Project Summary The prevention of excessive drinking and related negative consequences by underage drinkers and college students is an important objective for Healthy People 2020. This resubmission application is aimed at extending an R01 grant (R01 AA019511) in response to PA-15-295, “Screening and brief alcohol interventions in underage and young adult populations (R01).” The previous R01 focused on methodological developments for pooling and analyzing individual participant data (IPD) from 24 studies (N = 24,336 at baseline; 12,630 randomized) to examine the efficacy of brief motivational interventions (BMIs) for college students. Deploying newly developed methods to combine and analyze IPD, the resulting large, pooled data set showed that BMIs for college students may not be as powerful as prior reviews suggest, pointing to the need to better understand why some interventions succeed while others fail. Our previous research on IPD was limited in terms of its study-level sample size (24 studies) as well as its population representation. Moreover, recently published traditional meta-analyses have found overall intervention effects, contradicting our findings. The proposed research expands and enhances our earlier work by using the cutting-edge methodology with a comprehensive set of data with the end goal of providing an authoritative summary of the alcohol intervention field for adolescents and young adults. Beyond simply focusing on the omnibus question of “any effect,” our research is aimed at testing which interventions are better and exploring how to individualize intervention strategies to meet different needs of the individual for greater benefit (i.e., precision medicine). We will combine aggregated data (e.g., means, SDs) from approximately 350 independent brief alcohol intervention trials and IPD from 49 trials. Of these, aggregated data from 303 samples and IPD from 24 studies have already been secured with the support of two separate R01s (AA020286 to Tanner-Smith and AA019511 to Mun). We will maximize the scale and depth of the existing clinical data via the following state-of-the-art synthesis approaches: network meta-analysis (meta-regression) and multivariate meta-analysis, and their extensions for IPD. In a major extension of prior work, the proposed investigation will (1) respect the natural hierarchy of the data (i.e., participants nested within studies); (2) simultaneously accommodate multiple interventions (networks instead of any two pairs of interventions); (3) explain effect heterogeneity (i.e., strong to weak intervention effects) by examining factors at the individual- and study-level, as well as cross-level; and (4) allow joint analysis of multiple related outcomes (e.g., alcohol use and problems) by borrowing strength from one another. Our transdisciplinary team of leading experts, many of whom led the earlier, successful research will generate new evidence that will be “scalable” so that new trial data can straightf...