Scientific Publications by FDA Staff

J Pediatr Gastroenterol Nutr 2014 Jan;58(1):12-7

Alternate endpoints and clinical outcome assessments in pediatric ulcerative colitis registration trials.

Sun H, Lee JJ, Papadopoulos EJ, Lee CS, Nelson RM, Sachs HC, Rodriguez WJ, Mulberg AE

OBJECTIVES: Currently, there is no consensus on endpoint measures to assess clinical outcome for pediatric UC. This study reviewed the endpoints used in the registration trials of approved drugs for pediatric UC. METHODS: The primary efficacy endpoints of all registration trials completed from 1950 - 2008 that led to FDA approval for indications in pediatric and adult UC were reviewed. RESULTS: Colazal and Remicade have been approved for pediatric UC indication, and clinical response was used as a primary endpoint in these registration trials. The clinical response in the adult Colazal trials was defined as a reduction of rectal bleeding and improvement in at least one of the other assessed symptoms (stool frequency, patient functional assessment, abdominal pain, sigmoidoscopic grade, and physician's global assessment) assessed by the Sutherland UC Activity Index. The pediatric Colazal trial defined clinical response using the Modified Sutherland UC Activity Index, which excluded abdominal pain and functional assessment. Both adult and pediatric Remicade trials used clinical response defined by the Mayo score as the primary endpoint. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to measure various secondary endpoints in the pediatric Remicade trial. CONCLUSIONS: Pediatric-specific endpoints were used, but outcome measures and definition of clinical response was not consistent in pediatric UC trials. Consensus on definition of successful treatment outcome (clinical response and/or remission) and collaboration in the development of well-defined and reliable measures of signs and symptoms for use in conjunction with endoscopic parameters of mucosal healing will facilitate pediatric drug development.