Abstract
Objectives
Faecal immunochemical tests for haemoglobin (FIT) are used in colorectal cancer (CRC) screening programmes and to triage patients presenting with symptoms suggestive of CRC for further bowel investigations. There are a number of quantitative FIT analytical systems available. Currently, there is no harmonisation or standardisation of FIT methods. The aim of the study was to assess the comparability of numerical faecal haemoglobin concentrations (f-Hb) obtained with four quantitative FIT systems and the diagnostic accuracy at different f-Hb thresholds.
Methods
A subgroup of the National Institute for Health and Care Excellence (NICE) FIT study, a multicentre, prospective diagnostic accuracy study were sent four FIT specimen collection devices from four different FIT systems or two FIT devices for one FIT system. Faecal samples were examined and analysis of results carried out to assess difference between methods at thresholds of limit of detection (LoD), 10 µg haemoglobin/g faeces (µg/g) and 100 μg/g.
Results
233 patients returned specimen collection devices for examination on four different systems; 189 patients returned two FIT kits for one system. At a threshold of 100 μg/g the sensitivity is the same for all methods. At lower thresholds of LoD and 10 μg/g differences were observed between systems in terms of patients who would be referred and diagnostic accuracies.
Conclusions
The lack of standardisation or harmonisation of FIT means that differences are observed in f-Hb generated on different systems. Further work is required to understand the clinical impact of these differences and to minimise them.
Acknowledgments
The study supported by Croydon University Hospital and RM Partners in the design and conduct of the trial. Patients were recruited nationally through the NIHR Clinical Research Network, Principal Investigators and R&D teams at each site. Alpha Labs Ltd supported the study prior to funding with FIT kits and production of patient information. We thank Professor Stephen Duffy for his guidance with some of the statistical methodology.
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Research funding: This study is a sub-study of the NICE FIT study which was funded by an NHS England award to RM Partners, the West London Cancer Alliance hosted by The Royal Marsden NHS Foundation Trust. The study was supported by the National Institute for Health Research Clinical Research Network Portfolio. Alpha Labs Ltd, MAST Diagnostics, Sysmex and Abbott/ Alfresa supported the study by providing FIT kits and reagents without charge. The study funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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Author contributions: SCB drafted the manuscript. ZZ and CP carried out statistical analysis. CP, SOD and ZZ carried out laboratory analysis of samples. CGF provided guidance on statistical analysis. All authors provided significant input to the study, reviewed and revised drafts of the manuscript, and approved the submitted version. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013). The study was approved by the National Research Ethics Service Committee, London- South East. Full title: NICE Guidelines and The Faecal Immunochemical Test Study. REC No: 16/LO/2,174. IRAS project ID 218404.
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Principal investigators: Mark Austin (Brighton and Sussex University Hospitals NHS Trust); Gemma Faulkner (Bolton NHS Foundation Trust); John Stebbing (Royal Surrey NHS Foundation Trust); Jonathan Epstein (Salford Royal NHS Foundation Trust).
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Patient consent statement: No identifiable patient data is present in the manuscript, Permission to reproduce material from other sources, No material was reproduced from other sources.
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Permission to reproduce material from other sources: No material was reproduced from other sources.
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Clinical trial registration: ISRCTN49676259.
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