This is a competing continuation R01 proposal to support new biostatistical methodologic development and application of these new methods to individual level data on 11,939 adolescents in 42 existing or ongoing prevention and treatment intervention randomized trials aimed at depression. The central goal of our proposed work is the development and application of novel quantitative methods necessary to integrate findings across trials on preventing and treating depression in adolescence and their relevance for building and testing the next generation of comprehensive intervention strategies. Built on the past 22 years of NIH funding for the Prevention Science and Methodology Group (PSMG), this collaborative synthesis project will bring together expert methodologists and intervention scientists with the guidance of an external scientific advisory committee. The 42 prevention (n=24) and treatment (n=18) intervention trials we will use in this proposal focus on the child (e.g., cognitive behavioral, interpersonal therapy), parent/family (e.g., parent training), and/or antidepressants, each class known to have beneficial impact on adolescent depression. Our work will focus on examining the shared and unique mediators and moderators over these trials. Building on our data sharing agreements, we will conduct new cross-trial analyses of moderator effects involving demographic characteristics, symptomatology, and adversity across different clusters of prevention or treatment interventions. We will also examine the shared and unique mediational pathways of these interventions involving adherence/compliance, cognitive processes, and family processes. We propose new methodologic approaches to distinguish these shared and unique mediators and mediators using individual data across multiple trials. To minimize biases and maximize analytic comparability across trials, these new methods will account for individual and trial level differences in population/person level risk and protective factors, differences in the interventions including exposure, fidelity, or adherence, and differences in trial design including follow-up period, and assessment instruments. These new methodologic approaches are necessary because nearly all randomized trials are severely underpowered to address mediation or moderation within their own studies, and the statistical methods now available for data synthesis (e.g., meta-analysis), are not adequate for complex multi-trial analyses.
In Aim 1 we develop new biostatistical multilevel, longitudinal models to synthesize cross-trial analyses on mediation and moderation across related randomized trials.
In Aim 2 we apply these methods to trials on depression interventions for adolescents.
In Aim 3 we identify key gaps in our understanding of intervention efficacy to be addressed in the next generation of intervention trials, and develop scientific guidelines.

Public Health Relevance

Depression is the single leading cause of disability; and from a developmental perspective; its prevention ortreatment during adolescence can provide lifelong benefits. Despite the existence of generally efficaciousprevention and treatment interventions for depression; we have yet to assimilate this knowledge intopersonalized strategies that meet the public health needs of diverse populations to meet their acute as well aslonger term risk for recurrence. This work will specify who can benefit from different intervention optionsacross time and provide the knowledge to build effective personalized as well as contextualized interventionsto address depression in adolescence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH040859-26
Application #
8756157
Study Section
Special Emphasis Panel (ZRG1-RPHB-A (03))
Program Officer
Goldstein, Amy B
Project Start
1986-02-01
Project End
2015-03-31
Budget Start
2013-09-09
Budget End
2014-03-31
Support Year
26
Fiscal Year
2013
Total Cost
$420,580
Indirect Cost
$108,561
Name
Northwestern University Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Brincks, Ahnalee; Perrino, Tatiana; Howe, George et al. (2016) Preventing Youth Internalizing Symptoms Through the Familias Unidas Intervention: Examining Variation in Response. Prev Sci :
Pisani, Anthony R; Wyman, Peter A; Mohr, David C et al. (2016) Human Subjects Protection and Technology in Prevention Science: Selected Opportunities and Challenges. Prev Sci 17:765-78
Newcomer, Alison R; Roth, Kimberly B; Kellam, Sheppard G et al. (2016) Higher Childhood Peer Reports of Social Preference Mediates the Impact of the Good Behavior Game on Suicide Attempt. Prev Sci 17:145-56
Brown, C Hendricks; Brincks, Ahnalee; Huang, Shi et al. (2016) Two-Year Impact of Prevention Programs on Adolescent Depression: an Integrative Data Analysis Approach. Prev Sci :
Dagne, Getachew A; Brown, C Hendricks; Howe, George et al. (2016) Testing moderation in network meta-analysis with individual participant data. Stat Med 35:2485-502
Barch, Deanna M; Gotlib, Ian H; Bilder, Robert M et al. (2016) Common Measures for National Institute of Mental Health Funded Research. Biol Psychiatry 79:e91-6
Perrino, Tatiana; Brincks, Ahnalee; Howe, George et al. (2016) Reducing Internalizing Symptoms Among High-Risk, Hispanic Adolescents: Mediators of a Preventive Family Intervention. Prev Sci 17:595-605
Perrino, Tatiana; Pantin, Hilda; Huang, Shi et al. (2016) Reducing the Risk of Internalizing Symptoms among High-risk Hispanic Youth through a Family Intervention: A Randomized Controlled Trial. Fam Process 55:91-106
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
Cross, Wendi; West, Jennifer; Wyman, Peter A et al. (2015) Observational measures of implementer fidelity for a school-based preventive intervention: development, reliability, and validity. Prev Sci 16:122-32

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