Assessing the Effect of a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion

Study Overview
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Brief Summary
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Objectives: Colonoscopy and stool-based testing are the two predominant colorectal cancer (CRC) screening tests used in the US, and both reduce colorectal cancer mortality. However, only 62% of Americans are up to date with screening, partly because many individuals find these two tests inconvenient or unacceptable for a variety of reasons. There is an unmet need for a non-invasive test that does not require bowel preparation or handling stool, and the Septin9 DNA blood test may be an alternative for those individuals who would otherwise remain unscreened. Aims: Aim 1: To measure screening uptake with a blood test in screen-resistant patients who have declined both colonoscopy and fecal immunochemical testing (FIT) at the Manhattan VA Medical Center Sub-Aim 1a: To assess the proportion of those with a positive blood-based screening test who undergo diagnostic colonoscopy Sub-Aim 1b: To describe the endoscopic findings on diagnostic colonoscopy Aim 2: To survey screen-resistant patients to understand their beliefs and attitudes about colorectal cancer screening and testing options We hypothesize that a substantial proportion of patients who have refused colonoscopy and FIT will accept the blood test. We hypothesize this will be driven by the convenience of the blood test. Methods: This will be randomized controlled trial of individuals who have refused colonoscopy and FIT within past 6 months. Eligible patients will be randomized 1:1 to the intervention or control group. Both groups will be invited to participate in navigated colonoscopy or FIT by letter and telephone call. The intervention group will also be invited to participate in the blood test if they refuse colonoscopy and FIT. We will enroll 180 participants in each group (total n=360).

Detailed Description
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The proposed study is a randomized controlled trial that will 1) assess the uptake of a CRC screening blood test among patients who have declined both colonoscopy and FIT in the previous 6 months, including diagnostic evaluation of positive results and 2) survey patients about their beliefs and attitudes regarding CRC screening and testing options. All participants will be primary care patients at the Manhattan VA Medical Center. Based on a recent internal audit, there were 1502 patients who had at least one primary care visit from August 2016 through August 2017 and were not up to date with CRC screening. Up-to-date CRC screening is defined as either 1) a colonoscopy within the past 10 years or 2) FIT within the past year. We will perform an updated CRC screening audit at the beginning of the study to obtain the entire pool of eligible patients who are not up to date with screening. Eligible patients will then be randomized 1:1 to either an intervention group or a control group. All patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Patients who call will speak to a research assistant who is trained in patient navigation and can facilitate referrals for colonoscopy or FIT. Following the sequential testing approach, letters addressed to the intervention group will also include an option to participate in the blood test, with instructions to call the study number to schedule the blood draw. In addition to the letter, both groups will also receive a follow-up telephone call that reiterates information in the letter. The research assistant will make and receive all calls using a standard script. All patients will also be asked to complete a survey about their beliefs and attitudes regarding CRC screening. The survey will be mailed with the invitation letter and will also be administered over the telephone by the research assistant. The study team will notify patients and their primary care physicians of blood test results and will facilitate a colonoscopy referral for those with positive tests. Primary care physicians will not be asked to notify the patients or make the colonoscopy referral because most will not have adequate knowledge of the Septin9 test to provide appropriate patient education. Participants who are randomized to the blood test arm will undergo phlebotomy, which will be performed by the study research assistant. The blood sample will be temporarily stored on-site and then transported to an off-site commercial laboratory (Lenco Diagnostic Laboratory, Brooklyn, NY) to run the assay. Clinical outcomes for both the intervention and control group participants will be measured as a secondary outcome. This includes timing and result of a screening colonoscopy or FIT for individuals in the controls group as well as diagnostic colonoscopy for participants who had a positive blood test.

Official Title
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Assessing the Effect of Offering a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion in Patients Who Have Refused Colonoscopy and FIT

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Diagnostic Test: Septin9


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: not up-to-date with colorectal cancer screening, defined as a colonoscopy in the past 10 years, a stool test (FOBT/FIT) in the past year, or a flexible sigmoidoscopy in the past 5 years. Declined colorectal cancer screening (both colonoscopy and FIT) in the previous 6 months, which must be documented in the electronic health record Exclusion Criteria: Personal history of colonic adenomas (including sessile serrated adenomas), proximal hyperplastic polyps, CRC, inflammatory bowel disease, or hereditary gastrointestinal cancer syndrome First degree relative with CRC diagnosed at <60 years of age; family history of hereditary gastrointestinal cancer syndromes. Vulnerable populations Adult unable to consent Individuals who are not yet adults (infants, children, teenagers) Pregnant women Prisoners

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients will be randomized 1:1 to the intervention or control group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Patients who call will speak to a research assistant who is trained in patient navigation and can facilitate referrals for colonoscopy or FIT. Patients will receive a follow-up telephone call that reiterates information in the letter. Patients will also be asked to complete a questionnaire about their beliefs and attitudes regarding CRC screening. The questionnaire will be mailed with the invitation letter and will also be administered over the telephone by the research assistant. | |
| Experimental: Septin9<br>Patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Letters will also include an option to participate in the blood test, with instructions to call the study number to schedule the blood draw. This option will not appear in the letters sent to the control group. Patients will also receive a follow-up telephone call and a questionnaire. Participants who choose to the blood test (Septin9) will undergo phlebotomy. The blood sample will be run by an off-site commercial laboratory. The study team will notify patients and their primary care physicians of blood test results and will facilitate a colonoscopy referral for those with positive tests. | Diagnostic Test: Septin9<br>* Septin9 is a FDA-approved blood test for colorectal cancer screening<br>* Other names: Epigenomics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Undergo Screening Within 6 Months of Outreach | Percentage of participants who undergo screening in the intervention group vs. control group, measured 6 months after the initial letter was sent | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Completing Screening Strategy | Complete screening in both groups, which is defined as completion of the entire screening strategy. For colonoscopy, this requires cecal intubation and an adequate bowel preparation. For individuals who took Septin9 and FIT, positive results must be followed by a colonoscopy with cecal intubation and adequate bowel preparation. | 12 months | 
| Percentage of Participants With Colonoscopy Follow-up in Intervention Group | Among individuals in the intervention group who had a positive blood test, proportion who completed a follow-up colonoscopy within 6 months. | 6 months (after positive FIT) | 
| Self-reported Willingness to Take Blood Test for Colorectal Cancer Screening on Questionnaire | Percentage of both groups who answered that they would be willing to take a blood test for colorectal cancer screening | 1 day (assessed using baseline survey) | 
| Self-reported Most Common Advantages of Blood Test on Questionnaire | The most commonly cited advantages of a blood test compared to colonoscopy and stool test in both groups | 1 day (assessed using baseline survey) | 
| Self-reported Most Common Reasons for Refusing Blood Test on Questionnaire in Intervention Group | The most commonly cited reasons for not taking the blood test in the intervention group. | 1 day (assessed using baseline survey) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer screening, septin 9