Clinical trial NCT01538550: Pilot Study of a National Screening Programme for Bowel Cancer in Norway
Official title: Colorectal Cancer Screening in Norway: Pilot Study of a National Screening Programme With Randomised Comparison of Different Screening Strategies to Provide the Best Possible Service to the Population
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Colorectal Adenomas
Keywords: cancer
colon
rectum
adenoma
screening
iFOBT
flexible sigmoidoscopy
randomized trial
Lead sponsor: Norwegian Institute of Public Health
Sponsor class: OTHER_GOV
Collaborators: name: University of Oslo
First posted: 2012-02-24
Enrollment: 140000
Sex: ALL
Minimum age (years): 50
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The Norwegian government has funded a pilot study of a national colorectal cancer screening programme. This implies initiation of a screening pilot in the catchment area for two hospitals in Norway. The target population is average risk men and women at age 50-74 years. The programme is designed as a comparative effectiveness programme evaluating acceptance and test performance for two screening methods - fecal occult blood testing (FOBT) and flexible sigmoidoscopy (FS). This protocol describes the main methodological issues, necessary resources and the expected effects.

Detailed description: There are several candidate screening modalities - fecal occult blood (FOBT), flexible sigmoidoscopy, colonoscopy, CT and MRI colonography and a range of molecular markers. Of these, only FOBT and FS have been subjected to long-term follow-up in randomised trials (RCTs). These two modalities will be tested in a head-to-head comparison by 1:1 randomisation. Previous studies have suggested that the attendance for FS may be lower than for FOBT. However, participation has been shown to decline with repetitive rounds required for FOBT, while infrequent or once-only screening may suffice for FS. A better test performance for FS makes it uncertain which method may be most beneficial in a public health perspective. This is the first time a national screening programme is designed as a platform for comparative effectiveness studies.

The pilot study will be carried out in two hospital catchment areas in South-East Norway - each with a target population of 70,000 men and women at 50-74 years of age - altogether 140,000 individuals to be randomised 1:1 between screening with an immunochemical test for faecal occult blood (iFOBT) biennially or FS once only. The primary endpoint is colorectal mortality reduction after 10 years. Attendance for FS is expected to be 50% and 60% for iFOBT. Expected CRC mortality reduction is 30% (286 CRC deaths) in the FS arm and 15% (143 CRC deaths) in the iFOBT arm (intention-to-treat). In a 1:1 randomisation with 80% statistical power and a significance level of 5% it will require 70,000 individuals in each arm to disclose a statistically significant difference between FS and iFOBT screening in an intention-to-treat model. We expect 5% in the iFOBTs group to test positive and require colonoscopy work-up. A positive FS is defined as 'any advanced neoplasia' (CRC, adenoma \>10mm, adenoma with high-grade dysplasia or villous components). A finding of advanced neoplasia is expected in 5% of FS requiring full colonoscopy.

Study entry-date: All individuals were randomized to each of the two groups (iFOBT or sigmoidoscopy) before study start. Because first round screening of the iFOBT arm (70,000 invitees) will be finished in a shorter time frame compared to sigmoidoscopy, invitees in the flexible sigmoidoscopy arm are prone to more relevant time-dependent events between randomization and time of screening actually being offered. Therefore, primary entry-date was defined as day of mailed invitation in both screening groups. This approach means that the mean age at invitation in the sigmoidoscopy screening group will be older than in the iFOBT group, and analyses have to take this age-difference into account. Randomization date was chosen as a secondary study entry date to allow comparative analysis of effects of choosing the two entry date definitions. Sub-studies on lifestyle, psychological reactions comparing participants and control groups not invited to screening from neighbouring municipalities are performed. A randomized sub-study comparing various premedication in work-up colonoscopies is also performed.

Sub-studies

1. Changes in modifiable lifestyle factors such as not smoking, normal weight, high level of physical activity may reduce the risk of CRC. Correlation between these factors and endoscopic findings will be assessed. Limited intervention will be tested to improve life style.
2. The effect of screening on Psychological factors and the willingness to repeat screening will be assessed
3. Creation of a validated Sigmoidoscopy Bowel Preparation scale with subsequent testing of various bowel preparation modalities will be performed.
4. RCT with various strategies og analgesia during colonoscopy will be tested to improve patient experience.

Eligibility criteria: Inclusion Criteria:

* men and women
* age 50-74 years
* living in defined geographic areas in South-East Norway (catchment areas for two hospitals)

Exclusion Criteria:

* previous colorectal cancer

Primary outcomes:
measure: colorectal cancer mortality
timeFrame: 10 years
Secondary outcomes:
measure: Colorectal cancer incidence
timeFrame: 10 years
measure: Complications and quality assurance
timeFrame: 4 years
measure: Psychological effects of screening
timeFrame: 5 years
Other outcomes:
measure: Bowel preparation in Sigmoidoscopy
timeFrame: 1 year start Fall 2017
measure: Pain reduction during Colonoscopy
timeFrame: 18 months from Fall 2017
Locations:
city: Oslo
country: Norway
facility: Moss Hospital
city: Rud
country: Norway
facility: Bærum County Hospital
Study officials:
affiliation: Norwegian Institute of Public Health
name: Giske Ursin, MD, PhD
role: STUDY_DIRECTOR
affiliation: Norwegian Institute of Public Health
name: Kristin Randel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Randel KR, Botteri E, Romstad KMK, Frigstad SO, Bretthauer M, Hoff G, de Lange T, Holme O. Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening. Gastroenterology. 2019 May;156(6):1642-1649.e1. doi: 10.1053/j.gastro.2019.01.040. Epub 2019 Jan 25.
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