The traditional “bench-to-bedside” paradigm for clinical research has been successfully used for many decades. This model of knowledge generation has led to discoveries that have enhanced the quality and length of life. The combination of changes in research practice and in health care delivery, growing complexity in decision-making, increasing use of electronic health records (EHR), and growing resource constraints necessitate a shift to a user-driven research paradigm to generate new knowledge. This conceptual framework was created to clarify the perspective of the decision makers as well as the range of factors and the variability in thresholds used to make decisions. This framework may help researchers in creating actionable information to meet the needs of decision makers, which is needed for the transition to a user-driven research paradigm. Further, it is important to create an appropriate set of incentives to facilitate this transition to a user-driven research paradigm.