Els van de Vijver

32 Comparison with other studies We recently published a diagnostic meta-analysis (1) in which we summarised the best available evidence on the diagnostic accuracy of faecal calprotectin for screening. We included the reports of six adult studies and seven Phase II studies in children and teenagers. We concluded that calprotectin is accurate when screening for suspected IBD in adults, but less so in children. The pooled sensitivity and specificity in children and teenagers was 0.92 (95% CI 0.84 to 0.96) and 0.76 (95% CI 0.62 to 0.86), respectively. Gastrointestinal infections, especially bacterial infections with Shigella, Yersinia or Salmonella, can mimic the onset of IBD in children and teenagers and cause increased faecal calprotectin levels. Since the publication of our meta-analysis two new paediatric phase II study have been published.(5,6) In these studies a fully paired design was used in which all included children were subjected to endoscopic evaluation. In “real life”, when another diagnosis than IBD is more likely, paediatricians may wish to avoid this invasive and uncomfortable procedure. The major difference between the Diamanti study and ours was a remarkable high pre-test probability of 60 % that can be explained by the tertiary care setting in which a highly selected group of patients with suspected IBD was seen. In our study pretest probability was 36%. In the Henderson study the patients with a high calprotectin result and no endoscopy were not evaluated and followed up. Limitations of this study Although phase II studies give cause to overestimate diagnostic accuracy, the validity of a phase III study like ours is also compromised. As not all patients underwent the reference test, uncertainty remains about the correct diagnosis in some patients. We therefore decided to add another prognostic dimension to the reference standard, namely, the clinical course of patients. IBD is not a self-limiting disease and will usually become clinically manifest within a few months after the first diagnostic suspicion, in this study the moment of enrolment. Patients who remained free of disease for 6 months were believed not to have IBD. This “delayed type” diagnosis may not be ideal, but is the best achievable solution closely connected with the reality of clinical care.(7) Faecal calprotectin can give false-positive results when patients use non-steroidal anti- inflammatory drugs (8-10) or proton pump inhibitors.(11) We did not collect information Chapter 2