITY) trials. This analysis adds to existing knowledge by providing further data on the cost-effectiveness of clopidogrel in PCI across a wide spectrum of patients.

Methods: A combined decision tree and Markov model was created. The relative risks of myocardial infarction, cardiovascular death and of major bleedings with clopidogrel were based on a fixed-effects meta-analysis. The risk of ischaemic events in untreated patients and long-term survival were taken from the Swedish hospital and death registers. A societal perspective was used in Sweden and a payer perspective in Germany and France. Costs are stated in €2006 and effectiveness measured in quality-adjusted life-years (QALYs).

Results: The pooled effects of clopidogrel on the combined endpoint showed a relative risk of 0.711 (p = 0.003) at 30 days and 0.745 (p = 0.002) at end of follow-up (up to 1 year). Pre-treatment with clopidogrel compared with aspirin alone is a dominant strategy. Long-term treatment with clopidogrel compared with 1-month treatment leads to approximately 0.09 QALYs at an incremental cost of €393 in Sweden, €709 in Germany and €494 in France. The corresponding incremental cost-effectiveness ratios range from €4225/QALY to €7871/QALY.

Conclusion: The results of this modelling analysis suggest that pre-treatment and long-term treatment in PCI with clopidogrel for up to 1 year are cost-effective in a range of patient groups and settings given commonly accepted thresholds.     

The cost-effectiveness of bimatoprost,latanoprost and timolol in treatment of primary open angle glaucoma in five European countries

ABSTRACT

Objective: The objective of this cost-effectiveness analysis is to evaluate cost-effectiveness ratios of the intraocular pressure (IOP)-lowering agents bimatoprost, latanoprost and timolol in five major European countries: France, Germany, Italy, Spain and the UK.

Methods: The cost-effectiveness analysis is based on achievement of IOP targets between 13 and 18?mm Hg. Thus, the cost-effectiveness ratios express the costs of having one patient successfully achieving IOP target. The perspective of the analysis is that of the health care sector payer, including costs of medicine and costs of ophthalmologist visits. The time frame is first year of glaucoma treatment. Four treatment strategies are analysed: Timolol as first line with add-on latanoprost or bimatoprost if IOP targets are not met, and latanoprost and bimatoprost as first line with add-on timolol.

Results: In the UK, Spain, Italy and Germany the timolol first with add-on of bimatoprost is the least expensive treatment. This strategy dominates both strategies involving latanoprost (as add-on to timolol or as first line) in these four countries. The incremental cost-effectiveness ratio of bimatoprost first-line therapy versus timolol with add-on bimatoprost varies from each country and target (from £305 to €43 720 per patient). In France the timolol first line and latanoprost add-on is not dominated and is the cheapest alternative. The incremental cost-effectiveness ratio of timolol with add-on bimatoprost versus add-on latanoprost lies between £71 and €355 per patient depending on target (18 and 13?mm Hg, respectively).

Conclusion: First-line treatment of latanoprost is dominated in all countries. In four out of five countries the timolol first-line therapy with add-on latanoprost is also dominated. Based on this pharmacoeconomic analysis, the most costeffective strategy seems to be timolol first line with add-on bimatoprost if target is not met after 3 months.     

Cost-effectiveness analysis of pregabalin versus gabapentin in the management of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia

ABSTRACT

Objective: To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain.

Methods: Using stochastic simulation, we estimated the cost-effectiveness of PGB 150–600?mg/d vs. GBP 900–3600?mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0–10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with ≥ 30% and ≥ 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs.

Results: Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with ≥ 30% reduction in pain intensity, 9 (0.5) days with ≥ 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were €1049 (€35) for PGB and €951 (€38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of €12 (95% confidence interval, €1–24) per additional day with no or mild pain, €431 (dominant–€876) per additional patient with no or mild pain, and €20?535 (€1607–40?345) per QALY gained.

Conclusions: According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.     

Acarbose in addition to existing treatments in patients with type 2 diabetes: health economic analysis in a German setting

ABSTRACT

Objective: A recent retrospective meta-analysis of cardiovascular events from long-term studies with acarbose in type 2 diabetes showed that treatment was associated with a significant reduction in the risk of cardiovascular events, supporting the hypothesis that postprandial hyperglycemia is a risk factor for cardiovascular disease. The aim of the present study was to assess the cost-effectiveness of acarbose, given in addition to existing treatments, in type 2 diabetes patients, based on these findings, in the German setting.

Methods: The CORE Diabetes Model, a published, validated computer simulation model, was used to project long-term clinical and cost outcomes in type 2 diabetes patients receiving acarbose or placebo in addition to existing treatments. Direct costs were retrieved from published sources and projected over patient lifetimes from a third party payer perspective. Costs and clinical benefits were discounted at 5% annually. Extensive sensitivity analyses were performed.

Results: Acarbose treatment was associated with improvements in discounted life expectancy (0.21 years) and quality-adjusted life expectancy (QALE) (0.19 QALYs) but was on average marginally more expensive than treatment in the placebo arm (€135 per patient). This led to incremental cost-effectiveness ratios of €633 per life year and €692 per quality-adjusted life year gained. Sensitivity analysis showed that these findings were robust under variation in a range of assumptions.

Conclusions: Addition of acarbose to existing treatment was associated with improvements in life expectancy and quality-adjusted life expectancy, and provides excellent value for money over patient lifetimes in the German setting.     

Review of the cost of diabetes complications in Australia,Canada, France,Germany, Italy and Spain

ABSTRACT

Objectives: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model.

Methods: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (€). Major complication costs are presented.

Results: First year costs of non-fatal myocardial infarction varied between €19?277 in Spain and €12?292 in Australia. In subsequent years of treatment, this range was €1226 (France) to €203 (Australia). Angina costs were similar across all four countries: €1716 in Australia; €2218 in Canada; €2613 in France; €3342 in Germany; €2297 in Italy; and €2207 in Spain. Event costs of non-fatal stroke were higher in Canada (€23?173) than in other countries (Australia €13?443; France €11?754; Germany €19?399; Italy €6583; Spain €4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (€17?188–27?552); Canada (€33?811–58?159); France (€24?608–56?487); Germany (€46?296–68?175); Italy (€43?075–56?717); and Spain (€28?370–32?706). Lower extremity amputation costs were: €18?547 (Australia); €17?130 (Canada); €31?998 (France); €22?096 (Germany); €10?177 (Italy); and €14?787 (Spain).

Conclusions: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.     

A cost-effectiveness model of smoking cessation based on a randomised controlled trial of varenicline versus placebo in patients with chronic obstructive pulmonary disease

Objectives: Smoking is an important risk factor in chronic obstructive pulmonary disease (COPD). A recent clinical trial demonstrated the efficacy of varenicline versus placebo as an aid to smoking cessation in patients with COPD. This study examines the cost-effectiveness of varenicline from the perspective of the healthcare systems of Spain (base case), the UK, France, Germany, Greece and Italy.

Methods: A Markov model was developed to determine the cost-effectiveness of varenicline as an aid to smoking cessation, compared to a placebo, in a COPD population. Cost-effectiveness was determined by the incremental cost per quality-adjusted life year (QALY) gained.

Results: In the Spanish base case varenicline had an incremental cost of €1021/person for an average of 0.24 life years (0.17 QALYs), gained over the lifetime of a cohort of COPD patients, resulting in an incremental cost-effectiveness ratio (ICER) of €5,566. In the other European countries, the ICER varied between €4,519 (UK) and €10,167 (Italy). Probabilistic sensitivity analysis suggested varenicline had a high probability (>95%) of being cost-effective at a threshold of €30,000/QALY.

Conclusions: Varenicline is expected to be a cost-effective aid to smoking cessation in COPD patients in all of the countries studied.     

A cost-effectiveness analysis of immunotherapy with SQ allergen extract for patients with seasonal allergic rhinoconjunctivitis in selected European countries

ABSTRACT

Background: Seasonal allergic rhinoconjunctivitis can, for some people, reduce quality of life and the ability to cope with everyday tasks.

Scope: In this paper we investigate the cost-effective­ness of immunization therapy with Alutard SQ (ASQ) and compare the cost-effectiveness in countries where the therapy has been in use in order to assess the impact of national therapeutic practices on the results of health economic assessments. Data are obtained from a clinical trial carried out in 2001–2002. To evaluate the cost-effectiveness of immunization we have added data on resource use in Austria, Denmark, Finland, Germany, the Netherlands, and Sweden.

Findings: The computations result in cost-effectiveness ratios for allergen immunization between €10?000 and €20?000 per QALY even without provision for indirect costs, and achieving dominance in most countries where indirect costs have also been taken into account. The country comparisons show that the direct cost of administrating the up-dosing and maintenance differs considerably between countries, and that the cost of medical staff is substantial, constituting in most cases more than half of the direct costs of the immunization therapy.

Conclusion: The study shows that immunotherapy with SQ allergen extract is cost-effective in a wide range of national environments, and that cost-effectiveness differences by country are largely a result of different practices in the up-dosing phase.     

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands

ABSTRACT

Objective: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands.

Methods: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens.

Results: With voriconazole, the mean cost for treating invasive aspergillosis per patient was €32?651 (2.5th percentile and 97.5th of uncertainty distribution: €30?037; €36?859), compared to €33?616 (€30?920; €39?633) for conventional amphotericin B and €29?115 (€23?537; €61?414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was €150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%.

Conclusion: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.     

Cost-effectiveness in Italy of preventive treatment with ramipril in patients at high risk of cardiovascular events

ABSTRACT

Objectives: A cost-effectiveness analysis was conducted in Italy of preventive treatment with ramipril (an angiotensin converting enzyme [ACE] inhibitor) compared to no treatment in patients at high risk of cardiovascular death. The analysis was based on data extracted from the HOPE trial.

Methods: The current life table method was used in order to model a lifetime time horizon for outcomes and costs. The cohorts used were 1000 subjects on ramipril, and 1000 subjects on placebo enrolled in the HOPE trial. Kaplan–Meier curves at 5 years of the clinical study were fitted using an exponential model over a lifetime horizon, the outcome variables being myocardial infarction, stroke, revascularization and death. Total direct medical costs have been considered from a third-party payer's perspective – the Italian National Health Service. Resources involved in each event/activity were estimated using the modified Delphi technique with a panel of six clinicians. Types of resources reported included drug therapies, laboratory and imaging tests, physician visits, outpatient and inpatient rehabilitation, as well as medical and surgical hospital admissions. The incremental cost per life year gained was the main measure of the analysis.

Results: ICER (incremental cost-effectiveness ratio) decreases with the length of the treatment period. After the first year the ICER is €55?062 and subsequently decreases to about €12?770 at 5 years, €5945 at 10 years and €3726 at 20 years. The two ways sensitivity analysis showed that at 5 years ICERs range from a saving of €4059 to a cost of €22?929 (at 20 years they are €1814 and €4434), mainly depending on the cost of drug and cost of events. Previous analyses in other countries based on the HOPE study obtained ICER values which are comparable with our results, when taking into account the different cost structure of the health care systems.

Conclusions: On the basis of these results, the use of ramipril is likely to represent an efficient use of public health expenditure in the Italian healthcare system.     

Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men

ABSTRACT

Objective: This study evaluated the long-term cost-effectiveness of atorvastatin 20?mg, rosuvastatin 10?mg and simvastatin 40?mg in primary and secondary prevention of CHD in Finland.

Research design and methods: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3–6.6?%?baseline risk of dying from cardiovascular disease within a 10-year period.

Main outcome measures: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (€/LYG) and cost of quality adjusted life years gained (€/QALY).

Results: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was €10 834 and the cost of one QALY gained was €36 548 (discount rate 5?%?per annum). Corresponding figures for atorvastatin were €31 286/LYG and €105 599/QALY.

Conclusions: If the decision makers’ willingness to pay for a QALY gained is around €40 000 there is a high probability (?>?50?%?) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3–6.6?%?risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.     

Cost–effectiveness analysis of sacral neuromodulation (SNM) with Interstim for fecal incontinence patients in Spain

ABSTRACT

Introduction: Fecal incontinence (FI) is a condition with a high impact on the psychological and social life of healthy people. Interstim, the sacral neuromodulation (SNM) therapy, has shown higher effectiveness and safety rates than surgical procedures like dynamic graciloplasty or artificial anal sphincter in patients with intact anal sphincter (IAS) and after sphincteroplasty in patients with structurally deficient anal sphincter (SDAS).

Objective: To assess the cost-effectiveness of FI management in two scenarios – with and without SNM – and to estimate the potential budget impact of its progressive introduction in the Spanish setting.

Methods: Two decision analytical models were developed (IAS and SDAS patients) representing the possible clinical paths for each of the scenarios (with and without SNM), as well as its clinical and economic consequences in the mid-to long term with a Markov model. Clinical and resource use data were retrieved from the literature and validated by a clinician expert panel. Effectiveness was measured with both QALYs and symptom-free years (SFY). A 3% discount rate was used for future costs and benefits (time horizon = 5 years). Prevalence figures were combined with Interstim sales forecasts to estimate the total number of patients to receive therapy over the next 5 years and the associated budget impact.

Results: The introduction of Interstim in the therapeutic management of FI has an associated cost-effectiveness of €16?181 (IAS patients) and €22?195 (SDAS patients) per QALY gained. The progressive introduction of Interstim in 75 to 100 patients/year will have an estimated budget impact of 0.1% of incremental costs in patients with FI.

Conclusions: Introducing Interstim in the management of FI in IAS and SDAS patients in the Spanish setting has shown to be an efficient measure with an incremental cost–effectiveness ratio below the accepted Spanish threshold (around €35?000/QALY), and with a relatively low additional cost for the Spanish NHS.     

Acute coronary syndromes in Europe: 1-year costs and outcomes

ABSTRACT

Objective: This study aims to estimate costs (including medications prescribed, intervention rates and hospital utilization) and health outcomes of acute coronary syndromes (ACS) during the first year following diagnosis.

Research design and methods: Treatment pathways for ACS patients were developed and country-specific resource use was multiplied by unit costs. Countries examined were the United Kingdom (UK), France, Germany, Italy and Spain. Patients with unstable angina and acute myocardial infarction (ST-segment elevation and non-ST-segment elevation with/without Q-wave) were considered. The study models the incidence of ACS, 1-year mortality, investigations, revascularisation, pharmaceutical use and medical management. Economic outcomes were direct healthcare costs (in 2004 Euros), including total cost, cost per patient with ACS and cost per capita.

Results: The estimated number of deaths in the first year following ACS diagnosis ranged from around 22?500 in Spain to over 90?000 in Germany. The largest contributors to total costs are hospital stay and revascularisation procedures. Pharmaceuticals were estimated at 14–25% of ACS total cost. The total cost of ACS in the UK is estimated around €1.9 billion, compared with €1.3 billion in France, €3.3 billion in Germany, €3.1 billion in Italy and €1.0 billion in Spain. The cost per ACS patient ranges from €7009 (in the UK) to €12?086 (Italy).

Conclusions: Countries with higher expenditure on ACS patients tended to have lower case-fatality rates, and countries with the lowest incidence of ACS also had the lowest cost per capita. The costs of ACS constitute a large proportion of total healthcare expenditure of Western European economies.     

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial

ABSTRACT

Objective: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany.

Research design and methods: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n?=?368), or levofloxacin and ceftriaxone (n?=?365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5–7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective.

Results: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was €2190 for the moxifloxacin group, and €2619 for the levofloxacin + ceftriaxone group (difference –€430, 95% CI: –€138, –€740; p?<?0.05). Variability in total costs was wide, with some patients accruing up to €18?000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (–€470, 95% CI: –€522, –€421), and accounted for between 15 and 30% of total costs.

Conclusions: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.     

Modeling the economic and health consequences of managing chronic osteoarthritis pain with opioids in Germany: comparison of extended-release oxycodone and OROS hydromorphone

ABSTRACT

Objective: The Osmotic controlled-Release Oral delivery System (OROS) hydromorphone ensures continuous release of hydromorphone over 24 hours. It is anticipated that this will facilitate optimal pain relief, improve quality of sleep and compliance. This simulation compared managing chronic osteoarthritis pain with once-daily OROS hydromorphone with an equianalgesic dose of extended-release (ER) oxycodone administered two or three times a day.

Methods: This discrete event simulation follows patients for a year after initiating opioid treatment. Pairs of identical patients are created; one receives OROS hydromorphone the other ER oxycodone; undergo dose adjustments and after titration can be dissatisfied or satisfied, suffer adverse events, pain recurrence, or discontinue the opioid. Each is assigned an initial sleep problems score, and an improved score from a treatment dependent distribution at the end of titration; these are translated to a utility value. Utilities are assigned pre-treatment, updated until the patient reaches the optimal dose or is non-compliant or dissatisfied. The OROS hydromorphone and ER oxycodone doses are converted to equianalgesic morphine doses using the following ratios: hydromorphone to morphine ratio; 1:5, oxycodone to morphine ratio; 1:2. Sensitivity analyses explored uncertainty in the conversion ratios and other key parameters. Direct medical costs are in 2005 euros.

Results: Over 1 year on a mean daily morphine-equivalent dose of 90?mg, 14% were estimated to be dissatisfied with each opioid. OROS hydromorphone was predicted to yield 0.017 additional quality-adjusted life years (QALYs)/patient for a small additional annual cost (€141/patient), yielding an incremental cost-effectiveness ratio (ICER) of €8343/QALY gained. Changing the assumed conversion ratio for oxycodone:morphine to 1:1.5 led to lower net costs of €68 per patient, €3979/QALY, and for hydromorphone to 1:7.5 to savings.

Conclusion: Based on these analyses, OROS hydromorphone is expected to yield health benefits at reasonable cost in Germany.     

Cost-effectiveness of continuous combined hormone replacement therapy in long-term use: economic evaluation based on a 9‑year study in Finland

ABSTRACT

Objectives: To investigate the cost-effectiveness of continuous combined hormone replacement therapy (ccHRT) (Indivina) in postmenopausal women in Finland treated for up to nine consecutive years in the course of a randomised controlled trial.

Methods: In-study event data were accrued for cardiac and vascular events, cancers and fractures. These event incidence data were applied to first-year direct medical costs for these events, derived from published sources. Reference event incidence data were derived from hospital discharge records and relevant national registries for age-matched women (aged 50–70 years) in Finland with an assumed HRT usage rate of 40%. Cost-effectiveness was expressed as additional cost per quality-adjusted life year (QALY) gained for women on ccHRT compared with the general population. All input data were discounted at 3% per annum.

Results: The additional cost per QALY gained for ccHRT was less than €5000 throughout the nine calendar years examined and remained well below the threshold of acceptability of €50?000 in a range of sensitivity analyses. The lowest dose-combination of ccHRT examined improved quality of life at no greater cost than no treatment.

Conclusions: This appraisal, based on event data from a uniquely long study of ccHRT, indicates that this intervention is cost-effective for the relief of symptoms of menopause.     

Cost effectiveness of adding folinic acid to fluorouracil plus levamisole as adjuvant chemotherapy in patients with colon cancer in Germany

OBJECTIVE: To assess the cost effectiveness of the addition of folinic acid to fluorouracil plus levamisole in patients with colon cancer from the perspective of the German Social Health Insurance. STUDY DESIGN AND METHODS: Patients with International Union Against Cancer (Union International Contre Cancer; UICC) II/T(4) or UICC III colon cancer enrolled in an open-label randomised clinical trial in Germany (Forschungsgruppe Onkologie Gastrointestinaler Tumoren-1 [FOGT-1]) received either fluorouracil plus levamisole (A, standard) or fluorouracil plus levamisole and folinic acid (B) for 12 months as adjuvant chemotherapy after curative intended surgery. Outcome measures for economic evaluation were disease-free life-years gained (df-LYG) and overall life-years gained (LYG) derived from the respective Kaplan-Meier survival curves. Direct medical costs from the perspective of the German Social Health Insurance were estimated retrospectively (2000 values) and incremental cost-effectiveness ratios (ICERs) were calculated. A Markov model was used to project the trial results beyond 5 years for the patients' remaining life expectancy. RESULTS: Adding folinic acid to the fluorouracil/levamisole regimen results in an increase in time to progression and survival in patients with locally advanced colon cancer. Within the trial period of 5 years ICERs (B versus A) were 33,008 Euro per df-LYG and 51,225 Euro per LYG (costs and effects discounted at 5%). The Markov model yielded ICERs of 11,176 Euro per df-LYG and 11,020 Euro per LYG (costs and effects discounted at 5%). The model was robust for variations of key variables in the sensitivity analysis. CONCLUSIONS: Results of this cost-effectiveness analysis suggest that the addition of folinic acid offers clinical benefits at additional costs which are likely to be acceptable for decision makers in the long term. Cost-effectiveness ratios calculated within the clinical trial period were just above 50,000 Euro/LYG. Because treatment benefits, i.e. prolonged survival, are sustained beyond 5 years whereas incremental costs are mainly incurred in the first year, results of the Markov model yielded cost-effectiveness ratios that compare more favourably with other published ICERs.     

Cost-effectiveness of central automated unit dose dispensing with barcode-assisted medication administration in a hospital setting

BackgroundCentral automated unit dose dispensing (cADD) with barcode-assisted medication administration (BCMA) has been shown to reduce medication administration errors (MAEs). Little is known about the cost-effectiveness of this intervention.ObjectiveTo estimate the cost-effectiveness of cADD with BCMA compared to usual care.MethodsAn economic evaluation was conducted alongside a prospective before-and-after effectiveness study in a Dutch university hospital. The primary effect measure was the difference between the rate of MAEs before and after implementation of cADD with BCMA, obtained by disguised observation in six clinical wards and subsequent extrapolation to the entire hospital. The cost-analysis was conducted from a hospital perspective with a 12-month incremental costing approach. The total costs covered the pharmaceutical service, nurse medication handling, wastage, and materials related to cADD. The primary outcome was the cost-effectiveness ratio expressed as costs per avoided MAE, obtained by dividing the annual incremental costs by the number of avoided MAEs. The secondary outcome was the cost-effectiveness ratio expressed as costs per avoided potentially harmful MAE (i.e. MAEs with the potential to cause harm).ResultsThe intervention was associated with an absolute MAE reduction of 4.5% and a reduction of 2.7% for potentially harmful MAEs. Based on 2,260,870 administered medications in the entire hospital annually, a total of 102,210 MAEs and 59,830 potentially harmful MAEs were estimated to be avoided. The intervention was associated with an increased incremental cost of €1,808,600 annually. The cost-effectiveness ratio was €17.69 per avoided MAE and €30.23 per avoided potentially harmful MAE.ConclusionsThe implementation of cADD with BCMA was associated with a reduced rate of medication errors, including harmful ones, at higher overall costs. The costs per avoided error are relatively low, and therefore, this intervention could be an important strategy to improve patient safety in hospitals.     

Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries

Objective: Dabigatran and rivaroxaban have been approved by the US FDA to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. Newly published real-world evidence based on the US population found that elderly Medicare patients with NVAF treated with rivaroxaban experienced statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, and statistically nonsignificant decreases in thromboembolic stroke and acute myocardial infarction (AMI) compared with dabigatran. This study assessed the cost-effectiveness of dabigatran vs. rivaroxaban for the treatment of US Medicare NVAF patients.

Methods: A previously published Markov model was adapted to compare dabigatran and rivaroxaban. The model considered thromboembolic stroke, bleeding events, and AMI based on the published real-world event risks. Model outputs included clinical event rates, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).

Results: Dabigatran patients experienced fewer ICH and major extracranial bleeding events than rivaroxaban patients, but more stroke and AMI events. Dabigatran was found to yield lower costs and higher QALYs than rivaroxaban, with incremental costs of ?$3534 and incremental QALYs of 0.004. Results remained consistent in sensitivity analyses, with a positive net monetary benefit (willingness-to-pay thresholds of $50,000 and $100,000 per QALY) for dabigatran over rivaroxaban for all model inputs tested.

Conclusions: In this study using US Medicare real-world data, dabigatran was found to dominate rivaroxaban. The analyses were limited by the short follow-up period of the real-world data and results may not be generalizable to other patient populations.     

Changes to the Statin Prescribing Policy in Belgium

Background and Objective New policies in Belgium encourage prescribing of generic HMG-CoA reductase inhibitors (statins), but may lead to non-equivalent switching of patients from more potent second generation statins, as has occurred elsewhere. We sought to assess the potential health economic impact of the new policies. Design This was a cost-effectiveness analysis Methods A Markov model was constructed to simulate the onset of cardiovascular disease (CVD) and death among a representative cohort of 80 Belgian patients initially free of CVD and taking atorvastatin. Cardiovascular risks were estimated from calibrated Framingham equations, and utilities and costs from published data. Decision analysis assessed the potential impact of switching all 80 patients to simvastatin. Changes in lipid levels expected to arise from switching were based on a published meta-analysis. Results If the 80 patients remained on atorvastatin, the model predicted that 23 (29%) would develop CVD over 20 years. If they were switched to simvastatin, the predicted number was 25 (31%), equating to a ‘number needed to harm’ of 52. Switching would lead to a net cost saving of € 131 (2012) per subject, but also a loss of 0.03 quality-adjusted life-years (QALYs) per subject. These equated to a decremental cost-effectiveness ratio of €4777 per QALY lost. Sensitivity analyses indicated this result to be robust. Conclusion Recently introduced statin prescribing policies in Belgium are likely, as intended, to reduce statin costs, but also increase the burden of CVD due to non-equivalent switching. It would be cost effective to maintain patients on atorvastatin for primary prevention rather than switch them to simvastatin.     

Cost effectiveness of using carboxymethylcellulose dressing compared with gauze in the management of exuding venous leg ulcers in Germany and the USA

ABSTRACT

Objective: To assess the cost effectiveness of using carboxymethylcellulose dressing (CMCD; Aquacel Hydrofiber) compared to gauze in the management of exuding venous leg ulcers in Germany and the USA.

Design and setting: This was a modelling study performed from the perspective of payers (i.e. the sickness funds in Germany and the community sector in the USA).

Methods: Clinical outcomes attributable to managing exuding venous leg ulcers were obtained from the published literature in the English language. These data were combined with resource utilisation estimates derived from a panel of clinicians enabling us to construct two decision models depicting the management of venous leg ulcers with CMCD or gauze over 18?weeks in Germany and the USA. The models were used to estimate the cost effectiveness of CMCD compared to gauze in the management of exuding venous leg ulcers in both countries.

Main outcome measures and results: Starting treatment with CMCD instead of gauze in both Germany and the USA is expected to heal 30% of ulcers within 18?weeks compared to 13% with gauze (?p = 0.003). The healthcare cost of starting treatment with CMCD or gauze in Germany is expected to be €2020 and €2654 respectively at 18?weeks. Additionally, the healthcare cost of starting treatment with CMCD or gauze in the USA is expected to be $3797 and $5288 respectively at 18?weeks. Hence, using CMCD instead of gauze is expected to increase the probability of healing within 18?weeks by 130% and reduce healthcare costs by at least 24%. The healthcare cost of managing CMCD-treated patients was less than that of gauze-treated patients in both countries due to decreased nursing and physician costs associated with a lower frequency of CMCD dressing changes compared to gauze dressing changes. If it were assumed that treatment with gauze in both countries heals 30% of ulcers within 18?weeks (i.e. is identical to CMCD), then the expected healthcare cost of using gauze would be reduced by only 3% (from €2654 to €2562 in Germany and from $5288 to $5148 in the USA).

Conclusion: Within the limitations of our model, starting management of an exuding venous leg ulcer with CMCD instead of gauze is the cost effective strategy in both Germany and the USA. Moreover, the purchase price of a leg ulcer dressing should not be used as an indication of the cost effectiveness of a given method of care.