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(Chest. 2004;125:916-923.)
© 2004 American College of Chest Physicians

Asthma Treatment Preference Study*

A Conjoint Analysis of Preferred Drug Treatments

Gunnar Johansson, MD, PhD; Björn Ställberg, MD; Göran Tornling, MD, PhD, FCCP; Stina Andersson, DHS, MSC; Göran S. Karlsson, PhD; Krister Fält, MBA and Fredrik Berggren, PhD

* From the Department of Public Health and Caring Sciences (Drs. Johansson and Ställberg), Uppsala University, Uppsala; AstraZeneca Research and Development, Lund; (Drs. Tornling and Berggen), AstraZeneca Sweden (Dr. Karlsson and Ms. Andersson), Södertälje; KW Partners (Mr. Fält), Stockholm, Sweden.

Correspondence to: Gunnar Johansson, MD, PhD, Nyby Vårdcentral, Vårdcentral, Heidenstamsgatan 69, S-754 27 Uppsala, Sweden; e-mail: gunnar.johansson{at}lul.se


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective: Assessment of patient preferences for attributes of asthma treatments.

Methods: Two hundred ninety-eight patients (age range, 18 to 60 years) from 15 centers in Sweden completed a questionnaire concerning their asthma, and ranked 18 alternative treatments using conjoint analysis. Patients were receiving treatment with either inhaled corticosteroids (ICS) and short-acting bronchodilator (n = 123) or ICS and long-acting bronchodilator (separate inhalers, n = 87; combination inhaler, n = 88). Attributes analyzed were maintenance treatment, additional reliever, time to onset and duration of reliever, number of symptom-free days (SFDs) per month, and out-of-pocket cost per month.

Results: Conjoint analysis showed that the most important aspect of treatment was SFD. Forty percent of the patients had <= 15 SFDs per month. Eighty-five percent of the patients preferred another treatment over their current treatment. Treatment preferences were heterogeneous, and in 78% were not covered by current treatment guidelines. A total of 148 patients (50%) preferred a combination inhaler to separate inhalers, and 233 patients (78%) preferred a reliever that is both rapid and long acting. The most preferred treatment was a combination inhaler for maintenance and reliever use. On average, the patients were willing to pay an additional 328 Swedish krona [US $36] per month for the change to the preferred treatment.

Conclusion: SFDs were the most important attribute in asthma treatment. Patients were willing to pay for a switch to their preferred treatment. The most favored treatments were a reliever therapy that is both rapid and long acting and a combination inhaler for both maintenance and as-needed use.

Key Words: asthma treatment • conjoint analysis • treatment preferences


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
As in other diseases, treatments for asthma are investigated for their clinical efficacy, tolerability, effects on health-related quality of life, and cost-effectiveness. In asthma studies, outcome measures may include the number of exacerbations, frequency and severity of asthma symptoms, requirement for additional medication, and health-related quality of life. These measures have been used in numerous studies, and the results have been incorporated into asthma treatment guidelines.1 2

In a study by Osman et al,3 conjoint analysis was used to investigate the relative discomfort to patients of various asthma symptoms. The results showed that cough and breathlessness were the most disturbing symptoms, followed by wheeze, chest tightness, and sleep disturbance. One conclusion was that conjoint analysis of individual preferences appears to be a useful method for evaluating the relative importance of common symptoms. Balsbaugh et al4 utilized conjoint analysis for evaluation of patient preferences for controller medication, and found that the attributes with the strongest preferences were "no need for blood-test monitoring" and "low frequency of dosing."

Conjoint analysis was originally developed for market research into consumer preferences, and is a method that investigates the relative importance of groups of attributes, eg, products with certain properties or more abstract concepts such as treatment procedures.5 6 It has been applied to various aspects of health care; for reviews, see Ryan7 or Szeinbach et al.8 The method can thus be used to analyze patient preferences for various treatment alternatives. No asthma treatment regimen is likely to have all the attributes that patients would ideally like; for example, a regimen might be highly effective (desirable) but expensive (undesirable). Conjoint analysis provides a method of "trading off" desirable attributes against undesirable ones, and assessing which attributes are most important in determining the patient preferences for one regimen over another.

The purpose of this study was to evaluate, using conjoint analysis, asthma patients’ preferences for different aspects of pharmacologic asthma treatment, including efficacy, drug characteristics, and costs. The primary objective was to evaluate the relative importance for each of the described attributes and the patient’s preferences for different treatment concepts. The secondary objective was to study the patients’ monetary valuation (willingness to pay) for different aspects of asthma treatment and for different treatment concepts.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The Asthma Treatment Preference Study was a multicenter survey based on patients’ own experience. No asthma drugs were used. The study protocol was conducted in accordance with the Declaration of Helsinki and approved by local ethics committees, and all patients gave written informed consent.

Patients (n = 298) aged 18 to 60 years with a diagnosis of asthma and receiving ongoing asthma treatment with inhaled corticosteroids (ICS) plus a bronchodilator were recruited from 15 primary care centers in Sweden. Patients were classified into two groups based on their ongoing asthma treatment at the time of study entry. Patients in group A were receiving a daily dose of at least 400 µg of budesonide or an equivalent dose of another ICS, and used a short-acting bronchodilator at least once per week. Patients in group B were receiving an ICS plus a long-acting bronchodilator, either in one inhaler or in separate inhalers. The exclusion criteria were a diagnosis of COPD and participation in any other clinical study. Each center was scheduled to recruit 20 patients, with at least 8 patients included from each of the treatment groups described above.

Conjoint Analysis
In conjoint analysis, several attributes of treatment are selected and a range of possible values ("levels") are defined for each attribute. These are used to create a number of treatment concepts, each with different levels for the various attributes. The attributes used in our conjoint analysis were based on established attributes of asthma treatment taken from published clinical studies and asthma treatment guidelines.1 2 9 10 11 12 The selected attributes were as follows: type of maintenance treatment, need for an additional reliever inhaler, time to onset of action for reliever, duration of action for reliever, number of symptom-free days (SFDs), and monthly out-of-pocket cost.

Table 1 shows the different levels for each attribute. No oral asthma treatment was included among the alternatives. The number of possible treatment concepts that could be constructed from one attribute with three levels, three attributes with two levels, and two attributes with four levels is 3 x 23 x 42 = 384. The number of treatment concepts was reduced to 18. This was implemented by an experimental design that omitted redundant alternatives and provided an orthogonal design. The orthogonal design reduced the number of alternatives while minimizing the correlation between the remaining cards to allow the estimation of utilities in a statistically coherent way. Each of these 18 treatment concepts was presented on a separate card. Figure 1 is an example of a card; treatment concepts are recorded on these cards under the bold headings that are varied with the alternatives provided in Table 1 (the levels). The treatments on the cards were not necessarily covered by present guidelines. Sixteen of the cards were used to calculate preferences, and the remaining 2 were used to test the reliability of the results.


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  		Table 1.. Attributes and Levels Included in the Study

 


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  		Figure 1.. Example of treatment concept on a card.

 
Patient Information
Patients were asked, on a voluntary basis, to complete a questionnaire and to do the conjoint ranking during a visit to their primary care center. In the questionnaire, patients reported demographic information including age, sex, exercise, education, and economic situation, and their present view of their asthma, including current medication, reliever use, and symptoms. The patients filled in the first question regarding their asthma medication with assistance from a physician or nurse. After that, patients were instructed to complete the rest of the questionnaire and the ranking exercise on their own. Patients were presented with 18 different treatment concepts and an instruction folder explaining the ranking task. The treatment concepts included different combinations of medications and inhalers of which they may have had no experience. The patients were instructed to rank the presented treatments according to their own opinions, considering aspects that were important to them in their asthma treatment. As an aid, all patients received brief general information about asthma treatment, focusing on the different use of ICS and bronchodilators for maintenance and reliever therapy. The general information broke down these asthma treatment aspects into attributes and levels that were described in detail, without any substance name or product name.

Analysis of Conjoint Data
The ranking data were analyzed using the Linmap algorithm.5 Preference parameters were estimated for each patient, which means that preferences can be expressed for each patient in the survey, or for subgroups of patients with similar clinical status, sociodemographic profile, or preferences.

Utility Functions
A measure of preference often used in conjoint analysis is the term utility. The utility of a treatment concept is a function of the levels of the attributes in that concept. A higher level of utility expresses a greater preference for that treatment concept. For some asthma treatment attributes there is no natural best alternative. For example, different patients are likely to favor different maintenance treatment concepts, eg, combination inhaler or separate inhalers. For other attributes, the treatment becomes more attractive with an increasing level of the attribute. For example, if assuming rationality, patients will prefer more SFDs to fewer. When estimating parameters, restrictions on preferences were put on these attributes: time to onset (decreasing preference with longer onset time), SFD (increasing preference with more SFDs), and out-of-pocket cost (decreasing preference with higher cost). For some attributes, the relationship can be assumed to be continuous, eg, a linear relationship was applied for monthly cost. The other attributes were considered discrete, and coefficients were estimated for each attribute level.

The utility measure not only expresses which alternative is the most preferred, but also gives a measure of importance. A high relative level of utility indicated that the attribute was important to the patient and has had a high impact on the ranking of the treatments.

From the example of utilities in Table 2 , it can be seen that this hypothetical patient (based on the average of the study population) favored a combination inhaler. The difference in utility between the most and the least favorable maintenance treatments was 18 U. For duration of action of the reliever, the difference between the best and the worst level was 8 U. Hence, the ideal maintenance treatment was more than twice as important as the duration of reliever action to this person. The number of SFDs per month was even more important, with a difference of 33 between the best and worst levels.


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  		Table 2.. Utilities From a Single Hypothetical Patient Based on the Average in the Study Population*

 
Since the sum of differences in utilities between the best and the worst attribute levels for all attributes equals 100 in the Linmap solution for each individual, we can determine that the relative importance of SFD in this example was 33% (Table 2) , while "type of maintenance treatment" accounted for 18% in explaining the patient’s preferences.

Calculating Expected Preferences for Alternative Treatment Concepts
From the estimated utility functions it is possible to calculate the expected attractiveness of various treatment concepts for each person, provided that the concept can be expressed through the design parameters. Table 3 shows the utility function for the same hypothetical single patient as in Table 2 . The estimated utility function can be used to determine what treatment would be most favorable given the patient’s preference structure. Inhaled steroids, and short- and long-acting bronchodilators can be combined and represented in seven clinically relevant treatment concepts. All 296 subjects used one of these combinations at the time of the study. These treatment concepts are defined by the level of each attribute and are shown in Table 3 . The attractiveness of a treatment was calculated using the attribute levels for the concept, combined with the patient’s utilities for each attribute level. The sum of the partial utilities for each concept shows how attractive the concept is overall. In this example, concept 5, a combination inhaler, used both as maintenance medication and reliever, receives the highest total utility. In a situation with access to information about all potential treatment alternatives and free choice, the patient would be expected to choose the treatment with the highest utility, in this case concept 5.


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  		Table 3.. Calculation of Expected Treatment Preferences Using a Hypothetical Patient’s Utility Function*

 
Willingness to Pay
Since the full patient cost range of the treatment concepts was included on the cards as an attribute with four levels that covered the price range for the treatments, the willingness to pay, in addition to current expenditure on asthma drugs, can be estimated for all possible treatment combinations. To investigate the willingness to pay for a switch to the preferred treatment, we included data only from patients who had shown a negative price coefficient, ie, we included only patients who showed that they were sensitive to the price of the treatments. This is a conservative approach, since patients who did not rank treatments according to price might have done so for a variety of reasons, they could be truly insensitive to price, or they could have neglected this aspect as a protest, or they could have decided not to bother to incorporate this aspect into their ranking.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Patient Characteristics
The 298 patients surveyed were aged 18 to 60 years (mean ± SD, 41.2 ± 11.7), and 203 patients (68%) were female. Results from the initial questionnaire are presented in Table 4 . The current asthma treatment regimens were grouped into seven categories; these categories also formed the treatment concepts defined for the conjoint analysis. The numbers of patients treated in each category are shown in Table 5 . Two of the rankings for the conjoint analysis were classed as incomplete; hence, the conjoint analysis was conducted with responses from 296 patients.


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  		Table 4.. Patient Baseline Characteristics From Questionnaire

 

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  		Table 5.. Patients by Current Treatment, the Analysis of Switching Behavior from Current Treatment to Best Treatment According to Conjoint Data, and the Analysis of Willingness To Pay*

 
Conjoint Data
The average relative importance of the attributes, based on individual preferences, is presented in Table 2 . Individual utility values from the conjoint data for the seven treatment concepts corresponding to current treatments were used to identify the preferred treatment. The preferred treatment concepts according to the conjoint analysis are presented in Table 5 , in relation to current treatments. For example, the first row of the table shows that 123 patients were currently receiving ICS plus a short-acting bronchodilator (concept 1). Treatment concept 1 was rated as best by 15 patients in the conjoint analysis; treatment concept 2 was rated as best by 27 patients, and so on. In the example, 108 of 123 patients (88%) rated treatment concepts other than concept 1 (current treatment) as best, implying that they would prefer to switch to an alternative treatment. The treatment option of ICS plus long-acting bronchodilator for maintenance and as needed (treatment concept 3) had the lowest percentage of patients rating other treatments as best (53%). Overall, a total of 85% of the patients in the sample rated treatments other than their current treatment as best. A combination inhaler was preferred for maintenance treatment by 50% (concepts 5, 6, and 7) of the patients, and a reliever with rapid onset and long duration was preferred by 78% (concepts 2, 3, 5, and 7) of the patients. The relative preferences did not differ according to whether the patients had any previous experience of a long-acting bronchodilator or not (group A and B). Overall, the patients’ preferences showed a willingness to replace a short-acting bronchodilator with a treatment concept that contains a reliever, which is both rapid and long acting.

A substantial proportion (79%) of the patients receiving inhaled steroids and a short-acting bronchodilator (concept 1) preferred to switch to a treatment with a rapid- and long-acting reliever, and one of four patients preferred a combination inhaler for both maintenance and reliever use. Of the 61 patients who used inhaled steroids, a long-acting bronchodilator and a short-acting reliever (concept 4), 92% preferred to switch, most commonly to a rapid- and long-acting reliever, either as a combination inhaler for maintenance and reliever use (25%), or to inhaled steroids and a rapid- and long-acting bronchodilator used both for maintenance and reliever usage (26%), or a rapid- and long-acting bronchodilator as a separate inhaler as a reliever (25%). The 77 patients currently receiving a combination inhaler and a short-acting reliever (concept 6) preferred a treatment regimen that also used the combination inhaler as reliever medication (26%), a long-acting reliever on top of a combination inhaler (19%), or a long-acting bronchodilator for maintenance and reliever use on top of ICS (17%). Figure 2 presents the results aggregated by treatment concepts.



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  		Figure 2.. Current treatments and preferred treatments according to conjoint analysis aggregated by treatment concept. See Table 5 for expression of abbreviations.

 
Willingness to Pay
The willingness to pay for switching to the preferred treatment concept for patients in each current treatment group is presented in Table 5 . For example, patients currently treated with inhaled steroids plus a short-acting bronchodilator (concept 1) were willing to pay, on average, an additional 351 Swedish krona (SEK) monthly (US $39/mo; US $1 = SEK 9, January 2003) for the treatment they ranked as best. For the 54 patients who ranked concept 3 as the best treatment concept but received another treatment concept, the average willingness to pay was SEK 398 additionally per month (US $44/mo) for concept 3; similarly, the 75 patients who preferred but were not treated with concept 5 were on average willing to pay SEK 376/mo (US $42/mo) for this concept. The average willingness to pay for the preferred treatment concept was SEK 328/mo (US $36/mo).

Validity and Reliability of the Analysis
To verify that the attributes most important to the patients were included in the conjoint design, patients were asked to allocate 10 points between prespecified attributes, corresponding to attributes in the conjoint design in the questionnaire and an unspecified open alternative. This unspecified alternative received an average score of only 0.1 of 10 points, indicating that the attributes used in the conjoint study covered the most important aspects of their asthma treatment. The prespecified aspects received points as follows: medication to prevent symptoms (4.4), a rapid onset of action for the reliever (3.6), a low price for the treatment (1.0), and reduction of the number of inhalers (1.0).

Patients ranked a total of 18 treatments—only 16 of these were used to estimate utility functions—and expressed their preferences for various attributes. The remaining two treatments were used to validate the predictive accuracy of the preference model. Validation of this model was acquired by calculating utility scores using each patient’s utility function for all 18 treatments. Calculated scores were then rank ordered. Original rankings were compared pairwise with the theoretical rankings resulting from calculated utility scores.

On average, 13 of 16 pairwise comparisons were correctly predicted by the model. The Kendall rank order correlation coefficient, the Kendall {tau}, was calculated for each patient. On average, the Kendall {tau} was 0.64. This indicates that the model performs very well in predicting patient preferences.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study has investigated patient preferences for different attributes of inhaled asthma treatment. The overall result was that the most important feature for an asthma treatment in this study was SFD. However, this was conditional on the number of SFDs increasing from < 10 to > 20, which were the worst and the best levels of the SFD attribute. The highest-ranked treatment concepts included a reliever with fast onset and long duration. A combination inhaler for corticosteroids and long-acting bronchodilator was ranked higher than separate inhalers. Preferences varied between patients and consequently the ranking of treatment concepts varied.

The conjoint method has been used for decades in other research disciplines, notably consumer market research, but has only recently started to be used to study asthma. Osman et al3 used conjoint analysis to rank asthma symptoms. Another study4 investigated preferences for a limited number of aspects (need for blood test monitoring, frequency of dosing, and route of administration) for asthma controller medication. This study has extended this research by analyzing variation in patient preferences for a full set of inhaler treatments, including efficacy, mode of action, and costs, and calculated the preferences for different pharmacologic treatment concepts.

Results from the initial questionnaire indicated that the population in this study was representative of a broad asthma population in primary care. The patients reported that they had a clear burden from their asthma: almost 1 in 10 patients had at least one acute asthma attack requiring immediate health care during the previous year, nearly 1 in 7 patients used their reliever > 10 times in a normal week, and 1 in 4 patients had < 10 SFDs per month. However, according to the questionnaire 87% were satisfied with their current treatment. This pattern of relatively poor asthma control has been reported previously,9 and there is clearly room for improvement in asthma control to meet stipulated guideline targets. Taking account of patient preferences when selecting asthma treatment may help to improve compliance with treatment, and thereby improve control of asthma. There is a considerable discrepancy between the proportion of patients who reported that they were satisfied with their current treatment and the result that 85% preferred an alternative treatment according to the conjoint analysis. There could be several reasons for this observation. One reason could be the lack of knowledge in the patient population about alternative treatment options compared with their current treatment; the information provided in this study may have made it possible for the patient to choose according to their preferences based on the design with attributes and levels. Alternatively, it could be that all possible treatment concepts in this study are not covered in treatment guidelines and can therefore not be recommended by the patient’s physician.

Before beginning the conjoint ranking, patients were given an opportunity to identify other attributes of asthma treatment that they considered important, in addition to those included in the conjoint analysis. On average, only 0.1 out of 10 points were allocated to other attributes, indicating that the design of the conjoint study had included the majority of the important aspects of asthma drug treatments. The tests for internal consistency in the ranking conducted by the patients showed very good results with a low number of inconsistent replies. Concerning external validity, the initial questionnaire in the present study showed that patients reported breathlessness and cough as the most troublesome symptoms compared with chest tightness and sleep disturbance. This result is in accordance with the findings of Osman et al.3

In total, 85% of patients expressed preferences for an alternative treatment to their current regimen. The presented preference structure indicates variations in patient preferences that might need to be addressed in clinical practice. Some patients may benefit from treatments recommended in guidelines that allow increased flexibility in application. Furthermore, the conjoint analysis in this study underestimates the value of treatments with relatively higher effectiveness, ie, the addition of a long-acting bronchodilator for regular use to ICS,10 11 12 or the use of a rapid- and long-acting drug as needed (formoterol) instead of a rapid- and short-acting bronchodilator (eg, terbutaline)13 since, in the conjoint analysis, the effectiveness was considered to be constant with all alternative treatments.

The estimates of the willingness to pay for a preferred treatment were in most cases similar to, or higher than, the actual cost of the treatments. A relevant research approach to investigate this further could be to apply conjoint analysis in conjunction with a clinical and economic study that measures clinical benefits and cost-effectiveness.

The findings of this study based on the aggregated results from almost 300 patients can be summarized as follows. Patients focused primarily on the effectiveness of a treatment, ranking SFDs as the most important attribute of treatment. In terms of available therapies, treatment with a combination inhaler was preferred overall, while reliever therapy that was both rapid and long acting was preferred over short-acting drugs. The most preferred treatment was a combination inhaler for maintenance and as-needed use. Interestingly, 85% of patients preferred an alternative treatment over their current treatment, and they were prepared to pay extra for their preferred treatment.


   Footnotes
 
Abbreviations: ICS = inhaled corticosteroids; SEK = Swedish krona; SFD = symptom-free day

This study was funded through a research grant provided by AstraZeneca.

Received for publication February 19, 2003. Accepted for publication October 15, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. The British Guidelines on Asthma Management. Thorax 1997;52 (suppl 1),1-21
  2. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: NHLBI/WHO Workshop report 2002 National Heart, Lung and Blood Institute, National Institutes of Health. Bethesda, MD:
  3. Osman, LM, McKenzie, L, Cairns, J, et al Patient weighting of importance of asthma symptoms. Thorax 2001;56,138-142[Abstract/Free Full Text]
  4. Balsbaugh, TA, Chambers, CV, Diamond, JJ Asthma controller medications: what do patients want? J Asthma 1999;36,591-596[ISI][Medline]
  5. Srinivasan, V, Shocker, AD Linear programming techniques for multidimensional analysis of preferences. Psychometrika 1973;38,337-369[CrossRef]
  6. Green, PE, Srinivasan, V Conjoint analysis in consumer research: issues and outlook. J Consum Res 1978;5,103-123[CrossRef]
  7. Ryan, M Using consumer preferences in health care decision making: the application of conjoint analysis; Office of Health Economics. 1996 White Crescent Press. Luton, Bedfordshire, UK:
  8. Szeinbach, SL, Barnes, JH, McGhan, WF, et al Using conjoint analysis to evaluate health state preferences. Drug Inf J 1999;33,849-858
  9. Rabe, KF, Vermeire, PA, Soriano, JB, et al Clinical management in asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study. Eur Respir J 2000;16,802-807[Abstract]
  10. Pauwels, R, Löfdahl, CG, Postma, DS, et al Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997;337,1405-1411[Abstract/Free Full Text]
  11. O‘Byrne, P, Barnes, P, Rodriguez-Roisin, R, et al Low dose inhaled budesonide and formoterol in mild persistent asthma. Am J Respir Crit Care Med 2001;164,1395-1397
  12. Shrewsbury, S, Pyke, S, Britton, M Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000;320,1368-1373[Abstract/Free Full Text]
  13. Tattersfield, AE, Löfdahl, CG, Postma, DS, et al Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet 2001;357,257-261[CrossRef][ISI][Medline]



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