Advanced Methods and Modeling Core Abstract The Advanced Methods and Modeling Core (AMMC) is dedicated to advancing cutting-edge methods and modeling techniques to enhance the understanding of the PATC3H-IN Clinical Research Center (CRC) studies, which focus on the HIV epidemic among adolescents and young persons. The AMMC aims to synthesize heterogeneous findings from various strategies, interventions, settings, and populations into a cohesive framework capable of transforming the course of the epidemic. We recognize that strategies can have varying effects in different contexts and a central challenge to scientific coordination is weaving together findings from disparate interventions, settings, and populations. To meet this challenge, we begin with Appreciative Inquiry — a formal methodology in management science — that “listens” to the careful science already in progress at each of the eight CRCs in the network and then convenes a participatory process to define, design, and deliver on shared scientific goals. We will offer support for a range of flexible advanced methods (which are shaped by the content of the Request for Application as well as reading of existing study designs), but — in the spirit of co-creation — will continuously evaluate (with surveys and interviews), adapt, and re-design our activities. Our initial approach is also shaped by the analysis of available information about the projects in the network. We will draw from a transportability framework for external validity, longitudinal methods like group-based trajectory modeling, preference methodologies based on economic principles, and systems science, including agent- based modeling of effectiveness and cost-effectiveness. We are positioned to add qualitative evidence synthesis methods to meet emerging network needs. All methodologies enable connecting findings from different CRCs (e.g., projecting individual site findings onto shared epidemic dynamics through modeling to be usable at the onset, the middle, or the end of a trial to enhance opportunities for fit. Operationally, our support will be delivered through investigator-centered consultations, working groups, and a mini-consortium for systems science and modeling. The proposed Core will nurture advanced methods and modeling capacities for implementation science —which are operationally directly salient for adapting, scaling up, and sustaining evidenced-based interventions. We will ensure our services are user-friendly and catered to PATC3H-IN investigators, with a focus on early career researchers. The AMMC will work closely with the Capacity Supporting Core (to inform training in implementation science) and will play a crucial role in interpreting data generated by the network and informing implementation science, policy, and practice in coordination with the Community Engagement and Dissemination Core.