In 2009, the FDA approved 181 major safety regulatory actions, including 1 drug safety withdrawal, 25 new boxed warnings, 19 new contraindications, 90 new warnings, and 46 revisions of previous actions (Table). Among the newly identified adverse effects were suicidal behavior, life-threatening viral infections, renal failure, and increased cancer risk in children. Adverse event reports from drug manufacturers or through the MedWatch program were the predominant source of scientific information and formed the basis of 77 of 135 new regulatory actions (57%) and 19 of 25 new boxed warnings (76%). Clinical studies were cited as the evidence source for 26 of 135 actions (19%) but only 2 were derived from statistically significant differences and 1 was based on a single study case. A large FDA meta-analysis of suicidal behavior and antiepileptic drugs generated warnings for 19 drugs.3 In 23 of 135 new actions (17%), the scientific evidence was derived from other drugs, with 15 based on similar chemical structure and mechanism, and 8 based on the same indication and/or patient population. The safety actions occurred a median of 11 years after initial approval and included 61 drugs marketed for 15 years or more; only 36 actions involved drugs within first 5 years after approval.