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Cost-effectiveness of a Single Colonoscopy in Screening for Colorectal Cancer
Amnon Sonnenberg, MD, MSc;
Fabiola Delcò, MD, MPH
Arch Intern Med. 2002;162:163-168.
ABSTRACT
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Background A single colonoscopy at the age of 65 years has been recommended as
a potential option to screen for colorectal cancer. This study compares the
cost-effectiveness of 2 screening programs based on a single or repeated colonoscopy.
Methods The cost-effectiveness of screening is analyzed with a computer model
of a Markov process. A hypothetical population of 100 000 subjects aged
50 years undergoes a single colonoscopy at the age of 65 years or repeated
colonoscopy every 10 years starting at the age of 50. Transition rates are
estimated from US vital statistics and cancer statistics and published data
on polyp incidence, patient compliance, and efficacy of colonoscopy plus polypectomy
in cancer prevention. Costs of screening and cancer care are estimated from
the 1998 Medicare reimbursement data using the perspective of a third-party
payer.
Results Compared with no screening, the incremental cost-effectiveness ratio
of a single or repeated colonoscopy amounts to $2981 or to $10 983 per
life year saved, respectively. A single colonoscopy saves most life years
if done at the age of 60, but becomes most cost-effective after the age of
70. Depending on the level of compliance, repeated colonoscopies save 2 to
3 times more lives than a screening program based on a single colonoscopy.
Conclusions A repeated colonoscopy every 10 years offers better prevention against
colorectal cancer and represents a medically more desirable screening option.
If high costs or low patient compliance renders this option not feasible,
a single colonoscopy at the age of 65 would represent a highly cost-effective
alternative.
INTRODUCTION
SEVERAL ECONOMIC analyses1-5
have shown that screening of asymptomatic elderly subjects by colonoscopy
would represent a cost-effective means to reduce mortality from colorectal
cancer (CRC) in the general population. In a head-to-head comparison,5 colonoscopy once per 10 years was found to be more
cost-effective than a screening strategy based on flexible sigmoidoscopy every
5 or 10 years and annual fecal occult blood tests. Although screening with
either flexible sigmoidoscopy or fecal occult blood testing was cheaper than
screening with colonoscopy, in the long run colonoscopy prevented more cancers
and saved more life years. The seeming cost advantage of the 2 cheaper screening
programs became negated by subsequent costs for care of cancers that the initial
screening by fecal occult blood testing or flexible sigmoidoscopy failed to
prevent. The cost advantage of colonoscopy over the other screening options
held up under a wide range of medical and economic conditions. Even if performed
every 10 years, however, screening colonoscopy of the entire adult population
older than 50 years would lead to appreciable health care expenditures.5-6 Because of the high costs, predicted
low patient compliance, and potential for complications associated with repeated
colonoscopies, some researchers2, 7-8
have recommended a 1-time only screening colonoscopy during the entire lifetime.
The highest yield in life years by preventing death from CRC would be achieved
if the only colonoscopy per lifetime were scheduled between the ages of 65
and 70 years.8 To our knowledge, the outcomes
of 2 screening strategies based on a single or repeated colonoscopy have not
been compared in a head-to-head comparison. The present study, therefore,
aims to evaluate the cost-effectiveness of a screening program for CRC based
on a single colonoscopy. The 2 screening methods, single vs repeated colonoscopy,
are compared for the number of prevented CRCs and the costs spent per life
year saved.
MATERIALS AND METHODS
MARKOV MODEL
The cost-effectiveness of cancer screening is analyzed by a Markov process,
using a spreadsheet (Excel; Microsoft, Redmond, Wash).9
Medical events are modeled as transitions of patients among a set of predefined
health states, the occurrence of each transition being governed by a probability
value (Figure 1). The circles in Figure 1 symbolize the various health states,
while the arrows symbolize transition probabilities among them. The time of
the analysis is divided into equal increments of 1 year, during which patients
may cycle from one state to another. The initial population is composed of
100 000 subjects aged 50 years who at the start are offered the screening
colonoscopy. Depending on the initial compliance rate, subjects undergo a
colonoscopy or enter the pool of noncompliant persons. After a normal colonoscopy
result is obtained (there is no adenomatous polyp), subjects enter a new state
labeled "status postcolonoscopy." In subjects compliant with a repeated screening,
a colonoscopy is scheduled every 10 years. In the case of an adenomatous polyp,
surveillance colonoscopy is repeated every 3 years until adenomatous polyps
are no longer found. Subjects in any Markov state can develop CRC, the probability
being given by the age-specific incidence rate. The likelihood of developing
cancer is reduced in subjects after a normal colonoscopy result or after a
polypectomy, depending on the rate of preventive efficacy assigned to the
procedure. The time for which colonoscopy plus polypectomy provide protection
against CRC is equal to the screening interval. The population in each state
is also subjected to the annual age-specific death rate of the US population.10 Screening by a single colonoscopy at the age of 65
years is modeled similarly to screening by multiple colonoscopies (Figure 1). However, no repeated colonoscopy
is scheduled after the initial colonoscopy or after a successful polypectomy.
Between the ages of 50 and 64 years and after the age of 75 years, subjects
are exposed to the age-specific incidence rate of CRC without any potential
protection from colonoscopy and polypectomy.
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Figure 1. Markov state diagram of screening
for colorectal cancer (CRC) by repeated colonoscopy. Circles indicate various
health states; arrows, transitions between the various states; and noncompliant,
subjects noncompliant with initial or repeated colonoscopy.
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TRANSITION PROBABILITIES
The transition probabilities built into the model and their range tested
in the sensitivity analyses are listed in Table 1. Under baseline conditions, subjects are assumed to be compliant
with the screening program. In the sensitivity analyses, the compliance rates
are varied within the ranges shown in Table
1. In a multicenter trial13 of compliance
rates, 45% of a random population accepted the offer of a screening sigmoidoscopy.
Because no reliable data on colonoscopy are available, to our knowledge, compliance
with the initial colonoscopy is estimated to be similar to that reported for
flexible sigmoidoscopy. An 80% compliance rate for repeated colonoscopy is
based on similar rates reported for repeated sigmoidoscopy and surveillance
colonoscopy after polypectomy.11, 14
The prevalence rates of adenoma per 10-year age groups are available through
autopsy studies.12, 21 An annual
1% incidence rate is calculated as the average difference between the prevalence
rates of 2 consecutive age groups. The annual age-specific incidence rate
of CRC is taken from published statistics of the Surveillance, Epidemiology,
and End Results Program.18 The efficacy of
colonoscopy in reducing the incidence of CRC is estimated from data of the
National Polyp Study.14 Of all subjects with
CRC, 40% are assumed to die of their disease.18
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Table 1. Baseline Assumptions and Range Tested in the Sensitivity Analysis*
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EFFECTIVENESS AND COSTS
The effectiveness of screening is measured in life years saved through
prevention of death from CRC. The life years lost by the age-dependent fractions
of patients dying prematurely of CRC are accumulated for each cycle during
the entire expected lifetime. The life years saved through screening correspond
to the difference in life years lost from cancer-related deaths between 2
Markov models with and without screening.
Medical, surgical, and diagnostic services are assigned code numbers
using the physicians' Current Procedural Terminology22 or diagnosis-related group23
to identify the health care resources used for each patient. The code numbers
are converted into costs for each health care resource used (Table 1). The costs represent the average payments allowed for each
coded procedure by the US Health Care Financing Administration during fiscal
year 2000. The cost also includes the possibility of hospitalization for bleeding
or perforation after endoscopy with or without polypectomy.15-17,24
The most recent cost estimates for the medical care of subjects with CRC range
between $40 000 and $45 000.20, 25
All future costs arising from screening or care of CRC and all future life
years saved through screening are discounted by an annual rate of 3%.19
The incremental cost-effectiveness ratio compares each type of intervention
with the previous less effective option, including a strategy of no screening.
The incremental cost-effectiveness ratio is calculated as the difference in
costs divided by the corresponding difference in effectiveness.26-27
In the present analysis, a negative incremental cost-effectiveness ratio indicates
that a strategy would save lives and cost less than the comparative strategy
of no screening.
RESULTS
BASELINE ASSUMPTIONS
Table 2 shows the outcomes
of modeling screening programs to prevent CRC. The total number of CRCs represents
all cancers to be expected during the remaining lifetime of a cohort of 50-year-old
persons without screening. Under baseline conditions, screening by a single
colonoscopy prevents 23% of all CRCs, compared with 75% prevented by screening
with multiple colonoscopies. The higher fraction of cancers prevented through
screening with repeated vs single colonoscopy also results in more life years
saved. The fewer colonoscopies in single vs repeated screening translates
into fewer complications. In the repeated colonoscopy program, 85% of the
total costs arise from the endoscopic procedure itself. By contrast, the endoscopic
procedure contributes only 28% to the total costs of the single colonoscopy
screening program. In the latter program, the largest fraction of costs stems
from care for unprevented cancer. The total costs of managing CRC increase
going from no screening to single and then to repeated colonoscopy. At the
same time, the effectiveness of screening, as evidenced by the number of life
years saved, increases in the same order. Compared with no screening, single
colonoscopy represents a cost-effective screening strategy of less than $3000
per life year saved. Repeated colonoscopy triples the overall amount of life
years saved at the added expense of $14 878 per additional life year
saved compared with a single screening colonoscopy (Table 2). Compared with no screening, repeated colonoscopy is associated
with an incremental cost-effectiveness ratio of $10 983. In subsequent
1-way sensitivity analyses, the outcomes of the 2 screening strategies are
further evaluated by systematically varying all assumptions built into the
models.
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Table 2. Outcome of Screening Programs to Prevent CRC*
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VARIATIONS OF COMPLIANCE RATES
Because the initial compliance determines how many persons enter the
screening program, it influences in a linear fashion the overall number of
cancers prevented and the total costs of the screening program. The incremental
cost-effectiveness remains unaffected. For obvious reasons, any decrease in
the repeated compliance rate affects only the program composed of multiple
endoscopies. It reduces the overall number of cancers prevented and the number
of life years saved through colonoscopy. The loss in compliance for test repetition
makes the program of multiple colonoscopies become more similar to the program
of a single colonoscopy. Because the incidence of CRC is characterized by
an age-dependent increase, the yield of screening colonoscopy increases with
age. The program of multiple colonoscopies initiated at the age of 50 years
is especially hurt if many subjects leave the screening program after the
first or second colonoscopy, before they come to benefit from the higher effectiveness
of the screening program at an older age. Assuming a compliance rate of 80%
with repeated colonoscopy results in an incremental cost-effectiveness ratio
of $20 533 per additional life year saved compared with a single screening
colonoscopy and $13 081 compared with no screening.
VARIATIONS OF COSTS
A lesser efficacy of colonoscopy plus polypectomy in preventing CRC
reduces the overall effectiveness of both programs similarly, ie, fewer life
years are saved. Because the costs of colonoscopy remain unaffected by changes
in effectiveness, the incremental cost-effectiveness ratios of both programs
increase. For instance, a decrease of the efficacy rate from baseline of 75%
to 50% increases the incremental cost-effectiveness ratio of single and repeated
screening to $10 872 and $22 909, respectively, compared with no
screening.
The incremental cost-effectiveness ratio of both screening programs
(compared with no screening) decreases with decreasing cost of colonoscopy.
If the colonoscopy cost decreases below a certain threshold, screening saves
more money from preventing cancer than the money spent on the screening procedure
itself. For instance, varying the cost of colonoscopy between $100 and $1000
changes the incremental cost-effectiveness ratio of a single colonoscopy between -$5664
and $19 309, the threshold for the cost per colonoscopy being $304. Secondary
to the larger number of colonoscopies involved, the program of repeated screening
is more sensitive to changes in the colonoscopy cost. Varying the cost of
colonoscopy to between $100 and $1000 changes the incremental cost-effectiveness
ratio of repeated colonoscopy to between -$2086 and $35 661. The
threshold cost per colonoscopy is $150. Because complications of colonoscopy
make the procedure overall more expensive, changes in the incidence or the
cost of complications affect the outcome as similarly as the colonoscopy cost.
Secondary to their relatively infrequent occurrence, however, the overall
impact of complications on the cost-effectiveness ratio is rather small.
The introduction of new and expensive chemotherapy for advanced CRCs,
such as raltitrexed, irinotecan hydrochloride, and oxaliplatin, may increase
the costs associated with cancer care.28 As
a general rule, more expensive cancer care renders prevention a more cost-effective
medical option. Fewer cancers are prevented and more costs arise from cancer
care in the single vs the repeated screening program. Therefore, screening
with a single colonoscopy is more sensitive to changes in the costs of cancer
care than is screening with repeated colonoscopies. Assuming a higher cost
of cancer care, such as $60 000 per case, decreases the incremental cost-effectiveness
ratio of single colonoscopy to -$1199 and of multiple colonoscopies
to $6779.
VARIATIONS OF SCREENING AGE
The effectiveness of any type of screening is directly correlated with
the incidence of the disease for which it is designed. Because the incidence
rate of CRC shows a marked age-dependent increase, the number of cancers prevented
per single colonoscopy is higher in an older than a younger population of
screenees. If repeated screening is started at ages older than 50, the less
effective initial colonoscopy (at the age of 50) is saved at the expense of
missing some CRCs affecting relatively few subjects between the ages of 50
and 60. The subsequent colonoscopies performed every 10 years will still be
able to prevent most cancers that occur in the older age groups. Screening
by a single colonoscopy is far more likely to lose its preventive power if
scheduled too early or too late. Figure 2 shows the relationship between the age at a single screening and
the effectiveness of the program for the percentage of life years saved. The
analyses are based on the assumption of a 100% compliance rate. It appears
that most life years could be saved by a single colonoscopy done at the age
of 60. As subjects grow older, their risk of developing CRC increases, but
the benefit of cancer prevention decreases because of the concomitant decrease
in life expectancy. Preventing cancer in subjects much younger than 60 may
be associated with an appreciable increase in life expectancy for the individual
patient, but the chance of actually being able to do so is limited by the
overall low incidence rate of CRC.
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Figure 2. Influence of age at the single
colonoscopy on the percentage of life years saved.
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Figure 3 shows the relationship
between the age at screening and the incremental cost-effectiveness ratio
of a single colonoscopy screening program. The curve exhibits a steady decline
that crosses the 0 line at the age of 70. The negative ratios indicate that
beyond the age of 70, screening costs less than no screening. The costs spent
on screening are more than outweighed by the costs saved by less cancer care.
From a strictly money-saving perspective, the best age for a single screening
colonoscopy lies between 75 and 80, because the screening program may actually
save rather that incur costs.
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Figure 3. Influence of age at the single
colonoscopy on the incremental cost-effectiveness ratio of screening compared
with no screening.
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COMMENT
In previous studies,1-5
the use of colonoscopy every 10 years has been demonstrated to be a cost-effective
means to prevent mortality from CRC that compares favorably with flexible
sigmoidoscopy or annual fecal occult blood testing. When applied to the general
population, however, colonoscopic screening every 10 years after the age of
50 becomes a costly health measure.5 The aim
of the present economic analysis was to provide a head-to-head comparison
between 2 screening programs using either a single colonoscopy once per lifetime
or repeated colonoscopies every 10 years. Depending on the level of compliance,
repeated colonoscopies could save 2 to 3 times more lives than a screening
program based on a single colonoscopy. If third-party payers were able to
provide the financial resources and subjects were willing to participate,
a screening program composed of multiple colonoscopies represents the better
yet more expensive alternative. Under tighter economic conditions with only
limited funds available for cancer screening, a single colonoscopy between
the ages of 65 and 70 offers a relatively cheap and highly cost-effective
means of screening for CRC.
The same type of Markov process was used to model the impact of single
and repeated colonoscopies. In the past, this model was also used to study
fecal occult blood testing and flexible sigmoidoscopy.5
The comparisons among the different screening strategies are based on the
same set of transition probabilities and cost estimates built into the model.
This facilitates the direct comparisons between the various screening alternatives,
because it eliminates the need to adjust for differences in the assumptions
built into various economic models. To be able to compare a screening with
a no screening strategy, the cost estimates of cancer care also need to be
considered by the economic model. This increases the total costs associated
with each program, because each program is penalized for the cancers it fails
to prevent.
A previous analysis8 suggested that the
best age for a single colonoscopy to save most life years from death due to
CRC would be between 65 and 70 years. This previous analysis looked at the
gains of colonoscopy screening from a strictly medical perspective, with the
primary focus on the interests of the individual subject undergoing a single
screening procedure. Each remaining year lived at a different age was weighted
by an age-weight function that took into account the age-dependent decline
in life's social value.29-30 In
contradistinction, the present analysis looks at the gains of a single screening
colonoscopy from a societal perspective, with the primary focus on the amount
of life years saved in the total population. This variable is influenced not
only by the life expectancy of the individual screenee but also by the total
number of subjects within the population who at each age will benefit from
cancer prevention. Future gains in life years are discounted by a constant
annual rate of 3%, but not by an age-dependent weight function. Despite these
differences, both studies reach a similar conclusion. The greatest economic
advantage results from screening after the age of 70, while the greatest medical
advantage is achieved by screening at the age of 60. Screening at the age
of 65 seems to provide a good compromise between the 2 different perspectives.
At this age, the number of life years saved is still close to the maximum
value, yet the incremental cost-effectiveness ratio is markedly less than
at the age of 60. In any case, the incremental cost-effectiveness ratio of
a single colonoscopy is far less than that of any other competing screening
strategy.
The decision models of the present article are built on the assumption
that endoscopic prevention could negate cancer-related loss in life years
and that patients would fully benefit from the restored life expectancy of
an average population without CRC. The models do not consider the presence
of other competing medical risks in some of the subjects undergoing screening
at the age of 65 to 70 years. Such subjects may already have serious heart
disease, hypertension, or diabetes, which could shorten their life expectancy
irrespective of CRC. If relationships existed between CRC and other causes
of death and patients with CRC were more likely to die of other diseases as
well, they would gain less life years from endoscopic screening for CRC. Screening
in general tends to identify slow-growing cancers, which pose less of a lethal
threat to older subjects.31 Other factors,
such as sex-specific compliance or a decrease in the incidence of CRC in the
general population, may militate against the effectiveness of screening. Therefore,
models only serve as a guide for assessing the potential outcome of a medical
strategy. Decision models do not obviate the primacy of clinical data gathered
through controlled clinical trials, because they cannot account for all factors
that may eventually determine the cost-effectiveness of screening.
In conclusion, the present economic analysis suggests that a single
colonoscopy at the age of 65 years represents a cost-effective means to screen
for CRC. It is more cost-effective than fecal occult blood testing or flexible
sigmoidoscopy every 5 or 10 years. Such screening is, however, less effective
in saving life years than a repeated colonoscopy every 10 years. At an incremental
increase in cost-effectiveness that would seem still economically feasible,
repeated screening offers a much greater potential for prevention and represents
a medically more desirable option. For political and economic reasons, however,
repeated screening by colonoscopy every 10 years may remain an elusive goal.
It also may not be accepted by the general consumer as a worthwhile means
to prolong life expectancy. Under such circumstances, a single colonoscopy
at the age of 65 would represent the next best alternative.
AUTHOR INFORMATION
Accepted for publication May 8, 2001.
Corresponding author and reprints: Amnon Sonnenberg, MD, MSc, Gastroenterology
Section (111F), Department of Veterans Affairs Medical Center, 1501 San Pedro
Dr SE, Albuquerque, NM 87108 (e-mail: sonnbrg{at}unm.edu).
From the Gastroenterology Section, Department of Veterans Affairs Medical
Center, and the Division of Gastroenterology, University of New Mexico, Albuquerque.
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