Copyright © 2005 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online
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2005;36;1291-1293; originally published online May 12, 2005;
Lewis B. Morgenstern
Devin L. Brown, Ronald D. Chervin, Susan L. Hickenbottom, Kenneth M. Langa and
Screening for Obstructive Sleep Apnea in Stroke Patients: A Cost-Effectiveness
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Screening for Obstructive Sleep Apnea in Stroke Patients
A Cost-Effectiveness Analysis
Devin L. Brown, MD; Ronald D. Chervin, MD, MS; Susan L. Hickenbottom, MD, MS;
Kenneth M. Langa, MD, PhD; Lewis B. Morgenstern, MD
Background and Purpose—Obstructive sleep apnea (OSA) is common after acute ischemic stroke and predicts poor stroke
outcome is unknown. We used a cost-effectiveness model to estimate the magnitude of benefit that would be necessary to
make polysomnography (PSG) and OSA treatment cost-effective in stroke patients.
Methods—A decision tree modeled 2 alternative strategies: PSG followed by 3 months of CPAP for those found to have OSA
versus no screening. The primary outcome was the utility gained through OSA screening and treatment in relation to 2
common willingness-to-pay thresholds of $50 000 and $100 000 per quality-adjusted life year (QALY).
Results—Screening resulted in an incremental cost-effectiveness ratio of $49 421 per QALY. Screening is
cost-effective as long as the treatment of stroke patients with OSA by CPAP improves patient utilities by ?0.2 for
a willingness-to-pay of $50 000 per QALY and 0.1 for a willingness-to-pay of $100 000 per QALY.
Conclusions—A clinical trial assessing the effectiveness of CPAP in improving stroke outcome is warranted from a
cost-effectiveness standpoint. (Stroke. 2005;36:1291-1294.)
Key Words: cost–benefit analysis ? sleep apnea, obstructive ? stroke management
pressure (CPAP) soon after stroke improves neurological outcome.
Further, even if CPAP were proven to improve stroke outcome in
stroke patients with OSA, screening all stroke patients may not be
cost-effective given the costs of polysomnography (PSG). Before a
clinical trial is performed to determine the effects of CPAP after
stroke, the cost-effectiveness of screening all stroke patients should
PSG and OSA treatment cost-effective in patients with recent
stroke. In addition to its usefulness in clinical trial planning,
informative for cost-reducing strategies.
bstructive sleep apnea (OSA) is common in ischemic stroke
patients and is associated with poor stroke recovery.1,2It is
The primary outcome was the utility gained through OSA
screening and treatment in relation to 2 common willingness-to-
pay thresholds of $50 000 and $100 000 per quality-adjusted life
year (QALY). Utilities summarize patient preferences for specific
health states, ranging from 0 for death to 1 for perfect health. A
decision tree (Figure) modeled 2 alternative strategies (screen-
See Editorial Comment page 1293
ing versus no screening) for a hypothetical adult with recent
stroke resulting in a moderate deficit, with an associated health
state utility of 0.6. In the screening pathway, identification of
OSA led to CPAP titration, followed by 3 months of CPAP
treatment. It wasassumedthattherewerenodeathsorrecurrentstrokes
over this short time period because these are patients who survived their
initial stroke hospitalization.3The 3-month time horizon also allowed us
to assume that no patient in the no-screening arm would come to
medical attention due to symptomatic OSA and “crossover” to receive
CPAP, thus allowing for a simple model. Reference case estimates of
prevalence of OSA and probability of CPAP acceptance in addition to
estimated costs and utilities are found in Table 1. The actual short-term
acceptance of CPAP in stroke patients in unknown, but this value was
allowed to vary in sensitivity analysis. The analysis was performed from
a societal perspective using a 3-month time horizon. Costs were
estimated based on Medicare reimbursement.4,5No discounting of costs
or utilities was needed given the time horizon. One-way sensitivity
analyses were conducted using the ranges found in Table 1. Two-way
sensitivity analyses, in which 2 variables were allowed to vary over a
decision tree was analyzed by Data 4.0 (TreeAge Inc).
Model results are found in Table 2. In the base case, the
incremental cost-effectiveness ratio for screening was
$49 421 per QALY. Two-way sensitivity analysis per-
Received December 22, 2004; final revision received February 8, 2005; accepted February 16, 2005.
From the Stroke Program (D.L.B., S.L.H., L.B.M.), Sleep Disorders Center (R.D.C.), and Division of General Medicine (K.M.L.), University
of Michigan Health System, Ann Arbor.
Correspondence to Devin L. Brown, MD, TC 1920/0316, 1500 E Medical Center Dr, University of Michigan, Ann Arbor, MI 48109. E-mail
© 2005 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000166055.52742.2b
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formed on the utilities of stroke states showed that PSG has
a cost-effectiveness ratio ?$50 000 per QALY as long as the
utility for those with OSA on CPAP is ?0.2 higher than for
those with OSA not on CPAP. Therefore, for a willingness-
to-pay of $50 000 per QALY, the relative increment in utility
would have to be ?50% (from 0.4 to 0.6), meaning that
screening is cost-effective as long as the treatment of stroke
patients with OSA by CPAP improves quality of life (QOL)
by ?50%. For a willingness-to-pay of $100 000 per QALY,
the relative increment in utility would have to be only ?25%
for screening to be cost-effective.
This analysis suggests that if CPAP were shown to
improve stroke recovery, it would need to improve pa-
tients’ utilities by 0.2 in order to be cost-effective given a
willingness-to-pay of $50 000 per QALY and by 0.1 for a
willingness-to-pay of $100 000 per QALY. In general,
interventions that cost ?$50 000 to $100 000 per QALY
gained are judged to be worthwhile healthcare expendi-
tures.6The aforementioned changes in utility represent a
25% to 50% relative improvement in QOL (given the
assumption of 0.4 for the utility of a stroke in an OSA
One method for lowering costs associated with PSG
screening and CPAP titration would be to attempt to
combine the 2 in a split-night study. If the apnea–
hypopnea index is ?20 in the first half of the night, the
second half of the night may be used for CPAP titration.7
This would cut costs considerably to $26 918 per QALY.
With the use of a split-night study in all patients, only 16%
and 32% improvement in utility would be required to make
screening cost-effective given a willingness-to-pay of
$100 000 and $50 000 per QALY, respectively.
Another potential cost-saving mechanism would be to
use clinical criteria to help identify patients with OSA.
Unfortunately, clinical criteria currently identify less than
two-thirds of stroke patients with OSA correctly.8There-
fore, presently, PSG is necessary to screen stroke patients
The results of this analysis cannot be extended to those
with very mild or very severe strokes. Additionally, this
analysis is limited by the validity of the utility estimates
used. The utilities used were gathered from patients at risk
for stroke given the societal perspective taken. We also
performed sensitivity analyses on these values in attempt
to compensate for this limitation. Further studies obtaining
more precise estimates of QOL and cost information in
stroke patients with OSA are needed.
OSA after stroke is common and is associated with poor
outcome. A clinical trial assessing the effectiveness of
CPAP in improving stroke outcome is warranted from a
cost-effectiveness standpoint. The feasibility of perform-
ing split-night studies in stroke patients should be assessed
as a cost-saving mechanism.
Ranges Used for Sensitivity Analyses
List of Percentages, Utilities, and Costs for the Reference Case and
Prevalence of OSA in stroke
Cost of PSG
Cost of CPAP titration
Cost of CPAP plus supplies for 3 months
Utility of stroke without OSA
Utility of stroke with untreated OSA
Utility of stroke with treated OSA
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1. Turkington PM, Bamford J, Wanklyn P, Elliott MW. Prevalence and
predictors of upper airway obstruction in the first 24 hours after acute
stroke. Stroke. 2002;33:2037–2042.
2. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-
disordered breathing and poor functional outcome after stroke. Stroke.
3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM,
Wiebers DO. Survival and recurrence after first cerebral infarction: a
population- based study in Rochester, Minnesota, 1975 through 1989.
4. Centers for Medicare and Medicaid Services. CMS Files for
Download. Available at: http://www.cms.hhs.gov/providers/
pufdownload/#dme. Accessed April 20, 2005.
5. Centers for Medicare and Medicaid Services. Medicare Physician Fee
Schedule 2003. Michigan Locality 01. Available at: http://
www.cms.hhs.gov/physicians/pfs/#2003. Accessed April 20, 2005.
6. Ubel PA, Hirth RA, Chernew ME, Fendrick AM. What is the price of
life and why doesn’t it increase at the rate of inflation? Arch Intern
7. Chesson AL, Ferber RA, Fry JM, Grigg-Damberger M, Hartse KM,
Hurwitz TD, Johnson S, Littner M, Kader GA, Rosen G, Sangal RB,
Schmidt-Nowara W, Sher A. Practice parameters for the indications
for polysomnography and related procedures. Sleep. 1997;20:
8. Bassetti C, Aldrich MS, Chervin RD, Quint D. Sleep apnea in patients
with transient ischemic attack and stroke: a prospective study of 59
patients. Neurology. 1996;47:1167–1173.
9. Krieger J, Kurtz D, Petiau C, Sforza E, Trautmann D. Long-term
compliance with CPAP therapy in obstructive sleep apnea patients and
in snorers. Sleep. 1996;19(suppl):S136–S143.
10. Post PN, Stiggelbout AM, Wakker PP. The utility of health states after
stroke: a systematic review of the literature. Stroke. 2001;32:
How Much Is a Good Night’s Sleep Worth?
As Brown et al point out in this issue of Stroke, sleep
disordered breathing is associated both with increased
stroke risk and increased poststroke morbidity and mortal-
ity.1Obstructive sleep apnea (OSA) is common after
stroke, occurring in as many as 60 to 90% of patients,
although the natural history of OSA in stroke patients,
especially when OSA is first identified during the acute
hospitalization, is not well studied. Because effective
treatment, namely continuous positive airway pressure
(CPAP), is effective at reducing sleep apnea and has been
shown in small studies to be feasible in stroke patients, it
is reasonable to consider planning trials to evaluate
whether CPAP can improve stroke outcomes and reduce
subsequent vascular events.
The authors used decision–analytic modeling to identify
the magnitude of benefit that identification and treatment
of OSA would need to demonstrate to be considered
cost-effective. They estimated the magnitude of benefit of
screening and treatment of OSA by using quality-adjusted
life years (QALYs), a metric that combines one’s prefer-
ence for a health state with the time that one lives in that
health state. They estimated the cost-effectiveness by
calculating an incremental cost-effectiveness ratio or the
extra costs to screen and treat OSA compared to not screen
and treat to gain QALYs. Although the level at which a
treatment is considered cost-effective varies, in the US
interventions that cost less than $100 000 to $200 000 per
QALY are typically considered cost-effective.2
As far as decision–analytic models go, this model is
simple and thus is missing some elements that would
improve its face-validity.3The three-month time horizon is
not adequately justified, nor is the exclusion of mortality.
Important model inputs include the prevalence estimates of
OSA, the estimates of acceptance of CPAP, and the
estimates of utility of stroke with and without OSA.
Although the authors allowed these estimates to vary in
sensitivity analyses, the range of estimates in some cases is
not adequately justified. As the Cochrane collaboration
points out, acceptance of CPAP is almost certainly lower
than published studies suggest, so it would be helpful to
allow CPAP acceptance to vary below the stated 50%
acceptance rate.4Importantly, 1 study in a stroke cohort
found that only 4 of 34 patients with OSA demonstrated
objective compliance with home CPAP over a 3-month
period.5Key variables that were not directly tested in this
model include an estimate of the disutility of testing, and
the effect of any reduction in sensitivity or specificity of
polysomnography. This is especially important in stroke
patients where testing may be done during hospitalization
when sleep patterns are already disturbed by the associated
environmental and possibly pharmacological milieu. Other
treatments for OSA have also been shown to be effective
and, in some studies, preferred by patients over CPAP, so
including models of other treatment strategies would also
be informative.6Finally, a 50% increase in utility (from
0.4 to 0.6) associated with treatment may be a somewhat
TABLE 2.Model Results for the Reference Case
? ? ?? ? ?
$1757 $1757 0.0355$49 421
Brown et al Screening for Sleep Apnea in Stroke Patients
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discouraging target. For example, utility differences for Download full-text
persons with Parkinson disease initially treated with levo-
dopa showed a relative utility increase of only 5 to 10%.7
Further, although studies typically demonstrate reduction
in symptoms with treatment of OSA, this symptom im-
provement does not always translate to a corresponding
improvement in utilities.8,9
When evaluating any model, it is instructive to recall,
“All models are wrong, but some are useful.”10There is no
doubt that this model then, like all models, is wrong, but is
it useful? We think it so. Not so much in its ability to
predict truth or to inform current clinical decision-making,
but rather in its approach to technology assessment. This
study is an important illustration of the direction we need
to move in considering cost-effectiveness modeling in
clinical trial planning and ultimately clinical trial conduct.
Pilot clinical trial data from studies in OSA could serve to
inform not only the precision of the estimates of accep-
tance and efficacy of CPAP, but also the expected benefit
in utility scores, and could allow for evaluation of various
methods of assessing patient utilities which may also affect
the ability to detect meaningful group differences. Ideally,
clinical trial planning groups would include multidisci-
plinary teams of health economists and quality of life
experts to address this critical issue, to ensure that clinical
trials will not only address the question of “does this
treatment work,” but will also help policy makers and the
public with the question of “is the treatment worth the
Linda S. Williams, MD
Health Services Research and Development
Roudebush VAMC, and
Department of Neurology
Indiana University School of Medicine
Robert G. Holloway, MD, MPH
Neurology and Community & Preventive Medicine
University of Rochester School of Medicine and Dentistry
1. Brown DL, Chervin RD, Hickenbottom SL, Langa KM, Morgenstern LB.
Screening for obstructive sleep apnea in stroke patients: a cost-
effectiveness analysis. Stroke. 2005;36:1291-1294.
2. Ubel PA, Hirth RA, Chernew ME, and Fendrick AM. What is the price
of life and why doesn’t it increase at the rate of inflation? Arch Intern
3. Kassirer JP, Angell M. The journal’s policy on cost-effectiveness analy-
ses. N Engl J Med. 1994;331:669–670.
4. Haniffa M, Lasserson TJ, Smith I. Interventions to improve compliance
with continuous positive airway pressure for obstructive sleep apnoea.
Cochrane Database Syst Rev. 2004;4:CD003531.
5. Hui DS, Choy DK, Wong LK, Ko RW, Li TS, Woo J, Kay R. Prevalence
of sleep-disordered breathing and continuous positive airway pressure
compliance: results in Chinese patients with first-ever ischemic stroke.
6. White J, Cates C, Wright J. Continuous positive airways pressure for
obstructive sleep apnoea. Cochrane Database Syst Rev 2001;4:
7. Noyes K., Dick A., Holloway RG; and Parkinson Study Group.
Pramipexole vs levodopa as initial treatment for Parkinson’s disease: a
randomized clinical-economic trial. Med Dec Making. 2004;24:472–485.
8. Sandberg O, Franklin KA, Bucht G, Eriksson S, Gustafson Y. Nasal
continuous positive airway pressure in stroke patients with sleep apnoea:
a randomized treatment study. Eur Respir J. 2001;18:619–622.
9. Jenkinson C, Stradling J, Petersen S. Comparison of three measures of
quality of life outcome in the evaluation of continuous positive airways
pressure therapy for sleep apnoea. J Sleep Res. 1997;6:199–204
10. Box GEP, Hunter WG, and Hunter JS. Statistics for Experimenters: an
Introduction to Design, Data Analysis, and Model Building. New York:
John Wiley & Sons; 1978.
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