Thresholds adjustments and impact on clinical performance of three FIT assays in a colorectal cancer screening program
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Jean Dubé
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.
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.
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Research ethics: The study was approved by CHUS Research center Ethics Board (2021–3937).
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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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.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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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.
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Research funding: None declared
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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).
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