Scientific Publications by FDA Staff

J Pediatr Gastroenterol Nutr 2015 Jun;60(6):729-36

Well-defined and reliable clinical outcome assessments for pediatric crohn disease: a critical need for drug development.

Sun H, Papadopoulos EJ, Hyams JS, Griebel D, Lee JJ, Tomaino J, Mulberg AE

OBJECTIVES: To identify areas for further development of clinical outcome assessment (COA) in pediatric Crohn's disease (CD). METHODS: 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 FDA 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. Crohn's disease activity index (CDAI) and Harvey-Bradshaw's 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 FDA-approved indication in pediatric CD. Common issues in measurement properties of COA tools included: 1) absence of direct patient or caregivers' input to generate the items measuring signs and symptoms; 2) absence of evidence demonstrating correlation with clinically relevant inflammation observed with endoscopic measures; and 3) 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 endoscopic based endpoints and/or biomarkers is sorely needed.