CORE C: Clinical, Data Management and Statistical Modeling Core

SUMMARY (CORE C) The Clinical, Data Management, and Statistical Modeling Core (Core C) will be instrumental for the success of the P01 Program. In Aim 1, the Core will continue to conduct the Pediatric Dengue Cohort Study (PDCS) in Managua, Nicaragua. This cohort study is the longest continuous cohort study of dengue and as such is an invaluable source of samples and clinical data from children with natural sequential dengue virus (DENV) infections. Both retrospectively and prospectively collected samples and data will be available to the P01 Projects and Cores. Core C will oversee all aspects of running the PDCS including enrollment, sample collection and storage, data collection and management, quality control, provision of medical care, and human subjects documentation. In Aim 2, Core C will coordinate the compilation of clinical data and the distribution of samples available from the P01 Program dengue cohort studies in Nicaragua and the Philippines as well as a vaccine challenge study at the NIH. To this end, the Core will design, maintain, update and oversee the P01 Program databases, which will include clinical data and sample characteristics and availability. Core C will provide tailored data sets and assist in selection of analysis-specific biological specimens, ensuring efficient data sharing and sample distribution through the implementation of high levels of quality control. This will include having a data manager at the University of Michigan (UM) who will compile the data from the clinical sites and use it to assemble data sets, including the creation of any necessary variables for P01 Program sites. Core C personnel at UC Berkeley will be responsible for receiving samples from Nicaragua, maintaining an inventory, and distributing the samples to P01 Projects in response to requests and in coordination with the data manager at UM. Finally, sequencing and phylogenetic analysis of local dengue viruses will be performed in Nicaragua. In Aim 3, the Core will maintain a copy of immunological data generated through the Projects 1-3 and Core D and will deposit data into ImmPort. P01 investigators will be able to submit data for upload to and download data from ImmPort, facilitating the flow of information across all P01 Program partners and making data publicly available. In Aim 4, the Core will provide statistical and analytic support to all Projects and Cores, including sample selection, study design, sample size calculation, and statistical analysis, as well as machine learning, antigenic cartography and antibody landscapes. Core C will also integrate data collected through the P01, including a cross-P01 evaluation of assays (previously identified by the Consortium as potential correlates) to define the most appropriate biomarkers of protection and risk against dengue disease in the context of both natural infections and vaccines, different geographic regions, and different study designs. Taken together, the Clinical, Data Management and Statistical Modeling Core will play an essential role in the P01 Program by providing data and samples to scientific Projects and Core D for the ultimate purpose of identifying both natural and vaccine-induced immunological determinants of protection and risk against dengue disease.