1. The Importance of Stool Occult Blood Tests in Getting to 80% Durado Brooks, MD, MPH Director, Cancer Control Interventions American Cancer Society, Inc. 1

2. Getting to 80% Colonoscopy is essential but not sufficient to reach our goal. Access barriers for many Not all patients are willing Must use other evidence-based screening tests more effectively for average risk patients

3. Types of Stool Occult Blood Tests

4. Types of Stool Tests A) Tests that detect aberrant DNA – One test (Cologuard) available in U.S. – Very limited use at present B) Tests that detect blood (Fecal Occult Blood Tests – “FOBT”) – Two types (but multiple brands and variable performance) Guaiac-based FOBT Immunochemical (FIT)

5. Guaiac Tests  Most common type in U.S.  Solid evidence (3 RCT’s)  30 year f/u (NEJM Oct 2013)  Need specimens from 3 bowel movements  Non-specific  Results influenced by foods and medications  Better sensitivity with newer versions (Hemoccult Sensa)  Older forms (Hemoccult II) not recommended!

6. Fecal Immunochemical Tests (FIT)  Specific for human blood and for lower GI bleeding  Results not influenced by foods or medications  Some types require only 1 or 2 stool specimens  Higher sensitivity than older forms of guaiac-based FOBT  Costs more than guaiac tests (but higher reimbursement)

7. FOBT: Variation Among Brands FDA currently clears guaiac FOBTs and FITs only for “detection of blood” – no assessment of cancer detection capability required Approval is obtained through determination of “substantial equivalence” – and comparator for most new tests is old, low sensitivity guaiac FOBT Most newer FITs have no published data regarding their performance for CRC or adenoma detection Limited data on performance of single vs multiple sample analysis for some tests that are currently marketed as “single sample” tests FDA is updating criteria

8. Highly Sensitive Guaiac FOBTs With Published Data - Available in the US NameManufacturer Hemoccult II SensaBeckman-Coulter

9. FITs With Published Data* - Available in the US NameManufacturer InSureEnterix, Quest Company Hemoccult-ICTBeckman-Coulter OC Fit-ChekPolymedco OC Auto MicroPolymedco Hemosure One StepWHPM, Inc. Magstream Hem SpFujirebio, Inc. *This list may not be comprehensive

10. Fecal Occult Blood Testing Remains Important in the “Age of Colonoscopy” Colonoscopy is the most frequently used screening test for CRC (by a wide margin). However: – FIT and high sensitivity guaiac tests perform well for cancer detection. – When provided annually to average-risk patients with appropriate follow-up, stool occult blood testing with high-sensitivity tests can provide similar reductions in incidence and mortality compared to colonoscopy.

11. Efficacy and Accuracy

12. Colorectal Diisease, 2012

13. NEJM 2014

14. Fecal Occult Blood Tests: Accuracy Lee, JK et. al. Annals IM 2014

15. Meta-analysis of FIT and Hemoccult Sensa Conclusion: Both have high sensitivity for cancer detection. FITHemoccult Sensa Sensitivity:73-89%64-80% Specificity:92-95%87-90% Lee, JK et. al. Ann Intern Med. 2014 160 (3): 171

16. Colonoscopy every 10 years and FIT/FOBT annually prevent the same number of colon cancer deaths Zauber et. al. Ann Intern Med. 2008

17. Advantages of Stool Blood Testing Stool blood testing – Is less expensive. – Can be offered by any member of the health team. – Requires no bowel preparation. – Can be done in privacy at home. – Does not require time off work or assistance getting home after the procedure. – Is non-invasive and has no risk of causing pain, bleeding, bowel perforation, or other adverse outcomes. – Colonoscopy is required only if stool blood testing is abnormal.

18. FIT testing (2,000 patients) Making the Best Use of Scarce Resources: Screening colonoscopy vs. FIT Eligible population Patients with a positive FIT Screening colonoscopy (refer 1,000 patients) Eligible population, referred Patient refusal, no shows 1 cancer in 400- 1000 colonoscopies Represents 20 patients 1 cancer in 20 colonoscopies Slide courtesy of Dr. G.Coronado

19. PCPs and FOBT/FIT FOBT/FIT widely used, but: – Effectiveness questioned by many clinicians – Advantageous features often not considered – Lack of knowledge re: performance of new vs. older forms of stool tests, other quality issues Colonoscopy viewed as the best screening test, but many patients face barriers or not willing – Often recommended despite access or other challenges – Focus on colonoscopy associated with low screening rates in a number of studies – Patient preferences rarely solicited

20. Patient Preferences

21. Market Research on Unscreened Activating Messages that Motivate Colon cancer is the second leading cause of cancer deaths in the U.S., when men and women are combined, yet it can be prevented or detected at an early stage. There are several screening options available, including simple take home options. Talk to your doctor about getting screened. Preventing colon cancer, or finding it early, doesn’t have to be expensive. There are simple, affordable tests available. Get screened! Call your doctor today.

22. Many Patients Prefer Stool Testing Randomized clinical trial in which 997 ethnically diverse patients in San Francisco community health centers received different recommendations for screening. Inadomi, Arch Intern Med 2012

23. Many Patients Home Stool Testing 323 adults given detailed side-by-side description of FOBT and colonoscopy* 53% preferred FOBT. Almost half felt very strongly about their preference. 212 patients at four health centers in Texas rated different screening options with different attributes** 37% preferred colonoscopy. 31% preferred FOBT. *Community-based Preferences for Stool Cards versus Colonoscopy in Colorectal Cancer ScreeningCommunity-based Preferences for Stool Cards versus Colonoscopy in Colorectal Cancer Screening **Preferences for colorectal cancer screening among racially/ethnically diverse primary care patientsPreferences for colorectal cancer screening among racially/ethnically diverse primary care patients

24. Quality

25. Remember: Stool Collection Should Be Done AT HOME! Stool collected on rectal exam may not be sufficient or sufficiently representative of stool collected from a complete bowel movement. There is no evidence that any type of stool blood testing is sufficiently sensitive when used on a stool sample collected during a rectal exam. Largest study of samples from rectal exam missed 19 of 21 cancers found at colonoscopy!

26. Remember: Stool Collection Should Be Done AT HOME! Therefore, specimen collection for high sensitivity guaiac FOBT and FIT should be completed by the patient at home, and NOT as an in-office test.

27. UDS Measure 2014 CRC Screening Performance Measure “…Stool specimens for FOBT, including FIT, should be collected by patients at home, as recommended by the manufacturer. An in-office obtained stool specimen does not meet the measurement standard, nor does it comply with manufacturers’ recommendations or national screening guidelines ….”

28. Must increase use of high quality stool testing for those at Average Risk But to be effective must have: – Screening with FIT or highly sensitive guaiac – High compliance – Annual testing – Colonoscopy follow up of every positive stool test

29. High Quality Stool Testing Clinicians Reference: FOBT One page document designed to educate clinicians about important elements of colorectal cancer screening using fecal occult blood tests (FOBT). Provides state-of-the-science information about guaiac and immunochemical FOBT, test performance and characteristics of high quality screening programs.

30. Evidence Based Interventions

31. Standing Orders Promotes team engagement in CRC screening Empowering nursing staff or medical assistants to discuss screening options, provide FOBT/FIT kits and instructions, and submit referrals for screening colonoscopy has been demonstrated to increase CRC screening rates Staff training on risk assessment, components of the screening discussion, … is essential for a successful program. Rules vary – check your state medical practice regulations J Am Board Fam Med 2009

32. Standing Orders San Francisco Health Plan

33. Reminders Patient and provider reminders help ensure screening is offered; Educating patients on importance and personal relevance of CRC screening increases return rates; Provide patients with clear instructions on how to complete and return the FIT/FOBT kit (verbal and written instructions); Reminders* (phone call/postcard/email/text) are imperative if kit not returned within 10-14 days; *Studies show that reminders can double return rates!

34. Reminders Develop systems to support follow up for all patients who received FIT/FOBT kits Defined path to needed follow up care (all patients with a positive stool test must have colonoscopy!) Track test completion, reports, appropriate follow up for positives using: EMR “Tickler” System Logs and Tracking Endoscopy reports and pathology reports are critical! Ideal role for navigators/community health workers

35. Mailed Outreach Mailed invitations to CRC screening to patients from safety net hospital clinic who were not up to date with screening o Group 1 – mailed no-cost FIT kit o Group 2 – mailed invitation to no-cost colonoscopy o Group 3 – usual care, opportunistic PCP visit–based screening FIT and colonoscopy outreach groups received telephone follow-up to promote test completion. Gupta et al, JAMA IM 2013

36. Mailed Outreach Gupta et al, JAMA IM 2013

37. Mailed Outreach Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) Randomized controlled trial involving 26 FQHCs in Oregon and N. California. (PI – Dr. G. Coronado) Intervention arm o Automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening o Mailed FIT kits o Improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program Control arm o Opportunistic colorectal-cancer screening to patients at clinic visits

38. FluFIT Annual flu shot visits are an opportunity to reach many people who also need CRC screening Health center staff recommend CRC screening and provide FOBT kits to eligible patients when they get their annual flu shot FluFIT programs are well accepted by patients Studies show FluFOBT leads to higher CRC screening rates (including studies in community health centers)

39. Stool DNA Test  Polyps and cancer cells contain abnormal DNA  Stool DNA tests look for abnormal DNA in colon cells that are passed in the stool  Colon cells are shed continuously (whereas FOBT/FIT rely on bleeding, which is often intermittent)

40. NEJM 2014

42. Stool DNA Test One test (Cologuard) currently available Combines an FIT with tests for stool DNA markers associated w/ cancers and adenomas Every 3 year testing interval recommended by manufacturer FDA has cleared it for marketing as CRC screening test CMS has agreed to cover Cologuard for Medicare beneficiaries age 50 – 85 yrs – Medicare will reimburse $502 q 3 yrs for the test – Private insurance coverage – tbd All positive tests must be evaluated by colonoscopy

43. Getting to 80% Achieving 80% screening rate will require appropriate use of colonoscopy alternatives To increase screening rates PCPs must be aware of and embrace: Evidence of FOBT/FIT efficacy Stool test program quality features Value of exploring patient preferences and offering options Innovative approaches