Analytical evaluation of eight qualitative FIT for haemoglobin products, for professional use in the UK.

OBJECTIVES: Qualitative faecal immunochemical tests for haemoglobin (FIT), for triaging for colorectal cancer investigations, are available for professional use. The aim was to evaluate these lateral flow tests. No previous analytical evaluations have been published. METHODS: Analytical sensitivity (AS) was assessed using samples spanning manufacturers' quoted AS, concurrently with the quantitative OC-SENSOR PLEDIA, using Hb-spiked samples in manufacturers' buffer (n≥5; ≤9-99 ng Hb/mL buffer), Hb-spiked faeces (n=6; <2-34 µg Hb/g faeces) and natural faeces (n=17; <2-82 µg/g); concentrations for 50 %/100 % Hb-detected were compared with quoted AS. Compatibility with two external quality assessment schemes (EQAS) (n=9; 3-96 µg/g) and prozone compared with manufacturers limits (n=9; 2,500-10,000,000 ng/mL) were tested. Ease-of-use by five healthcare personnel was assessed. RESULTS: Seven products showed lower AS (ng/mL) than manufacturers quoted using Hb-spiked aqueous samples compared with OC-SENSOR, one was equivocal; six manufacturers quoted AS in µg/g, five showed lower AS using Hb-spiked faeces. Results were similar but less consistent for natural faeces. Result lines for low concentrations can be faint and open to interpretation. Results were consistent with manufacturers quoted prozone limits. Results were consistent for seven products for two EQAS. The ease-of-use was 68.5-85.6 %; products with lower scores could be improved with better instructions and sample bottles. CONCLUSIONS: AS was lower for seven products (aqueous samples) and five products (aqueous/faecal samples) and prozone consistent with manufacturers expected concentrations, compared with OC-SENSOR. EQAS results were mostly consistent with expected results; products can be used by healthcare professionals, though some manufacturer improvements could be made.

Faecal haemoglobin concentration and colorectal cancer site, stage and grade in a symptomatic cohort.

AIM: Minimal evidence exists regarding faecal immunochemical tests (FITs) for colorectal cancer (CRC) site, stage and grade in symptomatic patients. The primary aim is to determine any association between faecal haemoglobin concentration (f-Hb) (analysed with OC-Sensor™ Pledia) and these prognostic factors. The secondary aim is to determine the association between f-Hb and anaemia, microcytosis and iron deficiency (Hb, mean corpuscular volume [MCV] and ferritin). METHODOLOGY: Symptomatic 2-week wait CRC patients with FIT were included (July 2019-October 2022). Median f-Hb and interquartile range according to sex, stage, grade and site (right-sided, caecum to transverse colon, R-CRC; left-sided, splenic flexure to rectum, L-CRC) were compared using the Mann-Whitney U test. Hb, MCV and ferritin were categorized into two groups and the median f-Hb was compared using the Mann-Whitney U test. RESULTS: In all, 114 patients (57 women, 57 men) were studied; 46 had R-CRC (f-Hb = 113 µg Hb/g) and 68 had L-CRC (f-Hb = 342 µg Hb/g) (P = 0.07). Sixty-nine were moderately differentiated CRC (f-Hb = 183 µg Hb/g) and 29 were poorly differentiated (f-Hb = 866 µg Hb/g) (P = 0.04). By T-stage, 35 were early (T1/2) (f-Hb = 170 µg Hb/g) and 79 were advanced (T3/4) (f-Hb = 200 µg Hb/g) (P = 0.06). The relationship between f-Hb and Hb, MCV and ferritin was not significant. Poorly differentiated (P = 0.04) and later stage (P = 0.02) R-CRC had significantly lower f-Hb compared to L-CRC. CONCLUSIONS: Right-sided CRC is associated with lower f-Hb than left. Poorly differentiated and later staged L-CRC had higher median f-Hb. These data add to existing evidence suggesting that FIT may be less sensitive for right-sided CRC. Strategies to mitigate the potential for missed or FIT-negative right-sided CRC are required.

The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?

AIM: Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification. METHODS: This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 µg Hb/g of faeces [µg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 µg/g). CRC and SBD detection rates were compared by strategy. RESULTS: A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 µg/g, <6 µg/g for benign pathology. CONCLUSIONS: One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations.

Sample comparison of BÜHLMANN fCAL Turbo and OC-FCa faecal calprotectin methods.

BACKGROUND: Faecal calprotectin is an inflammatory marker used to triage patients for further investigation with suspected inflammatory bowel disease (IBD). Our current method requires faecal samples be sent to the laboratory, where calprotectin is extracted before analysis. This is a time-consuming, potential bottleneck in the pathway. We have recently evaluated the OC-SENSOR PLEDIA fCAL method that uses the same sampling device as used in some bowel cancer screening and symptomatic colorectal cancer programmes that detect faecal haemoglobin. The below study is a comparison of the OC-FCa method with the BÜHLMANN fCAL Turbo which is used routinely within BSPS. METHOD: 150 homogenised and 110 non-homogenised faecal samples were loaded into OC-Sampling Bottle 3 and BÜHLMANN CALEX cap sampling devices. The samples were then analysed on their respective systems according to manufacturer's instructions. RESULTS: The OC-FCa assay had a mean positive bias of 67.3% (homogenised) and 88.4% (non-homogenised). Homogenised samples showed substantial agreement between the methods for normal (<50 µg/g) and elevated (150+µg/g) risk categories (k = 0.794, k = 0.788, respectively) and moderate agreement for borderline (51-150 µg/g) (k = 0.25) according to the current Berkshire and Surrey Pathology Service (BSPS) guidelines. Non-homogenised samples had none to slight agreement for normal and borderline values (k = 0.02 for both) and moderate agreement for elevated (k = 0.596). CONCLUSION: The OC-FCa method is a viable alternative for faecal calprotectin testing, but requires an adjustment to clinical cut-off values due to the lack of standardisation and strong positive bias. A clinical comparative study is required to assess the impact of patients collecting their own samples into the devices, as this may negate any potential degradation samples may exhibit during transit to the laboratory.

A service evaluation of the use of faecal immunochemical tests in symptomatic patients aged under 50 years presenting to primary care.

BACKGROUND: Most colorectal cancers (CRCs) occur in individuals aged over 50 years; however, the incidence in younger age groups is increasing. Diagnosis in younger patients is frequently delayed due to non-specific symptoms and the relative frequency of benign disease. There is a need to identify patients who warrant further investigation for CRC. This study reviewed whether a faecal haemoglobin (f-Hb) ≥10 µg Hb/g faeces measured by the faecal immunochemical test for f-Hb (FIT) was associated with CRC in a local primary care population aged under 50 years. METHODS: f-Hb results from symptomatic patients aged 18-49 years presenting to primary care during a 17-month period were extracted from local laboratory information systems. Colonoscopy lists were obtained from three local trusts. The Somerset Cancer Registry was searched to identify CRCs. f-Hb and outcomes were matched using NHS numbers. RESULTS: A total of 3119 patients were included (median age 41 years); 313 of 2682 patients with f-Hb <10 µg/g (11.7%) and 305 of 437 patients with f-Hb ≥10 µg/g (69.8%) underwent colonoscopy. Twelve CRCs were detected. At a cut-off of 10 µg/g, the positivity rate was 14.0%, sensitivity was 100% (75.8-100%), specificity was 86.3% (85.1-87.5%), positive predictive value (PPV) was 2.7% (2.5-3.0%) and negative predictive value (NPV) was 100%. At a cut-off of 150 µg/g, sensitivity was 83.3% (55.2-95.3%), specificity was 95.2% (94.4-95.9%), PPV was 6.2% (4.7-8.2%) and NPV was 99.9% (99.8-100%). CONCLUSION: Our data supports the use of FIT to triage patients aged under 50 years presenting to primary care with symptoms suggestive of CRCs.

Effect of multiple loading FIT sample collection devices on faecal haemoglobin concentration.

BACKGROUND: Faecal immunochemical tests (FIT) are routinely used in colorectal cancer (CRC) screening programmes around the world. More recently, quantitative FIT has been recommended to help triage patients presenting to primary care with symptoms suggestive of CRC. Participants collect faecal samples using sampling probes which are inserted into sample collection devices (SCDs) containing preservative buffer. The SCDs have an internal collar designed to remove excess sample. The aim of this study was to investigate the impact of multiple loading on faecal haemoglobin concentration (f-Hb) using SCDs of four FIT systems. METHODS: Pools of f-Hb negative samples were spiked with blood, homogenised and loaded into SCDs 1, 3 and 5 times, with insertion of the sampling probes into the SCDs with and without mixing between loads. The f-Hb was measured using the relevant FIT system. The percentage change in f-Hb for multiple loads was compared with a single load for each system for the mixed and unmixed groups. RESULTS: The p values show a significant difference (p < 0.05) in the mass and f-Hb for the mixed and unmixed group, for 1-3 and 1-5 loads for all systems. The median percentage change in f-Hb for the mixed is higher than the unmixed group. CONCLUSION: This study showed that multiple loading does significantly increase the f-Hb in the SCDs.

Comparison and commutability study among four faecal immunochemical tests (FIT) systems.

OBJECTIVES: Faecal immunochemical tests for haemoglobin (FIT) are used in colorectal cancer screening programs around the world and increasingly for triage of symptomatic patients. FIT results are currently not traceable to a common reference standard and results obtained on various FIT systems may not be equivalent. The size of the bias between the systems is difficult to quantify due to the complex pre-analytical aspects of FIT. METHODS: This study aimed to quantify the bias and the correlation between four FIT systems by measuring a panel of 38 faecal samples while limiting the effect of the pre-analytical aspects. In addition, the commutability of seven candidate reference materials (RM) was assessed. RESULTS: Pairwise method comparisons based on faecal samples demonstrated Pearson correlation coefficients ranging between 0.944 and 0.970 and an average proportional bias of -30 to -35 % for one FIT system compared to the other three. The relative standard deviation among biases of the individual samples was around 20 %. Due to these sample specific differences, no decisive conclusions could be drawn in the commutability study. However, two candidate RMs, prepared in the FIT system-specific storage/extraction buffers, had a better commutable profile than the other five. CONCLUSIONS: The use of a common threshold for all FIT systems is currently not possible due to the presence of a proportional bias. We have identified potential commutable RMs to take to further studies on the production of a common calibrator, with the aim being to reduce the analytical bias observed on different FIT systems.

Risk-stratified faecal immunochemical testing (FIT) for urgent colonoscopy in Lynch syndrome during the COVID-19 pandemic.

BACKGROUND: Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing ('FIT') in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were limited. METHODS: An emergency service protocol was designed to improve colonoscopic surveillance access throughout the COVID-19 pandemic in England for people with Lynch syndrome when services were extremely restricted (1 March 2020 to 31 March 2021) and promoted by the English National Health Service. Requests for faecal immunochemical testing from participating centres were sent to the National Health Service Bowel Cancer Screening South of England Hub and a faecal immunochemical testing kit, faecal immunochemical testing instructions, paper-based survey, and pre-paid return envelope were sent to patients. Reports with faecal haemoglobin results were returned electronically for clinical action. Risk stratification for colonoscopy was as follows: faecal haemoglobin less than 10 µg of haemoglobin/g of faeces (µg/g)-scheduled within 6-12 weeks; and faecal haemoglobin greater than or equal to 10 µg/g-triaged via an urgent suspected cancer clinical pathway. Primary outcomes of interest included the identification of highest-risk Lynch syndrome patients and determining the impact of faecal immunochemical testing in risk-stratified colonoscopic surveillance. RESULTS: Fifteen centres participated from June 2020 to March 2021. Uptake was 68.8 per cent amongst 558 patients invited. For 339 eligible participants analysed, 279 (82.3 per cent) had faecal haemoglobin less than 10 µg/g and 60 (17.7 per cent) had faecal haemoglobin greater than or equal to 10 µg/g. In the latter group, the diagnostic accuracy of faecal immunochemical testing was 65.9 per cent and escalation to colonoscopy was facilitated (median 49 versus 122 days, χ2 = 0.0003, P < 0.001). CONCLUSION: Faecal immunochemical testing demonstrated clinical value for Lynch syndrome patients requiring colorectal cancer surveillance during the pandemic in this descriptive report of an emergency COVID-19 response service. Further longitudinal investigation on faecal immunochemical testing efficacy in Lynch syndrome is warranted and will be examined under the 'FIT for Lynch' study (ISRCTN15740250).

An observational study of replicate faecal immunochemical tests in the urgently referred symptomatic cohort.

INTRODUCTION: Triage of patients with suspected colorectal cancer (CRC) utilises a single faecal immunochemical test (FIT) at a defined threshold. Limited evidence exists regarding whether replicate FIT improves the positive and negative predictive value in symptomatic patients. This study examines urgently referred symptomatic patients undergoing replicate FIT. Primary aim is to assess two FITs and CRC/serious bowel disease. Secondary aims are to determine correlation and utility of replicate FIT. METHODOLOGY: Patients carried out one additional FIT during COVID-19 pandemic. FIT 1 and FIT 2 (the replicate sample) were analysed in relation to symptoms, diagnoses, investigations, future colonoscopy and missed CRC. Study period was 01/03/2020-31/07/2020. Three subgroups were compared; double positive (≥10 µg Hb/g faeces), double negative, and discordant FIT (one positive). RESULTS: 111 patients had replicate FIT (50 male, 61 female). 43 (38.7%) patients had double negative, 32 (28.8%) double positive and 36 (32.4%) had discordant FITs. Median time between FITs was 14 days (IQR = 11-19). 83% of double positive patients underwent colonoscopy/virtual colonoscopy (61% in double negative patients). Six CRC and one high-risk polyp were in double positive patients (none in other groups). One discordant patient was not investigated and a CRC missed. CONCLUSIONS: Replicate FIT as a triage strategy appears most effective where both FITs are negative. CRC risk is low when FIT results are discordant. Double negative FITs are reassuring given benign associated diagnoses, or for patients where endoscopic investigation is high-risk. Larger studies are required to evaluate discordant FITs, enabling refinement of urgent investigation pathways.

Comparison of faecal calprotectin using two collection and extraction strategies for the BÜHLMANN CALEX® Cap - possible implications for clinical cut-offs?

BACKGROUND: Faecal calprotectin has been identified as a useful biochemical marker in the differentiation of inflammatory bowel disease and irritable bowel syndrome. Typically, patients send faecal specimens in a pot for manual extraction by the laboratory. During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pandemic, the routine laboratory service was temporarily suspended due to the potential increased risk to staff. In this study we investigated the possibility of patients collecting samples directly into the faecal extraction tubes. METHOD: Patients submitted paired faecal samples for calprotectin analysis using a standard faecal container (current practice) and followed instructions for faecal collection using the BÜHLMANN CALEX® Cap device. Samples were returned to the laboratory immediately after collection. Laboratory staff manually extracted the calprotectin from the faecal samples using the CALEX® Cap prior to analysis of both extracts on the Cobas c702. RESULTS: 91 paired faecal samples were included in the study. Clinical correlation was found to be 70% with numerical correlation showing a positive bias for the patient-collected CALEX® Cap sample when compared to the laboratory-extracted faecal sample around the clinical decision points 100-250 µg calprotectin/g faeces. CONCLUSION: The study shows that collection of a faecal sample using the CALEX® Cap works well and is a good alternative to using standard containers. The correlation gives rise to the possibility that faecal calprotectin is not stable when collected into standard collection containers. Prior to further roll-out of this process, questions surrounding the current cut-offs would need to be addressed.

Efficacy and accuracy of faecal sampling by a digital rectal examination for faecal immunochemical testing.

AIM: A digital rectal examination (DRE) during routine assessment for patients with abdominal symptoms provides an opportunity to obtain faeces from the glove for faecal immunochemical testing (FIT). Here, we compared sampling via DRE to the standard faecal sampling by patients. METHOD: Patients were recruited to a prospective observational cohort study between July 2019 and March 2020. Patients provided a sample for the FOB Gold Wide® which was compared to a further sample taken at clinic via DRE. Clinicians reported whether they obtained a 'good' sample filling all the grooves, a 'poor' sample filling some of the grooves or no faecal sample. Cohen's kappa was used to compare percentage agreement around a negative threshold of <10 µg haemoglobin/g of faeces. Sensitivity for serious bowel disease (SBD) was calculated. RESULTS: Of 596 patients who underwent attempted DRE sampling, there were 258 (43.3%) 'good' samples, 117 (19.6%) 'poor' samples and 221 (37.1%) with no sample to wipe in the grooves. Cohen's kappa dropped from 0.70 to 0.30 for the 'good' and 'poor' samples, respectively. Of those with DRE samples and definitive diagnostic outcomes, the sensitivity for SBD dropped significantly from 76.0% to 41.7% between 'good' and 'poor' samples, respectively (p = 0.041). CONCLUSIONS: A 'good' sample obtained by DRE provides comparable results to samples obtained by patients. This creates potential benefit in speed and ease of testing for patients. However, not all DRE sampling attempts are successful, and the clinician must be satisfied that enough faeces is obtained to wipe adequately into all grooves.

Replicate and repeat faecal immunochemical tests in symptomatic patients: A systematic review.

BACKGROUND: Faecal Immunochemical tests (FITs) in the assessment of patients presenting with symptoms have generally used a single sample. Little evidence pertains to the use of replicate, where a number of tests are done prior to decision-making or repeat FIT, where additional FIT are performed following clinical decision-making. Overwhelmingly, research has focussed on FIT to help identify colorectal cancer (CRC). The aim of this review is to assess the available literature concerning replicate and repeat FIT in symptomatic patients to help generate consensus and guide future research. METHODS: The terms 'faecal immunochemical test' or 'FIT' were combined with 'multiple' or 'repeat'. EMBASE, Medline and PubMed database and other searches were conducted. All papers published in English were included with no exclusion date limits until November 2021. RESULTS: Of the 161 initial papers screened, seven were included for review. Qualitative and quantitative FIT outcomes were assessed in the studies. The primary aims of most related to whether replicate FIT increased diagnostic yield of CRC, with colonoscopy used as the reference standard. One publication assessed the impact of a new COVID-adapted pathway on CRC detection. No consensus on replicate FIT was apparent. Some concluded that FITs may help minimise missed CRC diagnoses: others showed no increase in diagnostic yield of CRC. CONCLUSIONS: Current evidence on replicate and repeat FIT is both minimal and conflicting. FIT is a superb clinical tool, but significant gaps surrounding application remain. Further studies relating to replicate and repeat FIT are required.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

A comparison of the faecal haemoglobin concentrations and diagnostic accuracy in patients suspected with colorectal cancer and serious bowel disease as reported on four different faecal immunochemical test systems.

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.

Evaluation of a faecal calprotectin method using the OC-SENSOR PLEDIA.

OBJECTIVES: The National Institute for Health and Care Excellence recommends faecal calprotectin (f-cal) to help differentiate inflammatory bowel diseases from irritable bowel syndrome. Faecal samples for calprotectin have historically been collected at home by patients into screw-top pots and sent to laboratories where calprotectin is extracted and analysed. Faecal haemoglobin (f-Hb) samples are collected at home into specific collection devices containing stabilising buffer. We evaluated the OC-FCa method for f-cal, developed by Eiken Chemical Co., Ltd. (Japan) that uses the same collection device and analyser as f-Hb. METHODS: OC-FCa was assessed for limit of blank (LOB), limit of detection (LOD), limit of quantification (LOQ), within and between-run imprecision, linearity, prozone, recovery and carryover. A method comparison against the BÜHLMANN fCAL® turbo (BÜHLMANN Laboratories AG, Switzerland) was performed using patient samples and EQA. RESULTS: The LOB was 3 µg calprotectin/g faeces (µg/g), LOD 8 µg/g and LOQ 20 µg/g. Within and between-run imprecision was <5%; linearity was good (R2 > 0.99); prozone was appropriately detected; recovery was 99.6%; no observed carryover. OC-FCa showed a strong positive bias compared with BÜHLMANN fCAL® turbo (Z=-5.3587, p < 0.001). When categorised using our local pathway, which interprets calprotectin concentrations and need for further investigation, Cohen's Kappa demonstrates substantial agreement at <50 µg/g (κ=0.80) and >150 µg/g (κ=0.63) and fair agreement (κ=0.22) in the borderline category 50-150 µg/g. CONCLUSIONS: The OC-FCa method performed well in the evaluation. With the lack of standardisation for f-cal a clinical study is required to evaluate the positive bias and establish suitable cut-off levels.

Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients.

OBJECTIVES: Faecal immunochemical testing for haemoglobin (FIT) is used to triage patients for colonic investigations. Point-of-care (POC) FIT devices on the market have limited data for their diagnostic accuracy for colorectal cancer (CRC). Here, a POC FIT device is compared with a laboratory-based FIT system using patient collected samples from the urgent referral pathway for suspected CRC. METHODS: A prospective, observational cohort study. Patients collected two samples from the same stool. These were measured by POC QuikRead go® (Aidian Oy, Espoo, Finland) and laboratory-based FOB Gold Wide® (Sentinel Diagnostics, Italy). Faecal haemoglobin <10 µg haemoglobin/g of faeces was considered as negative. At this threshold, comparisons between the two systems were made by calculating percentage agreement and Cohen's kappa coefficient. Proportion of negative results were compared with Chi squared testing. Sensitivities for CRC were calculated. RESULTS: A total of 629 included patients provided paired samples for FIT to compare the QuikRead go® and FOB Gold Wide®. The agreement around the negative threshold was 83.0% and Cohen's kappa coefficient was 0.54. The QuikRead go® reported 440/629 (70.0% of samples) as negative compared to 523/629 (83.1%) for the FOB Gold Wide®, this difference was significant (p-value<0.001). Sensitivities for CRC detection by the QuikRead go® and FOB Gold Wide® were 92.9% (95% confidence interval (CI): 68.5-98.7%) and 100% (CI: 78.5-100%) respectively. CONCLUSIONS: Both systems were accurate in their ability to detect CRC. Whilst good agreement around the negative threshold was identified, more patients would be triaged to further colonic investigation if using the QuikRead go®.

Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients.

AIM: Detection of early onset colorectal cancer is challenging, and remains a rare diagnosis amongst younger people with gastrointestinal symptoms. We investigated whether faecal immunochemical testing (FIT) could identify younger patients at higher risk of colorectal cancer or serious bowel disease including colorectal cancer, inflammatory bowel disease or advanced adenomas. METHODS: A subgroup analysis was performed of symptomatic patients under 50 years of age (<50) from the NICE FIT study, a multicentre, prospective diagnostic accuracy study of FIT conducted between October 2017 and December 2019. The diagnostic accuracy of FIT for colorectal cancer and serious bowel disease was investigated in younger patients at different faecal haemoglobin (f-Hb) cut-offs of 2, 10 and 150 µg blood/g faeces (µg/g). RESULTS: Early onset colorectal cancer was diagnosed in 1.5% (16/1103) of younger symptomatic patients. The sensitivity of FIT for younger patients aged <50 was 87.5% (95% CI 61.7%-98.4%), 81.3% (54.4%-96.0%) and 68.8% (41.3%-89.0%) at f-Hb cut-offs of 2, 10 and 150 µg/g, respectively. The positive predictive value for colorectal cancer increased from 4.2% (2.3%-6.9%) to 11.5% (5.9%-19.6%) at cut-offs of 2 and 150 µg/g, while the positive predictive value for serious bowel disease increased from 31.3% (26.3%-36.5%) to 65.6% (55.2%-75.0%) at the same cut-offs. The negative predictive value of FIT for colorectal cancer remained above 99.5% at all cut-offs. CONCLUSION: Detectable f-Hb on FIT in symptomatic younger patients may indicate referral for investigation of colorectal cancer and serious bowel disease.

Diagnostic accuracy of point of care faecal immunochemical testing using a portable high-speed quantitative analyser for diagnosis in 2-week wait patients.

AIM: Laboratory-based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2-week wait (TWW) colorectal patients. METHODS: The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre. Between July 2019 and March 2020, patients were invited to perform and bring a FIT sample to clinic. FIT was completed within the clinic appointment using a POC quantitative analyser that has a 2-min processing time (QuikRead go®). Patients and clinicians were blinded to results within the clinic appointment. The results were compared with subsequent diagnostic outcomes. Faecal haemoglobin of <10 µg haemoglobin/g of faeces was considered a negative result. Sensitivities for colorectal cancer (CRC) and combined serious bowel disease (SBD) were calculated using this pre-determined cut-off. RESULTS: A total of 553 patients were included for analytical comparison with diagnostic outcomes. There were 14 (2.5%) patients with CRC and 52 (9.4%) with SBD. The sensitivities for CRC and SBD were 92.9% (95% CI 68.5%-98.7%) and 76.9% (95% CI 63.9%-86.3%) respectively. 379 (68.5%) patients had a negative FIT result (negative predictive value for CRC was 99.7%). CONCLUSIONS: This POC FIT device is a useful adjunct to better manage TWW patients. The high observed sensitivity for CRC offers opportunities, within a single consultation, for improved triage and rationalization of investigation for those with bowel symptoms.

Impact of changing from a guaiac faecal occult blood test to a faecal immunochemical test in a national screening programme: Results from a pilot study within the national bowel cancer screening programme in England.

OBJECTIVE: Testing for occult blood in faeces is widely used in bowel cancer screening around the world. In many programmes, the faecal immunochemical test (FIT) is replacing the traditional guiaic faecal occult blood test (gFOBT). There have been a number of reports on the clinical impact of making this change; yet, no-one has considered the pre-analytical and analytical impact of moving from a gFOBT to a FIT bowel cancer screening programme. METHODS: We interrogated data obtained in a FIT pilot carried out in England in 2014 to assess the timeliness of specimen collection device return time and analysis for gFOBT and FIT, the impact of time to analysis on faecal haemoglobin (f-Hb) concentration, and any differences observed between analyses carried out at two different testing laboratories. RESULTS: FIT kits were returned on average 5.6 days sooner than gFOBT. The time to analysis for FIT leads to an overall rise in f-Hb concentration within the manufacturer's stated 14-day stability period. CONCLUSION: Both these factors are important considerations for laboratories when considering setting up a bowel cancer screening programme, especially if transitioning from gFOBT to FIT. Our data also support previous evidence of males having a higher f-Hb than females and demonstrate that after adjusting for sex, age and screening hub, neither index of multiple deprivation nor screening episode significantly affected f-Hb.