Els van de Vijver

50 Comparison with existing literature Well-designed studies on the discriminative power of calgranulin-C are scarce. An Australian research team previously reported on a study comparing calprotectin and calgranulin-C.(9) They obtained stool samples from 61 children (2-16 years old) who presented with gastrointestinal symptoms prior to admission for gastrointestinal endoscopy. The predefined threshold used for calgranulin-C in their study cohort (10 µg/g)(8) was substantially higher than the one we used (0.75 µg/g).(13) The difference is likely to be explained by differences in assays and selection of patients. We included a fair amount of patients that did not proceed to endoscopy, which increases the applicability of our results for populations seen in non- specialized centers. An important methodological flaw in the Australian study was the omission of a fair comparison of optimal thresholds for both markers, which may have resulted in an overinterpretation of calgranulin-C test accuracy. Several recently published meta-analyses have shown that the calprotectin stool test has good negative predictive (“rule-out”) value at the commonly used threshold (50 µg/g).(3,4,6) A large share of the studies included in these meta-analyses had a case-control design which gives rise to spectrum bias and overestimation of test accuracy relative to the real-life practice.(19) We avoided spectrum bias and therefore expected to find more modest accuracy measures than previously reported. Contrary to our expectations, we found that the good rule-out value of calprotectin still holds in a heterogeneous study population with chronic abdominal pain and diarrhoea. At the threshold of 50 µg/g, the specificity of the calprotectin test for the detection of IBD (71%) was comparable with previously reported values. The ROC-based optimal threshold was higher than in previously reported papers. We used the calprotectin ELISA assay of BÜHLMANN Laboratories, which is known to report higher concentrations than the Immunodiagnostik and Eurospittal assays.(20) This so-called between-assay variability indicates the need for assay standardization. In the meantime, each laboratory should investigate transferability of the manufacturer’s thresholds to its patient population and if necessary, determine its own local thresholds to optimally identify IBD and avoid the need for further costly and invasive investigations. Chapter 3