Prospective Clinical Validation of a Novel Multitarget FIT in CRC Screening

Study Overview
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Brief Summary
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The primary goal of the population-based colorectal (CRC) screening is early detection and interception of CRC and its precursors to decrease CRC-related morbidity and mortality. To improve current CRC screening programs, the investigators have developed and retrospectively validated a test that combines the detection of multiple proteins in stool (the multitarget faecal immunochemical test, mtFIT). mtFIT was found to have a higher accuracy to detect advanced neoplasia (AN), which includes CRC, advanced adenomas and advanced serrated polyps, in comparison to FIT. Thus, this multitarget test has the potential to improve the screening program's efficiency in reducing CRC-related incidence, morbidity and mortality. This new test, in comparison to FIT, shows specifically higher sensitivity in the detection of advanced adenomas, without affecting specificity.

Detailed Description
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Background: The primary goal of population-based CRC screening is early detection and interception of CRC and its precursors to decrease CRC-related morbidity and mortality. New tests, with higher sensitivity for advanced precursor lesions than the current FIT, are desired. The investigators have developed a protein-based multitarget faecal immunochemical test (mtFIT) that shows higher sensitivity for advanced adenomas without losing in specificity. Objective: To prospectively validate the better performance of the mtFIT in comparison to FIT in the setting of a population-based CRC screening program. Material and Methods: In this prospective study, participants of the Dutch National CRC screening program (55-75 years of age) will be invited to participate. Individuals who consent to participate in the study, will be asked to take two stool samples from the same bowel movement. In a central laboratory these two samples then will be analyzed. One with the standard of care faecal immunochemical test (FIT) and the other with the multi-target faecal immunochemical test (mtFIT). If either one of these two tests is positive, individuals will be referred to undergo a colonoscopy procedure. The performance of mtFIT, in comparison to FIT, will be evaluated against the colonoscopy findings. Expected results: mtFIT has higher sensitivity for AN, and in particular advanced adenomas, than FIT, at equal positivity rate.

Official Title
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Clinical Validation of a Multi-target Faecal Immunochemical Test (mtFIT) Versus a Faecal Immunochemical Test (FIT) for Detecting Advanced Neoplasia in Population Screening for CRC: a Prospective Cohort Study With Paired Design

Conditions
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CRC, Advanced Neoplasia

Intervention / Treatment
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* Diagnostic Test: Comparison of two tests (FIT and mtFIT) in the same bowel movement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of the Dutch population suitable for CRC screening (age between 55 and 75 years old) will be randomly selected. The participants will be invited in phases and are selected out of different age groups. The selected participants will participate in the population CRC screening program for either the first, second, third or fourth time. Exclusion Criteria: Collection of stool not complete for both tests (FIT and mtFIT)

Ages Eligible for Study
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Minimum Age: 55 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mtFIT<br>Individuals who consent to participate in the study, will be asked to take two stool samples from the same bowel movement. In a central laboratory these two samples then will be analyzed. One with the standard of care faecal immunochemical test (FIT) and the other with the multi-target faecal immunochemical test (mtFIT). If either one of these two tests is positive, individuals will be referred to undergo a colonoscopy procedure. The performance of mtFIT, in comparison to FIT, will be evaluated against the colonoscopy findings. | Diagnostic Test: Comparison of two tests (FIT and mtFIT) in the same bowel movement<br>* Invitees for the Dutch National CRC screening program will be randomly selected by the Screening Organization and invited to participate in this study, where next to the current FIT, participants will also perform the mtFIT in one bowel movement. Both tests will be analysed and if one of the two test results is positive, the individual will be referred for colonoscopy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of advanced neoplasia | Relative sensitivity of mtFIT compared to FIT in the detection of advanced neoplasia (AN; CRC, advanced adenomas and advanced serrated polyps) at an equal positivity rate. | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic yield of mtFIT in comparison to FIT | mtFIT detects more CRC, more early-stage CRC and more advanced polyps (advanced adenomas and advanced serrated polyps) compared to FIT. | 10 months |