Cost effectiveness of treatments for wet age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in people aged ≥50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination and Cochrane Library databases were searched for all wet AMD health technology assessments (HTAs). Overall, 44 publications were evaluated in full and included in this review. A broad range of cost-effectiveness analyses were identified for the most commonly used therapies for wet AMD (pegaptanib, ranibizumab and photodynamic therapy [PDT] with verteporfin). Three studies evaluated the cost effectiveness of bevacizumab in wet AMD. A small number of analyses of other treatments, such as laser photocoagulation and antioxidant vitamins, were also found. Ranibizumab was consistently shown to be cost effective for wet AMD in comparison with all the approved wet AMD therapies (four of the five studies identified showed ranibizumab was cost effective vs usual care, PDT or pegaptanib); however, there was considerable variation in the methodology for cost-effectiveness modelling between studies. Findings from the HTAs supported those from the PubMed and EMBASE searches; of the seven HTAs that included ranibizumab, six (including HTAs for Australia, Canada and the UK) concluded that ranibizumab was cost effective for the treatment of wet AMD; most compared ranibizumab with PDT and/or pegaptanib. By contrast, HTAs at best generally recommended pegaptanib or PDT for restricted use in subsets of patients with wet AMD. In the literature analyses, pegaptanib was found to be cost effective versus usual/best supportive care (including PDT) or no treatment in one of five studies; the other four studies found pegaptanib was of borderline cost effectiveness depending on the stage of disease and time horizon. PDT was shown to be cost effective versus usual/best supportive care or no treatment in five of nine studies; two studies showed that PDT was of borderline cost effectiveness depending on baseline visual acuity, and two showed that PDT was not cost effective. We identified no robust studies that properly evaluated the cost effectiveness of bevacizumab in wet AMD.     

Modelling the long term cost effectiveness of clopidogrel for the secondary prevention of occlusive vascular events in the UK

OBJECTIVE: To assess the long term cost effectiveness of clopidogrel monotherapy compared with acetylsalicylic acid (aspirin; ASA) monotherapy in patients at risk of secondary occlusive vascular events (OVEs) in the UK. DESIGN: Cost utility analysis based on clinical data from CAPRIE (a multicentre randomised controlled trial, involving 19185 patients); long-term effects were extrapolated beyond the trial period using a Markov model populated with data from UK observational studies. Health economic evaluation carried out from the perspective of the UK National Health Service. PARTICIPANTS: A representative cohort of 1000 UK patients aged 60 years (approximate mean age of the CAPRIE population), with the qualifying diagnoses of myocardial infarction, ischaemic stroke and peripheral arterial disease, who are at risk of secondary OVEs (non-fatal myocardial infarction, non-fatal stroke or vascular death). INTERVENTIONS: Patients were assumed to receive treatment with either clopidogrel (75 mg/day) for 2 years followed by ASA (325 mg/day, average) for their remaining lifetime, or ASA alone (325 mg/day, average) for life. MAIN OUTCOME MEASURES: Incremental cost per life year gained and incremental cost per quality-adjusted life year (QALY) gained. RESULTS: In the base case, the incremental cost effectiveness of clopidogrel versus ASA in this population is estimated at 18888 pounds per life year gained and 21 489 pounds per QALY gained. Multiple deterministic and probabilistic sensitivity analyses suggest the model is robust to variations in a wide range of input parameters. CONCLUSION: Two years of treatment with clopidogrel can be considered a cost effective intervention in patients at risk of secondary OVEs in the UK.     

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.     

Cost-effectiveness analysis of inhaled zanamivir in the treatment of influenza A and B in high-risk patients

OBJECTIVE: To evaluate the cost effectiveness of zanamivir 10 mg twice daily for 5 days in the treatment of influenza in high-risk patients. DESIGN: Bootstrap cost-effectiveness analysis incorporating within-trial analysis of pooled patient-level cost and effect data. SETTING: UK unit costs and utilities applied to high-risk patients drawn from 6 multinational clinical trials. PATIENTS: A total of 154 zanamivir and 167 placebo high-risk patients were included in the analysis. MAIN OUTCOME MEASURES: Cost per day of normal activities; cost per symptom-free day; cost per complication averted; cost per quality-adjusted life-year (QALY). RESULTS: The mean benefit was estimated to be 2.5 days [95% confidence interval (CI): 0.68 to 4.27] of normal activities gained; 2.0 (95% CI: 0.56 to 3.51) symptom-free days; and a 9% reduction in complications (95% CI: 0 to 18%). Excluding the effect of rare hospitalisation costs, the cost (1999 values) of gaining a day of normal activities was 9.50 Pounds (95% CI: 5 Pounds to 39 Pounds); cost per symptom-free day was 11.56 Pounds (95% CI: 6 Pounds to 43 Pounds); cost per complication averted was 262 Pounds (95% CI: 90 Pounds to 1574 Pounds). Influenza was estimated to reduce utility by 0.883 per day, demonstrating the debilitating effect of the disease. Extrapolating a day of normal activities to a standard utility measure resulted in a cost per QALY of 3900 Pounds excluding inpatient costs (7490 Pounds including inpatient costs). Cost-effectiveness acceptability curves demonstrated 90% certainty that zanamivir would be cost effective at 8000 Pounds per QALY. CONCLUSIONS: Significant health benefits can be obtained with zanamivir treatment in high-risk patients. The cost per QALY for zanamivir in these patients compares well with that of other commonly used pharmacological interventions.     

Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer's disease

OBJECTIVE: 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. METHODS: 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. 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. CONCLUSIONS: 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.     

Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis

OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD). METHODS: A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.     

Post-exposure influenza prophylaxis with oseltamivir: cost effectiveness and cost utility in families in the UK

OBJECTIVES: To assess the cost effectiveness and cost utility of preventing post-exposure influenza infection using the neuraminidase inhibitor oseltamivir from a healthcare payer's perspective in the UK. METHODS: A simulation model was developed, based on clinical trial results and published data, to predict morbidity and mortality due to influenza and to compare oseltamivir post-exposure prophylaxis (PEP) with no prophylaxis within families with members aged >or=13 years. Two scenarios were tested:1. Comparison of patients receiving PEP versus patients not receiving PEP and not being treated with oseltamivir should they become infected. 2. Comparison of patients receiving PEP versus patients not receiving PEP but being treated with oseltamivir should they become infected. The model was run with an attack rate in household contacts of 8% for the base case, with higher rates (up to 30%, representing pandemic conditions) tested in sensitivity analyses. A societal perspective and other key parameters were tested in sensitivity analysis. The year of costing was 2002. The time span for the model was up to 1 year (including one influenza season), but loss of life was included in the QALY calculation and based on expected life expectancy. RESULTS: PEP with oseltamivir results in reduced morbidity (i.e. fewer influenza cases) and associated reductions in complications, hospitalisations and mortality due to influenza. When comparing oseltamivir PEP with no prophylaxis for contact attack rates of 8%, 12% and 30%, the mean costs per QALY gained for scenario one were estimated at 29,938 pounds, 18,697 pounds and 5403 pounds, respectively; the mean costs per case avoided were 467 pounds, 293 pounds and 84 pounds, respectively. The corresponding results for scenario two were 52,202 pounds, 31,610 pounds and 9688 pounds per QALY gained. CONCLUSIONS: PEP with oseltamivir is likely to be a cost-effective strategy for family contacts in the UK from a healthcare payer perspective when influenza-like illness contact attack rates are 8% or higher and the only treatment given is 'usual care'.     

Pegaptanib: in exudative age-related macular degeneration

Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration (AMD). In two randomised, double-masked trials in patients with exudative AMD (n=1208), the proportion of responders (those losing <15 letters of visual acuity) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%; p<0.001). These trials were conducted concurrently and analysed as a single study; the treatments were given every 6 weeks for 48 weeks. The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints (e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye). These vision-improving effects of pegaptanib were associated with beneficial angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient. Serious injection-related adverse events occurred in 相似文献   

Cost effectiveness of dalteparin for preventing venous thromboembolism in abdominal surgery

INTRODUCTION: Patients undergoing abdominal surgeries face substantial risk of experiencing venous thromboembolic events in the perioperative period. The low-molecular-weight heparin dalteparin sodium is clinically effective in reducing the incidence of venous thromboembolism (VTE) in these patients. Dalteparin may be used in low (2500 units [U]) and high (5000 U) once-daily doses for this indication. However, the cost effectiveness of dalteparin 5000 U compared with dalteparin 2500 U and unfractionated heparin (UFH) for this indication has not been studied. OBJECTIVE: To conduct a cost-utility analysis to evaluate the cost effectiveness of dalteparin compared with UFH for preventing VTE in patients undergoing elective abdominal surgery. METHODS: A Markov model, from a healthcare perspective, was constructed to evaluate the cost effectiveness of dalteparin 5000 U and dalteparin 2500 U compared with UFH. A 69-year-old mixed sex patient population was studied using pooled probabilities of clinical outcomes from randomised, controlled trials. Cost data were mostly derived from Medicare reimbursement, in year 2002-03 values. Cost effectiveness was measured as cost per QALY gained over the patient's lifetime. RESULTS: Total costs for patients given UFH, dalteparin 2500 U and dalteparin 5000 U were US45,855 dollars, US45,882 dollars and US46,308 dollars, respectively, while QALYs were 9.5603, 9.5632 and 9.5811, respectively. Hence, the incremental cost effectiveness of dalteparin 5000 U over dalteparin 2500 U and UFH was US23,799 dollars/QALY and US21,779 dollars/QALY gained, respectively. Similarly, cost effectiveness for dalteparin 2500 U over UFH was US9310 dollars/QALY gained. Univariate sensitivity analysis showed that dalteparin 5000 U maintained its cost effectiveness (incremental cost-effectiveness ratio [ICER] or =90% patients receive the benefit of the medication, policy makers would need to commit substantially more resources than suggested by the baseline ICERs.     

Comprehensive decision-analytic model and Bayesian value-of-information analysis: pentoxifylline in the treatment of chronic venous leg ulcers

OBJECTIVE: To conduct a Bayesian value-of-information analysis of the cost effectiveness of pentoxifylline (vs placebo) as an adjunct to compression for venous leg ulcers. METHODS: A probabilistic Markov model was developed to estimate mean clinical benefits and costs associated with oral pentoxifylline (400mg three times daily) and placebo. Clinical data were obtained from a systematic review and synthesised using Bayesian methods. The decision uncertainty associated with the adoption of pentoxifylline as well as the maximum value associated with further research were estimated before and after the completion of the largest 'definitive' treatment trial. Resource use was obtained from a UK national audit and unit costs applied (pounds, 2004 values). RESULTS: The prior and posterior analyses suggest that pentoxifylline is a dominant therapy versus placebo. In the prior analysis, patients in the pentoxifylline group healed an average of 8.28 weeks quicker than patients in the placebo group (95% credibility interval [CI] 1.89, 14.56), had a 0.02 gain in QALYs (95% CI -0.12, 0.17) and an average reduction in cost of 153.4 pounds (95% CI -53.11, 354.9). Estimates of the uncertainty surrounding the cost effectiveness of pentoxifylline and the value of perfect information in both analyses did not suggest further research was justified. In the prior analysis, for willingness-to-pay values of 0 pounds, 100 pounds and 500 pounds per QALY gained, the estimated values of perfect information were 128,200 pounds, 127,100 pounds and 126,700 pounds, respectively. Incorporation of the information from the largest randomised controlled trial on pentoxifylline did improve the estimate of the clinical effect associated with this drug; however, the variation was not large enough to reverse either the decision regarding the dominance of pentoxifylline or the maximum value associated with further research. CONCLUSION: Bayesian value-of-information analysis represents a valuable tool for healthcare decision making. Had the results from this analysis been available before the largest trial was funded, a more efficient allocation of research and development resources could have been made.     

Population pharmacokinetics of pegaptanib in patients with neovascular, age-related macular degeneration

The anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib is eliminated primarily by renal clearance. Because renal function declines with age, pegaptanib exposure in patients with age-related macular degeneration (AMD) may increase. Therefore, a population pharmacokinetic (PK) analysis of pegaptanib was undertaken in Western and Asian AMD patients to determine the influence of renal function on apparent pegaptanib clearance (CL). Pegaptanib (0.3-3 mg per eye) was administered every 4 to 6 weeks to 262 AMD patients in 4 studies. Pegaptanib exposures (area under the concentration-time curve [AUC] and maximum plasma concentration) after 8 doses were similar to exposures following the first dose, consistent with the absence of plasma accumulation. A 1-compartment model parameterized in terms of the absorption rate constant, apparent volume of distribution, and CL was used to describe the pegaptanib plasma concentration data. Creatinine clearance (CLCR), body weight (WT), and age influenced pegaptanib PK. Decreasing CLCR from 70 to 30 mL/min doubled AUC. After adjustment for CLCR, WT, and age, the model predicted no race differences in CL or AUC. Given that the therapeutic 0.3 mg per eye dose of pegaptanib results in exposures one-tenth of those observed following the well-tolerated 3-mg dose, these results suggest that no dose adjustment is warranted for AMD patients with moderate renal insufficiency (CLCR >30 mL/min).     

Cost-effectiveness of levodopa/carbidopa/entacapone (Stalevo) compared to standard care in UK Parkinson's disease patients with wearing-off

BACKGROUND AND METHODS: A Markov model was developed to evaluate the cost-effectiveness of levodopa/carbidopa/entacapone (LCE;Stalevo), in the treatment of patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (wearing-off). LCE, with or without other antiparkinsonian medications, was compared to UK standard care, comprising traditional levodopa/ dopa-decarboxylase inhibitor (DDCI) with other antiparkinsonian medications (e.g. selegiline or dopamine agonists) added as needed. The costs and outcomes of both treatments were projected over a period of 10 years from the perspective (a) of society as a whole and (b) of the UK National Health Service (NHS). Sensitivity analyses, including second-order Monte Carlo simulations, were performed to assess the confidence level of the primary results. RESULTS: Treatment with LCE produced an average gain of +1.04 quality-adjusted life-years (QALYs) per patient (2.57 vs. 1.53) in the base-case analysis (discount rate 3.5%). This gain was accompanied by a reduction in the total 10-year direct cost of care to society of 10198 pounds per patient ( approximately E14800). From the societal perspective, therefore, LCE was dominant, producing better clinical outcomes with lower costs. This dominance was reiterated in all sensitivity analyses of society-focused analysis, including a shortening of the time-frame to 5 years.Although treatment with LCE resulted in an increase in direct costs per patient of 3239 pounds (25756 pounds versus 22517 pounds) to the NHS over the 10-year period analysed, the incremental cost-effectiveness ratio (ICER) of LCE was only 3105 pounds per QALY gained (approximately E4500). All ICERs to the NHS remained below 3800 pounds per QALY gained in univariate sensitivity analyses applying different discount rates. When a shorter, 5-year, time-horizon was analysed, the NHS-related ICER for LCE was 6526 pounds per QALY gained. All these ICERs are within the range usually considered to indicate acceptable or highly acceptable cost effectiveness (defined as < 30000 pounds per QALY gained).The results of the Monte Carlo simulations indicated that the likelihood of LCE being either 'dominant' or more effective at an 'acceptable cost' from either the societal or the NHS perspective was high, exceeding 96% in the base-case sensitivity analysis, and was 93% even when all the uncertainties associated with the model were taken into consideration simultaneously. In particular, compared to standard care, the probability that LCE would provide better outcomes at a lower cost to society as a whole was 77% in the base-case sensitivity analysis and 72% in the scenario involving the highest degree of uncertainty. CONCLUSIONS: In the UK the use of LCE to treat PD patients with wearing-off is beneficial to individual patients and likely to offer money savings to society as a whole, compared with UK standard therapy. The added cost of the medication itself is exceeded by the savings made in other direct costs of PD, mainly those relating to social care or PD-related private expenditures.     

Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer

BACKGROUND: In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]). OBJECTIVES: To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective. METHODS: Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness. RESULTS: The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival. CONCLUSIONS: The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.     

Assessing the cost-effectiveness of COX-2 specific inhibitors for arthritis in the Veterans Health Administration

OBJECTIVE: This study was designed to assess the cost-effectiveness of cyclooxygenase-2 specific (COX-2) inhibitors (rofecoxib and celecoxib) over nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in high-risk arthritis patients from the perspective of the Veterans Health Administration (VA). METHODS: This literature-based economic analysis (with data summarized from MEDLINE-indexed and other published sources, FDA reports, and data on file at VA San Diego Healthcare System) compared rofecoxib and celecoxib to NSAIDS in two arthritis patient populations considered at higher risk of developing clinically significant upper gastrointestinal events (CSUGIEs): (1) patients of any age with previous medical history of perforation/ulcer/bleed (PUB); and (2) patients 65 years and older (regardless of history of PUB). Two outcome measures were reported: (1) incremental cost per CSUGIE averted over 1 year; and (2) incremental cost per quality-adjusted life-year (QALY) gained, considering both the mortality and morbidity associated with gastrointestinal (including CSUGIEs) and cardiovascular-related adverse events. When possible, costs were modeled to reflect the VA perspective. Sensitivity analyses were conducted to test the robustness of the analysis. RESULTS: Compared to NSAIDS, rofecoxib and celecoxib increased costs but reduced the incidence of CSUGIE. Cost per CSUGIE avoided were $7476 and $16,379 (in patients with a PUB history) and $14,294 and $18,376 (in patients aged > or = 65 years) for celecoxib and rofecoxib, respectively. In both populations, celecoxib was associated with a cost per QALY less than $50,000. In contrast, rofecoxib was found to cost more and result in a net QALY loss, due in particular to the increase in the risk of cardiovascular complications, and was therefore considered cost-ineffective. Results were most dependent on assumptions about the incidence of cardiovascular events and CSUGIE and the COX-2 inhibitors' acquisition price. CONCLUSIONS: This analysis suggests that COX-2 inhibitors may be cost-effective from the perspective of the VA. However, cost-effectiveness appears to depend less on the specific characteristics of the high-risk target population considered but more on the agent evaluated. Celecoxib appears to be an alternative to traditional NSAIDs in the patient populations studied.     

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium

Background: Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. Objective: The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Methods: Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Results: Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40?000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30?000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38?514, &U20AC;22?220 and &U20AC;27?862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37?167, &U20AC;19?718 and &U20AC;19?638 per QALY for women with prevalent vertebral fractures. Conclusion: This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.     

Cost-utility analysis of melphalan plus prednisone with or without interferon-alpha 2b in newly diagnosed multiple myeloma. Results from a randomised controlled trial

This study evaluated the cost utility of adding interferon-alpha 2b to conventional treatment in patients with multiple myeloma. It also provides a methodology for transforming complex quality-of-life profiles into a single index value on the conventional 0 to 1 quality-adjusted life-year scale (QALY). From 1990 to 1992, 583 patients with newly diagnosed, symptomatic multiple myeloma were enrolled in a randomised, multicentre, phase III study to evaluate the addition of interferon-alpha 2b to treatment with melphalan and prednisone. Addition of interferon-alpha 2b yielded a 12% increase in median survival time, at the expense of a slight reduction in quality of life during the first year of treatment. The gain in survival time was not large enough to reach statistical significance. Patients receiving interferon-alpha 2b also had a 5- to 6-month prolongation of the plateau phase. Cost per QALY gained by adding interferon-alpha 2b was conservatively estimated at $US110,000. Potentially better cost effectiveness may be found in different treatment regimens or in certain patient subgroups.     

Cost-effectiveness comparison of current proton-pump inhibitors to treat gastro-oesophageal reflux disease in the UK

OBJECTIVE: Gastro-oesophageal reflux disease (GORD) is a recurring condition with many patients requiring long-term maintenance therapy. Therefore initial choice of treatment has long-term cost implications. The aim was to compare the costs and effectiveness of treatment of GORD the (unconfirmed by endoscopy) with seven proton pump inhibitors (PPIs: esomeprazole, lansoprazole (capsules and oro-dispersible tablets), omeprazole (generic and branded), pantoprazole and rabeprazole), over one year. DESIGN AND METHODS: A treatment model was developed of 13 interconnected Markov models incorporating acute treatment of symptoms, long-term therapy and subsequent decisions to undertake endoscopy to confirm diagnosis. Patients were allowed to stop treatment or to receive maintenance treatment either continuously or on-demand depending on response to therapy. Long-term dosing schedule (high dose or step-down dose) was based on current market data. Efficacy of treatments was based on clinical trials and follow-up studies, while resource use patterns were determined by a panel of physicians. MAIN OUTCOME MEASURES: The model predicts total expected annual costs, number of symptom-free days and quality-adjusted life-years (QALY). RESULTS: Generic omeprazole and rabeprazole dominated (i.e. cost less and resulted in more symptom-free days and higher QALY gains) the other PPIs. Rabeprazole had a favourable cost-effectiveness ratio of 3.42 pounds per symptom-free day and 8308 pounds/quality-adjusted life-year gained when compared with generic omeprazole. Rabeprazole remained cost-effective independent of choice of maintenance treatment (i.e. proportion of patients remaining on continuous treatment versus on-demand treatment).CONCLUSIONS: Economic models provide a useful framework to evaluate PPIs in realistic clinical scenarios. Our findings show that rabeprazole is cost-effective for the treatment of GORD.     

Cost effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a lifetime model

BACKGROUND: Recent randomised trials have demonstrated a statistically significant effect of trastuzumab on disease-free survival when used as adjuvant therapy for human epidermal growth factor receptor 2 protein (HER2)-positive resectable early stage breast cancer, with a treatment course lasting either 9 or 52 weeks. However, the cost effectiveness of adjuvant trastuzumab with respect to mortality remains uncertain, especially in an Australian setting. OBJECTIVE: To estimate the cost effectiveness of trastuzumab in Australia, in a cohort of 50-year-old patients with HER2-positive breast cancer over a lifetime, using (i) disease-free survival and cardiotoxicity data from recent randomised trials; (ii) information on long-term survival of patients with treated primary breast cancer; and (iii) costs of treating local and distant relapses and disease from causes other than breast cancer. METHODS: A Markov model consisting of four health states (remission, loco-regional recurrence, metastatic disease and death) was developed. Transition probabilities corresponded to patterns of relapse and metastases seen in recent trials. The model was run until age 100 years to allow calculation of average survival. Outcome measures were life-years and QALYs (calculated using utility weights reported in the literature).The model was calibrated to reflect literature evidence that the risk of breast cancer recurrence following primary treatment diminishes progressively to zero after about 20 years. It was assumed that the morbidity benefit of trastuzumab observed in trials would be present for 5 years but would then diminish progressively to zero after 8 years. Costs (year 2005 values) and benefits were discounted at 3% per annum. RESULTS: For every 1000 patients treated with a 52-week course of trastuzumab, there were 136 fewer breast cancer deaths (relative risk reduction 28%). The incremental cost-effectiveness ratios (ICERs) were Australian dollars ($ A)13 730 per year of life saved (YOLS) and $ A22 793 per QALY. The net incremental cost was $ A56.3 million ($ A414 012/cancer death avoided). Cost effectiveness declined (ICER = $ A27 734/QALY) in older patients (age 65 years at treatment initiation).The ICER was driven mainly by the drug acquisition costs, the assumption of the duration of benefit and the discount rate. Cost offsets from reduced costs of treating recurrent or metastatic breast cancer during follow-up were present but these factors were of less importance according to sensitivity analyses. The 9-week treatment schedule approached economic dominance (ICER = $ A1700/QALY) because of decreased costs, improved relative risk for prevention of metastases and more cancer deaths avoided (196). CONCLUSION: The results suggest that trastuzumab as adjuvant therapy for early breast cancer may be cost effective when given over either 52 or 9 weeks at current acquisition costs in Australia. However, the overall budget impact of the 52-week course is significant, and the 9-week course appears economically attractive.     

Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia

OBJECTIVE: To assess the cost effectiveness of primary prophylaxis with clotting factor instead of treatment following a bleed (on-demand) for individuals with severe haemophilia. DESIGN: Different data sources on the clinical effects and costs of treatments were combined using a Markov model. SETTING: English treatment centres. PERSPECTIVE: UK societal. PARTICIPANTS: Hypothetical cohorts of 100 individuals with severe haemophilia A or B or severe von Willebrands disease. INTERVENTIONS: Primary prophylaxis treatment on-demand with clotting factor. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost per QALY in UK pounds ( pound, 1999/2000 values). RESULTS: The baseline results showed that treating individuals with severe haemophilia A/severe von Willebrands disease or severe haemophilia B with primary prophylaxis instead of treatment on-demand cost an additional pound 46500 and pound 8600 per QALY gained, respectively. However, the results were extremely sensitive to a number of factors including the clotting factor unit cost, the time between prophylactic doses and the discount rate. CONCLUSIONS: Despite the high costs of treatment, primary prophylaxis was cost effective compared with treatment on-demand in some scenarios. Primary prophylaxis is more likely to be cost effective for individuals with severe haemophilia B compared with individuals with severe haemophilia A/severe von Willebrands disease. Further research is required to assess the relationship between methods of clotting factor infusion and health-related quality-of-life.     

Pegaptanib sodium for the treatment of neovascular age-related macular degeneration

This article reviews pegaptanib sodium, a compound developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular age-related macular degeneration (AMD). Traditional treatment approaches to neovascular AMD have included destructive therapies such as thermal laser photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a new treatment approach that is a non-destructive therapy based on the inhibition of vascular endothelial growth factor activity in the eye. This diminishes the neovascular drive in the pathologically hyperpermeable state of the diseased eye. Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics and rationale for the clinical use of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.