Adding Family History of Colorectal Cancer to the Dutch FIT-based Screening Program

Colorectal Neoplasms Clinical Trial

Official title:

Adding Family History of Colorectal Cancer to the FIT-based Screening Program in a Dutch Colorectal Cancer Population Sample

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02698462
• Other study ID #: 821748-140305-PG
• Secondary ID: TC 12-05
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: May 15, 2018

Study information

• Verified date: January 2019
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to identify more persons with advanced neoplasia in the current national CRC screening, by adding data on family history of CRC (using a validated online questionnaire) to FIT. In addition, the aim is to identify those persons and their family members who should not be participating in a FIT based screening but receive surveillance colonoscopies instead, because of a familial CRC syndrome. It is aimed to increase detection without affecting participation, thereby increasing the yield of screening.

Description:

This is a prospective CRC population-based screening trial, using FIT and a family history questionnaire, inviting those with a positive FIT, a familial CRC syndrome, or both for colonoscopy.

All invitees receive an invitation to complete a FIT (FOB-Gold) and a validated, online family history questionnaire. Answers from the questionnaire are compared with the Dutch criteria for referral for genetic testing and/or surveillance colonoscopies for persons at a potential familial risk for CRC. Invitees are invited to perform both tests, but if they only perform one this will be assessed. Participants with a positive FIT (cut-off value 275 ng/ml) and/or a positive family history and a diagnosis of familial CRC by a clinical geneticist will be referred for colonoscopy.

The investigators will compare the diagnostic yield, participation rate, and positive predictive value for two strategies: referral for colonoscopy based on FIT and family history versus referral for colonoscopy based on FIT-only.

The sample size is justified by the anticipated gain in diagnostic yield from combining FIT-only with family history screening. With a sample size of 6.000 persons the investigators expect to detect 130 persons with advanced neoplasia after a positive FIT (21.7 per 1.000 invitees). By adding the family history questionnaire, the investigators anticipate detecting an additional number of 11 persons with advanced neoplasia, resulting in a yield of combined FIT-based and family history screening of 141 persons with advanced neoplasia (23.5 per 1.000 invitees), which is an increase of 1.8 per 1.000 invitees. Using the McNemar test with the significance level set at 5%, there is a power of 91% to show that the gain in diagnostic yield is statistically significant. Previous CRC test screening studies using FIT showed that participation rates are approximately 60% in a first screening round. The participation rate in the Dutch national CRC screening in 2014 (the first year of introduction) was even higher, 68%. The investigators expect that 80% of these persons will fill out the familial risk questionnaire, resulting in 3.264 persons who perform both tests. As the investigators recommend invitees to perform the questionnaire in addition to FIT, the investigators assume that the percentage of persons only filling out the questionnaire and not performing FIT are negligible. Based on previous screening studies using a FIT positivity cut-off value of 50 ng Hb/mL for the OC-Sensor, it is assumed that 8% of these participants have a positive FIT result. In the current Dutch screening program, a different FIT is used (FOB-Gold) with a cut-off value of 275 ng Hb/ml. The FIT positivity rate with this test and with this cut-off value is unknown. However, a governmental announcement recently reported that the positivity rate is expected to remain 8% with this cut-off value. Therefore, the investigators expect 326 FIT positives in this study (8% of 4.080). Based on previous studies, approximately 40% of all persons with a positive FIT result will have advanced neoplasia. In our sample this concerns 130 persons. The percentage of persons with a familial CRC risk requiring surveillance colonoscopies in a screening population varies between 2.3% and 4%. Differences in the definition of an increased familial CRC risk could explain the variability in reported numbers. As the investigators are using a relatively large range in criteria for fulfilling the definition of a familial CRC risk, the highest reported percentage (4%) is assumed, which concerns 131 persons. The previously developed family history questionnaire has a sensitivity of 90% and 100% in identifying those persons qualifying for referral, in two subsequent validation phases respectively. For the purpose of this study, this validated questionnaire is adjusted to the recently renewed referral criteria. The investigators make the assumption that the questionnaire can identify all persons with a familial CRC syndrome based on referral criteria. Persons with a familial CRC syndrome who do not fulfill these criteria will be missed. This concerns an unknown number and will not be taken into account. A previous screening study showed that 6% of those with a positive FIT have an increased familial CRC risk. One can calculate that 3.8% of persons with a negative FIT have a familial CRC risk: 4% minus 6% of 8% (FIT positives), divided by 92% (FIT negatives). If one assumes that there is no difference in familial CRC risk between those who do and those who do not fill out the questionnaire, this involves 114 of 3.264 persons. Based on unpublished data by this research group it is estimated that 10% of those with a negative FIT have a familial CRC risk: 11 persons (10% of 114). A similar percentage was found in another screening study. Additionally, all participants with a familial CRC syndrome will be offered surveillance recommendations. In this sample, 131 persons are estimated to have a familial CRC syndrome. Of these, 16 persons (12%) will undergo a colonoscopy due to a positive FIT (6% of 8% FIT positives) and their familial CRC risk could be addressed at their visit to a colonoscopy center. The other 115 persons (88%) are expected to have a negative FIT and these persons (and their family members) would otherwise be unlikely to be identified as having a familial CRC syndrome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5979
• Est. completion date: May 15, 2018
• Est. primary completion date: May 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 59 Years to 75 Years

Eligibility

Inclusion Criteria: Six thousand persons eligible for the national CRC screening program, consisting of persons from the birth years 1941, 1945, 1953, 1955 and 1957 will be selected. These persons will be selected from four areas in North-Holland that are considered representative of the Netherlands regarding ethnical distribution and socioeconomic status: Aalsmeer, De Ronden Venen, Ouder-Amstel, Stichtse Vecht. These areas had an average participation-rate in 2014 that was comparable to the national participation rate (68.2%; a range from 65% to 75% is allowed). The distribution of age groups and gender will be comparable to the national screening distribution in 2016. Those who have been invited for a previous screening round in 2014 or for previous pilot-screening rounds will not be selected. In order to be eligible for participation, a subject must have been selected for participation in the national FIT-screening program in 2016.

Exclusion Criteria:

No specific exclusion criteria apply for participation in Family Matters, meaning that all invitees will receive a FIT as well as the questionnaire.

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Other:
• Family history questionnaire
All invitees receive an invitation to complete a FIT (FOB-Gold) and a validated, online family history questionnaire. Answers from the questionnaire are compared with the Dutch criteria for referral for genetic testing and/or surveillance colonoscopies for persons at a potential familial risk for CRC. Invitees are invited to perform both tests, but if they only perform one this will be assessed. Participants with a positive FIT (cut-off value 275 ng/ml) and/or a positive family history and a diagnosis of familial CRC by a clinical geneticist will be referred for colonoscopy.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Prof. Evelien Dekker, MD, PhD	Dutch Digestive Diseases Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The number of invitees with a familial CRC syndrome		1.5 years
Other	FIT result of participants with a familial CRC syndrome		1.5 years
Other	The number of family members of participants with a familial CRC syndrome who receive an advice for genetic testing and/or surveillance colonoscopies		1.5 years
Other	The number of questionnaire participants who need help completing the questionnaire		1.5 years
Other	The number of persons with a positive questionnaire with a confirmed familial CRC syndrome		1.5 years
Other	The number of persons with a false-positive questionnaire as confirmed when verifying the completed questionnaire		1.5 years
Other	The number of persons with a false-negative questionnaire as confirmed when verifying the completed questionnaire in a random sample of those with a negative questionnaire		1.5 years
Other	Attendance rate to the intake visit at the department of clinical genetics		1.5 years
Other	Reasons for non-participation to genetic testing after a familial CRC risk	This will be analyzed in a telephone interview	1.5 years
Other	Attendance rate to the pre-colonoscopy consultation after a positive FIT or a familial CRC syndrome		1.5 years
Other	Reasons for non-participation to colonoscopy after a positive FIT or a familial CRC syndrome	This will be analyzed in a telephone interview	1.5 years
Other	The number of persons with non-advanced lesions (SSA/P, hyperplastic polyps, non-advanced adenomas) after a positive FIT or a familial CRC syndrome		1.5 years
Other	Comparison of diagnostic yield in detecting advanced neoplasia of FIT with the national CRC screening yield		1.5 years
Primary	Diagnostic yield	number of participants in whom advanced neoplasia is detected relative to the number of invitees	1.5 years
Secondary	Participation rate	Number of invitees completing the screening tests relative to the number of invitees	1.5 years
Secondary	Positive predictive value	Number of participants in whom advanced neoplasia is detected, relative to the number of participants testing positive	1.5 years