From the Departments of Community and Preventive Medicine (A.I.M., J.Z.,
E.G., M.A., R.M., A.J.M.), Medicine (A.I.M., A.J.M.), and Biostatistics
(W.J.H., K.H.Z.), University of Rochester School of Medicine and Dentistry,
Rochester, New York.
Correspondence to Alvin I. Mushlin, MD, ScM, University of Rochester Medical Center, Department of Community and Preventive Medicine, Box 644, 601 Elmwood Ave, Rochester, NY 14642. E-mail mushlin{at}prevmed.rochester.edu
Methods and ResultsPatients were followed up to quantify their
use of healthcare services, including hospitalizations, physician
visits, medications, laboratory tests, and procedures, during the
trial. The costs of these services, including the costs of the
defibrillator, were determined in patients randomized to defibrillator
and nondefibrillator therapy. Incremental cost-effectiveness ratios
were calculated by relating these costs to the increased survival
associated with the use of the defibrillator. The average survival for
the defibrillator group over a 4-year period was 3.66 years compared
with 2.80 years for conventionally treated patients. Accumulated net
costs were $97 560 for the defibrillator group compared with $75 980
for individuals treated with medications alone. The resulting
incremental cost-effectiveness ratio of $27 000 per life-year saved
compares favorably with other cardiac interventions. Sensitivity
analyses showed that the incremental cost-effectiveness ratio
would be reduced to
ConclusionsAn implanted cardiac defibrillator is cost-effective
in selected individuals at high risk for ventricular
arrhythmias.
The recently reported Multicenter Automatic Defibrillator Implantation
Trial (MADIT) has shown for the first time that an ICD reduces
all-cause mortality in patients at high risk for
ventricular arrhythmias.5
Because the economic consequences of defibrillator management are an
important issue, an evaluation of costs was performed as an integral
part of the trial itself. We report the results of this
cost-effectiveness analysis.
Patients eligible for MADIT were those with asymptomatic
nonsustained ventricular tachycardia, a prior
myocardial infarction, an ejection fraction
When the trial started in December 1990, only transthoracic
implants were approved for use. Nonthoracotomy transvenous leads were
incorporated into the trial in August 1993. The trial used a sequential
stopping rule, with weekly data analyses until a stopping
boundary was reached. The trial ended in March 1996, with an estimated
reduction of 54% in the mortality rate (a hazard ratio of 0.46), at a
P value of .009.5
The first enrolled patient was followed up for 61 months and the last
for <1 month. The average duration of follow-up for the 181 patients
in the cost-effectiveness substudy was 27 months, with an average of 37
months for patients recruited when the earlier
transthoracic device was being used (n=98) and 14 months
for the later transvenous period (n=83).
Methods for Economic Evaluation
The nurse coordinator obtained an itemized bill or a copy of the
Uniform Billing Form (UB 82/92) from the hospital for all
hospitalizations and emergency room visits.
Physician visits were coded as brief, intermediate, or extended.
Outpatient diagnostic tests and procedures included all
reported radiographs, diagnostic procedures, blood tests,
and therapeutic procedures. Community services were all supplies,
ambulance services, home and nursing home care, and physical or
occupational therapy.
Data Completion
Sources for Costs and Charges
For inpatient hospital stays, we converted charges from patient bills
or UB82 forms into costs using hospital-specific cost-to-charge ratios.
The costs of the corresponding physician services were based on a
national study of Medicare claims that calculated the ratio of
physician to hospital costs for each Diagnosis Related Group
(DRG).8 Emergency department costs were
calculated similarly, with the facility component derived from a
cost-to-charge ratio and total billed charges. Emergency physician
costs were imputed on the basis of payment rates in the Medicare
Resource Based Relative Value Scale (RBRVS) together with its
geographic adjusters. Office visits were valued on the basis of the
RBRVS with its geographic adjusters. We calculated the costs of
outpatient tests using the Medicare payment scale for each Current
Procedural Terminology code. The costs of community, medical, and
social services and supply costs were based on the 1995 Health Care
Financing Administration Common Procedure Coding System Medicare codes
in each Medicare area or Medicaid payment rates for those services or
supplies not reimbursed by Medicare.9 Finally,
pharmaceutical costs were derived by use of the average wholesale
prices for each medication as indicated in the 1995 Drug Topics
Red Book.10
Statistical Methods
To summarize cost comparisons between the two arms without regard to
survival effects, we determined costs in each time period (periods 1 to
17, averaging over surviving patients in the respective arms), and then
averaged over the 17 periods (weighting proportionally to period
lengths). To assess statistical significance, we used bootstrap
resampling, as described below.
The cost-effectiveness analyses used methods that allowed for
varying levels of censorship.11 A discounted
years-of-life-saved measure was computed, representing the
difference in life expectancy (within 4 years) between patients in the
defibrillator and conventional therapy arms. This measure can be
visualized as the area between the two Kaplan-Meier survival curves
(similar to those in the primary paper5 ) over the
period 0 to 4 years, except that a 3% per annum discount factor was
applied.7
Discounted differential costs (within 4 years) were computed as
follows. For each period (0 to 17), the average costs in the period
were determined, multiplied by the Kaplan-Meier estimate of survival
through that period, multiplied by a discount factor (3% per annum),
and then accumulated over periods. The result is the "net present
value" of accumulated costs. The difference between these two
quantities, one for each arm of the trial, represents the
expected difference in costs (within 4 years) incurred by a patient in
the defibrillator arm compared with a patient in the conventional
therapy arm.
The ratio of differential costs to survival is the incremental
cost-effectiveness ratio (iCER): iCER=y/x, with
y the differential discounted accumulated cost and
x the discounted years of life saved (both x and
y limited to a 4-year span). The incremental
cost-effectiveness ratio represents the extra cost incurred to
save 1 year of life within 4 years for patients randomized to
defibrillator rather than conventional therapy.
Published methods for quantifying variability11
are not appropriate here because they treat only the case of nonrandom
cost data. We instead used a bootstrap analysis with 1000
bootstrap resamplings.12 13 This produces 1000
(x,y) pairs: an estimated years of life saved
(x) and an estimated differential 4-year cost
(y). This mimics results that would be obtained if 1000
studies identical to MADIT were performed and provides a basis for
construction of confidence intervals.
Because costs subsequent to the initial hospitalization were relatively
flat over time, we also determined average monthly costs (by type) for
each patient in the study, whether observed for 1 month or 61 months.
These numbers were analyzed by rank sum tests to compare the
two treatment arms and by regression methods (after logarithmic
transformations) to explore possible explanatory variable
dependencies.
Five patients randomized to receive the ICD did not in fact have a
device implanted. Eleven patients crossed over from conventional
therapy and received an ICD at varying times during the trial.
Cost-effectiveness analyses used the intention-to-treat
principle.
Medical Care Use and Costs
Figure 2
The categories of medical care used and their costs were highly
variable from patient to patient. Additionally, there were no clear
patterns or differences between the two treatment arms other than our
observation that the conventional therapy patients had somewhat higher
expenditures for antiarrhythmic medications and the ICD patients had
somewhat higher expenditures for other types of cardiac medications. We
found no other explainable (or significant) differences in the
categories of subsequent use or expenses between the groups.
Because ICD patients lived longer, they accumulated costs over longer
periods. The net present value in 1995 dollars for treating
patients with an ICD during the 4 years of the trial is estimated to be
$97 560 compared with $75 980 for the conventional therapy group
(line 1 of Table 4
Survival
Cost-effectiveness Ratios
The variability surrounding this estimate is illustrated in Figure 3
Sensitivity Analyses
During the study, defibrillator costs ranged from $18 500 to $27 400.
The average cost for a transvenous device was $2200 higher than for a
transthoracic system. The initial costs for patients
receiving a transvenous device were lower, however, by $8800 on
average. If one eliminates this difference of $6600, the incremental
cost-effectiveness ratio drops from $27 000 per life year to $22 800
per life year ($18 000/0.80=$22 800). Eighteen patients required a
replacement generator during the trial, primarily in year 4. An
assumption that modern devices with more generator capacity should not
require replacement within 4 years would drop the incremental
cost-effectiveness ratio to $12 500 per life year. To evaluate the
effect of the cost of the devices themselves, we reduced these by 25%
and by 50%, lowering the incremental cost-effectiveness ratio to
$13 100 or $3300 per life-year saved, respectively.
Four patients received either a heart transplantation or renal dialysis
during the study. All four were in the conventional therapy group.
Before identifying that all were in the conventional therapy group, we
reviewed the study records on each of these patients to establish
whether it was likely that the transplantation or dialysis was related
to the experimental intervention (either ICD or conventional treatment)
or could have been prevented by it. Because in each case this seemed
unlikely, we reduced these hospital costs to a maximum of $40 000, a
cost that would be expected with a complex hospitalization but not a
transplant or dialysis. Next, we eliminated these four patients
completely and repeated the analysis without them. The first
adjustment had only a modest effect on the incremental
cost-effectiveness ratio, moving it from $27 000 to $32 900 per
life-year. The second adjustment increased the incremental
cost-effectiveness ratio to $39 600 per life-year.
Some individuals crossed over from ICD to conventional therapy and vice
versa. We dropped the 11 conventional therapy patients who received an
ICD subsequently and reassigned to the conventional therapy group the 4
patients who were assigned to an ICD but refused one. This resulted in
an estimated incremental cost-effectiveness ratio of $32 900 per
life-year saved.
The statistical effect of the sequential stopping rule used in
MADIT6 could lead to biases in secondary survival
analyses, in particular to possible overestimation of years of
life saved, and in contrast to the primary survival-benefit
analysis,5 no formal adjustment methods
are available. However, on the basis of an analysis not
detailed here, we estimated that the years of life saved may need to be
reduced by 21% and the differential costs (which are also
affected by survival) by 14%. The resulting cost-effectiveness ratio
is not markedly different, namely, $29 300 instead of $27 000 per
life-year, an increase of 8.5%. This also serves as a basis for a
sensitivity analysis of the ICD effectiveness. Another
reduction of 21% in effectiveness would yield another 8.5% increase
in the incremental cost-effectiveness ratio to $32 000 per
life-year.
Our study lasted 5 years, and reliable information on which to
base cost-effectiveness calculations was limited to 48 months. To
evaluate the economic consequences more closely resembling a lifetime
strategy, we fit Weibull survival curves14 to the
survival data and extrapolated beyond the 4-year Kaplan-Meier curves.
Assuming that costs would remain on average $1915 per month for
conventional therapy and $1394 per month for ICD in surviving patients
(extrapolating from Figure 1
The adequacy and completeness of the information collected in this
study also limit our conclusions. We relied principally on patient
self-reports of health care use prompted by regular and systematic
follow-up by nurse clinical coordinators. Although we were successful
in achieving almost complete data collection for the economic
parameters of interest, it is impossible to be fully
confident that there were no reporting errors, which could have either
overstated or understated the costs. We used the best presently
available methods to convert charges to costs, but these approaches are
imperfect and rely on accounting procedures such as cost-to-charge
ratios and Medicare cost-reimbursement schedules. We also used an
indirect method for including the professional (physician and surgeon)
costs by relying on a national study of DRGs based on Medicare
databases. Still, hospital costs dominated, self-reporting of
hospitalizations should be reliable, and our billing information was
98% complete.
The trial itself was designed and powered to detect a difference in
mortality, not to obtain statistically stable estimates of a
cost-effectiveness ratio. The size of the population available to us
for analysis and the variability in the costs of care results
in fairly wide confidence limits around these estimations. Larger
studies that include data collection for effectiveness evaluation will
advance such assessments.
This study took place during the technical evolution of the ICD. In
fact, our results represent a mixture of an old
(transthoracic placement and single-purpose defibrillators)
and a relatively new (transvenous multipurpose devices) technology. We
explored what the effect of these changes might be on the resulting
cost-effectiveness ratios by simulating the changes that would occur if
all defibrillators had been placed transvenously, the costs of placing
the devices had been lower, and generators had lasted longer before
replacement. We therefore can estimate only indirectly the
cost-effectiveness of treatment with present-day technology.
Information about the cost-effectiveness of the ICD has been limited by
the scarcity of studies that have addressed this issue and by the
methods previously used for economic
assessment.16 17 18 19 20 21 22 23 This study, an integral part of
the randomized trial to test the effectiveness of ICD management,
provides the most direct evidence available concerning the
cost-effectiveness of this technology. Despite its high initial costs,
ICD therapy in selected individuals appears to be cost-effective.
Although there is not yet widespread agreement about the value (ie,
cost per life-year saved) that a new technology must achieve, our
estimate is clearly within the range considered acceptable and routine
within our healthcare system.24
The overall cost implications of adding this technology to
present-day spending are important to consider as well.
Extrapolating our results to 8 years, together with use of transvenous
devices with a modest reduction in cost (<25%), the estimated
incremental cost-effectiveness ratio would be
The most important challenge for both clinical practice and healthcare
policy, however, remains the more definitive definition of the clinical
characteristics used to select patients for this new technology versus
current alternatives so as to prevent both its overuse and its
underuse. In the future, such decisions will increasingly depend on the
economic as well as the survival implications for these
individuals.
The following investigators participated in the Multicenter
Automatic Defibrillator Implantation Trial: D. Cannom, Good Samaritan
Hospital, Los Angeles, Calif; J. Daubert, University of Rochester,
Rochester, NY; S. Higgins, Scripps Memorial Hospital, La Jolla, Calif;
H. Klein, University Hospital, Magdeburg, Germany; J. Levine, Saint
Francis HospitalHeart Center, Roslyn, NY; S. Saksena,
Eastern Heart Institute, Passaic, NJ; A. Waldo, Case Western Reserve
University and University Hospitals of Cleveland, Cleveland, Ohio; D.
Wilber, University of Chicago, Chicago, Ill; S. Sridhar, Affiliated
Cardiologist, Phoenix, Ariz; T. Mattioni, Arizona Heart Institute and
Foundation, Phoenix; J. Maloney and B. Wilkoff, Cleveland Clinic
Hospital, Cleveland, Ohio; R. Krol, Eastern Heart Institute, Passaic,
NJ; A. Leon, Emory Clinic, Atlanta, Ga; R. Cierpka and H.-J. Trappe,
Hanover Medical School, Hanover, Germany; S. Kutalek, Hahnemann
University Hospital, Philadelphia, Pa; J. Rottman, Jewish Hospital of
St. Louis, St. Louis, Mo; T. Guanieri and G. Tomaselli, Johns Hopkins
University Hospital, Baltimore, Md; B. Olshansky, Loyola University
Medical Center, Maywood, Ill; J. Salerno, Matteo Hospital, Pavia,
Italy; B. Crevey, Methodist Hospital, Indianapolis, Ind; C. Pratt and
D. Zhu, Methodist Hospital, Houston, Tex; M. Pritzker, Minneapolis
Heart Institute, Minneapolis, Minn; S. Winters, Morristown Memorial
Hospital, Chicago, Ill; F. Abi-Samra, Ochsner Clinic, New Orleans, La;
B. Hallperin, J. Kron, and J. McAnulty, Oregon Health Sciences
University, Portland; J. Steinberg, RooseveltSt. Luke's Medical
Center, New York, NY; S. Greenberg and D. Hoch, Saint Francis
HospitalHeart Center, Roslyn, NY; J. Gallagher, Sanger
ClinicCarolina Heart Institute, Charlotte, NC; J. Ilvento, Santa
Barbara Cottage Hospital, Santa Barbara, Calif; R. Winkle, Sequoia
Hospital, Palo Alto, Calif; M. Lechmann, Sinai Hospital, Detroit, Mich;
M. Scheinman, University of California Medical Center, San Francisco;
R. Myerburg, University of Miami Medical Center, Miami, Fla; T. Akiyama
and W. Zareba, University of Rochester Medical Center, Rochester, NY;
R. Ruffy, University of Utah School of Medicine, Salt Lake City; and E.
Platia, Washington Hospital Center, Washington, DC.
Data and Safety Monitoring Committee: D. Goldblatt, W. Hood, Jr
(chair), D. Oakes, and M. Tanner.
End-Point Review Committee: L. Cobb and R. Goldstein (chair).
Rochester Coordination and Data Center: E. Garcia, N. Kellogg, B.
MacKecknie, D. Ramsell, P. Severski, and M. Brown.
Statistical support: M. Heo and Ban Chuan Cheah.
2.
Ruskin JN, McGovern B, Garan H, Dimarco JP, Kelly E.
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Echt DS, Liebson PR, Mitchell LB, Peters RW,
Objas-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL,
Huther ML, Richardson DW, the CAST Investigators. Mortality
and morbidity in patients receiving encainide, flecainide, or placebo:
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4.
Mason JW. A comparison of seven antiarrhythmic drugs
in patients with ventricular
tachyarrhythmias. N Engl J Med. 1993;329:452458.
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Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL,
Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved
survival with an implanted defibrillator in patients with
coronary disease at high risk for ventricular
arrhythmia. N Engl J Med. 1996;335:19331940.
6.
MADIT Executive Committee. Multicenter Automatic
Defibrillator Implantation Trial (MADIT): design and clinical protocol.
Pacing Clin Electrophysiol. 1991;14:920927.[Medline]
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7.
Mushlin AI, Zwanziger J, Gajary E, Andrews M, Marron
R. Approach to cost-effectiveness assessment in the MADIT trial.
Am J Cardiol. 1997;80:33F41F.[Medline]
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8.
Mitchell JB, Surge RT, Lee AJ, McCall NT, Katz LW,
Dittus R, Heck D, Kinney EA, Parchman M, Iezzoni L. Per Case
Prospective Payment for Episodes of Hospital Care. Waltham, Mass:
Health Economics Research, Inc; 1995. Final report prepared for the
Health Care Financing Administration under contract No. 50092-0020.
9.
Health Care Financing Administration Common
Procedure Coding System, National Level II Medicare Codes. Los
Angeles, Calif: Practice Management Information Corp; 1995.
10.
Drug Topics Red Book. Montvale, NJ: Medical
Economics Company, Inc; 1995.
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Gardiner J, Hogan A, Holmes-Rovner M, Rovner D,
Griffith L, Kuppersmith J. Confidence intervals for cost-effectiveness
ratios. Med Decis Making. 1995;15:254263.
12.
Efron E, Tibshirani RJ. An Introduction to the
Bootstrap. New York, NY: Chapman & Hall; 1993;170171.
13.
Hlatky MA, Rogers WJ, Johnstone I, Boothroyd D, Brooks
MM, Pitt B, Reeder G, Ryan T, Smith H, Whitlow P, Wiens R, Mark DB.
Medical care costs and quality of life after randomization to
coronary angioplasty or coronary bypass surgery.
N Engl J Med. 1997;336:9299.
14.
Cox DR, Oakes DO. Analysis of Survival
Data. London, UK: Chapman & Hall; 1984:4143.
15.
Owens DK, Sanders GD, Harris RA, McDonald KM.
Cost-effectiveness of implantable cardioverter defibrillators relative
to amiodarone for prevention of sudden cardiac death. Ann
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Jr, Ruskin TN. An analysis of the cost-effectiveness of the
implantable defibrillator. Circulation. 1990;81:91100.
18.
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Estes NAM, Pauker SG. Cost-effectiveness of the implantable
cardioverter-defibrillator: effect of improved battery life and
comparison with amiodarone therapy. J Am Coll
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Kuppersmith J, Hogan A, Guerrero P, Gardiner J,
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A, Levine J, Saksena S, Griffith L. Evaluating and improving the
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© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
The Cost-effectiveness of Automatic Implantable Cardiac Defibrillators:
Results From MADIT
![]()
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
BackgroundThe recently reported
Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed
improved survival in selected asymptomatic patients with
coronary disease and nonsustained ventricular
tachycardia. The economic consequences of defibrillator
management in this patient population are unknown.
$23 000 per life-year saved if transvenous
defibrillators were used instead of the older devices, which required
thoracic surgery for implantation.
Key Words: cost-effectiveness cardioversion defibrillation
![]()
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
Sudden cardiac death
claims almost a half million lives in the United States per year and
occurs mostly in patients with underlying coronary artery
disease.1 Ventricular
arrhythmias are believed to be the major cause of such deaths.
Prevention of sudden death in high-risk patients has been the focus of
much attention and has resulted in the development of medications and
technologies for this purpose. These include new antiarrhythmic agents,
electrophysiological testing, and
implantable cardiac defibrillators (ICDs). To date, the usefulness of
antiarrhythmic medications has been
disappointing.2 3 4 During this same time, ICDs
have evolved to the point that they are smaller and easier to implant
than the older devices, which required a thoracotomy.
![]()
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
Overview of MADIT
In MADIT, 196 patients were enrolled from 38 centers (36 in the
United States and 2 in Europe). The cost-effectiveness analysis
was based on the 181 patients from the United States.
35%, and an inducible
ventricular tachyarrhythmia at
electrophysiological testing that was not
suppressed by procainamide.6 Patients
were randomly assigned to receive either an ICD or conventional medical
therapy. The enrollment procedures, clinical follow-up, and results
have been described in the primary
publication.5
Utilization Information
The methods and procedures used for the collection of
utilization data and economic information have been described
previously.7 Each month, nurse coordinators
queried patients regarding their healthcare use, including
hospitalizations, emergency room visits, office visits to physicians
and specialists, outpatient diagnostic tests and
procedures, community services, medical supplies, and prescription
medications. At the first clinic visit, patients provided their
healthcare use for the year before randomization.
Patients reported 697 hospitalizations; billing information was
obtained for all but 14 (2%) (Table 1
).
There were 82 reported emergency room visits, with billing information
for all but 6 (7%). Patients reported 5203 visits (including protocol
study visits) to primary care physicians, cardiologists, and other
specialists and 6324 outpatient diagnostic tests or
procedures (9 [0.1%] missing). This patient population reported
taking 471 distinct medications; for 20 cases (4%), we had
insufficient detail to code the entry. There were 214 separate services
or supplies used.
View this table:
[in a new window]
Table 1. MADIT Cost-effectiveness Study: Data
Completion
The methods used to translate utilization data into costs are
summarized in Table 2
. All costs were
adjusted to 1995 dollars on the basis of the medical consumer price
index.
View this table:
[in a new window]
Table 2. MADIT Cost-effectiveness Study: Cost
Data
Analyses were restricted to a 4-year period because cost
data beyond 4 years were sparse, with only 8 patients completing a
fifth year in the study. Cost and utilization data were assembled and
summarized in the following time periods: prior year (-1), initial
(0), 1 month (1), 3 months (2), 6 months (3), 9 months (4) ... 48
months (17), with each period accumulating costs reported since the
previous period. Costs in a period were averaged over patients observed
during the period.
![]()
Results
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
Study Population
The patients randomized to the ICD group were comparable to those
who were assigned to receive conventional medical
therapy.5 6 The use of medical services and
hospital expenditures over the year before entry into the trial were
also similar in the two treatment groups (Figure 1
).

View larger version (16K):
[in a new window]
Figure 1. Total medical costs per patient per month,
according to assigned treatment. For each month indicated (1 through
48), total medical costs during the preceding period were averaged over
the available surviving patients in the study, in the indicated
treatment group, and converted to a per month basis. Costs at month 0
represent costs for the initial hospitalization, averaged over
patients. Before month 0, the diamond represents hospital costs
during the prior year averaged over the defibrillator group and the
triangle represents hospital costs during the prior year
averaged over the conventional therapy group. Total costs include all
hospital, emergency room, physician, and specialist visits;
prescription medications; outpatient diagnostic tests and
procedures; community services; and medical supplies.
Total costs per patient month are plotted in Figure 1
and
enumerated in Table 3
. The average
initial costs of $44 600 experienced by the ICD group were
considerably higher than those for the conventionally treated patients
($18 900). This difference of $25 700 is attributable to the cost of
the device and the implantation procedure. Over the subsequent months
of the trial, there was a tendency for conventionally treated
individuals to have higher costs. This resulted in average monthly
costs, after the initial hospitalization, for surviving patients of
$1915 for conventionally treated patients compared with $1384 for those
assigned to the device (difference not statistically significant).
View this table:
[in a new window]
Table 3. MADIT Cost-effectiveness Study: Average Costs and
Utilization for Conventional Therapy and ICD
Patients
shows that medication costs
after the initial 30-day period were higher for conventionally treated
patients than for defibrillator patients throughout the 48-month
follow-up (P=0.03). The average medication costs were
$266/mo in the conventional therapy group versus $182/mo in the ICD
group (Table 3
). No additional explanatory variables, either
demographic or clinical, were associated with total subsequent
costs.

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Figure 2. Costs of medications per patient per month,
according to assigned treatment. For each month indicated, costs of all
prescription medication during the preceding period were averaged over
the available surviving patients in the study, in the indicated
treatment group, and converted to a per month basis.
). These higher costs
are almost entirely due to longer survival because the lower monthly
cost in the ICD group overcomes the higher initial cost in
4
years.
View this table:
[in a new window]
Table 4. MADIT Cost-effectiveness Study: Incremental
Cost-effectiveness Ratio of ICD Compared With Conventional
Therapy
The survival experienced by the ICD group was significantly better
than that in the conventionally treated
patients.5 On average, a person treated with an
ICD could expect to survive 3.66 out of 4 years and those treated
conventionally 2.80 out of 4 years. The survival discounted to
present value was 3.46 years for the ICD and 2.66 years for the
conventional therapy group. The benefit attributable to the ICD is the
difference between these, or 0.80 years out of 4 (line 2 of Table 4
).
The increased survival of 0.80 years for the ICD group was
associated with an incremental cost of $21 580. The resulting
incremental cost-effectiveness ratio (Table 4
) is $27 000 per
life-year saved.
, derived from bootstrap replications.
The solid line goes from the origin to the point
representing the differences in costs and survival that we
actually found; its slope (27.0) represents the incremental
cost-effectiveness ratio. This line thereby depicts a set of points
associated with an incremental cost-effectiveness ratio of $27 000 per
life-year. The points below this line would have a lower (ie, more
favorable) incremental cost-effectiveness ratio, while those above the
line represent less-favorable estimations of
cost-effectiveness. Although the majority (89%) of the points are
<$50 000 per life year (represented by the dashed line, a
value frequently used to judge cost-effectiveness), some are above this
line. The 95% confidence limits based on this analysis range
from a low of $200 to a high of $68 200 per life-year saved (Table 4
).

View larger version (30K):
[in a new window]
Figure 3. Bootstrap resampling of the difference in total
costs per patient between defibrillator and conventional therapy groups
and the corresponding years of life saved, along with the resulting
incremental cost-effectiveness ratio (iCER). Each point
represents a reestimation of the difference in total costs (net
present value of accumulated costs) and the corresponding years of
life saved, all within 4 years. The ratio is the corresponding iCER.
The study data yielded an actual iCER of $27 000 per life-year. A
bootstrap-based 95% CI for the iCER is $200 to $68 200 per life-year,
indicated by the dashed lines.
We explored ways to represent present-day technologies
and to assess variability in the incremental cost-effectiveness ratio
according to methodological issues and limitations of our study. (See
Table 5
.)
View this table:
[in a new window]
Table 5. MADIT Cost-effectiveness Study: Sensitivity of iCERs
to Technologies and
Methods
and Table 3
), the cost-effectiveness ratio
would fall to $16 900 per life-year in 8 years
($34 200/2.02=$16 900).
![]()
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
Our analyses indicate that when an ICD is used for the
prevention of sudden death in selected high-risk patients, this
therapeutic strategy is cost-effective. These conclusions are, of
course, limited to the clinical circumstances and the patient
characteristics actually included in the trial from which these data
are derived. Whether this technology would be as cost-effective when
used otherwise is an important question and one for which we can
provide only limited insights. In individuals with a lower probability
of fatal arrhythmias, in whom there is less potential for
benefit, the cost-effectiveness would be expected to be less
favorable.15
$10 000 per life-year
(combining effects shown in Table 5
). With estimated average savings of
2 years of life (the 8-year span projection), the lifetime cost
increase would be roughly $20 000 per patient. If one uses a current
estimate of 16 000 individuals in the United States annually meeting
the MADIT entry criteria25 and assumes each is
offered an ICD, the steady-state annual extra cost would be roughly
$320 million for 32 000 years of life saved annually. Both effects,
the additional years of life and the costs, must be kept in mind and
compared with other options for healthcare spending to inform health
policy.24 The device would be even more
attractive economically if its cost were lower and the generator
replacement time longer.
![]()
Acknowledgments
The study was supported by an independent research grant
to the University of Rochester from CPI/Guidant Corporation, St. Paul,
Minn. We are indebted to the patients who participated in this trial;
to the attending physicians who referred their patients to this study;
and to CPI/Guidant Corporation for its support and sustained
commitment, for supplying the defibrillators, and for the independence
it provided to the investigators to conduct the study. The data
collection for this study was greatly facilitated by the cooperation of
the MADIT Coordination and Data Center under the direction of Mary W.
Brown, MS.
![]()
Footnotes
1 The other investigators who participated in the Multicenter Automatic Defibrillator Implantation Trial are listed in the Appendix
.
![]()
Appendix 1
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
Received October 16, 1997;
revision received January 28, 1998;
accepted February 10, 1998.
![]()
References
Top
Abstract
Introduction
Methods
Results
Discussion
Appendix 1
References
1.
Gillum RF. Sudden coronary death in the
United States: 19801985. Circulation. 1989;79:756765.
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