Sean Hennessy uses pharmacoepidemiologic methods to generate real world evidence about the health effects of prescription drugs. His team has identified a survival benefit of potassium supplementation in users of loop diuretics(link is external) and studied serious health consequences of drug-drug interactions involving high-risk drugs including anticoagulants, antidiabetes agents and antiplatelet agents. His research has produced crucial knowledge about the cardiovascular safety of many widely-used drugs for mental health conditions including ADHD, depression and schizophrenia. He also evaluated an early approach to using medical insurance data to improve prescribing(link is external), finding it ineffective despite its federal mandate. This contributed to the omission of drug utilization review programs from Medicare Part D. He co-led a pair of studies demonstrating the effectiveness (link is external)and safety(link is external) of the SA14-14-2 vaccine for Japanese encephalitis (JE), which subsequently led to the immunization of millions of children per year in many populous countries including Cambodia, India, Malaysia, Nepal, Sri Lanka and Thailand. Use of that vaccine has been credited with reducing the incidence of JE. He co-developed the trend-in-trend research design(link is external) for study of the effects of rapidly increasing or declining exposures. He was also the senior author of a citizen petition(link is external) to the U.S. Food and Drug Administration that led to re-labeling of metformin, the best-proven oral drug for diabetes, to permit its use in persons with mild to moderate renal insufficiency.