ABSTRACT Analysis Core The overarching goal of the Analysis Core is to ensure the success of the MOST4 projects by providing an outstanding data analytic service for analysis plan management, advising on appropriate methodologic approaches, and implementation of high quality analyses. The Analysis Core will provide analytic support for the three major scientific projects in this grant cycle that address key gaps in knowledge in osteoarthritis (OA). This core will institute a process to ensure that rigorous and high quality study design and analytic methods will be instituted in MOST projects and studies, which will be critical for making valid inferences. The MOST Study has made major contributions to our understanding of the course of knee OA, largely due to the sophisticated analyses applied to the comprehensive data collected over the prior three funded cycles of MOST. The specific aims of the Analysis Core are as follows: 1) Provide detailed critical reviews of analysis plans to ensure that appropriate and high quality methods are used to ensure rigor and reproducibility of findings; 2) Develop detailed operational procedures with the Executive Committee to incorporate overall MOST4 study dissemination priorities and help ensure Project leads meet internal and external deadlines; 3) Conduct all analyses for MOST4- approved analysis plans using state-of-the-art methods that address unique statistical issues encountered in OA research and in MOST; 4) Provide ongoing education and training to MOST analysts and investigators to enable projects that rely on imaging and/or multidimensional data (e.g., Project 3: Mineralization) to take advantage of current and evolving methods in advanced analytic techniques including machine learning and visualization. By implementing high quality methods with standardized policies and procedures, the Analysis Core will efficiently manage a large number of analyses in an efficient, rigorous, and transparent manner to contribute to the scientific insights that will be made possible by the vast and rich data collection planned in MOST4.