Five recent significant events offer validation for resolving the dilemma about off-label drug use in children: 1) The FDA issued regulations for pediatric labeling of drugs in 1994, 2) Both the Drug Information Association and Pharmaceutical Research and Manufacturers of America held symposia to focus the attention of industry, i.e., about 80 percent of drugs are either not FDA approved for children or have extensive off-label use and inadequate dosing information, 3)The FDA Modernization and Accountability Act (PL 105-115) with its Pediatric component was enacted by Congress, 4) Five meetings of high international visibility addressed the issue, and 5) A Presidential directive to FDA caused a proposed rule on pediatric labeling. This dilemma can now be corrected by pediatric drug trials to meet FDA criteria for dose, efficacy and safety data. The NICHD PPRU Network Program provides resources for these trials. LSUMC-S PPRU contributes to 10 priority levels set by the 1993 RFA and by intercurrent National Steering Committee (NSC) meetings. Accomplishments for each priority are described in the Progress Report. Notable are pediatric therapeutic advances in a thermo-regulatory basis for antipyretic drug action, pentoxifylline for sickle cell disease, and clinical trial efficacy and safety data for a new formulation of acetaminophen submitted to FDA for labeling. LSUMC-S continued participation in this program sets two goals. 1. Provide a resource to acquire clinical data on new and marketed drugs, and 2. Investigate the pharmacology of new molecular entities for effective and safe use in children. To accomplish these goals, LSUMC-S offers: (1) A suitable clinical pharmacology program with willing investigators, a population of accessible patients, a children's clinical research facility, experienced principal investigator, evidence of industry collaboration, a core laboratory, data management resource, institutional commitments, and research nurse staff, (2) A description of two protocols which address major areas of pediatric therapeutics (sickle cell disease and adolescent smoking), (3) Continuation of active protocols for the Network, (4) Integration of a clinical and basic science team approach which applies pharmacokinetic/pharmacodynamic modeling techniques to our understanding of age-related differences in drug disposition and efficacy, (5) Matrix Management based on Good Laboratory and Clinical Practice (GLP and GCP) guidelines which are implemented by standard operating procedures for efficient utilization of resources, and (6) A training environment for those responsible for the health of children. The LSUMC-S PPRU research plan focuses on crucial pediatric pharmacotherapy issues to increase data for drug prescribing and FDA approval of labeling.
