Title: Decision Analysis of Colorectal Cancer Screening Tests by Age to Begin, Age to End, and Screening In
1Decision Analysis of Colorectal Cancer Screening
Tests by Age to Begin, Age to End, and Screening
IntervalsReport to the United States
Preventive Services Task Force from the Cancer
Intervention and Surveillance Modeling Network
(CISNET)Agency for Healthcare Quality and
ResearchSeptember 8, 2008
- MISCAN
- Memorial Sloan-Kettering Cancer Center -Ann
Zauber - Erasmus MC - Marjolein van Ballegooijen, Iris
Lansdorp-Vogelaar, Janneke Wilschut
SimCRC University of Minnesota Karen Kuntz
Massachusetts General Hospital Amy Knudsen
2What CMS reimbursement for a new CRC test?
2003 and 2007
4.54
22.22
Stool DNA test?
to be determined
National Coverage Determination (NCD) on stool
DNA (PreGen-Plus test, version 1.1 every 5 years
for average risk population)
3Questions addressed by CISNET for USPSTF 2007
- USPSTF addresses updates for 2002 colorectal
cancer screening recommendations - Evidence based literature review
- Task Force requested a decision analysis for
recommended CRC screening tests for - age to begin
- age to end
- rescreening interval
- Should the current recommendations be changed?
- Microsimulation models (MISCAN and SimCRC) of
CISNET consortium used for the decision analysis
to inform health policy
4Adenoma to Carcinoma Pathway
Normal Epithelium
Small Adenoma
Colorectal Cancer
Advanced Adenoma
5Microsimulation Modeling of Adenoma Carcinoma
Sequence with Potential Interventions
ADENOMA Preclinical screen-detectable adenoma
phase
Preclinical CANCER screen-detectable cancer phase
Clinical CANCER phase
clinical stage I clinical stage
II clinical stage III clinical stage IV
adenoma lt5 mm
death colorectal cancer
No lesion
adenoma 6-9 mm adenoma gt10 mm
Adenoma Autopsy studies Colonoscopy studies
Preclinical Cancer Dwell time
Clinical Cancer SEER Incidence
Death US Mortality
Datasources
6Colorectal Cancer Screening StrategiesCurrent
Age and Interval Recommendations
Screening Tests
Rescreening Intervals
Age Begin
Age End
Hemoccult II Hemoccult SENSA FIT Flex Sig Flex
Sig SENSA Colonoscopy
50
1 FOBT 5 Flex Sig 10 - Colonoscopy
None
Surveillance
No stop age
MultiSociety and ACS
7Colorectal Cancer Screening StrategiesCohort of
40 year olds in 2005
145 Test Strategies
Screening Tests
Rescreening Intervals
Age Begin
Age End
Hemoccult II Hemoccult SENSA FIT Flex Sig Flex
Sig SENSA Colonoscopy (No Screening)
40 50 60
1,2,3 FOBT 5,10,20- Endos
75 85
Surveillance
No stop age
Adherence 100
With biopsy
3 year for advanced adenomas, 5-10 (5) for
non-advanced adenomas
8Sensitivity and Specificity of Testsfrom
Literature Review
CRC Sensitivity
Specificity
Hemoccult II
Hemoccult SENSA
FIT
Percent
Sigmoidoscopy
Sig Hemoccult SENSA
Colonoscopy
Adenoma Sensitivity by Size
gt10mm
6-9mm
lt5mm
Percent
Sigmoidoscopy sensitivity for lesions within range
9Screening Test Costs per Test
4.54
4.54
22.22
161
498
649
USPSTF requested NOT to use costs
10Outcome Measures
- Most effective Greatest life years gained
relative to no screening - Weigh effectiveness against
resources required and exposure
to risks Colonoscopy as resource and risk
indicator - Endoscopy resources
- Perforation risk
- Life years gained (LYG) vs
Total colonoscopies in
lifetime - (per 1000 persons in population)
- .
11Effectiveness-Risk Analysis
- Determine efficient strategies for each test
- Plot life years gained versus colonoscopies
required - If strategy requires more colonoscopies but has
fewer life years gained (LYG) (ie less effective)
then eliminate - Of the remaining strategies, rank by increasing
effectiveness (LYG) Derive relative to each
other - Incremental number of colonoscopies ?Col
- Incremental LYG ?LYG
- Incremental number colonoscopies to gain a life
yr ?Col/ ?LYG - Efficiency Ratio of measure of the additional
number of colonoscopies required to gain one year
of benefit when considering a more effective
strategy relative to the next less effective
strategy - Efficiency frontier all strategies NOT
dominated (eliminated) - Near the efficiency frontier those strategies
that are with 98 of the LYG on the frontier
12Colonoscopy-MISCAN
13Colonoscopy-SimCRC
14Efficient Colonoscopy Strategies
15Age to End Screening
- No prior recommendations on stop age for CRC
screening - Age 75 and 85 considered
- Comorbidity and life expectancy rather than
chronological age important - Example for colonoscopy
If start screening at age
50 and stop at age 75 - Negative colonoscopy at age 50, 60, and 70
- 3 negative exams before stopping
- Those with adenomas or colorectal cancer detected
at screening colonoscopy would be in a
surveillance program with no stopping age
16Hemoccult II-MISCAN
17Hemoccult SENSA-MISCAN
18FIT-MISCAN
19Flexible Sigmoidoscopy-MISCAN
20Combination-MISCAN
21Comparisons Among Testswithout comparator of
costs
- To compare among tests, it is important to
consider that tests other than colonoscopy are
required (ie, FOBT, Flex Sig) - To pick an efficient strategy for each test we
would expect to find an ordering to the
efficiency ratios as follows - COL gt SENSA gt FIT, HII gt FSig, FSigSENSA
- Eg, SENSA should require fewer colonoscopies to
gain a benefit of 1 year compared with COL
because of the added number of FOBTs needed in
addition to the colonoscopies to achieve that
benefit.
22Approach to ChoosingEfficient Strategies
- Assume that a single start and end age would be
recommended for screening - Select strategies from all tests (including
combination of tests) that - are efficient (or near efficient) within the test
- have efficiency ratios with expected ordering (to
account for the burden of other testing) - have comparable effectiveness (LYG)
- Example start age 50 stop age 75 anchored
with 10-year colonoscopy (as a starting strategy)
23Efficient (near efficient) strategies for start
age 50 and stop age 75-(Table 9 bolded strategies)
24Sensitivity Analysis
- Comparative modeling (2 models) give similar
results - Similar rankings of strategies even if assume
better or worse estimates on sensitivity and
specificity - Adherence varied from 100, 80, 50
25MISCAN Adherence Plot
26CONCLUSIONS
- Current recommended guidelines are on or close
to the efficiency frontier - Beginning at age 50 balances life years gained
and number of colonoscopies required and
associated risk of perforation - To increase efficiency of current guidelines,
stop screening at age 75 - should depend on life expectancy of person rather
than strict chronological age
MultiSociety and ACS
27CONCLUSIONS (Continued 1)
- Annual SENSA or FIT have similar LYG as
colonoscopy every 10 years but with lower
colonoscopy requirements PROVIDED high
compliance for all tests - FlexSig every 5 years with annual FOBT with
Sensitive FOBT not recommended (high efficiency
ratio) - Original strategy for Flex Sig FOBT was for
Hemoccult II with lower sensitivity - Combination of Flex Sig and Hemoccult SENSA
could have one mid-interval FOBT between the 5
year repeat Flex Sig screening rather than annual
FOBT - FlexSig every 5 years and Hemoccult II not as
good in terms of effectiveness
28CONCLUSIONS for Adherence
- Adherence conclusions
- Life years gained and colonoscopies decreased
with decreased adherence BUT - The overall conclusions did not change
substantially as adherence varied from 50 to
100. - Hemoccult II and flexible sigmoidoscopy every 5
years remained the least two attractive
alternatives re life years gained - Colonoscopy every 10 years improved a bit
relative to the other strategies when adherence
was 80 but lost its health benefit advantage
when adherence as 50
29Limitations
- Analyses for whole population not specific by
sex or race - Potential of more proximal disease in older women
and blacks - Age of onset may vary by sex and race
- Inadequate data on adenoma prevalence age 40
- Chronological age rather than life expectancy
- Life expectancy of men 10.5 at age 75 and 5.9
at 85 - Life expectancy of women 12.5 at age 75 and 7.0
at 85 - Simulation models rely on assumptions of natural
history of disease - Comparing two models provides sensitivity
analysis of natural history assumptions
30Best Test is the One Which Gets Done- SJ
Winawer re Adherence
31(No Transcript)
32Thank You
Acknowledgements
Mary Barton, William Lawrence of AHRQ Diana
Pettit, Michael LeFevre, George Isham, and Steve
Teutsch of USPSTF
33 34Screening and Treatment Costs by Screening
Strategy
Per 1000 screened
No Screening
Hemoccult II
Hemoccult SENSA
FIT
Sigmoidoscopy
Sig Hemoccult SENSA
Colonoscopy
35Components of Screening Costs (per 1000
screened) (CMS analysis age 65)
Screening Test
Polyp Resection and Pathology
Follow-up of Positive Test
Surveillance
Complications
Hemoccult II
Hemoccult SENSA
FIT
Sigmoidoscopy
Sig Hemoccult SENSA
Colonoscopy
36Model Calibrations
- Process of matching model output with data
- Useful when data arent available to estimate
certain model parameters but are available on
model outcomes - Compare model output with empirical data
- Prevalence and number of adenomas
- (autopsy studies)
- Location and size of lesions
- (colonoscopy studies)
- Incidence, location, and stage of diagnosed CRC
- (SEER)
37SENSA, 50-75,1 Specificity of 92.5 (base
case) vs 87 (ER) Colonoscopy 50-75,10 given as
comparator
38Efficient Strategiesfor start age of 50 and stop
age of 75(Table 9 Page 31)
39Efficient Strategiesfor start age of 50 and stop
age of 75Rank order of strategies
40Comparisons
- First compare strategies within a screening test
- Efficient frontier derived for each screening
test or combination test - DCol/DLYG Efficiency Ratio
- A measure of the additional number of
colonoscopies required to gain one year of
benefit when considering a more effective
strategy relative to the next less effective
strategy - Colonoscopy resources across tests are comparable
but burden of all testing is not