REVIEW ARTICLE

Pharmacoeconomics 2001; 19 (6): 623-642

1170-7690/01/0006-0623/$22.00/0
Adis International Limited. All rights reserved.

An Economic Overview of Chronic

Obstructive Pulmonary Disease
Hirsch S. Ruchlin1 and Erik J. Dasbach2
1 Weill Medical College of Cornell University, New York, USA
2 Health Economics Statistics, Merck Research Laboratories, Blue Bell, Pennsylvania, USA

Contents
Abstract
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Data Selection and Presentation . . . . . . . . . . . . . . . . . . . . . .
3. Cost and Utilisation Patterns . . . . . . . . . . . . . . . . . . . . . . . . .
3.1 Overall Burden of Illness . . . . . . . . . . . . . . . . . . . . . . . . .
3.2 Cost of Care Relative to Other Illnesses . . . . . . . . . . . . . . . .
3.3 Cost by Disease Severity . . . . . . . . . . . . . . . . . . . . . . . . .
3.4 Utilisation Rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5 Correlates of Cost and Utilisation . . . . . . . . . . . . . . . . . . . .
4. Economic Evaluations of Clinical Interventions for Chronic Obstructive
Pulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1 Pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2 Oxygen Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3 Home Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4 Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5 Exercise and Rehabilitation . . . . . . . . . . . . . . . . . . . . . . .
4.6 Health Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5. Discussion and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . .

Abstract

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Chronic obstructive pulmonary disease (COPD) is a major cause of mortality

and morbidity. Relatively few pharmacoeconomic studies have been conducted
on this disease. This article reviews available information about the utilisation of
healthcare resources and cost of care, and the cost or cost effectiveness of therapeutic interventions reported for this disease.
Burden-of-illness data indicate that hospital care, medications and oxygen
therapy were the major cost drivers in these studies. Mean annual Medicare
expenditures in the US were $US11 841 (2000 values) for patients with COPD
compared with $US4901 for all covered patients. Utilisation was skewed; the
most expensive 10% of the Medicare beneficiaries accounted for nearly 50% of
total expenditures for this disease. Costs are associated with health status, age,
physician specialty, geographic location and type of insurance coverage.
Six types of interventions were assessed in the literature - pharmacotherapy,
oxygen therapy, home care, surgery, exercise and rehabilitation and health education. The studies used different analytic strategies (e.g. cost-minimisation and
cost-effectiveness analyses) and even within the realm of cost-effectiveness anal-

624

Ruchlin & Dasbach

yses, no uniformity existed as to how outcome was measured. Patient severity

was not always delineated, and the length of the follow-up period, while quite
short, varied. Only 11 of the 34 evaluations were based on randomised controlled
trials.
Cost-minimisation studies generally found no significant difference in the cost
of antimicrobial treatment for first-line, second-line and third-line agents. Studies
of bronchodilators indicated that ipratropium bromide alone or in combination
with salbutamol (albuterol) was the preferred medication.
The major area for achieving cost savings is by reducing hospital utilisation.
As the annual rate of hospitalisation is relatively low, large patient samples will
be required to demonstrate an economic advantage for a new therapy. The major
challenges will be financing such a study, and selecting an outcome measure that
satisfies both clinical and economic conventions.

1. Background
Chronic obstructive pulmonary disease (COPD)
is defined as a disease of the respiratory system characterised by chronic bronchitis and/or emphysema.[1]
The prevalence of chronic bronchitis per 1000
persons in the US rose from 49.7 in 1985 to 54.0
in 1994. However, the prevalence of emphysema
per 1000 persons declined from 8.9 in 1985 to 7.8
in 1994. Applying these rates to US 1996 census
data, Wilson et al.[2] estimated that there were 14.3
million cases of chronic bronchitis and 2.1 million
cases of emphysema in 1996, and an estimated
119 340 deaths (7.3 per 100 000 population) attributable to chronic bronchitis and emphysema 2980
deaths from chronic bronchitis (1.1/1000 000) and
116 360 from emphysema (6.2/100 000). COPD is
the fourth leading cause of death in the US.[3]
Worldwide information generated by the Global
Burden of Disease study[4] indicates that COPD
ranked sixth among the 30 leading causes of death,
accounting for 2 211 000 deaths. By 2020, it is projected to be the third leading cause of death.
Despite its prevalence and contribution to overall morbidity, National Institutes of Health (NIH)
research funding for COPD in the US in 1994 was
low. COPD-related research funding was 1.3%
of total funding, and ranked 21st among the 29
disease areas reported by Gross et al.[5] However, it
ranked 11th with regard to both incidence (670 000)
and prevalence (4 271 000) and fifth with regard to
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mortality (96 000). Among the 29 illnesses, COPD

was the most underfunded disease relative to its
illness burden.[5]
A key to developing new interventions for treating COPD will be establishing that the therapy can
reduce the economic burden associated with the
disease. In particular, government and managed
care formulary decision makers are increasingly
limiting access to therapies that do not demonstrate
economic benefits and/or cost effectiveness.[6]
This review highlights and assesses what is currently known about the cost of care and the economic attributes of therapeutic interventions for
COPD. It also highlights future research needs.
2. Data Selection and Presentation
We searched the English language medical literature for 2 types of economic studies: those describing the prevalence and incidence of healthcare
resources utilised and the cost incurred by persons
with COPD, including cost-of-illness studies, and
economic evaluations of treatment interventions.
To locate these articles of interest, we reviewed
government publications, professional society publications and Medline and Embase. Both searches
were confined to the 1980 to 2000 period. The key
search terms used for the Medline search were
lung diseases, obstructive AND cost and cost
analysis, patient care, inpatients, outpatients,
emergency service, hospital, economics, hospital and economics, pharmaceutical. For Embase
Pharmacoeconomics 2001; 19 (6)

Economics of COPD

we used chronic obstructive lung disease AND

health economics and healthcare utilisation. We
also obtained studies noted in the reference sections of articles that we reviewed, thereby further
widening our search effort. Collectively, we identified over 350 articles dealing with the delineated
subject matter. Articles were excluded from the review if they focused on any of the following: cost
savings created by adhering to guidelines or disease management programmes; screening costs;
costs reported for a single intervention without using any comparator (i.e. cost identification analyses); and reports which co-mingled COPD with
other illnesses. Fifty-eight articles qualified for inclusion.
The studies cover a broad time horizon. All data
are also presented in 2000 US costs, based on inflation using the medical services component of the
Consumer Price Index for all urban consumers.[7]
These values appear in parentheses after the actual
values. Annual average currency conversion rates
were used to translate costs reported in local currencies for other countries into US dollars.[8]
3. Cost and Utilisation Patterns
The material in this section reviews the various
cost-of-illness studies that have appeared in the literature and presents some estimates of utilisation
rates for the US. As no multivariate analyses were
found assessing the correlates of utilisation and
cost, individual bivariate relationships are noted.
This material can form the basis for subsequent
multivariate analyses and for hypothesising directions of association in such analyses.
3.1 Overall Burden of Illness

Cost-of-illness data have been reported for the

US, UK, The Netherlands and Sweden and are
summarised in table I. Differences in data sources
per country account for the differences in the US
and UK estimates reported in the table. Traditionally, COPD encompasses 4 International Classification of Diseases, version 9 (ICD-9) codes: bronchitis, not specified as acute or chronic (490); chronic
bronchitis (491); emphysema (492); and chronic
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625

airways obstruction, not elsewhere classified (494

to 496). Not all of the studies include the 4 ICD-9
codes; 2 studies present information only for the
largest 2 codes: chronic bronchitis and emphysema.
Direct medical costs per patient ranged from
$US930 in Sweden to $US2208 in the US (2000
values). Inpatient care, medications and oxygen therapy were the major cost drivers in each country.
Differences in medical treatment patterns unique
to each country undoubtedly account for much, if
not all, of the cost differences. In the 2 studies which
also included indirect costs, direct medical care
costs ranged from 39.3% of total cost in Sweden to
61.5% of total cost in the US. The higher cost of
medical care in the US relative to worker earnings
probably accounts for this differential.
3.2 Cost of Care Relative to Other Illnesses

Grasso et al.[14] reported that 1992 Medicare per

capita expenditures for patients with COPD were
2.4 times that of all Medicare beneficiaries
$US8482 vs $US3511 ($US11 841 vs $US4901; 2000
values). Hospital expenditures, 64% of the total,
were 2.7 times higher: $US5409 vs $US2001;
($US7551 vs $US2793) while physician care was
2.2 times higher: $US2604 vs $US1198 ($US3365
vs $US1672). The overall utilisation of care was
not evenly distributed across all patients; the most
expensive 10% of Medicare beneficiaries accounted for nearly half of total expenditures for
this population.
A larger differential was reported by Ireys et
al.[15] for children in Washington State in the fiscal
year (FY) 1993 on Medicaid; median payments for
children with chronic respiratory disease (detailed
data on COPD were not reported) were $US3353
($US4392; 2000 values) and chronic respiratory disease ranked second among the 8 conditions studied. The median payment for all children in that
year was $US290 ($US378), and $US891 ($US1167)
for children with at least 1 condition.
Using data from a health maintenance organisation (HMO), Mapel et al.[16] reported that patients
with COPD were 2.3 times more likely to be admitted to the hospital at least once during the year
Pharmacoeconomics 2001; 19 (6)

626

Ruchlin & Dasbach

Table I. Summary of cost-of-illness studies

Reference

Country

Year

Illness

Findings

Cost in $US (2000

values)a

Wilson et al[2]

US

1996

Chronic bronchitis
and emphysema

Direct medical costs = $US14.5 billion

$US16.6 billion

Sullivan et al.[9]

Ward et al.[10]

Sullivan et al.[9]

US

US

UK

1993

1994

1996

Chronic bronchitis
and emphysema

COPD

COPD

Guest[11]

UK

1996/7

COPD

Rutten-van Molken
et al.[12]

The
Netherlands

1993

COPD

Jacobson et al.[13]

Sweden

1991

COPD

Inpatient care = $US8.3 billion

$US9.5 billion

Outpatient care = $US6.2 billion

$US7.1 billion

Medical care cost per patient = $US1712

$US1959

Total cost = $US23.9 billion

$US31.3 billion

Direct medical cost = $US14.7 billion

$US19.3 billion

Indirect cost = $US9.2 billion

$US12.1 billion

Total cost per patient = $US1522

$US1994

Medical care cost per patient = $US936

$US1226

Direct medical costs = $US6.6 billion

$US8.2 billion

Inpatient care = $US2.8 billion

$US3.5 billion

Outpatient care = $US3.8 billion

$US4.7 billion

Medical care cost per patient = $US1772

$US2208

Direct medical care = 848 million

$US1.7 billion

Cost per patient = 1154 ($US2300b)

$US2631

Direct medical care = 818 million

$US1.3 billion

Cost per patient = 1158

$US1854

Direct medical costs = $US346 million

$US453.3 million

Cost per patient = $US876

$US1148

Total cost = SEK2.78 billion

$US600.6 million

Direct medical cost = SEK1.08 billion

$US271.8 million

Indirect cost = SEK1.70 billion

$US427.8 million

Total medical cost per patient ($US620)c

$US930

Conversion method provided in section 2.

Conversion noted in Sullivan et al.[9]

Estimated number of patients with COPD in 1991 = 292 390 based on a prevalence rate of 8% of the population above the age of 45.
(Personal communication, L. Jacobson, 2001 Feb 9)

COPD = chronic obstructive pulmonary disease; SEK = Swedish kronor; $US = US dollars; = pounds sterling.

compared with age- and gender-matched patients

with other conditions, and those admitted had longer
average lengths of stay (4.7 vs 3.9 days, p < 0.001).
Mean charges per patient in 1997 for inpatient care
were $US5093 vs $US2026 ($US5665 vs $US2453;
2000 values), $US5042 vs $US3050 ($US5607 vs
$US3392) for outpatient services and $US1545 vs
$US739 ($US1718 vs $US822) for outpatient pharmacy services (all p < 0.001).
3.3 Cost by Disease Severity

Using the American Thoracic Society staging

system, Hilleman et al.[17] reported that treatment
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costs were highly correlated with disease severity.

Annual median treatment costs (1993/1994) by
stage were: stage I = $US1681, stage II = $US5037
and stage III = $US10 812 (p < 0.01) [$US2177,
$US6523 and $US14 002; 2000 values]. [Stage criteria: stage I = forced expiratory volume in 1 second (FEV1) 50% to 65% of predicted; stage II =
FEV1 35% to 49% of predicted; stage III = <35%
of predicted]. An even greater differential was
noted in a French study[18] reporting the annual
costs, in 1979 US dollars, for chronic bronchitis:
stage I = $US90, stage II = $US900 and stage III =
$US2925 ($US355, $US3546 and $US11 525;
2000 values).
Pharmacoeconomics 2001; 19 (6)

Economics of COPD

627

3.4 Utilisation Rates

Adding prevalence data to the utilisation data

for the US reported by Wilson et al.[2] one can estimate annual (unadjusted) utilisation rates. These
rates are reported in table II for 1996. The overall
annual hospitalisation rate per patient with COPD
was 0.089, the physician office visit rate was 0.732,
the emergency department visit rate was 0.0009
and the rate of physician visits for inpatient care
was 0.4481. Patients with emphysema had higher
annual hospital utilisation rates (0.158 vs 0.080)
and physician inpatient care rates (0.7951 vs
0.4034) than those with chronic bronchitis, but patients with chronic bronchitis had higher physician
office visit rates (0.789 vs 0.283). Emergency department rates were practically equal, and quite
low for both conditions.
Analysing an age- and gender-matched sample
from the 1987 US National Medical Care Expenditure Survey, Strassels et al.[19] noted that patients
with COPD had higher rates of hospitalisation (0.7
vs 0.3) as well as longer hospital stays (4.6 vs 2.2
days) and costlier stays ($US4430 vs $US2019)
[$US9802 vs $US4139; 2000 values] compared
with the non-COPD sample. They further noted
that patients with COPD utilised more office visits
to a generalist physician (4.2 vs 2.6), emergency
room visits (0.7 vs 0.2) and prescribed medications
(6.7 vs 3.0). By resource area, average expenditures were: prescribed medications $US509 vs
$US213 ($US1043 vs $US437; 2000 values), outpatient hospital visits $US782 vs $US270
($US1603 vs $US554), physician office visits

$US630 vs $US372 ($US1292 vs $US763) and

emergency department visits $US118 vs $US43
($US242 vs $US88).
Patients with COPD are frequent users of care.
An analysis of utilisation patterns of an inception
cohort of Medicare patients conducted by Cydulka
et al.[20] noted that 14% of the patients hospitalised
in 1984 did not require a subsequent admission by
1991. 88% of those hospitalised were admitted 5
or more times during this period. A frequent rehospitalisation pattern was also noted by Connors
et al.[21] who followed a prospective cohort of 1016
hospitalised patients for 6 months. They reported
that after discharge, 446 patients were readmitted
754 times.
3.5 Correlates of Cost and Utilisation

Articles appearing in the literature have identified patient health status, illness severity, age, physician specialty, geographic location and type of
insurance coverage as potential correlates of cost
and utilisation.
Strassels et al.[19] noted that poor health status
is associated with higher resource utilisation. The
mean number of inpatient admissions were 0.3 for
those reporting excellent health, 0.5 for those reporting either good or fair health and 0.9 for
those reporting poor health. Average cost per admission follows a similar pattern. They were
$US1512 ($US4100; 2000 values) for those in
excellent health, $US4514 ($US7000) for those
in good health, $US2845 ($US5832) for those in

Table II. Resource utilisation in the US, 1996[1,2]

Condition

Hospital dischargesa

Physician office visits

Physician ER visits

Physician hospital or
nursing home visits

Prevalence Crude
annual rateb

Prevalence

Crude
annual rateb

Prevalence

Crude
annual rateb

Prevalence

Crude
annual rateb
0.4481

COPD

1 464 000

0.089

12 002 000

0.732

15 500

0.0009

7 349 700

Chronic bronchitis

1 168 000

0.080

11 473 000

0.789

13 600

0.0009

5 862 900

0.4034

296 000

0.158

529 000

0.283

1 900

0.0010

1 486 800

0.7951

Emphysema
a

First listed discharge.

Rate per patient diagnosed with condition.

COPD = chronic obstructive pulmonary disease; ER = emergency room.

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Pharmacoeconomics 2001; 19 (6)

628

fair health and $US6141 ($US12 589) for those

in poor health.
Crockett et al.,[22] in a study conducted in Australia, also noted a positive relationship between
the number of comorbid conditions and hospital
stay. Mean length of stay for patients with <3 comorbid conditions was 5.36 days; for patients
with more than 5 comorbid conditions it was 7.64
days.
Age is also related to utilisation and cost. Niederman et al.[23] reported that although mean inpatient
costs were fairly similar by age in 1995, averaging
$US5637 ($US6685; 2000 values) for those above
the age of 64 years and $US5716 ($US6779) for
those aged younger than 65 years, mean length of
stay differed by age, being 6.3 and 5.8 days, respectively, for each age group. An interesting pattern
prevailed for physician visit costs; for office-based
care and hospital outpatient clinic care, they were
lower for the older group $US60 vs $US74 ($US71
vs $US88) and $US102 vs $US159 ($US121 vs
$US189), respectively, but they were higher for the
older group for emergency room care $US90 vs
$US76 ($US107 vs $US90).
Strauss et al.[24] noted no significant difference
in cost (measured as charges) and outcome for care
rendered by pulmonary medicine specialists, general internists, or family physicians. However, they
noted large variations in practice patterns within
each group. Variations in physician prescribing
patterns were also noted in Europe by Rudolf,[25]
who also reported that COPD was both under- and
misdiagnosed, and that there were large differences
between different European approaches to drug
therapy. Reguerio et al.[26] also showed no significant difference in resource intensity and hospital
costs for patients receiving care from generalists
and pulmonologists. Hueston et al.[27] noted no statistically significant differences with regard to antibacterials prescribed or patient follow-up visits
for patients with acute bronchitis, but a higher use
of diagnostic test utilisation in an HMO setting
compared with fee-for-service care.
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Ruchlin & Dasbach

4. Economic Evaluations of Clinical

Interventions for Chronic Obstructive
Pulmonary Disease
34 economic evaluations of interventions for
COPD were identified in the literature. They are
grouped by type of study pharmacotherapy, oxygen therapy, home care, surgery, exercise and rehabilitation and health education and summarised
in table III. The table includes costs for the actual
year evaluated in each study as well as those converted to US dollars for the calender year 2000;
however, all costs noted in the following subsections are in US dollars for the calender year 2000
(see section 2 for conversion method).
4.1 Pharmacotherapy

15 articles address the cost attributes of various

pharmacotherapies; 6 are cost-minimisation studies, 8 are cost-effectiveness studies and 1 contains
both types of calculations. They are reported under
the first subheading of table III.
Six studies compared various antimicrobial
agents.[29,32,34,38,41,42] Assessing patients with acute
exacerbation of chronic bronchitis, Destache et
al.[32] found no significant difference in cost per
episode between first-line agents, second-line agents
and third-line agents. Costs per exacerbation were
in the $US700 to $US1000 range. Rosell and Miravitlles[38] analysed the cost of care for patients with
acute exacerbations of chronic bronchitis for patients receiving cefixime and 8 different antibacterials (most using amoxicillin/clavulanic acid). The
total monthly antibacterial and treatment failure
cost for the amoxicillin/clavulanic acid and other
antibacterial groups was $US100.52 and $US117.66,
respectively, while for cefixime treatment it was
$US85.30. Cefixime also had the best outcome, defined as the percentage of patients who did not require care due to treatment failure.
Using cost per patient who received successful
treatment as their cost-effectiveness measure, Backhouse et al.[29] reported that one first-line agent
amoxicillin, and one third-line agent amoxicillin/
clavulanic acid (co-amoxiclav) had the lowest cost,
Pharmacoeconomics 2001; 19 (6)

Author

Study
type

Country

Period

Type of cost
analysis

Perspective Sample Disease

size
severity

Comparators

Follow-up
period

Findingsa

Lifetime

The incremental cost in a 70kg AATdeficient patient receiving weekly

replacement therapy at 60 mg/kg is $US13
971 per life-year saved ($US15 047).
When effectiveness is varied from 10-70%,
the incremental cost per life-year saved
ranges from $US152 941 to $US7330
($US164 717-$US7894)

Pharmacotherapy
M,O

US

1998

CE

Third-party
payer

NR

Severe
emphysema
(FEV1 <50% of
predicted)

AAT replacement
therapy

Backhouse
et al.[29]

M,O

UK

1993

CE

National
health
system

NR

Moderate to
severe airflow
obstruction and
chronic
bronchial
sepsis

10-day
Amoxicillin,
amoxicillin/clavulanic treatment
period
acid (coamoxiclav),
ciprofloxacin,
cefaclor

Bergemann
et al.[30]

MA,
RCTs

Italy

1994

CE

NN

717

Acute
exacerbation of
chronic
bronchitis

Immunoactive
bacterial extract
OM-85 BV versus
placebo

6 months

Savings for treating with OM-85 BV are

L51 095 per patient per 6 months
[$US31.68 ($US39.47)]

Collet et
al.[31]

RCT

Canada

1994

CM

Provider

381

Acute
exacerbation
(FEV1 between
20-70% of
predicted)

Immunoactive
bacterial extract
OM-85 BV (n =
191) versus
placebo (n = 190)

6 months

Actual cost data were not presented. Study

noted that the risk of being hospitalised for
a respiratory problem was lower in the
treatment group (16.2% vs 23.2%, p =
0.09); and among those hospitalised,
patients in the treatment group had shorter
stays (1.5 days vs 3.4 days, p = 0.04)

Destache et
al.[32]

US

1994

CM

Provider

Acute
60
patients exacerbation of
(having chronic
bronchitisb
224
exacerb
ations)

Episode
First-line agents
(amoxicillin,
tetracyclines,
erythromycin),
second-line agents
(cephradine,
cefuroxime,
cefaclor, cefprozil)
and third-line
agents (amoxicillin/
clavulanic acid,
azithromycin,
ciprofloxacin)

Cost per patient who received successful

treatment: amoxicillin = 70.32
($US105.67); amoxicillin/clavulanic acid =
68.11 ($US102.34); ciprofloxacin =
79.91 ($US120.08); cefaclor = 105.72
($US158.80). Costs for amoxicllin and
amoxicillin/clavulanic acid were considered
equal, while other 2 therapies were higher.
($US138.43, $US134.07, $US157.30,
$US208.03)

No significant difference between the 3

groups in cost per acute exacerbation;
charges per episode were $US942
$US2173, $US563 $US2296 and
$US542 $US1946, respectively
($US1174 $US216, $US702 $US2861,
$US675 $US2428)

Contd over page

629

PharmacoEconomics 2000: 19 (6)

Alkins &
OMalley[28]

Economics of COPD

Adis International Limited. All rights reserved.

Table III. Summary of chronic obstructive pulmonary disease (COPD) cost studies

630

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Table III. Contd

Follow-up
period

Findingsa

Study
type

Country

Period

Type of cost
analysis

Perspective Sample Disease

size
severity

Comparators

Friedman et
al.[33]

RCT

US

1998

CM, CE

Provider

1067

Stable with
moderately
severe airflow
obstruction
(FEV1 = 65%
of predicted)

85 days
Salbutamol
(albuterol) [n =
347], ipratropium
bromide (n = 362),
salbutamol +
ipratopium bromide
(n = 358)

The mean total per patient cost over the

follow-up period for ipratropium bromide
alone ($US156 $US69) and ipratropium
+ salbutamol ($US197 $US84) was
significantly less than salbutamol alone
($US269 $US108) [$US168 $US74
and $US212 $US90 vs $US290
$US116]. Differences in cost of
ipratroprium bromide and ipratropium
bromide + salbutamol were not statistically
significant. Cost effectiveness, calculated
as cost per mean FEV1AUC0-4, for each
arm was $US408, $US236 and $US221,
respectively ($US439, $US254 and
$US238). These differences were not
statistically significant

Grossman et RCT, M Canada

al.[34]

1994

CE

Societal

222

Acute
exacerbation of
chronic
bronchitis

Lifetime
Ciprofloxacin (n =
115) vs usual care
(any antibiotic
other than a
quinolone, n = 107)

Incremental cost per QALY gained for

ciprofloxacin was $Can18 588. (Actual cost
difference in the RCT, $Can578/year
favouring usual care, was not statistically
significant) [$US13,619 and $US423;
$US16,969 and $US527]

Hay &
Robin[35]

M, O

US

1990

CE

Societal

NR

Congenital
AAT-deficient
patients

AAT replacement
therapy

Lifetime

At an efficacy of 70%, the cost per life-year

saved with AAT therapy would be $US28 000$US72 000 ($US45 752-$US117 648)
depending on patient age, gender and
smoking status. At 30% efficacy, the range
becomes $US50 000-$US128 000 ($US81
700-$US209 152)

Jurban et
al.[36]

US

1988

CE

Third-party
payer

600

NN

Theophylline (n =
311) vs ipratropium
bromide (n = 289)

1 year

Ipratropium bromide was less costly

($US441) [$US848] and also more
effective (0.62 more complication-free
therapy months)

Orens et
al.[37]

O, S

US

1989

CM

Provider

Hospitalised
patients not
managed in an
ICU

MDI vs small
volume nebulisers

Admission

Institutional savings range from $US8440$US422 000 ($US14 960-$US751 582)

depending on overall patient volume
(20 000-200 000 therapies per year) and
percentage of patients who received
treatment by MDI (20-100%). Average =
$US23 031 ($US41 018)

Ruchlin & Dasbach

PharmacoEconomics 2000: 19 (6)

Author

1997

CM

Provider

2323

Acute
exacerbation

1 month
Cefixime (400
mg/day, n = 1438)
and 8 other
antibacterials (363
received
amoxicillin/clavulanic
acid)

Sclar et al.[39] O

US

1994

CM

Provider

417

NN

Ipratropium
bromide (n = 109),
theophylline (n =
116), corticosteroid
(triamcinolone or
beclomethasone, n
= 64), salbutamol
(n = 128)

Summer et
al.[40]

RCT

US

1987c

CM

Provider

36

Patients with
>10% increase
in FEV1

Episode
Standard
bronchodilator
therapy [15mg of
orciprenaline
(metaproterenol)]
administered by
updraft
nebulisation (n =
18, UDN) vs 0.5mg
of bronchodilator
given by a MDI
(terbutaline, n = 18,
MDI)

Equivalent bronchodilation was achieved

with MDI therapy with a lower daily charge
($US174.15 [$US356.14], no test of
statistical significance was performed)

Torrance et
al.[41]

RCT, M Canada

1994/95 CE

Societal

222

Type I or II
acute
exacerbation of
chronic
bronchitis

RCT = 1
Ciprofloxacin (n =
115) vs usual care year; M =
lifetime
(any antibacterial
other than
ciprofoxacin or
quinolone, n = 107)

Incremental cost per QALY for

ciprofloxacin = $Can18 600; $US13 690
($US16 633)

1995

Third-party
payer

NR

NN

Ciprofloxacin,
Episode
rufloxacin,
clarithromycin and
amoxicillin/clavulanic
acid

Cost per patient who received successful

treatment: rufloxacin = L277 800/$US179
($US212); amoxicillin/clavulanic acid =
L270 000/$US174 ($US206);
clarithromycin = L377 500/$US244
($US289); ciprofloxacin = L354
400/$US229 ($US272)

Wool et al.[42] M

Italy

CE

6 months

Total cost (antibacterial plus therapeutic

failure) of treatment with
amoxicillin/clavulanic acid and other
antibacterials was $US90.56 ($US100.52)
and $US106.00 ($US117.66) while the
total cost for cefixime was $US76.81
($US85.30). One-month treatment failure
rates were: cefixime 17.2%,
amoxicillin/clavulanic acid 25.6% and other
antibacterials 26.6%
Additional expenditures per patient per
month were $US29.05 higher for
salbutamol, $US51.36 higher for
theophylline and $US30.06 higher for the
corticosteroids, than for ipratropium
bromide ($US36.20, $US63.99,
$US37.45). All differences significant at p =
0.05

Contd over page

631

PharmacoEconomics 2000: 19 (6)

Spain

Economics of COPD

Adis International Limited. All rights reserved.

Rosell &
O
Miravitlles[38]

632

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Table III. Contd

Author
S t u d y Country
type

Period

Type of cost
analysis

Perspective Sample Disease

size
severity

Comparators

Follow-up
period

Findingsa

Oxygen therapy
Anon et al.[43] O

Spain

1992-94 C/E

Third party
payer

20

Acute
respiratory
failure in
previously
stable patients
(exacerbation
free for 3
months)

Mechanical
ventilation in an
ICU

5 years

Cost per QALY = $US26 283-$US44 602

($US34 562-$US58 652) [best and worse
case scenarios]

Heaney et
al.[44]

O, S

UK

1996

CM

Provider

NR

NN

Oxygen therapy by
concentrator vs
cylinder

2 years

At 90 minutes usage per day at a flow rate

of 2 L/min the concentrator route saved
710.7 ($US1137) [$US1301]

Keenan et
al.[45]

O, S

Canada

1996

CM

Provider

NR

Severe acute
exacerbation

Adding
noninvasive
positive pressure
ventilation to
standard therapy

Hospital
admission

Cost saving per patient = $Can3244

($US2380) [$US2723]

Nava et al.[46] O

Italy

1995-96 CM

Provider

16

Acute
respiratory
failure

Noninvasive
mechanical
ventilation (n = 10)
vs invasive
ventilation (n = 6)

48 hours

Daily costs per group were similar

($US806 $US74 vs $US865 $US51)
[$US939 $US86 vs $US1008 $US59]

Neri et al.[47]

Italy

1995-96 CM

Societal

29

NN

Oxygen saver
1 year
device (Companion
5 oxygen saver)

RCT

US

1981-82 CM

Societal

301

1 year
FEV1/FVC
Specialised
<60% predicted respiratory home
care (n = 99),
standard home
care (n = 102),
office care (n = 100)

Annual saving of L530 114 L184 233

($US2492 $866) [$US2906 $US1009]

Home care
Both types of home care were more
expensive. Cost per year: $US9767,
$US8058 and $US5051, respectively (p =
0.02) [$US32 954, $US27 188, $US17
042]. Average annual cost for all patients =
$US7647 ($US19 950)

Ruchlin & Dasbach

PharmacoEconomics 2000: 19 (6)

Bergner et
al.[48]

US

1985-88 CM

Provider

17

End-stage
chronic
pulmonary
disease

Approximate Average monthly cost was $US2505

Multi-disciplinary
ly 1.5 years ($US5303) compared with $US2833
home care
($US5997) for the same time interval prior
programme vs
to the intervention (i.e. usual home care)
standard home care

Roselle &
DAmico[50]

US

1978-80 CM

Provider

553

NN

Home care
including
respiratory therapy
vs standard home
care

1 year

Prevention of hospitalisation in the year

after the addition of respiratory therapy
resulted in a saving of $US2625 ($US10
238) per patient per year compared with
the year before this intervention

Shepperd et
al.[51]

RCT

UK

1994-95 CM

Societal

32

NN

Hospital (n = 17)
vs home care (n =
15)

3 months

Hospital care was more expensive: 2380

vs 1248 (p = 0.01) [$US3702 vs
$US1941; $US4502 vs $US2360]

Al et al.[52]

M, O

The
1992
Netherlands

CE

Societal

125

Patients with
end-stage
pulmonary
disease with a
predicted life
expectancy
<18 months

Lung
transplantation
surgery (n = 57) vs
patients on the
waiting list (n = 68)

Lifetime

Cost/QALY for those receiving

transplantation = NLG194 000
($US323 333) [$US451 050]

Ko & Waters[53]

US

1995-97 CM

Provider

42

Severe
emphysema

Sternotomy (n =
19) vs thorascopy
(n = 23)

Surgical
episode

$US27 178 $US11 130 vs $US37 299

$US47 139 ($US31 173 $US12 766 vs
$US42 782 $US54 068) [NS]. Authors
note that neither surgical technique yielded
any medical advantage

Ramsey et
al.[54]

US

1993

CE

Provider

28

Lifetime
Patients
Lung
eligible for lung transplantation (n =
transplantation 28) vs wait list (n =
24) patients

1989

CE

Societal

78

NN

Economics of COPD

Adis International Limited. All rights reserved.

Haggerty et
al.[49]

Surgery

Incremental cost per QALY gained from

lung transplantation was $US176 817
($US231 630)

Goldstein et
al.[55]

RCT

Canada

Respiratory
rehabilitation
(exercise,
education and
psychosocial
support, n = 38) vs
usual care (n = 40)

6 months

The incremental cost of achieving

improvement beyond the clinically
meaningful important difference in
dyspnea, emotional function and mastery,
assessed through a chronic respiratory
quality-of-life questionnaire, (0.5 points per
question) was $Can11 597 ($US16 107)
[$US28 767]
Contd over page

633

PharmacoEconomics 2000: 19 (6)

Exercise and rehabilitation

634

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Table III. Contd

Author

Study
type

Follow-up
period

Findingsa

Country

Period

Type of cost
analysis

Perspective Sample Disease

size
severity

Comparators

Guell et al.[56] RCT

Spain

NN

CM

Provider

60

Moderate to
severe illness
(FEV1/FVC
<65% of
predicted)

Rehabilitation and 2 years

exercise (n = 30)
and usual care (n =
30)

Actual cost data were not presented, but

hospitalisation rate was the same in both
groups (0.6 1.0 vs 1.3 1.8)

Parker &
Walker[57]

US

1995-96 CM

Provider

47

NN

Exercise and
education

1 year

Charges per patient in post-programme

year were $US939 ($US1094) less than in
the pre-programme year (p < 0.01)

Scherer &
O
Schmieder[58]

US

NN

CM

Provider

72

NN

Pulmonary
rehabilitation
programme (36
1.5-hour sessions)

6 years

Statistically significant reduction in

hospitalisation was noted for the year after
rehabilitation vs the year before, for the
first 4 years of follow-up. (Sample size and
significance level per follow-up year: 1 =
72, p = 0.005; 2 = 66, p = 0.05; 3 = 47; p =
0.06; 4 = 29, p = 0.01; 5 = 15, p = 0.59; 6 =
9, p = 0.16)

Toevs et
al.[59]

RCT

US

1982c

CE

Provider

76

Moderate to
Exercise and
severe (FEV1 = rehabilitation
36% of
predicted)

18 months

Cost per well-year = $US24 256 ($US69

639)

Wright et
al.[60]

US

1980-81 CM

Provider

57

NN

Pulmonary
rehabilitation
programme (10week exercise and
patient education)

1 year

Number of hospitalisations decreased from

497 in the year before the programme to
34 in the year after

Denmark

1990

Provider

82

Hospitalised
patients

Individualised (n =
42) vs usual
inhospital patient
education (n = 40)

1 year

The increase in health services

consumption after the intervention was
DKK15 298 per patient less in the
individualised group than in the control
group (p = 0.05) [$US2479; $US4051]

Health Education
Tougaard et
al.[61]

CM

Cost data presented in parentheses are 2000 values.

Chronic bronchitis is defined as excessive tracheo-bronchial mucus production for at least 3 months of the year for at least 2 years.

Study period not noted; for cost inflation purposes it was assumed to be 2 years prior to publication year.

AAT = alpha1-antitrypsin; AUC0-4 = area under the FEV1 curve from time 0 to 4 hours; CE = cost-effectiveness; CM = cost minimisation; DKK = Danish kroner; FEV1 = forced expiratory
volume in 1 second; FVC = forced vital capacity; ICU = intensive care unit; L = Italian lira; M = modelling; MA = meta-analysis; MDI = metered dose inhalers; NLG = Dutch guilders;
NN = not noted (for sample size); NR = not relevant (for modelling, simulations, or meta-analyses); NS = not statistically significant at p = 0.05; O = observational; QALY = quality-adjusted
life year; RCT = randomised controlled trial; S = simulation; UDN = updraft nebulisation; $Can = Canadian dollars; $US = US dollars.

Ruchlin & Dasbach

PharmacoEconomics 2000: 19 (6)

Economics of COPD

approximately $US136. Ciprofloxacin, a third-line

agent, had the second best outcome $US157 per
patient who received successful treatment, and
cefaclor, a second-line agent, had the highest cost
$US208 per patient who received successful treatment.
Grossman et al.[34] and Torrance et al.[41] used
data from the same Canadian randomised controlled trial to model the cost per quality-adjusted lifeyear (QALY) of ciprofloxacin compared with
usual care. Their modelling adopted a societal perspective and was based on a fairly large sample.
Cost per QALY was about $US16 700 ($US16 969
and $US16 330 in each study), a value below all
thresholds used in the literature to denote a worthwhile social investment of resources.
Wool et al.[42] calculated the cost per patient
who received successful treatment with rufloxacin,
compared with clarithromycin or amoxicillin/
clavulanic acid and ciprofloxacin. The degree of
COPD severity was not noted in this article. Costs
were all in the $US200 range, with the lowest cost
being for amoxicillin/clavulanic acid ($US206),
followed by rufloxacin ($US212), ciprofloxacin
($US272) and clarithromycin ($US289). Although
tests of statistical significance were not reported,
the authors assert that rufloxacin was no more
costly than the other drugs which were more
widely used.
Four studies assessed the cost of bronchodilators.[33,36,37,40] Friedman et al.,[33] using data from a
randomised controlled trial, compared salbutamol,
ipratropium bromide and salbutamol plus ipratropium bromide and concluded that ipratropium bromide alone or in combination with salbutamol was
less expensive than salbutamol alone ($US168 and
$US212 compared with $US290). This saving resulted from fewer exacerbations and hospital days.
Using data from an observational data set, Jurban
et al.[36] compared theophylline to ipratropium bromide and reported an annual saving of $US848
favouring ipratropium bromide. These savings
were due to a reduced rate of unscheduled clinic
visits, emergency room visits and hospitalisations.
The Friedman et al. study[33] was based on a large
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635

sample and focused on patients with moderately

severe airflow obstruction, while the Jurban et
al.[36] study used a smaller sample and did not specify the extent of disease severity. With regard to
cost effectiveness, the studies reached different
conclusions. Friedman et al.[33] concluded that all
3 options were equally cost effective in terms of
change in airflow outcomes, while Jurban et al.[36]
reported that ipratropium bromide produced a better outcome (complication-free months) than theophylline. As the 2 studies did not adopt a long term
perspective, a common outcome measure and did
not include similar patients, the cost-effectiveness
findings can not be compared. However, the results
seem to note that ipratropium bromide is less
costly.
Two studies, Orens et al.[37] and Summer et al.,[40]
compared 2 different methods of administering
bronchodilator therapy. Summer et al.,[40] using data
from a randomised controlled trial conducted on a
small number of patients reported equivalent bronchodilation with both methods, but the metereddose inhaler resulted in reduced charges of $US356
per episode because of shorter hospitalisations. Orens et al.[37] also reported cost savings from a simulation using observational data as a result of reduced labour costs.
Sclar et al.[39] compared the cost of 2 bronchodilator agents salbutamol and theophylline and
corticosteroids to a third bronchodilator ipratropium bromide, over a 6-month period. Based on a
regression analysis, they reported a higher monthly
cost per patient for the other 3 drugs than for ipratropium bromide. The incremental costs for the 2
bronchodilators, based on a regression analysis,
were $US36.20 and $US63.99 for salbutamol and
theophylline. The incremental monthly cost for the
corticosteroids was close to that of the least expensive bronchodilator, at $US37.45. The study did
not attribute the cost difference to any specific resource use difference. As these data were derived
from an observational cohort and could be associated with different case severity, a measure not
included in the study, they must be used with caution.
Pharmacoeconomics 2001; 19 (6)

636

Two studies addressed the cost effectiveness of

1-antitrypsin replacement.[28,35] Both were simulations based on modelling using observational
(administrative) data. Although detailed case severity
data were not provided in the Hay and Robin
study[35] (i.e. FEV1 levels) it appears that both studies focused on comparable patients requiring this
therapy. Alkins and OMalley[28] reported a cost
per life-year saved of $US15 047. The incremental
cost per life-year saved values reported by Hay and
Robin[35] are higher; they range from $US45 752
to $US209 152. Part of the cost differential is accounted for by the different perspectives and discount rates (7% and 5%, respectively). In both
studies, the reported findings are quite sensitive to
the assumed effectiveness of the therapy. Greater
effectiveness leads to lower cost per life-year
saved. Until more definitive data are available on
the effectiveness of this therapy, a clear statement
on the cost effectiveness of this intervention must
be held in abeyance. If information is nevertheless
required here, the newer clinical data used by Alkins and OMalley[28] suggest that more credence
be placed in their findings.
Two studies assessed immunoactive bacterial
extract OM-85 BV versus placebo as a preventive
strategy in patients with acute exacerbations of
chronic bronchitis.[30,31] Both studies used data
from randomised controlled trials, adopted a 6month time horizon and were based on large samples (n 300). The Collet et al. study[31] suggested
that this therapy may reduce the rate of hospitalisation (as the finding is statistically significant only
at a relaxed threshold of p < 0.10), and does reduce length of stay per hospital episode by almost
2 days. The net saving calculated by Bergemann et
al.[30] over the 6-month follow-up period was
$US39.47 per patient.
4.2 Oxygen Therapy

Five evaluations focused on the use of oxygen

therapy.[43-47] They are summarised under the second subheading of table III. All are based on observational studies, and the 3 that are not based on
simulations[43,46,47] are based on relatively small
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Ruchlin & Dasbach

samples. Only Neri et al.[47] adopted a societal perspective; the follow-up periods in the nonsimulation studies ranged from 48 hours to 5 years.
Anon et al.[43] reported a cost per QALY for the
use of mechanical ventilation in an intensive care
unit ranging from $US34 562 to $US58 652 for patients with acute respiratory failure. Among the
cost-minimisation studies, Nava et al.[46] reported
comparable costs for noninvasive mechanical versus invasive ventilation, and Neri et al.[47] reported
annual cost savings of about $US3000 for the use
of an oxygen saver device which lowered the daily
consumption rate. Heaney et al.[44] reported a 2year supply saving slightly in excess of $US1300
for the use of a concentrator delivery device versus
a cylinder, and Keenan et al.[45] reported a $US2723
savings per admission for adding noninvasive positive pressure ventilation to standard therapy due
to a reduced probability of developing ventilationassociated pneumonia. As none of the studies were
based on randomised controlled trials or large samples, their findings should be regarded as suggestive rather than definitive.
4.3 Home Care

Four studies addressed the cost of home care;

they are summarised under the third subheading of
table III. Two studies were based on randomised
controlled trials and 2 were observational studies.
Bergner et al.[48] compared 2 types of home care in
a randomised controlled trial, 1 delivered by nurses
with special training in respiratory care and the
other by regular nurses, to care received in a physicians office in older patients (average age of
65 years). The 2 home care programmes led to
significantly higher annual costs $US32 954 and
$US27 188 vs $US17 042. Annual costs for the entire sample were $US19 950. This finding is not at
all uncommon in an older population; most studies
evaluating home care costs in this population have
found that this benefit is not associated with costoffsets of equal magnitude.[62]
Shepperd et al.[51] compared the cost of home
care versus inpatient care in a randomised controlled trial of a small sample of patients whose severPharmacoeconomics 2001; 19 (6)

Economics of COPD

ity of illness was not delineated. Not surprisingly,

they reported that inpatient care was more expensive $US2142 over a 3-month follow-up period.
The 2 observational studies reported cost savings from a multidisciplinary home care team (about
$US500/month)[49] and the addition of a respiratory therapist to standard home care ($US10 238/
year) using a pre-post study design.[50] In both
studies the savings were attributable to reduced
hospital use.
In assessing these studies it is important to recognise that the studies reporting savings did not
report the cost of the intervention; this information
is needed in assessing overall programme value.
Furthermore, 3 studies did not control for change in
illness severity over time, and in 1 case[49] the authors did not identify the component of the programme that produced the bulk of the savings. Finally, none addressed whether the savings continued
once the intervention was halted, and if they did,
for how long a period of time.
4.4 Surgery

Three studies addressed surgical techniques, 2

focused on lung transplantation and 1 on the relative cost of different surgical techniques. They are
summarised under the fourth subheading of table
III. Based on a convenience sample, Ramsey et al.[54]
estimated that the cost per QALY gained associated
with surgery was $US231 630. Al et al.[52] arrived
at a much higher figure $US451 050 in their
simulation. Both values would be judged as quite
high by any standard that has been used in the
health services research literature. Ko and Waters[53] reported costs for the 2 surgical techniques
sternotomy and thorascopy that were not significantly different. In discussing this finding they
noted that both procedures led to comparable surgical outcomes.
4.5 Exercise and Rehabilitation

Six studies focused on this type of intervention.[55-60] They are summarised under the fifth
subheading of table III. Since the actual interventions used in each study differed in scope and con Adis International Limited. All rights reserved.

637

tent, one cannot comment on the merits of any single approach. However, as a group they do provide
a basis for assessing this broad type of intervention.
Guell et al.[56] and Wright et al.[60] only reported
data on hospital utilisation. As hospital care is a
major cost driver, these studies could be quite useful for hypothesis generation. Unfortunately, their
findings are not consistent. Using patient randomisation, Guell et al.[56] failed to find a significant
difference in hospitalisation over a 2-year period
in patients with moderate to severe illness. Wright
et al.,[60] however, found a large 1-year reduction
in hospitalisations in their observational cohort. As
they failed to document illness severity in their article, one does not know if they studied patients
with an illness profile comparable to those studied
by Guell et al.[56]
Goldstein et al.[55] and Toevs et al.[59] performed
cost-effectiveness evaluations; severity of illness
was not reported in the Goldstein et al.[55] article,
whereas the Toevs et al.[59] sample had moderate to
severe illness. The studies adopted different analytic perspectives societal and provider, respectively; had different follow-up periods 6 months
and 18 months; and used clinical measures of outcome rather than QALYs. The reported costs in
these 2 studies were similar $US28 767 (for 6
months) and $US69 639 (1 year). Both imply that
such interventions are of moderate cost relative to
outcome.
The study by Scherer and Schmeider[58] reported the reduction in hospital utilisation in the 6
years after intervention compared with the year before intervention. Significant reductions were
noted for post-operative years 1, 2 and 4, and the
reduction in year 3 approached statistical significance at conventional levels. As this study was observational in nature, sample size declined rapidly
the longer the follow-up period and the case severity of the studied patients was not delineated, one
must use their findings with extreme caution. Parker and Walker[57] also reported a saving of
$US1094 due to reduced hospital care in their proPharmacoeconomics 2001; 19 (6)

638

gramme in the year after the intervention as compared with the year before.
As was the case with the studies that assessed
home care, none of the studies isolated the most
important component of the intervention, or evaluated the long term duration of savings once the
actual programme was over. The absence of case
severity data in 4 of the studies precludes extrapolating the reported results to other COPD patients.
4.6 Health Education

One study[61] assessed health education alone as

an intervention. It is summarised under the last subheading of table III. It should be noted that almost
all the exercise and rehabilitation studies had a
health education component in them. Using a prepost perspective for a randomised trial of personalised health education versus standard practice in an inpatient population, Tougaard et al.[61]
reported an annual savings of $US4051 due primarily to reduced hospital care for respiratory
treatments and reduced use of emergency services.
As the target population were hospitalised patients
rather than those receiving care in community settings and the full extent of the personalised intervention was not clearly delineated, the reported
findings cannot be used as a basis for making any
claims about the economic value of health education among patients with COPD.
5. Discussion and Conclusions
The literature on the economic aspects of COPD
is not all that voluminous compared with that of
other chronic conditions. This is true both for the literature focusing on utilisation and cost studies as well
as economic analyses of various medically related
interventions to treat or facilitate the treatment of the
disease.
Burden-of-illness data indicate an annual cost
of approximately $US2000 per prevalent patient,
although such data were found for only 4 countries
the US, the UK, the Netherlands and Sweden.
Hospital care, medications and oxygen therapy
were the major cost drivers in these studies. Mean
annual Medicare expenditures in the US in 2000
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Ruchlin & Dasbach

dollars were $US11 841 compared with $US4901

for all covered patients. Patients with emphysema
utilised more institutional care while those with
chronic bronchitis used more ambulatory care.
Utilisation was skewed; the most expensive 10%
of the Medicare beneficiaries accounted for nearly
50% of total expenditures for this disease.
With regard to cost and utilisation studies, no
multivariate analyses were found that assessed the
correlates of cost. Univariate analyses suggest that
costs can be related to health status, age, physician
specialty, geographic location and type of insurance coverage.
Six types of interventions were reviewed here
pharmacotherapy, oxygen therapy, home care, surgery, exercise and rehabilitation and health education. The studies reported in the literature adopt
different analytic strategies (e.g. cost-minimisation
and cost-effectiveness analyses), and even within
the realm of cost-effectiveness analyses, no uniformity existed as to how outcome was measured.
Outcomes varied from clinical (i.e. process) measures, to well-year, lives saved and QALYs. Patient
severity was not always delineated in the studies,
and where it was it was often quite broad. Two
other important elements of heterogeneity were the
length of the follow-up period and the study methodology randomised controlled trials or observational studies. The lack of an effective control
group in such studies is a major limitation. Finally,
many studies were based on very small samples.
Cost-minimisation studies generally found no
significant difference in the cost of antimicrobial
treatment for first-line, second-line and third-line
agents. Costs per exacerbation were in the $US700
to $US1000 range. A meta-analysis of randomised
controlled trials, conducted by Backhouse et al.,[29]
indicated that within a cost-effectiveness framework (cost per patient who received successful
treatment), first-line agents such as amoxicillin had
a relatively low cost (about $US136) as did ciprofloxacin (about $US157), a third-line agent. Secondline agents, such as cefaclor, had a higher cost
($US208). Two studies reported on the cost per
QALY associated with the use of ciprofloxacin
Pharmacoeconomics 2001; 19 (6)

Economics of COPD

about $US16 700 a value that is well within the

range of affordable interventions. Studies of bronchodilators indicated that ipratropium bromide
alone, or in combination with salbutamol were the
preferred drugs.
Evaluations of the cost effectiveness of 1antitrypsin replacement indicated that the cost per
life-year saved was very sensitive to drug efficacy.
Cost-effectiveness ratios over most ranges were in
excess of $US50 000, indicating that such interventions were not as attractive as pharmacotherapy.
Similarly, the costs of surgical interventions were
quite high; 1 study reported a cost per QALY for
lung transplantation in excess of $US450 000.
Comparisons of alternative surgical techniques for
lung reduction surgery indicated comparable costs
(about $US36 000) and outcomes.
Mechanical ventilation for patients with acute
respiratory failure had a cost per QALY below
$US60 000, a threshold usually considered acceptable in the health economics literature. Home
care services did not produce concomitant costoffsets in other resource use categories; this service
added approximately $US10 000 to $US15 000 in
cost per year. No studies were noted that assessed
the cost of home care relative to any measure of
benefit. Exercise and rehabilitation programmes
assessed cost relative to numerous outcome measures; one had a cost per well year below $US70 000,
a level that is comparable to mechanical ventilation.
Areas for future research follow directly from
the above summary. Studies are needed to clarify
the correlates of cost and utilisation. Two concerns
are associated with designing such studies. First,
budgetary considerations will probably favour the
use of administrative data sets, which may not be
able to adequately assess the impact of illness severity. Second, it is widely held that COPD is frequently unrecognised and untreated.[63] Thus available data sets will not permit easy extrapolation of
the cost of treating this disease to all who require
such care. It is reasonable to assume that the available data is biased in that only the most severely ill
seek treatment.
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639

The challenge with demonstrating cost effectiveness using QALYs is measuring quality-adjusted
survival. Only 2 economic evaluations of a COPD
intervention in the literature related the cost of
treating the illness to quality-adjusted survival.[34,41]
In these studies, the Health Utility Index was used
to measure quality-adjusted survival. Other instruments which could be used include the EuroQOL
instrument (EQ-5D), the time trade-off technique,
the Quality Well-Being scale and the 36-item Short
Form (SF-36). The latter would need to be transformed to a utility scale using algorithms available in the literature in order to measure qualityadjusted survival. In all cases, each measure has its
logistical trade-offs when used in clinical trials.
However the biggest challenge with these instruments is their lack of sensitivity to measure small
changes in health-related quality-of-life. Moreover, presuming these instruments can detect small
changes, the required sample size given the interindividual variation can be fairly significant. As an
alternative to using the recommended economic
metrics, disease-specific measures of effectiveness
have been used to make a cost-effectiveness argument. In fact, a number of economic studies of
COPD interventions have used improved lung
function, for example FEV1, as a measure of effectiveness. Unlike the QALY, the disadvantage of
this measurement approach is that there is no clear
economic methodology to value this gain. Although some benchmarks may be available from
the asthma literature which confronts similar problems, this still limits the domain of diseases across
which comparisons can be made.
Another challenge with demonstrating cost effectiveness is modelling the long term effects of
the intervention on quality-adjusted survival. No
existing models are available from the literature
and hence they would need to be developed. Even
if developed, selecting appropriate input data (e.g.
incidence data) from the literature to populate a
cost-effectiveness model may be difficult given
that the definition of COPD has changed over time,
and many studies have not measured COPD severity. In the absence of hard data from trials, one
Pharmacoeconomics 2001; 19 (6)

640

would have to rely on expert opinion to populate

the cost-effectiveness model; however, the potential bias inherent in such information is a methodological concern. One advantage with a modelling
approach is that its application can serve as an alternative to demonstrating the effect of treatment
on quality-adjusted survival in a clinical trial. In
particular, QALYs could be measured in a sample
of persons separate from the clinical trial and applied to the health states defined in the economic
model. The model would then be used to project
long term quality-adjusted survival.
Demonstrating cost reductions is just 1 type of
economic objective. Another economic objective is
to demonstrate that the intervention reduces the use
of healthcare resources. With this objective a variety of other types of challenges exist. The first of
these is that a large sample size may be necessary
to demonstrate an effect on reducing healthcare
resource use. When resource savings were identified, they almost always resulted from a reduced
use of hospital care, However, we have roughly
estimated that the annual rate of resource use in
general is relatively low for the costly hospitalisations (0.09 per year), although it is substantially
higher for the less costly outpatient visits (0.73 per
year). Reduced use of outpatient care produces
much smaller savings than reduced use of inpatient
care. These COPD use rates are very similar to the
rates of resource use in populations with asthma.
Like the rates for asthma populations, actual rates
will depend on the targeted population with higher
rates being experienced in the more severely ill
populations. An additional challenge is that these
studies may need to be at least 1 year in length to
be credible for economic decision-makers. A final
challenge is the selection of a relevant comparator.
Given that there is wide variation in treatment patterns, the selection of a single or combination comparator drug may be difficult. The evidence, however, appears to favour ipratropium bromide alone
or in combination with salbutamol.
All the challenges noted here are not meant to
discourage further research in this important area.
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Ruchlin & Dasbach

Rather, they serve as guideposts for designing future studies.

Acknowledgements
This research was supported by Merck Research Laboratories.

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Correspondence and offprints: Dr Hirsch S. Ruchlin, Department of Public Health, Weill Medical College of Cornell
University, 411 East 69th Street - KB 319, New York, NY
10021, USA.
E-mail: hsruchli@mail.med.cornell.edu

Pharmacoeconomics 2001; 19 (6)