|Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma
|Bruggenjurgen B, Selim D, Kardos P, Richter K, Vogelmeier C, Roll S, Meyer-Sabellek W, Buhl R, Willich S
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
Two strategies for the treatment of asthma were examined, adjustable maintenance versus fixed treatment. Both strategies were based on a combination of budesonide and formoterol in a single inhaler. Fixed dosing consisted of two inhalations of budesonide/formoterol (160 microg/4.5 microg) twice daily. Adjustable maintenance dosing consisted of one inhalation of budesonide/formoterol (160 microg/4.5 microg) twice daily, with the possibility to step up to two or four inhalations twice daily in the case of asthma worsening for 12 weeks. The criteria for stepping up or down were clearly described.
Economic study type
The study population comprised patients who had a history of at least 6 months of mild-to-moderate perennial asthma, according to American Thoracic Society criteria, and who were symptomatic despite inhaled corticosteroid pre-treatment.
The setting was secondary care. The economic study was carried out in Germany.
Dates to which data relate
The effectiveness and resource use data were derived from a study published in 2004. The price year was 2001 (but hospital costs were valued using 2000 costs).
Source of effectiveness data
The effectiveness evidence was derived from a single study.
Link between effectiveness and cost data
The costing was carried out prospectively on the same sample of patients as that used in the effectiveness analysis.
Limited information on the design and other characteristics of the primary study were reported as the effectiveness study had already been published. There were 1,679 patients (56.8% female) in the adjustable maintenance group and 1,618 patients (56.0% female) in the fixed group. The mean age of the patients was 37.3 (+/- 10.2) years (age range: 16 - 87) in the adjustable maintenance group and 37.6 (+/- 10.0) years (age range: 17 - 78) in the fixed group.
This was a prospective, randomised, open-label, parallel-group study that was carried out in 1,051 centres in Germany. All patients received run-in treatment (two inhalations of 160 microg budesonide/4.5 microg formoterol twice daily in a single inhaler) for 4 weeks to gain control of their asthma symptoms. After run-in, the patients were randomised to two study groups. The length of follow-up was 12 weeks. A total of 260 patients discontinued the study, 133 in the adjustable-dosing group and 127 in the fixed-dosing group.
Analysis of effectiveness
The analysis of the clinical study was conducted on an intention to treat basis. The primary outcome measure was the change in overall score of the standardised version of the Asthma Quality of Life Questionnaire (AQLQ(S)) from randomisation (week 0) to the end of the study (week 12). The minimum change in AQLQ(S) score for which health-related quality of life improvements were considered clinically relevant was 0.5 units. A secondary outcome measure was the percentage of symptom-free days (SFDs). An SFD was defined as no day- or night-time patient-reported symptoms. A sub-group analysis was also performed in which the patients were categorised into two strata of asthma severity. The two strata were peak expiratory flow (PEF) 60% to less than 80% predicted normal (moderate asthma) and PEF at least 80% predicted normal (mild asthma) at visit 1 (enrolment). The study groups were comparable at baseline in terms of their demographic and clinical characteristics.
Small improvements in the AQLQ(S) overall score occurred in both treatment groups. The mean change was 0.18 (+/- 0.67) in the adjustable-dosing group and 0.20 (+/- 0.70) in the fixed-dosing group. No statistically significant difference between the groups was observed. Similar results were obtained in the two sub-group analyses.
The mean percentage of SFDs was 48% with adjustable maintenance dosing and 49% with fixed dosing. Similar values were recorded in the individual strata. Patients in the PEF >/= 80% group experienced slightly more SFDs (51% adjustable maintenance dosing and 50% fixed dosing; difference not significant) than those in the PEF 60 to 80% group (46% adjustable maintenance dosing and 49% fixed dosing; p<0.05).
The clinical analysis showed that adjustable maintenance dosing and fixed dosing were equally effective in maintaining health-related quality of life.
Measure of benefits used in the economic analysis
No summary benefit measure was used as no statistically significant difference between the groups, in terms of clinical outcomes, was observed. In effect, a cost-minimisation analysis was carried out.
The cost analysis was carried out from a societal perspective, and the direct costs were assessed using the point of view of the health insurer. The health services included in the economic analysis were study medications, relief medications, hospital stay, doctor visits, home visits by a doctor, emergency visit to a doctor, and telephone contact with either a doctor or medical staff. Although the unit costs were presented, information on resource use was not provided for all items. Resource use was estimated with data derived from the clinical trial using case report forms. The costs were estimated on the basis of several different but publicly available sources in Germany and expert opinion. Discounting was not relevant given the short timeframe of the analysis. The price year was 2001 but the hospital costs were based on 2000 values.
Statistical analysis of costs
The differences in cost categories and total costs between the treatment groups were analysed by a non-parametric, Wilcoxon two-sample test. The analysis of the cost data was based on the intention to treat population considered in the clinical trial. Missing data were imputed.
The indirect costs (i.e. days of sick leave) were appropriately included in the analysis as a societal perspective was adopted. The unit cost of a day of sick leave, which was estimated from the average daily gross income for an employed person in Germany, was reported. The number of days off work was not reported. The estimation of resources was based on data derived from the clinical trial. The price year was 2001.
Sensitivity analyses were not performed.
Estimated benefits used in the economic analysis
See the 'Effectiveness Results' section.
From a societal perspective, the average asthma-related costs per patient were Euro 277 (+/- 964) (median costs Euro 158) with adjustable maintenance dosing and Euro 340 (+/- 991) (median costs Euro263) with fixed dosing, (p<0.001).
In the stratum with PEF 60% to less than 80%, the average asthma-related costs per patient were Euro 285 (+/- 1,012) (median costs Euro 154) with adjustable maintenance dosing and Euro 361 (+/- 1,009) (median costs Euro 263) with fixed dosing, (p<0.001).
In the stratum with PEF at least 80%, the average asthma-related costs per patient were Euro 259 (+/- 886 (median costs Euro 155) with adjustable maintenance dosing and Euro 314 (+/- 778) (median costs Euro 263) with fixed dosing, (p<0.001).
A similar pattern was observed when the total overall (asthma-related and non-asthma-related) costs per patient were considered. The adjustable-dosing group was associated with significantly lower total costs and total direct costs, (p<0.001), mainly because patients in this group took fewer daily inhalations of budesonide/formoterol than those in the fixed-dosing group (mean 2.63 versus 3.82 inhalations; p<0.001).
Synthesis of costs and benefits
A synthesis of the costs and benefits was not relevant since a cost-minimisation analysis was performed.
From the perspective of society in Germany, adjustable maintenance dosing with budesonide and formoterol in a single inhaler maintained health-related quality of life in adult patients with asthma at a significantly lower cost than fixed dosing. This conclusion held in sub-groups of patients with asthma.
CRD COMMENTARY - Selection of comparators
The authors justified the choice of the interventions examined in the study, which appear to have been appropriate for the study question. The dosages were accurately reported. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The effectiveness evidence came from a published clinical trial, which was appropriate for the study question. Such a trial usually ensures a high internal validity of the clinical evidence. Although limited information on the clinical trial was provided, as the study had already been published, the robustness of the analysis was high because of several characteristics of the study. In particular, the large sample of patients included in the analysis, the sub-group analysis, the use of intention to treat to deal with loss to follow-up, the baseline comparability of the study groups, and the use of a randomised design. Blinding was not performed because of the nature of the interventions. These issues enhance the internal validity of the analysis. The authors stressed that the clinical trial was characterised by a naturalistic, real-life design with open-label treatment, minimally restrictive inclusion and exclusion criteria and protocol requirements, and a large population of patients. Thus, the results of the trial are likely to be widely applicable to the treatment of asthma patients in everyday clinical practice.
Validity of estimate of measure of benefit
No summary benefit measure was used in the analysis because a cost-minimisation analysis was conducted. Please refer to the comments in the 'Validity of estimate of measure of effectiveness' field (above).
Validity of estimate of costs
The choice of a societal perspective for the analysis of the costs was appropriate. All the relevant categories of costs were included in the analysis. The indirect costs were estimated on the basis of average wages in Germany. The unit costs were reported for all items, whereas information on resource use was less comprehensive. The source of the costs was reported for all resources. Statistical analyses of the costs were carried out, but the impact of variations in the cost estimates was not investigated. Thus, the costs were specific to the study setting. The cost analysis was replicated in sub-groups, as in the analysis of the effectiveness. The price year was reported, which will facilitate reflation exercises in other time periods.
The authors stated that three studies of similar design to the current clinical trial, but of longer duration, showed better results associated for the adjustable maintenance programme in comparison with fixed dosing. With respect to the generalisability of the study results, the authors noted that the clinical analysis came from a large and robust trial, the results of which should be generalisable to other settings. However, sensitivity analyses were not performed and this, in part, limits the external validity of the study. It was also noted that resource use in a real-world setting might be higher than that observed in the trial, especially if additional resources are required for initial patient education and support. However, the authors noted that physicians were expected to deliver initial education in the course of initial consultation, thus extra fees were not relevant. Finally, the authors stated that a potential limitation of the analysis was the short-term time horizon. A longer period of follow-up could have captured differences in exacerbations or extra costs of asthma treatment.
Implications of the study
The study results supported the use of adjustable maintenance, based on a combination of budesonide and formoterol in a single inhaler, for the treatment of asthma.
Source of funding
Supported by AstraZeneca.
Bruggenjurgen B, Selim D, Kardos P, Richter K, Vogelmeier C, Roll S, Meyer-Sabellek W, Buhl R, Willich S. Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma. PharmacoEconomics 2005; 23(7): 723-731
Other publications of related interest
Buhl R, Kardos P, Baare A, et al. Adjustable dosing with budesonide/formoterol in asthma maintains HRQL at a lower drug load than fixed dosing. Curr Med Res Opin 2004;20:1209-20.
Stallberg B, Olsson P, Jorgensen LA, et al. Budesonide/formoterol adjustable maintenance dosing reduces asthma exacerbations versus fixed dosing. Int J Clin Pract 2003;57:656-61.
Schermer TR, Thoonen BP, van den Boom G, et al. Randomized controlled economic evaluation of asthma self-management in primary health care. Am J Respir Crit Care Med 2002;166:1062-72.
Fitzgerald M, Sears MR, Boulet LP, et al. Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a 5-month multicenter Canadian study. Can Respir J 2003;10:427-34.
Subject indexing assigned by NLM
Adolescent; Adult; Aged; Aged, 80 and over; Asthma /drug therapy /economics; Bronchodilator Agents /administration & Budesonide /administration & Cost-Benefit Analysis; Drug Administration Schedule; Drug Combinations; Ethanolamines /administration & Female; Formoterol Fumarate; Germany; Humans; Male; Metered Dose Inhalers; Middle Aged; Primary Health Care /economics; Quality of Life; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use
Date bibliographic record published
Date abstract record published