ABSTRACT The purpose of this proposal is to develop, test, and apply new statistical methodologies that can be used to identify low base rate drug adverse event (AE) interactions. These new methods will then be applied to a wide range of existing non- experimental datasets to examine the relationship between antidepressants and suicide attempts and completion. We have designed this research project as an integral collaboration between biostatisticians, research psychiatrists and clinicians, economists, and pharmacoepidemiologists, working with large ecological and medical records/claims electronic patient databases covering years where antidepressant use is varying dramatically. Three major specific aims are proposed: (a) the development of new statistical surveillance methods for detecting drug-AE interactions, (b) the development and application of analytic methods for ecological and population data, and (c) the development of and application of statistical methods for analysis of person-level data from large scale medical records/claims databases both in the U.S. and in Europe. The datasets that we have been granted access to include the FDA spontaneous reporting system (SRS/AERS/MedWatch), electronic medical record/claims databases in the U.S. (VA, and PHARMetrics), and similar data from the Netherlands (PHARMO). The work in this proposal will be carried out by a research consortium that will study national and international drug safety issues. The multidisciplinary group includes the areas of statistics (Drs. Gibbons, (PI), Brown (co-PI), Bhaumik, Hur, Marcus, and Rosenbaum), psychiatry from adult (Mann), and child (Brent) perspectives, health economics/econometrics (Heckman), and pharmacoepidemiology (Valuck). Collaboration with members of the VA (Cunningham), and PHARMO (Erkens, Herings) is an integral part of the proposal. PUBLIC HEALTH RELEVANCE: The enormous human cost of suicide makes research and prevention a national priority. Traditional approaches to drug safety have proved inadequate to address current public health issues. Providing statistical and methodological advances for the active surveillance of Drug-AE interactions, such as antidepressants and suicide, is a necessary first step in the establishment of a science-based health policy system, and is the primary goal of this proposal.

R01MH080122

2008-09-25

2014-06-30