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Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma |
Menendez R, Stanford R H, Edwards L, Kalberg C, Rickard K |
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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 Two drug therapies were compared for the treatment of patients suffering from persistent asthma. The first was an inhaled glucocorticoid, fluticasone propionate (FP), at a dose of 88 microg twice daily. The second was a leukotriene receptor antagonist, zafirlukast (ZA), at a dose of 20 mg twice daily. Salbutamol (albuterol) was used as the rescue medication for all the patient groups.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients older than 12 years diagnosed with asthma, who had an increase in the forced expiratory volume in 1 second (FEV1) of at least 12% over baseline with salbutamol inhalation. The patients were also required to have a medical history of asthma requiring short-acting beta2-antagonist bronchodilator therapy, and a baseline FEV1 of between 50 to 80% of the predicted normal value.
Setting The setting was not clearly reported, but it was presumably the community. The economic study was conducted in the USA.
Dates to which data relate The dates during which the effectiveness data and quantities of resources used were gathered were not reported. The price year was 1999.
Source of effectiveness data The effectiveness evidence was derived from a single study.
Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the effectiveness analysis.
Study sample It was not reported whether power calculations were used to determine the sample size. The method of sample selection was not stated. A total sample of 451 patients was recruited. There were 231 patients in the FP group with a mean age of 31.4 (standard deviation, SD=13.1) years. Of these, 52% were men. There were 220 patients in the ZA group with a mean age of 31.2 (SD=12.9) years). Of these, 49% were men.
Study design This was a multi-centre, randomised, double-blind, double-dummy, placebo-controlled trial. The methods of randomisation and blind assessment were not reported. After an 8- to 14-day run-in period, the patients were randomly assigned to the study groups and were then followed for 12 weeks. A total of 83 patients (83 reported in the paper: 31 in the FP group and 50 in the ZA group) withdrew from the trial. This was mainly due to the occurrence of adverse events (8 in the FP group and 12 in the ZA group) and the requirement of oral corticosteroids (8 in the FP group and 14 in the ZA group). The remaining 41 patients were lost at follow-up for several reasons, such as protocol violation and withdrawal of consent.
Analysis of effectiveness The clinical study was analysed on an intention to treat basis. The primary health outcomes were the proportion of successfully treated patients (those who experienced at least a 12% increase in FEV1) and the number of symptom-free days. The latter was defined as those days in which the patient reported no asthma symptoms, such as cough, wheeze, chest tightness, or shortness of breath. A 6-point scale was used to measure the symptoms. The study groups appear to have been comparable at baseline.
Effectiveness results The proportion of successfully treated patients was 53% in the FP group and 37% in the ZA group, (p=0.001).
The mean percentage of symptom-free days across each patient's treatment period was 33.4% in the FP group and 19.3% in the ZA group, (p<0.001).
Clinical conclusions The effectiveness analysis showed that FP was significantly more effective than ZA, both in terms of therapy success and the number of symptom-free days.
Measure of benefits used in the economic analysis The benefit measures were the proportion of successfully treated patients and the number of symptom-free days. Both measures were derived directly from the effectiveness analysis.
Direct costs Discounting was irrelevant since the time horizon of the study was 12 weeks. The unit costs and the quantities of resources used were reported separately. The cost/resource boundary was that of the third-party payer. The cost items included in the analysis were unscheduled physician visits, emergency room visits, clinical outpatient visits and hospitalisations due to asthma exacerbations, the amount of short-acting beta2-antagonist bronchodilator therapy used as rescue therapy, asthma medications used in the study, and medications for the treatment of drug-related adverse events. Scheduled visits were not included in the costing. The cost of oral corticosteroids was negligible and was not included in the analysis. The drug costs were derived from the actual average wholesale prices, while published data were used for the other cost items. The period during which the quantities of resources used were obtained was not reported. The price year was 1999.
Statistical analysis of costs No statistical analyses of the costs were conducted.
Indirect Costs The indirect costs were not included.
Sensitivity analysis Due to the uncertainty around some data estimations, sensitivity analyses were carried out. The variables were improvements in FEV1, and the costs of the drugs and hospitalisation. The type of analysis was not reported, but it is presumed to have been a one-way analysis.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The daily costs of the drug treatments were $1.56 for FP and $2.05 for ZA. These corresponded to 86% (FP) and 72% (ZA) of the total costs. The total daily costs were $1.84 for FP and $2.89 for ZA.
Synthesis of costs and benefits The costs and the benefits were combined by performing average and incremental cost-effectiveness analyses for both of the benefit measures. The average cost per 12% increase in FEV1 was $3.47 for FP and $7.81 for ZA. The average cost per symptom-free day was $5.51 for FP and $14.98 for ZA. An incremental cost-effectiveness analysis was not performed since FP therapy dominated (less costly and more effective) ZA treatment in terms of both benefit measures. FP treatment remained the dominant strategy even when lung function improvements were varied. For the ZA therapy to be as cost-effective as FP therapy, the acquisition cost would have to have been reduced by at least 50%.
Authors' conclusions Fluticasone propionate (FP) delivered greater asthma symptom control and greater improvements in lung function at a lower cost than zafirlukast (ZA).
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear. Inhaled corticosteroids (such as FP) and leukotriene receptor antagonists represented two classes of drugs routinely used for the long-term treatment of asthma. You should assess whether they represent widely used therapies in your own setting.
Validity of estimate of measure of effectiveness The effectiveness analysis used a multi-centre, randomised, double-blind, double-dummy, placebo-controlled trial that was carried out on a relatively large sample of patients. As a result, the internal validity of the study was likely to be high. However, the authors stated that the time horizon of the study was too short to capture the long-term symptoms of the disease and the resources used for patients with asthma. Several patients were also lost to follow-up, but the intention to treat analysis should take account of this.
Validity of estimate of measure of benefit Two different benefit measures were used in the economic analysis since there was a lack of consensus on the most appropriate outcomes to be used in the case of asthma. The authors reported that the National Asthma Education Prevention Programme working group proposed the concept of symptom-free days as the main outcome measure.
Validity of estimate of costs All the categories of costs relevant to the perspective adopted in the study appear to have been included in the analysis. The cost of oral corticosteroids was not included in the analysis, but this omission is unlikely to have affected the authors' conclusions. The unit costs and the quantities of resources used were reported separately. Although the period during which the resources used were collected was not reported, a specific price year was used. However, statistical analyses were not conducted on the quantities and the costs, the variability being dealt with in the sensitivity analyses.
Other issues The authors made few comparisons of their findings with those from other studies. The issue of the generalisability of the study to other settings was not explicitly addressed, although a few sensitivity analyses were conducted on the most uncertain variables.
Implications of the study The authors pointed out that the study provided useful information that would help third-party payers and physicians to make decisions concerning the most cost-effective treatment for patients with persistent asthma. Future research should assess the optimal source for effectiveness data, in order to obtain high internal and external validity.
Source of funding Funded by GlaxoSmithKline, North Carolina, USA. Dr. Menendez is a contracted clinical investigator and a consultant to GlaxoSmithKline.
Bibliographic details Menendez R, Stanford R H, Edwards L, Kalberg C, Rickard K. Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma. PharmacoEconomics 2001; 19(8): 865-874 Indexing Status Subject indexing assigned by NLM MeSH Adult; Androstadienes /economics /therapeutic use; Anti-Asthmatic Agents /economics /therapeutic use; Asthma /drug therapy /economics; Cost-Benefit Analysis; Female; Fluticasone; Hospitalization /economics; Humans; Male; Randomized Controlled Trials as Topic; Tosyl Compounds /economics /therapeutic use; Treatment Outcome AccessionNumber 22001008197 Date bibliographic record published 30/09/2002 Date abstract record published 30/09/2002 |
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