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Alternate Endpoints and Clinical Outcome Assessments in Pediatric Ulcerative Colitis Registration Trials

Sun, Haihao*; Lee, Jessica J.; Papadopoulos, Elektra J.; Lee, Catherine S.*; Nelson, Robert M.*; Sachs, Hari C.§; Rodriguez, William J.*; Mulberg, Andrew E.

Journal of Pediatric Gastroenterology and Nutrition: January 2014 - Volume 58 - Issue 1 - p 12–17
doi: 10.1097/MPG.0000000000000186
Special Feature

Objectives: Presently, there is no consensus on endpoint measures to assess clinical outcomes for pediatric ulcerative colitis (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 to 2008 that led to Food and Drug Administration 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 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 were not consistent in pediatric UC trials. Consensus on the 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.

*Office of Pediatric Therapeutics, Office of the Commissioner

Division of Gastroenterology and Inborn Errors Products

Study Endpoint and Labeling Development (SEALD)

§Pediatrics and Maternal Health Staff, Office of New Drug, Center for Drug Research and Evaluation, Food and Drug Administration, Silver Spring, MD.

Address correspondence and reprint requests to Andrew E. Mulberg, MD, FAAP, Division of Gastroenterology and Inborn Errors Products, Office of New Drug/Center for Drug Research and Evaluation/Food and Drug Administration, Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 5120, Silver Spring, MD 20993 (e-mail:

Received 8 July, 2013

Accepted 16 September, 2013

This article has been developed as a Journal CME Activity by NASPGHAN. Visit http:// to view instructions, documentation, and the complete necessary steps to receive CME credit for reading this article.

The views expressed in this article are those of the authors and do not necessarily reflect official positions or policies of the Food and Drug Administration.

The authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,