Randomized Comparison of Organized FIT Invitation, Organized Colonoscopy Invitation, and Usual Care for Colorectal Cancer Screening Among the Underserved Authors Samir Gupta, Marcia Hammons, Luisa Valdez, Elizabeth Carter, Mark Koch, Liyue Tong, Chul Ahn, Don C. Rockey, Jasmin Tiro, Ethan A. Halm, Celette Sugg Skinner Partnering Institutions John Peter Smith Health System, Harold C. Simmons Cancer Center, Moncrief Cancer Institute, UT Southwestern Medical Center Grant Support Cancer Prevention and Research Institute of Texas

Colorectal Cancer (CRC) is an Important Public Health Problem 2 nd leading cause of cancer death nationwide Screening can reduce CRC mortality – Fecal occult blood testing, sigmoidoscopy, and colonoscopy Mandel N Engl J Med Nov 30;343(22):1603-7; Kahi Clin Gastroenterol Hepatol Jul;7(7):770-5; Brenner J Natl Cancer Inst Jan 20;102(2):89-95; Brenner J Clin Oncol Oct 1;29(28):3761-7; Atkin Lancet May 8;375(9726): ; Scholefield Gut Jun;50(6):840-4; Kronborg Lancet Nov 30;348(9040): ; Mandel J Natl Cancer Inst Mar 3;91(5):434-7; Baxter Ann Intern Med Jan 6;150(1):1-8; Manser Gastrointest Endosc Apr 11. [Epub ahead of print].

Screening Participation is Substantial, but Suboptimal Screening has been promoted in the US for over 15 years, and steady gains have been realized – National screening rate is >55% However, not all populations have benefited from these gains – Uninsured – Pre-Medicare age – Medicaid – Minorities MMWR Morb Mortal Wkly Rep Jan 27;61(3):41-5. Klabunde Cancer Epidemiol Biomarkers Prev Aug;20(8):

Two Key Challenges to Improving Screening for the Underserved Identifying the unscreened Determining which test or tests to offer

Challenge 1: Identifying the Unscreened In the US, most screening is primary care visit- based Uninsured/underserved have limited access – No visit, no identification of need, no screening offer Recent NIH State of the Science Conference on Enhancing CRC Screening emphasized need to develop methods to identify unscreened underserved/uninsured individuals Steinwachs Ann Intern Med May 18;152(10):663-7.

Challenge 1: Identifying the Unscreened Potential solution is to leverage relationships safety-net systems have with the underserved – Care for uninsured, Medicaid, and minority groups – Have readily available administrative claims data that can be used to: 1)Measure and track screening rates 2)Individually identify the unscreened for interventions to boost screening

Challenge 1: Identifying the Unscreened We tested and validated this approach at John Peter Smith Health System, the safety net health system serving Fort Worth and Tarrant County, Texas and found: – Screening rate far below the national average: 22% – 16,000 unscreened patients could be individually identified Positioned us to test interventions to boost screening Gupta S et al. Cancer Epidemiol Biomarkers Prev Sep;18(9):2373-9; Gupta et al. Am J Med Sci at press; Marquez E, Gupta S, Cryer B. Clin Gastroenterol Hepatol Feb;9(2):106-9.

Challenge 2: Determining Test Type to Use Could recommend a “colonoscopy first” strategy for all underserved patients – Expensive, infrastructure required substantial – Does not take into account potential for test-specific differences in participation Fecal immunochemical testing (FIT), CT colonography, and colonoscopy may have different rates of participation Understanding test-specific differences is critical – Test specific participation rates may be more important that test-specific sensitivity for CRC – Possible that “Best test is the one that gets done” Zauber Ann Intern Med Nov 4;149(9):659-69; Gupta Ann Intern Med Mar 3;150(5):359; Marquez E, Gupta S, Cryer B. Clin Gastroenterol Hepatol Feb;9(2):106-9; Gupta Lancet Oncol Mar;13(3):e90.

The Two Challenges Offered an Opportunity to Increase CRC Screening at a Safety Net Baseline screening rates were far below national average, at just 22% Local data could be leveraged to individually identify the unscreened for interventions to boost screening Uncertainty regarding best test or tests to offer Compelled us to develop an intervention that could: – Boost screening, addressing barriers such as infrequent access to care – Determine which test would result in the highest screening rate for the population: FIT vs. colonoscopy Gupta S et al. Cancer Epidemiol Biomarkers Prev Sep;18(9):2373-9; Marquez E, Gupta S, Cryer B. Clin Gastroenterol Hepatol Feb;9(2):106-9.

Aims Among uninsured patients, not up-to-date with screening, to: 1)Determine if a organized outreach program boosts screening compared to usual care 2)Determine if organized outreach offering a fecal immunochemical test is more effective at boosting screening participation compared to organized outreach offering free colonoscopy

Methods - Design Randomized controlled trial Usual Care Organized outreach invitation to either FIT or colonoscopy – Mailed invitation, with information on screening English/Spanish, low literacy – FIT kit or phone number to schedule colonoscopy FIT one sample – Telephone reminders (automated and live) – Assistance with test completion and guideline appropriate follow up Clarified FIT process, colonoscopy scheduling, prep, and follow up

Methods - Design Inclusion Criteria Age 54 to 64 >1 primary care visit in last year Uninsured, but enrolled in medical assistance program Exclusion Criteria Up to date with CRC screening, based on: – FOBT within 1 year, sigmoidoscopy or barium enema within 5 years, colonoscopy within 10 years Prior CRC, inflammatory bowel disease, or polyps Missing address/phone number

Design - Analysis Primary outcome was screening participation, one year after randomization – Intension to screen analysis Secondary outcomes include: – Rate of lesion detection/patient invited – Costs Sample size/power – Based on maximizing screening delivery given local colonoscopy capacity – Planned to assign n=480 to colonoscopy, n=1600 to FIT, and > n=1600 to usual care – >90% power to detect differences of >10%, alpha=0.025

A Waiver of Informed Consent was Obtained Interventions an adjunct to, rather than a replacement for usual care Enhances interpretation and generalization of results – Requiring consent would have enrolled patients predisposed to complete screening – Reflects “real world” response to interventions – Fits with concept of comparative effectiveness trials Approved by UT Southwestern and JPS Institutional Review Boards ClinicalTrials.gov ID# NCT

Results

Excluded (n=6,301) Screening up-to-date (n=1,573) No recent primary care visit (n=1,217) Prior polyps, IBD, or CRC (n=1,905) Missing address/phone number (n=112) Age (n=836) 1° language not English/Spanish (n=658) Assessed for eligibility (n=12,295) Randomized (n=5994) FIT n=1600 Usual Medical Care n=3914 Colonoscopy n=480 Results

Results - Demographic Characteristics FIT (n=1600) Colonoscopy (n=480) Usual Care (n=3914) Age, median (IQR)59 (57 – 61)59 ( )59 (56 – 62) Sex, % Female Race/Ethnicity, % Caucasian41 African American Hispanic Other776 Primary Language, % English Spanish171417

Comparison of Usual Care & Organized Outreach Usual Care (n=204/3914) Organized Outreach (n=665/2080) p<0.0001

Comparison of Usual Care, Organized Colonoscopy, & Organized FIT* Usual Care (n=204/3914) Organized Colonoscopy (n=87/480) Organized FIT (n=578/1600) *p< all comparisons

Results – Neoplasia Detected Advanced AdenomaCRC*CRC + AA n%n%n% Colonoscopy (n=480) 81.67%10.21%91.88% FIT (n=1600) %30.19%161.00% *CRC Stages FIT: 1 TIS, 1 Stage I, 1 Stage III Colonoscopy: 1 Stage I

Results – Neoplasia Detected Advanced AdenomaCRC*CRC + AA n%n%n% Colonoscopy (n=480) 81.67%10.21%91.88% FIT (n=1600) %30.19%161.00% *CRC Stages FIT: 1 TIS, 1 Stage I, 1 Stage III Colonoscopy: 1 Stage I Neoplasia detection rate appears higher for colonoscopy, but: FIT achieved similar results with a much lower colonoscopy rate Results reflect one time screening

Conclusions Organized outreach is promising for boosting screening for large populations – May be particularly effective for underserved populations, such as the uninsured and minorities Screening participation rates may be highly test- specific – Differences may be large enough to overcome differences in test-specific sensitivity for neoplasia Overall, rapid improvement in screening rates is achievable for the underserved – We screened 665 patients, detected 21 patients with advanced polyps, and detected 4 patients with CRC

Acknowledgements Grant Support/Other Support Cancer Prevention and Research Institute Grant PP (Gupta, Project Director) – Becky Garcia, Ramona Magid Polymedco Corporation Moncrief Cancer Institute Harold C. Simmons Cancer Center JPS Partners Administration: Robert Earley, Gary Floyd, David Salsberry, Bobby Miller, Sue Crabtree, Patty Angell, Stacy Boatman, Teresa Carver, Jay Haynes Clinical Lab: Lonnie Dear, Donna Flowers, Mark Sackovich, Melissa Ruperto, Stephanie Zitrick Endoscopy Lab: Donna Franklin, Rohan Clarke, Shilpa Madadi, Sangameshwar Reddy Family Medicine and GI Clinics: Maria Asprilla, Rachel Stewart, Alba Perez Smith, Kathy Cabello IRB: Josephine Fowler, Karshena Valsin, Danielle Ramirez, Elie Choufani, Hao Wong Outreach Staff Marcia Hammons Luisa Valdez Data Management Dawn Houser Adam Loewen Wes Senter Collaborators Elizabeth Carter Mark Koch Keith Argenbright Celette Sugg Skinner Don C. Rockey Ethan A. Halm Jasmin Tiro Michael Kashner Chul Ahn Liyue Tong

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Best Test is the One that Gets Done: Thought Exercise Colonoscopy is 95% sensitive for CRC (one-time) Fecal Immunochemical Testing is 70% sensitive for CRC (one-time) 20,000 individuals to screen 1% have CRC (n=200) Should we implement population screening with colonoscopy or FIT? Parekh M Ail Pharm Ther Feb; 27: Woolf SH Ann Fam Med Nov-Dec;3(6):

CRC Screening Test Participation Rate Individuals with CRC Detected At Equivalent Participation, Colonoscopy Detects the Most CRCs 95% Sensitivity

CRC Screening Test Participation Rate Individuals with CRC Detected With Substantially Higher Participation, a FIT Strategy Might Have Similar--Even Superior--CRC Detection

CRC Screening Test Participation Rate Individuals with CRC Detected With Substantially Higher Participation, a FIT Strategy Might Have Similar--Even Superior--CRC Detection