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Cost-Effectiveness of Fluticasone
Propionate Administered Via Metered-Dose
Inhaler Plus Babyhaler™ Spacer in the
Treatment of Asthma in Preschool-Aged
Hans Bisgaard, MD; Martin J. Price, PhD; Claire Maden, MSc; and Niels A. Olsen, MSc 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 !g/d and 200 !g/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 !g/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
> 25% improvement in cough symptoms (57.9% vs 39.0%; p " 0.018). The costs per exacerbation-
free patient, per patient with a > 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 !g/d,
were achieved at a lower overall cost compared with placebo treatment.
Conclusions: From the perspective of the Danish health-care system, FP, 100 !g bid, administered via
the Babyhaler inhalation device was cost-effective relative to standard therapy with bronchodilators
(CHEST 2001; 120:1835–1842)
Key words: asthma; cost effectiveness; fluticasone propionate; preschool children
Abbreviations: CI ! confidence interval; DK ! Danish kroner; FP ! fluticasone propionate; ICER ! incremental cost-
effectiveness ratio Inhaledcorticosteroidsarethemosteffectivelong- pediatric asthma guidelines13 now recommend the
term control medication for asthma and are there- use of low-dose inhaled corticosteroids for the treat- fore the mainstay of treatment for the management ment of asthma during early childhood.
of the disease in both adults and children.1–3 These agents have been shown to improve lung function For editorial comment see page 1762
and reduce symptoms in children with asthma.4–12 In A randomized, placebo-controlled trial evaluated accordance with these findings, both the British the efficacy and tolerability of fluticasone propionate Thoracic Society guidelines1 and the recent US (FP) [Flixotide; Glaxo Wellcome; Middlesex, UK] *From the Copenhagen University Hospital (Dr. Bisgaard), This study was sponsored by Glaxo Wellcome (protocol reference Rigshospitalet, Copenhagen, Denmark; Global Health Outcomes (Dr. Price), Glaxo Wellcome Research and Development, Mid- Manuscript received November 6, 2000; revision accepted July 7, 2001.
dlesex, UK; Respiratory Therapeutic Development (Ms. Maden), Correspondence to: Hans Bisgaard, MD, Professor of Paediatrics, Glaxo Wellcome Research and Development, Uxbridge, UK; and Copenhagen University Hospital, Rigshospitalet, DK-2100 Glaxo Wellcome (Mr. Olsen), Brondby, Denmark.
Copenhagen, Denmark; e-mail: [email protected] CHEST / 120 / 6 / DECEMBER, 2001 by guest on March 20, 2010 2001 American College of Chest Physicians administered via a metered-dose inhaler using the Materials and Methods Babyhaler (Glaxo Wellcome) spacer device in chil-dren aged 12 to 47 months.11 FP, 200 "g/d, pro- Study Design duced improvements in terms of asthma exacerba- This was a retrospective economic analysis based on clinical tions, symptoms, and parental satisfaction with data from a 12-week, multicenter (33 centers in nine countries), treatment, providing support for the use of inhaled randomized, double-blind, parallel-group, placebo-controlled corticosteroid therapy in young children.
trial assessing the efficacy and safety of FP in children aged 12 to When considering whether to prescribe a new 47 months.11 FP, 50 "g (two puffs of 25 "g); FP, 100 "g (two puffs of 50 "g); or placebo were administered twice daily via a treatment, it is important to identify whether it is an metered-dose inhaler delivered through a Babyhaler spacer efficient use of health-care resources. This is accom- device. Patients were eligible for inclusion in the clinical trial if plished by evaluating net changes in both costs and they had a documented history of recurrent wheeze or asthma outcomes through economic evaluation. This is par- symptoms. Patients were randomized to study treatment if they demonstrated asthma symptoms or required relief salbutamol ticularly important in pediatric asthma because the treatment on at least 7 days of the 14-day run-in period. Those burden of this condition on the patient, caregiver, patients who had received treatment with inhaled or systemic and health-care system is high. Childhood asthma corticosteroids or methylxanthine in the 2 weeks prior to the can have a profound effect not only on the child but run-in period, or who had required any change to their asthma medication were excluded. Patients were also excluded if they also on the parents/caregivers in terms of distressing had been hospitalized for asthma or had received a course of respiratory symptoms, sleep disturbance, inability to antibiotics for a chest infection during this 2-week period.
undertake normal play or social activities, and time Salbutamol was used throughout the study as relief medication.
Children could continue to receive any regular medication, lost from school or work.14 In addition to negative including sodium cromoglycate, ketotifen, and/or antihistamines effects on quality of life, childhood asthma can be throughout the trial, provided the dose remained constant.
associated with substantial economic costs.15,16 Fur- Inhaled or systemic corticosteroids, anticholinergic medications, thermore, Smith et al15 estimated that preschool nedocromil sodium, #2-agonists (other than salbutamol rescue medication) and methylxanthines were not permitted during the asthma accounted for 369,000 bed days in the trial, unless used for the management of an asthma exacerbation.
United States annually, and the associated cost to Patients were assessed for adverse events, asthma exacerba- care for these children was $18.5 million (US dol- tions, and treatment compliance every 3 weeks during the lars); the direct costs of medication and hospitaliza- 12-week treatment period. Parents kept daily diary records of their child's symptoms, recording daytime and nighttime scores tion in this age group were estimated at $48.1 million for wheeze, cough, and shortness of breath on a scale of 0 to 3.
and $586.2 million, respectively. The costs for med- Parents were also asked to record daytime and nighttime use of ication and hospitalization represented 6.1% and rescue salbutamol and the number of occasions they were 74.1% of the total direct costs, respectively. This awoken at night because of their child's asthma symptoms.
Patients were withdrawn from the study if more than one contrasts with the asthma population as a whole, for exacerbation occurred that required additional treatment with which hospital costs typically represent a smaller oral or inhaled corticosteroids, or if symptoms became unaccept- proportion of overall direct costs than medication able or poorly controlled despite backup medication (short costs (20 to 25% and 37%, respectively).17 course of oral or inhaled corticosteroids).
Improving asthma control through effective inter- The study was conducted in accordance with good clinical practice and the Declaration of Helsinki, and was approved by vention is desirable from both clinical and economic the local ethics committee at each center. Written informed viewpoints. In Denmark, the rate of hospital admis- consent to participate in the study was obtained from the sions for pediatric asthma remained relatively con- parent/guardian of each patient.
stant between 1978 and 1993, despite a general increase in asthma prevalence.18 Importantly, during this period, the risk of hospital readmission fell by about one half. These data coincided with an im- A number of outcome measures were used to determine treatment effectiveness for the purpose of the economic analysis.
provement in the treatment of pediatric asthma in These included the proportion of patients remaining free of Denmark, as a result of the increased emphasis on asthma exacerbations throughout the study, improvement in early treatment with anti-inflammatory drugs.
cough and wheeze symptoms, and symptom-free days.
In light of the burden of pediatric asthma, it is An asthma exacerbation was defined as a worsening of the important to assess whether treatment interventions child's asthma symptoms that required either a change in medi- cation (other than relief salbutamol) and/or required the parents can reduce health-care resource utilization and im- to contact their general practitioner or the investigator. The prove clinical outcomes. The purpose of the present proportions of patients who either experienced an exacerbation, analysis was to evaluate whether adding the inhaled or remained free of exacerbations throughout the trial were corticosteroid FP to the treatment of asthma in calculated for each treatment arm. Patients who withdrew pre- maturely from the study for reasons other than an asthma preschool children is a cost-effective treatment in- exacerbation, and who had not previously experienced an asthma exacerbation, were excluded from the analysis. This was because Clinical Investigations by guest on March 20, 2010 2001 American College of Chest Physicians it was impossible to predict whether or not the patient would treatments and calculate additional expenditure required to have had an exacerbation if they had remained in the trial.
achieve additional health gains with a treatment relative to the The proportion of patients achieving a ! 25% improvement in comparator. This produces a better understanding of the true the median frequency of cough-free and wheeze-free days value of a new treatment, and so ICERs are more meaningful to compared to baseline was determined. For patients who with- health-care decision makers than mean cost-effectiveness ratios drew early from the study, the percentage of cough-free and as they more accurately reflect the types of treatment decisions wheeze-free days was calculated from the number of days they that must be undertaken in the real world.
were in the study. A symptom-free day was defined as a 24-h period during which the patient reported no daytime or night- time symptoms (score of 0 for cough, wheeze, and shortness of breath during the day and night).
Patients withdrawn from the study were assumed to have Data from the intent-to-treat population were used in the experienced no symptom-free days from the time of withdrawal statistical analysis. Between-treatment differences in the effec- until the end of the study if withdrawn due to asthma-related tiveness parameters were calculated using the van Elteren exten- adverse events or lack of efficacy. Patients withdrawn for other sion to the Wilcoxon rank sum test. Statistical tests were two sided, and all treatment comparisons were pairwise comparisons.
eg, unavailable for follow-up or unrelated adverse events) were assumed to have symptom-free days at the mean For analyses, p $ 0.05 was considered to be significant. Confi- rate equivalent to the treatment arm as a whole.
dence intervals for the ICERs were calculated using a nonpara- metric "bootstrap" method.22 To achieve this, 1,000 bootstrap resamples of the original cost/effect pairs were generated by Evaluation of Costs of Asthma Management taking a random sample from each treatment arm with replace- ment from the original data, and the ICERs were calculated for The economic analysis was conducted from the perspective of all the bootstrap resamples. The 95% confidence intervals (CIs) the Danish health-care system. Calculation of the direct costs of were calculated by ranking the bootstrap resamples from least asthma management were based on resources consumed by cost-effective to most cost-effective and selecting the values patients in the intent-to-treat population during the 12-week corresponding to the 26th and 975th points.
treatment phase of the study. Information on asthma-related direct health-care resource use was collected during the study using serious adverse event forms, concurrent medications forms, exacerbation data, and daily diary card data.
The following resource use data were collected and included in A range of sensitivity analyses was used to test underlying the cost analysis: hospital contacts (emergency department visits, assumptions in the economic analysis. For exacerbation-free inpatient hospital days), general practitioner contacts, the cost of patients, the impact of differences in effectiveness between the the Babyhaler device (included in the FP treatment arms only treatment arms was assessed using two scenarios for patients and not the placebo arm) and medications (study drugs, rescue withdrawn from the study (for reasons other than an asthma medications, concurrent prescription drugs related to the treat- exacerbation). The first scenario assumed that these patients had ment of asthma, asthma exacerbations, or treatment of adverse not experienced an exacerbation (classified as an exacerbation- effects). All visits included in the cost analysis were "unsched- free patient), and the second scenario assumed that these uled." Therefore, health-care contacts related to the study pro- patients had experienced an exacerbation. Such an analysis helps tocol and routine clinic visits associated with regular asthma to establish the limits that assumptions regarding patient with- management were excluded from the cost analysis.
drawals will have on the final results. Similarly, the sensitivity Unit costs of health-care services were derived from published analysis for symptom-free days was performed using two scenar- sources and quoted at 1999 prices in Danish kroner (DK).
ios. The first assumed that all days subsequent to premature Daily costs of medications were calculated using the cost to the withdrawal from the study were symptom free; the second pharmacist. Mean direct asthma treatment costs were calculated assumed that all days subsequent to premature withdrawal were for all patients in each treatment arm. When patients were not symptom free. For improvement in cough and wheeze, a withdrawn from the study, they were assigned a constant mean sensitivity analysis was conducted by redefining the percentage daily cost following withdrawal ( ie, the mean daily cost for the ! 50% and ! 75% (the base-case analysis was treatment arm during the study period). For ease of interpreta- tion, key cost data have been converted into approximate dollar and pound values as of November 1999 exchange rates.
Economic Analysis A total of 314 patients were recruited to the study, The mean cost-effectiveness ratio provides an indication of the and 237 patients were randomized to treatment average cost of achieving a given outcome with each treatment.
(intent-to-treat population). The main reasons for This was calculated by dividing the mean daily direct cost by the withdrawal prior to randomization were asthma ex- rate of success for each treatment (eg, exacerbation-free patients, improvement in wheeze and cough symptoms, and symptom-free acerbations or insufficient asthma symptoms. Demo- days). For example, for exacerbation-free patients, the mean graphic and baseline characteristics were compara- cost-effectiveness ratio was calculated by dividing the mean daily ble in the three treatment groups (Table 1).
direct cost by the proportion of exacerbation-free patients at the The clinical results showed that compared with end of treatment. Incremental cost-effectiveness ratios (ICERs) placebo, FP, 200 "g/d, produced a significant im- were calculated by dividing the difference in the mean daily direct health-care costs between the treatment groups by the provement from baseline in 8 of 10 diary card difference in the rate of success for each treatment. ICERs parameters (including days without any symptoms evaluate the net change in both cost and effectiveness between [wheeze, cough, shortness of breath], days without CHEST / 120 / 6 / DECEMBER, 2001 by guest on March 20, 2010 2001 American College of Chest Physicians Table 1—Demographic and Baseline Characteristics*
Patients, No.
Family history of asthma No exacerbations in the Use of one or more asthma medications in the monthprior to randomization *Data are presented as mean (SD) or No. (%) unless otherwise cough, nights without breathlessness, days and nights Figure 1. Summary of the effectiveness of placebo and both FP without wheeze or salbutamol, and sleep distur- dosages, 100 "g/d and 200 "g/d, in preschool children with bance; p $ 0.05).11 There was a significant reduction asthma. *p $ 0.03 vs placebo.
in 5 of the 10 parameters with FP, 100 "g/d, compared with placebo treatment (p $ 0.05). There were no significant differences between the two FP compared with six visits in the placebo group. More- groups. FP was well tolerated, with no differences in over, there were twice as many general practitioner the safety profile noted between the active treatment visits in the placebo group than in the FP, 200 "g/d, and placebo groups.
group (Table 2).
When drug treatment costs were also considered, the mean total direct health-care costs per patient The proportion of exacerbation-free patients was per day were lower in both FP-treated groups than significantly higher in the FP, 200 in the placebo-treated group (Fig 2): 13.85 DK "g/d, group than in the placebo-treated group (p ($1.73 [US]; " 1.17 DK), 14.39 DK ($1.80 [US]; ! 0.025), as was the proportion of patients with a " 1.22 DK), and 20.81 DK ($2.60 [US]; " 1.76 DK) ! 25% improvement in cough symptoms (p in the FP, 100 "g/d; FP, 200 "g/d; and placebo ! 0.018; Fig 1). The proportion of patients with a groups, respectively. Although medication costs were ! 25% improvement in wheeze symptoms and the proportion of symptom-free days higher in the FP arms than in the placebo-treated also favored the FP, 200 group, these costs were more than offset by lower "g/d, group, but did not reach statistical significance compared with placebo costs for hospital contacts and general practitioner treatment. Although there were trends in favor of visits in the active treatment arms. Overall costs were slightly higher in the FP, 200 "g/d, group than in the "g/d, over placebo treatment for three of the effectiveness end points (exacerbations, cough FP, 100 "g/d, group. This was due to higher study and wheeze), none of the differences reached the drug costs with the higher FP dose.
threshold for statistical significance (Fig 1). There were no significant differences in effectiveness end points between the two FP groups, although there Table 2—Summary of Asthma-Related Health-Care
were trends in favor of the higher dose (200 "g/d).
Resource Utilization (Excluding Medications) During
the 12-wk Treatment Period*
Use of Health-Care Resources Health-care resource utilization (excluding medi- Health-Care Resource Utilization (n ! 76) (n ! 82) cations) is summarized in Table 2. The number of Hospital contacts hospitalizations, emergency department visits, and Accident and emergency visits general practitioner contacts were lower in both the FP groups than in the placebo group. There were no General practitioner visits emergency department visits in either FP group *Data are presented as No.
Clinical Investigations by guest on March 20, 2010 2001 American College of Chest Physicians differences were found for FP, 200 "g/d, compared with placebo treatment for the exacerbation-free patient and improvement in cough symptoms end points. For both endpoints, the range of the 95% CIs were negative, indicating that the additional benefits with FP were achieved at a lower overall cost compared with the placebo arm with 95% certainty (Table 3). This indicated that using FP, 200 "g/d, in this group of patients not only improved outcomes but also reduced asthma management costs. ICERs for the other comparisons that failed to demonstrate a statistically significant between-group difference in effectiveness are presented for illustrative purposes Figure 2. Direct asthma treatment costs per patient per day over 12 weeks. Patients withdrawn from the study were assumed to only, as ICERs are not generally reported for non- continue to use resources at the same mean rate as those patients still in the trial in their respective treatment arm.
While there were no statistically significant differ- ences between the FP-treatment groups with respect to exacerbations, improvement in cough/wheeze, and symptom-free days, it is clear that from an The mean costs per exacerbation-free patient, per economic perspective, FP, 200 "g/d, is more cost- effective than FP, 100 "g/d. Although asthma man- ! 25% improvement in cough or wheeze symptoms, and per symptom-free day were consistently lower agement costs with FP, 100 "g/d, were lower than for both FP dosages (100 with placebo treatment and similar to FP, 200 "g/d, "g/d and 200 "g/d) than for placebo (Table 3), indicating that clinical benefits there were no significant differences in treatment with FP were consistently achieved at lower mean effectiveness relative to placebo, and so the net costs than with placebo (Table 3).
health gains demonstrated with the higher dose were ICERs were calculated to determine the addi- not realized with the lower dose. This result is tional health-care costs that must be paid to achieve consistent with the clinical findings.11 additional benefits with FP. These are summarized in Table 3. ICERs can only be meaningfully inter- preted for end points that have demonstrated a The data obtained were robust to changes in statistically significant difference in effectiveness be- underlying assumptions across a range of sensitivity tween treatment groups. In this study, significant analyses. Effectiveness results for the proportion of Table 3—Mean Cost-Effectiveness Ratios and ICERs
Cost per exacerbation-free patient* (US) Treatment vs placebo % 46.1 (% 294.0, % 19.0) FP 200 "g vs FP 100 "g Cost per ! 25% improvement in cough symptoms* (US) Treatment vs placebo % 34.0 (% 131.6, % 17.9) FP 200 "g vs FP 100 "g Cost per ! 25% improvement in wheeze symptoms (US) 106.7 DK ($13.15) Treatment vs placebo FP 200 "g vs FP 100 "g Cost per symptom-free day (US) Treatment vs placebo FP 200 "g vs FP 100 "g *Significant differences were found for FP, 200 "g/d, compared with placebo for the exacerbation-free patient and improvement in cough symptoms end points, and therefore CIs calculated around the ICER are reported. ICERs for the other comparisons that failed to demonstratea between-group difference in effectiveness (improvement in wheeze and symptom-free day) are reported for illustrative purposes only, and CIsfor these end points are not presented.
CHEST / 120 / 6 / DECEMBER, 2001 by guest on March 20, 2010 2001 American College of Chest Physicians Table 4—Sensitivity Analyses for Effectiveness Parameters*
Dropouts are exacerbation free Dropouts with exacerbation Improvement in cough symptoms ! 50% improvement ! 75% improvement Improvement in wheeze symptoms ! 50% improvement ! 75% improvement Symptom-free days Symptom-free days after study withdrawal No symptom-free days after study withdrawal *Data are expressed as mean proportions of patients (%) except for symptom-free days, which are presented as mean percentage of days.
exacerbation-free patients remained similar to the "g/d, group experienced a ! 25% improvement in base-case scenario (patients withdrawn for reasons the frequency of asthma cough symptoms. There other than an asthma exacerbation were excluded were no significant improvements in effectiveness in from the analysis) when patients who were prema- the FP, 100 "g/d (50 "g bid), group compared with turely withdrawn were assumed to be exacerbation- the placebo group, although the overall costs of free or to have had an exacerbation (Table 4).
treatment were still lower than in the placebo arm.
Similarly, effectiveness results remained consistently In both FP groups, health-care resource utilization in favor of FP, 200 "g/d, vs placebo treatment when was lower than that in the placebo arm, both in terms the proportion of patients achieving a ! 50% im- of primary care and secondary care contacts.
provement in cough symptoms and wheeze symp- In this study, the incremental cost-effectiveness toms was calculated. The differences between the analysis showed that FP, 200 "g/d, resulted in three treatment groups became smaller when the improved asthma control in terms of cough and proportions of patients achieving a ! 75% improve- incidence of exacerbations and was cost-saving rela- ment in wheeze and cough symptoms were deter- tive to placebo treatment (plus treatment with a mined, owing to a diminished number of patients short-acting #2-agonist when required). The study achieving this level of improvement (Table 4).
Sensitivity analyses performed on the ICERs showed that FP, 200 "g/d, remained consistently cost-saving relative to placebo treatment over a wide Table 5—Sensitivity Analysis for ICERs for the
range of assumptions. The results demonstrated that Exacerbation-Free Patient Outcome Measure*
the base-case assumption was rigorous, as there was always a trend in favor of the FP groups, regardless of the assumption used. Data from the sensitivity Using base-case costs analysis for the ICERs for the exacerbation-free Assuming dropouts to be outcome measure are presented in Table 5.
Treatment vs placebo FP, 200 "g vs FP, 100 "g Assuming dropouts to have had an This study showed that the improvement in Treatment vs placebo FP, 200 "g vs FP, 100 "g asthma outcomes achieved during treatment with Using sensitivity analysis costs inhaled FP, 200 "g/d (100 "g bid) via a metered- Assuming dropouts to be dose inhaler using the Babyhaler spacer device can lead to lower overall asthma management costs. This Treatment vs placebo was primarily the result of a lower proportion of FP, 200 "g vs FP, 100 "g Assuming dropouts to have had an patients experiencing asthma exacerbations, which can be costly to manage. In addition to a higher Treatment vs placebo proportion of exacerbation-free patients, a signifi- FP, 200 "g vs FP, 100 "g cantly greater number of patients in the FP, 200 *Data are presented as DK.
Clinical Investigations by guest on March 20, 2010 2001 American College of Chest Physicians did not differentiate explicitly between the two subjects, the study was relatively small. Similar find- doses, and this was not the primary objective of the ings were also reported in another study in older economic evaluation. The primary objective was to children (aged 7 to 16 years) in which treatment with assess whether adding FP to the treatment of asthma an inhaled corticosteroid plus bronchodilator re- patients aged 12 to 47 months receiving rescue sulted in lower overall costs and better clinical salbutamol and controller medications (regular so- outcomes than treatment with a bronchodilator dium cromoglycate, ketotifen, and/or antihistamines) alone.25 Both of these studies demonstrate that is cost-effective. A secondary objective was to eval- inhaled corticosteroid therapy improves outcomes uate which dose was most cost-effective, although and reduces asthma management costs in children.
the primary clinical analysis had already demon- These findings are consistent with those from the strated that FP, 200 "g/d, is more effective than FP, current study, which represents the first large-scale 100 "g/d.11 The economic analysis supports this economic evaluation of inhaled corticosteroids in this finding, with FP, 200 "g/d, demonstrating cost reductions and improved effectiveness. The lack of There are a number of limitations to this study that improved effectiveness with FP, 100 "g/d, despite need to be considered. The clinical study on which lower costs indicates that this dose is less cost- the economic analysis was based was of short dura- tion, which may underestimate the true long-term Improvements in the diagnosis of asthma in pre- economic consequences of poor asthma control. In school children and a better understanding of which particular, the cost of hospitalization, a rare but patients most benefit from inhaled corticosteroid expensive event, may have been underestimated.
therapy could produce even greater economic ben- Furthermore, this was a retrospective analysis and efits with FP. One study23 reported that children patients were not followed up after premature with- with frequent asthma symptoms (symptoms on ! 3 drawal from the study, so it was necessary to make a days per week or ! 21 days of symptoms over a number of assumptions about resource use and 4-week period) and those with a family history of outcomes during these periods. It is possible that asthma showed a greater response to treatment with these patients could have been the most severe FP, 200 "g/d, compared with placebo than children asthmatics, and therefore the true economic benefits with less frequent symptoms or no family history of of treatment may have been underestimated. How- asthma, in terms of a greater increase in symptom- ever, despite these limitations, this study provides free days and a greater reduction in exacerbations.
further evidence of the economic value of inhaled Future studies should attempt to characterize those corticosteroid therapy in preschool children. Further patients who are more likely to respond to treatment.
large-scale, long-term studies would be beneficial to It is possible that pharmacogenetics will enable us to predict which patients are most likely to respond to further validate the findings of this and other eco- inhaled corticosteroid therapy.
nomic studies in this age group.
Because all patients could continue receiving their In conclusion, the results of this study suggest that regular asthma treatment(s), this study demonstrates in children aged 12 to 47 months with a history of that adding an inhaled corticosteroid to existing asthma symptoms, FP, 100 "g bid, administered via asthma therapy is a cost-effective strategy in pre- the Babyhaler spacer device is a well-tolerated, school children, relative to their usual controller cost-effective management strategy, from the per- medication alone. This study also illustrates the very spective of the Danish health-care system. Thus, high burden of asthma in this age group. During this there is both clinical and economic rationale for 12-week study, there were nine hospitalizations, 6 using inhaled corticosteroids for asthma therapy in emergency department visits, and 66 unscheduled this age group.
primary-care visits as a result of the children's asthma. This emphasizes the importance of focusing ACKNOWLEDGMENT: The authors thank the following phy- sicians who participated in and randomized patients into this on reducing asthma exacerbations in children from a study: Belgium, Dr. C. de Boeck, Dr. A. Malfroot, Dr. H. Van health-care system perspective, as well as taking into Bever; Canada, Dr. D. Berube, Dr. S. Feanny, Dr. M. Gold, Dr.
account the impact of such events on the quality of S. Lavi, Dr. B. Lyttle, Dr. M. Montgomery; Denmark, Dr. K.
life of the patients and their families.
Ibsen; Ireland, Dr. P. Greally, Dr. D. Lillis, Dr. M. Taylor; New Zealand, Dr. J. Brown; Poland, Prof. J. Alkiewicz; Prof. D.
There have been few economic analyses of asthma Chmielewska, Dr. J. Gillies, Prof. R. Kurzawa; South Africa, Dr.
treatments in preschool children. Connett et al24 C. Bester, Dr. M. Groenewald, Dr. D. Luyt, Dr. A.I. Manjra; concluded that budesonide was cost-effective in Spain, Dr. J. Botey, Dr. A. Escribano, Dr. G. Ferres, Dr. M.
terms of improvement in asthma symptom control in Navarro, Dr. E. Gonzalez Perez-Yarza; United Kingdon, Dr.
J. Carter, Prof. A. Milner, Dr. A. Speight, Dr. D.A. Spencer.
children aged 1 to 3 years, although with only 40 Thanks are also due to Lisa Williams for the statistical analysis.
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Metered-Dose Inhaler Plus Babyhaler
Spacer in the Treatment of
Asthma in Preschool-Aged Children
Hans Bisgaard, Martin J. Price, Claire Maden and Niels A. Olsen Chest 2001;120; 1835-1842 March 20, 2010
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