Home Medicine Thresholds adjustments and impact on clinical performance of three FIT assays in a colorectal cancer screening program
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Thresholds adjustments and impact on clinical performance of three FIT assays in a colorectal cancer screening program

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Published/Copyright: November 10, 2025
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 64 Issue 3

Abstract

Objectives

Fecal immunochemical tests (FITs) from various manufacturers yield different results, leading to variable positivity rates and clinical performance. These differences can influence the healthcare costs of a colorectal cancer screening program (CRC-SP), specifically when switching among FIT manufacturers. The analytical and clinical performance of three FITs was investigated to determine adjusted thresholds using positivity rate harmonization.

Methods

A cohort of 6,600 participants from the Quebec CRC-SP received collection kits from three different manufacturers to sample the same fresh stool. Participants with positive results were referred for a colonoscopy which was considered positive if advanced neoplasia (AN) was detected. Positivity rates were determined for each FIT at an unadjusted threshold. Adjusted thresholds were determined using a positivity rate harmonization strategy. Clinical performance was then evaluated for each supplier at unadjusted and adjusted thresholds.

Results

Among 5,513 participants who fulfilled the inclusion criteria, 327 underwent colonoscopy. The FIT positivity rates at unadjusted thresholds differed between manufacturers. The adjusted thresholds determined to yield the same positivity rate were different for each FIT. A total of 69 participants were diagnosed with AN. Significant differences in concordance, discordance, sensitivity, and specificity were observed when using the unadjusted threshold. After applying adjusted thresholds, differences in clinical performance between manufacturers were no longer statistically significant.

Conclusions

Threshold adjustment using a positivity rate harmonization strategy render differences in clinical performance statistically nonsignificant and leads to a stable colonoscopy rate between manufacturers. CRC screening programs should determine adjusted thresholds when changing FIT suppliers or when using multiple assays.

Keywords: stool; gastro-intestinal; neoplasia; cancer; colorectal cancer screening; fecal immunochemical test
Corresponding author: Dr. Artuela Çaku, Centre de recherche du CHUS, CIUSSS de L’Estrie-CHUS, 3001 12e avenue Nord, Sherbrooke,QC, Canada; and Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001 12e avenue Nord, J1H 5N4, Sherbrooke, QC, Canada, E-mail:

Funding source: The Ministère de la Santé et des Services sociaux du Québec (MSSS).

Acknowledgments

We would like to express our sincere gratitude to Somagen Diagnostics (Eiken Chemical), QuidelOrtho (Sentinel Diagnostics), and Abbott Rapid Diagnostics (Alfresa Pharma) companies as well as the Ministère de la Santé et des Services sociaux for their financial support, which was vital for the success of this project. Additionally, we thank Centre de recherche du CHUS for their research support and M. Serge Simard for the statistical analysis which truly helped us in the advancement of this work.

  1. Research ethics: The study was approved by CHUS Research center Ethics Board (2021–3937).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: Jean Dubé et Artuela Çaku developed the idea of this study and secured the funding from companies and government. Jean Dubé, Charles Ménard, Artuela Çaku, Rosalie Plantefève, Luc Galarneau and François Corbin participated in the study design. Rosalie Plantefève and Maude Bonin, were involved in participant recruitment, data collection, and data management and analysis. Charles Ménard supervised the team of gastroenterologists and Jean-Denis Rousseau supervised the team of general surgeons for colonoscopy procedures Rosalie Plantefève, Jean Dubé, and Artuela Çaku prepared the main draft of the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: Dr. Dubé, Dr. Çaku, and Dr. Ménard received honorariums from Somagen Diagnostics (Eiken Chemical), QuidelOrtho (Sentinel Diagnostics), and Abbott Rapid Diagnostics (Alfresa Pharma) for the study. All other authors state no conflict of interest.

  6. Research funding: None declared

  7. Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0546).

Received: 2025-05-06
Accepted: 2025-10-22
Published Online: 2025-11-10
Published in Print: 2026-02-24

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0546
Keywords for this article
stool; gastro-intestinal; neoplasia; cancer; colorectal cancer screening; fecal immunochemical test

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The European Health Data Space: challenges and opportunities for laboratory medicine
  4. Review
  5. Saliva sampling matters for salivary diagnostics of viral infections
  6. Opinion Papers
  7. Mass spectrometry based precision diagnostics: on the cusp of selective testing
  8. Supporting trend detection in the cumulative display of electronic laboratory reports from multiple laboratories while preserving measurement provenance
  9. Secondary use of external quality assessment data – estimating inter-assay variation in LOINC-coded datasets
  10. Methodological evaluation and clinical interpretation of hs-cTnI and hs-cTnT variations: a reappraisal
  11. Point of care testing of biochemical markers for monitoring astronauts during long duration missions in deep space
  12. EFLM Paper
  13. Strategy of Laboratory Medicine – EFLM Vision
  14. Guidelines and Recommendations
  15. Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part III: Clinical and analytical recommendations for the study of monoclonal gammopathies by MALDI-TOF mass spectrometry
  16. Genetics and Molecular Diagnostics
  17. Optimization and comparison of genomic DNA extraction from whole blood collected in PAXgene blood RNA tube using automated platforms
  18. Small-scale external quality assessment of methylated SHOX2 and RASSF1A detection in China: findings from 2023–2024
  19. General Clinical Chemistry and Laboratory Medicine
  20. Development and validation of a machine learning model for accurate detection of wrong blood in tube errors in hospitalized patients
  21. Short- and medium-term pre-analytical stability of human serum insulin-like growth factor-1
  22. Creatinine measurement from finger stick dried blood spots with a routine chemistry analyzer for estimation of GFR
  23. Towards a global framework of entrustable professional activities for undergraduate clinical laboratory interns: a competency-based approach
  24. Spot urine is a suitable matrix for measurement of copeptin
  25. Reference Values and Biological Variations
  26. Use of indirect methods and machine learning algorithms for the estimation of reference intervals, taking cortisol measurements as an example
  27. ReferenceRangeR: a novel tool designed to facilitate reference interval estimation and verification
  28. VeRUS: verification of reference intervals based on the uncertainty of sampling
  29. Hematology and Coagulation
  30. Hemolysis index. Can we uncritically trust manufacturer declarations?
  31. Cancer Diagnostics
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  33. A robust ddPCR assay for the absolute quantification of miR-192-5p in hepatocellular carcinoma liquid biopsies
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