Is the randomized, controlled trial in children an endangered species?

OBJECTIVE: To discuss the potential effects of current Food and Drug Administration (FDA) policy in the United States facilitating the approval of novel therapies for use in children (based on safety trials) on pediatric randomized, controlled trials in the pediatric intensive care unit setting. Method: The history of randomized, controlled trials, the FDA, and the events that led to this ruling are discussed. RESULTS: A recent FDA ruling ensures increased drug testing in children; however, it also opens the possibility for drug approval for use in children without any requirement for randomized, controlled trial testing of the efficacy of the drug on disease-specific outcomes. CONCLUSIONS: In light of the high degree of instability of pediatric intensive care unit patients, the frequent use of multiple drugs in a given patient with resultant drug-drug interactions, the risk of toxicity in critically ill infants and children with impaired drug metabolism, and age-dependent differences in physiology, clinicians must strive to be informed of the meaning of FDA approval or disapproval of the drugs they use for children.