Table 1.

Overview of test characteristics used in the model.

Screen test (reference)	Specificity (per person, %)	Sensitivity (per lesion, %)*
		Adenoma			CRC
		Small (≤5mm)	Medium (6–9mm)	Large (≥10mm)	Early preclinical†	Late preclinical†	Average
FIT‡	96	0	11	34	50	83	64
Biomarker test variants
Sensitivity CRC 60%	88–100§	0	11	32	45	80	60
Sensitivity CRC 70%	88–100§	0	12	37	58	87	70
Sensitivity CRC 80%	88–100§	0	14	42	71	92	80
Sensitivity CRC 90%	88–100§	0	16	48	85	96	90
Sensitivity CRC 100%	88–100§	0	18	53	100	100	100
Colonoscopy||	90	75	85	95	95	95	95

CRC, colorectal cancer; FIT, fecal immunochemical test

^*The probability of a person to test positive (person-level sensitivity) is higher than per lesion sensitivity and depends on the number and type of lesions present as well as the probability to test positive because of other reasons, such as e.g. bleeding from a diverticulum.

^†It was assumed that the probability a CRC bleeds and thus the sensitivity of FIT for CRC depends on the time until clinical diagnosis, in concordance with findings for gFOBT, which were based on a prior calibration of the MISCAN-Colon model to three gFOBT trials.⁹ This result is to be expected when cancers that bleed do so increasingly over time, starting “occultly” and ending as clinically visible.

^‡The test characteristics of FIT (at a cut-off of 10 μg/g feces (50 ng/ml buffer)) were fitted to the positivity and detection rates of adenomas and CRC from two Dutch randomized trials.^16–18 We assumed that the sensitivity for small adenomas was 0%, and that small adenomas would only be detected because of a lack of specificity of the test.

^§We modeled five different sets of sensitivities for the biomarker test. All five sets of sensitivities were modeled with specificities ranging from 88% to 100%, at 2% increments, yielding a total of 35 (5×7) different sets of test characteristics for the hypothetical biomarker tests variants.

^||Colonoscopy was only used during follow-up and surveillance after a positive FIT or biomarker test.