Miguel Saps1, Harman S Biring, Cenk K Pusatcioglu, Stijn Mintjens, Damian Rzeznikiewiz. 1. *Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL †Department of Pediatrics, Emma Kinderziekenhuis, Academic Medical Centre, Amsterdam, The Netherlands.
Abstract
OBJECTIVES: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The Food and Drug Administration have published recommendations for clinical trials on AP-FGIDs in adults but not in children. The lack of methodological guidelines and accepted primary endpoints for clinical trials in children hampers the progress of the field, making the approval of new medications difficult. A necessary first step to determine the feasibility of clinical trials in children and provide recommendations on the best design for future trials is to review the methods, ability to recruit, attrition rate, and results of previous clinical trials. We designed a comprehensive review of pharmacological clinical trials in AP-FGIDs in children focused on study design. METHODS: Study eligibility was randomized controlled trials (RCTs) evaluating the efficacy of pharmacological interventions compared with that of placebo in children and adolescents with AP-FGIDs. RESULTS: There is no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous. Primary endpoints varied widely among studies. Many of the RCTs did not show a consistently significant benefit of the drug over placebo in some or all of the outcomes. We found a considerable risk of bias in most studies. None of the studies have considered minimal clinically important differences in their selection of primary endpoints. CONCLUSIONS: Few randomized clinical trials have been conducted. Most studies have methodological limitations and small sample size. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures.
OBJECTIVES: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The Food and Drug Administration have published recommendations for clinical trials on AP-FGIDs in adults but not in children. The lack of methodological guidelines and accepted primary endpoints for clinical trials in children hampers the progress of the field, making the approval of new medications difficult. A necessary first step to determine the feasibility of clinical trials in children and provide recommendations on the best design for future trials is to review the methods, ability to recruit, attrition rate, and results of previous clinical trials. We designed a comprehensive review of pharmacological clinical trials in AP-FGIDs in children focused on study design. METHODS: Study eligibility was randomized controlled trials (RCTs) evaluating the efficacy of pharmacological interventions compared with that of placebo in children and adolescents with AP-FGIDs. RESULTS: There is no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous. Primary endpoints varied widely among studies. Many of the RCTs did not show a consistently significant benefit of the drug over placebo in some or all of the outcomes. We found a considerable risk of bias in most studies. None of the studies have considered minimal clinically important differences in their selection of primary endpoints. CONCLUSIONS: Few randomized clinical trials have been conducted. Most studies have methodological limitations and small sample size. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures.