Clinical Validation of PROMIS Measures in a Pediatric Crohns Disease Clinical Trial

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Crohn's disease (CD) is a chronic inflammatory disorder that primarily affects the gastrointestinal tract. It causes significant suffering in affected children, who experience bouts of pain, bloody diarrhea, fatigue, emotional distress, and low levels of positive affect. In April 2015, the Patient-Centered Outcomes Research Institute approved funding for a randomized, double-masked, multicenter, pragmatic clinical trial of anti-TNF combination therapy with methotrexate versus monotherapy (anti-TNF with placebo) in pediatric CD. The trial will recruit patients from the offices of pediatric gastroenterologists who participate in ImproveCareNow, a national network (40% of the nation's pediatric gastroenterologists participate) devoted to improving the health of children with inflammatory bowel disease, both CD and ulcerative colitis. Fortuitously, the trial will begin the same month as the proposed project, creating a unique opportunity for evaluating the validity of PROMIS Pediatric measures. The purpose of the proposed research project is to evaluate the content validity, clinical meaning, responsiveness, and longitudinal construct validity of four PROMIS pediatric instruments (pain interference, fatigue, psychological stress experiences, and positive affect) in 319 children with CD. As a panel, these measures characterize a child's level of suffering and happiness. Relieving suffering by reducing disease activity or palliating symptoms in order to promote a child's well-being and happiness is often the primary objective of medical treatment for pediatric chronic conditions. The CD research project will be one of three linked studies within the Child-Centered Outcomes in Practice and Research (COPR) Center's program of research. Each of the studies will use similar measures, methods, and infrastructure to evaluate the clinical validity of PROMIS among children who are chronically ill. Our specific aims are to: (Aim1) Assess the content validity of the PROMIS Pediatric pain interference, fatigue, psychological stress experiences, and positive affect measures for children with Crohn's disease; (Aim 2) Establish clinically meaningful classifications for the PROMIS Pediatric pain interference, fatigue, psychological stress experiences, and positive affect measures for children with Crohn's disease; (Aim 3) Estimate minimal important differences (MIDs) for the PROMIS Pediatric pain interference, fatigue, psychological stress experiences, and positive affect measures in children with Crohn's disease; and, (Aim 4) Evaluate the longitudinal construct validity of PROMIS Pediatric pain interference, fatigue, psychological stress experiences, and positive affect measures by treatment with methotrexate, clinical markers of disease activity, and sociodemographic characteristics for children with Crohn's disease. If our aims are achieved through the clinical validation of the PROMIS instruments in the well phenotyped children in the anti-TNF trial, we will take major steps toward facilitating the use of PROMIS as standard endpoints in clinical trials and in routine clinical practice for pediatric CD.