Atorvastatin: a pharmacoeconomic review of its use in the primary and secondary prevention of cardiovascular events

Atorvastatin is a lipid-lowering agent that has been evaluated in a number of primary and secondary intervention studies. In the primary prevention trials ASCOT-LLA and CARDS, atorvastatin 10 mg/day significantly reduced cardiovascular events compared with placebo. A prospectively conducted economic analysis of the 3.3-year ASCOT-LLA trial showed that atorvastatin was associated with incremental cost-effectiveness ratios (ICERs) of euro11,693 (UK) and euro12,673 (Sweden) per event avoided (2002 values). Longer-term modelled analyses using data from CARDS showed ICERs of euro8046 (Spain) and 6471pound (UK) per QALY gained (2003/2004 values), and a US analysis showed atorvastatin was dominant versus no statin when modelled over the lifetime of a representative US diabetic primary prevention population. In a modelled analysis based on results of the IDEAL trial, which showed significant reductions in cardiovascular endpoints with high-dose atorvastatin (80 mg/day) compared with conventional-dose simvastatin in patients with stable coronary heart disease, ICER values were below the commonly used cost-effectiveness threshold of euro50,000 per QALY gained in Norway, Sweden and Denmark, but were above this threshold in Finland (2005 values). A modelled US analysis that also included data from IDEAL and other sources showed an ICER of $US33,400 per QALY gained, assuming the incremental difference in acquisition cost between high-dose atorvastatin and conventional-dose simvastatin was $US1.40/day (2005 value). Most cost-effectiveness analyses with atorvastatin in patients with acute coronary syndrome used data from the 16-week MIRACL study, which showed a significant reduction in cardiovascular events with high-dose atorvastatin compared with placebo. Analyses were conducted in North America and Europe and showed that 31-86% of the acquisition cost of high-dose atorvastatin was offset by reductions in costs associated with cardiovascular events. Across five countries, ICER values ranged from approximate $US850 to $US4100 per event avoided (2000/2001 values). Another analysis conducted in the US used longer-term data and showed that high-dose atorvastatin versus conventional-dose statin was associated with an ICER of $US12,900 per QALY gained, assuming the daily difference in acquisition cost was $US1.40 (2005 value). In conclusion, atorvastatin has demonstrated beneficial effects on various cardiovascular endpoints in large, well designed primary and secondary intervention trials. These benefits in moderate- to high-risk patients were achieved at a relatively low incremental cost and, across the economic analyses, a substantial proportion of atorvastatin acquisition costs was offset by reductions in healthcare resource use associated with cardiovascular events. Cost-effectiveness analyses based on major clinical trials comparing atorvastatin with placebo, usual medical care, simvastatin or pravastatin have generally shown that atorvastatin is associated with favourable ICER values, often well below commonly used cost-effectiveness thresholds. These modelled analyses have the inherent limitation that projecting long-term outcomes beyond the time period of a clinical trial imparts a degree of uncertainty to the results. Nevertheless, while some findings were sensitive to changes in model assumptions, such as the long-term benefits of statin therapy, most sensitivity analyses showed that results of the base-case analyses were robust to plausible changes in key parameters. Although a clear pattern is not evident from available data, intuitively, the value of atorvastatin would be expected to increase with the patient's risk for serious cardiovascular events.     

Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.     

Atorvastatin: a review of its use in the primary prevention of cardiovascular events in patients with type 2 diabetes mellitus

Atorvastatin (Lipitor) is an HMG-CoA reductase inhibitor with well documented lipid-lowering effects. It has recently been evaluated for the primary prevention of major cardiovascular events in patients with type 2 diabetes mellitus without elevated serum low-density lipoprotein (LDL)-cholesterol levels. Atorvastatin 10mg daily for 4 years was effective at reducing the risk of a first major cardiovascular event, including stroke, in a large, placebo-controlled, multicentre trial in patients with type 2 diabetes and at least one other coronary heart disease (CHD) risk factor, but without markedly elevated LDL-cholesterol levels. In this trial, known as CARDS (the Collaborative AtoRvastatin Diabetes Study), atorvastatin had a similar tolerability profile to that of placebo. Thus, atorvastatin has a potential role in the primary prevention of cardiovascular events in diabetic patients at risk of CHD, irrespective of pre-treatment LDL-cholesterol levels.     

Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus

OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical trials have shown ACE inhibitors can affect the development of nephropathy when initiated prior to the onset of microalbuminuria. Our objective is to examine the cost effectiveness of treating adults aged over 20 years with an ACE inhibitor (captopril) immediately following diagnosis of type 1 diabetes versus treating them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we calculated four main outcome measures: lifetime direct medical costs (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars. SETTING: All analyses were from the viewpoint of a single US payer responsible for all direct medical costs, including screening for microalbuminuria, ACE inhibitor treatment (captopril), management of major diabetic complications, and routine annual medical costs not specific to diabetes. METHODS: We applied the model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1 diabetes. Distribution of sex and race/ethnicity within the cohort is representative of the general US population. RESULTS: We estimated that the incremental cost of early use of captopril for the average adult with type 1 diabetes is USD 27,143 per QALY. This level varies considerably with age and glycaemic level. When the age at onset of diabetes is 20 years and glycosylated haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost-effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its underlying assumptions and data, suggests that early treatment with captopril provides modest benefit at reasonable cost effectiveness, from the US single-payer perspective, in the prevention of ESRD compared with delaying treatment until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors will provide similar cost effectiveness if they have equivalent efficacy, compliance and price per dose. Treatment may be considered among patients at age 20 years with new onset of type 1 diabetes. This conclusion is sensitive to the extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as the patient's age and glycaemic level must be considered when deciding to initiate early treatment.     

Cost effectiveness of tumour necrosis factor-alpha inhibitors as first-line agents in rheumatoid arthritis

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-alpha (TNFalpha) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFalpha inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective. METHODS: A Markov model was developed utilising a discount rate of 3% per annum, a cycle length of 1 year and a lifetime time-horizon for a hypothetical cohort of US females aged 55-60 years who had been diagnosed with RA. The source of data for predicted probabilities, expected mortality rates and treatment costs in year 2005 US dollars (drug, toxicity, monitoring and hospitalisation) was from the literature. These costs are assigned in 5-year cycles (calculated from initial 1-year estimates) along with the effect on quality-adjusted life-years (QALYs), which were calculated using the Health Assessment Questionnaire score. Univariate sensitivity analyses were conducted on all relevant parameters. RESULTS: Adalimumab, etanercept, adalimumab plus methotrexate and infliximab plus methotrexate had incremental cost-effectiveness ratios (ICERs) versus methotrexate monotherapy of $US63 769, $US89 772, $US194 589 and $US409 523 per QALY, respectively. When taking into consideration age at diagnosis, the ICER for etanercept ranged from $US84 129 to $US96 225 per QALY. In considering males for the base-case age at diagnosis, the ICER for etanercept versus methotrexate was $US85 100 per QALY. The average lifetime cost across all treatment arms in a woman diagnosed between 55 and 60 years of age was $US211 702. CONCLUSION: While these ICERs cannot be used to directly compare one biological agent with another since there are no comparative trials, they do provide a valid comparison versus methotrexate as first-line agents. Depending where the cost-effectiveness threshold is drawn (i.e. whether it is considered to be $US50 000 or $US100 000 per QALY), etanercept and adalimumab may be considered relatively cost-effective first-line treatments for RA compared with methotrexate monotherapy.     

Cost effectiveness of long-term treatment with eszopiclone for primary insomnia in adults: a decision analytical model

OBJECTIVE: Although the clinical benefits of pharmacological treatments for insomnia have been studied, no systematic assessment of their economic value has been reported. This analysis assessed, from a broad payer and societal perspective, the cost effectiveness of long-term treatment with eszopiclone (LUNESTA, Sepracor Inc., [Marlborough, MA, USA]) for chronic primary insomnia in adults in the US. METHODS: A decision analytical model was developed based on the reanalysis of a 6-month placebo-controlled trial, which demonstrated that eszopiclone 3mg significantly improved sleep and daytime function measures versus placebo in adults with primary insomnia. Patients were classified as either having remitted or not remitted from insomnia based upon a composite index of eight sleep and daytime function measures collected during the trial. These data were supplemented with quality-of-life and healthcare and lost productivity cost data from the published literature and medical and absenteeism claims databases. RESULTS: Compared with non-remitted patients, patients classified as remitted had lower monthly healthcare and productivity costs (in 2006 dollars) [a reduction of $US242 and $US182, respectively] and higher quality-adjusted life-year (QALY) weight (a net gain of 0.0810 on a scale ranging from 0 to 1). During the study, eszopiclone-treated patients were about 2.5 times more likely to have remitted than placebo-treated patients. Six months of eszopiclone treatment reduced direct (healthcare) and indirect (productivity) costs by an estimated $US245.13 and $US184.19 per patient, respectively. Eszopiclone use was associated with a cost of $US497.15 per patient over 6 months (including drug cost, dispensing fee, physician visit and time loss to receive care). Thus, after considering the above savings and the costs associated with eszopiclone treatment over 6 months, cost increased by $US252.02 (excluding productivity gains) and $US67.83 (including productivity gains) per person. However, eszopiclone treatment was also associated with a net QALY gain of 0.006831 per patient over the same period. Consequently, the incremental cost per QALY gained associated with eszopiclone was approximately $US9930 (including productivity gains [i.e. $US67.83 / 0.006831]) and $US36 894 (excluding productivity gains [i.e. $US252.02 / 0.006831]). Sensitivity analyses using a variety of scenarios suggested that eszopiclone is generally cost effective. CONCLUSIONS: This analysis suggested that long-term eszopiclone treatment was cost effective over the 6-month study period, particularly when the impact on productivity costs is considered. Given the increasing interest in new pharmacological interventions to manage insomnia, payers and clinicians alike should carefully consider the balance of health and economic benefits that these interventions offer. Accordingly, additional research in this area is warranted.     

Cost effectiveness of recombinant human insulin-like growth factor I therapy in patients with ALS.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterised by a progressive loss of voluntary motor activity. Recombinant human insulin-like growth factor I (rhIGF-I) has been shown to be useful in treating ALS. The purpose of this study was to examine the cost effectiveness of rhIGF-I therapy in patients who have ALS. DESIGN: We performed a cost-effectiveness analysis from the societal perspective on 177 patients who received treatment with rhIGF-I or placebo in a North American randomised clinical trial. We estimated the incremental cost-effectiveness ratio of rhIGF-I using resource utilisation and functional status measurements from the clinical trial. Costs were estimated from 1996 US Medicare reimbursement schedules. Utility weights were elicited from ALS healthcare providers using the standard gamble technique. MAIN OUTCOME MEASURES AND RESULTS: The overall cost per quality-adjusted life-year (QALY) gained for rhIGF-I therapy compared with placebo was $US67,440. For the subgroups of patients who were progressing rapidly or were in earlier stages of disease at enrolment, rhIGF-I cost $US52,823 and $US43,197 per QALY gained, respectively. CONCLUSIONS: Treatment with rhIGF-I is most cost effective in ALS patients who are either in earlier stages of the disease or progressing rapidly. The cost effectiveness of rhIGF-I therapy compares favourably with treatments for other chronic progressive diseases.     

Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis

Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost-utility ratios of euro28 600-56 100 (year of costing not reported) when direct costs were considered, and euro3440-48 200 when direct costs plus loss-of-productivity costs were considered. In conclusion, cost-utility analyses, which were based on modelling of data from the pivotal clinical trial of infliximab plus methotrexate, indicate that infliximab plus methotrexate is associated with acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained) relative to methotrexate monotherapy in patients with active rheumatoid arthritis who have not responded to previous methotrexate or other DMARD therapy. The cost effectiveness of infliximab versus other DMARDs is at present unclear, but will be clarified when appropriate data from directly comparative clinical and/or pharmacoeconomic studies become available. In patients in whom adequate courses of other DMARDs have failed to achieve satisfactory disease control, infliximab plus methotrexate may prevent or delay disability, which may produce reductions in nondrug costs that can help offset its acquisition cost.     

Economic benefits of amlodipine treatment in patients with coronary artery disease

OBJECTIVE: To estimate the potential savings in overall cardiovascular disease (CVD) treatment costs for the US population with coronary artery disease (CAD) resulting from the use of amlodipine. STUDY DESIGN AND METHODS: Using patient-level data from a retrospective analysis of the Prospective Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), a randomised, placebo-controlled clinical trial (n = 825), we constructed a Markov cohort simulation model to estimate the health economic outcomes of patients with CAD treated with either amlodipine or placebo. PERSPECTIVE: Healthcare payer perspective. RESULTS: The expected number of CVD events for amlodipine recipients was significantly lower than the number of CVD events in the placebo cohort (p < 0.01). The net present value of the cost per patient for CVD treatment was estimated to be $US14 117 for amlodipine recipients and $US16 683 (1999 values, assuming a 3% discount rate) for placebo recipients over 3 years of follow-up with cost savings realised in the amlodipine cohorts after 6 months. CONCLUSIONS: According to the model, amlodipine results in an expected per patient cost savings of $US2566 over a 3-year period, mainly due to a reduction in hospitalisations for cardiovascular-related events and procedures.     

A cost-effectiveness analysis of fondaparinux sodium compared with enoxaparin sodium as prophylaxis against venous thromboembolism: use in patients undergoing major orthopaedic surgery

OBJECTIVE: To determine the cost effectiveness of fondaparinux sodium compared with enoxaparin sodium for prophylaxis against venous thromboembolism in patients undergoing major orthopaedic surgery. METHODS: Using a cohort simulation model, two primary analyses were conducted from the perspective of the US healthcare payer. Probabilities for a trial-based analysis were obtained from patients participating in the fondaparinux clinical trial programme supplemented with data from published literature. Probabilities for a label-based analysis were estimated for a hypothetical cohort of US patients receiving either fondaparinux or enoxaparin as recommended by US FDA-approved labelling. Resource use and costs were obtained from large US healthcare databases. Outcome measures were rates of symptomatic thromboembolic events and healthcare costs. Costs were in 2003 values. RESULTS: In the trial-based analysis, fondaparinux was estimated to prevent 15.1 symptomatic venous thromboembolic events (per 1,000 patients) at 3 months for patients undergoing major orthopaedic surgery compared with enoxaparin. The cost savings (per patient) of using fondaparinux over enoxaparin are US 61 dollars at 30 days, US 89 dollars at 3 months, and US 155 dollars at 5 years. In the label-based analysis, fondaparinux was estimated to prevent 17.8 venous thromboembolic events (per 1,000 patients) at 3 months compared with enoxaparin, producing savings per patient of US 25 dollars at discharge, US 112 dollars over 1 month, US 141 dollars over 3 months and US 234 dollars over 5 years. Results remain robust to clinically plausible variation in input parameters and assumptions. CONCLUSION: Our model suggests that fondaparinux, when compared with the current standard regimen of enoxaparin for prophylaxis of venous thromboembolism in major orthopaedic surgery, improves outcomes and is cost saving from a US healthcare-payer perspective over the broad range of assumptions evaluated.     

Cost effectiveness of beractant in the prevention of respiratory distress syndrome

Beractant, a modified natural bovine surfactant extract, has been used successfully in the prevention of respiratory distress syndrome (RDS) in premature neonates. This analysis investigates the cost effectiveness of prophylactic surfactant therapy. Resource utilisation data were analysed retrospectively from 210 patients who had participated previously in a double-blind, placebo-controlled clinical trial. No baseline differences were apparent between the beractant and sham-air control groups. There was a significant difference in survival favouring the beractant-treated neonates. When the acquisition cost of the study drug was excluded, there was an incremental, daily cost-savings benefit for the beractant-treated group compared with the sham-air treated group. Costs per case per day were significantly lower for neonates treated with beractant ($US1442 beractant vs $US1544 sham-air; 1991 dollars p = 0.01). Costs for radiological and diagnostic procedures, respiratory care and drugs (excluding beractant) were all significantly lower. When the acquisition cost of beractant was included, the cost to produce a 28-day survivor was $US3319 less with beractant ($US41 020) than with sham-air ($US44 339). Thus, when viewed in terms of costs per year of life saved, beractant compares very favourably with other recently evaluated health technologies.     

Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective

BACKGROUND: Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. OBJECTIVE: To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. METHODS: A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. RESULTS: Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. CONCLUSION: Results of this analysis of the cost effectiveness of oral deferasirox versus infusional deferoxamine suggest that deferasirox is a cost effective iron chelator from a US healthcare perspective.     

Cost effectiveness of acute imipramine therapy versus two imipramine maintenance treatment regimens for panic disorder

OBJECTIVE: To examine the medical costs and effectiveness of acute treatment with imipramine versus acute treatment plus 2 different maintenance therapies for panic disorder. METHODS: A clinical decision model was constructed to estimate 18-month costs and outcomes associated with these treatment scenarios based on the medical literature and clinician judgment. The clinical parameters and outcomes for the model were derived from a series of systematic clinical trials with imipramine utilising uniform dosage procedures and validated response criteria. Costs were calculated based on standardised treatment regimens. The outcome measures were 18-month medical costs, quality-adjusted life years (QALYs) and costs per QALY gained. A sensitivity analysis was performed to explore the impact of treatment withdrawals on outcomes. STUDY PERSPECTIVE: US mental healthcare system. RESULTS: Over 18 months, the total costs (1997 values) and QALYs associated with half-dose maintenance therapy (imipramine 1.1 mg/kg/day) [$US3377; QALYs = 0.991] and full-dose maintenance therapy (imipramine 2.25 mg/kg/ day) [$US3361; QALYs = 0.991] were almost identical; both were cost saving compared with acute imipramine therapy (2.25 mg/kg/day) with no maintenance treatment ($US3691; QALYs = 0.979). Whether patients withdrawing from treatment were considered to have continued to respond to treatment or to have relapsed, the half-dose and full-dose maintenance treatments were still cost saving compared with acute treatment alone. CONCLUSIONS: The results indicate that imipramine maintenance treatment is cost effective compared with acute imipramine treatment for patients with panic disorder. The basic findings and conclusions are not affected after modifying model assumptions for clinical response in patients withdrawing from treatment.     

The long-term cost effectiveness of treatments for benign prostatic hyperplasia

INTRODUCTION: Excellent treatment outcomes with long-term durability and few adverse effects are expectations of treatments for chronic conditions. The long-term cost effectiveness of newer treatments for benign prostatic hyperplasia (BPH), including high-energy transurethral microwave thermotherapy (TUMT) and combination pharmaceutical therapy, has not been sufficiently studied against existing alternatives. The objective of this study was to estimate the incremental cost effectiveness of BPH treatment alternatives. METHODS: We employed a Markov model over a 20-year time horizon and the payer's perspective to evaluate the cost effectiveness of watchful waiting (WW), pharmaceuticals (alpha-adrenoceptor antagonists [alpha-blockers], 5-alpha-reductase inhibitors [5-ARIs], combination therapy), TUMT and transurethral resection of the prostate (TURP) in treating BPH. Markov states included improvement in symptoms, no improvement in symptoms, adverse effects and death.We used data from the published literature for outcomes, including systematic reviews whenever possible. Costs were estimated using a managed-care claims database and Medicare fee schedules, and were reported in Dollars US, 2004 values. Costs and effectiveness outcomes were discounted at a rate of 3% per year. Men (aged > or =45 years) with moderate to severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age and BPH symptom levels.Outcomes included costs, QALYs, incremental cost-utility ratios and cost-effectiveness acceptability curves. Sensitivity analysis was performed on important parameters, with an emphasis on probabilistic sensitivity analysis. RESULTS: alpha-Blockers and TUMT were cost effective for treating moderate symptoms using the threshold of Dollars US 50,000 per QALY. For example, at 65 years of age, the cost per QALY was Dollars US 16,018 for alpha-blockers compared with WW and Dollars US 30,204 for TUMT versus alpha-blockers. TURP was the most cost-effective treatment for severe symptoms (Dollars US 5824 per QALY ) versus WW. Model results were robust to changes in costs and sensitive to the assumed probabilities, utility weights, extent of improvement and life expectancy. Nevertheless, acceptability curves consistently demonstrated the same alternatives as most likely to be cost effective. CONCLUSIONS: Our model suggests that alpha-blockers and TURP appear to be the most cost-effective alternatives, from a US payer perspective, for BPH patients with moderate and severe symptoms, respectively. TUMT was promising for patients with moderate symptoms and the oldest patients with severe symptoms, but otherwise was dominated. Value of information analysis could be used to determine the net benefit of additional research.     

Cost effectiveness of pramipexole in Parkinson's disease in the US.

OBJECTIVE: Pramipexole was recently approved in the US for treatment of the symptoms of idiopathic Parkinson's disease (PD). Although pramipexole has been found to be safe and efficacious when compared with placebo, little data are yet available on its cost effectiveness when compared with baseline treatment. The aim of this study was to estimate the costs and cost effectiveness (cost utility) of pramipexole compared with baseline treatment in patients with early and advanced PD. DESIGN AND SETTING: We developed a cost-effectiveness (CE) model in the US setting that linked Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily life) and III (motor) scores to disease progression, costs and patient utility. Data for the model were obtained from clinical trials, a literature review and a survey of 193 patients' health resource use and utility. We used cost and quality-adjusted life-year (QALY) estimates from the model to estimate the incremental cost effectiveness of pramipexole relative to baseline treatment patterns. We performed separate analyses for patients with early and advanced PD. We also performed extensive sensitivity analyses by adding other dopamine agonists to the no-pramipexole treatment regimen and varying disease progression parameters. The study was conducted from the societal perspective, although data presentation allows interpretation of cost effectiveness from either the societal or payer perspective. MAIN OUTCOME MEASURES AND RESULTS: For patients with both early and advanced PD, treatment with pramipexole had higher costs but was more effective than baseline treatment. For patients with early onset of PD, the incremental total CE ratio for pramipexole was $US8837/QALY. For patients with advanced PD, the incremental CE ratio was $US12 294/QALY (1997 costs). These ratios were lower than the CE ratios of many widely used medical treatments. CONCLUSIONS: Subject to the inherent limitations of modelling chronic disease progression and subsequent healthcare costs and patient utility, the results suggested that pramipexole was a cost effective treatment for patients with early and advanced PD in the US.     

Cost-effectiveness and cost-utility of insulin glargine compared with NPH insulin based on a 10-year simulation of long-term complications with the Diabetes Mellitus Model in patients with type 2 diabetes in Switzerland

OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of insulin glargine compared with NPH insulin in patients with type 2 diabetes and in whom OAD (oral anti-diabetics) had failed in Switzerland. METHODS: Long-term diabetes outcomes were simulated with the Diabetes Mellitus Model (DMM) over a period of 10 years. The incidences of long-term complications (micro- and macrovascular events) were simulated for 10,000 patients over 10 years for six different scenarios. The scenarios were based on HbA1c reductions observed in clinical trials. For insulin glargine, HbA1c reductions of 0.96% (pessimistic case) and 1.24% (optimistic case) were simulated for three different HbA1c baseline values (10, 9 and 8%). For NPH insulin the HbA1c reduction was assumed to be 0.84%. A cost model and a utility model were developed in order to use the cumulated incidences of the simulations for the calculation of cost and QALYs (quality-adjusted life years). The unit costs of micro- and macrovascular events were assessed on the basis of published literature and guideline-projected resource-use estimations for Switzerland. Disutility values of diabetes-related long-term complications were derived from the literature. Total direct medical costs or QALYs were assessed by a combination of cumulated incidences of each event up to 10 years with the corresponding unit cost per event (in addition to the acquisition cost) or with disutility values per event, respectively. Events, total cost, and QALYs were discounted at 3%. In scenarios where no savings could be shown for insulin glargine, incremental cost-effectiveness ratios were calculated as the incremental cost per event prevented and the cost per QALY gained. RESULTS: Cost comparison demonstrated that insulin glargine is the dominant strategy for the optimistic case scenario starting at a baseline HbA1c value of 10% as savings in the management of complications exceeded the difference in acquisition costs after 8 years of treatment. Optimistic case scenarios for baseline HbA1c values of 9 and 8% achieved costs per QALY gained amounting to CHF 2,853 and CHF 5,711 and costs per event prevented amounting to CHF 2,054 and CHF 4,899, respectively. Pessimistic case scenarios for baseline HbA1c values of 10, 9 and 8% resulted in costs per QALY gained amounting to CHF 40,441, CHF 45,701 and CHF 49,468 and costs per event prevented amounting to CHF 27,742, CHF 32,451 and CHF 41,620, respectively. CONCLUSIONS: This study investigated the long-term health-economic implications of treating type 2 diabetes patients, in whom OAD had failed, with insulin glargine versus NPH insulin in Switzerland. The 10-year simulations demonstrated that the deltaHbA1c reductions of 0.4 and 0.12% achieved with insulin glargine led to a reduction of long-term complications, mortality and associated costs as well as to an improved quality of life. Insulin glargine proved to be cost-effective and represents good to excellent value for money compared to NPH insulin.     

利拉鲁肽和西格列汀在治疗2型糖尿病中的长期益处对比

目的：比较利拉鲁肽和西格列汀在治疗中国2型糖尿病（T2DM）患者中的长期临床和成本益处。方法：数据来源于一项随机对照试验（NCT02008682）,2型糖尿病患者随机分为注射利拉鲁肽1.2 mg·d^-1和口服西格列汀100 mg·d^-1。根据已发表和验证的CORE糖尿病模型,对临床结果和直接费用进行长期预测。未来成本和临床结果的贴现率为每年0%和5%。并进行敏感性分析。结果：与西格列汀相比,使用利拉鲁肽的预期寿命（14.12年 vs. 13.89年）和健康调整生命年[9.11 vs. 8.91（QALYs）]延长,并通过有效控制血糖,减少了肾病、心血管疾病、眼科、糖尿病足等相关并发症的发生。利拉鲁肽1.2 mg比西他列汀的增量成本效益比增加了72 101元/QALY。敏感性分析结果表明,使用利拉鲁肽的QALY和治疗成本均高于西格列汀,并且改善的血糖控制可能是临床获益的主要影响因素。结论：利拉鲁肽加入二甲双胍单药治疗可以改善健康调整生命年,是治疗T2DM的一种经济有效的方法。     

Modelling cost effectiveness of insulin glargine for the treatment of type 1 and 2 diabetes in Canada

BACKGROUND AND OBJECTIVE: Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control. METHODS: A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values). RESULTS: The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results). CONCLUSIONS: The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.     

Clopidogrel: a pharmacoeconomic review of its use in patients with non-ST elevation acute coronary syndromes

Clopidogrel (Plavix) is a selective inhibitor of adenosine diphosphate-induced platelet aggregation. In patients with acute coronary syndromes (ACS) [unstable angina or non-ST-segment elevation myocardial infarction], clopidogrel plus aspirin (acetylsalicylic acid) for up to 1 year significantly reduced the risk of cardiovascular events relative to placebo plus aspirin in the well designed clinical trial CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) and its substudy in patients undergoing percutaneous coronary intervention (PCI) [PCI-CURE]. In pharmacoeconomic evaluations based on data from these trials conducted in a number of countries that used a variety of models, methods and/or type of costs, clopidogrel plus aspirin was consistently predicted to be cost effective relative to aspirin alone in the management of patients with ACS, including those undergoing PCI. Clopidogrel plus aspirin in patients with ACS reduced the incremental cost per cardiovascular event prevented and/or life-year gained (LYG) relative to aspirin alone in analyses using within-trial data (including longer-term analyses incorporating life-expectancy estimates) from the CURE or PCI-CURE studies. In Markov models of cost effectiveness with a lifetime horizon from a healthcare payer perspective based on the CURE trial, relative to aspirin alone, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 8132Euro in Spain (2003 values) and 1365Euro in Sweden (2000 values). In similar Swedish analyses from a healthcare payer perspective, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 10,993Euro (2004 values) relative to aspirin alone based on data from the PCI-CURE substudy. Broadly similar results have also been reported in modelled analyses from other countries. Cost-utility analyses based on the CURE trial suggest that, relative to lifelong aspirin alone, clopidogrel plus aspirin for 1 year followed by aspirin alone is associated with incremental costs per QALY gained that are below the traditional threshold of cost utility in Spain, the UK and the US. In patients with ACS, including those undergoing PCI, the addition of clopidogrel to standard therapy with aspirin is clinically effective in preventing cardiovascular events. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of clopidogrel plus aspirin for up to 1 year as a cost-effective treatment relative to aspirin alone in this patient population.     

Alglucerase. A pharmacoeconomic appraisal of its use in the treatment of Gaucher's disease

Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient. Alglucerase has provided a breakthrough in treatment for patients with this relatively rare disease. With alglucerase infusions typical disease manifestations are ameliorated or normalised: hepatosplenomegaly is reduced, haematological parameters improve, and patients experience an increased quality of life usually within 4 to 6 months of treatment. Parameters of bone disease also respond, but generally over a longer period of treatment. Alglucerase is well tolerated by children and adults, with few adverse effects reported. Seroconversion occurs in approximately 15% of patients on high-dose therapy, but does not appear to affect the efficacy of treatment. Several dosage regimens have been used to deliver alglucerase, and the comparative benefits of these remain controversial. High-dose regimens of 60 IU/kg bodyweight administered every 2 weeks are clearly effective; however, smaller dosages given more frequently are also effective and incur a greatly reduced acquisition cost. Patient responses are variable, and the dosage regimen should be tailored to individual needs. Dosage regimens may be considerably reduced for the maintenance phase of treatment, but clinical experience is as yet insufficient to establish the minimum dosages required in the long term. Acquisition cost of alglucerase is $US3.70 per unit (1994 US dollars); thus, a dosage regimen of 60 IU/kg bodyweight administered every 2 weeks for a patient weighing 70kg costs $US404,040 per year. The minimal costs per quality-adjusted life year saved (QALY) have been estimated for 3 dosage regimens over a 10-year period. Cost per QALY was $US147,000 for 60 IU/kg bodyweight administered every 2 weeks, $US75,000 for 30 IU/kg every 2 weeks, and $US49,000 for 2.3 IU/kg administered 3 times per week. These costs were calculated assuming immediate death with no treatment, which suggests that the actual costs per QALY for most patients with type 1 or 3 disease are likely to be much higher. Drug administration costs may become a significant part of the cost during maintenance therapy; in addition, possible cost savings due to increased patient productivity and reduced palliative treatments remain unresolved. Although some patients may obtain increased benefit from high-dosage regimens, the very high cost may preclude general use of these regimens. Healthcare resources consumed by alglucerase therapy represent a large opportunity cost for other therapeutic areas.(ABSTRACT TRUNCATED AT 400 WORDS)