Cost effectiveness of fluticasone and budesonide in patients with moderate asthma Steinmetz K O, Volmer T, Trautmann M, Kielhorn A

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1 Cost effectiveness of fluticasone and budesonide in patients with moderate asthma Steinmetz K O, Volmer T, Trautmann M, Kielhorn A 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 Inhaled fluticasone (metered dose inhaler) was compared to inhaled budesonide (Turbuhaler(R) in corticosteroid-naive patients with moderate asthma. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The authors did not define the study population. The study sample comprised patients enrolled in a multi-centre trial, who were aged between 18 and 70 years with moderate asthma. Moderate asthma was defined as a combined morning and evening asthma symptom score of more than two or a daily peak expiratory flow rate (PEFR) variance of more than 15%, and a forced expiratory volume in one second (FEV1) between 50 and 80% of the potential volume or a PEFR between 50 and 80%. Exclusion criteria were patients with a serious concomitant disease or those requiring drugs likely to interfere with the study drugs. These criteria were not defined. Beta-agonist use was monitored throughout the clinical trial but was not used as an efficacy parameter. Any patients receiving corticosteroids prior to the study discontinued use of these drugs at least three weeks prior to the baseline assessment of their asthma status. Setting The study was based in primary care and outpatient departments in secondary care in Germany. Dates to which data relate The dates relating to when the effectiveness and resource use data were collected were not reported. The price year was Source of effectiveness data Effectiveness data were derived from a single study. Link between effectiveness and cost data Retrospective costing was carried out on the same patient sample as that used to collect effectiveness evidence. Study sample No power calculations were reported. No details about the method of sample selection were reported. There was no evidence that the initial study sample was appropriate for the clinical study question. A total of 457 patients with Page: 1 / 5

2 moderate asthma were randomised to treatment. Of these, 235 were randomised to the fluticasone group and 222 were randomised to the budesonide group. No details about the subjects invited to participate who refused, or subjects excluded for any reasons from the initial sample, were reported. Study design This study used an open-label (non-blinded), multi-centre, randomised, parallel-group study design. A total of 45 centres in Germany were included in the trial. The duration of follow-up was 6 weeks. The number of patients lost to follow-up was not reported. No masking procedures for the assessment of outcomes were reported. Analysis of effectiveness The analysis of the clinical study was based on intention to treat. The primary efficacy outcomes reported from the clinical analysis were changes in: morning PEFR (L/min) and evening PEFR (L/min). The secondary effectiveness outcomes were: number of successfully treated patients with more than 10% improvement in morning PEFR; number of successfully treated patients with more than 5% improvement in morning PEFR; changes in the average proportion of symptom-free days (defined as a 24-hour period without day- or night-time asthma symptoms); and physicians assessment of treatment (very effective, effective, fair, inadequate). The groups were comparable in terms of factors that can affect PEFR, for example, gender, age, height and weight, and duration of asthma and whether or not they smoked. Effectiveness results The primary efficacy outcomes were: morning PEFR +45 L/min fluticasone versus +30 L/min budesonide (p<0.01); and evening PEFR +34 L/min fluticasone versus +25 L/min budesonide (p<0.05). The secondary effectiveness outcomes were: percentage of successfully treated patients with more than 10% improvement in morning PEFR, 47% fluticasone and 42% budesonide; percentage of successfully treated patients with more than 5% improvement in morning PEFR, 52% fluticasone and 49% budesonide; changes in the average proportion of symptom-free days, +32% fluticasone and +24% budesonide (p<0.05); and physicians assessment of treatment: very effective, 49% fluticasone, 24% budesonide (p<0.01); effective, 36% fluticasone, 46% budesonide; fair, 7% fluticasone, 15% budesonide; inadequate, 3% fluticasone, 9% budesonide. Clinical conclusions The authors concluded that fluticasone was more effective than budesonide in terms of improved lung function for patients with moderate asthma. Measure of benefits used in the economic analysis The authors used the proportion of successfully treated patients and proportion of symptom free days as the measures of benefit for the economic analysis. Direct costs Quantities and costs were not reported or analysed separately. The direct costs for primary care and the hospital perspective were reported. The direct costs included in the analysis were the costs of: daily study medication; additional Page: 2 / 5

3 asthma-related medication; medications used to treat adverse events; office-based physician visits; and hospitalisation. The estimation of the quantities and costs were based on data from a number of sources and assumptions. The source of data about the use of drug therapies was not reported. The authors stated that, if actual data were absent for drug therapy it was assumed that: chronic therapies were taken over the whole treatment period; antibiotics were taken for 7-days; antifungals and other medications were taken according to data sheet recommendations. If a course of medication was started, a physician visit was assumed to occur. Hospitalisation data appear to have been estimated from the clinical trial database. Unit cost data for drug therapies were derived from market prices from the Rote List and were not adjusted for patient co-payments. The unit costs of physician visits and hospitalisation were estimated from published sources. All costs were reported for the year The time horizon for this study was six-weeks starting from the time patients had completed a run-in period of two weeks and were randomised to either the fluticasone or budesonide group. Discounting, appropriately, was not carried out because of the short-time frame of the study (less than one-year). Statistical analysis of costs No statistical analysis of costs was reported. Indirect Costs Indirect costs were not included in this analysis because they were not consistent with the study perspective. Currency German marks (DM). No conversion rate was reported. Sensitivity analysis A one-way sensitivity analysis was conducted for the following parameters: total treatment costs; increase in PEFR; reduction in the number and cost of inhalations of budesonide. Estimated benefits used in the economic analysis The percentage of successfully treated patients with more than 10% improvement in morning PEFR, was 47% fluticasone and 42% budesonide. The net (incremental) benefit from fluticasone was +5% (47-42). The change in the proportion of symptom free days at the end of the 6-week follow-up (proportion of symptom free days at end of treatment - proportion of symptom free days at baseline) was +32% fluticasone and +24% budesonide (p<0.05). The net (incremental) benefit from fluticasone was +8% (32-24). Cost results The mean daily treatment costs per patient for the fluticasone group were DM4.23. The mean daily treatment costs per patient for the budesonide group were DM5.19. Synthesis of costs and benefits Fluticasone was associated with a lower cost per day, higher proportion of successfully treated patients and higher increase in proportion of symptom free days. This meant that it was not appropriate to calculate an incremental costeffectiveness ratio. The authors reported that there was a saving of DM16 for each additional symptom free day. Page: 3 / 5

4 The sensitivity analysis found that the average cost-effectiveness ratios (e.g. cost fluticasone/benefit fluticasone) remained in favour of fluticasone after: a 20% increase or decrease in treatment costs; a 10% increase or decrease in PEFR; a 30% reduction in the cost per inhalation of budesonide; or a reduction in the number of inhalations per day of budesonide from 6 to 5, which is equivalent to 1,000 micrograms per day. Authors' conclusions The authors concluded that the results of this study showed that the use of fluticasone delivered by metered dose inhaler is more cost-effective than budesonide delivered by Turbuhaler in this population of corticosteroid-naive patients with moderate asthma. CRD COMMENTARY - Selection of comparators The two comparators used in this economic evaluation were appropriate to address the study question. The dose of fluticasone and budesonide used was in the normal dose range for use in adults. The authors did not report whether these or other asthma drugs are commonly used in routine clinical practice. The authors did not report whether these, or other inhaler devices, are commonly used in routine clinical practice. The authors did not give a clear rationale for the use of different inhaler devices when comparing the alternative drugs. The authors reported 1 study that suggested that budesonide, via a dry powder inhaler plus terbutaline, was more effective and cost-effective than budesonide via a metered dose inhaler plus a beta 2-agonists. However, the authors did not report whether the differences in effectiveness were due to the different inhaler devices used or the different adjunctive therapies. You, as a user of this database should consider whether the two alternative drugs, the doses and the inhaler devices compared in this study are relevant to practice in your own setting. Validity of estimate of measure of effectiveness The authors used data from an open label randomised trial. As the authors noted, this may have introduced bias into the estimates of effects and costs. For example, knowledge of treatment allocation may influence the subjective perception and measurement of outcomes by patients and investigators, and the need for additional or rescue medications. The authors reported that beta-agonist use was monitored throughout the clinical trial but was not used as an efficacy parameter. Patients should use beta-agonists as required, to relieve the symptoms of asthma, but corticosteroids should be used regularly to prevent the symptoms of asthma occurring. The use of beta-agonists could bias the observed effectiveness of the corticosteroids under observation in this study. However, the study did not report the extent of betaagonist use in the fluticasone or budesonide group. Therefore, no assessment can be made regarding the potential impact of beta-agonist use on the validity of the effectiveness of fluticasone or budesonide. The trial used different inhaler devices for the delivery of the two drugs, although both drugs can be used with metered dose or dry powder inhalers. This may bias the results if one inhaler device is more effective than the other is. The authors suggested that, ideally, studies such as this should involve a longer evaluation period than the six-weeks used in this study. However, they did not suggest what the ideal length of evaluation period should be. Furthermore, they suggested that it is unlikely that a longer evaluation period would have affected the results of this economic evaluation. This conclusion is only valid providing the long-term compliance of patients with therapy and the benefits of fluticasone and budesonide exhibit the same characteristics as the short-term (six-week) compliance and benefits. The study sample was limited to people with moderately severe asthma who had not previously used corticosteroid inhaled therapy. The authors did not establish whether this sample was representative of all patients with moderately severe asthma. The authors reported that there were no differences between the patient groups at baseline. The authors did not report whether there was sufficient power to detect statistically significant differences between the groups. Validity of estimate of measure of benefit The authors reported that there was no standard accepted measure of patient benefit available for asthma therapies and therefore, they reported two clinical measures of effectiveness for asthma over a six-week period. Page: 4 / 5

5 Powered by TCPDF ( Validity of estimate of costs Limited information was reported on the methods used to identify and estimate the direct costs included in this analysis. In particular there was inadequate information on the quantity of resources used. The study took the perspective of a third-party payer, the direct costs of other health and social care services (patients and informal carers) being excluded. There was insufficient information to determine whether these omissions would affect the overall conclusions of the study. A limited sensitivity analysis of costs was conducted. The authors did not provide a rationale for the choice of parameters tested or the range of values used. Other issues The authors compared the results of the study with 3 other studies of fluticasone (1 economic study, 1 open label clinical trial, and 1 double blind clinical trial). The results of these 3 studies were consistent with those of the evaluation considered here. The authors did not report whether these 3 studies comprised all the literature relevant to the study question or whether they were selectively reported. The authors did not discuss the generalisability of their results to other settings. Implications of the study The authors suggested that as a result of improvement in lung function and cost advantages, fluticasone is more costeffective than budesonide from a third-party payer perspective over a six-week period. The authors added that this conclusion is robust over a wide range of input parameters for the study, and that the study serves as a model for future cost comparisons between inhaled corticosteroids. Source of funding Funded by Glaxo Wellcome. Bibliographic details Steinmetz K O, Volmer T, Trautmann M, Kielhorn A. Cost effectiveness of fluticasone and budesonide in patients with moderate asthma. Clinical Drug Investigation 1998; 16(2): PubMedID Indexing Status Subject indexing assigned by NLM AccessionNumber Date bibliographic record published 31/01/2002 Date abstract record published 31/01/2002 Page: 5 / 5