Application of NICE guideline NG12 to the initial assessment of patients with lower gastrointestinal symptoms: not FIT for purpose?

Background The National Institute for Health and Care Excellence (NICE) published NG12 in 2015. The referral criteria for suspected colorectal cancer (CRC) caused controversy, because tests for occult blood in faeces were recommended. Faecal immunochemical tests for haemoglobin (FIT), which estimate faecal haemoglobin concentrations (f-Hb), might more than fulfil the intentions. Our aim was to compare the utility of f-Hb as the initial investigation with the NICE NG12 symptom-based guidelines. Methods Data from three studies were included. Patients had sex, age, symptoms, f-Hb and colonoscopy and histology data recorded. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of f-Hb and NG12 were calculated for all significant colorectal disease (SCD: CRC, higher risk adenoma and inflammatory bowel disease). Overall diagnostic accuracy was also estimated by the area under the receiver operating characteristic curve (AUC). Results A total of 1514 patients were included. At a cut-off of ≥10 µg Hb/g faeces, the sensitivity of f-Hb for CRC was 93.3% (95% confidence interval (CI): 80.7-98.3) with NPV of 99.7% (95%CI: 99.2-99.9). The sensitivity and NPV for SCD were 63.2% (95%CI: 56.6-69.4) and 96.0% (95%CI: 91.4-94.4), respectively. The NG12 sensitivity and NPV for SCD were 58.4% (95%CI: 51.8-64.8) and 87.6% (95%CI: 85.0-89.8), respectively. The AUC for CRC was 0.85 (95% CI: 0.87-0.90) for f-Hb versus 0.65 (95%CI: 0.58-0.73) for NG12 ( P < 0.005). For SCD, the AUC was 0.73 (95%CI: 0.69-0.77) for f-Hb versus 0.56 (95%CI: 0.52-0.60) for NG12 ( P < 0.0005). Conclusion f-Hb provides a good rule-out test for SCD and has significantly higher overall diagnostic accuracy than NG12.

The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients.

Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f-Hb), age and sex, may simplify CRC diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi-square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02-1.05), male sex: 1.6 (95% CI: 1.1-2.3) and f-Hb (0-<20 µg Hb/g feces): 2.0 (95% CI: 0.7-5.5), (20-<200 µg Hb/g): 16.8 (95% CI: 6.6-42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3-164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85-0.90) in the derivation and 0.91 (95% CI: 0.90-093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value-PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients.

Deprivation and faecal haemoglobin: implications for bowel cancer screening.

OBJECTIVE: To investigate the relationship between deprivation and faecal haemoglobin concentration (f-Hb). SETTING: Scottish Bowel Screening Programme. METHODS: A total of 66725 men and women, aged 50 to 74, were invited to provide a single sample for a faecal immunochemical test. Deprivation was estimated using the Scottish Index of Multiple Deprivation quintiles: f-Hb was measured (OC-Sensor, Eiken, Japan) on 38439 participants. The relationship between deprivation quintiles and f-Hb was examined. RESULTS: Median age was 60 years, 53.6% women, with 14.1%, 19.7%, 17.7%, 25.9% and 22.6% in the lowest to the highest deprivation quintiles respectively. No detectable f-Hb was found in 51.9%, ranging from 45.5% in the most deprived up to 56.5% in the least deprived. As deprivation increased, f-Hb increased (p < 0.0001). This trend remained controlling for sex and age (p < 0.001). Participants in the most deprived quintile were more likely to have a f-Hb above a cut-off of 80 µg Hb/g faeces compared with the least deprived, independent of sex and age (adjusted odds ratio 1.70, 95% confidence interval: 1.37 to 2.11). CONCLUSIONS: Deprivation and f-Hb are related. This has important implications for selection of cut-off f-Hb for screening programmes, and supports the inclusion of deprivation in risk-scoring systems.

Use of a faecal immunochemical test narrows current gaps in uptake for sex, age and deprivation in a bowel cancer screening programme.

OBJECTIVES: To investigate the characteristics of participants screened for bowel cancer using a faecal immunochemical test for haemoglobin (FIT). SETTING: Scottish Bowel Screening Programme. METHODS: 65909 men and women in two NHS Boards, aged 50 to 74, were invited to participate in an evaluation of FIT as a first-line test. Uptake was calculated by sex, age in quintiles, and deprivation in quintiles, and compared with a group who had completed a guaiac faecal occult blood test (gFOBT) and for whom details of sex, age and deprivation were well documented. RESULTS: FIT kits from 38672 participants were tested. The overall uptake of 58.7% was significantly higher than the 53.9% for gFOBT (p < 0.0001). Uptakes in the two NHS Boards were 57.6% and 54.4% for men and 63.2% and 59.1% for women, higher than the 49.5% and 58.1% completing gFOBT. Uptake was higher for FIT than gFOBT in all age and deprivation quintiles for both men and women in both NHS Boards. The difference in uptake fell with age for men but rose for women; the increase in uptake was greater for men than women. Uptake fell as deprivation decreased for both sexes, and was similar in both NHS Boards. CONCLUSIONS: Use of FIT increases uptake over gFOBT, and the greatest increases are seen in men, younger participants, and more deprived individuals, groups for which an increase in uptake is likely to be beneficial. The results support a move to FIT as a first-line screening test for those countries still using gFOBT.

Faecal haemoglobin concentration is related to severity of colorectal neoplasia.

AIMS: Guaiac faecal occult blood tests are being replaced by faecal immunochemical tests (FIT). We investigated whether faecal haemoglobin concentration (f-Hb) was related to stage in progression of colorectal neoplasia, studying cancer and adenoma characteristics in an evaluation of quantitative FIT as a first-line screening test. METHODS: We invited 66 225 individuals aged 50-74 years to provide one sample of faeces. f-Hb was measured on samples from 38 720 responders. Colonoscopy findings and pathology data were collected on the 943 with f-Hb ≥ 400 ng Hb/ml (80 µg Hb/g faeces). RESULTS: Of the 814 participants with outcome data (median age: 63 years, range 50-75, 56.4% male), 39 had cancer, 190 high-risk adenoma (HRA, defined as ≥ 3 or any ≥ 10 mm) and 119 low-risk adenoma (LRA). 74.4% of those with cancer had f-Hb>1000 ng Hb/ml compared with 58.4% with HRA, and 44.1% with no pathology. Median f-Hb concentration was higher in those with cancer than those with no (p<0.002) or non-neoplastic (p<0.002) pathology, and those with LRA (p=0.0001). Polyp cancers had lower concentrations than more advanced stage cancers (p<0.04). Higher f-Hb was also found in those with HRA than with LRA (p<0.006), large (>10 mm) compared with small adenoma (p<0.0001), and also an adenoma displaying high-grade dysplasia compared with low-grade dysplasia (p<0.009). CONCLUSIONS: f-Hb is related to severity of colorectal neoplastic disease. This has ramifications for the selection of the appropriate cut-off concentration adopted for bowel screening programmes.

Clinical outcomes using a faecal immunochemical test for haemoglobin as a first-line test in a national programme constrained by colonoscopy capacity.

INTRODUCTION: Because of their many advantages, faecal immunochemical tests (FIT) are superseding traditional guaiac-based faecal occult blood tests in bowel screening programmes. METHODS: A quantitative FIT was adopted for use in two evaluation National Health Service (NHS) Boards in Scotland using a cut-off faecal haemoglobin concentration chosen to give a positivity rate equivalent to that achieved in the Scottish Bowel Screening Programme. Uptake and clinical outcomes were compared with results obtained contemporaneously in two other similar NHS Boards and before and after the evaluation in the two evaluation NHS Boards. RESULTS: During the evaluation, uptake was 58.5%. This was higher than in the same NHS Boards both before and after the evaluation, higher than in the other two NHS Boards and higher than the 53.7% achieved overall in Scotland. The overall positivity rate was higher in men than in women and increased with age in both genders. Positive predictive values for cancer (4.8%), high-risk adenoma (23.3%), all adenoma (38.2%) and all neoplasia (43.0%) in the two test NHS Boards were similar in all groups. CONCLUSIONS: In summary, this evaluation of the FIT supports the introduction of FIT as a first-line test, even when colonoscopy capacity is limited.

Experience with a two-tier reflex gFOBT/FIT strategy in a national bowel screening programme.

OBJECTIVES: To evaluate a two-tier reflex guaiac-based faecal occult blood test (gFOBT)/faecal immunochemical test (FIT) algorithm in screening for colorectal cancer. SETTING: Fourth screening round in NHS Tayside (Scotland). METHODS: gFOBT were sent to 50-74-year-olds. Participants with five or six windows positive were offered colonoscopy. Participants with one to four windows positive were sent a FIT and, if positive, were offered colonoscopy. Participants providing an untestable gFOBT were sent a FIT and, if positive, were offered colonoscopy. Outcomes following positive results, cancer stages and key performance indicators were assessed. RESULTS: Of 131,885 invited, 73,315 (55.6%) responded. There were 66,957 (91.3%) negative, 241 (0.3%) strong positive, 5230 (7.1%) weak positive and 887 (1.2%) untestable results. The 241 participants who had five or six windows positive had more cancers than those positive by other routes: only 3 of the 30 cancers (9.7%) were Dukes' A. Among the 983 positive results from the weak positive gFOBT then positive FIT route, there were fewer cancers and more normal colonoscopies, but more adenomas than in the group with a strong positive gFOBT. In those with an untestable gFOBT, 77 had a positive FIT result, with fewer true and more false positive results than in the other groups. Fewer males had cancer and stages were earlier than in females, but more had adenoma. The detection rate for cancer was 0.18% and the PPV for cancer and all adenomas was 41.3%. CONCLUSIONS: The algorithm and FIT following a weak positive gFOBT have advantages. FIT following an untestable gFOBT warrants review.

Faecal haemoglobin concentrations by gender and age: implications for population-based screening for colorectal cancer.

BACKGROUND: Faecal immunochemical tests (FIT) are becoming widely used in colorectal cancer screening. Estimation of faecal haemoglobin concentration in a large group prompted an observational study on gender and age. METHODS: A single estimate of faecal haemoglobin concentration was made using quantitative automated immunoturbidimetry. Potential reference intervals were calculated for men and women and for age quintiles according to the Clinical and Laboratory Standards Institute Approved Guideline. The percentages of positive results were calculated at a number of concentrations. The percentages of individuals who fell into different risk groups were assessed. RESULTS: The 97.5 percentiles, potential upper reference limits, were 519 ng haemoglobin/mL (90% CI: 468-575) for men and 283 ng haemoglobin/mL (90% CI: 257-316) for women. Concentrations increased with age in both genders. Decision limits have advantages over reference intervals. At any cut-off concentration, more men are declared positive than women and more older people are declared positive than younger people. Future risk of neoplasia is higher in men than in women and in older people. CONCLUSIONS: Faecal haemoglobin concentrations vary with gender and age. More tailored strategies are needed in screening programmes. Faecal haemoglobin concentration could be included in individual risk assessment scores. These data should assist in screening programme design.

The Hallmarks Survey: for those who care enough to teach the very best.

The Hallmarks Survey is based on the 85 indicators recommended by the National League for Nursing (NLN) for the Hallmarks of Excellence in Nursing Education. With permission from the NLN, graduate students in nursing education developed this survey as a holistic and systematic tool for nurse faculty to use for assessment of program components. Analysis of data from 53 faculty respondents yielded areas of strength and areas for development for each hallmark category. Recommendations based on survey findings were disseminated to diverse audiences in multiple venues. A follow-up evaluation of the survey was also conducted. The Hallmarks Survey provides comprehensive assessment data that faculty may use to promote excellence in nursing education.