An expert planning committee will plan and conduct a public workshop to explore accelerating the use of large simple trials (LSTs) to improve the speed and practicality of knowledge generation for medical decision making and medical product development, including efficacy and effectiveness assessments, in a continuously learning health system. The committee will steer development of the agenda for the workshop, including selection of speakers and discussants. Workshop content will explore: the concepts of LST design; examples of successful LSTs; the relative advantages of LSTs (in terms of cost and utility of results); the infrastructure needed to build LST capacity as a routine function of care; the structural, cultural, and regulatory barriers hindering the development of such LST capacity; building public demand for, and participation in LSTs; and identifying near-term strategies for accelerating progress.