Safer, Better, More Appropriate: Clinical Trial Design for Pediatric Drug Labels

Abstract

Off-label use of drugs in pediatrics remains a national and international problem. The American Academy of Pediatrics determined in 1977, and reaffirmed in 1995, that there was a moral imperative to formally study drugs in children so they “have access to important medications and receive optimal drug therapy.” Congress passed legislation in 1997 that encouraged the study of patent drugs, or those with remaining exclusivity or patent protection, in pediatric patients. Manufacturers of new chemical entities could earn an incentive (in the form of pediatric exclusivity) for their product if a program of pediatric clinical research that met the requirements of a Written Request from the Food and Drug Administration was completed as scheduled. Such pediatric research must be expected to yield medically valuable information for pediatric patients. Additional legislation, the Best Pharmaceutical for Children Act, which renewed the exclusivity incentive for the “on-patent” drugs and provides a mechanism to facilitate the study of “off-patent drugs”, and the Pediatric Research Equity Act address ways to encourage obtaining safety and efficacy data in pediatric patients. Pediatric drug trials require a concerted effort from academia, industry and patient advocacy groups to obtain safety, efficacy, and pharmacokinetic data in placebo-controlled or active-controlled multicenter trials. Because of the unique nature of pediatric patients, data for pediatric drug labeling may need to be derived from creative clinical trial designs and population pharmacokinetic studies, randomized withdrawal trials, enrichment studies, as well as the utilization of extrapolation of clinical efficacy when appropriate. These novel approaches to clinical trial design as well as a discussion of more classical clinical trials are discussed in relation to pediatric clinical studies.