(Stroke. 1998;29:351-358.)
© 1998 American Heart Association, Inc.
Comparison of the Use of Medical Resources and Outcomes in the Treatment of Aneurysmal Subarachnoid Hemorrhage Between Canada and the United States
Henry A. Glick, MA;
Daniel Polsky, PhD;
Richard J. Willke, PhD;
Wayne M. Alves, PhD;
Neal Kassell, MD;
Kevin Schulman, MD
From the Division of General Internal Medicine and the Leonard Davis
Institute of Health Economics, University of Pennsylvania, Philadelphia (H.G.,
D.P.); Pharmacia and Upjohn Inc., Kalamazoo, Mich (R.W.); the Department of
Neurosurgery and the Virginia Neurological Institute, University of Virginia,
Charlottesville, Va (W.A., N.K.); and the Clinical Economics Research Unit,
Division of General Internal Medicine, Georgetown University Medical Center,
Washington, DC (K.S.).
E-mail hlthsvrs{at}mail.med.upenn.edu
 |
Abstract
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Objective—Using data from a
randomized trial of tirilazad mesylate, we assessed the differences
between Canada and the United States in the use of medical resources
and outcomes in the treatment of aneurysmal
subarachnoid hemorrhage during the first 90 days
after admission to the hospital.
Methods—Of the 877 patients for whom economic data were
available, 194 were enrolled in Canada and 683 were enrolled in the
United States. The differences between the countries in patient
characteristics, use of medical resources, and outcomes were
analyzed by comparing means and the 95% confidence intervals
(CIs) around the differences in means. These differences also were
predicted with use of multivariable regression
analysis.
Results—The average hospital stay was 4.2 days longer (95% CI,
1.3 to 7.1 days) in Canada, but most of the extra stay was among
patients admitted to the study in poor neurological condition. In
general, however, hospital stays in Canada were substantially less
intensive. Patients treated in Canada spent 3.7 fewer days (95% CI,
1.2 to 6.1 days) in nursing homes and rehabilitation centers than did
patients in the United States. No statistically significant differences
were seen for Glasgow Outcome Scale score, death, and occurrence of
vasospasm.
Conclusions—For patients admitted to the study in good
neurological condition, the apparent difference in length of stay
between Canada and the United States was caused by a shift in the sites
of formal care rather than to the length of this care. For those
admitted in poor neurological condition, both the length and sites of
care differed between the two countries. No significant difference in
outcomes appeared to justify these differences in the use of medical
resources.
Key Words: Canada • lipid peroxidation • subarachnoid hemorrhage
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Introduction
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Differences between
the health care systems of Canada and the United States have received
growing attention because Canada spends a smaller percentage of gross
domestic product on health care and exerts greater government
control over expenditure than does the United
States.1 2 3 4 5 6 7 8 9 10 11 Much research has focused solely on
variations in practice patterns, without simultaneous
assessment of the outcomes of this
variation.1 2 4 6 8 9 11 Recently, however,
investigators have used data from two multinational clinical trials of
drug therapies after acute myocardial infarction to assess treatment
differences for specific clinical populations and to assess differences
in the processes and outcomes of care.3 5 They
found that hospitalization in the United States was longer and more
intensive than that in Canada. In one study, these differences did not
translate into differences in mortality or the rate of a second
infarction,5 whereas in the other, after 1 year
patients treated in the United States had a significantly higher
survival and substantially greater improvement in functional
status.3 The latter finding, however, was
questioned in a series of letters to the
editor.12 13 14 15
We used data from a randomized trial of tirilazad
mesylate16 to assess differences between Canada
and the United States in the use of medical resources and in clinical
outcome in the treatment of aneurysmal subarachnoid
hemorrhage (SAH) during the first 90 days after randomization.
Studying aneurysmal SAH allowed us to determine whether the
cross-national differences found in the studies of myocardial
infarction can be generalized to another disease. Moreover, by
including postdischarge use of medical resources in our cross-national
comparisons, we gained a better understanding of the size and scope of
the differences in treatment between the two countries over an extended
period.
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Subjects and Methods
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Clinical Trial
The clinical trial was conducted from 1992 to 1994 in 54 centers
located in the United States and Canada.16
Patients were randomly assigned to one of three treatment groups:
vehicle (n=300) or tirilazad at 2.0 or 6.0 mg/kg of body weight per day
for 8 to 10 days (n=298 and n=299, respectively). Treatment began
within 48 hours of the development of SAH and ended 10 days after the
hemorrhage occurred. The primary clinical outcome was mortality
at day 76 after the first dose of study medication. Secondary outcomes
included diagnosis of clinical vasospasm in the 14 days after
randomization and functional status at 90 days (defined by the Glasgow
Outcome Scale17 ). Both clinical data and data on
use of medical resources for the first 90 days after admission to the
hospital were collected prospectively during the trial.
The clinical results of this study showed that there was no difference
in mortality or in symptomatic vasospasm between the
treatment groups. When patients were stratified by gender and
neurological grade on admission to the study, men with grades IV and V
who received tirilazad at 6 mg/kg per day had an 85% reduction in the
risk of death (5% versus 33% among patients who received placebo;
P=.03). Full results have been reported
elsewhere.16
Patients
Data on use of medical resources were available for 877 of the
897 patients who were enrolled in the trial and received at least one
dose of treatment or vehicle. Of these 877 patients,194 were enrolled
in Canada and 683 in the United States. All 20 patients who were
excluded from the analysis because of insufficient data on use
of medical resources were enrolled in the United States.
Measurements
Patient Characteristics
Data on the patients' clinical and demographic characteristics
were collected before randomization. These data included age,
characteristics of the aneurysm, blood pressure, pulse, days
between onset of SAH and randomization, sex, race, neurological grade
(range, I through V, with V the most severe), and distribution of
vasospasm. Data were also collected on the size of the hospital
(measured by number of beds) in which the patient was treated.
Medical Resources
For the initial hospitalization, use of a selected set of
resources was recorded daily for the first 21 days and weekly for
all days after the first 3 weeks. Data elements included total length
of stay subdivided by days in intensive care, step-down care, routine
care, and other units; number of surgical procedures by type of
procedure; drugs; days on which the patients received hypertension,
hypervolemia, and hemodilution therapy; use of albumin and
volume expanders; days on which a Swan-Ganz catheter was in place;
number of CT scans, transcranial Doppler
ultrasonograms, and radiographs; and number of chemistry panels, ECGs,
and lumbar punctures.
Many surgical procedures were performed during this trial. We
analyzed aneurysm clipping and shunt placement
separately because these procedures were the most common (performed in
842 and 148 patients, respectively). We also summarized total use of
surgery in the two countries by converting the number of surgical
procedures to a common relative value unit scale by use of the workload
and practice expense relative value units from the Medicare Fee
Schedule.18
Data were also collected on days spent in nonhospital facilities
(nursing homes and rehabilitation centers), days spent in the hospital
because of readmission, and days spent at home.
Clinical Outcomes
The clinical outcomes used in this analysis were the
occurrence of vasospasm by day 14 after randomization, death during the
initial hospitalization, death during the first 90 days after
randomization, and the Glasgow Outcome Scale score 90 days after
randomization. Among the 877 patients included in the study, 9 (2
treated in Canada and 7 treated in the United States) had missing
values for the Glasgow Outcome Scale score at 90 days; these patients
were excluded from the evaluation of this outcome.
Analysis
Patient Characteristics and Use of Medical Resources
We report means and standard deviations (continuous
variables) and percentages (categorical variables) for a
selected set of patient characteristics by country. We also report the
difference in means and percentages between the two countries and,
where applicable, the 95% confidence intervals (CIs) around the
difference.
Outcomes
We report percentages for the four clinical outcome
variables by country. We also report differences between the two
countries and, where applicable, 95% CIs around the
differences.
Accounting for Severity of Illness
Although data used in our study were derived from a randomized
controlled trial, randomization was by treatment and not by where
patients received their care. Thus, some of the differences that were
observed between the two countries may have been due to differences in
the patients' underlying severity of
illness.12 15 To limit the potential for such
bias, we used multivariate regression analysis
to reevaluate differences between Canadian and US use of a selected set
of resources (for the initial hospitalization, total length of stay,
stays in the intensive care, step-down care, and routine care units,
and surgery relative value units; after discharge from the initial
hospitalization, days in nursing homes or rehabilitation centers). We
also reevaluated differences between Canada and the United States in
the occurrence of vasospasm by day 14 and death during the first 90
days after randomization. These analyses controlled for
potential differences in severity of illness among the patients.
We used ordinary least squares regression for the prediction of total
length of stay, intensive care and routine care unit stays, and for
surgery relative value units. Due to the lower frequency of their use,
we used a two-stage procedure to predict step-down care unit and
nursing home and rehabilitation center stays, first predicting the
probability of any stay and then predicting the length of stay among
those who used these services. For the prediction of vasospasm and
death, we used logistic regression.
The explanatory variables for these regressions included the
country in which the patient was treated, age, a diagnosis of
hypertension prior to SAH, pulse rate at randomization, characteristics
of the SAH as diagnosed from the admission CT scan (the presence of
left to right or right to left shifts of the midline structures, the
presence of localized or generalized brain swelling, and evidence of
enlarged lateral ventricles), a borderline or abnormal finding on the
admission ECG, prior history of vasospasm, neurological grade on
admission to the study, location of the aneurysm, and the order
in which the patient was enrolled at the center where he/she received
care (a proxy for experience). These variables were selected
because they were highly correlated with the measures of use of
resources and outcome.
Variables that were considered for the analysis but which
were not used because they had insufficient independent predictive
ability included treatment group, gender, race, handedness, smoking
behavior, history of prior stroke, the number of abnormal items on the
medical history, the number of aneurysms, abnormalities on the
admission chest roentgenogram, employment status, blood pressure, and
hospital size.
In addition to evaluating whether our results were due in part to
differences in the severity of illness of patients treated in the two
countries, we evaluated whether the relative differences in the use of
medical resources and outcome observed between Canada and the United
States were similar for patients admitted to the study in good
neurological condition (grades I through III) and patients admitted in
poor neurological condition (grades IV through V). Neurological status
on admission to the study was assessed with a modified version of the
World Federation of Neurological Surgeons grading
scale.16
Statistical Tests
Differences between the countries were considered to be
statistically significant if the 95% CIs around the differences
excluded zero. For the univariate comparisons, we tested
whether these statistical results were sensitive to this
parametric test of significance by use of the Wilcoxon
rank sum test for continuous variables and the Fisher exact test
for categorical variables. For the ordinary least squares
regressions, we tested the sensitivity of the parametric
specification of the error terms by using least absolute value models
that predicted the median rather than the mean for the dependent
variables.19 We note cases in which the
detection of significance differs between the parametric and
nonparametric methods.
For the evaluation of differences by neurological condition on entry to
the study, we compared the coefficients for the differences between
Canada and the United States with an F test.
For the ordinary least squares regressions, we report
R2 values as the measure of the predictive
ability of the models; for logistic regressions, we report the
concordance index (which equals the area under the receiver operating
characteristic curve20 ). We did not adjust our
tests of significance to account for the multiplicity of comparisons
(ie, we were more likely to detect differences between Canada and the
United States in use of medical resources and outcomes than we would
have been had we made this adjustment).
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Results
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Patient Characteristics
Table 1
shows patient
characteristics by country measured when the patients were assigned to
one of the three treatment groups. Patients in Canada were more likely
to be white (absolute difference, 17.8%) and on average had 0.4 fewer
aneurysms; a lower diastolic blood pressure
(-3.3 mm Hg); a slower pulse rate (5 fewer beats per
minute); 0.1 more days between onset of SAH and randomization; and
treatment in hospitals that had 171 fewer beds. The neurological grade
did not significantly differ between patients treated in Canada and
those treated in the United States, nor were there differences in the
clot thickness as measured on the admission CT scan.
Medical Resources
Table 2 shows use of medical
resources after randomization during the initial hospitalization in
Canada and the United States. The average length of stay in Canada was
4.8 days longer (95% CI, 1.3 to 8.3 days) than the average length of
stay in the United States. In general, however, hospital stays in
Canada were substantially less intensive. On average, patients treated
in Canada spent 6.6 fewer days in intensive care units (95% CI, -8.0
to -5.2 days), had a lesser amount of surgery (as indicated by fewer
relative value units per patient [-6.9; 95% CI, -12.7 to -1.1]),
received 4.4 fewer types of drugs(95% CI, -5.7 to -3.0), and had
lower rates of diagnostic testing. In all but one case
(total surgery relative value units), the results of the
parametric statistical tests were confirmed by the
Wilcoxon rank sum test.
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Table 2. Selected Resource Utilization After Randomization
During the Initial Hospitalization for Subarachnoid
Hemorrhage Among Patients Treated in Canada and the United
States
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Table 3 reports the average number of
days of care by site in the first 90 days after SAH. Patients treated
in Canada spent 4.1 fewer days (95% CI, 1.7 to 6.5 days) in nursing
homes and rehabilitation centers than did patients treated in the
United States. This reduction almost completely offset the increased
length of stay for the initial hospitalization observed among patients
treated in Canada.
Outcomes
Table 4 reports outcomes among
patients treated in Canada and those treated in the United States. None
of the four outcomes statistically significantly differed between the
two countries.
Accounting for Severity of Illness
Table 5 reports the differences in
the use of medical resources and absolute differences in the
probability of the clinical outcomes between Canada and the United
States estimated from the regressions that predicted lengths of stay;
the number of relative value units for surgery; death at 90 days; and
the presence of vasospasm within 14 days after randomization.
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Table 5. Results of Analysis After Adjustment for
Differences in Severity of Illness Between Patients Treated in Canada
and the United States
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Although a number of the characteristics of the patients treated in
Canada and those treated in the United States differed, they had little
effect on the observed differences in the use of medical resources or
clinical outcomes. After adjustment using multivariable
analysis, differences in length of stay in the intensive care,
step-down, and routine care units as well as in nursing home and
rehabilitation centers were similar to the differences identified in
the univariate analyses. The difference in the
number of surgical relative value units was also similar. In addition,
the small nonsignificant difference for death at 90 days that was
observed in the univariate analysis became even
smaller (absolute difference, -0.5%, 95% CI, -5.0% to 5.3%). A
slightly larger difference was seen for the occurrence of vasospasm at
day 14 (absolute difference, -2.5%, 95% CI, –12.9% to 6.6%).
As with the univariate analyses, in all cases
except for surgery relative value units the results of the median
regression were similar to those for the ordinary least squares
regression predicting the mean values.
Table 5
also reports these same analyses repeated for patients
who were admitted into the study in good neurological condition (grades
I through III) and those who were admitted in poor neurological
condition (grades IV through V). These subanalyses indicated
that differences between Canada and the United States in the use of
intensive care units, surgery, and nursing home and rehabilitation
centers were similar for patients admitted to the study in good versus
poor neurological condition (P=.27, P=.62, and
P=.36 respectively; probability values not shown in the
table).
The relative use of step-down and routine care units in Canada and the
United States, on the other hand, differed between these two patient
groups. Patients admitted to the study in good neurological condition
spent 2.7 more days in step-down care units and 6.5 more days in
routine care units when treated in Canada compared with when they were
treated in the United States. Patients admitted to the study in poor
neurological condition spent 2.7 fewer days in step-down care units and
15.9 extra days in routine care units when treated in Canada compared
with when they were treated in the United States (P=.003 and
P=.001, respectively; probability values not shown in the
table).
Overall stay during the initial hospitalization tended to be slightly
longer for patients admitted in good neurological condition in Canada
compared with those admitted in the United States (P=.06),
but the length of the episode of care (including days in nursing homes
and rehabilitation centers) was similar in the two countries
(P=.46; data not shown). Stay during the initial hospital
was substantially longer for patients admitted in poor neurological
condition in Canada compared with those in the United States
(P=.01). The decreased use of nursing homes and
rehabilitation centers reduced but did not fully offset the differences
in the length of the treatment episode.
While our subanalysis of the clinical outcomes had little
power, we were unable to detect relative differences between Canada and
the United States in the clinical outcomes of patients admitted to the
study in good versus poor neurological condition (P=.36 for
being alive at 90 days and P=.91 for vasospasm by day 14;
probability values not shown in the table).
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Discussion
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We found that use of medical resources in the treatment of
patients with aneurysmal SAH differed substantially between
Canada and the United States. On average, the initial hospitalization
was 4.7 days shorter for patients treated in the United States compared
with those treated in Canada but involved 6.6 more days of intensive
care. After discharge for the initial hospitalization, patients treated
in the United States spent 3.7 more days in nursing homes and
rehabilitation centers than did those treated in Canada. The absolute
difference in the severity-adjusted probability of survival at 3 months
was -0.5% (Canada-United States) and was not statistically
significant.
We also found that the differences in the use of intensive care units
observed between Canada and the United States were similar for patients
admitted to the study in good as well as poor neurological condition,
but the differences in the use of step-down and routine care units
observed between Canada and the United States were not the same for
these two patient populations. Patients in good neurological condition
in the two countries had similar overall lengths of stay in the
hospital, but Canadian physicians substituted days in step-down and
routine care units for days in intensive care unit. Patients in poor
neurological condition who were treated in Canada had substantially
longer stays in the hospital than those treated in the United States,
and substantially more of their stays were in routine care units.
Our findings generally confirm and expand on the findings from previous
comparisons of use and outcome of health care between Canada and the
United States (these comparisons focused on care after myocardial
infarction). As did Rouleau and colleagues,5 we
found that patients treated in Canada had longer hospital stays. Like
Rouleau and colleagues, we found no significant difference in outcomes
to justify the additional use of medical resources in the United
States.
While the studies of treatment after myocardial
infarction3 5 did not comment on follow-up
institutionalization, we found that more patients in the United States
received follow-up care in nursing homes and rehabilitation centers
than those in Canada. For patients admitted to the study in good
neurological condition, the length of the episode of care was similar
in the two countries, but differed in the sites of care. In Canada more
days were spent in step-down care and routine care units during the
initial hospital stay; in the United States more days were spent in
intensive care units during the initial hospital stay and in nursing
homes and in rehabilitation centers after the discharge from the
hospital. For patients admitted to the study in poor neurological
condition, the episode of care for those treated in Canada was
substantially longer than for those treated in the United States, but
was marked by fewer days in intensive care units. These findings appear
to confirm prior observations that the US hospital payment system,
which is based on diagnosis related groups, may provide incentives for
earlier discharge from the hospital and more use of nursing homes and
rehabilitation centers after discharge.21 22 23
Hospital bills were available for most of the patients treated in the
United States but were unavailable for all patients treated in Canada.
Had we predicted the latter bills using multivariable
analysis that associated the resource use observed in the trial
with the total bills, and had we also adjusted for differences between
US costs and charges and between Canadian and US unit costs, we would
have found that on average, patients treated in Canada cost $15 300
(95% CI, $9800 to $20 900) less than those treated in the United
States. The difference in costs would have been greater among patients
admitted in good neurological condition ($17 300, 95% CI, $12 200 to
$22 300) and smaller among patients admitted in poor neurological
condition ($9800, 95% CI, $3300 to $16 200).
Our study is one of the few multinational comparison studies that
controlled for observed differences in severity of illness among the
patients treated in the different countries. Our univariate
analysis of patient characteristics indicated that study
investigators in the two countries may have enrolled different types of
patients in the trial (based on race, number of aneurysms,
etc). Nevertheless, our multivariable analyses showed that
adjustment for measured disease severity did not substantially affect
our results.
Our study has several limitations. First, our analysis (along
with the other two that have compared use of medical resources and
outcomes3 5 ) was based on data from a large
clinical trial rather than on data from observation of the usual care
of patients. Although the trial itself did not impose major
restrictions on the usual care of these patients, it may have resulted
in more monitoring and longer stays than would have occurred had the
patients not been enrolled in a randomized trial. On the other hand,
the investigators in the clinical study were carefully selected and may
have been more efficient than other providers in the community.
Second, although our results may accurately reflect differences in use
of medical resources among larger hospitals with substantial
neurosurgical capabilities in Canada and the United States, it is not
clear that the magnitude of differences we observed accurately reflects
the magnitude that might exist between community hospitals in the two
countries. For example, Taylor et al,24 in a
recent study of care after SAH in the United States, reported that
among older patients with SAH only 18.9% were treated surgically
(compared with over 90% of patients in our study who were surgically
treated). This difference in the rates of surgery was unlikely to have
resulted from differences in the ages of the populations in the two
studies (as with the overall sample, among the 84 patients in our study
who were aged 70 and above, over 90% were treated surgically). It may
instead have been due to the fact that the enrolling physicians in our
study generally were neurosurgeons.
In conclusion, our study highlights the potential, based on practices
observed in Canada and the United States, for physicians in both
countries to maintain their standard of care while potentially reducing
the use of medical resources. Patients and physicians in both countries
stand to benefit from comparative studies such as ours that identify
use and outcomes for relatively homogeneous groups of
patients with well-defined clinical characteristics.
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Acknowledgments
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Supported in part by a grant from Pharmacia and Upjohn Inc,
Kalamazoo, Mich. The authors thank Sankey Williams, MD, who read a
prior version of the manuscript.
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Footnotes
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Reprint requests to Henry Glick, University of Pennsylvania, Division of General Internal Medicine, Room 312A, 3615 Chestnut St, Philadelphia, PA 19104.
Richard Willke is an employee of Pharmacia and Upjohn.
Received September 17, 1997;
revision received November 18, 1997;
accepted November 18, 1997.
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Abstract
Introduction
