Development, Evaluation and Application of a Pediatric Ulcerative Colitis Index (PUCAI)

This thesis uses the methods of sychometrics and clinimetrics to develop and evaluate a Pediatric Ulcerative Colitis Activity Index (PUCAI). The initial phases of item generation and reduction were performed previously. This thesis comprises five main studies. Study one: the weighting and formatting of an initial draft PUCAI using a cohort of 157 children with ulcerative colitis, enrolled prospectively in five pediatric IBD centers. Study two: the validation of the final draft on a separate prospective cohort of 48 children undergoing complete colonoscopy. The PUCAI was highly correlated with physician global assessment (PGA) (r=0.91), Mayo score (r=0.95) and colonoscopic appearance (r=0.77). The PUCAI was able to differentiate the different categories of disease activity, and cutoff points were defined. Study three: Assessment of the responsiveness of the PUCAI. The index demonstrated excellent responsiveness on 75 children seen twice during the study period (effect size=1.9, standardized response mean=2.2, responsiveness statistics=2.6, correlation with PGA of change=0.84, and area under the ROC curve=0.97 95%CI 0.93- 0.99). Study four was aimed at evaluating the predictive validity of the PUCAI, on a retrospective cohort of 99 children with severe ulcerative colitis admitted for intravenous corticosteroid therapy. The PUCAI, calculated on the third and fifth day of therapy was highly predictive of therapy failure at discharge and one year post discharge (area under the ROC curve 0.84 (95%CI 0.76-0.92). Study five: a methodological study evaluating the preferred way to determine the minimal clinically important difference (MCID) of health-related outcome measures. This study was conducted using the PUCAI and three other well established instruments. It was concluded that the MCID should be determined primarily by the anchor-based approach using the ROC curve method on the entire cohort, supplemented by calculating the minimal detectable difference beyond statistical error using the standard error of measurement. Small, moderate and large MCID values could be presented based on the degree of expected relevant change. Together, these studies have contributed to the rigorous development and thorough evaluation of a novel, non-invasive tool for assessing disease activity in pediatric ulcerative colitis clinical studies and practice.Ph