Comparative Effectiveness of FITs With Colonoscopy

Comparative Effectiveness of Fecal Immunochemical Tests With Optical Colonoscopy

Colorectal cancer is a preventable and/or a treatable cancer, but at least 43% of the United States population is not up-to-date with screening. Although 90% of colorectal cancer screening is done using colonoscopy, most other countries use fecal immunochemical tests, reserving colonoscopy for those with a positive fecal immunochemical test. This project will provide the foundation for a paradigm shift for colorectal cancer screening in the United States by identifying how well 5 different FITs work for detecting screening relevant neoplasia, thus reducing morbidity and mortality for colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Device: Fecal immunochemical test (FIT)

Detailed Description

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in both men and women in the U.S., with nearly 50,000 deaths each year. Since CRC develops over a number of years from precursor lesions called polyps, it is largely detectable and preventable in early stages. As these polyps become larger, they, like most CRCs, tend to bleed, which is the rationale for the use of fecal occult blood tests (FOBTs) to detect both polyps and cancers early, while they are curable. However, early screening and detection is much less common than it could be, with about 43% of eligible individuals unscreened. Fecal immunochemical tests (FITs) are a type of FOBT that can be a sensitive, specific, and low cost alternative to colonoscopy for CRC screening. Modeling studies have shown that for population screening, a strategy of annual FIT testing from age of 50 to 75 years results in an equal number of life-years gained as compared with colonoscopy every 10 years. However, about 90% of screening in the U.S. is done with colonoscopy, the most expensive and invasive screening test. FITs are far less costly and largely replacing the guaiac test in CRC screening programs internationally, where only individuals with positive results are referred for a colonoscopy. Studies done on FITs in other countries often used FITs not available in the U.S. or studied high-risk populations; thus, results are not applicable in the U.S. It is critical to determine the FIT(s) with the best test characteristics in order to implement successful FIT-based screening programs in this country.

It is estimated that 24 million more individuals will need to be screened by 2018 to reach the "80% by 2018" goal set by the National Colorectal Cancer Roundtable. To address this knowledge gap, investigators propose to compare the test characteristics of three Clinical Laboratory Improvement Amendments (CLIA)-waived FITs and two automated FITs, using colonoscopy as the gold standard. The rationale for this proposed study is that, for almost all of the FITs currently marketed in the U.S., there is no evidence of the accuracy claimed. Specific aims are: Aim 1: To assess the diagnostic accuracy for advanced colorectal neoplasms of three of the most commonly used CLIA-waived FITs and two automated FITs, using colonoscopy as the gold standard.

Aim 2: To evaluate the diagnostic accuracy of two quantitative FITs using receiver operating characteristic (ROC) analysis. Aim 3: To assess factors associated with false positive and false negative FIT results for each device.

These findings will provide essential information about FITs with the best test characteristics for future expanded use of FIT, critically important to achieving the long-term goal of reducing morbidity and mortality from CRC. FITs are more acceptable to patients, will allow higher screening rates, and will reduce costs as compared with a screening strategy based on colonoscopy as the primary initial screening method.

• Study Type: Observational
• Enrollment (Anticipated): 3600

Contacts and Locations

• Study Contact: Name: Barcey T Levy, PhD, MD; Phone Number: 319-384-7000; Email: barcey-levy@uiowa.edu
• Study Contact Backup: Name: Jeanette M Daly, PhD; Phone Number: 319-384-8995; Email: jeanette-daly@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Jeanette M Daly, PhD; Phone Number: 319-384-8995; Email: jeanette-daly@uiowa.edu
      • Contact: Barcey T Levy, PhD, MD; Phone Number: 319-384-7622; Email: barcey-levy@uiowa.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina
      • Contact: Seth Crockett, MD, MPH; Phone Number: 919-966-7151; Email: seth_crockett@med.unc.edu
      • Contact: Dan Reuland, MD, MPH; Phone Number: 919-966-2276; Email: daniel_reuland@med.unc.edu
  • Texas
    • El Paso, Texas, United States, 79924
      • Recruiting
      • Texas Tech University Health Sciences Center
      • Contact: Navkiran Shokar, MD; Phone Number: 915-215-5574; Email: navkiran.shokar@ttuhsc.edu
      • Contact: Marc Zuckerman, MD; Phone Number: 915-215-5272; Email: marc.zuckerman@ttuhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients being scheduled for screening or surveillance colonoscopies meeting the study criteria at three academic health centers

Description

Inclusion Criteria:

• scheduled for a screening or surveillance colonoscopy

Exclusion Criteria:

• familial polyposis syndromes: ulcerative colitis or Crohn's disease: or active rectal bleeding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FIT Group; Fecal immunochemical tests will be completed.	Device: Fecal immunochemical test (FIT); FIT is a type of fecal occult blood test that uses antibodies to hemoglobin to detect blood in stool.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FIT Result	Individual FIT results of negative, positive, or invalid	From recruitment of first subject through study completion, an average of 4 years

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: Texas Tech University Health Sciences Center; University of North Carolina

Publications and helpful links

General Publications

• Smith RA, Andrews K, Brooks D, DeSantis CE, Fedewa SA, Lortet-Tieulent J, Manassaram-Baptiste D, Brawley OW, Wender RC. Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2016 Mar-Apr;66(2):96-114. doi: 10.3322/caac.21336. Epub 2016 Jan 21.
• Kuntz KM, Lansdorp-Vogelaar I, Rutter CM, Knudsen AB, van Ballegooijen M, Savarino JE, Feuer EJ, Zauber AG. A systematic comparison of microsimulation models of colorectal cancer: the role of assumptions about adenoma progression. Med Decis Making. 2011 Jul-Aug;31(4):530-9. doi: 10.1177/0272989X11408730. Epub 2011 Jun 14.
• Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, Halloran SP, Kuipers EJ, Seaman HE. Advances in Fecal Occult Blood Tests: the FIT revolution. Dig Dis Sci. 2015 Mar;60(3):609-22. doi: 10.1007/s10620-014-3445-3. Epub 2014 Dec 10.
• Fedewa SA, Sauer AG, Siegel RL, Jemal A. Prevalence of major risk factors and use of screening tests for cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2015 Apr;24(4):637-52. doi: 10.1158/1055-9965.EPI-15-0134.
• Robertson DJ, Imperiale TF. Stool Testing for Colorectal Cancer Screening. Gastroenterology. 2015 Oct;149(5):1286-93. doi: 10.1053/j.gastro.2015.05.045. Epub 2015 May 30.
• Allison JE. The best screening test for colorectal cancer is the one that gets done well. Gastrointest Endosc. 2010 Feb;71(2):342-5. doi: 10.1016/j.gie.2009.10.032. No abstract available.
• Hawley ST, Volk RJ, Krishnamurthy P, Jibaja-Weiss M, Vernon SW, Kneuper S. Preferences for colorectal cancer screening among racially/ethnically diverse primary care patients. Med Care. 2008 Sep;46(9 Suppl 1):S10-6. doi: 10.1097/MLR.0b013e31817d932e.
• Wolf RL, Basch CE, Brouse CH, Shmukler C, Shea S. Patient preferences and adherence to colorectal cancer screening in an urban population. Am J Public Health. 2006 May;96(5):809-11. doi: 10.2105/AJPH.2004.049684. Epub 2006 Mar 29.
• Xu Y, Levy BT, Daly JM, Bergus GR, Dunkelberg JC. Comparison of patient preferences for fecal immunochemical test or colonoscopy using the analytic hierarchy process. BMC Health Serv Res. 2015 Apr 23;15:175. doi: 10.1186/s12913-015-0841-0.
• Zauber AG, Lansdorp-Vogelaar I, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM. Evaluating test strategies for colorectal cancer screening: a decision analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2008 Nov 4;149(9):659-69. doi: 10.7326/0003-4819-149-9-200811040-00244. Epub 2008 Oct 6.
• Zavoral M, Suchanek S, Majek O, Fric P, Minarikova P, Minarik M, Seifert B, Dusek L. Colorectal cancer screening: 20 years of development and recent progress. World J Gastroenterol. 2014 Apr 14;20(14):3825-34. doi: 10.3748/wjg.v20.i14.3825.
• Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use--United States, 2012. MMWR Morb Mortal Wkly Rep. 2013 Nov 8;62(44):881-8.
• Zavoral M, Suchanek S, Zavada F, Dusek L, Muzik J, Seifert B, Fric P. Colorectal cancer screening in Europe. World J Gastroenterol. 2009 Dec 21;15(47):5907-15. doi: 10.3748/wjg.15.5907.
• de Wijkerslooth TR, Stoop EM, Bossuyt PM, Meijer GA, van Ballegooijen M, van Roon AH, Stegeman I, Kraaijenhagen RA, Fockens P, van Leerdam ME, Dekker E, Kuipers EJ. Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol. 2012 Oct;107(10):1570-8. doi: 10.1038/ajg.2012.249. Epub 2012 Jul 31.
• Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, Birkenfeld S, Leshno M, Niv Y. A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med. 2007 Feb 20;146(4):244-55. doi: 10.7326/0003-4819-146-4-200702200-00003.
• Seeff LC, Richards TB, Shapiro JA, Nadel MR, Manninen DL, Given LS, Dong FB, Winges LD, McKenna MT. How many endoscopies are performed for colorectal cancer screening? Results from CDC's survey of endoscopic capacity. Gastroenterology. 2004 Dec;127(6):1670-7. doi: 10.1053/j.gastro.2004.09.051.
• Sharara AI, El Reda ZD, Harb AH, Abou Fadel CG, Sarkis FS, Chalhoub JM, Abou Mrad R. The burden of bowel preparations in patients undergoing elective colonoscopy. United European Gastroenterol J. 2016 Apr;4(2):314-8. doi: 10.1177/2050640615594550. Epub 2015 Jul 3.
• 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.
• Levy BT, Bay C, Xu Y, Daly JM, Bergus G, Dunkelberg J, Moss C. Test characteristics of faecal immunochemical tests (FIT) compared with optical colonoscopy. J Med Screen. 2014 Sep;21(3):133-43. doi: 10.1177/0969141314541109. Epub 2014 Jun 23.
• Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, Birkenfeld S, Lieberman N, Klang S, Niv Y. Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDs, and anticoagulants. Am J Gastroenterol. 2009 Apr;104(4):933-8. doi: 10.1038/ajg.2009.14. Epub 2009 Mar 17.
• Crouse AL, De Koning L, Sadrzadeh SM, Naugler C. Sensitivity and Specificity of Community Fecal Immunotesting Screening for Colorectal Carcinoma in a High-Risk Canadian Population. Arch Pathol Lab Med. 2015 Nov;139(11):1441-5. doi: 10.5858/arpa.2014-0454-OA.
• Rozen P, Comaneshter D, Levi Z, Hazazi R, Vilkin A, Maoz E, Birkenfeld S, Niv Y. Cumulative evaluation of a quantitative immunochemical fecal occult blood test to determine its optimal clinical use. Cancer. 2010 May 1;116(9):2115-25. doi: 10.1002/cncr.25012.
• Levy BT, Daly JM, Xu Y, Crockett SD, Hoffman RM, Dawson JD, Parang K, Shokar NK, Reuland DS, Zuckerman MJ, Levin A. Comparative effectiveness of five fecal immunochemical tests using colonoscopy as the gold standard: study protocol. Contemp Clin Trials. 2021 Jul;106:106430. doi: 10.1016/j.cct.2021.106430. Epub 2021 May 8.

Helpful Links

• National Colorectal Cancer Roundtable. Tools & Resources - 80% by 2018

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 2, 2017
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): July 31, 2022

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (ACTUAL): August 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

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: R01CA215034 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once the key publications are accepted and finalized, de-identified data and the codebook will be made available to anyone with a legitimate request who follows the Data Sharing agreement.
• IPD Sharing Time Frame: Once study key publications have been accepted and finalized for publication.
• IPD Sharing Access Criteria: Researchers have to make a formal proposal for data and codebook.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No