Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy

Figures & data

Figure 1. Study flow chart.

Table 1. Basic characteristics of patients in the analyses (n = 242).

	N (%)
Sex
Men	102 (42.1)
Women	140 (57.9)
Age groups
≤39	21 (8.7)
40–49	28 (11.6)
50–59	45 (18.6)
60–69	57 (23.6)
70–79	74 (30.6)
≥80	17 (7.0)
Unit
Eskilstuna GDH	162 (66.9)
Handen outpatient clinic	56 (23.1)
Hötorget outpatient clinic	9 (3.7)
Örebro UH	15 (6.2)
Findings at colonoscopy
Colorectal cancer	13 (5.3)
Advanced adenoma	15 (6.2)
Non-advanced adenoma	23 (9.5)
Colitis NUD	8 (3.3)
Angiodysplasia	2 (0.8)
Diverticulosis	57 (23.6)
Miscellaneous	38 (15.7)
No abnormalities	86 (35.5)
Medication
Trombyl	23 (9.5)
Warfarin	12 (5.0)
Others and combinations	8 (3.3)
None	193 (79.8)
Missing data	6 (2.5)
Bowel cleansing
Satisfactory	140 (57.9)
No comments on bowel cleansing	80 (33.1)
Poor	22 (9.1)

Table 2. Reported symptoms and positive predictive value (PPV) for colorectal cancer among patients referred for colonoscopy (n = 242).

	Number of patients (%) reporting each symptom	Predictive value for CRC (%; 95% CI)
Rectal bleeding	60 (24.8)	6/60 (10.0; 2.4–17.6)
Rectal mucus	65 (26.9)	6/65 (9.2; 2.2–16.2)
Bloating	161 (66.5)	9/161 (5.6; 2.1–9.1)
Abdominal pain	126 (52.1)	7/126 (5.6; 1.6–9.6)
Weight loss	64 (26.4)	4/64 (6.3; 0.3–12.3)
Bowel habits
More often	51 (21.1)	4/51 (7.8; 0.4–15.2)
More seldom	23 (9.5)	2/23 (8.7; −2.5–19.9)
Bowel contents
Looser	65 (26.9)	4/65 (6.2; 0.3–12.1)
Harder	29 (12.0)	2/29 (6.9; −2.23–16.1)
Missing information on symptoms	14 (5.8)	–

Table 3. Faecal haemoglobin concentrations (µg Hb/g) of one FIT and max value/2 FITs by colonoscopy findings. Values in parenthesis are row percentages.

	<10	10–14.9	15–19.9	≥20	Total
One FIT
Cancer	1 (7.7)	0	1 (7.7)	11 (84.6)	13
AA	7 (46.7)	1 (6.7)	1 (6.7)	6 (40.0)	15
NAA	17 (73.9)	0	2 (8.7)	4 (17.4)	23
Colitis NUD	2 (25.0)	1 (12.5)	0	5 (62.5)	8
Angiodysplasia	1 (50.0)	0	0	1 (50.0)	2
Diverticulosis	44 (77.2)	4 (7.0)	5 (8.8)	4 (7.0)	57
Miscellaneous	28 (73.7)	4 (10.5)	1 (2.6)	5 (13.2)	38
No abnormalities	78 (90.7)	0	2 (2.3)	6 (7.0)	86
Total	178 (73.6)	10 (4.1)	12 (5.0)	42 (17.4)	242 (100)
Max/2 FITs
Cancer	0	1 (7.7)	0	12 (92.3)	13
AA	7 (46.7)	1 (6.7)	0	7 (46.7)	15
NAA	15 (68.2)	0	2 (9.1)	5 (22.7)	22
Colitis NUD	0	2 (25.0)	0	6 (75.0)	8
Angiodysplasia	1 (50.0)	0	0	1 (50.0)	2
Diverticulosis	40 (71.4)	2 (3.6)	8 (14.3)	6 (10.7)	56
Miscellaneous	25 (65.8)	7 (18.4)	0	6 (15.8)	38
No abnormalities	72 (86.7)	0	1 (1.2)	10 (12.0)	83
Total	160 (67.5)	13 (5.5)	11 (4.6)	53 (22.4)	237 (100)

Table 4. Accuracy and predictive values for colorectal cancer of one FIT and max value/2 FITs at cut-off 10, 15 and 20 µg Hb/g.

Cutoff	Sens (95% CI)	Spec (95% CI)	PPV (95 % CI)	NPV (95% CI)
One FIT
10	92.3 (77.8–100)	77.3 (71.9–82.7)	18.8 (9.2–28.4)	99.4 (98.2–100)
15	92.3 (77.8–100)	81.7 (76.7–86.7)	22.2 (11.1–33.3)	99.5 (98.5–100)
20	84.6 (65.0–100)	86.5 (82.1–90.9)	26.2 (12.9–39.5)	99.0 (97.6–100)
Max/2 FITs
10	100	71.4 (65.5–77.3)	16.9 (8.5–25.3)	100
15	92.3 (77.8–100)	76.8 (71.3–82.3)	18.8 (9.2–28.4)	99.4 (98.2–100)
20	92.3 (77.8–100)	81.7 (76.6–86.8)	22.6 (11.3–33.9)	99.5 (76.1–87.3)

Figure 2. (a) ROC curve for one FIT; (b) ROC curve for maximum value/2 FITs.

Table 5. Estimated odds ratio for colorectal cancer of uni- and multivariate analyses (n = 242).

	Univariate analysis			Multivariate analysis*
	OR	95% CI	p Value	OR	95% CI	p Value
One FIT
>10 ug Hb/g faeces	40.85	5.19–321.5	<.001*	32.03	4.01–255.9	.001
Demographics
Age	1.08	1.02–1.15	.01*	1.06	0.99–1.13	.08
Men	1.65	0.54–5.05	.38
Symptoms
Rectal bleeding	2.78	0.90–8.62	.08
Rectal mucus	2.47	0.80–7.64	.12
Bloating	1.14	0.34–3.82	.83
Abdominal pain	1.08	0.35–3.31	.90
Weight loss	1.25	0.37–4.22	.72
Change of bowel habits
Frequency^a	2.03	0.66–6.26	.22
Consistency^b	1.37	0.45–4.22	.58

* Covariates included in the multivariate analysis.

^a More often or more seldom.

^b Looser or harder.

Table

Specimen collection and handling
QuikReadGo, OrionDiagnostica Oy, Svärdvägen 21, Box 85, S-182 11 Danderyd, SwedenTel [phone]	Name of specimen collection device and supplier (address).	Essential
Quik Read FOB probe	Description of specimen collection device (vial with probe/stick, card, other).	Essential
Single faecal samples	Description of specimens used if an in vivo study (single or pooled faeces, artificial matrix with added blood, etc).	Essential for laboratory evaluations
Probe	Details of faecal collection method (sampling technique and number of samples).	Essential
Patients	Who collected the specimens from the samples (patient, technician, etc).	Essential
Two faecal specimens from two separate days	Number of faecal specimens used in the study (single, pooled, individual patient faeces).	Essential for laboratory evaluations
10 mg	Mean mass of faeces collected.*	Essential
Buffer into which specimen is taken by probe	Volume of buffer into which specimen is taken by probe, applicator stick or card.*	Essential
Kept at the most three days in fridge temperature at home before sent to the laboratory by ordinary post (1 day)	Time and storage conditions of faecal specimen from“passing” to sampling, including time and temperature (median and range).	Essential for laboratory evaluations
Specimen analysed on the day or arrival to the laboratory	Time and storage of collection devices from specimen collection to analysis, including time and temperature (median and range). A concise description of process from collection to analysis is recommended.	Essential
Analysis
QuikRead go, OrionDiagnostica Oy, Svärdvägen 21, Box 85, S-182 11 Danderyd, Sweden Tel [phone] Two instruments used during the study	Name of analyser, model, supplier (address), number of systems if more than one used.	Essential
One	Number of times each sample was analysed.	Essential
75-1000 ng Hb/mL buffer, 15-200 µg Hb/g faeces No reassays or dilutions	Analytical working range* and whether samples outside this range were diluted (factor) and reassayed.	Essential for laboratory evaluations
QuikRead go iFOBT. The reference material has been verified with a method comparable to the international Council of Standardizationin Heamatology (ISCH ) reference method.	Source of calibrator(s) (supplier with address), number of calibrator(s), how concentrations were assigned* and details of calibration process including frequency.	Essential for laboratoryevaluations
∼ 600 samples analysed. 64 patients had > 10 µg Hb/g faeces, and mean (SD) was 76 (74) µg Hb/g faeces.	Analytical imprecision*, ideally with number of samples analysed, concentrations, and mean, SD and CV.	Essential for all studies
Quality management
Quik Read FOB positive control Cat.No 06027 Hb in buffert >1000 ng/mL or > 200 µg Hb/g faeces. One control performed per kit (50 tests)	Source (address) or description of internal quality control materials, number of controls, assigned target concentrations and ranges, how target concentrations were assigned, rules used for acceptance and rejection of analytical runs.	Desirable for laboratory evaluations
No	Participation in external quality assessment schemes: (name and address of scheme), frequency of challenges, performance attained.	Desirable for laboratory evaluations
Unilabs Inc, Dep of Clinical Chemistry, Mälarsjukhuset S-631 88 Eskilstuna Sweden	Accreditation held by the analytical facility (address).	Desirable for laboratory evaluations
5 biomedical scientists	The number, training and expertise of the persons performing the analyses and recording the results.	Essential
Result handling
Electronic and manual recording, single reading	Mode of collection of data – manual recording or via automatic download to IT system, single or double reading.	Desirable
μg Hb/g faeces	Units used, with conversion to μg Hb/g faeces if ng Hb/mL used.	Essential
Assigned by instrument 15 μg Hb/g faeces and then complementary analyses by manufacturer	Cut-off concentration(s) if used and explanation of how assigned locally or by manufacturer.*	Essential
Yes	Were the analysts blinded (masked) to the results of the reference investigation and other clinical information	Essential

Table

Section & Topic	No	Item	Reported on page #
TITLE OR ABSTRACT
	1	Identification as a study of diagnostic accuracy using at least one measure of accuracy (such as sensitivity, specificity, predictive values, or AUC)	1
ABSTRACT
	2	Structured summary of study design, methods, results, and conclusions (for specific guidance, see STARD for Abstracts)	2
INTRODUCTION
	3	Scientific and clinical background, including the intended use and clinical role of the index test	4
	4	Study objectives and hypotheses	4
METHODS
Study design	5	Whether data collection was planned before the index test and reference standard were performed (prospective study) or after (retrospective study)	5
Participants	6	Eligibility criteria	5
	7	On what basis potentially eligible participants were identified (such as symptoms, results from previous tests, inclusion in registry)
	8	Where and when potentially eligible participants were identified (setting, location and dates)	5
	9	Whether participants formed a consecutive, random or convenience series
Test methods	10a	Index test, in sufficient detail to allow replication	5-6
	10b	Reference standard, in sufficient detail to allow replication	6
	11	Rationale for choosing the reference standard (if alternatives exist)	–
	12a	Definition of and rationale for test positivity cut-offs or result categories of the index test, distinguishing pre-specified from exploratory	7
	12b	Definition of and rationale for test positivity cut-offs or result categories of the reference standard, distinguishing pre-specified from exploratory	6
	13a	Whether clinical information and reference standard results were available to the performers/readers of the index test	6
	13b	Whether clinical information and index test results were available to the assessors of the reference standard	6
Analysis	14	Methods for estimating or comparing measures of diagnostic accuracy	7
	15	How indeterminate index test or reference standard results were handled	5-6
	16	How missing data on the index test and reference standard were handled	8
	17	Any analyses of variability in diagnostic accuracy, distinguishing pre-specified from exploratory	7
	18	Intended sample size and how it was determined	6-7
RESULTS
Participants	19	Flow of participants, using a diagram	Fig 1
	20	Baseline demographic and clinical characteristics of participants	Table 1
	21a	Distribution of severity of disease in those with the target condition	–
	21b	Distribution ofalternative diagnoses in those without the target condition	Table 1
	22	Time interval and any clinical interventions between index test and reference standard	Fig 1
Test results	23	Cross tabulation of the index test results (or their distribution) by the results of the reference standard	Table 3
	24	Estimates of diagnostic accuracy and their precision (such as 95% confidence intervals)	Table 4
	25	Any adverse events from performing the index test or the reference standard	NA
DISCUSSION
	26	Study limitations, including sources of potential bias, statistical uncertainty, and generalisability	11
	27	Implications for practice, including the intended use and clinical role of the index test	12
OTHER INFORMATION
	28	Registration number and name of registry	2
	29	Where the full study protocol can be accessed	Clinicaltrials.gov
	30	Sources of funding and other support; role of funders	12