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Cost-utility of inhaled corticosteroids in patients with moderate-to-severe asthma |
Marchetti M, Cavallo M C, Annoni E, Gerzeli S |
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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 Four inhaled corticosteroids (ICS) for the treatment of moderate-to-severe asthma were studied. The ICS were beclomethasone (BDP), beclomethasone-extrafine (BDP-EF), fluticasone (FP) and budesonide (BUD).
In patients with moderate asthma, the ICS were compared at daily doses of 1,000 microg BDP, 400 microg BDP-EF, 400 microg FP and 800 microg BUD.
In patients with severe asthma, the ICS were compared at daily doses of 1,500 microg BDP, 800 microg BDP-EF, 1,000 microg FP and 1,600 microg BUD.
Study population The study population comprised a hypothetical cohort of patients with moderate-to-severe asthma.
Setting The setting was secondary care. The economic study was carried out in Italy.
Dates to which data relate The effectiveness evidence came from studies published between 1996 and 2002. No dates for the resource use data were reported. The price year was 2004.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of completed studies and authors' opinions.
Modelling A decision tree was constructed to assess the costs and benefits of the four ICS under examination. Each branch of the decision tree led to a Markov model with seven health states. Each state corresponded to a defined level of preference-based QoL, which was described according to the Asthma Symptom Utility Index (ASUI), a questionnaire used to elicit the utility of patients with asthma. In the ASUI, disease intensity, duration and adverse events associated with each medication were taken into consideration. The time horizon of the model was 2 months and the cycle length was 1 day. A simplified structure of the tree was reported.
Outcomes assessed in the review The outcomes estimated from the literature were:
the percentages of patients with wheezing, cough, dyspnoea and night awakening before day 4 and after day 7 (for both moderate and severe asthma), associated with the different medications;
ASUI distributions for each medication (both for moderate and severe asthma);
the mean ASUI score for each medication;
the utility values associated with each health state; and
the rates of exacerbations.
Study designs and other criteria for inclusion in the review A systematic review of the literature was undertaken to identify the primary studies. Published clinical trials comparing two of the four ICS were selected, provided that they were administered at medium-to-high doses and were not associated with other drugs for asthma care. The approach used to convert the percentage of days (or nights) free of asthma symptoms into utility values was described extensively in the appendix.
Sources searched to identify primary studies MEDLINE was searched from 1998 to 2003 using the terms "Beclomethasone", "clinical trials" and "English".
Criteria used to ensure the validity of primary studies The use of randomised clinical trials ensured the internal validity of the primary studies.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included Eight primary studies provided the clinical data.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The percentage of patients with wheezing before day 4 for moderate asthma (severe asthma) was 17% (13%) with no medication, 44% (28%) with BDP-EF, 35% (19%) with FP, 25% (15%) with BUD and 21% (16%) with BDP.
The percentage of patients with wheezing after day 7 for moderate asthma (severe asthma) was 57% (68%) with no medication, 18% (31%) with BDP-EF, 37% (52%) with FP, 37% (62%) with BUD and 47% (61%) with BDP.
The percentage of patients with cough before day 4 for moderate asthma (severe asthma) was 7% (1%) with no medication, 45% (22%) with BDP-EF, 24% (22%) with FP, 23% (23%) with BUD and 21% (18%) with BDP.
The percentage of patients with cough after day 7 for moderate asthma (severe asthma) was 85% (96%) with no medication, 22% (43%) with BDP-EF, 39% (45%) with FP, 41% (41%) with BUD and 47% (55%) with BDP.
The percentage of patients with dispnoea before day 4 for moderate asthma (severe asthma) was 12% (12%) with no medication, 52% (18%) with BDP-EF, 18% (16%) with FP, 26% (14%) with BUD and 17% (13%) with BDP.
The percentage of patients with dispnoea after day 7 for moderate asthma (severe asthma) was 72% (72%) with no medication, 20% (53%) with BDP-EF, 53% (58%) with FP, 35% (65%) with BUD and 57% (67%) with BDP.
The percentage of patients with night awakening before day 4 for moderate asthma (severe asthma) was 15% (15%) with no medication, 43% (20%) with BDP-EF, 37% (26%) with FP, 39% (25%) with BUD and 25% (19%) with BDP.
The percentage of patients with night awakening after day 7 for moderate asthma (severe asthma) was 62% (62%) with no medication, 21% (48%) with BDP-EF, 17% (35%) with FP, 15% (37%) with BUD and 37% (52%) with BDP.
ASUI distributions will not be reported here. The mean ASUI for moderate asthma (severe asthma) was 0.563 (0.544) with no medication, 0.624 (0.592) with BDP-EF, 0.603 (0.584) with FP, 0.618 (0.575) with BUD and 0.586 (0.565) with BDP.
The utility values were 0.35 for health state 1, 0.45 for health state 2, 0.55 for health state 3, 0.65 for health state 4, 0.75 for health state 5, 0.85 for health state 6 and 0.95 for health state 7.
The frequency of exacerbations was 2 to 3% over a 2-month period.
Methods used to derive estimates of effectiveness Due to the lack of evidence from clinical trials, the authors made an assumption regarding the frequency of local adverse effects with ICS.
Estimates of effectiveness and key assumptions The authors assumed that local adverse events occurred at the same rate, independently of the ICS used. The rate was 2% in moderate asthma and 4% in severe asthma. Therefore, the utility score was reduced by 0.03 since adverse events lasted only 2 weeks over the 2-month time horizon.
Measure of benefits used in the economic analysis The summary benefit measure used was the quality-adjusted life expectancy (QALE). This was estimated for the 2-month timeframe of the analysis and presented in terms of the quality-adjusted life-days.
Direct costs The analysis of the costs was carried out from the perspectives of the Italian NHS and society. The health services included in the economic analysis were ICS, general practitioner and specialist visits, day hospital, emergency department visit, hospital stay, diagnostic tests (e.g. gas analysis, haematochemical panel and chest X-ray), respiratory rehabilitation sessions, spirometry, spacers and oxygen. The unit costs were presented separately from the quantities of resources used for all items. In addition, a detailed list of all categories of costs was provided. The costs were mainly estimated using national fee-for-service data, considered to be the best available proxy for costs. Details of the calculations of inpatient and outpatients services were extensive. Retail prices were used for drugs. The resource use data were estimated from a panel of seven pneumologists and two general practitioners, whose clinical profiles were reported in the appendix to the paper. The experts estimated pulmonary function, daily doses and access to health care services. Since the costs were estimated over a 2-month period, discounting was not relevant and was not carried out. The price year was 2004.
Statistical analysis of costs The costs were treated deterministically. However, monthly consumption of all resources was strictly correlated with pulmonary function and utility scores.
Indirect Costs The indirect costs (i.e. productivity losses) were included in the analysis because a societal perspective was adopted. Out-of-pocket expenses were also included in the societal analysis, even though these are direct costs. The days off work due to asthma were estimated from a UK study and were reported. However, the cost of a day off work, which was derived from the average annual wage, was not given. The other aspects of the analysis (i.e. discounting and price year) were the same as in the analysis of direct costs.
Sensitivity analysis Univariate and multivariate sensitivity analyses were carried out to assess the robustness of the base-case results to variations in clinical and economic inputs. The impact of changes in the unit costs of ICS, indirect costs and transition rates was investigated. In addition, the analysis was replicated using a 12-month time horizon to consider possible deaths occurring during this timeframe. The alternative values, the sources of which were not stated, were likely to have been set by the authors.
Estimated benefits used in the economic analysis For moderate asthma, the expected QALE was 38.49 days with BDP, 40.82 days with BDP-EF, 39.08 days with FP and 39.58 days with BUD.
For severe asthma, the expected QALE was 34.23 days with BDP, 35.77 days with BDP-EF, 35.27 days with FP and 34.79 days with BUD.
Cost results When the societal perspective was adopted, the expected costs for moderate asthma were Euro 701 with BDP, Euro 658 with BDP-EF, Euro 705 with FP and Euro 686 with BUD. For severe asthma, the expected costs were Euro 880 with BDP, Euro 839 with BDP-EF, Euro 895 with FP and Euro 906 with BUD.
When the NHS perspective was adopted, the expected costs for moderate asthma were Euro 412 with BDP, Euro 391 with BDP-EF, Euro 425 with FP and Euro 411 with BUD. For severe asthma, the expected costs were Euro 526 with BDP, Euro 514 with BDP-EF, Euro 562 with FP and Euro 566 with BUD.
Synthesis of costs and benefits Average and incremental cost-utility ratios were calculated to combine the costs and QALE of the different ICS. BDP and BDP-EF were considered as the reference strategies.
The average cost per quality-adjusted life-day was:
Euro 18.21 with BDP, Euro 16.12 with BDP-EF, Euro 18.03 with FP and Euro 17.33 with BUD for moderate asthma from a societal perspective;
Euro 25.70 with BDP, Euro 23.45 with BDP-EF, Euro 25.37 with FP and Euro 26.04 with BUD for severe asthma from a societal perspective;
Euro 10.70 with BDP, Euro 9.58 with BDP-EF, Euro 10.87 with FP and Euro 10.38 with BUD for moderate asthma from an NHS perspective; and
Euro 15.36 with BDP, Euro 14.37 with BDP-EF, Euro 15.93 with FP and Euro 16.26 with BUD for severe asthma from an NHS perspective.
The incremental analysis showed that, regardless of the perspective and asthma severity, BDP-EF was the dominant strategy.
The sensitivity analysis showed that BDP-EF remained the dominant strategy, except in cases of substantial reductions in the prices of other ICS. Changes in the other model inputs did not alter dramatically the conclusions of the analysis.
Authors' conclusions Over a 2-month timeframe, beclomethasone-extrafine (BDP-EF) represented a cost-effective strategy for the treatment of moderate-to-severe asthma in Italy.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear since the four ICS available in Italy were included. Dosages for both moderate and severe asthma were reported. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The clinical evidence came from published studies and a systematic review of the literature was undertaken. Some details of the methods used to conduct the review were provided. All the data came from randomised clinical trials, which ensure a high internal validity. The method used to calculate the primary estimates was reported in the appendix to the paper. The issue of homogeneity across the primary studies was not addressed. Some assumptions were also made. The issue of uncertainty surrounding key clinical data was tested in the sensitivity analysis.
Validity of estimate of measure of benefit The summary benefit measure was QALE. This was estimated using a validated measure, then converted into utility measures using a specific approach that was described clearly. Discounting was not applied because of the short time horizon of the analysis. The use of quality-adjusted survival enables comparisons with the benefits of other health care interventions. However, the authors stated that the ASUI scale was not anchored on death and, therefore, caution is required when comparing the current benefits with other benefit measures related to death.
Validity of estimate of costs A broad perspective was adopted in the study and the indirect costs were included. Nevertheless, the cost/resource boundary of the NHS was also analysed. Extensive information on the unit costs, quantities of resources used and price year was provided, which enhances the possibility of replicating the analysis in other settings and performing reflation exercises in other time periods. The source of the costs was reported for all items. Data on resource consumption were obtained from an expert panel. Statistical analyses of the costs were not carried out. The cost estimates were specific to the study setting but key cost items were varied in the sensitivity analysis.
Other issues The authors compared their findings with those from other studies, but did state that their study was the first Markov model assessing the cost-utility of more than two ICS. The issue of the generalisability of the study results to other settings was not explicitly addressed, although sensitivity analyses were carried out. The study referred to patients with moderate-to-severe asthma and this was reflected in the authors' conclusions. Some limitations of the analysis were highlighted. First, the model considered only transition from worse to better health states and the opposite transition was not modelled. Second, clinically relevant differences in utility scores were not established. Third, the impact of different asthma devices was not investigated.
Implications of the study The study results suggested that the recommendation of using BDP-EF would save from Euro 7 million to Euro 29 million per year from the perspective of the Italian NHS.
Bibliographic details Marchetti M, Cavallo M C, Annoni E, Gerzeli S. Cost-utility of inhaled corticosteroids in patients with moderate-to-severe asthma. Expert Review of Pharmacoeconomics and Outcomes Research 2004; 43(5): 549-564 Other publications of related interest Price MJ, Briggs AH. Development of an economic model to assess the cot-effectiveness of asthma management strategies. Pharmacoeconomics 2002;20:183-94.
Malone DC, Armstrong EP. Economic burden of asthma: implications for outcomes and cost-effectiveness analyses. Expert Rev Pharmacoeconomics Outcomes Res 2001;1:177-86.
Indexing Status Subject indexing assigned by CRD MeSH Albuterol /adverse effects /administration & Anti-Inflammatory Agents /adverse effects /administration & Asthma /diagnosis /prevention & Beclomethasone /adverse effects /administration & Budesonide /adverse effects /administration & Cost-Benefit Analysis; Costs and Cost Analysis; Drug Costs; Health Care Costs; Health Planning; Health Status; Hospitalization; Ipratropium /adverse effects /administration & Methylprednisolone /adverse effects /administration & Prednisone /adverse effects /administration & Quality of Life; Quality-Adjusted Life Years; Radiography, Thoracic; Spirometry; control /drug therapy; dosage /therapeutic use /economics; dosage /therapeutic use /economics; dosage /therapeutic use /economics; dosage /therapeutic use /economics; dosage /therapeutic use /economics; dosage /therapeutic use /economics; dosage /therapeutic use /economics AccessionNumber 22004008336 Date bibliographic record published 30/04/2006 Date abstract record published 30/04/2006 |
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