Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) (CONFIRM)

CSP #577 - Colonoscopy vs. Fecal Immunochemical Testing in Reducing Mortality From Colorectal Cancer

Colorectal cancer (CRC) is currently the second most common cause of cancer death in the United States, and one of the most preventable cancers. It has been shown in several randomized controlled trials that screening using fecal occult blood testing (FOBT) reduces CRC mortality by 13-33%. While there is strong consensus amongst experts regarding the value of CRC screening, the best approach to screening is not clear. Of the widely recommended modalities, FOBT and colonoscopy are the most commonly used within the United States. FOBT is inexpensive, non-invasive, and its use as a screening tool is supported by the highest quality evidence (i.e. randomized controlled trials). Moreover, newer FOBT, such as fecal immunochemical tests or FITs, have advantages over conventional FOBT in terms of both test characteristics and ease of use that make them quite attractive as a population-based screening tool.

While colonoscopy is invasive and has higher up-front risks and costs than FOBT, it does afford the opportunity to directly assess the colonic mucosa and is widely believed to be the best test to detect colorectal cancer. In addition, colonoscopy allows for the detection and removal of colorectal adenomas -a well recognized colorectal cancer precursor. There is indirect evidence that suggests colonoscopy is effective in reducing colorectal cancer mortality, but to date, no large clinical trials have been completed to support this assumption. While colonoscopy use is increasing, data is emerging that colonoscopy may not be as effective as previously believed. Prior support for colonoscopy as a screening test relied upon effectiveness estimates that now appear to be overly optimistic. Given the invasive nature of colonoscopy, the associated small, but real risk of complications, and dramatically higher costs than other screening tests, it is especially important to determine the true comparative effectiveness of colonoscopy relative to other proven non-invasive options.

The investigators propose to perform a, large, simple, multicenter, randomized, parallel group trial directly comparing screening colonoscopy with annual FIT screening in average risk individuals. The hypothesis is that colonoscopy will be superior to FIT in the prevention of colorectal cancer mortality measured over 10 years. Individuals will be enrolled if they are currently eligible for CRC screening (e.g. no colonoscopy in the past 10 years and no FOBT in the past 1 year) and are between 50 and 75 years of age. The investigators will exclude individuals for whom colonoscopy is indicated (e.g. signs or symptoms of CRC, first degree family member with CRC, personal history of colorectal neoplasia or inflammatory bowel disease).

All participants will complete baseline demographic, medication, and lifestyle questionnaires (e.g. diet, non-steroidal anti-inflammatory use, frequency of exercise) prior to randomization in a 1:1 ratio to either screening colonoscopy or annual FIT screening (Figure 1). Those testing positive by FIT will undergo evaluation to determine appropriateness for colonoscopy. Screening will be performed in a manner consistent with the currently accepted standard of care in order to determine the comparative effectiveness of the two screening strategies. Participants will be surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC.

The primary study endpoint will be CRC mortality within 10 years of enrollment. The secondary endpoints are (1) the incidence of CRC within 10 years of enrollment and (2) major complications of colonoscopy. Mortality will be determined through queries of the VA Vital Status File. Cause of death will be determined primarily using death certificates from the National Death Index-Plus database, augmented by adjudication of medical records for known CRC cases where CRC is not listed as a cause of death on the death certificate. The investigators postulate that screening colonoscopy will result in a 40% reduction in CRC mortality over 10 years relative to annual FIT screening. Using a log-rank test with a 2-sided test of significance, =0.05, a sample size of 50,000 participants will be required to test the primary hypothesis with 82% power, assuming a 1% annual rate of crossover from FIT to colonoscopy and a 0.5% annual rate of loss to follow-up. The planned study duration is 12.5 years with 2.5 years of recruitment and 10 years of follow-up for all enrolled participants.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Colonoscopy; Procedure: FIT

• Study Type: Interventional
• Enrollment (Actual): 50126
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00921
    • VA Caribbean Healthcare System, San Juan, PR
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Phoenix VA Health Care System, Phoenix, AZ
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-5484
      • Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
  • California
    • Fresno, California, United States, 93703
      • VA Central California Health Care System, Fresno, CA
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System, Loma Linda, CA
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System, Long Beach, CA
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System, San Diego, CA
    • West Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
  • Colorado
    • Denver, Colorado, United States, 80220
      • VA Eastern Colorado Health Care System, Denver, CO
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Washington DC VA Medical Center, Washington, DC
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System, Gainesville, FL
    • Miami, Florida, United States, 33125
      • Miami VA Healthcare System, Miami, FL
    • Orlando, Florida, United States, 32803
      • Orlando VA Medical Center, Orlando, FL
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans' Hospital, Tampa, FL
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical and Rehab Center, Decatur, GA
  • Hawaii
    • Honolulu, Hawaii, United States, 96819-1522
      • VA Pacific Islands Health Care System, Honolulu, HI
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Jesse Brown VA Medical Center, Chicago, IL
  • Indiana
    • Indianapolis, Indiana, United States, 46202-2884
      • Richard L. Roudebush VA Medical Center, Indianapolis, IN
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Robley Rex VA Medical Center, Louisville, KY
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Healthcare System, Ann Arbor, MI
    • Detroit, Michigan, United States, 48201
      • John D. Dingell VA Medical Center, Detroit, MI
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center, Kansas City, MO
    • Saint Louis, Missouri, United States, 63106
      • St. Louis VA Medical Center John Cochran Division, St. Louis, MO
  • New Hampshire
    • Manchester, New Hampshire, United States, 03104
      • Manchester VA Medical Center, Manchester, NH
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
  • New York
    • Northport, New York, United States, 11768
      • Northport VA Medical Center, Northport, NY
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center, Durham, NC
    • Salisbury, North Carolina, United States, 28144
      • Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes VA Medical Center, Cleveland, OH
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City VA Medical Center, Oklahoma City, OK
  • Oregon
    • Portland, Oregon, United States, 97239
      • VA Portland Health Care System, Portland, OR
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Philadelphia MultiService Center, Philadelphia, PA
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Providence VA Medical Center, Providence, RI
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Memphis VA Medical Center, Memphis, TN
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center, Houston, TX
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • VA Salt Lake City Health Care System, Salt Lake City, UT
  • Vermont
    • White River Junction, Vermont, United States, 05009-0001
      • White River Junction VA Medical Center and Regional Office, White River Junction, VT
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center, Richmond, VA
  • Washington
    • Seattle, Washington, United States, 98108-1532
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Clarksburg Louis A. Johnson VA Medical Center, Clarksburg, WV
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • William S. Middleton Memorial Veterans Hospital, Madison, WI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female adults aged 50-75 years of age
• Veteran
• Able to provide informed consent

Exclusion Criteria:

• Symptoms of lower gastrointestinal tract disease warranting colonoscopic evaluation, including:

  • More than one episode of rectal bleeding within the past 6 months
  • Documented iron deficiency anemia
  • Significant documented unintentional weight loss (>10% of baseline weight) over 6 months
• Family history of CRC in a first degree relative at any age

• Prior history of colonic disease including:

  • Inflammatory bowel disease (e.g. ulcerative colitis or Crohn's disease)
  • One or more colorectal neoplastic polyps (i.e. adenomas)
  • Colorectal cancer
• Prior history of colonic resection

• Prior colonic examination, including:

  • Colonoscopy within the past 9.5 years
  • Sigmoidoscopy within the past 5 years
  • Barium enema within the past 5 years
  • CT colonography within the past 5 years
• gFOBT or FIT in the past 10 months
• Stool DNA test within the past 3 years
• Pregnancy
• Prisoner
• Significant comorbidity that would preclude benefit from screening or pose significant risk for the performance of colonoscopy (e.g. severe lung disease, end-stage renal disease, end-stage liver disease, severe heart failure, recent diagnosis of cancer (with the exception of non-melanoma skin cancer))
• Participation in a concurrent interventional study pertaining to the colon or rectum (including studies of colonoscopy or colorectal cancer screening. Waivers to this exclusion criteria can be requested and granted with the approval of the CONFIRM study co-chairs, the Cooperative Study Program and the leadership of the other study.
• Likely inability to track the individual over time (e.g. no permanent address at the time of screening for study entry)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm 1; Colonoscopy (one time screening)	Procedure: Colonoscopy; One time screening Colonoscopy to screen for colorectal cancer
Other: Arm 2; FIT (annually)	Procedure: FIT; Annual FIT testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is colorectal cancer mortality.	The primary outcome is colorectal cancer mortality. Patient survival will be monitored for 10 years, with survival assessed by both annual surveys and data reported to vital status registries, including the VA Vital Status File, which is comprised of the VA Beneficiary Identification and Records Locator System (BIRLS), the Medical SAS Inpatient Data Sets, and the Social Security Administration's Death Master File. The National Center for Health Statistics' National Death Index database will be used to find cause of death.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FIT Positive - If Colonoscopy is Warranted	There are no physical risks associated with performance of FIT screening. However, those with a positive FIT will be referred for evaluation by their primary care provider or site principal investigator to determine if colonoscopy is warranted. Those subsequently referred for colonoscopy will be exposed to its risks, and complications will be tracked as a secondary outcome measure	10 Years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Study Chair: Jason A. Dominitz, MD MHS, VA Puget Sound Health Care System Seattle Division, Seattle, WA; Study Chair: Douglas J Robertson, MD MPH, White River Junction VA Medical Center, White River Junction, VT

Publications and helpful links

General Publications

• Shaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol. 2021 Mar 1;116(3):458-479. doi: 10.14309/ajg.0000000000001122.
• May FP, Yano EM, Provenzale D, Neil Steers W, Washington DL. The Association Between Primary Source of Healthcare Coverage and Colorectal Cancer Screening Among US Veterans. Dig Dis Sci. 2017 Aug;62(8):1923-1932. doi: 10.1007/s10620-017-4607-x. Epub 2017 May 20.
• Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014 Apr 3;370(14):1287-97. doi: 10.1056/NEJMoa1311194. Epub 2014 Mar 19.
• Dominitz JA, Robertson DJ, Ahnen DJ, Allison JE, Antonelli M, Boardman KD, Ciarleglio M, Del Curto BJ, Huang GD, Imperiale TF, Larson MF, Lieberman D, O'Connor T, O'Leary TJ, Peduzzi P, Provenzale D, Shaukat A, Sultan S, Voorhees A, Wallace R, Guarino PD. Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design. Am J Gastroenterol. 2017 Nov;112(11):1736-1746. doi: 10.1038/ajg.2017.286. Epub 2017 Oct 10.
• Robertson DJ, Dominitz JA, Beed A, Boardman KD, Del Curto BJ, Guarino PD, Imperiale TF, LaCasse A, Larson MF, Gupta S, Lieberman D, Planeta B, Shaukat A, Sultan S, Menees SB, Saini SD, Schoenfeld P, Goebel S, von Rosenvinge EC, Baffy G, Halasz I, Pedrosa MC, Kahng LS, Cassim R, Greer KB, Kinnard MF, Bhatt DB, Dunbar KB, Harford WV Jr, Mengshol JA, Olson JE, Patel SG, Antaki F, Fisher DA, Sullivan BA, Lenza C, Prajapati DN, Wong H, Beyth R, Lieb JG 2nd, Manlolo J, Ona FV, Cole RA, Khalaf N, Kahi CJ, Kohli DR, Rai T, Sharma P, Anastasiou J, Hagedorn C, Fernando RS, Jackson CS, Jamal MM, Lee RH, Merchant F, May FP, Pisegna JR, Omer E, Parajuli D, Said A, Nguyen TD, Tombazzi CR, Feldman PA, Jacob L, Koppelman RN, Lehenbauer KP, Desai DS, Madhoun MF, Tierney WM, Ho MQ, Hockman HJ, Lopez C, Carter Paulson E, Tobi M, Pinillos HL, Young M, Ho NC, Mascarenhas R, Promrat K, Mutha PR, Pandak WM Jr, Shah T, Schubert M, Pancotto FS, Gawron AJ, Underwood AE, Ho SB, Magno-Pagatzaurtundua P, Toro DH, Beymer CH, Kaz AM, Elwing J, Gill JA, Goldsmith SF, Yao MD, Protiva P, Pohl H, Kyriakides T; CONFIRM Study Group. Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2321730. doi: 10.1001/jamanetworkopen.2023.21730. Erratum In: JAMA Netw Open. 2023 Aug 1;6(8):e2330304.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2012
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 9, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (Estimated): November 11, 2010

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 577

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No