human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 . METHO 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 . METHO 
    Output:
    