Population Exposure Required to Assess Clinical Safety: Report to the International Conference on Harmonization Working Group *

Abstract

Although available information suggests that most serious adverse events (SAEs) first occur and are most frequent within the first 3–6 months of drug treatment, some SAEs may increase in frequency or severity over time, or may occur only after exposure for more than six months. Data on this topic, however, are limited. Thus, the Tufts Center for the Study of Drug Development and the Centre for Medicines Research surveyed pharmaceutical firms in the United States and Europe, respectively, regarding the time of occurrence, incidence, and types of SAEs occurring during premarketing clinical exposure. The drug sponsors reported that 190 SAEs were possibly, probably, or definitely related to drug treatment. Eighty-two percent of those SAEs occurred during the first six months of treatment, while 81% first occurred during this time. This supports the contention that most SAEs first occur and are most frequent during the first six months of drug treatment.