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The cost effectiveness of eformoterol via Turbohaler and salmeterol via pressurised metered dose inhaler and metered dose powder inhaler in mild to moderate asthma |
Campbell L M, Berggren F, Emmas C |
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Record Status 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. Health technology The use of eformoterol and salmeterol in the treatment of patients with mild to moderate asthma. Eformoterol was delivered via the Turbohaler (12 microg twice daily). Salmeterol (50 microg twice daily) was delivered via either a metered-dose powder inhaler (MDPI) or a pressurised metered-dose inhaler (pMDI).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients aged 12 years or older with a documented diagnosis of asthma, who had received at least 200 microg/day inhaled steroid at a constant dose for at least 4 weeks. The patients also had to have been using a short-acting bronchodilator and to have a requirement for the addition of a long-acting beta-2 agonist. Patients were considered ineligible if they had any disease which, in the opinion of the investigator, could interfere with the administration of the study medication.
Setting The setting was primary care. The economic study was carried out in the UK and Republic of Ireland.
Dates to which data relate The dates during which the effectiveness and resource use data were collected were not reported. The price year was 1999.
Source of effectiveness data The effectiveness data were derived from a single study, the main details of which had been published elsewhere (see Other Publications of Related Interest).
Link between effectiveness and cost data The costing was carried out prospectively on the those patients that were included in the effectiveness study.
Study sample The study had a power of 90% to detect a clinically relevant difference of 20 L/minute in the primary efficacy variable. Of the 600 patients identified at the study centres, 469 were allocated to the groups. The other 131 patients were excluded mainly because they did not fulfil the randomisation criteria. A further 9 patients were excluded due to no assessment of efficacy or due to the patient taking no study medication. There were 230 patients in the eformoterol group, 119 patients in the salmeterol MDPI group, and 111 patients in the salmeterol pMDI group. The mean age was 40.3 (+/- 16) years in the eformoterol group, 40.4 (+/- 17.5) years in the MDPI group and 39.9 (+/- 15.9) years in the pMDI group. The number of male patients was 84 (eformoterol), 53 (MDPI) and 48 (pMDI), respectively.
Study design This was a prospective, randomised controlled trial that was carried out in 110 general practices and 2 hospital centres in the UK and Republic of Ireland. After 7 to 14 days during which the baseline values were established, the patients were randomised via sealed code envelopes to receive eformoterol, salmeterol MDPI, or salmeterol pMDI in a ratio of 2:1:1 for 8 weeks. A set of randomisation criteria was defined. This follow-up period was then followed by a crossover period of 4 weeks, which was used to assess the patients' preferences for the devices. Randomisation was blinded. Of the initial 469 patients, 92 were lost to the final follow-up assessment. Thirty-four in the eformoterol group, 17 in the MDPI group and 19 in the pMDI group discontinued on or before the end of their first treatment period. The remaining 22 discontinuations occurred during the crossover period.
Analysis of effectiveness The analysis of the clinical study was conducted using the all patients treated approach. The primary health outcome was the change in peak expiratory flow (PEF), which was assessed from data on diary cards. The secondary outcomes were:
changes in daytime asthma symptoms after 4 weeks,
sleep disturbance due to asthma,
patient preferences for the device,
the percentage of symptom-free days (SFDs), and
the occurrence of adverse events.
Difference between the groups were investigated using an analysis of variance in which the baseline data were included as covariates. At study entry, the groups were comparable in terms of all demographic and disease characteristics.
Effectiveness results During the 8-week follow-up period, the change in PEF across the three groups was not statistically significant. However, significant improvements from baseline to final assessment were observed within each of the three groups. The improvements were 9.5% with eformoterol, 8.7% with salmeterol MDPI and 10.7%V with salmeterol pMDI.
The improvement in daytime symptom severity after 4 weeks was significantly greater in eformoterol patients (-0.54) than in MDPI patients (-0.35), (p=0.0140). However, there were no statistically significant differences between the eformoterol and pMDI groups and between the two salmeterol groups.
No statistically significant differences in sleep disturbance due to asthma were observed.
Significantly more patients found the Turbohaler more convenient to carry around than the salmeterol pMDI (59% versus 41%; p=0.0168).
The percentage of SFDs was 32.8% (+/- 2.3) in the eformoterol group, 24.1% (+/- 2.6) in the salmeterol MDPI group and 28% (+/- 3.2) in the salmeterol pMDI group. None of the differences reached statistical significance.
A total of 1,171 adverse events were observed in 390 patients. There were 526 adverse events in 235 eformoterol patients, 266 in 120 MDPI patients and 257 in 113 pMDI patients. These differences failed to reach statistical significance.
Clinical conclusions The effectiveness study showed that eformoterol delivered via the Turbohaler proved to be at least as effective as salmeterol in achieving asthma control. Significantly more patients preferred the Turbohaler to the salmeterol devices.
Measure of benefits used in the economic analysis The summary benefit measure was the percentage of SFDs. This was derived directly from the effectiveness study.
Direct costs Discounting was not relevant because the time horizon of the study was 8 weeks, and it was not carried out. The unit costs were presented separately from the quantities of resources used. The categories of costs included in the analysis were study medications, rescue medications, inhaled steroids, additional respiratory medications, and health care costs (general practitioner visits, accident and emergency department visits, and in-hospital stay). The perspective of the NHS was applied. The resource use data were estimated from the sample of patients who were included in the effectiveness study. The drug costs were estimated from UK prices. Other health care costs came from actual data reported in the Personal Social Services Research Units. The price year was 1999.
Statistical analysis of costs The costs were presented as average values with standard deviations. The costs estimated in each group were compared using the Wilcoxon rank sum test.
Indirect Costs The indirect costs were not considered.
Sensitivity analysis Sensitivity analyses were carried out to test the robustness of the differences in total costs and average cost-effectiveness ratios. To assess the impact of concomitant steroids, the total costs were estimated assuming that all patients received the mean dose for their group of the most commonly prescribed device in the UK, BDP via a generic pMDI. A second sensitivity analysis was performed in which the cost of the short-acting beta-2 agonist was removed. Finally, a third sensitivity analysis was carried out to construct 95% confidence intervals (CIs) around the effectiveness results.
Estimated benefits used in the economic analysis See the Effectiveness Results' section.
Cost results The average daily cost was 1.38 (+/- 0.04) with eformoterol, 1.43 (+/- 0.05) with salmeterol MDPI and 1.47 (+/- 0.06) with salmeterol pMDI.
Only the difference between eformoterol and salmeterol MDPI reached statistical significance, (p=0.039).
The main cost driver that was significantly lower in the eformoterol group was study medication.
The total average costs of treatment during the 8-week period were 77.46 with eformoterol, 80.12 with salmeterol MDPI and 82.41 with salmeterol pMDI.
Synthesis of costs and benefits Average and incremental cost-effectiveness ratios were calculated to combine the costs and benefits. An incremental cost-effectiveness analysis was not performed since eformoterol was both more effective and less costly than the two salmeterol options.
The average cost of achieving an SFD with salmeterol was between 25% (pMDI) and 41% (MDPI) more than achieving the same results with eformoterol. These results held in the sensitivity analysis.
Authors' conclusions All the medications were comparable in terms of improvement in asthma control. However, the treatment costs were significantly lower with eformoterol delivered via the Turbohaler, which was the preferred device.
CRD COMMENTARY - Selection of comparators The authors provided a justification for the choice of the comparators. Salmeterol was selected because it represented the most widely prescribed long-acting inhaled bronchodilator for asthmatic patients. On the other hand, prior studies have shown eformoterol, which has a rapid onset of action (one minute), to be an effective treatment for mild to moderate asthma. 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 study design exhibited several strong points. For example, the blind outcome assessment, the randomisation procedure used to allocate the patients to the study groups, the use of power calculations, and the baseline comparability of the groups. In addition, some statistical tests were carried out to assess the impact of potential confounding factors. However, the analysis of the clinical study was conducted on only those patients who completed the treatment, although the authors did report the reasons why patients were excluded. The high percentage of patients who did not fulfil the inclusion or randomisation criteria casts some doubts on how representative the study sample was. A further limitation to the internal validity of the study was the fact that blinding was limited to the randomisation phase.
Validity of estimate of measure of benefit The authors stated that the summary benefit measure (SFDs) was chosen because it was recommended in published guidelines for asthmatic patients. However, it is not easy to compare SFDs with the benefits of other health care interventions. The use of measures that assess the impact of the intervention on quality of life would have been helpful.
Validity of estimate of costs The authors stated explicitly which perspective was adopted in the study. It appears that all the relevant categories of costs have been included. The indirect costs were not considered because data on productivity losses were not available from the trial. The unit costs and the quantities of resources used were presented separately and the price year was reported. This enhances the possibility of replicating and reflating the results of the study in other settings. The source of the cost data was reported. The costs estimated in the two groups were compared using statistical tests. Sensitivity analyses were also performed on some key cost estimates.
Other issues The authors compared their findings with those from long-term studies showing eformoterol was comparable with salmeterol over a 6-month period. This suggested that cost-savings could have been maintained over time. Some comparisons were also made with studies referring to other countries. The authors stated that the external validity of the analysis was maximised by considering standard treatment patterns, which were based on nationally accepted treatment guidelines. The study referred to patients with mild to moderate asthma and this was reflected in the conclusions of the analysis.
Implications of the study The authors attempted to extrapolate the results of the study to the population of asthmatic patients in the UK. They stated that an annual cost-saving of approximately 11 million could be realised by using eformoterol in place of salmeterol. This would correspond to savings of up to 20,000 per primary care organisation, which covers about 100,000 patients.
Source of funding Supported by AstraZeneca Pharmaceuticals UK Ltd.
Bibliographic details Campbell L M, Berggren F, Emmas C. The cost effectiveness of eformoterol via Turbohaler and salmeterol via pressurised metered dose inhaler and metered dose powder inhaler in mild to moderate asthma. Journal of Drug Assessment 2000; 3(2): 133-144 Other publications of related interest Campbell LM, Anderson TJ, Parashchak MR, et al. A comparison of the efficacy of long-acting beta-2 agonist: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Respiratory Medicine 1999;93:236-44.
Indexing Status Subject indexing assigned by CRD MeSH Adrenergic beta-Agonists /economics /therapeutic use /administration & Adult; Albuterol /economics /therapeutic use; Asthma /drug therapy; Beclomethasone /economics /therapeutic use; Clinical Trials as Topic; Comparative Study; Cost-Benefit Analysis; Drug Costs; Emergency Service, Hospital; Ethanolamines /economics /therapeutic use; Female; Great Britain; Health Care Costs; Hospitalization; Humans; Male; Nebulizers and Vaporizers /economics; Primary Health Care; Randomized Controlled Trials as Topic; Respiratory Tract Diseases /drug therapy /etiology; Steroids /economics /therapeutic use; Terbutaline /economics /therapeutic use; dosage AccessionNumber 22003007644 Date bibliographic record published 30/09/2004 Date abstract record published 30/09/2004 |
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