Els van de Vijver

51 Strengths and limitations This large-scale multicenter cross-border accuracy study better reflects ‘real-life’ practice than any other previously published study on stool tests for screening and selecting children for endoscopy. We used an automated IBD Risk Stratifier to standardize the assignment of patients to either the high or low risk stratum. The cooperation of both secondary and tertiary level hospitals in this study promotes the generalizability of our results and conclusions. The attending paediatricians were not blinded to the calprotectin results. This led to a deviation from the automated advice of the IBD Risk Stratifier in 25% of cases. In supplementary file 5 we show that this especially happened in the calprotectin grey zone between 50 and 400 ug/g. Knowledge of the calprotectin concentration also led to a diagnostic work-up bias that is usually the case in screening studies where only patients with a positive index test result move on to the reference standard. We reduced this bias by following the low-risk patients for 6 months for possible latent IBD to become visible. One might argue that this observation period was not sufficiently long, but we are confident that the majority of initially missed cases with IBD would become apparent within this time. Clinical implications Both calprotectin and calgranulin-C have excellent test characteristics to predict IBD in children and teenagers with chronic abdominal pain and diarrhoea and justify endoscopy. In this inception cohort the calprotectin action threshold for proceeding to endoscopy is around 400 μg/g, and this underlines the relevance of using a ‘two-threshold strategy’ as proposed in several publications.(7,21-23) The grey zone between the commonly used threshold of 50 μg/g that demarcates the normal range and the action threshold gives room for shared decision making with the patient and his/her parents, in which presence of major red flag symptoms and impact on daily functioning of the child may additionally guide management. One can opt for watchful waiting with monthly monitoring of stool calprotectin or decide to move on to endoscopic evaluation. When calprotectin concentrations are truly out of range, and gastrointestinal infections and nonsteroidal anti-inflammatory drug use are excluded, the patient should proceed to endoscopy to rule in IBD. A two-threshold strategy does not seem to be of added value when the calgranulin-C stool test is picked as the triaging tool of preference. Head-to-head comparison Calgranulin C and Calprotectin 51