title: Well-defined and reliable clinical outcome assessments for pediatric Crohn disease: a critical need for drug development.
abstract: OBJECTIVE
  The aim of the present study was to identify areas for further development of clinical outcome assessment (COA) in pediatric Crohn disease (CD).
  
  
  METHODS
  The study analyzed the measurement properties of all existing COA tools for pediatric CD in literature and published registration trials of approved drugs for pediatric CD based on criteria described in Food and Drug Administration guidance for patient-reported outcome (PRO) development.
  
  
  RESULTS
  The Pediatric Crohn's Disease Activity Index (PCDAI) and its derivatives (abbreviated, short, modified, and weighted PCDAIs) were reviewed. The Crohn's Disease Activity Index (CDAI) and Harvey-Bradshaw index (HBI), designed for adult patients, have been adapted for use in a few pediatric CD studies. The use of PCDAI as an endpoint in Remicade and Humira trials led to the Food and Drug Administration-approved indication in pediatric CD. Common issues in measurement properties of COA tools included the absence of direct patient or caregivers' input to generate the items measuring signs and symptoms; absence of evidence demonstrating correlation with clinically relevant inflammation observed with endoscopic measures; lack of standardization in measurement, age-appropriate interviewer script, and response rating criteria for the physician interviewer.
  
  
  CONCLUSIONS
  Available evidence indicates that CDAI, HBI, and 5 versions of the PCDAI lack adequate measurement properties for use as a primary endpoint for phase 3 trials intended to support approval of products intended to treat pediatric CD. In order to facilitate pediatric drug development, a well-defined, reliable, sensitive, and globally recognized PRO that measures signs and symptoms in children with CD and that can be used in conjunction with endoscopy-based endpoints and/or biomarkers is sorely needed.
authors: *Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration †Study Endpoint and Labeling Development, Office of New Drugs, Center for Drug Research and Evaluation, Food and Drug Administration, Silver Spring, MD ‡Connecticut Children's Medical Center, Hartford §Division of Gastroenterology and Inborn Errors Products, Office of New Drug, Center for Drug Research and Evaluation, Food and Drug Administration, Silver Spring, MD.
authors: Haihao
authors: H
authors: Sun
authors: Elektra J
authors: EJ
authors: Papadopoulos
authors: Jeffrey S
authors: JS
authors: Hyams
authors: Donna
authors: D
authors: Griebel
authors: Jessica J
authors: JJ
authors: Lee
authors: Juli
authors: J
authors: Tomaino
authors: Andrew E
authors: AE
authors: Mulberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D004341:Drug Evaluation / Q000379:methods*; D006801:Humans; D012720:Severity of Illness Index; D016896:Treatment Outcome