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Health policy and outcome research involves measuring and assessing access, costs, effectiveness, quality, and value of health care delivered in the everyday practice. In this talk, I introduce several health policy research questions and show different approaches to making inference on the basis of observational data. The goals of the research are to provide insights regarding how to reduce unwarranted variations in clinical practice, to organize, and deliver high quality care. An overview of future research developments that can be used in the quest for better population health will be also discussed.