Trial Information

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

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 65,000 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: First round screening of the iFOBT arm (70,000 invitees) has to be
finished in years 1 and 2 of the trial while the flexible sigmoidoscopy arm (70,000
invitees) requires years 1-4 to be completed. Randomization of altogether 140,000 invitees
was performed in year 1 of the trial - thus rendering the flexible sigmoidoscopy arm 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 real (for those
attending) or suggested appointment (for non-attenders) in the screening arm as all letters
of invitation stated a suggested day for appointment chosen by randomization. Primary entry
date in the iFOBT arm was similarly defined as date of iFOBT sampling for those attending
and date of mailing iFOBT-kits plus one week for non-compliant invitees. Randomization date
was chosen as a secondary study entry date to allow comparative analysis of effects of
choosing the two entry date definitions.