Every scientific investigation takes place in the context of uncertain evidence about a question of interest. We believe that the primary goal of research synthesis is to bring differing opinions concerning such questions to consensus. The focus of our application is the question regarding the evidence for an association between antidepressant use and suicidality and builds on our reanalysis of the FDA meta-analysis of antidepressant use and suicidality in youth (Kaizar, Greenhouse, Kelleher, Seltman 2005). Our work is motivated by the recognition that the existing evidence base that can inform this question is available from both experimental and non-experimental studies, and is neither perfect, in the sense that experiments may be rigorous but restricted, and non-experimental studies more general but may be biased nor complete, in the sense that the available outcomes of interest may be indirect (e.g., suicidal ideation/behavior and not completed suicide). The primary work of this application is the conduct of a research synthesis to help advance our understanding of the relationship among antidepressant use, suicide, and suicidality. Specifically, we will use cross-design synthesis, a relatively new research strategy for combining data from studies with complementary designs, to evaluate and combine evidence from both randomized trials and non-experimental studies. Our primary synthesis will include randomized trials of antidepressants both with and without psychotherapy along with data from at least two larger studies that include antidepressant use. We are particularly concerned with the development and application of methods that will facilitate the combining of evidence from multiple data sources, including methods for adjusting studies for factors that affect their external validity, and methods for exploring the effects of biases that affect internal validity. Our approach will be based on the use of Bayesian hierarchical models. We focus on Bayesian hierarchical models as one solution to the problem of making inferences when syntheses require not only modeling of within and between study heterogeneity, but also the qualitative differences of study types. The Bayesian approach will also help facilitate sensitivity analyses for assessing the robustness of inferences to various model inputs. We will also develop accessible and user friendly statistical software programs to implement the methodology that we develop.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH078629-04
Application #
7683005
Study Section
Special Emphasis Panel (ZMH1-ERB-W (07))
Program Officer
Rupp, Agnes
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$294,518
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Greenhouse, Joel B (2012) On becoming a Bayesian: early correspondences between J. Cornfield and L.ýýýJ. Savage. Stat Med 31:2782-90
Bridge, Jeffrey A; Greenhouse, Joel B; Sheftall, Arielle H et al. (2010) Changes in suicide rates by hanging and/or suffocation and firearms among young persons aged 10-24 years in the United States: 1992-2006. J Adolesc Health 46:503-5
Kelleher, Kelly J; Stevens, Jack (2009) Evolution of child mental health services in primary care. Acad Pediatr 9:7-14
Greenhouse, Joel B; Kaizar, Eloise E; Kelleher, Kelly et al. (2008) Generalizing from clinical trial data: a case study. The risk of suicidality among pediatric antidepressant users. Stat Med 27:1801-13
Cohen, Judith A; Kelleher, Kelly J; Mannarino, Anthony P (2008) Identifying, treating, and referring traumatized children: the role of pediatric providers. Arch Pediatr Adolesc Med 162:447-52
Bridge, Jeffrey A; Greenhouse, Joel B; Weldon, Arielle H et al. (2008) Suicide trends among youths aged 10 to 19 years in the United States, 1996-2005. JAMA 300:1025-6