PROJECT SUMMARY/ABSTRACT Background and Goal. More than 90% of children with cancer live in low-resourced settings, where survival is only 20%. Sustainable evidence-based (EB) interventions yielding ongoing beneficial patient outcomes is critical to improve childhood cancer survival. A better understanding of factors promoting intervention sustainability in these settings is urgently needed. The goal of our project is to provide an empirical understanding of how clinical capacity, or the resources needed to sustain an intervention, impacts sustainment of a Pediatric Early Warning System (PEWS), EB interventions that improves pediatric oncology outcomes in low-resource hospitals by quickly detecting clinical deterioration in children with cancer, preventing the need for more intense treatment. Aims and Methods: We will conduct a prospective, longitudinal study of 92 low-resource hospitals implementing and sustaining PEWS. This work will build on an ongoing St. Jude-Wash U Implementation Science Collaborative and Proyecto EVAT, a quality improvement collaborative of Latin American pediatric oncology centers. Aim 1: We will evaluate how clinical capacity for sustainability changes over time through 5 to 9 prospective measurements of capacity via survey of clinical staff using PEWS (n=13 per center) during the phases of PEWS adoption, implementation, and sustainability. Aim 2: We will determine the relationship between capacity and a) PEWS sustainment and b) clinical deterioration mortality among pediatric oncology patients at centers sustaining PEWS for 2 to 10 years using chart review and an existing patient outcomes registry. Aim 3: We will develop novel strategies to promote sustainability by gaining a deeper understanding of perceived challenges to building capacity and PEWS sustainment. In combination with quantitative outcomes, we will conduct 24 focus groups with hospital staff (doctors, nurses, and administrators) from hospitals with both high (n=4) and low capacity (n=4). We will then use implementation mapping to generate theoretically driven, empirically-supported strategies which promote sustainability. All aims will be informed by an External Advisory Board and the EVAT steering committee. Innovation and Impact: Few EB sustainability strategies exist for low-resource settings. This study will advance implementation science by providing a theoretically-driven, foundational understanding of factors that predict sustainability among a large, diverse cohort of low-resource hospitals. We will then use this knowledge to develop sustainability strategies that optimize capacity and promote long- term sustainment of PEWS and improvements in patient outcomes in low-resource settings - ultimately promoting equity in childhood cancer care globally.