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Management of Asthma: Beyond the Cost

Pharmacoeconomics

Paul Jones
St. Georges Medical School
London, United Kingdom

Introduction

Health economics is a discipline covering many aspects of the costs of health, although pharmaco-economics tends to be concerned more with the value that is attached to a treatment. Many pharmaco-economic analyses produce results that are expressed as a ratio of health outcome divided by cost. There is a wide choice of outcomes in asthma and there are many different factors that may be taken into consideration when calculating costs. Thus the potential variety of analyses, and methods of expressing results, is very great.

Types of Health Economic Analysis

There are four general types of health-economic evaluation. Cost-Minimization: in which a comparison is made of two treatments whose consequences (i.e. outcomes) are equal. These analyses are limited by the assumption that the therapies have equal effectiveness. Cost-Benefit: in which all costs and outcomes are given a monetary value. They are restricted by the difficulty in assessing all the costs associated with therapy. Cost-Effectiveness: in which a single outcome is selected and treatments are compared in terms of the cost required to achieve improvement in that particular outcome. These analyses have the advantage that they measure the effectiveness of therapy, but even they are limited in scope because they can only handle one therapeutic outcome at a time. The fourth type of evaluation, Cost-Utility Analysis, attempts to overcome some of these limitations. It is a more comprehensive and generalisable variant of the cost-effectiveness analysis, since a utility measure attempts to express the overall effect of a disease upon the patient in a single continuous scale that ranges from perfect health to death (1).

Most pharmaco-economic analyses are of the cost-effectiveness type, designed to ask: "Which treatment is more effective?" The simplest form of analysis is to calculate a mean cost-effectiveness ratio that gives an indication of the average cost of achieving a given outcome with each treatment. [Note: There is another health economic question, not addressed in this review, but asked by healthcare commissioners and governments, which is: "Are we going to treat the patients?"]

Health Economic Perspectives

Interest in health economic analyses in asthma may be grouped into three broad categories. The first includes the perspectives of governments and the pharmaceutical industry. The second, organizations involved in the purchase of health care such as health authorities or health maintenance organizations and those that provide care such as hospitals and clinics. The third is that of the individual - the patient who has to meet the direct and indirect costs of their disease and the clinician who has to work within a finite budget. None of these groups is more important than the other, however, their perspectives all differ. As a result, the equations used for pharmaco-economic analyses in different settings may have different components, but the basic approach is common to all, in that output is divided by input (i.e. the consequence of the therapy is divided by the cost). The choice of outcome and choice of factors that make up the cost will depend upon the purpose of the analysis, particularly the perspective from which the analysis is being carried out. In large measure, this review will address these issues from the perspective of the clinician and patient, but this cannot be divorced from the others.

Type of Health Outcome

The range of possible outcomes that can be used in these analyses is very wide. Indeed any clinically relevant measurement can be used. Interestingly, physiological measurements do not appear to be very useful in this setting, Consider, for example, an analysis that reported the cost in $ per day for each 5% increase from baseline in morning Peak Expiratory Flow (PEF). One asks immediately: What does that mean - what is the clinical value of a 5% improvement in PEF? Whilst such a parameter might appear to be useful when comparing different long acting bronchodilators, the use of physiological outcomes does not seem to provide the type of information that is most appropriate when trying to assess the value of treatment in asthma. Symptom or event-based outcomes have greater usefulness. Compare the previous example with the cost of preventing one exacerbation or providing an additional undisturbed night's sleep. These outcomes seem to be more appropriate, but they must be chosen appropriately.

Asthma has both episodic and chronic effects. Episodic events are, in theory, very attractive as outcome measures in health economic analyses because they may be easy to identify and count, but episodes such as death, hospital admissions and severe exacerbations requiring oral corticosteroids are relatively infrequent. Furthermore, with the obvious exception of death (which is too infrequent to be considered as an outcome in health economic analyses in asthma, except on an epidemiological scale) these outcomes are not standardized. Admissions are dependent on local policies and resources, and there is no agreed method of defining an exacerbation that allows direct comparisons between studies.

Outcomes such as hospital admissions and acute exacerbations reflect only occasional events. With good asthma control, these may be relatively rare, yet the patients can still experience some disturbance to their daily lives due to asthma. There are two basic approaches to assessing the level of the daily effects of asthma: diary cards and health-related quality of life measurements. Diary cards may be used in a number of ways, but one of the most useful is to calculate the number of symptom-free days or undisturbed nights. The latter is quite easy, but the definition of a symptom-free day is not so straight forward. For example, in a recent study, patients reported more days with no disturbance of daily activities than days without symptoms (2). Symptom-free days are used quite frequently in health economic analyses (3) . Diary cards may also be used to record use of short-acting bronchodilator, so permitting the calculation of rescue-free days (4). This of course begs the question - What is the clinical value of one rescue medication-free day ? A further refinement of the diary card approach is to produce a composite score made up of: absence of an asthma attack, and no need for rescue medication, sleep disturbance or adverse event due to the treatment - i.e. an 'episode-free day' (3, 5) .

Health-related quality of life measures can also be used as an outcome, and in this respect may be used because of their ability to provide an estimate of whether the improvement in health is clinically significant. A comparison between the disease-specific Asthma Quality of Life Questionnaire (AQLQ) and a number of utility measures suggested that the AQLQ is more sensitive and reliable than existing utility instruments (6). The AQLQ can provide an estimate of whether an improvement in health is clinically significant, thus it is possible to provide an estimate of the treatment cost needed to produce one patient who has a clinically significant improvement in health (7).

Health Costs

Health costs may be both direct and indirect. Direct costs are the easiest to obtain because these relate to health resource use (not just the cost of the drug). Indirect costs are those related to lost employment etc, and these may be high. For example, in Spain direct costs of asthma were found to rise with asthma severity, but at each level of severity the indirect costs were twice as high as the direct costs (8). A recent study from the US found that wage replacement costs associated with asthma-induced disability or absence were equal to the medical care costs (9). Measurement of direct costs has shown that admissions are the highest cost item by a large measure, which is one reason why a minority of patients incur a large proportion of the total asthma costs (8). There are however, big differences in healthcare costs and management strategies between countries such that it is difficult to make comparisons between countries. For example, in analysis of adding formoterol to budesonide, in Sweden the extra costs of formoterol were offset by savings from reduced exacerbations; in Spain the picture was mixed: adding formoterol to low dose budesonide generated savings, whereas for moderate doses of budesonide about 75% of extra formoterol costs could be recouped. In the UK, other savings offset half the cost of formoterol (10).

Example of a Pharmaco-economic Analysis

In a comparison of two treatments (3), the direct costs of treatment were very similar (Treatment A $2.4/d; Treatment B $2.2/d). Treatment A was significantly more effective: 46% of study days in patients receiving Treatment A were symptom-free compared with 35% with Treatment B. As a result, costs with treatment A were $5.1 per symptom-free day vs $6.4 with Treatment B. This is not the whole picture, because we generally start from the assumption that the patient is being treated for their asthma (i.e. we are not asking whether we can afford to treat the asthma, but: Which is the best 'value for money'?). Thus we are more often interested in the question: What is the cost of changing treatments? This requires calculation of the incremental cost effectiveness ratio (ICER), which evaluates the net difference in cost and effects between treatments and shows the cost of switching from one treatment to another. In this case, the ICER for Treatment A was an extra $1.1 per day for each additional symptom-free day compared to treatment B. In this context it is worth noting that an ICER $5 has been judged to be an acceptable premium to pay for a day without asthma symptoms (11).

Conclusions

Most pharmaco-economic analyses in asthma have been carried out by pharmaceutical companies, so it is not surprising that where comprehensive data are published, they usually favour the products produced by that company. One company, in particular has a very productive health economic department with many papers in the asthma therapeutic field. In most cases comparisons of differences in cost-effectiveness of similar classes of agents produced by different companies are relatively small. A recent health-utility study carried out by an independent group of health economists concluded that the cost of one symptom free day gained by the use of inhaled corticosteroids was $7.50. They judged that this treatment gave good comparative value (12). It would be of interest to see cost-effectiveness analyses of inhaled corticosteroid vs leukotriene receptor antagonists, but to date only retrospective total asthma cost studies have been published (13, 14). Health economic studies are becoming more widely available, and whilst it is unlikely that clinicians will make decisions based solely upon such analyses , such data may increasingly aid clinical choices.

References

  1. Blumenschein K, Johannesson M. Relationship between quality of life instruments, health state utilities, and willingness to pay in patients with asthma. Annals of Allergy, Asthma, & Immunology 1998;80(2):189-94.
  2. Barley EA, Jones PW. A comparison of global questions versus health status questionnaires as measures of the severity and impact of asthma. European Respiratory Journal 1999;14(3):591-596.
  3. Lundbäck B, Jenkins C, Price MJ, Thwaites RMA. Cost-effectiveness of salmeterol/fluticasone proprionate combination product 50/250 mcg twice daily and budesonide 800 mcg twice daily in the treatment of adults and adolescents with asthma. Respir Med 2000;94:724-32.
  4. Everden P, Lloyd A, Hutchinson J, Plumb J. Cost effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma. Respir Med 2002;96:250-8.
  5. Sculpher MJ, Buxton MJ. The episode-free day as a composite measure of effectiveness. An illustrative economic evaluation of formoterol versus salbutamol in asthma therapy. Pharmacoeconomics 1993;4:345-352.
  6. Juniper EF, Norman GR, Cox FM, Roberts JN. Comparison of the standard gamble, rating scale, AQLQ and SF-36 for measuring quality of life in asthma. European Respiratory Journal 2001;18(1):38-44.
  7. Price D, Haughney J, Duerden M, Nicholls C, Moseley C. The cost effectiveness of chlorofluorocarbon-free beclomethasone dipropionate in the treatment of chronic asthma: a cost model based on a 1-year pragmatic, randomised clinical study. Pharmacoeconomics 2002;20(10):653-64.
  8. Serra-Batlles J, Plaza V, morejon E, Comella A, Bruges J. Costs of asthma according to the degree of severity. Eur respir J 1998;12:1322-6.9.
  9. Birnbaum HG, Berger WE, Greenberg PE, Holland M, Auerbach R, Atkins KM, et al. Direct and indirect costs of asthma to an employer. Journal of Allergy & Clinical Immunology 2002;109(2):264-70.
  10. Anderson F, Stahl E, Barnes PJ, Lofdahl CG, O'Byrne PM, Pauwels RA, et al. Adding formoterol to budesonide in moderate asthma - health economic results from the FACEt study. Respir Med 2001;95:505-12
  11. Rutten-van Molken MPMH, Van Doorslaer EKA, Jansen MCC, Kerstjens HA, Rutten KK. Costs and effects of corticosteroids and bronchodilators in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;151:975-982.
  12. Paltiel AD, Fuhlbrigge AL, Kitch BT, Liljas B, Weiss ST, Neumann PJ, et al. Cost-effectiveness of inhaled corticosteroids in adults with mild-to-moderate asthma: results from the asthma policy model. Journal of Allergy & Clinical Immunology 2001;108:39-49.
  13. Stempel DA, Mauskopf J, McLaughlin T, Yazdani C, Stanford RH. Comparison of asthma costs in patients starting fluticasone propionate compared to patients starting montelukast. Respiratory Medicine 2001;95(3):227-34.
  14. Bukstein DA, Henk HJ, Luskin AT. A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy. Clinical Therapeutics 2001;23(9):1589-600.


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