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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2369-2372
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Financial analysis of chronic transfusion for stroke
prevention in sickle cell disease
Alan S. Wayne,
Steve E. Schoenike, and
Charles
H. Pegelow
From the Department of Pediatrics, Division of
Pediatric Hematology Oncology, Sickle Cell Center, and Pediatric
Pharmacy Department, University of Miami School of Medicine, Jackson
Memorial Medical Center, Miami, FL.
 |
Abstract |
Chronic red blood cell transfusion can prevent many of the
manifestations of sickle cell disease. The medical costs of chronic transfusion and management of associated side effects, especially iron
overload, are considerable. This study was undertaken to evaluate the
financial impact of chronic transfusion for stroke prevention in
patients with sickle cell anemia. Outpatient charges pertaining to
hospital-based Medicare uniform bill (UB-92) codes, professional fees,
and iron chelation were evaluated. Data were collected on 21 patients
for a total of 296 patient months (mean, 14; median, 14 months/patient). Charges ranged from $9828 to $50 852 per patient per
year. UB-92, chelation, and physician-related charges accounted for
53%, 42%, and 5% of total charges, respectively. Of UB-92 charges,
58% were associated with laboratory fees and 16% were related to the
processing and administration of blood. Charges for patients who
required chelation therapy ranged from $31 143 to $50 852 per patient
per year (mean, $39 779; median, $38 607). Deferoxamine accounted for
71% of chelation-related charges, which ranged from $12 719 to
$24 845 per patient per year (mean, $20 514; median, $21 381). The
financial impact of chronic transfusion therapy for sickle cell disease
is substantial with charges approaching $400 000 per patient decade
for patients who require deferoxamine chelation. These data should be
considered in reference to cost and efficacy analyses of alternative
therapies for sickle cell disease, such as allogeneic bone marrow transplantation.
(Blood. 2000;96:2369-2372)
© 2000 by The American Society of Hematology.
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Introduction |
The medical care required for persons with sickle
cell disease (SCD) has been recognized as a significant burden in
regard to health care expenditures.1,2 Chronic transfusion
therapy can prevent many of the complications of SCD, including
stroke.3-7 Monthly red cell transfusion is required to
adequately suppress hemoglobin-S production. With long-term
administration, complications eventually develop, most notably iron
overload that in turn requires treatment with deferoxamine (DFO)
chelation. This approach to managing SCD, although effective, is
expensive, and no systematic analysis of the costs of such management
has been published. This study was undertaken to evaluate the financial
impact of chronic transfusion therapy for stroke prevention in SCD.
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Materials and methods |
Patients
Study subjects included all patients with the diagnosis of
sickle cell anemia who were receiving outpatient chronic transfusion therapy for stroke prevention at Jackson Children's Hospital and at
the University of Miami Division of Pediatric Hematology Oncology. Sixteen patients had experienced a prior stroke and 5 patients were
enrolled in the Stroke Prevention (STOP) Trial in Sickle Cell
Anemia.7 This study was approved by the institutional review board.
Data collection
A retrospective review was conducted for the period from January
1997 to April 1998. Outpatient hospital charges were generated from the
hospital database, using Medicare uniform bill (UB-92) charge
codes.8 All UB-92 charges were reviewed, and those charges related to emergency room visits, inpatient hospitalization, or management of comorbid conditions were excluded from the analysis. Monthly charges for chelation therapy were estimated, based on the
prescribed patient dose for 30 days/month, DFO average wholesale price
of $11.19/500 mg,9 and standard allowed fees for
dispensing and home care administration based on State of Florida
Agency for Health Care Administration Medicaid
guidelines.10 Patient records were reviewed to verify the
number of outpatient visits, DFO dose, and number of packed red blood
cell units administered during the study period. Hematology attending
physician charges were estimated by using a fee of $108 per clinic
visit, which is the standard University of Miami professional charge
for an established outpatient receiving the level of service provided (CPT code 99213).
Statistical analysis
Total patient charges for the study period were tabulated, and
the percentage of expenditures was calculated by UB-92, chelation, and
physician charge categories. Monthly patient charges were calculated as
follows: Total UB-92 code charges  number of data collection months,
total physician charges number of data collection months, and DFO
chelation-associated monthly charges.
Patient charges were analyzed in 3 groups: all patients, patients not
receiving DFO chelation, and patients receiving DFO chelation. Charges
were annualized and regressed by group against the variables of patient
age, weight, annualized transfusion volume in units, and annualized DFO
dose in grams. Parametric and nonparametric measures of association
were calculated, using the methods of Pearson and
Spearman.11 Descriptive statistics, analysis of variance,
and regression calculations were performed, using SAS System for
Windows (Release 6.12 SAS Institute Inc.)
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Results |
Patient and treatment characteristics
Data were collected on 21 patients for a total of 296 patient
months (mean, 14; median, 14 months/patient; Table
1). Patient age ranged from 6 to 22 years
(mean, 13; median, 14) and weight from 18 to 66 kg (mean, 42; median,
43). Patients received 1 to 3 units (mean, 2.5; median, 2.2) of packed
red blood cells every 3 to 4 weeks as needed to maintain the
hemoglobin-S level  30%. Red cell units were leukodepleted by
filtration for 17 patients and by washing for the remaining 4. To
decrease the risk of alloimmunization, the 19 patients with known red
cell phenotype received blood matched for ABO, Rh(C, c, D, E, e), and
Kell antigens.3 Routine laboratory studies performed at
each visit included a complete blood count, reticulocyte count, type
and crossmatch, and hemoglobin electrophoresis. In addition, chemistry
panels with liver function tests and iron indices were monitored at
least every 3 months. DFO chelation therapy was administered via
nightly subcutaneous injection to 14 patients with confirmed iron
overload in doses ranging from 750 to 2500 mg/day (mean, 43 mg/kg/day).
Patients treated with DFO tended to be older, to weigh more, and to
require larger transfusion volumes than those not on chelation therapy
(Table 1).
Patient charges
Total charges for the 21 patients during the study period were
$678 559 (Table 2). UB-92, chelation,
and physician-related fees accounted for 53%, 42%, and 5% of the
total charges, respectively. Of the UB-92 charges, 58% were associated
with laboratory fees, and 16% were related to the processing and
administration of blood. Physician fees were the smallest charge
category, representing less than 10% of the total charges for each
patient group.
Annualized charges for the 14 patients who received chelation therapy
ranged from $31 143 to $50 852 per patient per year (mean, $39 779;
median, $38 607) and were greater than those for the 7 patients not on
DFO (range, $9828-$25 922; mean, $17 378; median, $19 652;
P = .0001). Charges related to iron chelation therapy
ranged from $12 719 to $24 845 per patient per year (mean, $20 514;
median, $21 381). Of chelation-related charges, 71% were associated
with DFO and 29% with home health care services. Patient age,
transfusion volume, and DFO dose were all strongly correlated with
charges for those on chelation therapy (parametric correlation data not
shown; Table 3).
| |
Discussion |
Survival in SCD has improved dramatically over the past decades
because of the change in living conditions and improvements in
supportive care.12,13 The current cost of care for
individuals with SCD is substantial, varying with the severity of
disease manifestations. A recent study by the National Association of Children's Hospitals and Related Institutions (NACHRI) found that annual charges for children with mild SCD were less than $10 000, whereas individuals with severe manifestations (including stroke) incurred charges of approximately $70 000 per year.14 The
mean Medicaid expenditure for children with SCD in a 1993 Washington State study was $8221 per child per year (range,
$142-$177 014).2 This figure amounted to 8.8 times the
mean expenditure for all children in the State Medicaid Program.
Notably, 10% of the children with SCD accounted for 56% of the total
SCD-related expenditures. The total direct yearly cost of
hospitalization in the United States for children with SCD was
estimated to be between $24 300 000 and $119 800 000 (in 1996 U.S.
dollars) with an average direct cost per hospitalization of $4200 to
$5600.15 This estimate is comparable to inpatient
hospitalization charges at our institution in 1997 for 323 patients
classified under diagnosis-related group (DRG) 396 (Red Blood Cell
Disorders, Age 0-17 years) that averaged $5906 per patient (data not
shown). The cost of care for adults with SCD would be expected to be
higher than for pediatric patients because of an increased frequency of
certain complications as well as greater costs of treatments based on
weight (eg, medications, transfusions). Notably, a study of adults with
SCD found charges for health care use exceeded $100 000 per patient
year (1991 U.S. dollars).1
Stroke, a frequent and devastating complication of SCD, has an
estimated lifetime prevalence of 5%-17%.16-19 Children
most commonly develop ischemic infarction because of occlusion of large cerebral blood vessels. Without chronic red cell transfusion, the risk
of recurrent stroke is extremely high with reported prevalence rates of
50%-90%.5,16,20 Maintenance of the hemoglobin-S level
below 30% with chronic transfusion dramatically decreases the
recurrence risk to about 10%5,6; however, prolonged
transfusion is required.21,22 Chronic transfusion has also
recently been shown to prevent first-time strokes in pediatric patients
at high risk.7
To our knowledge, an analysis of the cost of chronic transfusion
therapy for preventing complications of SCD has not been previously
reported. The median charge of approximately $40 000 per year for
patients receiving chelation therapy is within the general range of
data from the NACHRI14 and Washington State2 studies. Our data also correspond with previous estimates of the cost
of chronic transfusion and DFO chelation for patients with homozygous
beta-thalassemia and SCD that were believed to exceed $30 000 per
patient year (1990 U.S. dollars).23,24
The true societal costs of this therapy are difficult to assess. Our
data reflect patient charges rather than actual health care costs. At
our institution, cost-to-charge ratios averaged 66% (range,
20%-184%) for services provided for similar patients (DRG 396) in
fiscal year 1997 (data not shown). However, this study underestimates
total patient charges for several reasons. The calculated charges
include conservative professional fees and Medicaid reimbursement rates
for chelation therapy below those customarily charged to private
insurance carriers. Furthermore, we attempted to exclude health care
services provided for comorbid conditions and restricted our analysis
to those charges associated with the delivery of outpatient chronic
transfusion therapy, treatment of overload, and monitoring for
associated complications (eg, hepatic dysfunction).
Notably, approximately 30% of patient charges in this study were
related to laboratory testing. Efforts to modify the frequency of
laboratory monitoring for patients on chronic transfusion are likely to
offer the greatest opportunity for cost containment in this setting.
DFO accounted for 30% of total patient charges. Although charges were
substantially lower for those who did not require chelation therapy,
all patients who remain on chronic transfusions would be expected to
eventually need DFO. Although oral chelators may someday decrease the
costs associated with combating iron overload, currently DFO is the
only medication proven effective for the prevention and management of
transfusional hemochromatosis. Exchange rather than simple transfusion
can be employed to reduce iron accumulation, but this approach incurs the additional expense of apheresis.25 Ultimately, the
most effective way to reduce costs would be to limit the duration of chronic transfusion therapy, stopping before iron chelation becomes necessary. However, at least for patients who have sustained a previous
stroke, prolonged, possibly lifelong transfusion appears to be
required.21,22 A modest cost reduction could be achieved by decreasing the volume of transfusion and allowing higher
hemoglobin-S levels,26 although the long-term efficacy of
this approach in preventing different complications of SCD is unknown.
Finally, even though the specialized blood products employed for
patients with SCD are more expensive than standard red cell units,
their use decreases the incidence of a number of transfusion-associated complications that might otherwise increase future costs.3
The financial impact of transfusion therapy for SCD is substantial with
charges approaching $400 000 per patient decade. Furthermore, the
benefits of chronic transfusion are not permanent, and toxicity can
limit long-term effectiveness. These factors should be considered in
reference to cost and efficacy analyses of alternative therapies for
SCD, such as hydroxyurea27,28 and allogeneic bone marrow transplantation.29
| |
Acknowledgments |
We gratefully acknowledge the assistance of Janice Rowntree for
providing UB-92 data and David Lee, PhD, for statistical support and
review. We also wish to thank our patients and their families as well
as nurse, blood bank, and physician staff colleagues.
| |
Footnotes |
Submitted April 24, 2000; accepted June 1, 2000.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
Reprints: Alan S. Wayne, Clinical Director, Pediatric
Oncology Branch, National Cancer Institute, National Institutes of
Health, Bldg 10, Rm 13N240, 10 Center Dr, MSC 1928, Bethesda, MD
20892-1928; e-mail: waynea{at}mail.nih.gov.
| |
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Abstract
Introduction