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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Rupp, Agnes
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University of Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
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Siddique, Juned; Reiter, Jerome P; Brincks, Ahnalee et al. (2015) Multiple imputation for harmonizing longitudinal non-commensurate measures in individual participant data meta-analysis. Stat Med 34:3399-414
Gibbons, Robert D; Coca Perraillon, Marcelo; Hur, Kwan et al. (2015) Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents. Pharmacoepidemiol Drug Saf 24:208-14
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan et al. (2013) Suicide risk and efficacy of antidepressant drugs--reply. JAMA Psychiatry 70:123-5
Gibbons, Robert D; Mann, J John (2013) Varenicline, smoking cessation, and neuropsychiatric adverse events. Am J Psychiatry 170:1460-7
Marcus, Sue M; Lu, Bo; Lim, Sungwoo et al. (2013) Suicide attempts in patients with bipolar disorder tend to precede, not follow, initiation of antiepileptic drugs. J Clin Psychiatry 74:630-1
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan et al. (2013) Inappropriate data and measures lead to questionable conclusions--reply. JAMA Psychiatry 70:122-3
Gibbons, Robert D; Hur, Kwan; Brown, C Hendricks et al. (2012) Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry 69:572-9
Bhaumik, Dulal K; Amatya, Anup; Normand, Sharon-Lise et al. (2012) Meta-Analysis of Rare Binary Adverse Event Data. J Am Stat Assoc 107:555-567
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan et al. (2012) Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry 69:580-7
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan (2012) Is the rate of suicide among veterans elevated? Am J Public Health 102 Suppl 1:S17-9

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