|
Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma |
Rutten-van Molken M P, van Doorslaer E K, Till M D |
|
|
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 long acting inhaled beta 2-agonists, salmeterol and formoterol as a part of a treatment regimen for patients requiring regular treatment of asthma and for nocturnal asthma.
Economic study type Cost-effectiveness analysis.
Study population Patients over the age of 18 with asthma who potentially might benefit from the use of long acting beta 2-agonists.
Setting Community and primary care. The economic analysis was conducted in Rotterdam, the Netherlands.
Dates to which data relate Data on clinical outcomes and resources were collected during a six month period, but the year was not mentioned in the paper. 1995 prices were used.
Source of effectiveness data Effectiveness data were derived from a single study.
Link between effectiveness and cost data Costing was undertaken prospectively on the same sample as the one used in the effectiveness study.
Study sample 482 patients were included in the study sample, with 241 patients being randomised to the formoterol and salmeterol groups respectively. Potential patients who might benefit from treatment by long acting beta 2-agonists were identified by their respiratory physicians. Power calculations were not used to determine the sample size.47 patients had previously been excluded from the study for not meeting the necessary criteria.
Study design The study was a randomised controlled trial including 41 centres in six European countries (France, Italy, Spain, Sweden, Switzerland and the UK). The average duration of follow up for the formoterol and salmeterol groups respectively was 168 (+/- 36) days and 166 (+/- 36) days. Patients were allocated to either group using a computer generated random numbers list. There was an overall loss to follow up of 48 patients (10%), of which 21 (9%) dropped out of the formoterol group and 27 (11%) from the salmeterol group. Neither physicians nor patients were blinded to the assessment of outcomes.
Analysis of effectiveness The analysis of effectiveness was based on intention to treat. The primary health outcomes measured were the number of episode free days (EFDs) and improvement in quality of life. Groups were shown to be comparable in demographic and other baseline characteristics (mean duration of illness, mean evening peak flow, mean morning peak flow, mean quality of life scores measured on the St George's Respiratory Questionnaire score, and number of smokers).
Effectiveness results The average number of EFDs per patient per six months in the formoterol and salmeterol groups respectively were 97 (+/- 64) and 95 (+/- 62) and the number of patients reaching a clinically determined improvement in quality of life score were 64% and 62% in the two groups. Neither of these findings were statistically significant.
Clinical conclusions No differences were found in the clinical effectiveness of the two drugs, or in the tolerability and impact on quality of life between the two drugs.
Measure of benefits used in the economic analysis The number of episode free days and the proportion of patients reaching a clinically relevant improvement in quality of life were estimated. Quality of life was measured on the St George's Respiratory Questionnaire Scale, which was administered to patients.
Direct costs Resources used were identified through the case record form recorded monthly by physicians participating in the study. This included information on: number of GP contacts at home or in practice; number of specialist contacts; emergency room contacts; nurse contacts; number and duration of hospital admissions; number of puffs/actuations of relief medication (from patient diaries); other medication used; lung function and laboratory tests; X-rays and ECGs and other diagnostic tests or therapies received. The questionnaire also recorded information on mode of transportation and distance travelled.
Costs were analysed separately from resources using national and local sources in the different countries, and included fees paid by health care funders and also co-payments from patients. Medication costs were taken from national market prices excluding value added tax, although in Italy and Spain the price for formoterol was estimated by the company as this drug is not currently on the market in these countries. Hospital per diem prices in Italy andFrance were estimated using a weighted average of costs and length of stay for DRGs related to respiratory disease and in Spain and the UK the per diem price was based on information from several hospitals. Costs for laboratory tests were not available in the UK and were assumed to be the average from the other five countries. All costs were analysed from a societal perspective and were valued in 1995 prices. Costs were not discounted.
Statistical analysis of costs As costs were observed to be skewed to the right, the non parametric Mann Whitney U test was used to test the difference between formoterol and salmeterol.
Indirect Costs Indirect costs were estimated using the human capital approach and information on absence from employment was recorded during the clinical study, when this was deemed by the patients to be related to asthma. In all countries except Italy these costs of production loss were based on a weighted average of daily earnings from different sectors of the economy derived from the 1995 International Labour Organisation, yearbookof labour statistics. In Italy, where these statistics were not available, an estimate of national earnings was derived from the national average gross yearly retribution in 1994, divided by the number of annual working days (261).
Currency Local currencies were converted into US dollars ($) at the following rates: 1627 Italian Lira, 124.48 Spanish pesetas, 4.996 French Francs, 0.633 Pounds Sterling, 1.18 Swiss Francs and 7.14 Swedish kroner.
Sensitivity analysis One way sensitivity analysis was conducted to examine the impact of different approaches to costing; specifically the impact of using treatment completers only rather than intention to treat, use of the friction cost approach (which reduces productivity losses) where a friction period of only the first three months absenteeism was costed and the use of GDP Purchasing Power Parities instead of pooled exchange rates.
Estimated benefits used in the economic analysis The mean number of episode free days in the two groups respectively were 96.76 and 94.15 for the formoterol and salmeterol groups. Similarly the proportion of patients attaining a clinically relevant improvement in quality of life was 63.72% and 62.04%. None of these outcomes were significantly different.
Cost results The mean costs per patient per 6 months for the formoterol and salmeterol groups respectively were $1,559.22 (+/- 2,759.74) and $1,737 (+/- 3,561.97). These differences in costs were not statistically significant. The authors did report significant differences in overall costs between countries, and stated that Swiss patients had significantly higher costs, and Italian patients significantly lower costs, than those in the other countries. No exact figures were stated. One way sensitivity analyses also did not produce any statistically significant difference in costs. Costs of adverse effects and concomitant medication required were included in the costing analysis.
Synthesis of costs and benefits An incremental cost effectiveness analysis was not conducted because the outcomes were not significantly different. However the average cost per episode free day for formoterol and salmeterol respectively was $10.60 (range: 8.00 - 13.60)and $12 (range: 8.60 - 16.10). Similarly the mean cost per patient reaching a clinically relevant improvement in quality of life was $1,602.18 (range: 1197 - 2097) and $1,825.13 (range: 1,282-2,496).
Authors' conclusions The authors concluded that there were no significant differences in terms of outcomes or costs between the two drugs and recommended that physicians use the lower priced of the two drugs in each country.
CRD COMMENTARY - Selection of comparators The authors provided a justification for the two comparators used. Both formoterol and salmeterol have been demonstrated in the literature to be effective treatments as part of a regimen to manage and control asthma. As noted by the authors an economic analysis comparing these long acting beta 2-agonists with short acting beta 2-agonists would also have been useful.
Validity of estimate of measure of benefit The clinical results were taken from a multi-centre open label randomised controlled trial for a six month period. Physicians and patients were not, however, blinded to participation in the study.
Validity of estimate of costs Adequate details were given of the sources of estimates, resource use and price data and costs were determined from a societal perspective. Sensitivity analyses demonstrated that the cost results were robust.
Other issues This is a well reported study, which has taken into account some of the potential uncertainties with the data. The results, however, may not be generalisable outside the health care systems of the six European countries in the study.
Implications of the study There is a need to conduct a well designed economic evaluation to compare long acting and short acting beta 2 agonists for asthma.
Source of funding Financially supported by Novartis.
Bibliographic details Rutten-van Molken M P, van Doorslaer E K, Till M D. Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma. PharmacoEconomics 1998; 14(6): 671-684 Indexing Status Subject indexing assigned by NLM MeSH Adrenergic beta-Agonists /economics /therapeutic use; Adult; Albuterol /analogs & Asthma /drug therapy /economics; Bronchodilator Agents /economics /therapeutic use; Cost-Benefit Analysis; Ethanolamines /economics /therapeutic use; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; derivatives /economics /therapeutic use AccessionNumber 21999008009 Date bibliographic record published 31/03/1999 Date abstract record published 31/03/1999 |
|
|
|