Maarten Cozijnsen

46 methods with strong clinical input should be the basis of developing outcome measures, as done here 29–32 . All judgmental decisions have been, however, justified by our results and prior literature while providing strong clinical rationale. This is by far the largest dataset of pediatric CD yet to study the association between non-invasive activity measures and mucosal inflammation. Data were gathered in multiple countries, giving rise to inter-observer and cross-cultural diversity, which is strongly encouraged when developing outcome measures. Furthermore, there was room for site- dependent and observer-dependent variations in our results: CRP and ESR were performed locally, endoscopies were not centrally read and both endoscopy and lab work-up was not always conducted on the same day, but up to 2 weeks intervals were allowed as long as treatment was unchanged. These variations, however, reflect clinical practice, and the fact that the MINI index performed well even outside the “sterile” condition of clinical trials lends further support for its real world clinical utility. The MINI index was validated on three independent prospective cohorts and, reassuringly, its accuracy to reflect mucosal inflammation remained good. Due to its non-invasive nature, the MINI index allows tight monitoring of mucosal inflammation and facilitating appropriate selection of children for colonoscopic assessment. It may also serve as an outcome measure in clinical trials instead or in addition to ileocolonoscopy to increase feasibility and enrollment rates. It may now also be tested in adults as the included items are not specific to children.