Type of intervention Treatment. Economic study type Cost-effectiveness analysis.

Transcription

1 Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 micro g twice daily and budesonide 800 micro g twice daily in the treatment of adults and adolescents with asthma Lundback B, Jenkins C, Price M J, Thwaites R M 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 Salmeterol/fluticasone propionate combination product (SFC), a new dry powder inhaler, 50/250 micro g twice daily in the treatment of adults and adolescents with asthma. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population Patients aged 12 years or over with a documented history of reversible airway obstruction receiving inhaled corticosteroids (budesonide or beclomethasone dipropionate micro g/day or fluticasone propionate micro g per day) for 4 weeks or more before the 2-week run-in period were eligible for study entry. Patients were randomised to study treatment if, during the run-in period, they had a pre-bronchodilator forced expiratory volume in 1 sec (FEV_1) or peak expiratory flow (PEF) greater than or equal to 50% and less than or equal to 85% of the predicted normal value, an increase in FEV_1 greater than or equal to 15% or mean morning PEF less than or equal to 85% of maximum achievable after inhalation of a short-acting beta_2-agonist; used salbutamol more than twice a day or had a total daytime plus night-time symptom score greater than or equal to 2 (defined as symptoms at least twice during the day or symptoms causing the patient to awake at least twice during the night) on 4 or more of 7 days. Patients were excluded if, in the 4 weeks before the run-in period, they had had an acute exacerbation requiring hospitalisation, had received oral, parenteral or depot corticosteroids, or had had a lower respiratory tract infection or change in asthma medication. Other exclusion criteria included treatment with a long-acting beta_2-agonist or slow-release bronchodilator in the 2 weeks before the run-in period and a smoking history of 10 or more pack-years. Pregnant or lactating females were also excluded from study entry. Setting Hospital. The economic analysis was carried out in Sweden. Dates to which data relate The dates during which the effectiveness and resource use data were collected were not given; the effectiveness results were published in The price year was Source of effectiveness data The evidence for the final outcomes was based on a single study. Page: 1 / 5

2 Link between effectiveness and cost data Costing was conducted prospectively on the same patient sample as that used in the effectiveness analysis. Study sample Power calculations were used to determine the sample size (assuming a standard deviation of 401/min for morning PEF and the requirement for 90% power, it was calculated that data for 300 evaluable patients would be required to demonstrate a difference of 151/min with 95% confidence). A total of 353 patients with symptomatic moderate to severe asthma were included in the study. There were 180 randomly assigned patients with a mean (SD) age of 45 (15) years in the SFC group and 173 randomly assigned patients with a mean (SD) age of 48 (16) years in the budesonide group. Study design This was a multi-centre, double-blind, double-dummy, randomised controlled trial, carried out in 44 centres. The duration of the follow-up appears to have been 24 weeks. Regarding the number of patients who were lost to follow-up, it was reported that, after randomisation, 59 patients were withdrawn, 29 in the SFC group and 30 in the budesonide group. At the beginning of the 2-week run-in period, all asthma medications were withdrawn except the patients' usual inhaled corticosteroid; and salbutamol was provided for symptomatic relief as required. Patients were randomised at the end of the run-in period. Throughout the study patients kept a daily diary card record of their morning and evening PEF; daytime and night-time symptoms; and use of rescue salbutamol during the day and night. Analysis of effectiveness The principle used in the analysis of effectiveness was intention to treat. The clinical outcomes were successfully treated weeks (defined as an improvement of 5% or more in morning PEF), episode-free days (a composite measure defined as a day without the need for rescue medication, no nocturnal awakening or adverse events) and symptom-free days. The other outcomes were evening PEF values, daily symptom scores, use of rescue medication, and patient satisfaction. Adjustments were made for the effects of sex, age, country, and baseline morning PEF in the comparison between the treatment groups for morning PEF over weeks 1 to 24. Logistic regression analysis was used to analyse the proportion of patients with at least one asthma exacerbation during treatment allowing for effects of age, sex, and country. The two treatment groups were found to be comparable in terms of baseline demographic and clinical characteristics. Effectiveness results The effectiveness results were as follows: Patients in the SFC treatment arm had a significantly higher proportion of successfully-treated weeks (mean proportion, about 68% versus about 45%; (presented as a chart in the original paper)), episode-free days (about 38% versus about 45%) and symptom-free days (about 45% versus about 35%) throughout the treatment period, (p<0.001). Mean morning PEF increased by 451/min (baseline 3,611/min) in the SFC group and by 191/min (baseline 3,581/min) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the greater than three-fold lower corticosteroid dose (406 versus 3,801/min; p<0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 versus 3,981/min; p<0.001). SFC also provided significantly better control of daytime symptoms, a significantly greater reduction in the requirement for rescue salbutamol, and patient satisfaction with treatment compared with budesonide. Page: 2 / 5

3 Clinical conclusions These results demonstrate that SFC 50/250 micro g twice daily is superior to budesonide 800 micro g twice daily in the management of patients with moderate to severe asthma who were symptomatic on their existing dose of corticosteroid. Measure of benefits used in the economic analysis Successfully treated weeks, episode-free days, and symptom-free days. Direct costs Costs were not discounted due to the 6-month time frame of the cost analysis. Quantities were reported separately from the costs but cost items were not reported separately. The cost analysis covered the costs of hospital contacts (emergency room visits, intensive care unit days, inpatient days and outpatient clinic visits), general practitioner contacts (home and office/practice visits, and telephone calls), and medications (study drugs, rescue medications and other asthma-related prescription drugs to treat asthma symptoms or acute exacerbations). The perspective adopted in the cost analysis was that of the (Swedish) health care system. The source of unit costs was Swedish government statistics. Patients who were withdrawn from the study were assumed to continue to use resources at the same mean rate as those patients still in the trial in their respective treatment arm. The price year was Indirect Costs Indirect costs were not included. Currency Swedish kroner (Sek) converted to US dollars ($). Sensitivity analysis A series of one-way sensitivity analyses was performed on the definition of successfully-treated weeks (redefined on the basis of the percentage improvement in PEF required to achieve a success from 1 to 10% in 1% increments), assumptions regarding patients prematurely withdrawn from the study (in the best case scenario, they were assumed to be symptom-free and episode-free from the time of withdrawal; in the worst-case scenario, they were assumed to be symptomatic and not episode-free from the time of withdrawal). Estimated benefits used in the economic analysis In the original paper these results were presented in the form of charts rather than as exact figures. Patients in the SFC treatment arm had a significantly higher proportion of successfully-treated weeks (mean proportion, about 68% versus about 45%), episode-free days (about 38% versus about 45%) and symptom-free days (about 45% versus about 35%) throughout the treatment period, (p<0.001). Cost results The mean total direct healthcare costs per patient per day were very similar between the two groups; Sek 19.6 ($2.38) in the SFC arm compared with Sek 18.5 ($2.24) in the budesonide arm. Synthesis of costs and benefits The mean cost per successfully-treated week was Sek 204 ($24.75) in the SFC group versus Sek 300 ($36.40) in the budesonide group; the incremental cost-effectiveness ratio (ICER) (95% confidence interval (CI) using a nonparametric 'Bootstrap') for an additional week of improved lung function with SFC relative to budesonide was Sek 31.6 (-37.6 to 113.6). The mean costs per episode-free day were Sek 51.1 ($6.20) and Sek 75.1 ($9.11), respectively, corresponding to an ICER of Sek 7.7 (-7.8 to 29.5). The mean cost per symptom-free day was Sek 42.2 ($5.12) and Sek 53.0 ($6.43), respectively, corresponding to an ICER of Sek 9.2 (-11.8 to 47.8). Sensitivity analysis showed that the Page: 3 / 5

4 results were stable over a wide range of assumptions. Authors' conclusions The results suggest that SFC is a more cost-effective treatment than budesonide in the management of moderate to severe asthma. CRD COMMENTARY - Selection of comparators No specific justification was given for the choice of budesonide as the comparator; the authors simply stating that it was among the existing asthma treatments. You, as a database user, should consider whether this is a widely used health technology in your own setting. It was mentioned that the design of this study allowed comparison of the recommended two possible treatment options for patients who remain uncontrolled on inhaled corticosteroid therapy alone (asthma management guidelines specifically recommended the addition of a long-acting beta2-agonist, or an increase in the ICS dose). Validity of estimate of measure of effectiveness The effectiveness results are likely to be internally valid given the double-blind randomised nature of the study design, the power calculations which were performed, the comparability of the study groups, and intention to treat basis of the analysis conducted. The study sample appears to have been representative of the study population. Validity of estimate of measure of benefit Estimation of benefits was directly derived from the effectiveness analysis. Regarding the justification for the choice of the benefit measures, it was mentioned that a range of benefit measures was used in the cost-effectiveness analysis as there is no single outcome measure for asthma that reflects the full range of treatment benefits for patients, clinicians and healthcare decision-makers. The chosen measures were deemed to reflect the multiple aims of asthma management. However, it is not entirely clear why the authors did not choose other more widely-used benefit measures such as lifeyears, or quality-adjusted life-years gained. Validity of estimate of costs The following positive features may have enhanced the validity of the cost results: resource use profile was reported separately from the costs; adequate details of methods of cost estimation were given; the price year and perspective adopted in the cost analysis were specified. However, the following features may have adversely affected the validity: it is not entirely clear whether unit costs were based on charges or true costs (although it is likely to have been actual costs relevant to the Swedish healthcare system); the cost breakdown was not reported; statistical analyses do not appear to have been performed on resource use and cost data; the effects of alternative procedures on indirect costs were not addressed; and the cost results may not be generalisable outside the study setting. Other issues The authors' conclusion appears to be justified given the randomised nature of the study design and the sensitivity analyses performed. The issue of generalisability to other settings or countries was not addressed, although appropriate comparisons were made with other studies. Some implicit comments were made regarding the degree to which the study sample was representative of the study population. With respect to the chronic nature of the disease, a cost-utility approach may have been a more informative framework for the analysis in order to incorporate the subjective assessment of the patients in the study. One of the limitations of the study, as with all clinical trial-based economic analyses, was deemed to have been the highly controlled environment, close patient monitoring and likely high levels of patient compliance; which may have resulted in an underestimation of the true economic consequences of poor asthma control. Implications of the study Page: 4 / 5

5 Powered by TCPDF ( Clearly, there is a need for further economic evidence of alternative asthma therapies if economic evaluation is to play a greater role in decision-making in asthma. Source of funding None stated. Bibliographic details Lundback B, Jenkins C, Price M J, Thwaites R M. Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 micro g twice daily and budesonide 800 micro g twice daily in the treatment of adults and adolescents with asthma. Respiratory Medicine 2000; 94(7): PubMedID Other publications of related interest Jenkins C, Woolcock A J, Saarelainen P, Lundback B, James M H. Salmeterol/fluticasone propionate combination product 50/250 mu g twice daily is more effective than budesonide 800 mu g twice daily in treating moderate to severe asthma. Respiratory Medicine 2000;94: Indexing Status Subject indexing assigned by NLM MeSH Adult; Albuterol /administration & dosage /economics; Androstadienes /administration & dosage /economics; Anti- Inflammatory Agents /administration & dosage /economics; Asthma /drug therapy /economics /physiopathology; Bronchodilator Agents /administration & dosage /economics; Budesonide /administration & dosage /economics; Cost- Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate /drug effects; Prospective Studies; Treatment Outcome AccessionNumber Date bibliographic record published 31/07/2001 Date abstract record published 31/07/2001 Page: 5 / 5