Printed in U.S.A. Spontaneous Adverse Event Signaling Methods: Classification and Use with Health Care Treatment Products

Since the systematic recording of health care treatment-associated adverse events (AEs) was first proposed by Finney after the thalidomide tragedy (1-3), regulators, pub-lic health organizations, and manufacturers have been faced with the difficult task of interpreting postmarketing AE sig-nals. A reexamination of the methodology supporting this process is now occurring as a result of several important developments, including guidances by the International Conference on Harmonisation (4), directives from the European Committee for Proprietary Medicinal Products (5, 6), new signaling procedures for screening multiproduct reporting systems (7), and an Institute of Medicine report in the United States that documented the need for enhanced preventive measures aimed at AEs (8). Such initiatives reflect the critical role of pharmaceutical interventions i