Clinical researchers persistently struggle to engage study subjects. An unacceptable number of trials are delayed or fail to launch because of slow or low enrollment, at vast cost to sponsors and incalculable cost to patients when innovations languish. Because many populations remain significantly under-engaged in research, research does not represent the populations it is intended to serve. Individual and collective efforts to solve these challenges have produced only marginal improvements. At this time of incredible scientific opportunity, we will not succeed if we cannot solve the challenge of the reach and accessibility of research. But systems-level change to create an ecosystem that is patient-centric and inclusive, integrated into health care, accommodating to new entrants, and responsive to new technologies demands fundamentally different approaches supported by policy and practice change. This panel will discuss how leaders across sectors can reduce administrative burdens and streamline regulatory regimes to enable new approaches to flourish in clinical research.