Decision Analysis of Colorectal Cancer Screening Tests by Age to Begin, Age to End, and Screening Intervals: Report to the United States Preventive Services Task Force from th

Slide Presentation from the AHRQ 2008 Annual Conference

On September 8, 2008, Ann Zauber, Marjolein van Ballegooijen, Iris Lansdorp-Vogelaar, Janneke Wilschut, Karen Kuntz, Amy Knudsen, made this presentation at the 2008 Annual Conference. Select to access the PowerPoint® presentation (2.7 MB).

Slide 1

Decision Analysis of Colorectal Cancer Screening Tests by Age to Begin, Age to End, and Screening Intervals: Report to the United States Preventive Services Task Force from the Cancer Intervention and Surveillance Modeling Network (CISNET)

Agency for Healthcare Quality and Research-September 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

Slide 2

What Centers for Medicare & Medicaid Services (CMS) reimbursement for a new Colorectal Cancer (CRC) test? 2003 and 2007

There are two, separate images of "Stool DNA" tests separated by a black line running down the center. One test retails for $4.54 and the other for $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).

Slide 3

Questions addressed by CISNET for the U.S. Preventive Services Task Force (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.

Slide 4

Adenoma to Carcinoma Pathway

The slide shows three colored photographs presenting the sequence of colorectal cancer.

• First photograph shows normal epithelium.
• Second photograph shows a small adenoma/advanced adenoma.
• Third photograph shows colorectal cancer.

Slide 5

Microsimulation Modeling of Adenoma Carcinoma Sequence with Potential Interventions

The diagram shows the Adenoma Carcinoma sequence.

• No lesion.
• Adenoma: Preclinical screen-detectable adenoma phase.
  • Adenoma ≤5 mm
  • Adenoma 6-9 mm
  • Adenoma ≥10 mm
    • Datasources: Adenoma: Autopsy studies; Colonoscopy studies.
• Preclinical Cancer: Screen-detectable cancer phase.
  • Preclinical stage I
  • Preclinical stage II
  • Preclinical stage III
  • Preclinical stage IV
    • Datasources: Preclinical Cancer: Dwell time.
• Clinical Cancer Phase
  • Clinical stage I
  • Clinical stage II
  • Clinical stage III
  • Clinical stage IV
    • Datasources: Clinical Cancer: Surveillance, Epidemiology, and End Results (SEER). Incidence.
• Death Colorectal Cancer
  • Data sources: Death: U.S. Mortality.

Slide 6

Colorectal Cancer Screening Strategies Current Age and Interval Recommendations*

• Screening Tests:
  • Hemoccult II
  • Hemoccult SENSA
  • FIT
  • Flex Sig
  • Flex Sig + SENSA
  • Colonoscopy
• Age Begin: 50
• Rescreening Intervals:
  • 1—fecal occult blood testing (FOBT)
  • 5—Flex Sig
  • 10—Colonoscopy
• Age End:
  • None
• Surveillance:
  • No stop age
• Note: *MultiSociety and American Cancer Society (ACS)

Slide 7

Colorectal Cancer Screening Strategies Cohort of 40 year olds in 2005

• 145 Test Strategies.
• Screening Tests:
  • Hemoccult II
  • Hemoccult SENSA.
  • FIT
  • Flex Sig*
  • Flex Sig* + SENSA.
  • Colonoscopy.
  • (No Screening).
• Age Begin:
  • 40
  • 50
  • 60
• Rescreening Intervals:
  • 1, 2, 3—FOBT.
  • 5, 10, 20—Endos.
• Age End
  • 75
  • 85
• Surveillance**
  • No stop age
• Adherence 100% throughout.
• Note: * With biopsy.
• Note: **3 year for advanced adenomas 5-10 (5) for non-advanced adenomas.

Slide 8

Sensitivity and Specificity of Tests from Literature Review

The slide shows three separate bar graphs measuring CRC Sensitivity, Specificity, and Adenoma Sensitivity by Size for Hemoccult II, Hemoccult SENSA, FIT, Sigmoidoscopy, and Colonoscopy.

• CRC Sensitivity:
  • HII: 40%
  • HS: 70%
  • FIT: 70%
  • SIG: 95%
  • COL: 95%
• Specificity:
  • HII: 99%
  • HS: 92%
  • FIT: 95%
  • SIG: 92%
  • COL: 90%
• Adenoma Sensitivity by Size:
  • Greater than or equal to 10 mm
    • HII: 12%
    • HS: 25%
    • FIT: 21%
    • SIG: 95%
    • COL: 95%
  • 6-9 mm:
    • HII: 5%
    • HS: 12%
    • FIT: 11%
    • SIG: 85%
    • COL: 85%
  • Less than or equal to 5 mm:
    • HII: 3%
    • HS: 9%
    • FIT: 5%
    • SIG: 75%
    • COL: 75%

Slide 9

Screening Test Costs $ per Test

The bar graph measures the cost per test.

• Hemoccult II: $4.54
• Hemoccult SENSA: $4.54
• FIT: $22.22
• Sigmoidoscopy: $161.00
• Colonoscopy: $498.00
• Colonoscopy/Polyps: $649.00

Slide 10

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).

• Note: There is an image of a scale.

Slide 11

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 = ΔCol.
  • Incremental LYG = ΔLYG.
  • Incremental number colonoscopies to gain a life yr = ΔCol/ΔLYG.
    • 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.

Slide 12

Colonoscopy-MISCAN

• The line graph shows placement of Colonoscopy Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 9,000.
• Arrows point out colonoscopy strategies at 2,200 colonoscopies, 160 life-years (60-75.20); at 3,300 colonoscopies, 200 life-years (50-75.20); at 4,100 colonoscopies, 230 life-years (50-75.10); and highlighted, at 4,600 colonoscopies, 240 life-years (50-85.10).

Slide 13

Colonoscopy-SimCRC

• The line graph shows placement of Colonoscopy Strategies and Start Age 40, while measuring the Frontier and Frontier 40. The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 350 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 9,000.
• Arrows point out colonoscopy strategies at 1,800 colonoscopies, 160 life-years (60-75.20); at 2,900 colonoscopies, 250 life-years (50-75.20); at 3,800, 270 life-years (50-75.10); and highlighted, at 4,100 colonoscopies, 270 life-years (50-85.10).

Slide 14

Efficient Colonoscopy Strategies

The table shows the results for Number Col (per 1000); Number LYG (per 1000); ΔCol (per 1000); ΔLYG (per 1000); and ΔCol/ΔLYG for six MISCAN Strategies and six SimCRC Strategies.

• Note: * Test, begin age—end age, interval.
  ΔCol = incremental number of colonoscopies compared with the next best strategy.
  ΔLYG = incremental number of life years gained compared with the next best strategy.

Slide 15

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.

Slide 16

Hemoccult II-MISCAN

• The line graph shows placement of Hem II Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 3,000.
• Arrows point out Hem II strategies at 700 colonoscopies, 90 life-years (60-75.3); at 1,100 colonoscopies, 120 life-years (50-75.3); at 1,900 colonoscopies, 190 life-years (50-75.1); and highlighted, at 2,200 colonoscopies, 200 life-years (50-85.1).

Slide 17

Hemoccult SENSA-MISCAN

• The line graph shows placement of Sensa® Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 5,000.
• Arrows point out Sensa® strategies at 1,400 colonoscopies, 140 life-years (60-75.3); at 2,200 colonoscopies, 180 life-years (50-75.3); at 3,400 colonoscopies, 230 life-years (50-75.1); and highlighted, at 3,600 colonoscopies, 240 life-years (50-85.1).

Slide 18

FIT-MISCAN

• The line graph shows placement of FIT Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 4,500.
• Arrows point out FIT strategies at 1,200 colonoscopies, 130 life-years (60-75.3); at 1,800 colonoscopies, 170 life-years (50-75.3); at 2,900 colonoscopies, 230 life-years (50-75.1); and highlighted, at 3,200 colonoscopies, 240 life-years (50-85.1).

Slide 19

Flexible Sigmoidoscopy-MISCAN

• The line graph shows placement of Flexible Sigmoidoscopy Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 2,500.
• Arrows point out Flexible Sigmoidoscopy strategies at 1,100 colonoscopies, 110 life-years (60-75.20); at 1,500 colonoscopies, 160 life-years (60-75.5); at 1,800 colonoscopies, 200 life-years (50-75.5); and highlighted, at 2,000 colonoscopies, 210 life-years (50-85.5).

Slide 20

Combination-MISCAN

• The line graph shows placement of FSig plus Sensa® Strategies and Start Age 40, while measuring the Frontier and Frontier 40.The vertical axis, Life-Years Gained per 1,000 Persons, goes from 0 to 300 and the horizontal axis, Colonoscopies per 1,000 Persons, goes from 0 to 6,000.
• Arrows point out FSig plus Sensa® strategies at 1,900 colonoscopies, 160 life-years (60-75,20,3); at 2,800 colonoscopies, 220 life-years (50-75,5,3); and highlighted at 3,600 colonoscopies, 240 life-years (50-85,5,1).

Slide 21

Comparisons Among Tests without 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 > SENSA > [FIT, HII] > [FSig, FSig+SENSA]
  • E.g., 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.

Slide 22

Approach to Choosing Efficient Strategies

• Assume that a single start and end age would be recommended for screening.
• Select strategies from all tests (including combination of tests) that:
  1. Are efficient (or near efficient) within the test.
  2. Have efficiency ratios with expected ordering (to account for the burden of other testing).
  3. Have comparable effectiveness (LYG).
• Example: start age = 50; stop age = 75; anchored with 10-year colonoscopy (as a starting strategy).

Slide 23

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

The table shows the results for Number Col (per 1000); Number LYG (per 1000); ΔCol/ΔLYG; Number FOBT; and Number Fsig for six MISCAN Strategies and six SimCRC Strategies.

Slide 24

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%.

Slide 25

MISCAN Adherence Plot

The line graph presents COL, SENSA, FIT, Hem II, FSIG, and FSIG-SENSA and marks their Adherence at 50%, Adherence at 80%, and Adherence at 100%. The vertical axis, Life-Years Gained per 1,000 Screened, goes from 0 to 250 and the horizontal axis, Colonoscopies per 1,000 Screened, goes from 0 to 5000. The range for all begins between 1000-2000 colonoscopies, 120-140 life-years and ends between 1800-4200 colonoscopies, 200-230 life-years.

Slide 26

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.
• Note: *MultiSociety and ACS.

Slide 27

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.

Slide 28

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%.

Slide 29

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.

Slide 30

'Best' Test is the One Which Gets Done-SJ Winawer re Adherence

There are two, separate images of "Stool DNA" tests separated by a black line running down the center, and a third image of surgical equipment for a colonoscopy placed slightly lower and centered between the two.

Slide 31

The black and white cartoon shows St. Peter at the pearly gates sitting behind a desk with a book of names and a line of people. The elderly gentleman speaking to St. Peter tells him, "I'd have been here sooner if it hadn't been for early detection."

Slide 32

Thank You

Acknowledgements

• Mary Barton, William Lawrence of AHRQ.
• Diana Pettit, Michael LeFevre, George Isham, and Steve Teutsch of USPSTF.

Slide 33

Blank Slide

Slide 34

Screening and Treatment Costs by Screening Strategy

The bar graph measures both treatment and non treatment for Hemoccult II, Hemoccult SENSA, FIT, Sigmoidoscopy, SIG plus Hemoccult SENSA, and Colonoscopy.

• No Screening: 4,000,000
• Hemoccult II:
  • Non treatment: 700,000
  • Treatment: 2,900,000
• Hemoccult SENSA:
  • Non treatment: 1,200,000
  • Treatment: 2,500,000
• FIT:
  • Non treatment: 1,200,000
  • Treatment: 2,600,000
• Sigmoidoscopy:
  • Non treatment: 1,400,000
  • Treatment: 2,400,000
• Sig plus Hemoccult SENSA:
  • Non treatment: 1,700,000
  • Treatment: 2,200,000
• Colonoscopy:
  • Non treatment: 1,600,000
  • Treatment: 2,200,000

Slide 35

Components of Screening Costs (per 1000 screened) (CMS analysis age 65+)

The slide shows five separate bar graphs measuring the costs of Screening Tests; Polyp Resection and Pathology; Follow-Up of Positive Tests; Surveillance; and Complications.

• Screening Test:
  • No Screening: $0
  • HII: $50,000
  • HS: $30,000
  • FIT: $180,000
  • SIG: $380,000
  • Sig plus HS: $270,000
  • COL: $780,000
• Polyp Resection and Pathology:
  • No Screening: $0
  • HII: $90,000
  • HS: $120,000
  • FIT: $110,000
  • SIG: $120,000
  • Sig plus HS: $150,000
  • COL: $160,000
• Follow-up of Positive Test:
  • No Screening: $0
  • HII: $200,000
  • HS: $380,000
  • FIT: $310,000
  • SIG: $280,000
  • Sig plus HS: $410,000
  • COL: $0
• Surveillance:
  • No Screening: $0
  • HII: 410,000
  • HS: $700,000
  • FIT: $610,000
  • SIG: $630,000
  • Sig plus HS: $850,000
  • COL: $680,000
• Complications $0
  • No Screening: $0
  • HII: $15,000
  • HS: $20,000
  • FIT: $20,000
  • SIG: $20,000
  • Sig plus HS: $30,000
  • COL: $40,000

Slide 36

Model Calibrations

• Process of matching model output with data.
• Useful when data aren't available to estimate certain model parameters but are available on model outcomes.
• Compare model output with empirical data.
  1. Prevalence and number of adenomas (autopsy studies).
  2. Location and size of lesions (colonoscopy studies).
  3. Incidence, location, and stage of diagnosed CRC (SEER).

Slide 37

SENSA®, 50-75,1: Specificity of 92.5% (base case) vs 87% (ER), Colonoscopy 50-75,10 given as comparator

The table shows the results for Number Col (per 1000) and Number LYG (per 1000) for three MISCAN Strategies and three SimCRC Strategies.

Slide 38

Efficient Strategies for start age of 50 and stop age of 75 (Table 9 Page 31)

The table shows the results for Number Col (per 1000); Number LYG (per 1000); ΔCol/ΔLYG; Number FOBT; and Number Fsig for six MISCAN Strategies and six SimCRC Strategies.

• Note: * Test, begin age—end age, interval.
  ΔCol = incremental number of colonoscopies compared with the next best strategy.
  ΔLYG = incremental number of life years gained compared with the next best strategy.

Slide 39

Efficient Strategies for start age of 50 and stop age of 75: Rank order of strategies

The table shows the results for Number Col (per 1000); Number LYG (per 1000); and ΔCol/ΔLYG for six MISCAN Strategies and six SimCRC Strategies.

• Note: * Test, begin age—end age, interval.
  ΔCol = incremental number of colonoscopies compared with the next best strategy.
  ΔLYG = incremental number of life years gained compared with the next best strategy.

Slide 40

Comparisons

• First compare strategies within a screening test.
• Efficient frontier derived for each screening test or combination test.
• ΔCol/ΔLYG—'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.