Jcaai.readyportal.net

Current reviews of allergy and clinical immunology
(Supported by a grant from Astra Pharmaceuticals, Westborough, Mass)
Series editor: Harold S. Nelson, MD
Health economics of asthma and rhinitis.
II. Assessing the value of interventions
Sean D. Sullivan, PhD,a and Kevin B. Weiss, MDb Seattle, Wash, and Chicago, Ill
Health care providers and payers are being asked to weigh
data on the economic impact of new interventions along with
clinical evidence when making decisions about the care of
patients. The notion of incorporating formal health economic
assessments into clinical and resource decisions is a difficult
concept for many in the health care sector. However, it is the
reality in today’s environment. To effectively participate in
these ongoing discussions, clinicians and other decision makers
must be able to understand and critically assess the evidence
on economic impact of medical interventions. This second of 2
articles describes the elements of comparative economic evalu-
able to then take a position that only high-quality eco- ations, reviewing the published literature on asthma and rhini-
nomic evidence should be used. The purpose of this 2- tis in an attempt to critically appraise the studies from the per-
part review is to provide decision makers with the tools spective of one who might use data for decision making.
to evaluate economic evidence for treatments for asthma Unfortunately, the quality of the economic evidence in these
two disease states is not extensive. Until better economic analy-
ses are conducted and made available, the allocation of
The first part of this review characterized the econom- resources for asthma and allergic rhinitis will continue to pri-
ic burden of asthma and rhinitis.3 This second portion of marily rely on expert opinion rather than evidence-based liter-
the review focuses on the critical elements of compara- ature. (J Allergy Clin Immunol 2001;107:203-10.)
tive economic analyses that are useful for decision mak-ers. Part II is specifically written for clinicians and deci- Key words: Asthma, allergic rhinitis, economics, cost-effectiveness
analysis, costs
sion makers who are not well versed in the purposes andmethods of cost-effectiveness analysis (CEA). It argues Evidence-based medicine is concerned with the con- that cost-effectiveness studies have much in common scientious, explicit, and judicious use of the current best with the clinical literature that most clinicians are com- evidence in making decisions about the care of individual fortable reading and critically appraising. Thus it will patients.1 Increasingly, health care providers are being highlight important similarities and differences between asked to weigh economic evidence alongside clinical evi- sound economic and sound clinical evaluations. Some of dence when making decisions about the care of their the more subtle aspects of CEA (eg, discounting of future patients.2 This review takes the position that today’s costs and benefits, comparative measures of benefit) are health care environment makes some consideration of not emphasized here. The interested reader can find economics for determining resource use inevitable. If one greatly expanded discussions of these issues, along with accepts the notion that economic considerations are the major themes discussed below, in several excellent unavoidable in clinical decision making, it seems reason- Before discussing the major issues that should be addressed when evaluating economic evidence, thisreview first outlines the important similarities and differ- From athe Departments of Pharmacy and Health Services, University of ences between clinical evidence and economic evidence.
Washington School of Pharmacy, Seattle; and bCenter for Health ServicesResearch, Rush Primary Care Institute, Rush-Presbyterian-St Luke’s Med- CEAs take a “population” viewpoint for decision mak- ing. This viewpoint involves basing decisions on evi- Supported in part by an educational grant from the Asthma and Allergy Foun- dence gathered from studies of populations rather than on evidence gathered on a case-by-case basis. So, for Received for publication November 7, 2000; accepted for publication example, the clinician who is deciding whether a partic- Reprint requests: Kevin B. Weiss, MD, Director, Center for Health Services ular controller treatment is appropriate for his or her asth- Research, Rush Primary Care Institute, Rush-Presbyterian-St Luke’s Med- ma patient would look to the literature reporting results ical Center, 1653 W Congress Pkwy, Chicago, IL 60612.
from clinical trials rather than considering how this treat- ment worked on his or her last patient (or even a col- 1/10/112851
league’s patients). Similarly, CEA is designed to help 204 Sullivan and Weiss
health care providers and payers make informed resource The results presented in CEA papers are derived from allocation decisions based on evidence gathered from a simple equation that integrates estimates of total costs studies of populations, including the study types that are and clinical outcomes. This simple equation has been familiar to clinical readers (eg, randomized controlled described as depicting an intervention’s value for money; trials, case-control studies, cohort studies).
that is, the cost-effectiveness of a new intervention in a Although clinical and economic impact studies have defined population of patients represents the added total much in common, there are important differences costs required to achieve an incremental improvement in between the two methodologies. First, the perspective is outcome when compared with a currently accepted treat- generally different. Clinical decisions are usually made ment. If the added cost-to-clinical benefit ratio is accept- from the perspective of what is best for the patient. Eco- able to decision makers, it is said to have value. The cost- nomic analyses are generally conducted from the broader societal perspective, that is, including all costs and bene- fits that are attributable to the intervention, even if they do not necessarily involve the patient directly. Taking a soci-etal perspective is important in CEA because costs and Here, 2 therapies are compared: A (usually the new benefits from medical treatments often “spill over” to oth- technology) and B (the established or usual therapy). The ers beyond the person receiving treatment. For example, incremental cost-effectiveness of A versus B is thus the when a child is vaccinated against chicken pox, he or she attributable benefit per incremental level of expenditure benefits from the vaccine, but so do other children who for the new technology. The most common result of a would have been exposed to the virus if the child had not cost-effectiveness evaluation for new medical interven- been vaccinated and had contracted the disease. Some- tions is one in which health benefits improve compared times, taking the societal perspective leads to different with standard care, but at an additional expense to the conclusions than taking the perspective of the patient. health care system. It is important to note that interven- Second, although clinical effectiveness is necessary tions that marginally increase costs and provide better for a therapy to be cost-effective, a treatment can have health outcomes for patients are necessarily useful and clinical effectiveness and still not be cost-effective. Thus worth paying for. In a health care system with a fixed the clinical information provided from randomized trials budget, these additional expenditures on new treatments may not necessarily help with economic decisions. This for asthma or allergic rhinitis must be weighed in relation fact has not been lost on the proponents of evidence- to alternative uses of these funds in other disease states.
based medicine, who note that practicing evidence-basedhealth care is at least as likely to increase medical care ASSESSMENT OF VALUE IN THE CARE OF
PERSONS WITH ASTHMA AND RHINITIS
Third, economic analyses are conducted under a framework in which the decision maker operates within Following is a concise review of studies of both asth- a limited resource environment. Decisions to spend more ma and allergic rhinitis that highlight the utility of eco- on one program will necessarily mean spending less on nomic evaluations for clinical and resource decision other programs. As a result, economic analyses almost making. Only a few of these studies have met recom- always involve a comparison between alternative thera- mended standards for economic evaluation.9-11 The pies to ascertain which therapy offers the best health review emphasizes studies that conform to appropriate value per dollar expended. Clinical evidence more com- scientific rigor but also points out notable studies that fail monly compares a new therapy with placebo care, even to meet guidelines. Also identified are important or con- when placebo care (ie, no care) is not the standard of temporary interventions that lack even basic published evidence of economic benefit. These areas would befruitful for research. The methodology used for the liter- BASIC PRINCIPLES OF CEA
ature search was described in part I of this series.3 CEA can be defined as a set of related methods to assess Economic evaluations in asthma
and quantify the costs and clinical consequences of med- Diagnostic testing. Asthma is principally diagnosed
ical care treatments to estimate the “economic value” of and managed with objective measures of lung function.
the intervention in relation to alternative treatments. These For persons already diagnosed, national guidelines rec- methods were described briefly in the first part of this ommend periodic monitoring of pulmonary function by review.3 A CEA of competing medical treatments should either spirometry or peak flow measurements.12 To date, incorporate evidence on the clinical consequences (effica- there have been no health economic evaluations to assess cy and safety) and the costs and relative cost-effectiveness this recommendation. There has been one report of the of treatment alternatives.7,8 Guidelines for designing and economic consequences of use of pulmonary function reporting CEAs—including methods for incorporating tests to screen for asthma.13 This study of an adult popu- evidence on costs and effects—are now available and lation in The Netherlands examined both asthma and should be read by those who are interested in conducting chronic obstructive pulmonary disease collectively, mak- or critically appraising these types of studies.
ing it impossible to single out the value of diagnostic Sullivan and Weiss 205
TABLE I. Summary of randomized health economic studies of pharmacotherapy for persistent asthma
Treatments
Health outcomes
Economic
Reference
method used
Perspective
of study measured
measured
outcomes
saved $9.43 foreach symptom-free day gained Adapted from Sullivan SD, Weiss KB. Pharmacoeconomics of asthma treatments. In: Barnes PJ, et al, editors. Asthma: basic mechanisms and clinical manage-ment. 3rd ed. San Diego: Academic Press; 1998. p. 909.
RCT, Randomized controlled trial; BID, twice daily; PEFR, peak expiratory flow rate; ED, emergency department.
*Study had a planned 3-year follow-up but only 39 patients reached a follow-up period of 22 months.
testing for asthma alone. There appear to be no health or they were of too short a duration to assess outcome and economic evaluations of the use of other types of diag- economic impact on a chronic condition such as asth- nostic tests such as x-ray films, serologic tests, or skin ma.14,17-22 Table I provides an overview of selected stud- ies that meet many of the economic-evaluation standards.
Management. Pharmacotherapy represents the founda-
Inhaled corticosteroids. The National Guidelines for the tion for clinical management of asthma. Not surprisingly, Diagnosis and Management of Asthma12 recommend there are a number of studies that present findings on the inhaled corticosteroids (ICSs) in addition to as-needed economic impact of drug treatments. Many of these stud- bronchodilator therapy as treatment for persons with per- ies did not meet 2 of the basic criteria for cost analysis.
sistent asthma. There is substantial evidence to support this This was because they either failed to include all costs14-16 recommendation.23,24 However, addition of ICS medica- 206 Sullivan and Weiss
tions to an existing regimen of inhaled or oral bronchodila- gest a favorable economic profile for adding ICSs to short- tor therapy contributes significantly to the overall cost of treating these patients. An important research question is Data are beginning to appear that compare different whether ICSs along with as-needed bronchodilators are anti-inflammatory therapies, but as yet, these studies do cost-effective compared with as-needed bronchodilators not meet many of the criteria for a well-designed CEA.37 alone (BA) for treating persons with mild-to-moderate or However, it is precisely these types of head-to-head stud- moderate-to-severe asthma. Although several observational ies that most decision makers want to see. studies have attempted to examine this issue,25-30 this Long-acting β2-agonists. One study examined the rel- review focuses on randomized trials because of the strength ative economic consequences of treating persons with asthma with twice daily powder formoterol 12 µg as One of these studies was a 16-week randomized trial of compared with salmeterol 50 µg.38 However, the authors budesonide, 400 µg/d and 800 µg/d, and placebo in 57 concluded that there were no statistically significant dif- adults with mild asthma.33 Low-dose budesonide demon- ferences in symptom-free days between the two treat- strated better control of morning and nocturnal symp- ment groups, and because of this, no incremental cost- toms, improved peak flow measurements, and was judged to be cost-beneficial compared with placebo. High-dose Of current interest in the United States is the potential budesonide did not improve lung function or symptom economic impact of combination bronchodilator and cor- scores relative to low-dose budesonide. In another study ticosteroid products. Investigators examined the costs and Connett et al34 examined the cost-effectiveness of inhaled effects of use of the salmeterol/fluticasone propionate budesonide compared with placebo in a 6-month random- fixed-dose combination product (SFC) 50/250 µg twice ized trial of 40 children aged 1 to 3 years with persistent daily versus budesonide 800 µg twice daily.39 This study asthma. The results indicated that budesonide produced a involved 353 adult and adolescent participants (≥12 favorable clinical response, increasing symptom-free years) who were symptomatic while receiving current days when compared with placebo. The results also sug- doses of ICSs. The patients were followed up for 24 gested that compared with placebo, budesonide increased weeks. The results indicated that patients taking SFC had overall effectiveness and reduced overall costs by about significant improvements in several outcomes. The incre- mental cost-effectiveness for SFC was $1.12 per symp- Rutten-van Mölken et al35 reported on the cost- tom-free day gained. This study suggests that this combi- effectiveness of adding ICSs to an as-needed bron- nation therapy may have a favorable economic profile for chodilator regimen (ICS + BA) compared with as-needed patients with asthma whose symptoms are otherwise BA in a 12-month randomized trial of 116 children with poorly controlled with moderate doses of inhaled steroids.
asthma aged 7 to 16 years. The investigators evaluated Inhaled cromolyn sodium and nedocromil. There FEV1 as the primary outcome and frequency of symptom- appear to be no randomized controlled economic evalua- free days and school absences as secondary outcome tions of inhaled cromolyn sodium or nedocromil. How- measures. ICS + BA was estimated to cost about $4.75 ever, 2 published studies attempt to estimate the eco- per symptom-free day gained relative to use of BA.
nomic value of these compounds. One study is based on One of the most comprehensive trials to date investigat- retrospective analysis of 53 patients categorized into 2 ed the costs and effects of adding inhaled anti-inflamma- groups: those who received cromolyn sodium for at least tory therapy to inhaled β2-agonist. This study was based 1 year and those who did not receive cromolyn sodium as on 274 adult participants aged 18 to 60 years with moder- part of their treatment regimen.40 Another, more recent ately severe asthma or chronic obstructive pulmonary dis- study of nedocromil sodium was conducted that used a ease as defined by pulmonary function criteria.36 Each retrospective pre-post design to examine this therapy for patient was randomly assigned to either inhaled fixed-dose 553 adults with asthma.41 These 2 studies suffer from terbutaline plus inhaled placebo, inhaled terbutaline plus selection and other biases common to retrospective 800 µg of inhaled beclomethasone per day, or inhaled analyses and therefore provide little information about terbutaline plus inhaled ipratropium bromide 160 µg per the health economic value of these compounds. day. Patients were followed up for as much as 2.5 years.
Leukotriene antagonists. One health economic study The economic objective of this study was to determine the of the use of zafirlukast for children and adults with relative cost per unit of benefit for the 3 therapeutic arms.
mild-to-moderate asthma was reported; however, the The clinical results indicated that addition of the ICS to study did not report on the cost of the study drug, there- fixed-dose terbutaline led to a significant improvement in by making this an incomplete assessment of economic pulmonary function and symptom-free days, whereas impact.14 There are presently no other published studies addition of inhaled ipratropium bromide to fixed-dose that meet current standards to provide an understanding terbutaline produced no significant clinical benefits over placebo. The incremental cost-effectiveness for ICS was Other pharmacotherapy. There have been a few stud- approximately $5 per symptom-free day gained. The ies of various other pharmacotherapeutic strategies. One incremental cost-effectiveness of ipratropium bromide suggested that inhaled anticholinergics might be of ben- was not evaluated because of the lack of clinical benefit efit in treating children with asthma.42 There also appears relative to placebo. The results from these studies do sug- to be only 1 health economic evaluation of asthma phar- Sullivan and Weiss 207
macotherapy conducted within a developing country.
issues: (1) acute care delivered in emergency depart- This cost-minimization study, conducted in India, found ments and hospitals, and (2) managed care disease- the use of oral β-agonists provided no additional clinical benefit and increased costs for persons using as-needed Studies of asthma care in emergency departments and hospitals. A number of studies have examined ways in Other literature has explored the cost consequences of which emergency departments or hospitals might achieve nebulizers versus metered-dose inhalers (MDIs) with or optimal asthma care outcomes at lower costs. Several without spacers in the acute care setting.44-49 Although studies have characterized the use of short-stay observa- most of these studies have design limitations, collectively tion units in the emergency department.71-73 Collectively, they suggest that there is no significant difference in clini- these studies suggest that there are cost benefits to the cal outcomes between nebulizers and MDIs.44,50 These studies also suggest that MDIs offer modest cost savings.
Several other studies have examined the economics of Although there are published studies of various other types asthma clinical pathways designed to improve and of medication-delivery devices,51-53 they do not meet streamline hospital care.74-78 These studies, all nonran- many of the standards for health economic evaluations.
domized and mostly retrospective in design, uniformly Economic studies of asthma patient education, self-
focused on length of stay without clearly defining the management programs, and specialty consultation.
costs associated with the intervention. While a majority Several publications document the clinical and econom- of these studies reported decreased length of stay, the ic impact of patient-oriented asthma education programs.
actual cost benefit of the pathway intervention remains These educational interventions vary from formal class- unclear. For example, one well-designed trial resulted in room-based medication compliance programs to asthma self-management programs for adults and children/par- Studies of disease-management programs. Disease ents. Overall, the economic evaluations of these pro- management has become popular during the past grams are quite favorable, especially when the programs decade.79-81 Although there is currently no standard defi- are aimed at high-risk patients or those with high-end nition for this term, most program descriptions focus on health care utilization (such as a prior hospitalization).54-65 population management and include some type of multi- These studies nearly all take the form of cost-benefit faceted team approach to improving the delivery of care.
analyses, with costs attributed to program costs and ben- There are now a number of health economic studies eval- efits related to changes in emergency department and uating asthma-specific disease-management programs.82-90 hospital utilization. One particularly well-designed ran- Each of these studies has notable design limitations, par- domized controlled trial of an inner-city population was ticularly in relation to sample selection, controls, and eco- able to demonstrate cost savings from a program of five nomic analyses. However, together they suggest that a 1-hour asthma education sessions targeted to children comprehensive approach to asthma management— who had been hospitalized during the previous year.64 beyond pharmacotherapy—may have some merit. Further True cost-effectiveness studies in the field of asthma research in the form of prospective randomized clinical education and training for self-management are infre- trials will help to better elucidate the economic value of quent. Two separate cost-effectiveness studies of asthma this approach to improving asthma outcomes. self-management programs in Finland arrived at conflict- Other miscellaneous asthma-related health economic ing conclusions. One study resulted in a cost-effective- studies. There are a number of other health economic stud- ness ratio of 118 Finish Marks per health day gained.66 ies related to asthma care that span the spectrum from exam- Another similar study in Finland found no significant ining the value of diagnosis and treatment of gastroe- health economic value at either 1 or 3 years.67 Another sophageal reflux for asthma91 to psychosomatic therapy92 to study of asthma self-management in India met a number use of pharmacists in guiding therapy93,94 and use of physi- of the standards for economic evaluation but fell short of cian audit with feedback.95 The methods used in these stud- calculating a cost-effectiveness ratio.68 This study sug- ies do not meet many of the established standards for health gested that there were health improvements in terms of economic studies, making the results difficult to interpret.
peak flow measurements and productive days lost, aswell as average marginal cost savings of 22%.
Economic evaluations in allergic rhinitis
There have also been studies examining the economic The economic-evaluation literature in asthma is limit- impact of referrals to specialists for persons with moder- ed but growing and becoming increasingly relevant and ate-to-severe asthma.69,70 Retrospective chart reviews rigorous. This is not the case for the economic-evaluation found significant reductions in sick office visits, emer- literature in allergic rhinitis. The paucity of literature is gency department visits, hospital days, and costs of care.
compounded by the lack of a standardized approach to However, the results must be interpreted with caution in undertaking CEA for this condition. Most notable is the light of limitations imposed by the choice of study design lack of standard outcome measure to use in the denomi- nator of the cost-effectiveness equation.
Economic evaluation of innovations in health care
This review describes 4 studies of pharmacotherapy delivery. The health economic literature exploring new
and 1 study of immunotherapy for treatment of allergic strategies in asthma care delivery addresses 2 general rhinitis. There are no existing reports on the economic 208 Sullivan and Weiss
impact of the myriad of avoidance strategies and medical asthma. There also appears to be a favorable economic and disease-management interventions in this disease.
benefit to targeted and sustained asthma education direct- In a randomized controlled clinical trial of the use of ed at self-management for selected subgroups of patients.
intranasal fluticasone propionate (200 µg once daily) Disease-management programs may, with further study, versus terfenadine tablets (60 µg twice daily) versus provide a comprehensive intervention strategy that adds placebo, the authors reported cost-efficacy ratios for flu- value to current clinical care of persons with asthma.
ticasone to be more favorable than those of terfenadine or Beyond these modest conclusions, there remain signifi- placebo in reducing nasal symptoms.96 Unfortunately, cant questions about the value of other treatments.
the study reported only drug costs and focused exclu- A number of problems need to be addressed before sively on adults with allergies to mountain cedar. The studies of this type can be effectively used to determine utility of these data are questionable.
optimal clinical strategies. First is the lack of standardized Another retrospective analysis of budesonide aqueous outcomes for use in health economic analysis of both asth- nasal spray and intranasal fluticasone propionate for treat- ma and rhinitis. For asthma, the symptom-free day is ment of perennial allergic rhinitis reported budesonide to beginning to emerge as a standard measure. Researchers in be more cost-effective.97 However, the economic analysis the field of rhinitis have not, as yet, benefited from nation- was distilled into a simple cost comparison because of al or international discussions aimed at standardizing out- lack of statistically significant differences in clinical end- come measures for this condition. Second, investigators points. More troubling was the fact that the results of this need to more carefully apply appropriate research designs, 6-week study were extrapolated to predict 12-month with sufficient time horizons, relevant comparators, and costs, which could be seen to adversely affect the face accurate measures of resource use and cost, before these data will be taken seriously by decision makers. Another study explored the “willingness-to-pay” Finally, clinicians should be a part of the process of approach to valuing the benefits of 2 types of intranasal critically evaluating economic evidence for new medical budesonide compounds for treatment of seasonal allergic interventions, in the same way they now evaluate clini- rhinitis.98 The authors of this study found no difference cal evidence. The task of becoming an effective evalua- in willingness to pay for aqueous versus dry-powder tor of CEAs is not as daunting as it may first seem because these studies have more similarities than differ- There appears to be only 1 study modeling the long- ences with the clinical literature. The knowledgeable term economic consequences of specific immunotherapy clinician can play a role in ensuring that only high-qual- in the treatment of allergic rhinitis.99 This model sug- ity cost-effectiveness studies are used for decision mak- gests that for a small subset of patients with 3 years of ing in their organizations. In addition, enlarging the continuous symptoms, there may be an economic advan- audience of critical readers of CEAs will likely improve tage to treatment with immunotherapy. Although this the quality of studies that are published in the medical study is interesting, the next step would be to challenge literature. As economic evidence becomes more impor- the results in the form of an experimental clinical trial. tant in medical decision making, it is essential that clin- One other comparative study of rhinitis attempted to icians participate in the process of translating this evi- examine the economic impact of a disease-treatment pro- gram.100 However, this study did not clearly define the Until better economic analyses are conducted and actual disease-intervention program, thereby limiting made available, the allocation of resources for asthma and allergic rhinitis will continue to rely primarily onexpert opinion rather than evidence-based literature.
CONCLUSION
We thank Ms Robin Wagner for her editorial assistance and Ms Josephine Diaz and Ms Monica Blumthal for their assistance with The health economic literature for asthma and rhinitis has evolved considerably during the past decade. CEA isnow recognized as a standardized methodology for REFERENCES
assisting decision makers in selecting and reimbursinghealth care interventions that maximize the health of 1. Sackett DL, Richardson WS, Rosenberg W, Haynes RB, editors. Evi- dence-based medicine: how to practice and teach EBM. New York: populations, given the conflicts generated by constrained health budgets and the rising demand for medical care.
2. Counsel on Ethical and Judicial Affairs, American Medical Association.
Unfortunately, much of the literature in asthma and rhini- Ethical issues in managed care. JAMA 1995;273:330-5.
tis, while evolving, does not currently meet accepted 3. Weiss KB, Sullivan SD. The health economics of asthma and rhinitis. I.
Assessing the economic impact. J Allergy Clin Immunol 2000;107:3-8.
standards. Thus very few definitive conclusions can be 4. Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. 2nd ed. New York: The literature is relatively conclusive that the use of ICSs for moderate persistent asthma is cost-effective 5. Gold MR, Siegel JE, Russell LB, Weinstein MC, editors. Cost-effective- when compared with the use of β-agonist alone. There is ness in health and medicine. New York: Oxford University Press; 1996.
6. Haddix AC, Teutsch SM, Shaffer PA, Dunet DO, editors. Prevention no information on the cost-effectiveness of early inter- effectiveness: a guide to decision analysis and economic evaluation. New vention with controller therapy in patients with mild York: Oxford University Press; 1996.
Sullivan and Weiss 209
7. Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the 30. Holzer SS, Engelhart L, Crown WH, L’Herrou TA, Kennedy ST. Asthma economic evaluation of health care programmes. 2nd ed. New York: treatment costs using inhaled corticosteroids. Am J Managed Care 8. Banta HD, Luce BR. Health care technology and its assessment. New 31. Barton S. Which clinical studies provide the best evidence? The best York: Oxford University Press; 1993.
RCT still trumps the best observational study. BMJ 2000;321:255-6.
9. Warner KE, Luce BR. Cost-benefit and cost-effectiveness analysis in 32. Popcock SJ, Elbourne DR. Randomized trials of observational tribula- health care: principles, practice, and potential. Ann Arbor (MI): Health tions? N Engl J Med 2000;342:1907-9.
33. O’Byrne P, Cuddy L, Taylor DW, Birch S, Morris J, Syrotuik J. Efficacy 10. Garber AM, Weinstein MC, Torrance GW, Kamlet MS. Theoretical foun- and cost benefit of inhaled corticosteroids in patients considered to have dations of cost-effectiveness analysis. In: Gold MR, Siegel JE, Russell mild asthma in primary care. Can Respir J 1996;3:169-75.
LB, Weinstein MC, editors. Cost-effectiveness in health and medicine.
34. Connett GJ, Lenney W, McConchie SM. The cost-effectiveness of budes- New York: Oxford University Press; 1996. p. 25-53.
onide in severe asthmatics aged one to three years. Br J Med Econ 11. Sullivan S, Elixhauser A, Buist AS, Luce BR, Eisenberg J, Weiss KB.
National Asthma Education and Prevention Program working group 35. Rutten-van Mölken MP, Van Doorslaer EK, Jansen MC, Van Essen-Zand- report on the cost-effectiveness of asthma care. Am J Respir Crit Care vliet EE, Rutten FF. Cost-effectiveness of inhaled corticosteroid plus bronchodilator therapy versus bronchodilator monotherapy in children 12. National Asthma Education and Prevention Program. Expert panel report: with asthma. Pharmacoeconomics 1993;4:257-70.
guidelines for the diagnosis and management of asthma. Bethesda (MD): 36. Rutten-van Mölken MP, Van Doorslaer EK, Jansen MC, Kerstjens HA, National Institutes of Health; April 1997. Publication No. 97-4051.
Rutten FF. Costs and effects of inhaled corticosteroids and bronchodila- 13. van den Boom G, van Schayck CP, van Mollen MP, Tirimanna PR, den tors in asthma and chronic obstructive pulmonary disease. Am J Respir Otter JJ, van Grunsven PM, et al. Active detection of chronic obstructive pulmonary disease and asthma in the general population. Am J Respir 37. Barnes NC, Thwaites RM, Price MJ. The cost-effectiveness of inhaled fluticasone propionate and budesonide in the treatment of asthma in 14. Suissa S, Dennis R, Ernst P, Sheehy O, Wood-Dauphinee S. Effectiveness adults and children. Respir Med 1999;93:402-7.
of leukotriene receptor antagonist zafirlukast for mild-to-moderate asth- 38. Rutten-van Mölken MP, van Doorslaer EK, Till MD. Cost-effectiveness ma: a randomized, double-blind, placebo-controlled trial. Ann Intern analysis of formoterol versus salmeterol in patients with asthma. Phar- 15. O’Reilly JF, Weir DC, Banham S, Basran GS, Boyd G, Patel KR. Is high- 39. Lundback B, Jenkins C, Price MJ, Thwaites MA. Cost-effectiveness of dose fluticasone propionate via a metered-dose inhaler and Volumatic as salmeterol/fluticasone propionate combination product 50/250 micro- efficacious as nebulized budesonide in adult asthmatics? Respir Med grams twice daily and budesonide 800 micrograms twice daily in the treatment of adults and adolescents with asthma. Respir Med 2000; 16. Lord J, Ducharme FM, Stamp RJ, Littlejohns P, Churchill R. Cost effec- tiveness analysis of inhaled anticholinergics for acute childhood and ado- 40. Ross RN, Morris M, Sakowitz SR, Berman BA. Cost-effectiveness of lescent asthma. BMJ 1999;319:1470-1.
including cromolyn sodium in the treatment program for asthma: a retro- 17. Booth PC, Wells NE, Morrison AK. A comparison of the cost effective- spective, record-based study. Clin Ther 1988;10:188-203.
ness of alternative prophylactic therapies in childhood asthma. Pharma- 41. Thomas P, Ross RN, Farrar JR. A retrospective assessment of cost avoid- ance associated with the use of nedocromil sodium metered-dose inhaler 18. Campbell LM, Simpson RJ, Turbitt ML, et al. A comparison of the cost- in the treatment of patients with asthma. Clin Ther 1996;18:939-52.
effectiveness of budesonide 400 µg/day and 800 µg/day in the manage- 42. Lord J, Ducharme FM, Stamp RJ, Littlejohns P, Churchill R. Cost effec- ment of mild-to-moderate asthma in general practice. Br J Med Econ tiveness analysis of inhaled anticholinergics for acute childhood and ado- lescent asthma. BMJ 1999;319:1470-1.
19. Sculpher MJ, Buxton MJ. Episode-free days as endpoints in economic 43. Thomas K, Peter JV, Cherian AM, Guyatt G. Cost-effectiveness of evaluations of asthma therapy. Pharmacoeconomics 1993;4:345-52.
inhaled beta-agonists versus oral salbutamol in asthma: a randomized 20. Johansson G, Price MJ, Sondhi S. Cost-effectiveness analysis of salme- double blind cross over study. Natl Med J India 1996;9:159-62.
terol/fluticasone propionate 50/100 microgram versus fluticasone propi- 44. Camargo CA, Kenny PA. Assessing costs of aerosol therapy. Respir Care onate 100 microgram in adults and adolescents with asthma. III: Results.
45. Jasper AN, Mohsenifar Z, Kahan S, Goldberg HS, Koerner SK. Cost- 21. Palmqvist M, Price MJ, Sondhi S. Cost-effectiveness analysis of salme- benefit comparison of aerosol bronchodilator delivery methods in hospi- terol/fluticasone propionate 50/250 microgram versus fluticasone propionate talized patients. Chest 1987;91:614-8.
250 micrograms versus fluticasone propionate 250 micrograms in adults and 46. Summer W, Elston R, Tharpe L, Nelson S, Haponik EF. Aerosol bron- adolescents with asthma. IV: Results. Pharmacoeconomics 1999;16:23-8.
chodilator delivery methods. Relative impact on pulmonary function and 22. Pieters WR, Lundback B, Sondhi S, Price MJ, Thwaites RM. Cost-effec- cost of respiratory care. Arch Intern Med 1989;149:618-23.
tiveness analysis of salmeterol/fluticasone 50/500 micrograms versus flu- 47. Bowton DL, Goldsmith WM, Haponik EF. Substitution of metered-dose ticasone propionate 500 micrograms in patients with corticosteroid- inhalers for hand-held nebulizers: success and cost savings in a large, dependent asthma. V: Results. Pharmacoeconomics 1999;16:29-34. acute-care hospital. Chest 1992;101:305-8.
23. Barnes PJ, Pedersen S. Efficacy and safety of inhaled corticosteroids in 48. Orens DK, Kester L, Fergus LC, Stoller JK. Cost impact of metered dose asthma. Am Rev Respir Dis 1993;148:S1-26.
inhalers vs small volume nebulizers in hospitalized patients: the Cleve- 24. The Childhood Asthma Management Program Research Group. Long- land Clinic experience. Respir Care 1991;36:1099-114.
term effects of budesonide or nedocromil in children with asthma. N Engl 49. Turner MO, Gafni A, Swan D, Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.
25. Gerdtham UG, Hertzman P, Jonsson B, Boman G. Impact of inhaled cor- ticosteroids on acute asthma hospitalization in Sweden 1978-1991. Med 50. Cates CJ. Holding chambers versus nebulizers for beta agonist treatment of acute asthma (Cochrane Review). In: The Cochrane Library. Issue 3.
26. Price DB, Appleby JL. Fluticasone propionate: an audit of outcomes and cost-effectiveness in primary care. Respir Med 1998;92:351-3.
51. Kelloway JS, Wyatt R. A cost-effectiveness analysis of breath-actuated 27. Balkrishnan R, Norwood GJ, Anderson A. Outcomes and cost-benefits metered-dose inhalers. Managed Care Interface 1997;10:99-107.
associated with the introduction of inhaled corticosteroid therapy in a 52. Langley PC. The technology of metered-dose inhalers and treatment Medicaid population of asthmatic patients. Clin Ther 1998;20:567-80.
costs in asthma: a retrospective study of breath actuation versus tradi- 28. Adelroth E, Thompson S. Advantages of high-dose inhaled budesonide.
tional press-and-breathe inhalers. Clin Ther 1999;21:236-53.
53. Liljas B, Stadhl E, Pauwels RA. Cost-effectiveness analysis of a dry pow- 29. Perera BJ. Efficacy and cost effectiveness of inhaled steroids in asthma in der inhaler (Turbuhaler) versus a pressurized metered dose inhaler in a developing country. Arch Dis Child 1995;72:312-6.
patients with asthma. Pharmacoeconomics 1997;12:267-77.
210 Sullivan and Weiss
54. Green L. Toward cost-benefit evaluations of health education: some con- 77. Kelly SX, Anderson CL, Pestian JP, Wenger AD, Finch AB, Strope GL, cepts, methods and examples. Health Educ Monogr 1974;2:34-64.
et al. Ann Allergy Asthma Immunol 2000;84:509-16.
55. Boulet L, Champan K, Green L, FitzGerald J. Asthma education. Chest 78. Kwan-Gett TS, Lozano P, Mullin K, Marcuse EK. One-year experience with an inpatient asthma clinical pathway. Arch Pediatr Adolesc Med 56. Windsor RA, Bailey WC, Richards JM Jr, Manzella B, Soong SJ, Brooks M. Evaluation of the efficacy and cost effectiveness of health education 79. Hunter DJ, Fairfield F. Disease management. BMJ 1997;315:50-3.
methods to increase medication adherence among adults with asthma.
80. Harris JM. Disease management: new wine in new bottles? Ann Intern 57. Muhlhauser I, Richter B, Kraut D, Weske G, Worth H, Berger M. Evalu- 81. Epstein RS, Sherwood LM. From outcomes research to disease manage- ation of a structured treatment and teaching programme on asthma. J ment: a guide for the perplexed. Ann Intern Med 1996;124:832-7.
82. Integrated care for asthma: a clinical, social, and economic evaluation.
58. Lawrence G. Asthma self-management programs can reduce the need for Grampian Asthma Study of Integrated Care. BMJ 1994;308:559-64.
hospital-based asthma care. Respir Care 1995;40:39-43.
83. Kelly CS, Morrow AL, Shults J, Nakas N, Strope GL, Adelman RD. Out- 59. Trautner C, Richter B, Berger M. Cost-effectiveness of a structured treat- comes evaluation of a comprehensive intervention program for asthmat- ment and teaching programme on asthma. Eur Respir J 1993;6:1485-91.
ic children enrolled in Medicaid. Pediatrics 2000;105:1029-35.
60. Bolton MB, Tilley BC, Kuder J, Reeves T, Schultz LR. The cost and 84. Gilmet GP, Zeitz HJ, Lewandowski JJ. Pediatric asthma outcomes after effectiveness of an education program for adults who have asthma. J Gen implementation of a disease management model: the Asthmatter of Fact Program. Disease Management 2000;3:11-9.
61. Soondergaard B, Davidsen F, Kirkeby B, Rasmussen M, Hey H. The eco- 85. Levenson T, Grammer LC, Yarnold PR, Patterson R. Cost-effective man- nomics of an intensive education programme for asthmatic patients: a agement of malignant potentially fatal asthma. Allergy Asthma Proc prospective controlled trial. Pharmacoeconomics 1992;1:207-12.
62. Fireman P, Friday GA, Gira C, Vierthaler WA, Michaels L. Teaching self- 86. Jowers JR, Schwartz AL, Tinkelman DG, Reed KE, Corsello PR, Mazzei management skills to asthmatic children and their parents in an ambula- AA, et al. Disease management program improves asthma outcomes. Am tory care setting. Pediatrics 1981;68:341-8.
63. Lewis CE, Rachelefsky G, Lewis MA, de la Soto A, Kaplan M. A ran- 87. Greineder DK, Loane KC, Parks P. A randomized controlled trial of a domized trial of ACT (asthma care training) for kids. Pediatrics pediatric asthma outreach program. J Allergy Clin Immunol 1999; 64. Clark NM, Feldman CH, Evans D, Levison MJ, Wasilewski Y, Mellins 88. Watanabe T, Ohta M, Murata M, Yamamoto T. Decrease in emergency RB. The impact of health education on frequency and cost of health care room or urgent care visits due to management of bronchial asthma inpa- use by low income children with asthma. J Allergy Clin Immunol tients and outpatients with pharmaceutical services. J Clin Pharm Ther 65. Neri M, Migliori GB, Spanevello A, Berra D, Nicolin E, Landoni CV, et 89. Curtin K, Hayes BD, Holland CL, Katz LA. Computer-generated inter- al. Economic analysis of two structured treatment and teaching programs vention for asthma population care management. Effective Clinical Prac- 66. Lahdensuo A, Haahtela T, Herrala J, Kava T, Kiviranta K, Kuusisto P, et al.
90. Rossiter LF, Whitehurse-Cook MY, Small RE, Shasky C, Bovbjerg VE, Pen- Randomised comparison of cost effectiveness of guided self management berthy L, et al. The impact of disease management on outcomes and costs of and traditional treatment of asthma in Finland. BMJ 1998;316:1138-9.
care: a study of low-income asthma patients. Inquiry 2000;37:188-202.
67. Kauppinen R, Sintonen H, Tukiainen H. One-year economic evaluation 91. O’Connor JF, Singer ME, Richter JE. The cost-effectiveness of strategies of intensive vs conventional patient education and supervision for self- to assess gastroesophageal reflux as an exacerbating factor in asthma. Am management of new asthmatic patients. Respir Med 1998;92:300-7.
68. Ghosh CS, Ravindran P, Joshi M, Stearns SC. Reductions in hospital use 92. Deter HC. Cost-benefit analysis of psychosomatic therapy in asthma. J from self management training for chronic asthmatics. Soc Sci Med 93. Munroe WP, Kunz K, Dalmady-Israel C, Potter L, Schonfeld WH. Eco- 69. Freund DA, Stein J, Hurley R, Engel W, Woomert A, Lee B. The Kansas nomic evaluation of pharmacist involvement in disease management in a City asthma care project: specialty differences in the costs of treating community pharmacy setting. Clin Ther 1997;19:113-23.
94. Knoell DL, Pierson JF, Marsh CB, Allen JN, Pathak DS. Measurement of 70. Westley CR, Spiecher R, Starr L, Simons P, Sanders B, Marsh W, et al.
outcomes in adults receiving pharmaceutical care in a comprehensive Cost effectiveness of an allergy consultation in the management of asth- asthma outpatient clinic. Pharmacotherapy 1998;18:1365-74.
ma. Allergy Asthma Proc 1997;18:15-8.
95. McCowen C, Neville RG, Crombie IK, Clark RA, Warner FC. The facil- 71. Zwicke DL, Donohue JF, Wagner EH. Use of the emergency department itator effect: results from a four-year follow-up of children with asthma.
observation unit in the treatment of acute asthma. Ann Am Med 1982; 96. Kozma CM, Schulz RM, Sclar DA, Kral KM, Mackowiak JI. A compar- 72. Marks MK, Lovejoy FH Jr, Rutherford PA, Baskin MN. Impact of a short ison of costs and efficacy of intranasal fluticasone propionate and terfe- stay unit on asthma patients admitted to a tertiary pediatric hospital.
nadine tablets for seasonal allergic rhinitis. Clin Ther 1996;18:334-46.
Quality Management in Health Care 1997;6:14-22.
97. Stahl E, van Rompay W, Yang EC, Thomson DM. Cost-effectiveness 73. Rydman RJ, Isola ML, Roberts RR, Zalenski RJ, McDermott MR, Mur- analysis of budesonide aqueous nasal spray and fluticasone propionate phy DG, et al. Emergency department observation unit versus hospital nasal spray in the treatment of perennial allergic rhinitis. Ann Allergy inpatient care for a chronic asthmatic population. Med Care 1998; 98. Keith PK, Haddon J, Birch S, for the Rhinocort Study Group. A cost-ben- 74. Doan T, Grammer LC, Yarnold PR, Greenberger PA, Patterson R. An efit analysis using a willingness-to-pay questionnaire of intranasal bude- intervention program to reduce the hospitalization cost of asthma patients sonide for seasonal allergic rhinitis. Ann Allergy Asthma Immunol requiring intubation. Ann Allergy Asthma Immunol 1996;76:513-8.
75. McDowell KM, Chatburn RL, Myers TR, O’Riordan MA, Kercsmar CM.
99. Schadlich PK, Brecht JG. Economic evaluation of specific immunother- A cost-saving algorithm for children hospitalized for status asthmaticus.
apy versus symptomatic treatment of allergic rhinitis in Germany. Phar- Arch Pediatr Adolesc Med 1998;152:977-84.
76. Bailey R, Weingarten S, Lewis M, Mohsenifar Z. Impact of clinical path- 100. Santos R, Cifaldi M, Gregory C, Seitz P. Economic outcomes of a tar- ways and practice guidelines on the management of acute exacerbations geted intervention program: the costs of treating allergic rhinitis patients.
of bronchial asthma. Chest 1998;113:28-33.

Source: http://www.jcaai.readyportal.net/file_depot/0-10000000/20000-30000/27387/folder/62846/health_economics_asthma_part2.pdf