Acute Appendicitis in Young Children: Cost-effectiveness of US versus CT in Diagnosis-A Markov Decision Analytic Model

Abstract

To compare the cost-effectiveness of different imaging strategies in the diagnosis of pediatric appendicitis by using a decision analytic model.
Approval for this retrospective study based on literature review was not required by the institutional Research Ethics Board. A Markov decision model was constructed by using costs, utilities, and probabilities from the literature. The risk of radiation-induced cancer was modeled by using the Biological Effects of Ionizing Radiation VII report, which is based primarily on data from atomic bomb survivors. The three imaging strategies were ultrasonography (US), computed tomography (CT), and US followed by CT if the initial US study was negative. The model simulated the short-term and long-term outcomes of the patients, calculating the average quality-adjusted life span and health care costs.
For a single abdominal CT study in a 5-year-old child, the lifetime risk of radiation-induced cancer would be 26.1 per 100,000 in female and 20.4 per 100,000 in male patients. In the base-case analysis, US followed by CT was the most costly and most effective strategy, CT was the second-most costly and second-most effective strategy, and US was the least costly and least effective strategy. The incremental cost-effectiveness ratios (ICERs) of CT to US and of US followed by CT to US were both well below the societal willingness-to-pay threshold of $50,000 (in U.S. dollars). The ICER of US followed by CT to CT was less than $10,000 in both male and female patients.
In a Markov-based decision model of pediatric appendicitis, the most cost-effective method of imaging pediatric appendicitis was to start with a US study and follow each negative US study with a CT examination.

Full text

Acute Appendicitis in Young
Children: Cost-effectiveness of US
versus CT in Diagnosis—A Markov
Decision Analytic Model1
Michael J. Wan, BSc
Murray Krahn, BA, MSc, MD
Wendy J. Ungar, MSc, PhD
Edona C¸ aku, BSc
Lillian Sung, MD, PhD
L. Santiago Medina, MD, MPH
Andrea S. Doria, MD, PhD, MSc
Purpose: To compare the cost-effectiveness of different imaging
strategies in the diagnosis of pediatric appendicitis by us-
ing a decision analytic model.
Materials and
Methods:
Approval for this retrospective study based on literature
review was not required by the institutional Research Eth-
ics Board. A Markov decision model was constructed by
using costs, utilities, and probabilities from the literature.
The risk of radiation-induced cancer was modeled by using
the Biological Effects of Ionizing Radiation VII report,
which is based primarily on data from atomic bomb survi-
vors. The three imaging strategies were ultrasonography
(US), computed tomography (CT), and US followed by CT
if the initial US study was negative. The model simulated
the short-term and long-term outcomes of the patients,
calculating the average quality-adjusted life span and
health care costs.
Results: For a single abdominal CT study in a 5-year-old child, the
lifetime risk of radiation-induced cancer would be 26.1 per
100 000 in female and 20.4 per 100 000 in male patients.
In the base-case analysis, US followed by CT was the most
costly and most effective strategy, CT was the second-most
costly and second-most effective strategy, and US was the
least costly and least effective strategy. The incremental
cost-effectiveness ratios (ICERs) of CT to US and of US
followed by CT to US were both well below the societal
willingness-to-pay threshold of $50 000 (in U.S. dollars).
The ICER of US followed by CT to CT was less than
$10 000 in both male and female patients.
Conclusion: In a Markov-based decision model of pediatric appendici-
tis, the most cost-effective method of imaging pediatric
appendicitis was to start with a US study and follow each
negative US study with a CT examination.
娀RSNA, 2008
1From the Department of Diagnostic Imaging (M.J.W., E.C¸.,
A.S.D.), Division of Child Health Evaluative Sciences (W.J.U.),
and Department of Haematology/Oncology (L.S.), the Hospital
for Sick Children, 555 University Ave, Toronto, ON, Canada
M5G 1X8; the Division of Clinical Decision-Making and
Health Care, Toronto General Research Institute, Toronto,
Ontario, Canada (M.K.); and the Department of Radiology,
Miami Children’s Hospital, Miami, Fla (L.S.M.). From the
2007 RSNA Annual Meeting. Received January 15, 2008;
revision requested February 28; revision received August 8;
accepted September 2; final version accepted September 3.
A.S.D. supported by a Canadian Child Health Clinician-Scien-
tist Program Career Development Award and by a Depart-
ment of Medical Imaging of the University of Toronto Faculty
Development Award. Address correspondence to A.S.D.
(e-mail: andrea.doria@sickkids.ca ).
姝RSNA, 2008
ORIGINAL RESEARCH 䡲EVIDENCE-BASED PRACTICE
378 Radiology: Volume 250: Number 2—February 2009
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Acute appendicitis is the most com-
mon surgical emergency in chil-
dren (1,2). Despite the relatively
high incidence, the clinical diagnosis is
very commonly delayed or missed, lead-
ing to high rates of appendiceal perfora-
tion, particularly in young children less
than 5 years of age (3–6). Perforated
appendicitis can cause serious compli-
cations such as peritonitis and abscess
formation, which increase patient mor-
bidity and hospital costs (7–9). Because
diagnostic delays arise chiefly from the
interpretation of the history and physi-
cal examination results, diagnostic im-
aging has become an essential tool in
the evaluation of children suspected of
having appendicitis.
Diagnostic imaging of pediatric ap-
pendicitis currently involves ultrasonog-
raphy (US) and computed tomography
(CT). When both are available, clini-
cians must decide if the greater diagnos-
tic accuracy of CT outweighs the higher
operating costs and associated radiation
exposure (10,11). Data from atomic
bomb survivors have indicated that
there is a small but substantial risk of
developing a radiation-induced malig-
nancy from a single abdominal CT ex-
amination (12). Children are particu-
larly sensitive to the adverse effects of
radiation exposure and have longer life
spans during which a radiation-in-
duced cancer can manifest (13). For-
tunately, increasing awareness of the
malignancy risk from low-dose radia-
tion has motivated efforts to reduce
iatrogenic radiation exposure. It has,
for instance, become common prac-
tice to reduce the tube current setting
and overall radiation dose for pediat-
ric CT studies. In addition, many insti-
tutions are now using US before CT to
try to diagnose conditions such as ap-
pendicitis without exposing children
to ionizing radiation (14).
To facilitate the decision-making
process, we sought to quantify the costs
and effectiveness of different imaging
strategies for pediatric appendicitis,
taking into account the risk of radiation-
induced malignancy. We chose to use a
Markov decision model because it pro-
vided a method of predicting the overall
impact of radiation-induced cancer on a
cohort of individuals exposed to radia-
tion at a young age (15). Therefore, the
purpose of this study was to compare
the cost-effectiveness of US, CT, and US
followed by CT in the diagnosis of pedi-
atric appendicitis by using a Markov de-
cision analytic model.
Materials and Methods
The Research Ethics Board at our institu-
tion does not require approval for retro-
spective studies based on literature review.
Decision Analytic Model
We constructed a Markov-based decision
model by using software (DATA Profes-
sional; Tree Age Software, Williamstown,
Mass) to simulate the course of events for
pediatric patients clinically suspected of
having appendicitis. As the base-case sce-
nario, we selected a 5-year-old child clini-
cally suspected of having appendicitis at
presentation. The age of 5 years was cho-
sen because the risk of radiation-induced
malignancy is highest and most relevant for
young patients (12,16), but appendicitis is
uncommon in the first 4 years of life (6,17).
The patients were divided into three hypo-
thetical cohorts, each undergoing imaging
with a different strategy. It was assumed
that each patient underwent imaging with
only a single strategy at presentation; any
subsequent imaging was not included in the
analysis. The model simulated the course of
events, starting from the initial diagnostic
imaging test at the age of 5 years (Fig 1) and
ending when the patient died or reached
100 years of age. During the simulation,
there were four possible health states in
which patients could exist: appendicitis,
well, radiation-induced cancer, or dead.
Each health state was associated with a util-
ity value taken from the literature (18,19).
In health economics, a utility value is a num-
ber that represents a given quality of life or
state of health. An individual with a medical
condition such as cancer can be assigned a
utility value between 0 (death) and 1 (per-
fect health) depending on how substantially
the disease affects his or her quality of life.
In the model, patients could enter the
appendicitis health state only once and did
so at the age of 5 years. The lifetime of each
patient was then divided into 1-week cycles
Published online before print
10.1148/radiol.2502080100
Radiology 2009; 250:378–386
Abbreviations:
BEIR ⫽Biological Effects of Ionizing Radiation
ICER ⫽incremental cost-effectiveness ratio
QALY ⫽quality-adjusted life-year
SEER ⫽Surveillance, Epidemiology and End Results
Author contributions:
Guarantor of integrity of entire study, A.S.D.; study con-
cepts/study design or data acquisition or data analysis/
interpretation, all authors; manuscript drafting or manu-
script revision for important intellectual content, all au-
thors; manuscript final version approval, all authors;
literature research, M.J.W., A.S.D.; statistical analysis,
M.J.W., A.S.D.; and manuscript editing, M.J.W., E.Ç.,
A.S.D.
Authors stated no financial relationship to disclose.
Advances in Knowledge
䡲Using a Markov decision analytic
model that considered the radia-
tion-induced cancer risk after a
single abdominal CT study, we
found that even in children as
young as 5 years old, CT and US
followed by CT are both cost-ef-
fective imaging strategies for pe-
diatric appendicitis.
䡲When the incidence of appendici-
tis in patients referred for imaging
was very low (⬍5%), US was the
most effective and least costly im-
aging strategy; conversely, if the
incidence was greater than 21%,
the strategy of US followed by CT
was most effective.
Implication for Patient Care
䡲While clinicians can avoid the risk
of radiation exposure by exclu-
sively using abdominal US in sus-
pected appendicitis, our analysis
suggests that the use of CT, alone
or in tandem with US, is cost-ef-
fective; therefore, we hope the
results of this study will encour-
age clinicians to avoid radiation
exposure in children whenever
possible but to recognize that the
use of CT can be justified when
the diagnosis of appendicitis is in
question.
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
Radiology: Volume 250: Number 2—February 2009 379

such that with each cycle, patients had a
specific probability of staying in the same
heath state or moving to a different health
state (Fig 2). For instance, patients in the
well health state could transition to
“dead” (on the basis of the background
mortality rate for their age, according to
the U.S. life tables), develop a radiation-
induced cancer (on the basis of their
radiation exposure and the estimated
risk of cancer from the BEIR VII re-
port), or remain in the well state. If
patients developed a radiation-induced
cancer, they could either transition to
“dead” (on the basis of cancer survival
data from the SEER database) or con-
tinue to live with cancer. The program
kept track of the health care costs and
quality-adjusted life span associated
with each strategy. After the base-case
analysis, the potential variability and
uncertainty of key parameters within
the model were tested by using sensitiv-
ity analyses. For most parameters, a
one-way sensitivity analysis was per-
formed in which the single parameter
was varied over a relevant range while
all of the other parameters remained
constant. For pairs of closely related pa-
rameters (described below), two-way
Figure 1
Figure 1: Decision tree of the short-term events in the model, including the initial imaging strategy and the subsequent treatment protocol for patients suspected of
having appendicitis.
Figure 2
Figure 2: Chart of Markov process shows the mutually exclusive health states in which patients could exist over their life span and the transitions that could occur with
each cycle. BEIR ⫽Biological Effects of Ionizing Radiation, SEER ⫽Surveillance, Epidemiology and End Results, US ⫽United States.
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
380 Radiology: Volume 250: Number 2—February 2009

sensitivity analyses were used to deter-
mine the impact of changing one param-
eter at different levels of a second pa-
rameter. The model probabilities,
costs, and utilities, with the ranges of
values used in the sensitivity analyses,
are listed in Table 1 and are further
described below.
General Population Mortality Rate
The age-specific mortality rates for the
general population were taken from the
unabridged 1999 United States Life Ta-
bles (34).
Organ-specific Radiation Doses
Organ-specific radiation doses for an
abdominal CT examination were ob-
tained from a survey published by the
National Radiological Protection Board
in the United Kingdom (35). Because
children receive higher effective radia-
tion doses from CT examinations com-
pared with adults (36), the dose esti-
mates were adjusted for a 5-year-old
child by using scaling factors calculated by
Khursheed et al (37). The initial survey
was based on the use of parameters of
404 mA and 15.5 9.3-mm-thick sections
for a routine abdominal CT study. How-
ever, evidence (20) has shown that the
tube current settings can be reduced by
up to 75% for children without a detri-
mental effect on diagnostic accuracy.
Therefore, we assumed a base-case tube
current setting of 100 mA and conducted
a sensitivity analysis from 50 to 400 mA.
Cancer Incidence and Mortality
The incidence of radiation-induced can-
cer after a single abdominal CT study
was estimated by using the BEIR VII
report of the National Academy of Sci-
ences (38). The report is based primar-
ily on data from atomic bomb survivors
from Hiroshima and Nagasaki and pro-
vides organ-specific cancer incidence
rates as a function of effective radiation
dose, age, and sex, assuming a linear
extrapolation of risk from intermediate-
to low-dose radiation (30,39). Organ-
specific radiation doses from an abdomi-
nal CT examination were correlated with
the BEIR VII report to calculate incidence
rates for bladder cancer, breast cancer,
colon cancer, gastric cancer, lung cancer,
and leukemia. Because there is still ex-
treme uncertainty associated with esti-
mates of radiation-induced cancer risk,
the sensitivity analysis of radiation dose
was extended over a huge range (from
zero to 30 times baseline) to show how
changing estimates of cancer risk might
impact the results.
For the accuracy of the model, it was
critical to estimate the age of onset for each
radiation-induced cancer to calculate the
number of quality-adjusted life-years
(QALYs) that would be lost. Therefore, all
of the raw data used in the BEIR VII report
were collected and the algorithm was re-
constructed in full to calculate a year-by-
year incidence rate for each type of malig-
nancy. The model incorporated a risk-free
latent period between radiation exposure
and the development of cancer. For solid
cancers, the latent period was 5 years, and
for leukemia, the latent period was 2 years.
To model the mortality rates of radi-
ation-induced cancers, we used survival
Table 1
Model Probabilities, Utilities, and Costs
Parameter Baseline Value
Range Used in
Sensitivity Analysis Reference(s)
CT tube current setting 100 mA 50–400 mA 12, 20
Probabilities
US
Sensitivity 0.88 0.86, 0.90* 10
Specificity 0.94 0.92, 0.95* 10
CT
Sensitivity 0.94 0.92, 0.97* 10
Specificity 0.95 0.94, 0.97* 10
CT after negative or indeterminate US study
Sensitivity 0.97 0.88–1.00 14
Specificity 0.94 0.87–1.00 14
Appendicitis
Prevalence if referred for imaging 0.572 0–1.00 21
Perforation rate at presentation 0.387 0.20–0.76 22
Perforation rate after missed diagnosis 0.774 0.40–1.00 22–24
Death rate with normal appendectomy 0.0014 0–0.0070 25
Death rate with uncomplicated appendicitis 0.0024 0–0.0120 25
Death rate with perforated appendicitis 0.0166 0–0.0830 25
Utilities
Acute appendicitis 0.73 18
Well (age dependent) 0.88–0.94 19
Cancer (age dependent) 0.74–0.92 19
Costs ($)
†
Diagnostic imaging
US 342 161–907 8, 26, 27
CT 808 332–2146 8, 26, 27
Appendicitis without rupture 10 361 6931–17 732 22
Appendicitis with rupture 20 072 9543–38 441 22
Cancer treatment
Bladder cancer 89 728 0–897 280 28
Breast cancer 78 548 0–785 480 28
Colon cancer 46 275 0–462 750 29
Leukemia (weighted mean) 48 666 0–486 660 30–32
Lung cancer 45 439 0–454 390 28
Stomach cancer 28 088 0–280 880 28, 33
* 95% Confidence intervals.
†
In 2006 U.S. dollars.
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
Radiology: Volume 250: Number 2—February 2009 381

data from the SEER Cancer Statistics Re-
view published by the Cancer Statistics
Branch of the National Cancer Institute
(40). The SEER database was used be-
cause, for the types of cancer included in
the study, there was no evidence that ra-
diation-induced malignancies behaved
differently from non–radiation-induced
malignancies of the same type (38).
Therefore, when a patient developed a
radiation-induced cancer in the model, a
separate mortality rate was generated
each year depending on the age of the
patient and the type of cancer.
US and CT Diagnostic Characteristics
The sensitivity and specificity of US and
CT for pediatric appendicitis were
taken from the results of a recent meta-
analysis (10). These mean sensitivity
and specificity values were used in the
base-case analysis, and their 95% confi-
dence intervals were tested in two-way
sensitivity analyses for both US and CT.
The sensitivity and specificity of CT af-
ter a negative US study were taken from
a study by Garcia Pena et al (14).
Prevalence of Appendicitis in Patients
Referred for Imaging
A previous decision model of pediatric
appendicitis (26) revealed that it was
only cost-effective to refer patients for
imaging if they had equivocal clinical
signs of appendicitis, while patients
with a high clinical probability should
go directly to surgery and those with a
low probability should be discharged
to their homes. Therefore, the preva-
lence of acute appendicitis in patients
referred for imaging was taken from a
study by Pena et al (21), who followed
920 children in whom appendicitis
was clinically suspected at presenta-
tion and found that 57.2% were even-
tually given a diagnosis of the disease.
However, from a practical standpoint,
rural hospitals may not have ready ac-
cess to diagnostic imaging, while large
urban institutions may image every case of
suspected appendicitis while simulta-
neously obtaining a surgical consult to save
time. Therefore, the prevalence of appen-
dicitis in patients referred for imaging was
varied over the entire range of 0%–100% in
a sensitivity analysis to determine how dif-
ferent referral practices could affect the
cost-effectiveness of diagnostic imaging.
Rate of Appendix Perforation
The rate of appendix perforation was
taken from a study by Newman et al
(22), who reported data from 3393
cases of pediatric appendicitis at 30
children’s hospitals. The median perfo-
ration rate (39%) was used in the base-
case analysis, and the entire range re-
ported in the study (20%–76%) was
tested in a sensitivity analysis. The per-
foration rate after a missed diagnosis
was derived from a large study by Pearl et
al (23) of 100 cases of missed appendicitis
(of 1366 cases of appendicitis) and a
smaller study by Reynolds (24) of six
cases of missed appendicitis (of 87 cases
of appendicitis). Both studies demon-
strated that the perforation rate approxi-
mately doubled if the diagnosis was
missed initially and the patient was dis-
charged from the hospital. Therefore, it
was assumed that the perforation rate
doubled after a missed diagnosis.
Appendicitis-related Mortality Rates
The mortality rates for negative appen-
dectomies, acute uncomplicated appen-
dicitis, and perforated appendicitis (ap-
pendicitis-related mortality rates) were
taken from a study (25) that integrated
published literature over a period of 15
years, incorporating more than 10 000
appendectomies. The mortality rates in
that study were 0.14% for negative ap-
pendectomies, 0.24% for acute uncom-
plicated appendicitis, and 1.66% for
perforated appendicitis. Because mor-
tality rates have been declining in recent
years, the baseline values for all three
appendicitis-related mortality rates were
varied simultaneously from 0% to 100%
in a one-way sensitivity analysis.
Model Utilities
The utility associated with acute appen-
dicitis was taken from a study (18) that
measured utility health values in seri-
ously ill hospitalized patients. The utili-
ties for the health states “well” and “ra-
diation-induced cancer” were taken
from a survey (19) of 17 626 communi-
ty-dwelling individuals that calculated
age-specific Health Utilities Index scores
for both healthy individuals and individ-
uals living with cancer.
Costs
The analysis was conducted from the
perspective of a third-party payer. Indi-
rect costs such as lost parental income
were not accounted for in the study.
Long-term costs were discounted at a
rate of 3% annually (41), and all costs
were converted to 2006 U.S. dollars.
The baseline imaging costs for US
and CT were based on a study (27) from
the Children’s Hospital in Boston, Mas-
sachusetts, and included radiographic
interpretation. A two-way sensitivity
analysis for the variables “cost of CT”
and “cost of US” was performed by us-
ing the entire range of relevant cost data
found in the literature. Total treatment
costs for both perforated and nonperfo-
rated appendicitis were obtained from a
large study by Newman et al (22). The
median costs in that study were used for
the base-case analysis, and the entire
range of reported costs was tested in a
two-way sensitivity analysis.
For radiation-induced malignancies,
the diagnosis-to-death treatment costs as-
sociated with bladder cancer, breast can-
cer, colon cancer, lung cancer, and leuke-
mia were taken from studies based on the
SEER Medicare-linked database
(28,29,31,32,42–44). For gastric cancer,
the total health care costs were calculated
by using a prospective observational
study from England (33). Owing to the
inherent uncertainty associated with all
estimates of future health care costs, a
wide one-way sensitivity analysis was per-
formed on the cancer treatment cost data
to determine how changing treatment
costs might impact the results.
Results
For a single abdominal CT study in a
5-year-old child, it was found that the
lifetime risk of radiation-induced malig-
nancy would be 26.1 per 100 000 in fe-
male and 20.4 per 100 000 in male pa-
tients. The breakdown of radiation-in-
duced cancer according to site is
presented in Table 2, with comparisons
to baseline risk of lifetime malignancy
(45). With the strategy of performing
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
382 Radiology: Volume 250: Number 2—February 2009

an initial US study followed by CT if the
US study was negative, the number of
CT studies would be reduced by 53%,
thereby reducing the radiation-induced
malignancy rate by slightly more than
half. In the base-case analysis, US fol-
lowed by CT was the most costly and
most effective strategy, CT was the sec-
ond-most costly and second-most effec-
tive strategy, and US was the least costly
and least effective strategy (Table 3). For
female patients, US followed by CT had
an incremental cost-effectiveness ratio
(ICER) of $17 108 per QALY to US and
$7852 per QALY to CT, while CT had an
ICER of $26 260 per QALY to US. For
male patients, US followed by CT had an
ICER of $18 096 per QALY to US and
$8684 per QALY to CT, while CT had an
ICER of $26 624 per QALY to US.
Varying the tube current settings at
the abdominal CT examination from 50
to 400 mA did not change the relative
order of either the costs or the effective-
ness. For female patients, the CT tube
current settings would have to be
greater than 547 mA for US to be more
effective than CT and greater than 1976
mA for US to be more effective than US
followed by CT. For male patients, the
CT tube current settings would have to
be greater than 722 mA for US to be
more effective than CT and greater than
2615 mA for US to be more effective
than US followed by CT.
For the appendicitis-related mortal-
ity rates in female patients (ie, the mor-
tality rates of negative appendectomies,
acute uncomplicated appendicitis, and
perforated appendicitis), US was more
effective than CT if all three mortality
rates were reduced by more than 82%
and was more effective than US fol-
lowed by CT if the mortality rates were
reduced by more than 96%. For male
patients, US was more effective than CT
if the mortality rates were reduced by
more than 87% and was more effective
than US followed by CT if the mortality
rates were reduced by more than 97%.
This means that, for US to be more
effective than US followed by CT, the
risk of mortality would have to be less
than one per 10 000 for negative appen-
dectomies, less than one per 10 000 for
simple appendicitis, and less than six
per 10 000 for perforated appendicitis.
Changing the incidence of appendi-
citis in patients referred for imaging
also had a marked impact on the re-
sults. For female patients, US was the
most effective strategy if the incidence
of appendicitis in patients referred for
imaging was less than 7%, CT was most
effective if the incidence was between
7% and 21%, and US followed by CT
was most effective if the rate was
greater than 21%. For male patients,
US was the most effective strategy if the
incidence of appendicitis was less than
4%, CT was most effective if the inci-
dence was between 4% and 14%, and
US followed by CT was most effective if
the incidence was greater than 14%.
For both male and female patients, US
was the least costly strategy unless the
rate of appendicitis in patients referred
for imaging was greater than 80%, in
which case US followed by CT was the
least costly.
The remaining sensitivity analyses
(appendiceal perforation rate, appen-
dicitis treatment costs, cancer treat-
ment costs, imaging costs, and diag-
nostic characteristics of US and CT)
did not change the relative order of
the costs or effectiveness in either
male or female patients. In addition,
the cost-effectiveness of US followed
by CT was very resistant to parameter
uncertainty, as it remained cost-
effective compared with US (ie,
ICER ⬍$50 000 per QALY) through-
out all of the remaining sensitivity
analyses and cost-effective compared
with CT except in the single case when
the sensitivity and specificity of CT
were both at the highest tested levels
(ie, sensitivity ⫽0.97, specificity ⫽
0.97). CT was cost-effective compared
Table 2
Sex-specific Risk of Radiation-induced Malignancy for a Single Abdominal CT
Examination at 100 mA in a 5-year-old Patient, with Comparison to Lifetime Risk of
Malignancy at Baseline
Malignancy
Male Patients Female Patients
Radiation-induced
Cancer Rate Baseline Cancer Rate
Radiation-induced
Cancer Rate Baseline Cancer Rate
Bladder 3.2 3800 4.0 1200
Breast NA NA 2.2 12 800
Colon 6.7 5700 4.4 5200
Leukemia 2.9 700 2.2 600
Lung 2.4 8100 6.6 6400
Stomach 5.2 1100 6.7 700
Total 20.4 19 400 26.1 26 900
Note.—All rates are given as numbers per 100 000 patients. Data regarding baseline cancer rates are from reference 45.
NA ⫽not applicable.
Table 3
Average Costs and Effectiveness of Imaging Strategies in Base-Case Analysis
Sex and Outcome US CT US Followed by CT
Female
Cost ($)* 8942 9237 9323
Effectiveness
†
3879.0 3879.5 3880.1
Male
Cost ($)* 8942 9236 9323
Effectiveness
†
3638.3 3638.8 3639.4
* In 2006 U.S. dollars.
†
In quality-adjusted life-weeks.
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
Radiology: Volume 250: Number 2—February 2009 383

with US except in the following situa-
tions: When the sensitivity and speci-
ficity of US were both at the highest
tested levels (sensitivity ⫽0.90, spec-
ificity ⫽0.95), the sensitivity and
specificity of CT were both at the low-
est tested levels (sensitivity ⫽0.92,
specificity ⫽0.94), the imaging costs
were at the highest tested values (cost
of US ⫽$907, cost of CT ⫽$2146),
or when the perforation rate was
either very low (⬍25%) or very
high (⬎75%).
Discussion
Although previous studies (14,46–49)
have directly compared US and CT in
the diagnosis of pediatric appendicitis,
to our knowledge, none have incorpo-
rated the health care costs and loss of
life associated with radiation-induced
cancer. Therefore, our model was de-
signed to determine which imaging
strategy was most cost-effective for pe-
diatric appendicitis, taking into account
the risk of radiation-induced cancer
from iatrogenic radiation exposure. On
the basis of the results, it was found that
US was the cheapest and least effective
strategy, CT was more effective and
more costly, and US followed by CT was
the most effective and most costly strat-
egy. So that we could determine if the
more expensive imaging strategies were
cost-effective, we calculated ICERs. The
ICER is a measure of how much addi-
tional money is required to achieve an
additional outcome—in this case, the
cost to the health care system per QALY
gained. The intervention is considered
cost-effective if the ICER falls below a
societal willingness-to-pay threshold,
which is usually set at $50 000 (in U.S.
dollars) per QALY (50). In our decision
model, the ICER of CT to US was below
the willingness-to-pay threshold of
$50 000 in both male and female pa-
tients, suggesting that CT alone is a
cost-effective method of imaging pediat-
ric appendicitis. However, the ICERs of
US followed by CT to US and US fol-
lowed by CT to CT were both well below
$50 000. Therefore, in a Markov deci-
sion analytic model of pediatric appen-
dicitis, the most cost-effective imaging
strategy was to start with a US study
and to follow each negative US study
with a CT examination, despite the risk
of radiation-induced cancer.
To test uncertainty in the analysis,
we conducted one- and two-way sensi-
tivity analyses of key values in the
model. As expected, increasing the ra-
diation dose decreased the effectiveness
of both CT and US followed by CT.
However, it was found that the tube
current settings would have to have
been more than 400 mA for CT to be
less effective than US and more than
1900 mA for US followed by CT to be
less effective than US. Given the fact
that most health care centers use low
radiation doses (⬍200 mA) for abdomi-
nal CT examinations in children, our
study results suggest that the higher di-
agnostic accuracy of CT currently out-
weighs the risk of radiation-induced
cancer in the diagnosis of pediatric ap-
pendicitis.
Clinicians may assume that because
appendicitis-related mortality is very
low, it would be preferable to have
more short-term adverse events than to
expose children to ionizing radiation,
which could potentially induce a termi-
nal cancer. However, it is important to
remember that a single death in a young
child causes a much greater total loss of
QALY than a radiation-induced malig-
nancy that manifests many years later.
Therefore, while appendicitis-related
mortality has declined with improved
treatment, it is unlikely that the mortal-
ity rates have decreased by over 95% in
the past several years, which is what
would be required for US alone to be
the most effective imaging strategy.
Other than radiation dose and ap-
pendicitis-related mortality, the only
other sensitivity analysis that markedly
changed the results was the prevalence
of appendicitis in children referred for
imaging. When the prevalence of ap-
pendicitis was very low (less than 4%),
US was the most effective and least
costly strategy, which is logical, because
as the risk of appendicitis decreases to-
ward zero, the risk of radiation expo-
sure becomes comparatively greater.
Therefore, when the prevalence of ap-
pendicitis is very low, the main risk to
the patient is from radiation-induced
cancer, and the most effective strategy
is to eliminate radiation exposure by us-
ing US. Conversely, if the prevalence of
appendicitis is high, then the risk of
missing the diagnosis is much greater.
As a result, US followed by CT becomes
the most effective strategy because the
risk of missed appendicitis outweighs
the risk of radiation-induced cancer.
Therefore, in the majority of centers
where children are only referred for im-
aging if they are at intermediate to high
risk of appendicitis, the most cost-effec-
tive imaging strategy would be US fol-
lowed by CT.
There were several limitations to
this study. The principal limitation was
that there is still an extreme degree of
uncertainty associated with current es-
timates of radiation-induced cancer, es-
pecially at very low doses. Another as-
sumption, common to all decision mod-
els, is that data from many different
sources could be reasonably combined
into a single model to yield useful re-
sults. The sensitivity analyses within the
decision model are also a substantial
limitation in that we were able to exam-
ine the variability only in one or two
parameters at a time while artificially
assuming that all of the other variables
would stay constant. Finally, by design,
the model did not completely account
for all of the possible pathways in the
assessment and treatment of appendici-
tis. For instance, the model did not in-
clude the common practice of perform-
ing a CT examination prior to perform-
ing percutaneous abscess drainage for
perforated appendicitis. For this study,
we decided to keep the model as
straightforward as possible in order to
investigate the basic principles of radia-
tion exposure in the imaging of pediatric
appendicitis; we hope this work will lay
the groundwork for more complex mod-
els in the future.
The decision of how to image sus-
pected appendicitis in children depends
on many factors. Indeed, availability
may determine which modality will be
used before issues such as radiation ex-
posure are even considered. Increas-
ingly, however, both US and CT are ac-
cessible to emergency room physicians.
EVIDENCE-BASED PRACTICE: Acute Appendicitis in Young Children: US versus CT Wan et al
384 Radiology: Volume 250: Number 2—February 2009

When the physician can decide which
imaging modality to use, our study re-
sults suggest that even in children as
young as 5 years old, CT and US fol-
lowed by CT are both cost-effective im-
aging strategies. Therefore, clinicians
must recognize that diagnostic accuracy
is a crucial factor in the imaging of pedi-
atric appendicitis, even though the risk
of radiation-induced cancer from a sin-
gle abdominal CT examination is not
negligible and should always be consid-
ered in the decision-making process.
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