Decision Analysis of Colorectal Cancer Screening Tests by Age to Begin, Age to End, and Screening In

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Decision 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
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What 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)
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Questions 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

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Adenoma to Carcinoma Pathway
Normal Epithelium
Small Adenoma
Colorectal Cancer
Advanced Adenoma
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Microsimulation 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
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Colorectal 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
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Colorectal 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
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Sensitivity 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
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Screening Test Costs per Test
4.54
4.54
22.22
161
498
649
USPSTF requested NOT to use costs
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Outcome 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)
• .

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Effectiveness-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

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Colonoscopy-MISCAN

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Colonoscopy-SimCRC
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Efficient Colonoscopy Strategies
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Age 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

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Hemoccult II-MISCAN
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Hemoccult SENSA-MISCAN
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FIT-MISCAN
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Flexible Sigmoidoscopy-MISCAN
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Combination-MISCAN
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Comparisons 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.

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Approach 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)

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Efficient (near efficient) strategies for start
age 50 and stop age 75-(Table 9 bolded strategies)
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Sensitivity 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

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MISCAN Adherence Plot
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CONCLUSIONS

• 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
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CONCLUSIONS (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

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CONCLUSIONS 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

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Limitations

• 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

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Best Test is the One Which Gets Done- SJ
Winawer re Adherence
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(No Transcript)
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Thank You
Acknowledgements
Mary Barton, William Lawrence of AHRQ Diana
Pettit, Michael LeFevre, George Isham, and Steve
Teutsch of USPSTF
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Screening and Treatment Costs by Screening
Strategy
Per 1000 screened
No Screening
Hemoccult II
Hemoccult SENSA
FIT
Sigmoidoscopy
Sig Hemoccult SENSA
Colonoscopy
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Components 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
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Model 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)

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SENSA, 50-75,1 Specificity of 92.5 (base
case) vs 87 (ER) Colonoscopy 50-75,10 given as
comparator
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Efficient Strategiesfor start age of 50 and stop
age of 75(Table 9 Page 31)
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Efficient Strategiesfor start age of 50 and stop
age of 75Rank order of strategies
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Comparisons

• 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