The goal of this pragmatic randomized clinical trial is to compare two colorectal (CRC) screening outreach approaches (FIT and Cologuard) in community health centers (CHC) in patients overdue for CRC screening. The main questions the project aims to answer are: What screening test has a higher completion rate? What screening test is more feasible and acceptable in a CHC setting? Patients will be sent a CRC screening test in the mail and will be asked to complete it at home and mail it back. Researchers will compare the completion rates for each screening test and will also look at the overall completion rate of both tests.

This is a 3-year pragmatic trial with four levels of intervention, including system-, provider-, patient-, and community-level components at each of the CARES clinical sites. Health system components will include the development and implementation of a CRC screening registry and tracking database to systematically and actively track patients overdue for screening, screening test completion, and abnormal screening results. Data systems will be coupled with process re-design to improve clinical workflow for screening outreach. Providers will receive educational support through a training session about the importance of CRC screening, screening test options, population management, and an instructional on how to complete a Cologuard kit (Cologuard arm only) or a FIT kit (FIT arm only). Patient components of the intervention vary by study arm. In sites randomized to Cologuard, patients will receive a mailed Cologuard kit and the Exact Sciences patient support program. Patients in clinics randomized to FIT will receive a mailed FIT kit with systematic reminders. Patients who test positive will be offered patient navigation to assist with completing a diagnostic colonoscopy.

Inclusion Criteria:

1. Age 45-75
2. Has had a visit at a participating community clinic within the last two years.
3. Alive
4. Patient's preferred language is English or Spanish

Exclusion Criteria:

Exclusion Criteria:

1. Has Ulcerative Colitis or Crohn's disease documented in the problem list. (Codes below).
2. Has colorectal cancer documented in the problem list. (Codes below).
3. Has had a FIT in the past 1 year
4. Has had a colonoscopy in the past 10 years

ICD-10 codes for exclusion criteria:

Ulcerative colitis:

• K51.0
• K51.2
• K51.3
• K51.4
• K51.5
• K51.8
• K51.9
• K52.8
• K52.9

Crohn's disease:

• K50.0
• K50.1
• K50.8
• K50.9

Colorectal cancer

• C18 (malignant neoplasm of colon)
• C18.0 (malignant neoplasm of cecum)
• C18.1 (malignant neoplasm of appendix)
• C18.2 (malignant neoplasm of ascending colon)
• C18.3 (malignant neoplasm of hepatic flexure)
• C18.4 (malignant neoplasm of transverse colon)
• C18.5 (malignant neoplasm of splenic flexure)
• C18.6 (malignant neoplasm of descending colon)
• C18.7 (malignant neoplasm of sigmoid colon)
• C18.8 (malignant neoplasm of overlapping sites of colon)
• C18.9 (malignant neoplasm of colon, unspecified)
• C19 (malignant neoplasm of rectosigmoid junction)
• C20 (malignant neoplasm of rectum)
• C21.8 (malignant neoplasm of overlapping sites of rectum, anus and anal canal)
• C26.0 (malignant neoplasm of intestinal tract, part unspecified)
• C78.5 (secondary malignant neoplasm of large intestine and rectum)
• C78.6 (secondary malignant neoplasm of retroperitoneum and peritoneum)
• D37.4 (neoplasm of uncertain behavior of colon)
• D37.5 (neoplasm of uncertain behavior of rectum)

From enrollment through 180 days for negative test result or an additional 180 days after a positive FIT or Cologuard was returned, up to 1 year.

Boston and LA used different FIT kit brands. No access to patient-level data about outreach attempts or contacts from the Exact Science patient support program because this information is proprietary.

Unable to comment on cost-effectiveness. Unable to randomize the South Dakota site because unable to identify another CHC in the region to participate.