Post-traumatic stress disorder in UK police officers

ABSTRACT

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 19?185 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 £18?888 per life year gained and £21?489 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.     

Potential costs and effects of the National Service Framework for Coronary Heart Disease in the UK

OBJECTIVE: To estimate the costs and effect of implementing the National Service Framework for Coronary Heart Disease (CHD) in the UK. DESIGN: Decision trees were built on the results from randomised controlled trials on improving coronary revascularisation. All costs were presented in UK pounds (1997 values). PATIENTS: Each year 6600 new patients with CHD are expected to require revascularisation in the UK. INTERVENTIONS: The new patients would be equally divided into those undergoing coronary artery bypass grafting (CABG) and those undergoing a percutaneous coronary intervention (PCI) i.e., percutaneous transluminal angioplasty (PCTA). PTCA could be administered with or without abciximab (a glycoprotein IIb/IIIa receptor antagonist), stent, or stent plus abciximab (stent+). RESULTS: CABG/stent alone has an incremental cost of more than 115,489 pounds per additional quality-adjusted life-year (QALY) gained compared with CABG/ PTCA+. This high incremental cost is not attractive because if CABG/ stent would be added to abciximab (CABG/stent+) its incremental cost-effectiveness ratio would be 2529 pounds per extra QALY compared with CABG/stent. Therefore, the debate should not be limited to the issue of stents but it should focus on the need for administering abciximab in addition to stent. The 5-year direct costs of implementing such a strategy in the UK is expected to be 50.6 million pounds (1997 values). CONCLUSIONS: Abciximab and probably any glycoprotein IIb/IIIa receptor antagonists should be added to any PCI, especially if stents are used.     

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.     

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.     

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'.     

Oral antiplatelet therapy in secondary prevention of cardiovascular events: an assessment from the payer's perspective

BACKGROUND: A wide variety of oral antiplatelet trials have been carried out, and a large number of cost-effectiveness estimates based on them have been published. OBJECTIVE: To assess the cost effectiveness of oral antiplatelet treatments in the prevention of cardiovascular events. METHODS: A comprehensive literature search was carried out in PubMed and the Cochrane Library and the data reviewed. Cost-effectiveness or cost-utility studies of oral antiplatelets published since 2000 were selected. Cost-effectiveness analyses from the perspective of the UK NHS were then carried out using a Markov model with a 6-month cycle length and a lifetime horizon. Inputs from the CAPRIE, CHARISMA, (PCI)-CURE, CREDO, COMMIT, CLARITY, ESPS 2 and ESPRIT trials were included. All estimates of cost found (per event avoided, per QALY gained or per life-year gained) were included. Results were analysed in light of the National Institute for Health and Clinical Excellence (NICE) guidelines for the use of antiplatelets for the prevention of cardiovascular events and all estimates were updated to pound (year 2006 values) for easy comparison. RESULTS: Of the initial 141 studies found, 21 were included in the initial review. The literature and the Markov model subsequently used suggest that aspirin (acetylsalicylic acid) dominates placebo for the secondary prevention of cardiovascular events, as it is effective, is also less costly and is as well tolerated as placebo. Additionally, in periods or patients with elevated risk, more intensive treatment with clopidogrel (alone or together with aspirin) is cost effective compared with aspirin alone for the secondary prevention of ischaemic events. For secondary stroke prevention, combination therapy with aspirin and dipyridamole has a favourable incremental cost-effectiveness ratio (ICER) when compared with aspirin alone and, based on an indirect comparison, also when compared with clopidogrel. CONCLUSIONS: The cost-effectiveness estimates presented in this article support the NICE guidelines for the use of antiplatelets for the prevention of cardiovascular events. Based on these pharmacoeconomic data alone, aspirin should be prescribed for primary or secondary prevention among patients at high risk of cardiovascular events, dipyridamole for the secondary prevention of stroke (for a maximum of 5 years), and clopidogrel for the treatment of symptomatic cardiovascular disease or acute coronary syndrome (for a maximum of 2 years). The cost effectiveness of antiplatelets hinges on the patient's initial risk, the risk reduction associated with treatment, and the price of the treatment. Evidence suggests that the cost effectiveness of antiplatelets can be optimized by individualising the treatment decision based on patient risk and expected risk reduction.     

Cost-utility analysis of treatment with olanzapine compared with other antipsychotic treatments in patients with schizophrenia in the pan-European SOHO study

OBJECTIVE: To determine the cost utility of treating schizophrenic patients with olanzapine compared with other antipsychotics in a naturalistic outpatient setting. METHODS: The pan-European SOHO study is a 3-year, prospective, outpatient, observational study of outcomes associated with antipsychotic treatment, focusing on olanzapine, in ten European countries. For the cost-utility analysis, healthcare resource use (inpatient care, day care, outpatient psychiatric consultations and antipsychotic and concomitant medication use) and EQ-5D data were collected at baseline and at 3, 6 and 12 months. The perspective was that of the health service payer. UK healthcare unit costs (year 2004 values) were applied to the resource use data for the ten countries. UK population tariffs were applied to the EQ-5D data to determine utility values.An Epoch analysis was used to analyze the longitudinal data. Multivariate regression analyses that adjusted for baseline covariates were used to estimate the incremental cost and utility gains for patients treated with olanzapine compared with each of the other antipsychotics (risperidone, quetiapine, amisulpride, clozapine and oral or depot typical antipsychotics). RESULTS: A total of 10 972 patients were enrolled at baseline, of which 9107 completed the 12-month study period. Treatment with olanzapine was more effective in terms of QALYs gained than all of the other antipsychotic treatments. Treatment with olanzapine dominated quetiapine and amisulpride. The incremental cost for olanzapine compared with risperidone was pound sterling 226 per patient over 12 months and the incremental cost per QALY gained was pound 5156, with bootstrap analyses showing 100% of the replications falling below a pound sterling 30 000 per QALY gained threshold. Compared with treatment with clozapine, olanzapine was found to be marginally more effective, at an additional cost of pound sterling 13 per patient over 12 months and to have an incremental cost per QALY gained of pound sterling 775. Bootstrap analyses showed that 81% of replications fell below a pound sterling 30 000 per QALY gained threshold. Comparing olanzapine with oral and depot typical antipsychotics, the incremental cost was pound sterling 849 and pound sterling 1106 per patient over 12 months and the incremental cost per QALY gained was pound sterling 15 696 and pound sterling 23 331, respectively. Bootstrap analyses showed that 98% of the replications fell below a pound sterling 30 000 per QALY gained threshold for the comparison with oral typical antipsychotics, and 79% of replications for the comparison with depot preparations. CONCLUSIONS: Among SOHO patients, if a funding threshold of pound sterling 30 000 per QALY gained is assumed, this analysis suggests that olanzapine has a high probability of being the most cost-effective treatment compared with other antipsychotic treatments. However, comparison of olanzapine with clozapine and typical depot antipsychotics should be viewed with caution because clozapine is a second-line treatment and depot treatment is used for patients who do not adhere to their oral medication.     

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.     

Clopidogrel: a review of its use in the prevention of atherothrombosis

Clopidogrel is an ADP receptor antagonist that is indicated for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. In the 19 185 patients enrolled in the multicentre, randomised double-blind CAPRIE study, the annual risk of the combined end-point of ischaemic stroke, myocardial infarction and death from vascular disease (vascular death) was significantly lower during treatment with clopidogrel 75 mg/day than aspirin 325 mg/day [5.3 vs 5.8%/year, respectively; relative risk reduction (RRR) 8.7%, p = 0.043] after a mean follow-up of 1.9 years. Clopidogrel provided even greater reductions in the risk of recurrent ischaemic events than aspirin in patients with a history of coronary artery bypass surgery, diabetes mellitus and in those receiving concomitant lipid-lowering therapy. Moreover there was a significant reduction in the incidence of hospitalisation in patients treated with clopidogrel. In a patient population (Saskatchewan, Canada) with a greater risk of ischaemic events than the CAPRIE study population, the number of patients needed to be treated with clopidogrel to prevent 1 ischaemic event was estimated to be 70 (vs 200 in the CAPRIE study). In randomised trials and registry surveys, clopidogrel 75 mg/day plus aspirin had similar efficacy (as measured by adverse cardiac outcomes) to ticlopidine 250mg twice daily plus aspirin during the 30 days after placement of intracoronary stents. Tolerability of clopidogrel was significantly better than ticlopidine in the randomised, double-blind CLASSICS study. Among patients treated with clopidogrel or aspirin in the CAPRIE study, the overall gastrointestinal tolerability of clopidogrel was generally better than that of aspirin; the frequency of gastrointestinal haemorrhage was significantly lower among patients treated with clopidogrel than aspirin. Diarrhoea, rash and pruritis were significantly more common with clopidogrel than aspirin. CONCLUSION: Clopidogrel was significantly more effective than aspirin in the prevention of vascular events (ischaemic stroke, myocardial infarction or vascular death) [corrected] in patients with atherothrombotic disease manifested by recent myocardial infarction, recent ischaemic stroke or symptomatic peripheral arterial occlusive disease [corrected] in the CAPRIE study. The overall tolerability profile of the drug was similar to that of aspirin, although gastrointestinal haemorrhage occurred significantly less often in clopidogrel recipients. The drug is widely used in combination with aspirin for the prevention of atherothrombosis after placement of intravascular stents, and available data suggest that this combination is as effective as ticlopidine plus aspirin for this indication.     

The costs and benefits of community thrombolysis for acute myocardial infarction : a decision-analytic model

BACKGROUND: There is evidence that the earlier a patient reaches hospital and receives thrombolysis, the better the outcome. The GREAT (Grampian Region Early Anistreplase Trial) directly addressed the issue of early thrombolysis by evaluating, in a randomised controlled trial, the efficacy of thrombolysis in the community compared with that administered in hospital. OBJECTIVE: This paper aimed to model the cost and benefits of community compared with hospital thrombolysis from the UK NHS perspective, using efficacy data from the GREAT. METHODS: A decision-analytic approach was used to model these two alternatives. Resource use and cost estimates were estimated for a single tertiary centre. Estimates of effectiveness in life-years were obtained from the 4-year follow-up for patients recruited to the GREAT, using declining exponential approximation of life expectancy. Costs are in pounds sterling, 2000/1 values. RESULTS: Community thrombolysis had an average life expectancy of 12.48 years and hospital thrombolysis had an average life expectancy of 12.39 years. Costs were 361 pounds sterling for community thrombolysis and 300 pounds sterling for hospital thrombolysis. Community thrombolysis led to an additional 0.09 years of life-expectancy gained compared with hospital thrombolysis at an additional cost of 61 pounds sterling per patient. Therefore, the incremental cost per life-year gained for the community thrombolysis service over the hospital thrombolysis service was 667 pounds sterling. Sensitivity analysis showed that estimates of cost per life-year gained were most sensitive to the estimates of survival. CONCLUSION: This model suggests that, from the UK NHS perspective, implementing community thrombolysis may lead to extra survival but at extra cost over hospital thrombolysis. Although the incremental cost per life-year is modest, judgements still have to be made, however, as to whether the extra benefits estimated are worth the additional resources required. This requires consideration of the local context in which the service may be introduced.     

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.     

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.     

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

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

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

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

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

Cost effectiveness of pegaptanib for the treatment of age-related macular degeneration in the UK

BACKGROUND: Age-related macular degeneration (AMD) is the primary cause of vision loss in the elderly and results in significant economic and humanistic burden. The selective vascular endothelial growth factor inhibitor, pegaptanib (Macugen) is indicated for patients with neovascular AMD. Guidance is needed regarding the cost effectiveness of treatment, any variation between sub-populations of differing clinical characteristics and the optimum duration of treatment. OBJECTIVE: To estimate the cost effectiveness of pegaptanib versus best supportive care (BSC) for AMD from the perspective of the UK government, and to evaluate the impact of patient characteristics and differing treatment discontinuation scenarios. METHODS: A cohort of 1000 patients aged >45 years with a best-corrected visual acuity (VA) in their better-seeing eye of < or =6/12 was modelled. Patients were either treated with pegaptanib (0.3mg every 6 weeks for a maximum of 2 years in their better-seeing eye only) or received BSC (no active treatment). Supportive services were provided for patients with a VA < or =6/60. A 10-year Markov model composed of 12 VA states (defined by individual Snellen lines) and a dead state was constructed. The model reported herein was used to support submissions to the National Institute for Health and Clinical Excellence (NICE) and the Scottish Medicines Consortium (SMC). NICE guidance is expected to be available in October 2007 and the SMC advice was issued on 7 July 2006. SMC accepted pegaptanib for use in patients with visual acuity between 6/12 and 6/60 (inclusive) and should be stopped if visual acuity falls below 6/60 during treatment or where severe visual loss is experienced. Time-dependent transition probabilities for the loss and gain of Snellen lines were derived from parametric survival curves fitted to patient-level data from the VISION trials. Survival curves were fitted with treatment and baseline Snellen scores as covariates; additional curves were fitted with the addition of age, gender, lesion type or lesion size as covariates. Mortality rates were adjusted for the age, gender and VA of the population. Cost effectiveness was expressed as the incremental cost (IC) per vision-year saved and IC/QALY. Uncertainty was explored by probabilistic and univariate sensitivity analysis. Costs (year 2005 values) and outcomes were discounted at 3.5% per anum. RESULTS: In the base-case analysis, treatment was targeted to patients with a VA of 6/12 to 6/95 and discontinued after 2 years, or earlier if VA fell below 6/95 or by > or =6 lines. The IC/QALY was estimated as 8023 pounds(upper 95% CI 20,641 pounds). Cost effectiveness varied by age (age <75 years = 2033 pounds/QALY; age > or =75 years = 11,657 pounds/QALY) and by pre-treatment VA (6/12-6/95 = 8023 pounds/QALY; 6/12-6/60 = 6664 pounds/QALY; 6/12-6/24 = 1920 pounds/QALY). Gender and lesion type or size had little effect. Cost effectiveness was not sensitive to precise rules for treatment discontinuation, but was maximised if treatment was discontinued in patients no longer likely to benefit. CONCLUSIONS: The results suggest that pegaptanib treatment is likely to be cost effective across all groups studied, and marginally more cost effective in younger patients and those with better pre-treatment VA. Cost effectiveness appears to be optimised if treatment is discontinued after 1 year if individual patients' VA has dropped by > or =6 lines from pre-treatment levels, or at any time if it drops below 6/95. However, strict application of discontinuation rules does not appear to be necessary for pegaptanib to be cost effective. Clinical judgement and patient preference should be an important determinant in decisions about stopping treatment.     

Zoledronic acid: a pharmacoeconomic review of its use in the management of bone metastases

Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with > or =1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid.In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness.In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.     

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis patients in the UK

INTRODUCTION: The objective of this study was to evaluate the potential economic implications of using etoricoxib versus non-selective NSAID alternatives in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in the UK. STUDY DESIGN: Decision-analytical modelling was used to calculate the expected costs and consequences of the use of etoricoxib compared with non-selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous treatment period of 1 year. METHODS: The model considered direct medical costs from the perspective of the UK National Health Service (NHS) and used data from phase IIb and III clinical trials of etoricoxib to determine probabilities of gastrointestinal (GI) events. Model outcomes were defined as resource-consuming GI-related events, including clinically evident gastroduodenal perforations, symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002 values) for the treatment of OA and RA as well as GI events were based on published literature and information available from UK-specific sources. MAIN OUTCOME MEASURES AND RESULTS: The model suggests that etoricoxib is cost saving compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus misoprostol. The model also suggests that etoricoxib is cost effective in terms of the incremental cost per QALY gained for non-selective NSAIDs alone (pound 19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non-selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2 antagonists. For patients without the presence of specific GI risk factors (history of GI event, corticosteroid use or disability), etoricoxib may be cost effective for patients over age 56 years, assuming a cost-effectiveness threshold of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in patients of all ages who had at least one specific GI risk factor. CONCLUSIONS: The model suggests, with its underlying assumptions and data, that etoricoxib is a cost-effective alternative to therapeutic regimens involving non-selective NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving and dominant over non-selective NSAIDs used together with a PPI or misoprostol. When compared with non-selective NSAIDs alone or non-selective NSAIDs co-prescribed with H2 antagonists, the incremental cost per QALY gained with use of etoricoxib was within the generally accepted threshold for cost effectiveness (less than pound 30,000 per QALY gained).     

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.     

The value of clopidogrel versus aspirin in reducing atherothrombotic events: the CAPRIE study

Atherothrombotic disease is a growing health problem, and is increasingly more costly to manage. Clopidogrel is an advanced, specific adenosine diphosphate receptor antagonist, which has been shown to be a highly potent antiplatelet agent. Data from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) study have demonstrated the significantly superior clinical benefit of clopidogrel over aspirin for secondary prevention of atherothrombotic disease, with a relative risk reduction in myocardial infarction, stroke or vascular death of 8.7% (95% confidence interval 0.3, 16.5; P = 0.043). Moreover, clopidogrel demonstrated an amplified clinical benefit versus aspirin in patients at high risk of atherothrombotic events, such as those with a previous history of symptomatic atherothrombotic disease or with major risk factors such as diabetes mellitus or hypercholesterolaemia. On the basis of commonly accepted threshold criteria (Euros 20000 per life-year gained; LYG), clopidogrel in comparison with aspirin is cost-effective for the secondary prevention of atherothrombotic disease (cost per LYG ranging from Euros 19462 to Euros 3256). Economic analyses have demonstrated consistent cost-effectiveness results with clopidogrel in different countries. Moreover, in high-risk patient subgroups the cost-effectiveness of clopidogrel in comparison with aspirin was evenbetter (cost per LYG ranging from Euros 5900 to Euros 6310). Compared with other treatment strategies used for the prevention of ischaemic or atherothrombotic events, the cost-effectiveness of clopidogrel in comparison with aspirin based on CAPRIE is favourable, with most analyses in the intermediate range of cost-effectiveness. The available data thus support the use of clopidogrel as a clinically efficient and cost-effective option for secondary prevention of atherothrombotic disease, particularly in high-risk patients.     

Cost-effectiveness of detemir-based basal/bolus therapy versus NPH-based basal/bolus therapy for type 1 diabetes in a UK setting: an economic analysis based on meta-analysis results of four clinical trials

BACKGROUND: A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients. METHODS: A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually. RESULTS: Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions. CONCLUSIONS: Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).