|Cost-effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma
|Sheth K, Borker R, Emmett A, Rickard K, Dorinsky P
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 initial maintenance treatments for patients with persistent asthma were examined. Salmeterol-fluticasone propionate (SF; salmeterol 50 microg and fluticasone propionate 100 microg) delivered twice daily via the Diskus device versus montelukast (MONT; 10 mg) once daily, for 12 weeks.
Economic study type
The study population comprised patients suffering from asthma for at least 6 months, who had been treated with an oral or inhaled short-acting beta2-agonist on a scheduled, or as-needed basis for at least 6 weeks before screening. The patients were required to have a forced expiratory volume in 1 second (FEV1) of between 50 and 80% of the predicted normal value, and an increase in FEV1 of at least 12% within 30 minutes of inhaling two puffs (180 microg) of albuterol.
The setting was primary and secondary care. The economic study was carried out in the USA.
Dates to which data relate
The effectiveness evidence and resource use data were derived from a study published in 2001. The price year was 2001.
Source of effectiveness data
The effectiveness evidence was derived from a single study, the methods and main results of which had been published elsewhere (Calhoun et al., see Other Publications of Related Interest).
Link between effectiveness and cost data
The costing was performed prospectively on the same sample of patients as that used in the effectiveness study.
Limited information on the study sample and methods used in the analysis were reported. Of the 1,217 patients screened for participation, 423 patients were included in the final sample. There were 211 patients in the SF group and 212 in the MONT group. In the SF group, the mean age of the patients was 37 years (age range: 16 - 72) and 50% were female. In the MONT group, the mean age was 36 years (age range: 15 - 66) and 49% were females.
This was a prospective, randomised, double-blind, double-dummy, multi-centre trial. The methods of randomisation and blinding were not reported. The length of follow-up was 12 weeks. The proportion of patients lost to follow-up was 12% in the SF group and 18% in the MONT group.
Analysis of effectiveness
The analysis of the clinical study was conducted on an intention to treat basis, although this was not explicitly stated for the effectiveness analysis. The outcome measures used were the proportion of patients achieving a 12% or greater increase in FEV1 and the proportion of symptom-free days (SFDs) achieved over the 12-week period. An SFD was defined as any day in which the patient recorded no symptoms in terms of chest tightness, wheezing and shortness of breath. The study groups were comparable in terms of their demographics and baseline FEV1.
The proportion of patients achieving a 12% or greater increase in FEV1 was 71% in the SF group and 39% in the MONT group, (p<0.001).
The proportion of SFDs was 46.8% in the SF group and 21.5% in the MONT group, (p<0.001).
The effectiveness study showed that SF patients experienced a statistically significant increase in FEV1 and SFDs in comparison with MONT patients.
Measure of benefits used in the economic analysis
The summary benefit measures were the proportion of patients achieving a 12% or greater increase in FEV1 and the proportion of SFDs achieved over the 12-week period. Both were derived directly from the effectiveness study.
Discounting was not relevant due to the short time horizon of the study. The unit costs were presented separately from the quantities of resources used. The health services included in the economic evaluation were drugs, emergency department visits, physician office visits, rescue medication and the treatment of adverse drug reactions. The cost/resource boundary of the study was that of the payer. Resource use was estimated from actual data estimated alongside the clinical trial. The costs were derived from several sources, such as published studies (for emergency department visits), average market prices (for drugs) and the Current Procedural Terminology (for physician office visits). All the costs were adjusted to 2001 values using the medical care component of the consumer price index. The basis of the cost analysis was the intention to treat approach.
Statistical analysis of costs
The costs were treated deterministically in the base-case.
The indirect costs were not considered.
One-way sensitivity analyses were conducted to assess the robustness of the estimated cost-effectiveness ratios to variations in the percentage improvement in FEV1 (range: 10 - 15%). Two scenarios were considered for the proportion of SFDs. In the first scenario, it was assumed that all patients who prematurely withdrew from the study were symptom free from the time they withdrew. In the second scenario, it was assumed that all patients who prematurely withdrew from the study were symptomatic from the time they withdrew. Finally, a bootstrapping analysis (1,000 iterations) was carried out to obtain the 95% confidence intervals (CIs) around the average and incremental cost-effectiveness ratios.
Estimated benefits used in the economic analysis
See the 'Effectiveness Results' section.
The daily costs per patient were $3.55 in the SF group and $3.12 in the MONT group, (p<0.001).
The daily study drug costs per patient were $3.37 in the SF group and $2.68 in the MONT group.
The daily non-study drug costs per patient were $0.18 in the SF group and $0.44 in the MONT group, (p<0.001).
Synthesis of costs and benefits
Average and incremental cost-effectiveness ratios were calculated to combine the costs and benefits of the two alternative strategies.
The average cost per patient achieving at least a 12% improvement in FEV1 was $5.03 (95% CI: 4.61 - 5.50) in the SF group and $8.25 (95% CI: 6.98 - 9.93) in the MONT group.
The incremental cost per additional patient achieving at least a 12% improvement in FEV1 with SF over MONT was $1.33 (95% CI: 0.80 - 2.02).
The average cost per SFD was $7.63 (95% CI: 6.90 - 8.50) in the SF group and $14.89 (95% CI: 12.36 - 17.98) in the MONT group.
The incremental cost per additional SFD with SF over MONT was $1.69 (95% CI: 1.01 - 2.48).
The results continued to favour SF in all sensitivity analyses.
From the perspective of the payer, maintenance treatment with salmeterol-fluticasone (SF) was cost-effective in comparison with montelukast (MONT) in patients with persistent asthma. This conclusion held over wide assumptions and scenarios.
CRD COMMENTARY - Selection of comparators
The authors justified the choice of the comparators as two recently approved medications for the maintenance treatment of persistent asthma. The authors stressed that the two drugs were indicated for comparable patient populations. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The analysis of effectiveness was based on a randomised trial, which was appropriate for the study question. The internal validity of the analysis was further enhanced by the double-blind design and the baseline comparability of the two groups. Also, by the use of intention to treat as the basis for the clinical analysis, and the multi-centred nature of the study. It appears difficult to further evaluate the study since most of the details, such as sample size calculations and the use of other statistical tests, were presented in a separate article.
Validity of estimate of measure of benefit
The summary benefit measures used in the analysis were specific to the disease considered in the study, although they represented common measures of benefit for the interventions under evaluation. Therefore, they would probably only be comparable with the benefits of other interventions related to asthma treatment.
Validity of estimate of costs
The authors explicitly stated which perspective was adopted in the study. It appears that all the relevant categories of costs have been included in the analysis. Both the unit costs and the price year were provided. This allows the replication of the study and the performance of reflation exercises in other settings. The source of the cost data was reported for each item. Individualised, trial-based resource consumption data were used in the analysis. The costs were treated deterministically. The estimates were specific to the study setting since sensitivity analyses were not conducted on the costs. An intention to treat analysis of the costs was conducted.
The authors showed that their findings were consistent with those from other trials and "real-world" studies (based on claims databases). The issue of the generalisability was not explicitly addressed and sensitivity analyses were conducted only on the effectiveness estimates. Therefore, caution is required when extrapolating the results of the study to other settings. The study referred to patients with persistent uncontrolled asthma and this was reflected in the authors' conclusions.
Implications of the study
The authors suggested that studies with longer follow-up should be conducted to estimate better the long-term impact of the treatments under evaluation.
Source of funding
Supported by a grant from GlaxoSmithKline, Research Triangle Park (NC), USA.
Sheth K, Borker R, Emmett A, Rickard K, Dorinsky P. Cost-effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma. PharmacoEconomics 2002; 20(13): 909-918
Other publications of related interest
Calhoun W, Nelson H, Nathan R, et al. Comparison of fluticasone propionate-salmeterol combination therapy and montelukast in patients who are symptomatic on short acting beta2-agonist alone. American Journal of Respiratory and Critical Care Medicine 2001;164:759-63.
Subject indexing assigned by NLM
Acetates /economics /therapeutic use; Adolescent; Adult; Aged; Albuterol /analogs & Androstadienes /economics /therapeutic use; Anti-Asthmatic Agents /economics /therapeutic use; Asthma /drug therapy /economics; Chronic Disease; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines /economics /therapeutic use; Salmeterol Xinafoate; derivatives /economics /therapeutic use
Date bibliographic record published
Date abstract record published