How the US Food and Drug Administration defines and detects adverse drug events

Background: Examination of pediatric adverse drug events (ADEs) requires an understanding of the US Food and Drug Administration's (FDA's) regulatory definitions of ADEs and methods for their assessment. Objective: The aim of this paper was to characterize the tools used by the FDA to define ADEs. Methods: FDA regulations and ADE reporting databases and resources were examined, including the Adverse Event Reporting System (AERS), drug-use profiles, population databases, and active surveillance systems. Results: The US Code of Federal Regulations defines ADEs and degrees of seriousness of ADEs for regulatory reporting purposes. Drug manufacturers must report certain ADEs to the FDA, whereas health care professionals and consumers may report such events voluntarily using the MedWatch program. All reported ADEs constitute the FDA's AERS, which is used along with other postmarketing surveillance components to determine drug safety signals. AERS detects rare ADEs well and inexpensively, but underreporting and the variable quality of reports can limit its usefulness. AERS is best used in conjunction with other data resources, such as active surveillance systems, information on the volume and patterns of medication use, disease-specific background incidence rates, and population databases that can link outcomes with drug exposures. Conclusions: The FDA uses a network of data resources to supplement detection of ADEs via AERS. These data resources can be used to amplify, validate, and quantify ADE signals and then compare them to their expected background occurrence in the population. Use of additional databases and perspectives will improve the ability to detect ADEs in all settings, including the pediatric population, and to monitor risk management efforts to curtail the occurrence of known ADEs.