THE UNIQUE NEEDS OF CHILDREN, ALONG WITH THE DISeases that are particular to the pediatric age group, have been responsible for the development of pediatrics as a specialty and for the creation of children’s hospitals as distinct from general hospitals for the care of children. These same factors have also driven the creation of the child health research enterprise. At its best, child health research stands as a model for the advancement of knowledge to improve health and health care. More than 200 hospitals in North America, Europe, Australia, and New Zealand participate in the National Cancer Institute–supported Children’s Oncology Group, and more than 90% of children diagnosed with cancer in the United States are treated at one of the participating hospitals. Discoveries from this research network have transformed the 5-year survival rate for all childhood cancers combined from virtually 0% to 80% and have led to far more rapid advancement in treatment of childhood cancer than adult cancer. The National Institute of Child Health and Human Development supports the Neonatal Research Network, a national multicenter collaborative that has provided important advances in neonatal care, with current survival of infants as small as 24 weeks’ gestation. Research by the Pediatric Emergency Care Applied Research Network (PECARN) has placed pediatric emergency care on a firmer evidence base. At least one large prospective life-history study has been funded and data collection begun. The National Children’s Study, examining the effects of the environment and genetics on the growth, development, and health of children, is the largest long-term study of child health ever conducted. It will involve more than 100 000 children who will be followed up from conception to age 21 years. However, child health research has not always met the challenges to excellence. The quantity and quality of child health research are limited in many areas, leaving physicians with no choice but to extrapolate from adult studies, using interventions that may not have been properly evaluated or medications that may be potentially harmful. Fewer research studies involve children than adults. Two analyses of randomized controlled trials published over 20 years found a greater increase in those conducted among adults than children. In 174 specialty journals, the number of trials involving adults increased by 91 per year compared with only 17 trials per year involving children. In 5 high-impact general medical journals, adult trials increased by 4.71 per year while those in children increased by 0.4 per year. In addition, child health research is often of lower quality than that involving adults. Most child health research studies are cross-sectional and often single-center studies with small sample sizes. Other problems include reliance on surrogate rather than hard clinical end points and outcome assessment instruments that have not been validated in children. Drug studies may rely on off-label or unlicensed medications as the standard, dosing regimens that are not empirically based, or inappropriate formulations. A number of unique challenges may affect the child health research enterprise. In the developed world, the majority of children are healthy, limiting the pool of potential participants in research studies and underscoring the need for multicenter research networks. The types of diseases in children, including many behavioral and emotional conditions, may be challenging to study. Research in pediatrics needs to consider a child’s age and developmental stage, which may require a larger study population and a longer time frame. Unlike studies in adults, studies in children are complicated by the necessary participation of the parent or caregiver. Children depend on adults to recognize their illness, take them for care, and make decisions about treatment, adding another layer of complexity in studying child health. In addition, parents or caregivers often provide information to researchers, rather than the data being obtained directly from the child-participant. In attentiondeficit hyperactivity disorder, for example, ratings by parents and teachers are required. Parents must provide informed consent for their child’s participation in a study, which can lower the participation rate. For example, parents may be reluctant to agree to research participation if a potentially painful procedure is involved. In addition, ethi-