|Cost effectiveness of inhaled fluticasone propionate vs inhaled triamcinolone acetonide in the treatment of persistent asthma
|Stanford R H, Edwards L D, Rickard K A
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 inhaled corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TA), were compared. The patients were treated with FP (250 microg twice daily) and placebo TA (two puffs four times daily) or TA (200 microg four times daily) and placebo FP (twice daily) for 24 weeks. A further group received placebo FP twice daily and placebo TA four times daily.
Economic study type
The study population consisted of corticosteroid-dependent patients with persistent asthma, who were aged 12 years and over. The patients were screened for 3 weeks prior to randomisation, during which time they continued their usual drug regimens. At the end of this period they had to meet a number of inclusion criteria for entry into the study. These criteria included asthma stability, level of forced expiratory volume in one second (FEV1), and adequate compliance.
The settings were primary and secondary care. The economic study was carried out at a number of centres throughout the USA.
Dates to which data relate
The dates during which the effectiveness evidence and resource data were collected were not reported. The price year was 1999.
Source of effectiveness data
The data were derived from two single studies of effectiveness.
Link between effectiveness and cost data
The resource utilisation, costs and clinical data were obtained prospectively from two randomised controlled trials.
The study sample consisted of 397 corticosteroid-dependent patients with persistent asthma, who were selected according to the specific inclusion criteria reported. There were 195 patients treated with FP and 202 treated with TA. No power calculations were provided to determine whether or not the sample size was sufficient to detect clinically significant differences.
The findings were derived from data from two multi-centre, randomised, parallel-group, double-blind, double-dummy, placebo-controlled studies. Each study was conducted over a 24-week period. There were 62 dropouts (16 due to lack of efficacy, 12 due to adverse events, 2 lost to follow-up, and 32 for other reasons) from the FP arm and 93 (46 due to lack of efficacy, 13 due to adverse events, 4 due to follow-up, and 30 for other reasons) from the TA arm, (p<0.05).
Analysis of effectiveness
The clinical study was analysed on an intention to treat basis. The primary health outcomes were an increase of at least 12% in FEV1 from baseline, and the percentage change in symptom-free days (SFD) from baseline. It was not stated whether the two groups were comparable.
The proportion of patients achieving at least a 12% improvement in FEV1 from baseline was 53% (103 out of 195) for the FP-treated patients and 32% (53 out of 202) for the TA-treated patients.
The mean change in SFD from baseline was significantly higher, (p<0.02), in the FP-treated group (18%) than in the TA-treated group (9.6%).
The patients in the FP group enjoyed greater improvements in measures of effectiveness than did those patients in the TA group.
Measure of benefits used in the economic analysis
The outcome measures used in the economic analysis were the improvements in FEV1 (at least 12% increase in FEV1 from baseline) and the percentage increase in the number of SFDs from baseline. These were measured at baseline and at 24 weeks.
The quantities and the costs were analysed separately. Asthma-related health care resources were used in the analysis, with resource utilisation in each setting of care prospectively collected for each asthma exacerbation. The resource utilisation costs were determined from various sources. The adverse events reported by the patient and related to drug therapy were included in the cost analysis. The cost of asthma treatment was the sum of all the costs related to the treatment of asthma. These included medications (average wholesale prices), emergency room visits, unscheduled physician visits (reimbursement rates), and hospitalisations. The costs and the quantities were estimated using both actual data and published studies. Protocol-driven resources were not included. Discounting was not appropriate due to the short time period of the study (24 weeks). The costs were adjusted to 1999 values where necessary.
Statistical analysis of costs
Only the mean costs were calculated. The costs were not treated in a stochastic manner.
The indirect costs were not included in the analysis. No justification was provided for their exclusion.
A sensitivity analysis was performed for a variety of parameters (for example, FEV1) to take into account the variability in the data. A univariate analysis appears to have been conducted
Estimated benefits used in the economic analysis
The proportion of patients achieving at least a 12% improvement in FEV1 from baseline was 53% for the FP-treated patients and 32% for the TA-treated patients, (p<0.001).
The mean change in SFD from baseline was significantly better, (p<0.02), in the FP-treated group (18%) than in the TA-treated group (9.6%).
The duration of benefits was 24 weeks.
The average daily direct cost for the TA-treated group ($2.38 per patient) was lower than that for the FP-treated group ($2.52 per patient).
Other than oral candidiasis, patients in the FP group had fewer resource events than the TA group.
In terms of the costs, although the drug costs in the FP group were higher ($2.18 per patient per day versus $1.85 in TA group), other health care costs were lower than those for the TA group.
The costs of adverse event medications were included in the costing.
Synthesis of costs and benefits
An incremental analysis was carried out to combine the costs and the benefits. The daily cost per patient achieving at least a 12% increase in FEV1 was $4.76 for the FP-treated group and $7.43 for the TA-treated group.
The cost per additional SFD was $14.01 for the FP-treated group and $24.88 for the TA-treated group.
The incremental cost-effectiveness ratio (ICER) that would be incurred if patients were switched from the less effective treatment, TA, to the more effective treatment, FP, was $1.70 per day for an additional SFD. The ICER was $0.68 per day for an additional patient to achieve a 12% improvement in FEV1.
When FEV1 was varied by 1% increments from 10% to 15% increases, the difference between the treatment groups (FP versus TA) was statistically significant at all levels of efficacy, (p<0.001). The cost-effectiveness ratios and the ICER remained constant at all levels of effectiveness.
The ICER for FEV1 improvement did not approach $5/day until the acquisition cost of TA was discounted by 50%.
The ICER of $5/day was approached for SFD when TA was discounted by 15%.
From the perspective of third-party payers, fluticasone propionate (FP; 250 microg twice daily) was more cost-effective than triamcinolone acetonide (TA; 200 microg four times daily) in patients with persistent asthma over a period of 24 weeks. The small savings seen with the acquisition cost of TA were offset by the increased number of health care resources associated with TA, and the superior improvement in lung function and symptom control of FP observed in these clinical trials.
CRD COMMENTARY - Selection of comparators
The authors justified the choice of inhaled corticosteroids as the comparators by stating that little research had been conducted on the cost-effectiveness of the different inhaled corticosteroid treatments. However, there did not appear to be any justification given in this paper for the choice of these particular corticosteroids. As the efficacy results have been discussed and published separately from the two randomised controlled trials, it may be that the original papers discussed the rationale for choosing FP and TA as the comparators. You should assess whether they represent widely used treatments in your own setting.
Validity of estimate of measure of effectiveness
The internal validity should have been improved through randomisation and by the results being presented on an intention to treat basis. However, no power calculations were provided so it is unclear whether the sample size was sufficient to detect any clinically significant differences. In addition, there was no information on the comparability of the groups at baseline for the two studies and, hence, the effect any confounding variables might have had on the outcomes.
Validity of estimate of measure of benefit
The study does not differentiate between the effectiveness and the benefits, as both benefit measures were derived directly from the effectiveness analysis. While the authors noted that improvements in FEV1 and SFDs represent common outcomes for asthma-related interventions, an assessment of quality issues would have been interesting.
Validity of estimate of costs
No justification was provided for the exclusion of the indirect costs in the analysis, although this may be less relevant as the perspective adopted was that of the third-party payer rather than society. The costs and the resources were collected and reported separately, and were also collected prospectively alongside randomised clinical trials. This should have improved the validity and generalisability of the results.
All the relevant categories of direct costs appear to have been included in the analysis for the study period (including the costs of adverse events). However, as the authors recognised, the duration of the study was relatively short and thus may not have adequately captured all the symptomatic episodes of chronic asthma. Thus, it may be a conservative estimate of the costs and resources, particularly as those patients who dropped out of the study (155 out of 397) were assumed not to use any additional health care resources beyond those they had already accumulated. The authors also pointed out that these clinical trials were not powered individually to detect statistically significant differences in the economic analysis.
The authors made comparisons with other studies and stated that their findings were similar to published findings. The issue of generalisability to other settings was not discussed. Generalisability will have been enhanced by the use of sensitivity analysis, although it is unclear exactly how many parameters were tested. Also, by the collection of the resource and cost data separately and alongside randomised controlled trials. The authors highlighted some limitations of their analysis.
Implications of the study
The implications of the study are that FP 500 microg daily was more cost-effective than TA 800 microg daily under these conditions over a 24-week period. The authors did not provide any specific recommendations relating to changes in policy or practice and/or the need for further research.
Source of funding
Funded by Glaxo Wellcome, Inc.
Stanford R H, Edwards L D, Rickard K A. Cost effectiveness of inhaled fluticasone propionate vs inhaled triamcinolone acetonide in the treatment of persistent asthma. Clinical Drug Investigation 2000; 20(4): 237-244
Subject indexing assigned by CRD
Adult; Androstadienes /economics /therapeutic use; Anti-Asthmatic Agents /economics /therapeutic use; Asthma /drug therapy /economics; Cost-Benefit Analysis; Treatment Outcome; Triamcinolone Acetonide /therapeutic use /economics
Date bibliographic record published
Date abstract record published