Introduction

Abstract

Gastroesophageal reflux disease (GERD) occurs frequently in infants and children and can impair the health-related quality of life not only of our young patients but also of their parents. Acid-suppressive therapy is the standard of care in adults with GERD, but pediatric studies of antireflux treatments have rarely been undertaken. Moreover, it is inappropriate to extrapolate information from adult studies to the care of infants and younger children with GERD. As a result, evaluation of the efficacy, safety, and appropriate dosing of acid-suppressive medications in the pediatric population warrants a high priority on our research agendas. On December 6 to 8, 2000, a conference was held in Washington, D.C., to discuss issues relating to the conduct of pediatric trials in reflux disease. Presentations and open discussions focused on our current understanding of GERD and the limitations in what we know about the epidemiology, pathogenesis, natural history, and management of this disorder in children. Our meeting objective was to help lay the foundation upon which future clinical trials will be based and to stimulate collaborative efforts. Specifically, when acid-suppressing medications are ready for evaluation in infants and children, we hope the meeting will have contributed to the establishment of guidelines for study design. The meeting addressed the following questions: What are the relevant clinical questions to be addressed? Do we need an age-appropriate case definition of GERD? Do we need to perform endoscopy or intraesophageal pH monitoring as part of the protocol, either to document the presence of GERD or to assess drug efficacy? What outcome measures are appropriate? Do we need age-appropriate outcome measures? How do we monitor drug safety? Ultimately, our goal is to achieve labeling of acid-suppressive drugs for use in children, with the knowledge that the medications are safe and effective. The conference was organized by the Children's Digestive Health and Nutrition Foundation (CDHNF) in conjunction with the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). The mission of CDHNF is to stimulate research and provide funding for scientific research and educational initiatives that will improve the health of children and adolescents with digestive and nutritional disorders. The meeting was international and multidisciplinary in scope. The varied perspectives of investigators from different specialties, participants from industry, and representatives from regulatory authorities informed our discussions. It is our firm belief that this process of bringing together sponsors, regulators (such as the Food and Drug Administration [FDA]), and investigators is invaluable. The authors thank members of the FDA for their help in framing the questions that have been addressed and for their participation. Without the support of our industry partners, this meeting would not have been possible. We are grateful to AstraZeneca LP, Eisai Inc., Johnson and Johnson Pharmaceutical Research and Development LLC, Procter & Gamble Health Sciences Institute, Reliant Pharmaceuticals LLC, TAP Pharmaceutical Products Inc., and Wyeth Pharmaceuticals for their unrestricted educational grants. We are indebted to our colleagues in pediatric gastroenterology and to our colleagues from other pediatric subspecialties and other fields, including adult gastroenterology and clinical pharmacology, for generously sharing their thoughts and expertise. Since the meeting, NASPGHAN has published guidelines for the evaluation and treatment of pediatric gastroesophageal reflux (1). The CDHNF has recognized that GERD beginning in childhood and adolescence is a condition for which increased awareness and research are needed. The CDHNF has initiated a national campaign to educate primary care providers and specialists about the diagnosis and treatment of GERD in this vulnerable age group. Much remains to be done. Our hope is that these conference proceedings will contribute to the realization that multidisciplinary collaboration is needed to better understand and treat children with chronic GERD.