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Supplementary Appendix
Appendix 1. Model descriptions and standardized model inputs.
Page 2
Appendix 1a. Description of MISCAN-COLON for natural history and intervention
Page 2
Appendix 1b. Description of SimCRC for natural history and intervention
Page 8
Appendix 1c. Comparison of MISCAN and SimCRC on natural history outcomes
Page 10
Appendix 1d. Description of standardized model inputs
Page 11
Appendix 2. Overview of sensitivity analyses performed
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Appendix 3. Cumulative CRC screening, treatment, and total costs (billions of US dollars) at ten year intervals
in the current trends and enhanced participation scenarios (undiscounted).
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Appendix 4. Overview of intermediate model results.
Page 18
References
Page 20
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Appendix 1. Model descriptions and standardized model inputs.
We used two independently-developed microsimulation models, MISCAN-COLON (Microsimulation
Screening Analysis Colon) and SimCRC (Simulation model of Colorectal Cancer), to compare the costs of
colorectal cancer screening and treatment under current trends in screening participation and under a scenario
with enhanced screening participation among the pre-Medicare population. Both models are part of the Cancer
Intervention and Surveillance Modeling Network (CISNET), a consortium funded by the National Cancer
Institute. The models used common inputs and assumptions concerning the screening tests but use their
independently developed natural history models in addressing these questions.
Appendix 1a. Description of MISCAN-COLON for natural history and intervention
MISCAN Model overview
MISCAN is a semi-Markov microsimulation model to simulate the effect of screening and other
interventions on colorectal cancer incidence and mortality. The model has been programmed in Borland Delphi
7 Enterprise. With microsimulation we mean that each individual in the population is simulated separately. The
model is semi-Markov in the sense that:
- distributions other than exponential are possible in each disease state
- transitions in one state can depend on transitions in earlier states,
- transitions can be age and calendar time dependent
All events in the model are discrete, but the durations in each state are continuous. Hence, there are no annual
transitions in the model.
The development of colorectal cancer in the model is assumed to occur according to the adenoma
carcinoma sequence. This means that adenomas arise in the population, some of which eventually develop into
colorectal cancer. We assume that there are two types of adenomas: progressive and non-progressive adenomas.
Non-progressive adenomas can grow in size, but will never develop into a cancer. Progressive adenomas have
the potential to develop into cancer, if the person in whom the adenoma develops lives long enough.
All adenomas start as a small (≤5 mm) adenoma. They can grow in size to medium (6-9 mm) and large
(≥10 mm) adenomas. Progressive medium and large adenomas can transform into a malignant cancer stage I,
not yet giving symptoms (preclinical cancer). The cancer then progresses from stage I (localized) eventually to
stage IV (distant metastasis). In each stage there is a probability of the cancer giving symptoms and being
clinically detected. The time between the onset of a progressive adenoma and the clinical detection of colorectal
cancer is assumed to be on average 20 years. After clinical detection a person can die of colorectal cancer, or of
other causes based on the survival rate. The survival from colorectal cancer is highly dependent on the stage in
which the cancer was detected.
MISCAN Simulation of an individual
Figure 1a shows how the model generates an individual life history. First MISCAN generates a time of
birth and a time of death of other causes than colorectal cancer for an individual. This is shown in the top line of
Figure 1a. This line constitutes the life history in the absence of colorectal cancer. Subsequently, MISCAN
generates adenomas for an individual. For most individuals no adenomas are simulated, for some multiple. In
this example MISCAN has generated two adenomas for the individual. The first adenoma occurs at a certain age
and grows in size from small to medium and large adenoma. However this is a non-progressive adenoma, so this
adenoma will never transform into cancer. The second adenoma is a progressive adenoma. After having grown
to 6-9 mm, the adenoma transforms into a malignant carcinoma, causing symptoms and eventually resulting in
an earlier death from colorectal cancer.
2
Life history without colorectal cancer
Death from
other causes
Birth
Development of adenoma and cancer
Adenoma
≤5mm
Adenoma
6-9mm
Preclinical
cancer stage I
Clinical cancer
stage I
Death from
colorectal cancer
Combined life history with colorectal cancer and without screening
Birth
Adenoma
≤5mm
Adenoma
6-9mm
Preclinical
cancer stage I
Clinical cancer
stage I
Death from
colorectal cancer
Figure 1a: Modeling natural history into life
The life history without colorectal cancer and the development of the two adenomas are combined into a
life history in the presence of colorectal cancer. This means that the state a person is in is the same as the state of
the most advanced adenoma or carcinoma present. If he dies from colorectal cancer before he dies from other
causes, his death age is adjusted accordingly. The combined life history with colorectal cancer is shown in the
bottom line of Figure 1a.
MISCAN simulation of screening
The complete simulation of an individual life history in Figure 1a is in a situation without screening taking
place. After the model has generated a life history with colorectal cancer but without screening, screening is
overlaid. This is shown in Figure 1b. The first three lines show the combined life history with colorectal cancer
and the development of the two adenomas from Figure 1a. At the moment of screening both adenomas are
present, detected and removed. This results in a combined life history for colorectal cancer and screening
(bottom line), where the person is adenoma-carcinoma free after the screening intervention. Because the
precursor lesion has been removed this individual does not develop colorectal cancer and will therefore not die
of colorectal cancer. The moment of death is delayed until the moment of death from other causes. The benefit
of screening is equal to the difference between life-years lived in a situation with screening and the situation
without screening.
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Combined life history for colorectal cancer but not for screening
Birth
Adenoma
≤5mm
Adenoma
6-9mm
Preclinical
cancer stage I
Clinical cancer
stage I
Death from
colorectal cancer
Development of first adenoma
Adenoma
≤5mm
Adenoma
6-9mm
Adenoma
≥10mm
Development of second adenoma
Adenoma
≤5mm
Adenoma
6-9mm
Preclinical
cancer stage I
Clinical cancer
stage I
Death from
colorectal cancer
Combined life history with colorectal cancer and screening
Birth
Adenoma
≤5mm
Adenoma
6-9mm
Effect of
screening
Adenoma, carcinoma free
Death from
other causes
Screening intervention
Figure 1b: Modeling screening into life history
Many other scenarios could have occurred. A person could have developed a third adenoma after the
screening moment and could still have died of colorectal cancer. Another possibility would have been that one
of the adenomas was missed, but in the presented example the individual really benefited of the screening
intervention.
The effectiveness of screening depends on the performance characteristics of the test performed:
sensitivity, specificity and reach (see Appendix 1d for an overview of the test characteristics assumed). In the
model, one minus the specificity is defined as the probability of a positive test result in an individual irrespective
of any adenomas or cancers present. For a person without any adenomas or cancers, the probability of a positive
test result is therefore equal to one minus the specificity. In individuals with adenomas or cancer the probability
of a positive test result is dependent on the lack of specificity and the sensitivity of the test for the present
lesions. Sensitivity in the model is lesion-specific, where each adenoma or cancer contributes to the probability
of a positive test result.
See the model profiler http://cisnet.cancer.gov/profiles/ for a more detailed discussion of the dwell
time distributions for the adenomas and colorectal cancer.
4
Natural history parameters
The parameters for the natural history model that could not be directly estimated from data or fit to reference
data, were established based on expert opinion. At two expert meetings at the NCI on June 5–7, 1996, and May
12–13, 1997, a model structure was devised in agreement with the currently accepted model of the adenoma–
carcinoma sequence. It was assumed that all cancers are preceded by adenomas.
The average duration between onset of a progressive adenoma and the transition to preclinical cancer was
calibrated to data from the UK flexible sigmoidoscopy screening trial.(1) The duration of cancer in preclinical
stages was estimated based on the results of three large randomized controlled screening trials.(2) This resulted
in an average duration of 2.5 years, 2.5 year, 3.7 years, and 1.5 year, for stages I-IV respectively, with a total
average duration of 6.7 years because not every cancer reaches stage IV before clinical diagnosis. All durations
were governed by an exponential probability distribution. Durations in each of the invasive cancer stages as well
as durations in the stages of the noninvasive adenomas were assumed to be 100% associated with each other, but
the durations in invasive stages as a whole were independent of durations in noninvasive adenoma stages that
precede cancer. These assumptions resulted in an exponential distribution of the total duration of progressive
noninvasive adenomas and of the total duration of preclinical cancer, which has also been used in other cancer
screening models.(3, 4)
It was assumed that 30% of the cancers arise from adenomas of 6–9 mm and that 70% arise from larger
adenomas. Initially, the preclinical incidence of progressive adenomas was chosen to reproduce the colorectal
cancer incidence by age, stage, and localization in the US in 1975-1979.(5) During this period, almost no
screening was performed. The size distribution of adenomas over all ages was assumed to be 73% for stages less
than or equal to 5 mm, 15% for stages 6–9 mm, and 12% for stages greater than or equal to 10 mm.(6) The
preclinical incidence of non-progressive adenomas that will never grow into cancer was varied until the
simulated prevalence of all adenomas was in agreement with data from autopsy studies.(7-16) In addition, the
overall adenoma incidence was adjusted to ensure the model-predicted CRC incidence rate matched the
incidence rate in 2009 as observed in the Surveillance, Epidemiology, and End Results (SEER) registry data.(5)
The anatomic site distribution of both progressive and non-progressive adenomas and thus of preclinical and
clinical cancers is assumed to be equal to the site distribution of colorectal cancers in the US in 1975-1979. The
stage-specific survival after the clinical diagnosis of colorectal cancer is taken from SEER from the period 2000
through 2003.(5) Table 1a.1 contains a summary of the model input values and their data-sources.
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Table 1a.1: Main natural history assumptions in the MISCAN-Colon model
Model parameter
Distribution of risk for adenomas
over the general population
Value
Gamma distributed, mean 1.1072,
variance 1.98
Source
Fit to multiplicity distribution of
adenomas in autopsy studies (7-16)
and to CRC incidence from SEER in
2009.(5)
Adenoma incidence in general
population
Age dependent:
0-19 years: 0.04% per year
20-24 years: 0.43% per year
25-29 years: 0.48% per year
30-34 years: 0.79% per year
34-39 years: 1.73% per year
40-44 years: 2.82% per year
45-49 years: 3.16% per year
50-54 years: 3.54% per year
55-59 years: 3.67% per year
60-64 years: 3.67% per year
65-69 years: 3.68% per year
70-74 years: 3.69% per year
75-79 years: 6.03% per year
80-84 years: 1.57% per year
85-100 years: 0.65% per year
Fit to adenoma prevalence in autopsy
studies (7-16) and to CRC incidence
from SEER in 2009.(5)
Probability that a new adenoma is
progressive
Dependent on age at onset,
varying from 0-89%
Fit to adenoma prevalence in autopsy
studies, (7-16) and to CRC incidence
from SEER in 1975-1979 (prescreening era).(5)
Regression of adenomas
No significant regression of
adenomas
6.7 years
Expert opinion
25%
Fit to size distribution of adenomas
in colonoscopy study (percentages
corrected for colonoscopy
sensitivity): (6)
1-5mm: 73%
6-9mm: 15%
10+mm: 12%
Mean duration of preclinical
cancer
Percent of non-progressive
adenomas that stay 6-9mm
Estimated from FOBT trials.(2)
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Model parameter
Percent of non-progressive
adenoma that become 10mm or
larger
Value
75%
Source
Fit to size distribution of adenomas
in colonoscopy study (percentages
corrected for colonoscopy
sensitivity): (6)
1-5mm: 73%
6-9mm: 15%
10+mm: 12%
Expert opinion
Percent of cancers that develops
from 6-9mm adenoma and from
10+mm adenoma
30% of cancer develops from 6-9
mm, 70% from 10+mm
Localization distribution of
adenomas and cancer
Rectum: 21%
Distal colon: 42%
Proximal colon: 37%
Directly estimated from SEER in
1975-1979 (pre-screening era).(5)
10-year survival after clinical
diagnosis of CRC
Dependent on age, stage and
localization
Example: age 65 years, colon
Stage I: 94%
Stage II: 85%
Stage III: 74%
Stage IV: 8%
Directly estimated from SEER in
2000-2003.(5)
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Appendix 1b. Description of SimCRC for natural history and intervention
Model description
The Simulation Model of Colorectal Cancer (SimCRC) from the University of Minnesota (Minneapolis, MN)
and Massachusetts General Hospital (Boston, MA) is one of three simulation models of colorectal cancer (CRC)
in the National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET).
SimCRC simulates the natural history of colorectal cancer among the US population over time and incorporates
the effects of screening interventions. Its findings, together with those of the two other CISNET CRC models -MISCAN (from Erasmus MC, Rotterdam, The Netherlands) and CRC-SPIN (from Group Health Research
Institute, Seattle, WA) -- have been used to inform the 2008 screening recommendations of the US Preventive
Services Task Force,(17) as well as national coverage of CRC screening tests by the Centers for Medicare and
Medicaid Services.(18, 19)
SimCRC is programmed in Microsoft Visual Studio C++ 2010 Express (Seattle, Washington). It is a populationbased microsimulation model, meaning that is simulates outcomes for individual persons according to year of
birth, with new persons entering the model over time (and persons exiting the model through death). Outcomes
are summed across individuals to generate population-level estimates (e.g., CRC incidence and mortality rates
by calendar year). Outcomes can also be tallied according to year of birth to generate outcomes such as life
expectancy and lifetime risk of developing or dying from CRC.
There are two key components of SimCRC – a natural history module and a screening module. The natural
history module simulates the life history of simulated persons in the absence of screening. The screening module
is overlaid on the natural history model to determine if screening interrupts the natural history process.
In this analysis, we used SimCRC to estimate and compare the implications of enhancing screening participation
among the pre-Medicare population (i.e., those aged 50-64 years) on the costs related to CRC screening and
treatment in the pre-Medicare and Medicare (i.e., those aged 65 years and older) populations. SimCRC’s natural
history and screening modules are described below, followed by descriptions of the calibration and validation
approaches.
SimCRC Natural History Module
SimCRC’s natural history module describes the disease process, specifically the development of adenomas and
their possible progression to CRC, in the absence of any intervention. SimCRC begins by generating the age of
birth and the age of death from causes other than CRC for each simulated person. Simulated individuals are also
stochastically assigned an individual risk index that is based on a truncated normal distribution (and is restricted
to positive values).
Each simulated person is assumed to be free of adenomas and CRC at birth. Over time, each person is at risk of
forming one or more adenomas, with risk depending on an individual risk index, age, and sex. SimCRC models
three adenoma size categories—small (1–5 mm), medium (6-9 mm), and large (≥10 mm)—and six locations of
lesions within the colon (cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and
rectum). All adenomas start small and can transition through larger size categories, with each adenoma
stochastically assigned an adenoma-specific growth index based on a truncated normal distribution, which
allows between-adenoma variability in the probability of transitioning to larger sizes. The risk of transitioning to
the next adenoma size depends on an individual’s age and sex and the adenoma’s location in the colorectum,
with risks varying for the proximal colon (cecum, ascending colon, transverse colon), distal colon (descending
colon and sigmoid colon), and rectum. Medium and large adenomas may progress to preclinical CRC, although
most will not in an individual’s lifetime. The likelihood of progression to CRC depends on an individual’s age
and sex and the adenoma’s location in the colorectum (proximal colon, distal colon, and rectum). SimCRC does
not allow for regression of adenomas.
Preclinical cancers may progress in stage (from stage I to stage IV) and may be detected by the presence of
symptoms, becoming a clinical case. Individuals with CRC may die of their cancer (based on stage- and
location-specific (colon versus rectum) models of relative survival according to sex, race, age at diagnosis, time
since diagnosis, and diagnosis year estimated from SEER data(20)) or of other causes (based on sex, race, and
calendar-year-specific US Life Tables from the National Center for Health Statistics).(21) All persons are
assumed to die by the end of their 100th year of life.
In SimCRC, the ages at which discrete events occur are drawn from cumulative probability distributions that are
derived from monthly or annual (often age-specific) probabilities that define the likelihood of transitioning
through health states. The exact timing of a transition at a particular age is determined from a uniform
distribution.
For comparison with other CRC models, SimCRC’s mean total dwell time (i.e., mean time from adenoma onset
to clinically presentation of CRC for adenomas that make it to CRC within a person’s lifetime) has been
estimated at 25.2 years, with a mean time of 21.2 years in the adenoma state and 4.0 years in a preclinical cancer
state.(22)
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SimCRC Screening Module
SimCRC’s screening module allows for the detection and removal of adenomas and the diagnosis of preclinical
CRC. When screening is performed, a person with an underlying (i.e., undiagnosed) adenoma or preclinical
cancer may have their lesion detected based on the sensitivity of a screening test for that lesion and, for
endoscopic tests, whether the lesion is within the reach of the endoscope. For a person without an underlying
adenoma or cancer, the test’s false-positive rate is used to determine whether or not that person will undergo an
unnecessary follow-up colonoscopy. Non-adenomatous polyps are not simulated explicitly but are reflected in
the test’s false-positive rate. Each detected adenoma is assumed to be completely removed, thereby preventing
its potential progression to CRC. SimCRC incorporates the risk of fatal and non-fatal complications associated
with screening procedures. It also accounts for the fact that not all individuals adhere with CRC screening
guidelines and that adherence patterns may be correlated within an individual.
SimCRC utilizes the technique of common random numbers(23) to simulate (hypothetical) individuals with
identical characteristics (e.g., identical date of birth, date of death from causes other than CRC, timing of
adenoma onset, etc.) across multiple replications of the model. With this approach, outcomes for a given
simulated individual in a situation with CRC screening can be compared with his or her outcomes in a situation
without screening. This assures that differences in aggregate outcomes (e.g., life-years, CRC cases, CRC deaths)
in scenarios with and without screening are due to screening rather than to stochastic noise.
Calibration and Validation of SimCRC
Because the development of adenomas and their growth and malignant transformation is unobservable, limited
data are available for direct estimation of natural history model parameters. Accordingly, SimCRC’s natural
history component has been estimated by calibrating model outcomes to simultaneously match data from
observational studies. These data include estimates of adenoma prevalence (by age, sex, and number of
adenomas), adenoma size distribution, adenoma location, and prevalence of preclinical cancer (by age and sex)
from as many as 10 autopsy studies and to CRC incidence (by sex, age, race, tumor location, and stage at
diagnosis) from the Surveillance, Epidemiology, and End Results Program prior to the introduction of screening
(1975-1979).
SimCRC was calibrated separately by sex and race. The simultaneous fit of the model to the calibration data was
assessed by summing the differences between the −2 log-likelihoods of the model predictions and of each set of
calibration data. SimCRC used a simulated annealing algorithm to search the parameter space. This algorithm
initially allows for large steps across the parameter space to avoid becoming trapped in a local minimum. As the
search progresses, the step size decreases, allowing the algorithm to hone in on a (local) minimum. The
algorithm was initiated at multiple randomly-selected points in the parameter space and was run until multiple
iterations converged to approximately the same parameter set.
SimCRC has been validated by simulating outcomes of screening trials, including the Minnesota Colon Cancer
Control Study of annual and biennial screening with a guaiac fecal occult blood test.(24-26) It has also been
validated with the UK Flexible Sigmoidoscopy Screening Trail of once-only flexible sigmoidoscopy.(1)
See the model profiler http://cisnet.cancer.gov/profiles/ for a more detailed discussion of the
transition probabilities for adenomas and colorectal cancer.
9
Appendix 1c. Comparison of MISCAN and SimCRC on natural history outcomes
MISCAN
SimCRC
Adenoma prevalence, age 65:
39.8%
Adenoma prevalence, age 65:
Number of adenomas per 1000 by site and size, age 65
≤5 mm
6-9 mm
≥10 mm
Proximal colon
129.0
96.7
48.2
Distal colon
125.5
94.0
Rectum
148.7
111.4
37.1%
Number of adenomas per 1000 by site and size, age 65
≤5 mm
6-9 mm
≥10 mm
Proximal colon
171.8
185.8
23.9
46.9
Distal colon
123.9
18.3
41.4
55.5
Rectum
8.7
16.0
15.6
Distribution of adenomas by site and size, age 65 (%)
Distribution of adenomas by site and size, age 65 (%)
≤5 mm
6-9 mm
≥10 mm
Total
≤5 mm
6-9 mm
≥10 mm
Total
Proximal colon
15
11
6
32
Proximal colon
28
31
4
63
Distal colon
15
11
5
31
Distal colon
20
3
7
30
Rectum
17
13
6
37
Rectum
1
3
3
7
CRC incidence among cancer-free 65-year-old population, %
CRC incidence among cancer-free 65-year-old population, %
Stage 1
Stage 2
Stage 3
Stage 4
Total
Stage 1
Stage 2
Stage 3
Stage 4
Total
10-year
0.4
0.7
0.5
0.5
2.2
10-year
0.4
0.7
0.5
0.5
2.1
20-year
0.8
1.5
1.1
1.1
4.6
20-year
0.8
1.5
1.0
1.2
4.4
Lifetime
1.1
2.0
1.4
1.4
5.8
Lifetime
0.9
1.9
1.3
1.5
5.7
10
Appendix 1d. Description of standardized model inputs
Test characteristics
The sensitivity and specificity of the screening tests used in the models are presented in Table 1d.1. It is
assumed that the test characteristics were independent of age and past screening. In addition, it is assumed that
small adenomas do not bleed and cannot be detected by FOBT and fecal immunochemical test (FIT). The
sensitivity of FOBT and FIT for adenomas ≤5 mm is based on the false-positive rate (that is, 1 - specificity).
Hyperplastic polyps, which do not follow the adenoma-carcinoma sequence, are not modeled explicitly but are
reflected in the specificity of endoscopic tests.(27) Additional biopsy costs were assumed for procedures without
adenomas detected.
Table 1d.1 – Sensitivity and specificity of screening tests used in the models.
Screen test
Sensitivity (%)
Specificity (%)
FOBT HCII
Adenoma
≤5 mm
2
Adenoma
6-9 mm
5
Adenoma
≥10 mm
12
Preclinical
CRC
40
98
FOBT Sensa
8
12
24
70
92
FIT*
5
10
22
70
95
Stool DNA*
12
26
36
92
88
Sigmoidoscopy
75
85
95
95
92
Colonoscopy
75
85
95
95
90
CRC = colorectal cancer; FOBT HCII = fecal occult blood test, Hemoccult II; FOBT Sensa = fecal occult blood
test, Hemoccult Sensa; FIT = fecal immunochemical test.
* FIT and stool DNA were only used in the sensitivity analyses. The test characteristics of stool DNA were
fitted to the positivity and detection rate of the Cologuard multitarget stool DNA test, developed by Exact
Sciences (Madison, WI).(28)
11
Appendix 2. Overview of sensitivity analyses performed
Table 2.1 – Description of assumptions in the sensitivity analyses.
Sensitivity analysis
Description
Base case
Under enhanced participation the proportion of individuals up-to-date with screening is increased to 70%,
compared to 60% under current trends. In both scenarios 87% of screening participants receive colonoscopy and
13% receive FOBT screening.
Focus on FOBT
All individuals changing their screening behavior in the enhanced participation scenario would be screened with Hemoccult
Sensa. Individuals who were screened with Hemoccult II or endoscopy in the current trends scenario and did not change
their screening behavior, would continue to receive Hemoccult II and endoscopy screening respectively.
Focus on colonoscopy
All individuals changing their screening behavior in the enhanced participation scenario would be screened with
colonoscopy. Individuals who were screened with Hemoccult II in the current trends scenario and did not change their
screening behavior, would continue to receive Hemoccult II screening.
Increased treatment costs
Treatment costs for terminal care in all stages and initial care in stage IV CRC were increased by 30% to reflect the
increasing proportion of patients receiving surgery and adjuvant chemotherapy and the increasing costs of these
therapies.(29, 30)
Colonoscopy with anesthesia
Costs of colonoscopy procedures were increased by $152 (with polypectomy) and $135 (without polypectomy) to reflect
use of monitored anesthesia*
Colonoscopy privately insured
Colonoscopy costs in the privately insured pre-Medicare population were increased to three times the Medicare
reimbursement rate, to reflect the higher reimbursement rate for privately insured individuals
FIT replaces Sensa
All individuals screened with Hemoccult Sensa in the base case received FIT instead. The Medicare reimbursement rate for
FIT was assumed to be $23, compared to $5 for Hemoccult Sensa.
Stool DNA replaces Sensa
All individuals changing their screening behavior in the enhanced participation scenario would be screened with
stool DNA. Individuals who were screened with Hemoccult II or endoscopy in the current trends scenario and did
not change their screening behavior, would continue to receive Hemoccult II and endoscopy screening respectively.
The screening interval with stool DNA was three years and the assumed Medicare reimbursement rate was
$493.(31)
Modified societal perspective
Next to direct medical costs, patient time costs and beneficiary copayments were included in the analysis. An overview of
cost inputs is provided in Appendix Table 2.2.
65% up-to-date with screening
65% of individuals were up-to-date with screening and 72.5% were ever screened in the enhanced participation scenario,
compared to 70% and 75% respectively in the base case.
Lower sensitivity proximal lesions The sensitivity of colonoscopy for proximal lesions was decreased to 65%, 77%, and 92% for small, medium, and large
adenomas and CRC,(32) compared to 75%, 85%, and 95% for distal lesions (same as base case values for entire colon and
rectum).
Improved CRC survival
CRC relative survival by age and stage at diagnosis was increased by 25% for all individuals.
FOBT = fecal occult blood test; CRC = colorectal cancer; FIT = fecal immunochemical test; CRC = colorectal cancer.
* Based on personal communication with Joel V. Brill MD, AGAF, Predictive Health LLC, Paradise Valley AZ. 2011 estimates.
12
Table 2.2 – Cost inputs used in the sensitivity analysis “modified societal perspective”. Unit costs of CRC screening and treatment, in 2010 US dollars, in the preMedicare and Medicare populations.
Screening costs (per procedure)
Pre-Medicare population ($)*
Medicare population ($)
FOBT (Hemoccult II and Sensa)
24
23
Sigmoidoscopy without biopsy
48
41
Sigmoidoscopy with biopsy
725
667
1,332
1,143
Colonoscopy with polypectomy
831
749
Diagnostic test outside program
1,587
1,343
- Colonoscopy
1,544
1,308
- Sigmoidoscopy
9,328
7,749
Pre-Medicare population ($)*
Medicare population ($)
Colonoscopy without polypectomy
Treatment of complications from:†
CRC treatment costs (per person, per
year of care‡)
Stage I
Stage II
Stage III
Stage IV
Stage I
Stage II
Stage III
Stage IV
Initial phase
44,082
58,881
71,290
92,552
34,547
46,145
55,870
72,533
Continuing phase
3,709
3,489
4,840
14,485
2,907
2,734
3,793
11,352
Terminal phase, death CRC
76,201
75,902
80,012
105,159
59,719
59,484
62,705
82,413
Terminal phase, death other causes
23,572
21,335
26,261
59,760
18,473
16,720
20,581
46,834
FOBT = fecal occult blood test; CRC = colorectal cancer.
Direct medical costs were based on the values presented in Table 2 in the main text. The value of an hour of patient or caregiver time was assumed to be $18, the 2010 U.S.
median hourly wage rate for civilians.(33) We assumed 24 hours of patient and escort time for colonoscopies and sigmoidoscopies,(34) and one hour for stool-based tests. In
addition, we assumed $22.54 for bowel preparation,(35) and 25% beneficiary copayment for colonoscopies and sigmoidoscopies. CRC treatment costs in the Medicare
population have been published before.(35) Estimates include beneficiary copayments, and 244, 19, and 283 hours of patient time in the initial, continuous and terminal
phases of care respectively.(36, 37) Treatment costs for the pre-Medicare population were inflated to account for differences in reimbursement rates between insurers in the
same way as was done in the estimates of direct medical costs (Table 2 in the main text).
13
Table 2.3. Results of the sensitivity analysis for MISCAN. Cumulative cost difference (billions of 2010 US dollars, 3% discounted) of the enhanced participation scenario,
compared to current trends by the year 2060.
Base
case
Focus on
FOBT
Focus on
colonoscopy
Increased
treatment
costs
Colonoscopy
with
anesthesia
Colonoscopy
privately
insured
FIT
replaces
Sensa
Stool
DNA
replaces
Sensa
Modified
societal
perspective
65% upto-date
with
screening
Lower
sensitivity
proximal
lesions
Improved
CRC
survival
Pre-Medicare population (50-64 years)
Screening
38.5
19.9
43.1
38.5
46.1
74.0
39.4
64.9
62.0
18.7
37.0
38.5
Treatment
-2.7
1.0
-3.7
-4.0
-2.8
-2.9
-2.7
1.2
-3.1
-1.4
-2.2
-3.3
Total
35.7
21.0
39.4
34.4
43.3
71.1
36.6
66.1
58.9
17.4
34.8
35.1
Medicare population (65+ years)
Screening
12.6
7.8
13.7
12.6
15.1
12.6
12.8
20.7
22.0
6.3
9.8
12.6
Treatment
-30.9
-24.3
43.1
-34.9
-31.0
-30.9
-30.9
-20.9
-39.7
-15.4
-27.0
-32.6
Total
-18.3
-16.5
-18.7
-22.3
-15.9
-18.3
-18.0
0.2
-17.7
-9.1
-17.2
-20.0
Total population (50+ years)
Screening
51.0
27.8
56.8
51.0
61.2
86.6
52.2
85.7
84.0
25.0
46.9
51.0
Treatment
-33.6
-23.3
39.4
-38.9
-33.7
-33.8
-33.6
-19.7
-42.8
-16.8
-29.2
-35.9
Total
17.4
4.5
20.7
12.1
27.4
52.8
18.6
65.9
41.2
8.2
17.6
15.1
Screening, treatment and total costs are presented for the pre-Medicare (50-64 years), Medicare (65+ years) and total (50+ years) population.
14
Table 2.4. Results of the sensitivity analysis for SimCRC. Cumulative cost difference (billions of 2010 US dollars, 3% discounted) of the enhanced participation scenario,
compared to current trends by the year 2060.
Base
case
Focus
on
FOBT
Focus on
colonoscopy
Increased
treatment
costs
Colonoscopy
with
anesthesia
Colonoscopy
privately
insured
FIT
replaces
Sensa
Stool DNA
replaces
Sensa
Modified
societal
perspective
65% upto-date
with
screening
Lower
sensitivity
proximal
lesions
Improved
CRC
survival
Pre-Medicare population (50-64 years)
Screening
38.2
23.0
41.7
38.2
45.7
73.7
39.3
68.1
60.8
19.1
37.4
37.4
Treatment
-10.1
-6.4
-10.9
-11.9
-10.2
-10.4
-10.1
-4.2
-12.6
-5.1
-9.7
-10.1
Total
28.1
23.0
30.8
26.3
35.6
63.3
29.2
63.9
48.2
14.0
27.7
27.3
Medicare population (65+ years)
Screening
11.6
9.3
12.3
11.6
13.9
11.6
11.9
24.1
20.0
5.8
11.2
12.1
Treatment
-44.3
-40.3
41.7
-48.9
-44.4
-44.3
-44.3
-31.7
-57.7
-22.1
-42.6
-44.5
Total
-32.7
-31.0
-32.9
-37.3
-30.5
-32.7
-32.4
-7.6
-37.7
-16.4
-31.5
-32.4
Total population (50+ years)
Screening
49.7
32.3
53.9
49.7
59.6
85.2
51.2
92.2
80.9
24.9
48.6
49.4
Treatment
-54.4
-46.6
30.8
-60.8
-54.5
-54.6
-54.4
-35.9
-70.3
-27.2
-52.3
-54.6
Total
-4.6
-8.0
-2.2
-11.0
5.1
30.6
-3.2
56.3
10.5
-2.3
-3.7
-5.1
Screening, treatment and total costs are presented for the pre-Medicare (50-64 years), Medicare (65+ years) and total (50+ years) population.
15
Appendix 3. Cumulative CRC screening and treatment costs (billions of 2010 US dollars) at ten year intervals in the current trends and
enhanced participation scenarios, in the US population of 50 years and older (undiscounted).
MISCAN ($)
2010
2020
SimCRC ($)
2030
2040
2050
2060
2010
2020
2030
2040
2050
2060
Current trends scenario
Pre-Medicare population (50-64 years)
Screening
5.4
61.0
115.9
169.5
228.7
292.1
4.1
49.4
95.0
141.3
193.1
247.4
Treatment
3.7
41.5
78.5
114.5
154.8
197.8
4.2
47.0
88.1
128.1
172.7
219.9
Total
9.0
102.5
194.4
284.0
383.5
489.9
8.2
96.4
183.1
269.4
365.8
467.3
Medicare population (65+ years)
Screening
3.4
42.8
95.8
158.5
225.0
296.8
2.3
31.4
72.6
122.1
174.2
230.7
Treatment
7.3
86.0
186.5
310.4
446.8
592.4
7.5
87.1
182.5
294.5
414.6
541.9
10.7
Total population (50+ years)
128.9
282.3
468.9
671.8
889.2
9.8
118.5
255.1
416.6
588.9
772.6
Screening
8.8
103.8
211.7
328.0
453.7
588.8
6.4
80.8
167.7
263.5
367.3
478.1
Treatment
11.0
127.5
265.0
424.9
601.7
790.2
11.7
134.1
270.6
422.5
587.4
761.8
Total
19.8
231.4
476.8
752.9
1055.3
1379.1
18.1
214.9
438.2
686.0
954.6
1239.9
Total
Difference between enhanced screening and current trends scenario
Pre-Medicare population (50-64 years)
Screening (A)
1.7
16.4
30.2
43.3
57.6
72.7
1.8
16.1
29.9
42.8
57.1
72.1
Treatment
0.5
0.8
-1.2
-3.2
-5.5
-8.0
0.2
-0.9
-6.3
-11.6
-17.5
-23.9
2.1
Medicare population (65+ years)
17.3
28.9
40.1
52.1
64.6
2.0
15.2
23.5
31.3
39.6
48.3
Screening (B)
0.1
2.0
7.1
14.4
20.9
28.1
0.0
1.2
5.9
12.7
19.5
27.2
Treatment (C)
0.0
-1.5
-11.1
-30.0
-53.7
-79.2
0.0
-1.9
-14.7
-41.5
-76.7
-115.2
Total
0.1
0.5
-4.0
-15.7
-32.8
-51.1
0.0
-0.7
-8.8
-28.8
-57.2
-88.1
Total
16
(continued)
Total population (50+ years)
Screening
1.8
18.5
37.3
57.7
78.6
100.8
1.8
17.3
35.7
55.5
76.6
99.3
Treatment
0.5
-0.6
-12.4
-33.3
-59.3
-87.2
0.2
-2.7
-21.0
-53.1
-94.2
-139.1
Total
2.3
17.8
24.9
24.4
19.3
13.5
2.0
14.5
14.7
2.4
-17.6
-39.8
-
8%
30%
52%
68%
79%
-
11%
41%
75%
100%
116%
% offset (C/(A+B))*
* The proportion of increased screening costs in the pre-Medicare and Medicare populations offset by savings in Medicare treatment costs.
17
Appendix 4. Overview of intermediate model results.
Appendix 4.1. Intermediate model results from MISCAN. Cumulative number (x1,000) of tests performed and life years lived in CRC care, between 2010 and 2060.
FOBTs
Sigmoidoscopies
Colonoscopies
- Screening
- Diagnostic
- Surveillance
Pre-Medicare population (50-64 years)
Enhanced
Current trends
participation
Difference
63,633
128,287
64,654
5,037
4,405
-632
Medicare population (65+ years)
Enhanced
Current trends
participation
Difference
79,477
99,684
20,208
5,431
4,822
-608
244,439
3,983
69,567
301,443
9,291
87,038
57,003
5,309
17,471
247,608
7,819
157,129
243,610
8,497
197,389
-3,998
678
40,260
CRC stage at diagnosis
- Stage I
- Stage II
- Stage III
- Stage IV
31.8%
29.1%
21.8%
17.3%
38.3%
28.2%
19.9%
13.6%
6.5%
-0.8%
-1.9%
-3.7%
29.5%
32.5%
20.3%
17.7%
34.7%
31.6%
18.7%
15.0%
5.2%
-0.9%
-1.6%
-2.7%
Life years in CRC care
- Initial phase
- Continuing phase
- Terminal phase, death CRC
- Terminal phase, death other causes
2,131
16,330
541
172
2,134
17,217
462
178
4
887
-80
6
5,283
78,753
2,003
6,900
4,539
74,867
1,554
6,414
-744
-3,886
-449
-487
Life years in CRC care
- Stage I
- Stage II
- Stage III
- Stage IV
7,224
6,498
4,511
941
8,316
6,508
4,370
797
1,092
10
-141
-144
38,050
33,085
18,738
3,066
39,516
29,402
16,114
2,341
1,466
-3,682
-2,624
-725
18
Appendix 4.2. Intermediate model results from SimCRC. Cumulative number (x1,000) of tests performed and life years lived in CRC care, between 2010 and 2060.
FOBTs
Sigmoidoscopies
colonoscopies
- Screening
- Diagnostic
- Surveillance
Pre-Medicare population (50-64 years)
Enhanced
Current trends
participation
Difference
92,897
173,317
80,421
18,953
16,647
-2,307
Medicare population (65+ years)
Enhanced
Current trends
participation
Difference
103,562
131,166
27,604
20,124
18,066
-2,058
205,090
4,698
53,970
263,676
10,656
67,236
58,586
5,958
13,266
151,251
9,079
155,157
157,001
9,698
184,671
5,749
619
29,513
CRC stage at diagnosis
- Stage I
- Stage II
- Stage III
- Stage IV
32.3%
31.6%
18.8%
17.4%
39.0%
29.9%
16.7%
14.5%
6.7%
-1.7%
-2.1%
-2.9%
28.0%
32.0%
20.2%
19.8%
32.7%
31.0%
18.8%
17.5%
4.7%
-0.9%
-1.5%
-2.3%
Life years in CRC care
- Initial phase
- Continuing phase
- Terminal phase, death CRC
- Terminal phase, death other causes
2,206
20,198
639
206
1,988
20,228
524
200
-218
30
-115
-6
4,556
75,781
1,811
6,502
3,416
66,397
1,289
5,613
-1,140
-9,384
-522
-888
Life years in CRC care
- Stage I
- Stage II
- Stage III
- Stage IV
9,492
8,533
4,155
1,068
10,282
8,027
3,748
883
789
-506
-407
-185
36,990
32,832
15,902
2,926
35,219
26,916
12,480
2,100
-1,771
-5,916
-3,422
-825
19
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