Multivariate Probabilistic Sensitivity Analyses Research Articles

Clinical benefits, costs, and cost-effectiveness of neonatal intensive care in Mexico.

Neonatal intensive care improves survival, but is associated with high costs and disability amongst survivors. Recent health reform in Mexico launched a new subsidized insurance program, necessitating informed choices on the different interventions that might be covered by the program, including neonatal intensive care. The purpose of this study was to estimate the clinical outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico. A cost-effectiveness analysis was conducted using a decision analytic model of health and economic outcomes following preterm birth. Model parameters governing health outcomes were estimated from Mexican vital registration and hospital discharge databases, supplemented with meta-analyses and systematic reviews from the published literature. Costs were estimated on the basis of data provided by the Ministry of Health in Mexico and World Health Organization price lists, supplemented with published studies from other countries as needed. The model estimated changes in clinical outcomes, life expectancy, disability-free life expectancy, lifetime costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for neonatal intensive care compared to no intensive care. Uncertainty around the results was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive care for infants born at 24-26, 27-29, and 30-33 weeks gestational age prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively, compared to an alternative of no intensive care. The ICERs of neonatal intensive care at 24-26, 27-29, and 30-33 weeks were US$1,200, US$650, and US$240, per DALY averted, respectively. The findings were robust to variation in parameter values over wide ranges in sensitivity analyses. Incremental cost-effectiveness ratios for neonatal intensive care imply very high value for money on the basis of conventional benchmarks for cost-effectiveness analysis. Please see later in the article for the Editors' Summary.

Cost-effectiveness of autologous retinal pigment epithelium and choroid translocation in neovascular AMD.

To assess the cost-effectiveness of autologous retinal pigment epithelium and choroid translocation (PATCH) in neovascular age-related macular degeneration (AMD). Visual acuity and complication rates of published patient series were used to determine the incremental utility of treatment for the patient. The utility data applied assume that the better eye was affected. Comparator was a meta-analysis of recent control groups, in which patients received best supportive care. To assess cost-effectiveness, costs per quality adjusted life years (QALYs) and costs of avoiding low vision ("legal blindness", i.e. ≤20/200) were calculated. Costs were based on a German sick fund perspective and in a scenario on US costs. Robustness of the model was investigated by univariate and probabilistic multivariate sensitivity analysis (PSA). Cost-utility analysis showed surgery to be the dominant ("cost-saving") strategy for Germany and for the US in both, cost-effectiveness and cost-utility analysis (costs per QALY). In the sensitivity analysis the intervention remained dominant or cost-effective in all scenarios investigated. Clinical outcomes and duration of modeling were the most influential factors in the sensitivity analyses. Therapy of neovascular AMD by PATCH is a cost-effective treatment option for selected patients, who are not well suitable for other current treatment options.

Cost-effectiveness of statin therapy for vascular event prevention in adults with elevated C-reactive protein: implications of JUPITER

Objectives:High-sensitivity C-reactive protein (hs-CRP) has been explored for use in predicting cardiovascular risk. The recent Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study found that statin therapy reduced cardiovascular events in those with low-density lipoprotein (LDL) cholesterol levels below current treatment thresholds (≤130 mg/dL, 3.4 mmol/L), but with elevated hs-CRP levels (≥2.0 mg/L). This study examines the cost-effectiveness of statin treatment for individuals with elevated hs-CRP but normal LDL cholesterol.Methods:A Markov decision-analytic model was conducted from the U.S. societal perspective. Data from JUPITER were used to estimate rates of myocardial infarction, angina and stroke. Statin costs were based on generic simvastatin 80 mg, equipotent to the rosuvastatin 20 mg dose used in JUPITER. Primary prevention was the focus and secondary prevention was not modeled explicitly. Quality-adjusted life-years (QALYs) were calculated using nationally representative preference-based utility weights. One-way sensitivity analyses and multivariate probabilistic sensitivity analysis were used to explore uncertainty in model parameters as well as estimate the likelihood of cost-effectiveness when all event rates, costs and utilities were drawn randomly from distributions reflecting uncertainty.Results:Statin therapy cost $10,889/QALY for vascular event prevention in this population. Results were sensitive to the cost of statin treatment. Based on 10,000 simulations, statin therapy was cost-effective in 99.5% of simulations, using a willingness-to-pay threshold of $20,000/QALY, and 100% of simulations using a threshold of $50,000/QALY.Conclusions:Treatment with statins in patients with elevated hs-CRP but normal cholesterol appears to be cost-effective. Limitations of this study include the assumption that an equipotent dose of simvastatin resulted in the same risk reduction as rosuvastatin. Further, post-event states simulated the average experience of a patient. Continued statin use, subsequent events and/or heart failure were not explicitly modeled.

Cost Effectiveness of Long-Acting Risperidone in Sweden

In Sweden, risperidone long-acting injectable (RLAI) is generally used in a population of schizophrenia patients who are at a high risk of being non-compliant. However, RLAI might also be suitable for use in the general schizophrenia population. To analyse the clinical and economic effects of RLAI in the Swedish treatment practice using a discrete-event simulation (DES) model. Treatment outcomes and direct costs were analysed for both the high-risk non-compliant patient population and the general schizophrenia population. An existing DES model was adapted to simulate the treatment of schizophrenia in Sweden. Model inputs were based on literature research and supplemented with expert opinion. In the high-risk non-compliant schizophrenia population, RLAI was compared with haloperidol LAI. The analysis was built upon differences in symptom reduction, time between relapses, compliance and adverse effect profile between the two drugs. Main outcomes were the predicted incremental (discounted) costs (€) and effects (QALYs). In the general schizophrenia population, RLAI was compared with oral olanzapine. This analysis was built upon differences in compliance and adverse effects between the drugs. Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess the sensitivity of the results of the two analyses. In the high-risk non-compliant patient population, RLAI was predicted to generate 0.103 QALYs per patient over 3 years while realizing cost savings of €5013 (year 2007 values) compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI was the difference in Positive and Negative Syndrome Scale (PANSS) reduction between the two drugs, followed by the difference in adverse effects. The PSA showed that, in this setting, RLAI had a probability of 100% of being cost effective at a willingness-to-pay (WTP) threshold of €43,300 per QALY gained, compared with haloperidol LAI. The probability that RLAI combines additional effectiveness with cost savings compared with haloperidol LAI was estimated at 94%. When analysing RLAI in the general schizophrenia population, it was predicted to generate 0.043 QALYs and save €239 per patient over 5 years compared with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI in this scenario. In the PSA it was shown that RLAI had a probability of 78% of being cost effective at a WTP threshold of €43,300 per QALY gained, compared with olanzapine. The estimated probability that RLAI combines additional effectiveness with cost savings was 50% and the probability that RLAI is less effective and more costly than olanzapine was negligible (0.2%). Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.

The cost effectiveness of radon mitigation in existing German dwellings – A decision theoretic analysis

Radon is a naturally occurring inert radioactive gas found in soils and rocks that can accumulate in dwellings, and is associated with an increased risk of lung cancer. This study aims to analyze the cost effectiveness of different intervention strategies to reduce radon concentrations in existing German dwellings. The cost effectiveness analysis (CEA) was conducted as a scenario analysis, where each scenario represents a specific regulatory regime. A decision theoretic model was developed, which reflects accepted recommendations for radon screening and mitigation and uses most up-to-date data on radon distribution and relative risks. The model was programmed to account for compliance with respect to the single steps of radon intervention, as well as data on the sensitivity/specificity of radon tests. A societal perspective was adopted to calculate costs and effects. All scenarios were calculated for different action levels. Cost effectiveness was measured in costs per averted case of lung cancer, costs per life year gained and costs per quality adjusted life year (QALY) gained. Univariate and multivariate deterministic and probabilistic sensitivity analyses (SA) were performed. Probabilistic sensitivity analyses were based on Monte Carlo simulations with 5000 model runs. The results show that legal regulations with mandatory screening and mitigation for indoor radon levels >100 Bq/m 3 are most cost effective. Incremental cost effectiveness compared to the no mitigation base case is 25,181 € (95% CI: 7371 €–90,593 €) per QALY gained. Other intervention strategies focussing primarily on the personal responsibility for screening and/or mitigative actions show considerably worse cost effectiveness ratios. However, targeting radon intervention to radon-prone areas is significantly more cost effective. Most of the uncertainty that surrounds the results can be ascribed to the relative risk of radon exposure. It can be concluded that in the light of international experience a legal regulation requiring radon screening and, if necessary, mitigation is justifiable under the terms of CEA.

Cost-effectiveness of ranibizumab for the treatment of neovascular age-related macular degeneration in germany: Model analysis from the perspective of germany's statutory health insurance system

Background: In clinical trials, ranibizumab has been associated with stabilization and even improvement of visual acuity among patients with neovascular agerelated macular degeneration (AMD), but its use is also associated with considerable costs. Objective: The aim of this work was to compare ranibizumab with best supportive care or photodynamic therapy (PDT) for AMD by means of economic costutility and cost-effectiveness analysis from the perspective of Germany's Statutory Health Insurance System. Methods: Visual acuity data from the Anti-VEGF (vascular endothelial growth factor) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) studies were applied, based on a ranibizumab dose of 0.5 mg. A Markov model simulated visual acuity and costs over 10 years (discounted at 3%). The base-case analysis assumed 5 injections per year over 2 years. Treatment costs were based on year-2008 euros (using German prices) and recommendations for procedure reimbursement from a public health insurance perspective. To assess cost-effectiveness, costs per year of legal blindness avoided (ie, vision-year gained [VYG]) and per quality-adjusted life-year (QALY) were calculated. The model assumed each patient's affected eye had better sight than the other eye, and the 2 comparators against which ranibizumab treatment was assessed were best supportive care and PDT. The robustness of the results was investigated in a univariate sensitivity analysis of all relevant parameters and a multivariate probabilistic sensitivity analysis. The multivariate 95% CIs for incremental cost-effectiveness ratios were obtained by conducting 1000 Monte Carlo simulations. Results: Compared with best supportive care, costs per VYG for ranibizumab were €6767 in occult choroidal neovascularization (CNV) and €6020 in minimally classic CNV. In classic CNV, costs were €5734/VYG for ranibizumab compared with supportive care and €778/VYG for ranibizumab compared with PDT. Costs per QALY for ranibizumab treatment for occult, minimally classic CNV, and classic CNV were €22,320, €22,538, and €25,036, respectively, and €3294 for classic CNV compared with PDT. Results were sensitive to the cost of blindness, injection frequency, and duration. The multivariate 95% CIs for the incremental costeffectiveness ratios were €14,438 to €41,110/QALY for occult CNV, €13,463 to €43,614/QALY for minimally classic CNV, and €15,634 to €51,106/QALY for classic CNV. Conclusion: In this model analysis using costs and clinical trial data from Germany, ranibizumab appeared to be a cost-effective treatment option for all angiographic subtypes of neovascular AMD, from the perspective of Germany's Statutory Health Insurance System.

The cost-effectiveness of treatment with desloratadine in patients with persistent allergic rhinitis

Objectives:A new classification of persistent allergic rhinitis (PER) has been developed by the ARIA working group. Although the burden of AR is significant, treatment itself is also costly. It is unclear if treatment based on the new definition of PER is cost-effective.Methods:The current study simulated the cost-effectiveness of desloratadine compared to placebo in the treatment of PER from the French societal perspective. Decision analysis was used to model the costs, effectiveness and cost-effectiveness over 12 months. Costs included medical expenditures (physician visits and prescription drugs) attributable to PER and related comorbidities and lost productivity due to absenteeism and presenteeism. Prices, tariffs and national wages were estimated from French national sources. Measures of effectiveness included: symptom-based visual analogue scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Total 5 Symptoms Score (T5SS), categorical improvement in therapeutic response, interference with activities of daily living (ADL) and sleep outcomes. Mild or symptom-free days and ‘responders’ were also captured as outcomes. Univariate and second-order multivariate probabilistic sensitivity analyses were conducted.Results:Treatment with desloratadine dominated placebo (cost less and resulted in greater effectiveness) for all measures of effectiveness. Of the individuals taking desloratadine 46.8% were classified as ‘responders’ vs. 34.8% for placebo (p = 0.0012). Individuals taking desloratadine experienced mild/no symptoms for 57.6% of study days vs. 36.5% for placebo (p = 0.002). The expected annual cost of treatment with desloratadine (€1819) was less than placebo (€2618). Lost productivity was the most significant contributor to total cost. Results of the 10,000 Monte Carlo simulations showed that treatment was cost-saving in 99.6% of simulations.Conclusions:Treatment of PER with desloratadine resulted in improved effectiveness and significant savings. While the cost of drug treatment is greater than that of no treatment, the downstream costs associated with not treating PER significantly outweigh the cost of treatment. Key limitations include the comparison of desloratadine to placebo and the sources of cost and effectiveness measures. Future studies should examine the cost-effectiveness of all available treatments for PER. In addition, many utilization, productivity and effectiveness measures were taken from clinical trials and may not accurately reflect ‘real world’ treatment patterns and outcomes.

Modeling the Cost-Effectiveness of Galantamine for Mild to Moderately Severe Alzheimer's Disease in Korea

The aim of the study was to determine the cost-effectiveness, from the third-party payer viewpoint, of galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease (AD). An existing Markov model was adapted to Korea to predict long-term outcomes over a 5-year time horizon and to estimate the cost-effectiveness of galantamine for the treatment of AD. The model structure is informed by a review of national and international literature on the clinical and cost-effectiveness of galantamine and on the costs and outcomes associated with treatment for AD. The main outcome measure used was the cost per quality-adjusted life year (QALY) gained. All costs were indexed to US$ (2007 value). Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. The study findings indicate that the clinical benefits on AD progression from galantamine treatment resulted in an incremental cost per QALY gained of US$4939 over 5 years (vs. usual care). Probabilistic sensitivity analysis and cost-effectiveness acceptability curve suggest that the probability of galantamine treatment having an incremental cost per QALY over US$6740 is zero. Incremental cost per QALY gained according to scenario analyses ranged from US$2271 to US$8335. These findings suggest that the use of galantamine may be a cost-effective use of Korean national health-care resources, considering the gross domestic product per capita of US$21,695 in 2007.

Cost Utility of Adalimumab versus Infliximab Maintenance Therapies in the United States for Moderately to Severely Active Crohnʼs Disease

To determine and compare the cost utilities of the tumour necrosis factor (TNF) antagonists adalimumab and infliximab as maintenance therapies for patients in the US with moderately to severely active Crohn's disease. Maintenance regimens of adalimumab (40 mg every other week) and infliximab (5 mg/kg) were compared using primary data from the CHARM and published data from the ACCENT I clinical trials. Differences in study samples were minimized by matching and weighting baseline characteristics (Crohn's Disease Activity Index score, age and sex) between the patient groups using the primary clinical trial data. Utilization data were estimated from trial data. Unit costs of TNF antagonists (year 2007 values), hospitalizations (year 2006 values), and other medical costs (year 2006 values) were derived from a systematic literature search. Standard gamble-calculated primary data were used to derive health-utility estimates. Data were analysed in a cost-utility framework from a private payer perspective over a 56-week time horizon. Univariate and probabilistic sensitivity analyses were used to explore uncertainty related to the base-case cost-utility analysis. Given the time horizon, costs and effects were not discounted. Adalimumab- and infliximab-treated patients were in remission for 47.2% and 37.1% of the 56-week period, respectively. Hospital admissions were 34-40% lower for adalimumab than for infliximab, based on the model and observed data, respectively. Patients treated with adalimumab accrued greater expected QALYs (0.014; 95% CI 0.000, 0.022) and lower costs (-$US4852; 95% CI -6758, 491) in the first year of therapy than patients treated with infliximab. Compared with infliximab maintenance therapy, adalimumab had lower drug and administration costs, less drug waste, and lower hospitalization rates. Univariate and multivariate probabilistic sensitivity analyses suggested that these results were robust. This analysis suggests that adalimumab maintenance therapy is a dominant strategy versus infliximab maintenance therapy for patients with moderate to severe Crohn's disease. Adalimumab appeared more effective and less costly than infliximab.

TPF versus PF as induction therapy in unresectable head and neck cancer: A pharmacoeconomic analysis

6075 Background: Adding docetaxel to induction therapy with PF has been shown to improve overall survival of patients with head and neck cancer. On the basis of the raw data from the EORTC trial 24971/TAX 323 a pharmacoeconomic analysis has been performed. A National Healthcare System perspective and a 5-years temporal horizon have been adopted. Methods: A decision-analytic approach has been adopted, and a Markov model has been used to represent patient's weekly transitions among different health states, related to treatment (chemotherapy, radiotherapy, surgeries, palliative care) and disease status (complete/partial/no response, progression, recurrence). Constant or time-variant costs and quality of life adjustment factors have been assigned to each health state, together with transition probabilities to other states. A 3% discount factor has been used for costs sustained after the first year. The model allowed calculating expected life years (LYs), quality adjusted life years (QALYs) and costs. From these figures, incremental cost/effectiveness (ICER) and cost/utility (ICUR) ratios have been calculated. Robustness of results obtained with baseline values has been tested with probabilistic multivariate sensitivity analysis. Results: In the base case analysis, treatment with TPF yields an expectancy of 2.38 LYs and 1.53 QALYs at a cost of Euro (E) 23,018, which for PF were 1.93 LYs, 1.11 QALYs, and E 19,567, respectively. ICER and ICUR were E 7,669/LY and E 8,217/QALY, respectively. Sensitivity analyses were performed varying transition probabilities of 10%, costs of 30% and utility scores of 20% of their basal values. The analyses showed that 86% and 84% of the results lie below the threshold of E 50,000/LY and E 50,000/QALY, respectively. Conclusions: In our analysis TPF induction chemotherapy proved to be cost-effective with respect to PF, having an ICER and ICUR comparable to other widely accepted healthcare interventions. [Table: see text]

Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France

It is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of 50 000 Euro per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies. The results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected.

Cost effectiveness of zoledronic acid in the prevention of skeletal related events in renal cell carcinoma patients with bone metastases: An exploratory analysis for France

16085 Background: Previous European analyses have shown that zoledronic acid (ZOL) is cost effective in patients with bone metastases secondary to breast cancer, lung cancer, and other solid tumors. A recent analysis suggests that ZOL significantly reduce the risk of new skeletal related events (SREs) such as spinal cord compression, pathological fracture, radiation or surgery to bone, in renal cell carcinoma (RCC) patients with bone metastases. The present study assessed the cost effectiveness of ZOL in this population, adopting a French health care payer perspective. Methods: This analysis was based on a retrospective analysis of a trial of ZOL which randomized RCC patients with bone metastases to ZOL (n=27) or placebo (n=19) plus concomitant antineoplastic therapy for 9 months. A model was developed to simulate the costs and quality-adjusted life-years (QALYs) of the trial patients. SRE costs were estimated by pooling data from SRE studies in the Netherlands and Portugal. These estimates were supplemented with literature-based costs. Drug costs were obtained from French tariffs. Consistent with similar economic analyses, it was assumed that quality of life decreased for 1 month after each SRE experienced. Uncertainty was addressed via bootstrapping and multivariate probabilistic sensitivity analyses (PSA), which involved 10,000 model simulations using input values drawn from probability distributions. Results: ZOL and placebo patients experienced an estimated 0.527 vs. 0.402 discounted QALYs, respectively. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (€3,754 v. €10,531, respectively). After taking into consideration drug therapy costs, ZOL saved €4,732 and increased QALYs by 0.125. Thus, ZOL is preferred over placebo both in terms of costs and quality of life. In the PSA, therapy with ZOL saved costs in 93% of simulations. The cost per QALY gained was below the €50,000 per QALY gained threshold in 97% of PSA simulations. Conclusions: The present analysis suggests that ZA is cost saving and increases QALYs compared to placebo in RCC patients with bone metastases in France. These results may need to be confirmed via a larger prospective clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis

Cost‐effectiveness of primary cytology and HPV DNA cervical screening

Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3-5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly.

Long-Term Clopidogrel Therapy in Patients Receiving Percutaneous Coronary Intervention

The PCI-CURE (Percutaneous Coronary Intervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events) and CREDO (Clopidogrel for the Reduction of Events During Observation) studies have demonstrated that, in addition to aspirin, pre-treatment with clopidogrel followed by long-term (i.e. 9-12 months) therapy significantly reduces the risk of atherothrombotic events in patients undergoing percutaneous coronary intervention (PCI). To examine the economic implications, from the Dutch healthcare perspective, of the use of clopidogrel in patients undergoing PCI (elective procedures or in patients with acute coronary syndrome), comparing pre-treatment followed by long-term therapy with only 4 weeks of treatment. A lifetime Markov model was used to combine data from the PCI-CURE and CREDO trials with data from the literature concerning epidemiology, costs and quality of life. The model was run separately for each trial. Only direct healthcare costs (euro, year 2004 values) were considered. Costs and outcomes were discounted at 4% per anum. For each trial, the cost effectiveness is expressed as costs per life-year and QALY gained. Uncertainties are addressed by uni- and probabilistic multivariate sensitivity analysis. When starting with the data from the PCI-CURE trial, pre-treatment plus 9-month clopidogrel therapy was predicted to save 1119 euros and gain 0.03 life-years and 0.07 QALYs per patient compared with short-term treatment. When starting with the data from the CREDO trial, the combination of pre-treatment and prolonged clopidogrel therapy (1 year) was estimated to save 497 euros and gain 0.10 life-years and 0.14 QALYs per patient. Univariate and probabilistic multivariate sensitivity analyses suggested that the conclusions were generally robust, but that the expected gain in survival for the PCI-CURE population was very sensitive to the effects on mortality within the combined endpoint of myocardial infarction/stroke-free survival. In The Netherlands, pre-treatment plus long-term (9-12 months) therapy with clopidogrel is estimated to save costs and increase (quality-adjusted) survival in the prevention of ischaemic events among patients undergoing elective PCI (CREDO) and in patients with acute coronary syndrome (PCI-CURE) compared with short-term treatment with clopidogrel without pre-treatment.

Cost effectiveness of rimonabant use in patients at increased cardiometabolic risk: estimates from a Markov model

SummaryRimonabant, the first selective CB-1 receptor blocker, is expected to reduce cardiometabolic risk substantially. This study assesses the economics of such treatment in patients at elevated cardiometabolic risk.A Markov model was developed using data from the Rimonabant in Obesity (RIO) trial, published risk equations, and UK cost and utility data. Patients begin either in a diabetic or a non-diabetic state and can transition to cardiovascular disease or to death (based on UK life tables). Transitions to diabetes and subsequent cardiovascular events are also counted. Resource use due to events and long-term management were translated to UK costs (2005 GBP). Tariffs for events and states were applied to age-dependent utilities. Extensive univariate and multivariate probabilistic sensitivity analyses were carried out.Over 10 years, 8% will suffer a cardiovascular event with a loss of more than 1,000 quality-adjusted life years (QALYs) and a cost of more than £500,000 per 1,000 patients. Projecting risk for a lifetime, 1 year of rimonabant use is estimated to gain >65 QALYs at £8,574/QALY. In probabilistic sensitivity analysis, incremental cost-effectiveness ratios varied from £2,657 to £22,141/QALY.Based on the metabolic effects seen in clinical trials, rimonabant should reduce cardiovascular risk in obese or overweight people at reasonable cost.

The Cost Effectiveness of Anticoagulation Management Services for Patients with Atrial Fibrillation and at High Risk of Stroke in the US

Anticoagulation therapy with warfarin is widely considered the standard of care for stoke prophylaxis in patients with atrial fibrillation who are at high risk of stroke. Community-based studies in the US have reported that the effectiveness of anticoagulation varies by management approach and that patients receiving warfarin have international normalised ratio (INR) values within the target therapeutic range less than half the time. To estimate the lifetime societal costs and health benefits of warfarin therapy to prevent strokes, specifically in elderly patients (mean age 70 years) with atrial fibrillation who are at high risk of stroke, when anticoagulation is managed through usual care versus anticoagulation management services, where dedicated anticoagulation professionals (e.g. physician or pharmacist) monitor and oversee patients. Semi-Markov decision model with a 30-day cycle length and 10-year time horizon (to reflect the mean life expectancy of the study population). Univariate sensitivity analyses and Bayesian second-order multivariate probabilistic sensitivity analysis using Monte Carlo simulation were performed. Outcomes measures were costs and QALYs. Most of the probability and outcome estimates included were derived from the recent SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) V trial. Utility values were derived from a large, nationally representative sample of individuals in the Medical Expenditure Panel Survey and were adjusted for age, sex, race, ethnicity, income, education and co-morbidity. Resource utilisation was based on experience at the University Medicine Group Practice Anticoagulation Clinic (University of Colorado, Denver, CO, USA) and costs ($US; 2004 values) included were for warfarin and aspirin (acetylsalicylic acid) use and those associated with major bleeding, treatment of primary events, routine INR and biochemistry monitoring, ECGs, and clinic visits. Costs and outcomes were discounted by 3% per annum. The anticoagulation management service improved effectiveness by 0.057 (95% credible interval 0, 0.36) QALYs and reduced costs by $US2100 (95% credible interval -$US19,800, $US300) [2004 values] compared with usual care. Results were sensitive to the extent of the increase in risk of primary events (all strokes and systemic embolic events attributable to usual care, but were robust to variation in other input variables). The anticoagulation management service was the dominant strategy in 91% of Monte Carlo simulations. The anticoagulation management service appears to cost less and provide greater effectiveness than usual care. To enhance stroke prophylaxis among high-risk patients with atrial fibrillation, physicians and Medicare plans may wish to consider augmenting 'usual care' by the addition of patient-monitoring technology strategies such as formally organised anticoagulation monitoring programmes.

Assessing Cost-Effectiveness in Mental Health: Vocational Rehabilitation for Schizophrenia and Related Conditions

Existing evidence suggests that vocational rehabilitation services, in particular individual placement and support (IPS), are effective in assisting people with schizophrenia and related conditions gain open employment. Despite this, such services are not available to all unemployed people with schizophrenia who wish to work. Existing evidence suggests that while IPS confers no clinical advantages over routine care, it does improve the proportion of people returning to employment. The objective of the current study is to investigate the net benefit of introducing IPS services into current mental health services in Australia. The net benefit of IPS is assessed from a health sector perspective using cost-benefit analysis. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis of the net benefit, defined as the benefits of IPS (comprising transfer payments averted, income tax accrued and individual income earned) minus the costs. The second stage involves application of 'second-filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using the multivariate probabilistic sensitivity analysis. The costs of IPS are 10.3M Australian dollars (95% uncertainty interval 7.4M-13.6M Australian dollars), the benefits are 4.7M (3.1M-6.5M Australian dollars), resulting in a negative net benefit of 5.6M Australian dollars (8.4M-3.4M Australian dollars). The current analysis suggests that IPS costs are greater than the monetary benefits. However, the evidence-base of the current analysis is weak. Structural conditions surrounding welfare payments in Australia create disincentives to full-time employment for people with disabilities.

Modelling the Cost Effectiveness of Cholinesterase Inhibitors in the Management of Mild to Moderately Severe Alzheimer??s Disease

To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer's disease assessment scale-cognitive subscale score of 24. A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer's disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer's disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to pounds sterling (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from 53,780 pounds sterling to 74,735 pounds sterling, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of < 30,000 pounds sterling is < 21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression. Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources.

Assessing cost-effectiveness in mental health: family interventions for schizophrenia and related conditions.

Existing evidence suggests that family interventions can be effective in reducing relapse rates in schizophrenia and related conditions. Despite this, such interventions are not routinely delivered in Australian mental health services. The objective of the current study is to investigate the incremental cost-effectiveness ratios (ICERs) of introducing three types of family interventions, namely: behavioural family management (BFM); behavioural intervention for families (BIF); and multiple family groups (MFG) into current mental health services in Australia. The ICER of each of the family interventions is assessed from a health sector perspective, including the government, persons with schizophrenia and their families/carers using a standardized methodology. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted. The second stage involves application of 'second filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using multivariate probabilistic sensitivity analysis. The most cost-effective intervention, in order of magnitude, is BIF (8000 Australian dollars per DALY averted), followed by MFG (21,000 Australian dollars per DALY averted) and lastly BFM (28,000 Australian dollars per DALY averted). The inclusion of time costs makes BFM more cost-effective than MFG. Variation of discount rate has no effect on conclusions. All three interventions are considered 'value-for-money' within an Australian context. This conclusion needs to be tempered against the methodological challenge of converting clinical outcomes into a generic economic outcome measure (DALY). Issues surrounding the feasibility of routinely implementing such interventions need to be addressed.

A Comparison of the Direct Costs and Cost Effectiveness of Serotonin Reuptake Inhibitors and Associated Adverse Drug Reactions

The economic burden of depression is known to be high and was estimated to be USD 83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy. This study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression. A decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates. The expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram (USD 3891; 0.341), citalopram (USD 3938; 0.340), generic fluoxetine (USD 4034; 0.335), venlafaxine XR (USD 4226; 0.336), sertraline (USD 4250; 0.335), generic paroxetine (USD 4385; 0.332), paroxetine CR (USD 4440; 0.332) and venlafaxine (USD 4613; 0.326). Monte Carlo simulation results suggested that escitalopram was the most likely (77%) to be cost effective for a willingness to pay < or = USD 50,000 per QALY, followed by citalopram (22%), generic fluoxetine (0.3%) and all other SRIs (0%). Sensitivity analyses indicated that the results of the study were robust to the assumptions underpinning the model. SRI-related ADRs have a significant impact on the direct cost and cost effectiveness of treatment. Escitalopram, with the lowest ADR rate of the SRIs, had the lowest expected treatment cost and greatest effectiveness when compared with citalopram, generic fluoxetine, generic paroxetine, paroxetine CR, sertraline, venlafaxine and venlafaxine XR.