Sun Haihao, Papadopoulos Elektra J, Hyams Jeffrey S, Griebel Donna, Lee Jessica J, Tomaino Juli, Mulberg Andrew E
*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.
J Pediatr Gastroenterol Nutr. 2015 Jun;60(6):729-36. doi: 10.1097/MPG.0000000000000793.
The aim of the present study was to identify areas for further development of clinical outcome assessment (COA) in pediatric Crohn disease (CD).
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.
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.
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.
本研究旨在确定儿童克罗恩病（CD）临床结局评估（COA）进一步发展的领域。
该研究根据美国食品药品监督管理局（FDA）患者报告结局（PRO）开发指南中描述的标准，分析了文献中所有现有的儿童CD的COA工具的测量特性，以及已批准的儿童CD药物的已发表注册试验。
对儿童克罗恩病活动指数（PCDAI）及其衍生指标（简化版、简短版、改良版和加权版PCDAI）进行了综述。为成年患者设计的克罗恩病活动指数（CDAI）和哈维-布拉德肖指数（HBI）已在一些儿童CD研究中采用。在Remicade和Humira试验中使用PCDAI作为终点，促成了FDA批准其用于儿童CD的适应症。COA工具测量特性中的常见问题包括：缺乏直接来自患者或护理人员的意见来生成测量体征和症状的条目；缺乏证据表明与内镜检查观察到的临床相关炎症存在相关性；在测量、适合年龄的访谈脚本以及医生访谈者的反应评分标准方面缺乏标准化。
现有证据表明，CDAI、HBI以及PCDAI的5个版本缺乏足够的测量特性，无法用作旨在支持治疗儿童CD产品获批的3期试验的主要终点。为了促进儿童药物开发，迫切需要一种定义明确、可靠、敏感且全球公认的PRO，用于测量CD儿童的体征和症状，并可与基于内镜检查的终点和/或生物标志物结合使用。
