Budesonide/formoterol as maintenance and reliever treatment compared to fixed dose combination strategies - a Canadian economic evaluation. Cost-Effectiveness Analysis of Omalizumab for the Treatment of Severe Asthma in Japan and the Value of Responder Prediction Methods Based on a Multinational Trial. Cost-effectiveness analysis of early intervention with budesonide in mild persistent asthma. Cost-Effectiveness Analysis of Formoterol Versus Salmeterol in Patients with Asthma Cost-effectiveness of inhaled corticosteroids in adults with mild-to-moderate asthma: results from the asthma policy model. Salmeterol xinafoate: an analysis of outcomes and cost-effectiveness using a primary care database. Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies. Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Cost-effectiveness of fluticasone propionate administered via metered-dose inhaler plus babyhaler spacer in the treatment of asthma in preschool-aged children. Development of an Economic Model to Assess the Cost Effectiveness of Asthma Management Strategies Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma Cost Effectiveness of Fluticasone Propionate and Flunisolide in the Treatment of Corticosteroid-Naive Patients with Moderate Asthma [Cost effectiveness of treatment with salmeterol/fluticasone compared to montelukast for the control of persistent asthma in children]. Efficacy and cost effectiveness of inhaled steroids in asthma in a developing country. Principal findings of systematic reviews of acute asthma treatment in childhood Cost-effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma. Cost-effectiveness of early intervention with once-daily budesonide in children with mild persistent asthma: results from the START study. An economic evaluation of budesonide/formoterol for maintenance and reliever treatment in asthma in general practice Cost-effectiveness of inhaled beta-agonists v. oral salbutamol in asthma: a randomized double-blind cross-over study. A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma. Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma:an efficacy and cost-effectiveness study Hydrofluoroalkane-134a beclomethasone as a dominant economic asthma therapy. Cost-Effectiveness Comparison of Salmeterol/Fluticasone Propionate versus Montelukast in the Treatment of Adults with Persistent Asthma Cost-effectiveness of pazopanib: an example of improved transparency and accessibility of industry-sponsored economic evaluations through publication in peer-reviewed journals. The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients:adaptation of INNOVATE to Sweden The cost effectiveness of chlorofluorocarbon-free beclomethasone dipropionate in the treatment of chronic asthma: a cost model based on a 1-year pragmatic, randomised clinical study. Economic analysis of asthma practices. Cost Effectiveness of Budesonide/Formoterol for Maintenance and Reliever Therapy versus Salmeterol/ Fluticasone plus Salbutamol in the Treatment of Asthma Fluticasone propionate: an audit of outcomes and cost-effectiveness in primary care. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. Economic Analysis of Health Care Technology: A Report on Principles An economic evaluation of adjustable and fixed dosing with budesonide/formoterol via a single inhaler in asthma patients: the ASSURE study Cost-effectiveness analysis of budesonide/formoterol compared with fluticasone in moderate-persistent asthma. Cost Effectiveness of Fluticasone Propionate Plus Salmeterol Versus Fluticasone Propionate Plus Montelukast in the Treatment of Persistent Asthma MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children. Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 microg twice daily and budesonide 800 microg twice daily in the treatment of adults and adolescents with asthma. International Study Group. Reporting format for economic evaluation. Part II: Focus on modelling studies. Cost-Efficacy Analysis of Fluticasone Propionate versus Zafirlukast in Patients with Persistent Asthma Cost effectiveness of leukotriene receptor antagonists versus inhaled corticosteroids for initial asthma controller therapy: a pragmatic trial. Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial. Cost-effectiveness analysis of fluticasone versus montelukast in children with mild-to-moderate persistent asthma in the Pediatric Asthma Controller Trial.
OBJECTIVE To compare the cost-effectiveness of budesonide/formoterol in a single inhaler used as Maintenance and Reliever Therapy ( SMART ) versus fixed higher-dose budesonide/formoterol plus as-needed terbutaline reliever ( FHDBF ) or fixed dose fluticasone/salmeterol plus as-needed terbutaline reliever ( FDFS ) in controlling asthma in adults and adolescents . METHODS An economic evaluation was conducted by applying Canadian costs to the results of a large ( N=3,335 ) international r and omized , double-blind , controlled trial in which health re source utilization was prospect ively collected . Although no Canadian subjects were enrolled in this clinical trial , it was assumed that the results would apply to Canadian patients . Primary outcome measurements included time to first exacerbation and the number of severe exacerbations . Costs included direct medical costs ( physician/emergency room visits , hospitalizations , asthma drug costs ) and productivity ( absenteeism ) . The time horizon was six months , which corresponded to the duration of the trial . Prices were obtained from 2006 Canadian sources . Both healthcare and societal perspectives were considered . Deterministic univariate sensitivity analyses were conducted . RESULTS In the clinical trial , SMART was superior to FHDBF and FDFS with respect to total number of severe exacerbations ( RR 0.72 ; 95 % CI 0.57 , 0.90 ; p=0.0048 ; RR 0.61 ; 95 % CI 0.49 , 0.76 ; p<0.001 , respectively ) . Exacerbation rates ( reported as events per patient per 6 months ) were 0.12 for SMART , 0.16 for FHDBF , and 0.19 for FDFS . All treatments provided similar improvements in lung function , asthma control days and asthma-related quality of life . The mean cost per patient per 6 months was $ 545 in the SMART arm versus $ 690 in the FHDBF arm and $ 842 in the FDFS arm from the healthcare perspective ; and $ 676 for SMART , $ 838 for FHDBF , and $ 954 for FDFS from the societal perspective . SMART was dominant ( more effective , less expensive ) in the base case analysis from both the healthcare and societal perspectives . The results were robust under sensitivity testing . CONCLUSIONS The SMART strategy , which allows budesonide/formoterol to be used as both maintenance and reliever medication , is dominant over the alternate strategies of fixed higher dose budesonide and formoterol plus as-needed terbutaline or fixed dose salmeterol and fluticasone plus as-needed terbutaline OBJECTIVES Omalizumab improves health outcomes for patients with severe asthma . The purpose of this study was to conduct a cost-utility analysis of omalizumab from a societal perspective by using the results from a r and omized controlled trial in Japan , and explore the efficient use of omalizumab . METHODS We developed a Markov model to compare omalizumab add-on therapy with st and ard therapy .  Patients transitioned between symptom-free , day-to-day , and exacerbation states . Our model had a lifetime horizon in which 5-year omalizumab add-on therapy was followed by st and ard therapy .  Preference-based utilities were extracted from another study . We estimated the expected value of perfect information for patients ' response to omalizumab . RESULTS In the base case , incremental cost-effectiveness ratio ( ICER ) for omalizumab add-on therapy was US $ 755,200 ( 95 % credible interval [ CI ] $ 614,200-$1,298,500 ) per quality -adjusted life-year gained , compared with st and ard therapy alone . One-way sensitivity analyses indicated that the results were sensitive to asthma-related mortality , exacerbation risk , and omalizumab cost . The ICER for a responder subgroup was 22 % lower than that in the base case . Individual and population expected value of perfect informations for the response were $ 4100 ( 95 % CI $ 2500-$6000 ) and $ 28 million ( 95 % CI $ 17 million-$42 million ) per year , respectively . CONCLUSIONS With a willingness-to-pay of $ 45,000 per quality -adjusted life-year , omalizumab was not cost-effective in Japan . Confining omalizumab therapy to previously predicted responders , however , may be a reasonable strategy to reduce the ICER , as the cost-effectiveness was observed to improve for these patients . Further studies should be conducted to explore responder prediction methods . Decreasing the price of omalizumab would improve cost-effectiveness BACKGROUND The Inhaled Steroid as Regular Therapy in Early Asthma ( START ) study reported that early intervention with budesonide in mild persistent asthma reduces severe asthmatic events and improves symptom outcomes and lung function in adults and children . OBJECTIVE We sought to estimate the incremental cost-effectiveness of early intervention with budesonide , as observed within the START study . METHODS START was a r and omized , 3-year controlled trial of budesonide in early onset mild asthma among 7165 subjects ages 5 to 66 years . Three age groups ( 5 - 10 , 11 - 17 , and > or=18 years ) were studied separately and overall . Differences in the probability of emergency treatments , symptom-free days ( SFDs ) , and costs of health care were determined . Incremental cost-effectiveness ratios were estimated from the health care payer and societal perspectives . RESULTS Compared with usual therapy , patients receiving budesonide experienced an average of 14.1 ( SE , 1.3 ) more SFDs per year ( P < .001 ) , fewer hospital days ( 69 % , P < .001 ) , and fewer emergency department visits ( 67 % , P < .05 ) . From the health care payer perspective , the net cost of early use of budesonide was an additional US dollars 0.42 ( SE , dollars 0.04 ) per day , and the result ant cost-effectiveness ratio was US dollars 11.30 ( 95 % CI , US dollars 8.60-US dollars 14.90 ) per SFD gained . From the societal perspective , the cost offsets of lower absence from school or work reduced the net cost of early budesonide to US dollars 0.14 ( SE , US dollars 0.07 ) per day and decreased the cost-effectiveness ratio to US dollars 3.70 ( 95 % CI , US dollars 0.10-US dollars 8.00 ) . Early intervention was more effective and cost saving in the youngest age group . CONCLUSION Long-term treatment with budesonide appears to be cost-effective in patients with mild persistent asthma of recent onset Abstract Objective : The aim of this study was to determine the relative economic consequences of treating asthmatics with twice daily dry powder formoterol 12 mg as compared with salmeterol 50 mg from a societal perspective . Design and Setting : A r and omised , 6-month , open-label study including 482 patients with asthma was conducted in Italy , Spain , France , Switzerl and , the UK and Sweden .  Medical costs included the costs of medications , physician services , emergency room visits , hospital admissions and lung function and other tests . Travel costs and costs of production loss were also calculated . Unit prices were estimated from external sources . To pool the costs of the 6 countries , European currencies were converted to US dollars using 1995 exchange rates . Outcome measures were the number of episode-free days ( EFDs ) and the number of patients reaching a clinical ly relevant improvement in quality of life as measured using the St. Georges Respiratory Question naire . Main outcome measures and results : There were no significant differences between the 2 treatment arms in the frequency of emergency room visits , hospital admissions , use of rescue medication or contacts with general practitioners ( GPs ) , specialists or nurses . Median medical costs over 6 months were $ US828 per patient with formoterol and $ US850 with salmeterol . This difference was not statistically significant . In both groups , about 60 % of all days were episode-free . Average costs per EFD were about $ US9 for both treatments . The average cost per patient reaching a clinical ly relevant improvement in quality of life was between $ US1300 and $ US1400 . Incremental cost-effectiveness ratios were not calculated because both costs and outcomes were not significantly different . Asthma-related absenteeism ranged between 3 days and 6 months per patient in both groups . Conclusions : There was no evidence to suggest that either treatment was more cost effective than the other BACKGROUND Inhaled corticosteroids remain underused among United States-based clinicians in treating mild-to-moderate adult asthma . OBJECTIVE The purpose of this investigation was to estimate the clinical impact , health-related quality of life , cost , and cost-effectiveness of inhaled corticosteroid therapy in a population of patients aged 18 years and over with FEV(1 ) = 60 % to 100 % of predicted normal . METHODS We performed a cost-effectiveness analysis of quick relievers ( eg , short-acting beta-agonists ) on an as-needed basis plus inhaled corticosteroid therapy versus quick relievers alone . A mathematical simulation model was developed to forecast symptoms , acute exacerbations , quality -adjusted life-years ( QALYs ) , health care costs , and cost-effectiveness , measured in both dollars per QALY gained and dollars per symptom-free day gained . All evaluation outcomes were discounted at an annual rate of 3 % and measured over a 10-year planning horizon . Data on the natural history of disease , drug efficacy , patient preferences , and economic costs were obtained from a variety of observational cohorts , r and omized trials , and patient surveys . RESULTS Over a 10-year period , use of inhaled corticosteroids increases total health costs from roughly $ 5,200 to $ 8,400 and improves QALYs from 6.8 to 7.0 , implying an incremental cost of $ 13,500 per QALY gained . Costs per symptom-free day gained are $ 7.50 . Both per-person acute exacerbations and hospitalizations are reduced by 33 % . The cost-effectiveness findings are sensitive to the assumed efficacy and side-effects of inhaled corticosteroid therapy . CONCLUSIONS Inhaled corticosteroids appear to deliver good comparative value in adults with mild-to-moderate asthma . Although more research is needed to underst and their impact on preferences regarding side effects and compliance , these findings might be useful for priority- setting in limited re source situations Long-acting inhaled /&-agonists ( LABS ) , used in conjunction with low-dose inhaled steroids , are a recommended alternative to high-dose inhaled steroids for asthmatics with persistent symptoms ( 1 ) . There are , however , few published data regarding their cost-effectiveness . The drugs are relatively expensive and the aim of this study was to evaluate LAB cost-effectiveness in primary care , in terms of improved clinical outcomes ( associated with reduced NHS costs ) off setting higher prescription costs . A controlled , retrospective , non-r and omized analysis utilized the computerized Thorpewood Primary Care Data base and compared clinical outcomes and asthma management costs 1 yr prior to and 1 yr after initiation of therapy with salmeterol xinafoate BACKGROUND Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma . OBJECTIVE To compare the cost-effectiveness of these two treatment strategies in clinical practice , in an open-label , pharmacoeconomic clinical trial . METHODS Health economics were evaluated in 138 children , ages 5 to 11 years , with unstable asthma not previously treated with corticosteroids or cromones . The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily . The children were then r and omly allocated to one of the two treatment strategies aim ing at maintaining asthma control for 12 months ; budesonide 400 microg/day ( N = 69 ) or sodium cromoglycate 60 mg/day ( N = 69 ) . If asthma control was judged unsatisfactory , the doses were increased or the children were switched to the alternate treatment . RESULTS In children continuing on the same treatment , the degree of asthma control was similar in the two groups at study end . To maintain asthma control , 42 % of cromoglycate children switched to budesonide , and then experienced a 14 % increase in symptom-free days . No budesonide patient had to switch therapy because of lack of asthma control . Although not statistically significant , total annual cost per patient was 24 % ( Swedish kronor 4195 ; US $ 487 ; Euro 485 ) lower in the budesonide than the cromoglycate group , mainly due to a lower cost for asthma medication . CONCLUSIONS A budesonide strategy for continued maintenance treatment , after an initial period of stabilizing treatment with budesonide , result ed in lower costs and less drug switches than did a strategy with sodium cromoglycate OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built BACKGROUND The choice of treatment can have a major impact on the total costs associated with asthma care . OBJECTIVE To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus , 100/50 microg , with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone . METHODS Data from a r and omized , double-blind , double-dummy , 12-week clinical trial were analyzed . Efficacy end points included ( 1 ) symptom-free days ( SFDs ) during the 12-week period and ( 2 ) a 12 % or greater increase in forced expiratory volume in 1 second ( FEV1 ) from baseline . The economic analysis was performed from a payer 's perspective , and hence only direct costs were included in the analysis . The incremental cost-effectiveness ratio ( ICER ) , which is the mean difference in average costs divided by the mean difference in average effectiveness , was calculated for both effectiveness outcomes ( SFDs and FEV1 ) . RESULTS For the SFDs end point , the ICER for fluticasone propionate-salmeterol vs montelukast was $ 2.87 ( 95 % confidence interval , -$1.08 to $ 6.65 ) , indicating that it costs , on average , an extra $ 2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast . With regard to FEV1 , the ICER was $ 1.79 ( 95 % confidence interval , -$0.72 to $ 3.86 ) , indicating that it costs , on average , an extra $ 1.79 per day to achieve a lung function improvement of 12 % or greater from baseline with fluticasone propionate-salmeterol than with montelukast . At a widely acceptable ceiling ratio of $ 9.95 per day , the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8 % for SFDs and was almost 100 % for an FEV1 improvement of 12 % of greater . CONCLUSIONS Treating 2 main components of asthma , inflammation and smooth muscle dysfunction , using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone , such as montelukast , as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only STUDY OBJECTIVES To evaluate the cost-effectiveness of inhaled fluticasone propionate ( FP ) in children aged 12 to 47 months with asthma symptoms . DESIGN A retrospective economic analysis conducted from the perspective of the Danish health-care system , based on clinical data from a 12-week study . SETTING Thirty-three outpatient centers in nine countries . PATIENTS Two hundred thirty-seven children aged 12 to 47 months with documented history of recurrent wheeze or asthma symptoms . INTERVENTIONS Two dosages of FP , 100 microg/d and 200 microg/d , and placebo administered in two divided doses via a metered-dose inhaler and a Babyhaler ( Glaxo Wellcome ; Middlesex , UK ) spacer device . MEASUREMENTS Effectiveness in terms of asthma exacerbations , control of cough and wheeze symptoms , symptom-free days , overall direct costs of asthma management in Danish kroner at 1999 prices , and mean and incremental cost-effectiveness ratios . RESULTS FP , 200 microg/d , was significantly more effective than placebo treatment in terms of the proportion of exacerbation-free patients ( 73.7 % vs 59.8 % ; p = 0.025 ) and patients experiencing a > or = 25 % improvement in cough symptoms ( 57.9 % vs 39.0 % ; p = 0.018 ) . The costs per exacerbation-free patient , per patient with a > or = 25 % improvement in cough and wheeze symptoms from baseline , and per symptom-free day were lower in the FP groups than in the placebo group . The incremental cost-effectiveness ratios for these end points indicated that the additional benefits of FP , 200 microg/d , were achieved at a lower overall cost compared with placebo treatment . CONCLUSIONS From the perspective of the Danish health-care system , FP , 100 microg bid , administered via the Babyhaler inhalation device was cost-effective relative to st and ard therapy with bronchodilators alone Abstract Background and objective : Asthma is a chronic-episodic disease characterised by acute , symptomatic episodes of varying severity . We developed a Markov model that can be used to estimate the cost effectiveness of alternative asthma treatments . Because of the costs they incur , asthma exacerbations ( ‘ attacks ’ ) requiring intervention by a healthcare professional were a central consideration in the development of the model . Methods : Treatment success was assessed as asthma control , a composite measure based on goals defined in world-wide asthma management guidelines and in terms of quality -adjusted life-years ( QALYs ) . The data from which the transition probabilities were derived came from patients with asthma who received either salmeterol/fluticasone propionate combination ( SFC ) 50/100μg or fluticasone propionate ( FP ) 100μg , administered twice daily via an inhaler , in a 12-week , r and omised , double-blind , clinical trial . Costs were estimated from re source profiles defined for each of the model states . A key aspect of the model was the use of probabilistic sensitivity analysis techniques to examine the uncertainty in the cost-effectiveness results . Distributions were fitted to transition probabilities and to cost input parameters and values were sample d at r and om from these distributions using a second order Monte Carlo simulation technique . This produced a distribution for incremental cost effectiveness that was employed to construct 95 % uncertainty intervals and to construct cost effectiveness acceptability curves . Results : In this analysis , the model was run over a 12-week period using transition probabilities derived from the trial data . The results showed that treatment with SFC result ed in a higher proportion of successfully controlled weeks per patient than treatment with FP(66 vs 47 % ) , and higher mean weekly direct asthma management costs ( £ 15.77 vs £ 11.83 ; 2000 values ) . The average incremental cost per successfully controlled week with SFC was £ 20.83.Probabilistic sensitivity analysis showed that the 95 % uncertainty intervals for the incremental cost-effectiveness ratio was −£64.94 to £ 112.66 . In approximately 25 % of cases , SFC was dominant ( more effective and less costly ) , but in the remaining cases , it was both more effective and more costly . It was shown that if decision makers are willing to pay approximately £ 45 for an additional successfully controlled week , SFC will be the more cost-effective strategy in this patient population for 80 % of the time . Conclusions : This is one of the first decision-analytic models of asthma to incorporate probabilistic sensitivity analysis techniques to explore uncertainty . The model ’s flexible yet st and ardised framework permits the cost effectiveness of alternative asthma management strategies in different healthcare setting s to be established Abstract Objectives : To compare the costs and effectiveness of adjustable maintenance dosing with budesonide/formoterol in a single inhaler versus fixed dosing in adults with asthma . Methods : In this prospect i ve , r and omised , open-label , parallel-group , multicentre trial conducted in Germany , patients with asthma received budesonide/formoterol 160µg/4.5 µg in a single inhaler ( Symbicort ® Turbuhaler ® ) with two inhalations twice daily for a 4-week run-in period . Patients were then r and omised to either adjustable maintenance dosing ( one inhalation twice daily , stepping up to four inhalations twice daily for 1 week if asthma worsened ; n = 1679 ) or fixed dosing ( two inhalations twice daily ; n = 1618 ) for 12 weeks . The primary efficacy variable was the change in health-related quality of life ( HR-QOL ) , measured using the Asthma Quality of Life Question naire ( st and ardised ) during the r and omised treatment period . Re source utilisation data were collected in parallel and combined with German unit costs to estimate direct and indirect costs ( year 2001 values ) . Results : Both treatment regimens were equally effective in maintaining HR-QOL and asthma control during the r and omised treatment period . However , overall , patients in the adjustable maintenance dosing group took fewer daily inhalations of budesonide/formoterol  than those in the fixed-dosing group ( mean : 2.63 vs 3.82 inhalations ; p < 0.001 ) . Adjustable maintenance dosing was associated with significantly lower asthma-related direct costs  compared with fixed dosing ( mean : € 221 vs € 292 ; p < 0.001 ) . This pattern was maintained when patients were stratified into those with peak expiratory flow ( PEF ) of 60 % to < 80 % predicted normal and those with PEF of ≥80 % predicted normal and when total costs were considered . Conclusion : Adjustable maintenance dosing with budesonide/formoterol in a single inhaler maintained HR-QOL in adult patients with asthma at a significantly lower cost than fixed dosing Abstract Objective : The aim of this study was to determine the cost effectiveness of 2 inhaled corticosteroids , fluticasone propionate and flunisolide , in the management of asthma from a third-party payer perspective in Germany ( German Sickness Fund ) . Design and setting : Direct treatment costs were retrospectively applied to 2 prospect i ve r and omised parallel group clinical trials conducted in Germany comparing fluticasone propionate and flunisolide : one 6-week open-label study ( n = 332 ) and one 8-week double-blind study ( n = 308 ) in corticosteroid-naive patients with asthma of moderate severity aged between 18 and 70 years . All costs were adjusted to 1997 Deutschmarks . Efficacy parameters included changes in morning and evening peak expiratory flow rate ( PEFR ) measurements , the number of successfully treated patients ( defined as those with a PEFR improvement of ≥10 % ) and proportion of symptom-free days . Main outcome measures and results : The fluticasone propionate groups had higher respective proportions of successfully treated patients and symptom-free days than the flunisolide groups in both the open-label ( 56.8 vs 39.6 % and 36.4 vs 28.5 % ) and double-blind ( 55.3 vs 44.5 % and 35.1 vs 31.1 % ) studies . Improvements in both morning and evening PEFR measurements were also significantly ( p < 0.01 ) greater with fluticasone propionate than with flunisolide . Although average daily treatment costs were slightly higher in the fluticasone propionate groups than in the flunisolide groups , all cost-effectiveness ratios ( daily cost per successfully treated patient and daily cost per symptom-free day ) favoured fluticasone propionate . Sensitivity analysis showed that these results were robust over a wide range of assumptions . Conclusion : In these patients , management with fluticasone propionate was more cost effective than with flunisolide in the German healthcare setting OBJECTIVE To assess the incremental cost-effectiveness of SFC compared with MON for the control of persistent asthma in children . METHODS We conducted an economic evaluation on a 12-week prospect i ve r and omized open-label parallel-group comparison of SFC versus MON in children with symptomatic asthma receiving inhaled corticosteroids and short-acting β2-agonists .  Asthma-related medication , unscheduled physician contacts and hospitalizations were collected prospect ively . The main effectiveness measure was percentage of asthma-controlled week with no short-acting β2-agonist use during the study period . The analysis was conducted from the Mexican healthcare perspective using 2010 unit cost prices , and only direct costs were considered , all costs are reported in US dollar . . The model was made fully probabilistic to reflect the joint uncertainty in the model parameters . RESULTS Over the whole treatment period , the median percentages of asthma-controlled weeks were 83.3 % in the SFC group and 66.7 % in the MON group ( SFC-MON difference , 16.7 % ; 95 % CI , 8.3 - 16.7 ; P < 0.001 in favor of SFC ) . The mean total cost of the SFC regimen was $ 2,323 compared with $ 3,230 for the MON regimen . The SFC was the dominant strategy ( both more effective and less expensive ) using the SFC was associated with an incremental cost per additional asthma-controlled of $ ( 5,467 ) . Probabilistic sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes . CONCLUSIONS This analysis demonstrates that , compared with MON , SFC may be cost saving from the Mexican health care perspective for the treatment of pediatric patients with asthma .  SFC  provided a reduction in the number of severe exacerbations , frequent asthma symptoms and rescue medication use . Incremental cost-effectiveness analysis indicated the dominance of SFC because of both lower costs and greater efficacy Eighty six children with troublesome wheezing were studied , in a semi prospect i ve clinical trial with the patients acting as their own controls , to assess the efficacy and cost effectiveness of inhaled steroids . Improvement in school attendance , hospitalisations , breakthrough wheezing , and acute severe attacks were used to assess clinical efficacy . Expenditure for the family , on a cost of illness framework , before and after treatment , was used to estimate cost effectiveness . Highly significant numbers of patients showed improvement in clinical parameters , confirming efficacy . Mean monthly cost before inhaled steroid treatment was Rs 2652.33 ( 36.33 pounds ) and Rs 449.42 ( 6.16 pounds ) after starting treatment . The mean cost per unit satisfaction ( cost utility value ) which was Rs 255.54 ( 3.50 pounds ) before starting prophylaxis came down to Rs 5.42 ( 0.07 pound ) after starting treatment . There are no previous reports of cost-benefit assessment of inhaled steroids in childhood asthma . It is concluded that , even for developing countries with financial constraints , inhaled steroid treatment for prophylaxis of asthma is a cost effective and rational form of treatment Abstract Objective : The objective of this study is to summarize the principal findings in the literature about acute asthma management in children . Methods : Systematic review s of r and omized clinical trials ( S RCTs ) with or without meta- analysis in children ( 1–18 years ) admitted to the emergency department ( ED ) were retrieved using five data bases . Method ological quality was determined using the AMSTAR tool . Results : One hundred and three studies were retrieved . Among those , 28 S RCTs were included : seven S RCTs related to short-acting beta2-agonists ( SABA ) , three to ipratropium bromide ( IB ) , eight to corticosteroids , one to racemic adrenaline , one to leukotriene receptor antagonists ( LTRA ) , four to magnesium sulfate , one to intravenous ( IV ) SABA , one to IV aminophylline , one to IV ketamine , and one to antibiotics . It was determined that administering SABA by MDI-VHC is superior to using a nebulizer , because it decreases the hospital admission rate , improves the clinical score , results in a shorter time in the ED , and causes fewer adverse effects .  Levalbuterol and albuterol were similar . In patients with moderate to severe exacerbations , IB+SABA was superior to SABA , decreasing hospital admission and improving the clinical score .  SABA heliox administered by nebulizer decreased exacerbation severity compared to oxygen . Inhaled corticosteroids ( ICS ) , especially administered by nebulizer , showed results similar to oral corticosteroids ( OCS ) with respect to reducing hospital admission , unscheduled visits , and the requirement of additional systemic corticosteroids . ICS or OCS following ED discharge was similar with regard to relapse . Compared with a placebo , IV magnesium reduced hospital admission and improved lung function . Conclusions : S RCTs are useful for guiding decisions in acute asthma treatment We conducted an economic evaluation in a UK setting based on a 12-week prospect i ve r and omized open-label parallel-group comparison of eformoterol Turbohaler 12 microg b. i.d . with salmeterol Accuhaler 50 microg b. i.d . in children aged 6 - 17 with symptomatic asthma receiving inhaled corticosteroids and short-acting beta2-agonists .  The principal effectiveness measure was percentage of symptom-free days with no short-acting beta2-agonist use during the study period . Asthma-related medication , unscheduled physician contacts and hospitalizations were collected prospect ively and cost to the UK NHS calculated using year 2,000 prices . The economic evaluation included 73 patients in the eformoterol group and 72 patients in the salmeterol group . The mean age of patients was 11.6 years ( eformoterol ) and 11.8 years ( salmeterol ) . The mean percentage of symptom-free days with no short-acting beta2-agonist use was 39 % in the eformoterol group and 30 % in the salmeterol group . Mean per patient daily cost was 1.15 pounds in the eformoterol group and 1.39 pounds in the salmeterol group . Both cost and effectiveness differences favoured eformoterol ( P < 0.05 ; one-sided ) . Sensitivity analysis confirmed the results to be robust to changes in effectiveness , price and re source utilisation parameters . Eformoterol delivered by Turbohaler was found to be significantly more effective and less expensive than salmeterol Accuhaler in this study The inhaled Steroid Treatment As Regular Therapy in early asthma ( START ) study has shown that early intervention with inhaled budesonide in mild persistent asthma improves clinical outcomes in both adults and children . The aim of this study was to estimate the incremental cost-effectiveness of early treatment with budesonide Turbuhaler in children aged 5 - 10 yr who participated in START .  Direct and indirect costs associated with asthma were determined for 1974 children participating in the double-blind , 3-year part of the study . R and omization was to placebo or to budesonide 200 microg once daily in each case in addition to usual asthma care . Cost-effectiveness ratios were calculated from the healthcare payer 's and societal perspectives ( using US prices ) . The addition of once-daily budesonide therapy to usual asthma care was associated with 16 additional symptom-free days ( SFDs ) per child over the 3-yr period ( p < 0.001 ) , with a substantial reduction ( 50 % ) in the mean number of days spent in hospital , and with reduced frequency of emergency room visits and missed school and caregiver work days . From the healthcare payer 's perspective ( direct costs ) , the increase in mean direct cost over 3 yr with budesonide was 169 dollars , which translated into an incremental cost of early intervention with budesonide in children of 10.50 dollars ( 95 % CI 1.20 - 33.30 dollars ) per SFD gained . From the societal perspective , there was a cost reduction over 3 yr of 192 dollars with budesonide relative to placebo . From a societal perspective , budesonide was therefore dominant . In conclusion , early intervention with once-daily budesonide added to usual asthma care in children with mild persistent asthma is cost-saving from a societal perspective and is acceptably cost-effective when viewed from a healthcare payer perspective Introduction In budesonide/formoterol ( Symbicort ® Turbuhaler ® , AstraZeneca , Lund , Sweden ) maintenance and reliever therapy ( SMART ) , patients with asthma take a daily maintenance dose of budesonide/formoterol , with the option of taking additional doses for symptom relief instead of a short-acting β2-agonist ( SABA ) . This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherl and s from a societal perspective . Methods The study was linked to a r and omized , active-controlled , open-label , multicenter , 12-month clinical trial , with a prospect i ve collection of re source use . One hundred and two patients ≥18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids ( ICS ) prior to the trial were included .  SMART was given as two inhalations of budesonide/formoterol ( 100/6 μg ) once daily , plus additional doses as needed . The control group was treated according to guidelines , which prescribe medium daily doses of ICS plus an SABA if needed . A long-acting β2-agonist ( LABA ) is added if necessary . Effectiveness was measured as the proportion of asthma-control days , Asthma Control Question naire ( ACQ ) scores , the net proportion of patients with relevant ACQ improvement , and the proportion of well-controlled patients . Costs included asthma medication , physician contacts , and absence from work . Results Mean total costs for SMART were € 134.81 lower ( 95 % CI : −€439.48 ; € 44.85 ) . Production losses were € 94.10 ( 95 % CI : −€300.60 ; € 0.29 ) lower for SMART ( € 10.77 vs. € 104.87 ) . No significant differences in health outcomes were seen , with 3.81 fewer asthma-control days per patient-year for SMART ( 95 % CI : −36.8 ; 30.8 ) , a 0.049 better ACQ score ( 95 % CI : −0.21 ; 0.29 ) , a 5.8 % larger net proportion of improved patients ( 95 % CI : t15.6 % ; 27.3 % ) , and a 2.1 % ( 95 % CI : −25.5 ; 20.8 % ) smaller increase in the proportion of well-controlled patients . Conclusions Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs ; therefore , is likely to be an alternative for guideline -directed treatment , from a health and economic perspective BACKGROUND Oral beta-stimulants are widely used in the management of chronic asthma in India , in spite of evidence suggesting the superiority of inhaled medication in achieving maximum bronchodilatation . An economic evaluation was performed in a r and omized double-blind cross-over trial to evaluate the role of adjuvant oral beta-stimulants in the treatment of asthma . METHODS Patients who had seasonal or perennial asthma and were using metered dose inhalers for control of symptoms were r and omly selected for the study . They received either 4 mg of oral salbutamol or placebo as adjuvant treatment . During the study they controlled their symptoms by adjusting the dose of the inhaler medication . A cost minimization technique was used to assess the economic impact of this intervention in the treatment and control periods . A sensitivity analysis was performed to assess the robustness of the conclusions . RESULTS The mean cost was significantly greater in the treatment period and a patient lost approximately Rs 20 per month ( CI : 13 to 27 ; p = 0.001 ) as a result of the adjuvant treatment . There was no significant difference in the quality of life or peak expiratory flow rate during the two periods . The patients also noted mild but significantly increased tremors ( p = 0.01 ) and palpitations ( p = 0.001 ) during the treatment period . There was no treatment-to-period interaction . CONCLUSION Adjuvant oral beta-agonists do not improve the quality of life or bronchodilatation in asthmatics using an inhaled beta-agonist for control of symptoms OBJECTIVE To evaluate direct asthma-related costs in Swedish primary care in a real-life setting . DESIGN 12-month open-label study . SETTING Swedish primary care in a real-life setting . PARTICIPANTS 1776 patients with persistent asthma . INTERVENTIONS Patients with persistent asthma were r and omised to one of three treatments : a free adjustable combination of budesonide ( 100 - 400 microg/inhalation ) and formoterol ( 4.5 or 9 microg/inhalation ) via separate inhalers plus terbutaline as needed ; budesonide/formoterol ( 160/4.5 microg or 80/4.5 microg , two inhalations twice daily ) plus terbutaline as needed ; budesonide/formoterol ( 160/4.5 microg or 80/4.5 microg , one inhalation twice daily or two inhalations once daily ) , for maintenance plus additional inhalations as needed . Doses depended on previous inhaled corticosteroid dose . Patients attended the clinic at 0 , 1.5 , and 12 months . Telephone interviews were conducted at 4 , 6 , 8 , and 10 months . MAIN OUTCOME MEASURES The primary endpoint was direct asthma-related healthcare costs . RESULTS Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol ( -13 % , P<0.001 ) and fixed-dose budesonide/formoterol plus terbutaline ( -20 % , P<0.001 ) . Time to first severe exacerbation did not differ significantly across treatment groups , with a mean reduction of 28 % versus the free adjustable combination of budesonide and formoterol ( P=0.076 ) . Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide  compared with the conventional ( P<0.001 ) . CONCLUSIONS This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy ABSTRACT Objective : To evaluate efficacy and costeffectiveness of budesonide/formoterol ( Symbicort * ) maintenance ( one dose once or twice daily ) plus additional doses as needed ( Symbicort Maintenance And Reliever Therapy , SMART ) compared with a higher fixed dose of budesonide/ formoterol with formoterol as needed in patients with persistent asthma .  * Symbicort is a registered trade name of the AstraZeneca group of companies Study design and methods : 6‐month , open , r and omised study of 465 patients either not well controlled on an inhaled corticosteroid ( ICS ) , or well controlled on a combination of ICS and a long-acting β2‐agonist ( LABA ) . Treatments : budesonide/formoterol 160/4.5 µg , one inhalation , once or twice daily maintenance plus additional doses as-needed ( 1 × SMART or 2 × SMART ) , or budesonide/formoterol 160/4.5 µg two inhalations twice daily plus formoterol 4.5 µg as needed ( 2 × 2 FIX + F ) . Children 6–11 years old used an 80/4.5 µg dose strength . Primary variables of efficacy were the changes in the Asthma Control Question naire ( ACQ5 ) and morning peak expiratory flow ( PEF ) . Results : Mean age of patients 40 years ( range 6–82 years ) ; 53 % female . No differences between the groups were found in ACQ5 scores or asthma exacerbation rates . Morning PEF was higher in the 2 × 2 FIX + F group vs. the 1 × SMART and 2 × SMART groups ( differences 13 L/min and 9 L/min , respectively ; p < 0.002 ) . The 1 × SMART group showed a significant decrease in asthma controlled days compared with the two other groups . No difference was seen between the 2 × SMART group and the 2 × 2 FIX + F group . Treatment costs were significantly lower in the SMART groups compared with the 2 × 2 FIX + F group . Conclusion : Compared with the 2 × 2 FIX + F treatment the use of budesonide/formoterol was 30–40 % lower in the SMART groups while maintaining equal ACQ5 scores . Daily asthma control improved equally with 2 × SMART compared to 2 × 2 FIX + F with a reduction in asthma medication cost . The one dose once daily maintenance treatment ( 1 × SMART ) result ed in a low level of treatment failure ( exacerbations ) but led to more days with symptoms . Therefore , a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma Inhaled corticosteroids for asthma treatment have become mainstay of therapy for patients with persistent asthma . Numerous inhaled corticosteroids are available but to date no prospect i ve cost-effectiveness studies have been reported using exclusively US patients and costs . The purpose of this study was to examine the cost-effectiveness of HFA-bectomethasone ( QVAR ) compared to CFC-beclomethasone ( Vanceril ) using data from a year-long prospect i ve r and omized , open label , parallel multicenter trial . Eligibility criteria required patients to have been on a stable dose of CFC-BDP prior to enrollment . Patients were r and omized to either HFA-BDP at approximately half their previous daily dose of CFC-BDP or to continue CFC-BDP Effectiveness data , in terms of symptom-free days ( SFDs ) , were used in a cost-effectiveness analysis conducted from the viewpoint of managed care . Patients receiving HFA-BDP reported a greater increase ( median = 22.1 ) in the number of SFDs than those receiving CFC-BDP ( median = 14.3 ) ( P = 0.03 ) . Total costs of care were less for patients taking HFA-BDP ( median = dollars 668 ) compared to CFC-BDP ( median = dollars 977 ) . The median incremental cost-effectiveness ratio was dollars -5.77 ( 95 % CI : dollars -68.08 to dollars -4.08 ) . The results of this analysis indicate that HFA-BDP was a dominant therapy ( more effective , less costly ) compared to CFC-BDP Abstract Objective : To compare the relative cost effectiveness of salmeterol (50μg)/ fluticasone propionate ( 100μg ) with that of oral montelukast ( 10 mg ) as initial maintenance therapy in patients with persistent asthma uncontrolled on short-acting β2-agonist therapy alone . Study design : A cost-effectiveness analysis was performed based on effectiveness and re source utilisation data that was prospect ively collected from a r and omised , double-blind , double-dummy , 12-week trial . Patients and methods : Patients ( > 15 years of age ) who had asthma for at least 6 months . Effectiveness measurements in this analysis included improvement in forced expiratory volume in 1 second ( FEV1 ) and symptom-free days ( SFDs ) . Cost of asthma drug treatment as well as costs related to an asthma exacerbation were used in the cost analysis . The study assumed a payer ’s perspective . All costs are in 2001 US dollars . Results : Of the 423 patients eligible for the study , 211 were r and omised to salmeterol/fluticasone propionate and 212 to montelukast . Treatment with salmeterol/fluticasone propionate result ed in a significantly higher proportion of patients who achieved a 12 % increase in FEV1 ( successful treatment ) [ salmeterol/fluticasone propionate : 71 % vs montelukast : 39 % ; p < 0.001 ] and percentage of SFDs  ( salmeterol/fluticasone propionate : 46.8 % vs montelukast : 21.5 % ; p < 0.001 ) compared with montelukast . The mean daily costs per successfully treated patient were lower in the salmeterol/fluticasone propionate group ( $ US5.03 , 95 % CI $ US4.61 to $ US5.50 ) compared with the montelukast group ( $ US8.25 , 95 % CI $ US6.98 to $ US9.93 ) . Furthermore , per patient mean daily cost per SFD was lower with salmeterol/fluticasone propionate ( $ US7.63 , 95 % CI $ US6.90 to $ US8.50 ) compared with montelukast ( $ US14.89 , 95 % CI $ US12.36 to $ US17.98 ) . Incremental cost-effectiveness ratios ( ICERs ) showed that the additional costs to achieve these benefits with salmeterol/fluticasone propionate were minimal . With regards to improvement in lung function , the ICER was $ US1.33 ( 95 % CI $ US0.80 to $ US2.02 ) and with regards to SFD , the ICER was $ US1.69 ( 95 % CI $ US1.01 to $ US2.48 ) . Sensitivity analysis demonstrated the stability of the results over a range of assumptions . Conclusions : From a third-party payer perspective , this analysis shows that based on increased efficacy and only a slight increase in cost , twice-daily treatment with salmeterol/fluticasone propionate is more cost effective than once-daily treatment with montelukast as initial maintenance therapy for persistent asthma . This finding complements the results of the clinical analyses indicating that treatment of both inflammation and bronchoconstriction with products such as salmeterol/fluticasone propionate may be more cost effective as initial maintenance asthma therapy than the use of leukotriene modifiers such as montelukast We congratulate Amdahl et al.1 on publishing their paper about the cost-effectiveness of pazopanib compared with sunitinib in metastatic renal cell carcinoma ( mrcc ) in Canada . The article reports an analysis similar to the one su bmi tted to the pan-Canadian Oncology Drug Review to support the funding request for pazopanib in mrcc , up date d with final overall survival ( os ) data from the pivotal trial2 . Economic evaluations in oncology are increasingly important to guide both policy and practice . We commend the efforts of these authors to put their su bmi tted analyses into the public domain for transparency and to support and inform future research . The base-case analysis ( using the list prices of pazopanib and sunitinib ) by Amdahl et al.1 found that , compared with sunitinib , which is the st and ard of care for first-line therapy in mrcc , first-line pazopanib is likely cost-saving . The base case analysis also suggested that pazopanib might be slightly more effective than sunitinib numerically , with an incremental gain of 0.057 life-years and 0.059 quality -adjusted life-years . Before concluding that pazopanib is dominant ( that is , it provides more benefit for a lower cost ) with respect to sunitinib , it is important to review the clinical data comparing pazopanib and sunitinib in mrcc to assess the comparative efficacy and preference-based measures of health-related quality of life ( hrqol ) associated with those agents — that is , their health utilities — to examine the face validity of the economic model in its base case . The efficacy differences between the pazopanib and sunitinib in the comparz study 3 were not statistically significant , median progression-free survival for pazopanib and sunitinib being 8.4 months [ 95 % confidence interval ( ci ) : 8.3 to 10.9 months ] and 9.5 months ( 95 % ci : 8.3 to 11.1 months ) respectively , with a hazard ratio of 1.05 ( 95 % ci : 0.90 to 1.22 ) . The study met its primary endpoint of non-inferiority in progression-free survival . No os difference was observed in the comparz study , in which median os was 28.4 months for pazopanib ( 95 % ci : 26.2 to 35.6 months ) and 29.3 months for sunitinib ( 95 % ci : 25.3 to 32.5 months ) , with a hazard ratio of 0.91 ( 95 % ci : 0.76 to 1.08 ) . At the up date d analysis , os was similar in the two groups ( hazard ratio for pazopanib vs. sunitinib : 0.92 ; 95 % ci : 0.79 to 1.06 ; p = 0.24)2 . With similar survival results for pazopanib and sunitinib based on the comparz study , one might ask , “ How did the model project an incremental gain of 0.057 life-years in favour of pazopanib ? ” The model actually projected a shorter life expectancy while patients were taking pazopanib than while their counterparts were taking sunitinib ( 0.013 life-years lost in the progression-free state ) . However , the model also projected that , after patients progressed and stopped taking pazopanib , their life expectancy was longer than it was for patients who received sunitinib ( 0.070 life-years gained in the post-progression state ) . Together , the loss and the gain result ed in a net gain in life expectancy for pazopanib , implying that the survival benefit of pazopanib acted only after progression , when patients were no longer taking pazopanib . There is no biologic basis for that phenomenon , and it likely simply reflects small numerical differences between the pazopanib and sunitinib progression-free survival and os curves , without accounting for uncertainty . Interestingly , the model also predicted that pazopanib would be more effective in at least 80 % ( or possibly all ) of the simulations despite the nonsignificant result . Although the comparz study 3 collected some hrqol measures , it did not collect preference-based measures of hrqol to allow for the calculation of quality -adjusted life-years for the purpose of economic evaluation . The pisces study 4—a r and omized , double-blind trial with a crossover design ( that is , pazopanib→sunitinib vs. sunitinib→pazopanib)—had , as its primary endpoint , an examination of patient preference for either pazopanib or sunitinib , which suggested that patients preferred pazopanib over sunitinib . However , the study had a few limitations 5 , including a relatively high proportion of the r and omly assigned patients ( 33 % ) not being evaluable for the primary endpoint , and the analysis of the pazopanib preference being based on a “ modified ” intention-to-treat population . The EQ-5D ( EuroQoL Group , Rotterdam , Netherl and s ) was also collected as the preference-based measure of hrqol in the pisces study 4 , but the EQ-5D results would have been subject to similar limitations . The data from the pisces study were used in the su bmi ssion to the pan-Canadian Oncology Drug Review . In the up date d analysis 1 , the authors conducted a regression based on patients in a trial comparing pazopanib with placebo6  , assuming that the effect of adverse events ( aes ) were driving the differences in hrqol , regardless of actual treatment received . For the analysis , the aes were grouped by severity and whether the aes were more commonly occurring in the sunitinib or the pazopanib group of the comparz trial . Using that approach , the regression model found that the health utility decrement was larger for the group of aes more commonly occurring in patients who used sunitinib than for the remaining aes more frequently occurring in patients who used pazopanib in the comparz trial . The results of the regression model were combined with the incidence and duration of aes in each treatment arm to derive the mean utility values used in the model , producing mean utility values of 0.7089 ( st and ard error : 0.0193 ) for pazopanib and 0.6832 ( st and ard error : 0.0236 ) for sunitinib , an incremental difference of 0.0257 in the progression-free period1 . Given that the comparz trial demonstrated similar efficacy and a more favourable toxicity profile for pazopanib , it is not unreasonable that the point estimate of the utility score could slightly favour the pazopanib group . However , these mean utility values were not directly derived and might be neither statistically nor clinical ly different , especially because the difference was smaller than the reported estimates of minimal important differences for health utilities ( which are in the range of 0.05–0.08 for the EQ-5D)7,8 . Thus , it is somewhat difficult to conclude from those data that pazopanib is associated with better utility than sunitinib . It might be reasonable to conservatively expect that the utilities of pazopanib and sunitinib are fairly similar given the size of the st and ard errors of the two utilities , subject to a reasonable amount of uncertainty9,10 . Given that clinical trials did not demonstrate a statistically significant survival benefit or EQ-5D health utility benefit for pazopanib over sunitinib , we feel that an appropriate interpretation could be that the study findings suggest similar efficacy and health utility for the two drugs . Reasonably , the pan-Canadian Oncology Drug Review ’s Expert Review Committee also concluded that it is reasonable to assume similar efficacy and to focus on the cost comparison between pazopanib and sunitinib in this setting 11 . We appreciate that the sensitivity analyses by Amdahl et al.1 address all the considerations discussed here , including the importance of the relative price of the two drugs . The authors demonstrate as part of their additional analyses that — assuming similar efficacy , health utility , and daily price of the two therapies — only minor cost differences remain . Thus , interpreting the analyses in light of the evidence , it appears that these two options for first-line therapy in mrcc might be largely similar and , taking into account the relative prices of the two drugs , the hope would be that , after confidential negotiations , they will also be similar in cost . In that case , having both drugs available would give patients the option to choose based on individual preference and side effect profile , especially in the case of intolerance to one of the drugs , and would ensure that health care re sources are being efficiently used . The generalizability of the study findings remains to be seen in practice . Verification from experience is needed to know whether the comparative outcomes as laid out will be realized . In Canada , jurisdictions have an important opportunity and challenge to evaluate the real-world effectiveness and cost-effectiveness of therapies in clinical practice after drugs are funded . Moreover , post-market research can provide valuable insights into practice patterns when two alternatives are funded and can possibly inform continued uncertainties such as sequencing and long-term adverse effects . We applaud the approach of the authors to share their analyses with the broader clinical and research communities , and we encourage more authors of economic evaluations created and su bmi tted to review bodies ( for example , the Canadian Agency for Drugs and Technologies in Health , the pan-Canadian Oncology Drug Review ) to follow suit . We expect that this activity will build on the principle of transparency being increasingly championed by the review organizations and will improve the rigour of the economic evidence used to inform policy . Finally , we call on the community to continue to pursue both academic merit and clinical and policy relevance by supporting the availability of peer- review ed publications of economic evaluations to inform the reimbursement review process . Ideally , it would be helpful if economic evaluations were to be published before decision-making so as to engage more stakeholders in the discussion 12 . In doing so , the clinical and economic evidence bases supporting the health technology assessment processes in Canada might be brought into better alignment , improving the robustness of decision-making and ultimately helping health care systems in Canada to provide effective and appropriate care to patients ABSTRACT Background : Severe allergic asthma patients may not be controlled even with guideline recommended care , including inhaled corticosteroids , long-acting beta-2 agonists , theophylline , oral steroids and anti-leukotrienes . They experience exacerbations requiring intensive healthcare use and which may be fatal . Omalizumab , a new monoclonal antibody for use in IgE-mediated allergic diseases , reduces exacerbations and daily symptoms in this patient population . The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized st and ard therapy ( ST ) in patients with severe persistent IgE-mediated ( allergic ) asthma . Methods : A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST , was developed based on efficacy data from the INNOVATE trial ( 28 weeks , N = 419 ) and Swedish life table and cost data . This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinical ly significant severe asthma exacerbation . Patients in a steady-state of having no exacerbations are defined to be in an ‘ optimized asthma control ’ state . Re source use data and utilities were obtained from INNOVATE and from a UK observational study . Costs from a societal perspective include estimates for drugs , routine care , exacerbations and costs in added years of life ; benefits are expressed in QALYs . The response to omalizumab was evaluated after 16 weeks of trial , and non-responders stopped taking omalizumab for the remaining time . Results : Total lifetime discounted costs and QALYs on ST were € 52 702 and 11.60 . Omalizumab add-on therapy cost an additional € 42 754 for 0.76 additional QALYs , result ing in an incremental cost-effectiveness ratio of € 56 091 . A probabilistic sensitivity analysis indicates that the 95 % CI around the ICER is [ € 31 328 ; € 120 552 ] . One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate , the time horizon and the discount rates . Conclusions : Based on the model and the assumptions used , our results suggest that omalizumab provides cost offsets , improves quality of life and may have an attractive ICER in treating the severe allergic asthma population OBJECTIVE To compare the cost effectiveness of hydrofluoroalkane 134a-beclomethasone dipropionate ( HFA-BDP ; Qvar ) [ corrected ] with chlorofluorocarbon-beclomethasone dipropionate ( CFC-BDP ) in patients with chronic stable asthma previously receiving CFC-BDP , from the perspective of a healthcare provider . DESIGN Cost-effectiveness analysis based on a 12-month pragmatic , r and omised , parallel group , open-label clinical trial assessing safety and efficacy of HFA-BDP at approximately half the dose of CFC-BDP in patients with stable asthma . SETTING International , multicentre study at 57 study sites in the US , UK , The Netherl and s , and Belgium .  Healthcare costs were calculated for UK-based healthcare [ in 1999 as pounds ( pounds sterling ) ] . PATIENTS AND PARTICIPANTS Patients ( n = 473 ) > or = 12 years of age with currently stable asthma that had been stable ( i.e. no exacerbations requiring oral corticosteroid use in the last 4 weeks ) for at least the preceding month . MAIN OUTCOME MEASURES Average and incremental cost-effectiveness ratios based upon symptom-free days , improvement in health-related quality of life , and total and drug-only direct healthcare costs . RESULTS Patients in the HFA-BDP group experienced a significantly higher percentage of symptom-free days than patients in the CFC-BDP group by the end of the study period ( 42.4 vs 20.0 % ; p = 0.006 ) . A greater percentage of patients in the HFA-BDP group had a clinical ly significant improvement in health-related quality of life than in the CFC-BDP group [ 35.3 ( n = 116/329 ) vs 16.1 % ( n = 18/112 ) ] . Total per patient healthcare costs were similar between the two groups . The average cost per symptom-free day per patient was 1.36 pounds sterling for HFA-BDP and 1.81 pounds sterling for CFC-BDP based on total healthcare costs . The incremental cost per symptom-free day for using HFA-BDP instead of CFC-BDP was negative , indicating that HFA-BDP is a dominant strategy and may be a cost-saving intervention compared with CFC-BDP . A sensitivity analysis varying both cost and outcome parameters further supported this finding for most scenarios tested . The cost to achieve a clinical ly significant improvement in health-related quality of life over the study period was 13.24 pounds sterling per improved patient per week for HFA-BDP and 29.38 pounds sterling per patient per week for CFC-BDP . CONCLUSIONS These findings indicate that HFA-BDP is a cost-effective intervention when compared with CFC-BDP in this group of patients with stable asthma . In the majority of scenarios HFA-BDP provides more effective asthma control at a similar cost to CFC-BDP When deciding on treatment for patients with asthma , clinicians should consider the following : basic science that supports the therapeutic agent , r and omized clinical trials that demonstrate clinical efficacy , and " real world " economic evidence that confirms the basic science and clinical study findings . When selecting first-line controller therapy for persistent asthma , clinicians should look for the single agent that produces the greatest improvement in lung function and patient outcomes , has minimal adverse effects , and is cost effective . To determine whether there is one first-line controller that achieves all of these goals , physicians should evaluate findings of r and omized controlled trials that assess a drug 's effect on asthma symptoms , lung function , and albuterol use compared with placebo or a comparator . They should also consider findings from retrospective cl aims analyses . This combination of data provides a truer picture and more robust evidence of a drug 's clinical and economic performance . Similar evaluations need to be undertaken when deciding on the most cost-effective add-on therapy Abstract Introduction : Budesonide/formoterol ( Symbicort ® ) Maintenance And Reliever Therapy ( SMART ) is an effective and well tolerated treatment option for patients with asthma . We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate ( Seretide ® ) plus salbutamol ( albuterol ) as needed ( Seretide ® Fixed Combination [ SFC ] ) . Study design : A cost-effectiveness analysis was performed based on effectiveness and re source -utilisation data collected prospect ively in a r and omised , 12-month study performed in 2143 patients in 16 countries . Re source utilisation data were pooled and unit costs ( € , year 2003 values ) from Italy , France , the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided . Methods : Adolescents and adults with asthma ( n = 2143 ; mean forced expiratory volume in 1 second [ FEV1 ] 73 % predicted ; mean inhaled corticosteroid [ ICS ] dose 884 µg/day ) were r and omised to SMART or SFC . The effectiveness measure used was the number of severe exacerbations per patient per year . Direct costs included medication use ( budesonide/formoterol 160µg/4.5 µg or salmeterol/fluticasone 50µg/100 µg , 50µg/250 µg or 50µg/500 µg plus salbutamol ) and nonmedication-related re source use , including days in hospital , emergency room visits , specialist or primary care physician visits and other healthcare provider contacts . Indirect costs , including the number of days when the patient or their carer was unable to attend to their normal daily activities , were also assessed . The study assumed a European societal perspective ( i.e. including direct and indirect costs ) . Results : Treatment with SMART result ed in significantly fewer severe exacerbations per patient per year compared with SFC ( 0.24 vs 0.31 events per patient per year ; p = 0.0025 ) . Re source use was low in both groups . Medication costs accounted for the majority of the total costs . The increased  effectiveness of SMART was achieved at a reduced or similar cost compared with SFC . SMART dominated when German unit costs were applied ( i.e. there was a statistically significant reduction in both costs and number of exacerbations ) . In all other countries , the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided ; however , this difference was not statistically significant . Conclusion : This analysis demonstrates that , compared with SFC , SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy , Germany , France and the UK . SMART provided a reduction in the number of severe exacerbations per patient per year , at no statistically significant increase in cost — or even at a lower cost — compared with SFC plus as-needed reliever salbutamol The inhaled corticosteroid fluticasone propionate ( FP ) was introduced into the Thorpewood General Practice , Norwich , U.K. in 1993 -initially in treating relatively severe asthmatics . Observed beneficial effects led to exp and ed use particularly for poorly controlled asthma not responsive to increased inhaled anti-inflammatories . However , an early review suggested little advantage over existing agents ( l ) , and FP was marketed at a price premium . The aims of this study were to investigate whether continued and exp and ing use of FP was justified in terms of improved clinical outcomes , and if such improvements were associated with reduced NHS costs ( off setting more expensive prescriptions ) . A controlled , retrospective , nonr and omized primary care audit compared clinical outcomes and asthma management costs 1 year prior to and 1 year into FP therapy BACKGROUND Omalizumab can reduce hospitalization and emergency department visits and improve quality of life in patients with moderate-to-severe , suboptimally controlled allergic asthma . Given the high cost and modest efficacy of this agent , it is not clear that it is cost-effective if given to a broad population with asthma . OBJECTIVE The purpose of this study was to evaluate the cost-effectiveness of omalizumab in adults and adolescents with moderate-to-severe allergic asthma . METHODS A retrospective economic analysis was performed to determine the cost-effectiveness of omalizumab using 52-week data from 2 r and omized controlled clinical trials in adults and adolescents with moderate-to-severe allergic asthma . The analysis was conducted from a third-party payer 's perspective , and only direct costs were considered . RESULTS The incremental cost-effectiveness ratios showed that the cost to achieve an additional successfully controlled day was $ 523 , and the daily cost to achieve at least a 0.5-point increase in Asthma Quality of Life Question naire score was $ 378 in 2003 dollars . CONCLUSION From a pharmacoeconomic st and point , omalizumab would be better used in allergic asthmatic patients with poorly controlled symptoms despite maximal therapy , given the high cost and modest efficacy of this agent . It could be cost saving if given to nonsmoking patients who are hospitalized 5 or more times or 20 days or longer per year despite maximal asthma therapy Preamble Although economic outcomes research is an evolving field in health services research , there are correct and incorrect ways to conduct and report on economic outcomes studies . Research practice s that help to minimize real or perceived bias will increase the quality and usefulness of such studies for those who sponsor , publish , and use them . Because of public concerns about the potential for bias in the design , analysis , and reporting of economic analyses of health care technology , we formed a task force to develop principles to enhance the credibility of these studies . The Task Force on Principles for Economic Analysis of Health Care Technology included participants from academia , the pharmaceutical industry , the public sector , and private research organizations . As health care re sources become increasingly constrained , the information used to make re source allocation decisions must be as reliable , valid , and free of bias as possible . Getting it right at the level at which economic results are produced will help to protect consumers and will advance the health of the public . Bias stems from two broad categories : lack of appropriate independence for research ers and lack of consensus about methods . We focused heavily on the first of these categories for two major reasons . First , few have yet considered the unique issues of research er independence in economic outcomes research [ 1 , 2 ] . Second , other investigators have begun to consider and define proper methods for economic outcomes work ( an area of considerable controversy ) [ 3 - 5 ] . We also looked closely at the requirements for the reporting of economic analyses , which are intended to ensure method ologic transparency and accountability . The Need for Voluntary Guidelines Widespread use of economic analysis as part of the development of pharmaceutical , biotechnologic , and medical devices is relatively new . To date , many economic analyses of health care have focused on pharmaceutical agents , and many such studies have been funded by pharmaceutical companies . Results of these economic outcomes studies are used by medical technology firms to support the pricing and marketing of new interventions and to influence national health care systems and third-party payers in their development of coverage and payment decisions . Managed care organizations , hospitals , and government-subsidized health care programs rely on economic analysis of medical technology to help make formulary purchasing and utilization decisions . Physicians may use the results of these analyses to help guide treatment and prescription decisions . Health care economic outcomes projects are sponsored and conducted by pharmaceutical , biotechnologic , and medical device companies ; government agencies ; nonprofit foundations ; academic investigators ; and private research and consulting firms . The st and ards and methods used to evaluate the safety and efficacy of pharmaceutical products in r and omized , controlled trials have evolved over 50 years of collaboration among research ers in private , public , and academic setting s. Compared with those established to ensure the safety and efficacy of clinical trials , the principles and methods for the conduct of economic studies of health care technology are far less developed . Problems of conduct , reporting , and bias exist in all types of research [ 6 - 14 ] . In response , codes of conduct , such as those developed by the American Federation for Clinical Research and the Institute of Medicine , have been developed for many scientific disciplines [ 15 - 24 ] . These are good models on which to base principles of conduct for economic outcomes analysis . Although many published principles apply to economic studies , others should be modified and new ones should be developed to guide the conduct and reporting of economic outcomes analyses . Economic outcomes research requires unique guidelines for the following reasons : 1 ) As a field , it continues to evolve and is often misunderstood by end users ; 2 ) peer review of it requires special expertise that often exceeds the capabilities of review ers and scientific journals ; 3 ) it often uses secondary data and requires that many assumptions be made [ for example , attribution of a dollar cost to a unit of re source use ] ; 4 ) it offers unique method ologic choices , such as which types of costs to include ( direct , indirect , intangible , induced ) , which perspective to apply ( that of society , payer , provider , patient ) , which design to adopt ( cost- identification , costbenefit , cost-effectiveness , costutility ) , from where to obtain costs [ indemnity data base , managed care or capitated data base , hospital cost systems , Medicare , Medicaid ] , and whether to collect re source consumption data prospect ively or retrospectively through various modeling techniques ; and 5 ) economic studies play an increasingly important role in health care decision making because of increasing financial constraints throughout the health care industry . The financial and medical implication s of decision making done on the basis of these studies , coupled with the lack of widely accepted guidelines about the conduct and reporting of economic analyses , undermine the credibility of this research . A major issue is that the primary source of funding for this research is often the primary financial beneficiary of positive study results . Unfortunately , even valid studies done under the best of circumstances may be suspect [ 25 - 29 ] . This has led at least one major journal to conclude that these analyses should be viewed much like editorials or review articles are viewed in terms of potential for conflicts of interest [ 30 ] . We developed the guidelines reported here after extensive consultation with experts from the public , private , and academic sectors . We recommend that research ers and sponsors adhere to these guidelines , and we suggest they state publicly within their manuscripts that they have done so . End users , including journal editors and readers , consumers , and social decision makers , may then feel more secure in accepting the results of the research , while recognizing that intensive critique of the research will always be necessary . Operations of the Task Force The Task Force on Principles for Economic Analysis of Health Care Technology was initiated and organized by faculty from the Leonard Davis Institute ( LDI ) Center for Health Policy of the University of Pennsylvania . However , because not all LDI faculty were involved , this paper does not represent an official LDI position statement . The Task Force was funded by a coalition of pharmaceutical companies ( Appendix A ) . Funding was also requested ( but not obtained ) from various government and private foundations . All funding was provided in the form of unrestricted research grants or gifts to the University of Pennsylvania . Guidelines derive their credibility in part from the composition of the panel that creates them and the process by which they are developed . C and i date s for participation in the Task Force from the private sector and the academic research community were identified by the frequency with which they were cited in the health economics literature , which was obtained using a MEDLINE search of literature related to economic analyses of medical technology published between 1983 and 1992 . Approximately 15 members attended each meeting . Minutes were distributed after each meeting and approved by all members present . Members from the sponsoring pharmaceutical companies and the academic organizers rotated so that they numbered three and one , respectively , at the table for each formal Task Force meeting . Several professional and governmental organizations , including the Institute of Medicine , the Agency for Health Care Policy and Research , the Food and Drug Administration ( FDA ) , the Health Care Financing Administration , the Centers for Disease Control and Prevention , and a managed care organization , were asked to suggest persons who might participate . In addition , other organizations with a stake in economic analyses were each asked to suggest a person who , because of his or her professional background , had extensive knowledge of or experience with economic analyses . An academic pharmacist , an academic research er , a private research er , an ethicist and patient advocate , and an attorney specializing in medical ethics rounded out the Task Force ( Appendix B ) . Two members withdrew from participation . A small audience consisting of industry sponsors , academic organizers , staff , and a few other interested parties were invited to each meeting and allowed to comment . Four formal meetings of the Task Force were held in Philadelphia during 1993 and 1994 , and the most substantial work was done by various subcommittees between these meetings . The three main subcommittees were titled Ethical Conduct , Responsibility and Control ( the findings of these two subcommittees were later merged into one report ) , and Reporting Requirements for Economic Evaluations ( Appendix C ) . The Task Force was assisted by a professional facilitator . Although Task Force members sought consensus wherever possible on the key issues , consensus was not forced and recommendations were issued only when substantial agreement existed among the members . Task Force members were not asked to formally represent any organization . Formal endorsement of the final document was not sought . Copies of this report will be distributed to all organizations that were asked to suggest a participant and to other parties who responded to announcements placed in The New Engl and Journal of Medicine , Scrip , and the Pink Sheet . The Task Force findings will also be reported at academic conferences , medical profession meetings , and appropriate trade conventions . Findings and Recommendations Valid approaches to economic analyses can be defined ; acceptable methods can be differentiated from unacceptable ones . Bias in economic research stems from two major sources : lack of appropriate independence for BACKGROUND The severity of asthma varies between individuals and over time . As a result individuals may have marked variation in their need for asthma treatment . Adjustable dosing enables patients to assume greater involvement in managing their own condition . OBJECTIVE To compare the costs and effectiveness of fixed dosing of budesonide/formoterol ( Symbicort Turbohaler ) with adjustable maintenance dosing . METHODS A cost-effectiveness analysis was conducted from the perspective of the UK NHS . Adults with established asthma currently maintained on > or = 400 microg per day inhaled corticosteroid were enrolled in 365 primary care centres in the UK . Patients were run-in on 2 inhalations twice daily of budesonide/formoterol 80/4.5 microg or budesonide/formoterol 160/4.5 microg ( depending on steroid requirement ) for 4 weeks and were then r and omised to the Symbicort adjustable maintenance dosing plan ( SAMD ) ( n = 782 ; budesonide/formoterol 1 - 4 inhalations twice daily depending on symptoms ) or Symbicort fixed dosing ( n = 771 ; 2 inhalations twice daily ) for a further 12 weeks . The primary effectiveness variable was clinical ly meaningful change in quality of life ( QoL ) assessed by the miniasthma quality of life question naire ( AQLQ ) . Secondary effectiveness measures included symptom-free days with no short-acting beta-agonist use . We assessed the costs of study medication , asthma-related concomitant medication , primary care and hospital contacts . Confidence intervals were generated by nonparametric boot-strapping . RESULTS Clinical ly meaningful improvement in QoL during the first 4 weeks was reported by 40.8 % of enrolled patients . During the following 12 weeks , a net 1 % ( 95 % CI : -4 % , 6 % ) of SAMD patients and 6 % ( 95 % CI : 1 % , 10 % ) of fixed dosing patients reported further improvement . Effectiveness parameters did not differ significantly between groups during the study period . Mean daily cost per patient was pound sterling 1.13 ( 95 % CI : pound sterling 1.08 , pound sterling 1.18 ) in the SAMD group and pound sterling 1.31 ( 95 % CI : pound sterling 1.27 , pound sterling 1.34 ) in the fixed dosing . The difference in mean daily cost result ed in an annual per patient cost difference of pound sterling 65.70 . Adjustable maintenance dosing with budesonide/formoterol provided equivalent QoL to fixed dosing at significantly lower cost In this economic evaluation , conducted alongside a r and omized , double-blind clinical trial , economic data were collected from 339 patients with moderate-persistent asthma r and omized to receive twice-daily , double-blind treatment with budesonide/formoterol 160/4.5 microg  in a single inhaler ( n=166 ) or fluticasone propionate 250 microg ( n=173 ) for 12 weeks . The mean number of episode-free days ( EFD ) per patient was significantly greater in the budesonide/formoterol group than the fluticasone group ( 48.71 compared with 42.34 , P=0.0185 ) . Data on medication use , visits to healthcare professionals , and hospitalization were pooled across all six countries and combined with German and Dutch unit cost data to calculate total healthcare costs . Using German unit costs , budesonide/formoterol was associated with significantly lower total healthcare costs per patient over the 12-week period compared with fluticasone ( euro 131 compared with euro 210 , P=0.0043 ) . Using Dutch unit costs , total healthcare costs were slightly numerically lower in the budesonide/formoterol group than the fluticasone group ( euro 102 compared with euro 104 ) , but the difference did not reach statistical significance . Budesonide/formoterol in a single inhaler is more effective than a higher microgram dose of fluticasone alone . It is cost-neutral and may provide cost-savings in some countries Abstract Background : Asthma is a chronic disease , the two main components of which are inflammation and bronchoconstriction . Fluticasone propionate ( FP ) and salmeterol , a strategy that treats both main components of asthma , has been recently compared with FP plus montelukast in a r and omised clinical trial . The present study reports economic evaluation of these two strategies . Objective : To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50μg twice daily administered via a single Diskus ® inhaler device versus treatment with FP 100μg twice daily via a Diskus ® inhaler plus oral montelukast 10 mg once daily . Study design : A cost-effectiveness analysis was performed by applying cost unit data to re source utilisation data collected prospect ively during a US r and omised , double-blind , 12-week trial of  FP/salmeterol ( n = 222 ) versus FP + montelukast ( n = 225 ) . Patients were ≥15 years of age and were symptomatic despite inhaled corticosteroid ( ICS ) therapy . Patients and methods : Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second ( FEV1 ) and symptom-free days . Direct costs included those related to study drugs , emergency room department visits , unscheduled physician visits , treatment of drug-related adverse events ( oral c and idiasis ) , and rescue medication ( salbutamol [ albuterol ] ) . The study assumed a US third-party payer ’s perspective with costs in 2001 US dollars . Results : Treatment with FP/salmeterol result ed in a significantly higher proportion ( p < 0.001 ) of patients who achieved a ≥12 % increase in FEV1 than treatment with FP + montelukast ( 54 % [ 95 % CI 47 % , 61 % ] vs 32 % [ 95 % CI 26 % , 38 % ] ) . Lower daily costs and greater efficacy of FP/salmeterol result ed in a cost-effectiveness ratio of $ US6.77 ( 95 % CI $ US5.99 , $ US7.66 ) per successfully treated patient in the FP/salmeterol group compared with $ US14.59 ( 95 % CI $ US12.12 , $ 17.77 ) for FP + montelukast . In addition , FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast ( 31 % [ 95 % CI 26 % , 35 % ] vs 27 % [ 95 % CI 23 % , 32 % ] ) , but at a significantly lower daily per-patient cost ( $ US3.64 [ 95 % CI $ US3.60 , $ US3.68 ] vs $ US4.64 [ 95 % CI $ US4.56 , $ US4.73 ] ) . Sensitivity analyses demonstrated the stability of the results over a range of assumptions . Conclusion : From a US third-party payer ’s perspective , these findings suggest that treating the two main components of asthma ( inflammation and bronchoconstriction ) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma . The results were found to be robust over a range of assumptions BACKGROUND There are few data on the role of nebulised magnesium sulphate ( MgSO4 ) in the management of  acute asthma in children . Those studies that have been published are underpowered , and use different methods , interventions and comparisons . Thus , no firm conclusions can be drawn . OBJECTIVES Does the use of nebulised MgSO4 , when given as an adjunct to st and ard therapy in acute severe asthma in children , result in a clinical improvement when compared with st and ard treatment alone ? DESIGN Patients were r and omised to receive three doses of MgSO4 or placebo , each combined with salbutamol and ipratropium bromide , for 1 hour . The Yung Asthma Severity Score ( ASS ) was measured at baseline , r and omisation , and at 20 , 40 , 60 ( T60 ) , 120 , 180 and 240 minutes after r and omisation . SETTING Emergency departments and children 's assessment units at 30 hospitals in the UK . PARTICIPANTS Children aged 2 - 15 years with acute severe asthma . INTERVENTIONS Patients were r and omised to receive nebulised salbutamol 2.5 mg ( ages 2 - 5 years ) or 5 mg ( ages ≥ 6 years ) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 ( 250 mmol/l , tonicity 289 mOsm ; 151 mg per dose ) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals . MAIN OUTCOME MEASURES The primary outcome measure was the ASS after 1 hour of treatment . Secondary measures included ' stepping down ' of treatment at 1 hour , number and frequency of additional salbutamol administrations , length of stay in hospital , requirement for intravenous bronchodilator treatment , and intubation and /or admission to a paediatric intensive care unit . Data on paediatric quality of life , time off school/nursery , health-care re source usage and time off work were collected 1 month after r and omisation . RESULTS A total of 508 children were recruited into the study ; 252 received MgSO4 and 256 received placebo along with the st and ard treatment . There were no differences in baseline characteristics . There was a small , but statistically significant difference in ASS at T60 in those children who received nebulised MgSO4 { 0.25 [ 95 % confidence interval ( CI ) 0.02 to 0.48 ] ; p = 0.034 } and this difference was sustained for up to 240 minutes [ 0.20 ( 95 % CI 0.01 to 0.40 ) , p = 0.042 ] . The clinical significance of this gain is uncertain . Assessing treatment-covariate interactions , there is evidence of a larger effect in those children with more severe asthma exacerbations ( p = 0.034 ) and those with a shorter duration of symptoms ( p = 0.049 ) . There were no significant differences in the secondary outcomes measured . Adverse events ( AEs ) were reported in 19 % of children in the magnesium group and 20 % in the placebo group . There were no clinical ly significant serious AEs in either group . The results of the base-case economic analyses are accompanied by considerable uncertainty , but suggest that , from an NHS and Personal Social Services perspective , the addition of magnesium to st and ard treatment may be cost-effective compared with st and ard treatment only . The results of economic evaluation show that the probability of magnesium being cost-effective is over 60 % at cost-effectiveness thresholds of £ 1000 per unit decrement in ASS and £ 20,000 per quality -adjusted life-year ( QALY ) gained , respectively ; it is noted that for some parameter variations this probability is much lower , reflecting the labile nature of the cost-effectiveness ratio in light of the small differences in benefits and costs shown in the trial and the relation between the main outcome measure ( ASS ) and preference based measures of quality of life used in cost-utility analysis ( European Quality of Life-5 Dimensions ; EQ-5D ) . CONCLUSIONS This study supports the use of nebulised isotonic MgSO4 at the dose of 151 mg given three times in the first hour of treatment as an adjuvant to st and ard treatment when a child presents with an acute episode of severe asthma . No harm is done by adding magnesium to salbutamol and ipratropium bromide , and in some individuals it may be clinical ly helpful . The response is likely to be more marked in those children with more severe attacks and with a shorter duration of exacerbation . Although the study was not powered to demonstrate this fully , the data certainly support the hypotheses that nebulised magnesium has a greater clinical effect in children who have more severe exacerbation with shorter duration of symptoms . TRIAL REGISTRATION Current Controlled Trials IS RCT N81456894 . FUNDING The National Institute for Health Research Health Technology Assessment programme Despite a good underst and ing of the disease and its treatments , asthma continues to place a large economic burden on healthcare systems . As such , it is important to consider the economic impact of alternative therapeutic options for the treatment of this condition to ensure that scarce re sources are used in the most efficient manner possible . Thus , the aim of asthma management from an economic perspective is to reduce the burden of this disease through maximizing health gain with available re sources . A prospect i ve economic analysis was conducted as part of a multicentre , r and omized , double-blind , comparative trial of salmeterol/fluticasone propionate combination product ( SFC ) 50/250 microg twice daily vs. budesonide ( 800 microg twice daily ) in adults and adolescents with asthma who were symptomatic despite treatment with inhaled corticosteroids at doses of 800 - 1200 microg day(-1 ) .  Treatment effectiveness was measured in terms of successfully-treated weeks , defined as a > or = 5 % improvement in morning peak expiratory flow , episode-free days ( a day without the need for rescue medication , no nocturnal awakening or adverse events ) and symptom-free days . Cost-effectiveness analyses were performed using direct healthcare and drug costs , from the perspective of the Swedish healthcare system ( 1998 prices ) , with appropriate sensitivity analyses to test the robustness of the findings . Overall , SFC produced significantly higher ( P<0.001 ) proportions of successfully-treated weeks , episode-free days and symptom-free days . Direct asthma management costs were similar between the two groups [ SEK19.6 ( $ US2.4 ) for SFC vs. SEK18.5 ( SUS2.2 ) for budesonide ] . The cost per successfully-treated week was lower for SFC than for budesonide [ SEK204 ( $ US24.8 ) vs. SEK300 ( $ US36.4 ) per week ] , as were the costs per episode-free day [ SEK51.1 ( $ US6.2 ) vs. SEK75.1 ( $ US9.1 ) per day ] and symptom-free day [ SEK42.2 ( $ US5.1 ) vs. SEK53.0 ( $ US6.4 ) per day ] . Incremental cost-effectiveness ratios showed that the additional costs to achieve additional benefits with SFC were minimal . Costs per additional successfully-treated week , symptom-free day and episode-free day with SFC were SEK31.6 ( $ US3.9 ) , SEK9.2 ( $ US1.1 ) and SEK7.7 ( $ US0.9 ) , respectively , relative to budesonide . Sensitivity analysis showed that the results were stable over a wide range of assumptions . The results suggest that SFC is a more cost-effective treatment than budesonide  in the management of moderate to severe asthma This article presents the first version of a reporting format for modelling studies  which is based on a general reporting format by our taskforce , which was published in the previous issue of this journal . The use of decision-analytical models for economic evaluations is increasing because , in practice , it is not always possible to derive information from prospect i ve studies . However , the acceptance of modelling studies is generally lower than prospect i ve studies not only because of the use of secondary data , but also because the reports of modelling studies do not always have sufficient transparency . Hence , a st and ardised reporting format may improve the transparency and , consequently , the acceptance of modelling studies . This article presents an example of a reporting format for  economic evaluation based on modelling studies , which may facilitate the development of future guidelines for modelling studies . The format consists of a number of headings , which are followed by a brief recommendation on the content . This format does not deal with methodology and data management , but especially addresses validation and quality assurance , which may increase the transparency of the report Abstract Objective : To compare the relative value of an inhaled corticosteroid , fluticasone propionate 88μg twice daily , versus an oral leukotriene receptor antagonist , zafirlukast 20 mg twice daily , in patients with persistent asthma currently receiving short acting β2-agonists alone . Study design : A cost-efficacy analysis using re source utilisation and clinical data obtained prospect ively from a multicentre , r and omised , double-blind , double-dummy , placebo-controlled 12-week clinical trial conducted in the US . Perspective : Third-party payor . Patients and methods : A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88μg twice daily or zafirlukast 20 mg twice daily . All patients were given salbutamol ( albuterol ) to be used as rescue medication . Data were examined using intent-to-treat analysis . Results : Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second ( FEV1 ) [ ≥12 % increase from baseline ] were $ US3.47 for fluticasone propionate compared with $ US7.81 for zafirlukast ( 1999 values ) . The mean daily per person cost-efficacy ratios for symptom-free days obtained were $ US5.51 for fluticasone propionate compared with $ US14.98 for zafirlukast . These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis . Conclusions : Treatment with fluticasone propionate 88μg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial . This analysis supports the use of fluticasone propionate 88μg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting β2-agonist alone BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness -- in a primary -care setting --of leukotriene receptor antagonists ( LTRAs ) as an alternative to inhaled corticosteroids ( ICS ) for initial asthma controller therapy . OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy . METHODS An economic evaluation was conducted alongside a 2-year , pragmatic , r and omized controlled trial set in 53 primary -care practice s in the UK . Patients aged 12 - 80 years with asthma and symptoms requiring regular anti-inflammatory therapy ( n = 326 ) were r and omly assigned to LTRAs ( n = 162 ) or ICS ( n = 164 ) . The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Question naire , per point improvement in the Asthma Control Question naire and per QALY gained from the UK NHS and societal perspectives . RESULTS Over 2 years , re source use was similar between the two treatment groups , but the cost to society per patient was significantly higher for the LTRA group , at pounds sterling 711 versus pounds sterling 433 for the ICS group ( adjusted difference pounds sterling 204 ; 95 % CI 74 , 308 ) [ year 2005 values ] . Cost differences were driven primarily by differences in prescription drug costs , particularly study drug costs . There was a nonsignificant ( imputed , adjusted ) difference between treatment groups , favouring ICS , in QALYs gained at 2 years of -0.073 ( 95 % CI -0.143 , 0.010 ) . Therapy with LTRAs was , on average , a dominated strategy , and , at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained , the probability of LTRAs being cost effective compared with ICS was approximately 3 % from both societal and NHS perspectives . CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK , at 2005 values , compared with ICS for initial asthma controller therapy . TRIAL REGISTRATION UK National Research Register N0547145240 ; Controlled Clinical Trials IS RCT N99132811 BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness -- in a real-life primary -care setting --of leukotriene receptor antagonists ( LTRAs ) and long-acting beta2 adrenergic receptor agonists ( beta2 agonists ) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids ( ICS ) . OBJECTIVE To estimate the cost effectiveness of LTRAs compared with long-acting beta2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS . METHODS An economic evaluation was conducted alongside a 2-year , pragmatic , r and omized controlled trial set in 53 primary -care practice s in the UK . Patients aged 12 - 80 years with asthma insufficiently controlled with ICS ( n = 361 ) were r and omly assigned to add-on LTRAs ( n = 176 ) or long-acting beta2 agonists ( n = 185 ) . The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Question naire ( MiniAQLQ ) , per point improvement in the Asthma Control Question naire ( ACQ ) and per QALY gained from perspectives of the UK NHS and society . RESULTS Over 2 years , the societal cost per patient receiving LTRAs was pounds sterling 1157 versus pounds sterling 952 for long-acting beta2 agonists , a ( significant , adjusted ) increase of pounds sterling 214 ( 95 % CI 2 , 411 ) [ year 2005 values ] . Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs ( 95 % CI -0.077 , 0.103 ) . The incremental cost per QALY gained from the societal ( NHS ) perspective was pounds sterling 22,589 ( pounds sterling 11,919 ) . Uncertainty around this point estimate suggested that , given a maximum willingness to pay of pounds sterling 30,000 per QALY gained , the probability that LTRAs are a cost-effective alternative to long-acting beta2 agonists as add-on therapy was approximately 52 % from both societal and NHS perspectives . CONCLUSIONS On balance , these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting beta2 agonists as add-on therapy to ICS for asthma . However , there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs . TRIAL REGISTRATION UK National Research Register N0547145240 ; Controlled Clinical Trials IS RCT N99132811 BACKGROUND Cost-effectiveness analyses of asthma controller regimens for adults exist , but similar evaluations exclusively for children are few . OBJECTIVE We sought to compare the cost-effectiveness of 2 commonly used asthma controllers , fluticasone and montelukast , with data from the Pediatric Asthma Controller Trial . METHODS We compared the cost-effectiveness of low-dose fluticasone with that of montelukast in a r and omized , controlled , multicenter clinical trial in children with mild-to-moderate persistent asthma . Analyses were also conducted on subgroups based on phenotypic factors .  Effectiveness measures included ( 1 ) the number of asthma-control days , ( 2 ) the percentage of participants with an increase over baseline of FEV(1 ) of 12 % or greater , and ( 3 ) the number of exacerbations avoided . Costs were analyzed from both a US health care payer 's perspective and a societal perspective . RESULTS For all cost-effectiveness measures studied , fluticasone  cost less and was more effective than montelukast . For example , fluticasone treatment cost $ 430 less in mean direct cost ( P < .01 ) and result ed in 40 more asthma-control days ( P < .01 ) during the 48-week study period . Considering sampling uncertainty , fluticasone cost less and was more effective at least 95 % of the time . For the high exhaled nitric oxide ( eNO ) phenotypic subgroup ( eNO ≥25 ppb ) and more responsive PC(20 ) subgroup ( PC(20 ) < 2 mg/mL ) , fluticasone was cost-effective compared with montelukast for all cost-effectiveness measures , whereas not all the effectiveness measures were statistically different for the other 2 phenotypic subgroups . CONCLUSION For children with mild-to-moderate persistent asthma , low-dose fluticasone had lower cost and higher effectiveness compared with montelukast , especially in those with more airway inflammation , as indicated by increased levels of eNO and more responsivity to methacholine
Objective The objective of this article was to summarize the findings of all the available studies on alternative pharmacological treatments for asthma and assess their method ological quality , as well as to identify the main drivers of the cost effectiveness of pharmacological treatments for the disease .