Research questions around real-world evidence development can include a breadth of evidence needs including the prevalence, clinical characteristics, treatment patterns and effect, etc. of a given cohort and/or sub-cohort. Addressing the question(s) can be complicated by the size/characteristics of the cohort and the complexities of the health system. Consequently, we propose a practical and feasible approach to assessing study design options which we believe will meet both the research objectives as well as consider the realities of timelines and budget constraints. We will discuss a number of options for study design and cohort identification, including use of administrative claims and/or electronic healthcare records, sitebased recruitment, and web-survey panelists. We will identify a set of common methodological challenges and discuss the relative strengths of each approach in addressing these issues.