Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design

Abstract

The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs. the annual fecal immunochemical test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening colonoscopy will be superior to a FIT-based screening program in the prevention of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical centers. Participants are randomized to either colonoscopy or annual FIT. Results of colonoscopy are managed as per usual care and study participants are assessed for complications. Participants testing FIT positive are referred for colonoscopy. Participants are surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC mortality. The secondary endpoints are (1) CRC incidence (2) complications of screening colonoscopy, and (3) the association between colonoscopists' characteristics and neoplasia detection, complications and post-colonoscopy CRC. CONFIRM leverages several key characteristics of the VA's integrated healthcare system, including a shared medical record with national databases, electronic CRC screening reminders, and a robust national research infrastructure with experience in conducting large-scale clinical trials. When completed, CONFIRM will be the largest intervention trial conducted within the VA (ClinicalTrials.gov identifier: NCT01239082).

Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society

“…There is limited direct evidence of screening effectiveness in adults younger than 50 years, in large part because of early CA CANCER J CLIN 2018;68:250-281 VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 expert judgments, based on disease burden, that screening should begin at age 50 years. 23,67,68 Most of the RCTs of CRC screening demonstrating benefit had a starting age of 50 years, as do the RCTs of colonoscopy/FIT 25,69 and CTC/colonoscopy/FIT/FS [70][71][72] that are currently in progress. Three of the European gFOBT trials conducted in the 1980s and 1990s that demonstrated a CRC mortality benefit enrolled persons starting at age 45 years (45-74 years or 75 years).…”

Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know

“…In a ‘real world’ setting, FIT are implemented serially over time (ie, every 1–2 years) and as such the programmatic sensitivity is a better measure of actual performance than the one-time application sensitivity reported in trials to date. Two large, well designed randomised trials comparing serial FIT to endoscopy over time for the outcome of CRC mortality are underway and will address this limitation 57 58…”

“…A quarter of the US population have adenomas by age 50 years and up to half of individuals will develop an adenoma in their lifetime; however, most people die with and not from their adenomas 63 64. Unfortunately, the currently available data is insufficient to decide this question; the final results of the Spanish study58 are needed, which compares the efficacy of one-time colonoscopy to biennial FIT for the reduction of CRC mortality at 10 years, and a similar American VA study57 due to report final results in the 2020s.…”

A blueprint for cancer screening and early detection: Advancing screening’s contribution to cancer control

“…Once RCT data have confirmed the efficacy of screening, additional RCTs usually are judged to be both unnecessary and impractical to answer enduring and new questions; instead, observational study designs, such as prospective cohort studies, trend studies, ecological designs, case‐control studies, and microsimulation models, are used to address important screening questions. There are exceptions, such as when a national system seeks to directly measure the efficacy of a test that has not been evaluated with an RCT, such as the UK trial of once‐only flexible sigmoidoscopy (FS), the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer Trial (CONFIRM), or the Tomosynthesis Mammographic Imaging Screening Trial (TMIST), which is comparing digital breast tomosynthesis (DBT) with conventional digital mammography . However, since the efficacy of screening has been demonstrated, with few exceptions, these trials generally do not have a group invited to usual care, and primary endpoints tend to be screening outcomes rather than mortality, although some may build in the potential for long‐term evaluation of mortality differences between the 2 study arms.…”