4 The diagnostic tests

4 The diagnostic tests

The interventions

4.1 Several faecal calprotectin tests are available to the NHS in England, including fully quantitative laboratory-based technologies (many of which use an enzyme‑linked immunosorbent assay [ELISA] platform), fully quantitative rapid tests and semi-quantitative point‑of‑care tests (POCTs). Rapid tests have not been characterised as POCTs in this assessment because they need a dedicated reader to process the tests but with appropriate training and quality assurance processes they may be appropriate for use in point‑of‑care settings. In principle, all technologies can be used to provide a faecal calprotectin testing service to either primary or secondary care.

Table 1 Technologies included in the assessment

Manufacturer

Test

Platform

Bühlmann

EK-CAL calprotectin ELISA test

ELISA – quantitative

Range: 10–600 micrograms/g

Bühlmann

EK-CAL calprotectin ELISA test

ELISA – quantitative

Range: 30–1800 micrograms/g

Bühlmann

LF-CAL25 Quantum Blue calprotectin test

Rapid test – Immunoassay designed for the quantitative determination of faecal calprotectin in combination with the BÜHLMANN Quantum Blue reader

Range: 30–300 micrograms/g

Bühlmann

LF-CHR 25 Quantum Blue calprotectin test

Rapid test – Immunoassay designed for the quantitative determination of faecal calprotectin in combination with the BÜHLMANN Quantum Blue reader

Range: 100–1800 micrograms/g

Calpro

CALPRO CALPROTECTIN ELISA TEST (ALP) – formerly known as the Phical test

CAL0100

ELISA – quantitative

Range: up to 1250 mg/kg

Calpro

CALPROLAB CALPROTECTIN ELISA (ALP) – formerly known as the Phical test

CALP0170

ELISA – quantitative

Range: up to 2500 mg/kg

Eurospital

Calprest

ELISA – quantitative

Eurospital

CalFast

Rapid test – Quantitative determination of faecal calprotectin in combination with a dedicated reader

Immundiagnostik

ELISA (K6927)

ELISA – quantitative

Phadia AB, part of Thermo Fisher Scientific

EliA Calprotectin

EliA – quantitative

Quantitative fluorescence enzyme immunoassay (FEIA) test

Range 15–3000 mg/kg

Preventis (sister company to Immundiagnostik)

KST11005 CalDetect Calprotectin Rapid test (version 1 – Caldetect)

POCT – immunochromatographic rapid test

A semi-quantitative test with 3 lines corresponding to: Calprotectin 'negative', Calprotectin≤15 micrograms/g, Calprotectin 16–60 micrograms/g and Calprotectin>60 micrograms/g stool

Preventis (sister company to Immundiagnostik)

CalDetect Calprotectin Rapid test (version 3 – CalScreen)

POCT – immunochromatographic rapid test

A yes/no test with only 1 test‑line corresponding to the cut‑off value of 50 micrograms/g stool (no inflammation=<50 micrograms/g and inflammation present=≥50 micrograms/g)

Abbreviations: ELISA, enzyme-linked immunosorbent assay; POCT, point‑of‑care test

4.2 Immundiagnostik tests K6967 and K6937 were included in the scope but were not included in the assessment conducted by the External Assessment Group because one is a variant (K6967) and the other (K6937) was superseded by the Immundiagnostik test K6927, which was included in the assessment.

4.3 In total, 12 tests were included in the assessment conducted by the External Assessment Group. The reference standard was histology after endoscopy.

4.4 Because faecal calprotectin correlates with the level of bowel inflammation, test results need to be interpreted in the context of a cut‑off value, below which the test is deemed negative and above which is deemed positive. In the context of distinguishing between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), this would mean a negative result would support a diagnosis of IBS (a disease not characterised by inflammation) and a positive result would support a diagnosis of IBD (a disease characterised by inflammation). For a quantitative test, the output is often a single number representing micrograms of calprotectin per gram of stool sample (for example, 15 micrograms/g). If the cut‑off value is selected as 50 micrograms/g for distinguishing between IBS and IBD, then a person with a faecal calprotectin level of 15 micrograms/g would be classified as negative (indicating the person is likely to have IBS). The cut‑off value selected influences the diagnostic accuracy of the tests under consideration and different cut‑off values can be selected for different purposes. Cut‑off values can include a middle range in which results are considered indeterminate, below which are deemed negative and above which are deemed positive. Although a cut‑off value needs to be selected for interpreting results of a quantitative test, the cut‑offs for a POCT might be pre‑specified in the design of the test. For example, CalDetect reports 1 of 4 results when the test runs correctly: negative – faecal calprotectin is not detectable; negative – faecal calprotectin level is equal to or less than 15 micrograms/g; positive – faecal calprotectin level is 16–60 micrograms/g; and positive – faecal calprotectin level is more than 60 micrograms/g. Users might apply local cut‑offs for interpreting the results of POCTs; for example, a cut‑off of 60 micrograms/g might be applied, test results below which are deemed negative and above which are deemed positive. The most common cut‑off recommended by manufacturers is 50 micrograms/g. It should be noted that, in some cases, people with IBS can have raised levels of faecal calprotectin above the selected cut‑off value and the opposite is true for people with IBD (faecal calprotectin levels can be below the selected cut‑off).

The comparator

4.5 The comparator is standard clinical practice in England. The main tests currently used to measure inflammation are erythrocyte sedimentation rate and C‑reactive protein, which can indicate inflammation but not localise it.

  • National Institute for Health and Care Excellence (NICE)