Federal legislation and the advancement of neonatal drug studies.

T he directive from the US Congress, through laws and regulations mandating that manufacturers of pharmaceuticals demonstrate proof that new drugs are both safe and efficacious in target groups, has been in place for 50 years. However, children and, in particular, neonates remain disproportionately underrepresented in the majority of drug clinical trials. To date, federal legislation has been slow to respond to the need for improvement in this regard, and it has only been in the last one and a-half decades that attempts have been made to rectify this unacceptable situation. Children remain therapeutic orphans, and it has taken the might of the federal government to include them in drug development processes. The common practice of extrapolating data from studies conducted in adults and older children to neonates is problematic, even if the effects of the drugs and course of the disease are similar. Applicability of such data is limited by the unique physiology in neonates, an ever-changing body composition, rapid developmental processes, and a nonlinear relationship between body weight and pharmacologic variables. Dire consequences associated with the use of chloramphenicol (gray baby syndrome), sulfisoxazole and penicillin (kernicterus), novobiocin (hyperbilirubinemia), and vitamin E (neonatal sepsis and necrotizing enterocolitis) are some of the reminders of the danger of adopting therapies without adequate scientific information supporting the safety of the medications in the relevant populations. This review assesses efforts by government agencies to extend the benefits of federal legislations pertaining to drugs administered to infants and children, applauds its successes, highlights areas where knowledge gap exists, and offers suggestions on where efforts need to be focused.