ISSUE: Since first being described more than 50 years ago, the pragmatic clinical trial (PCT) has been considered the most scientifically rigorous of all real-world research designs. Yet, despite its promise, the PCT design has been relatively underutilized in comparison to other approaches for real-world evidence (RWE) generation, such as prospective observational research and retrospective studies of electronic health records (EHRs) and administrative claims databases. More recently, a variety of organizations have focused attention on the potential to embed clinical trials in real-world practice settings as a means of involving practicing physicians, recruiting real-world patients, and leveraging existing EHR systems for data capture. Is this approach better suited to RWE generation? Should we be talking “embedded” rather than “pragmatic” for real-world clinical trials?

OVERVIEW: In its RWE Program Framework, the US Food & Drug Administration highlighted the benefits of integrating clinical trials into real-world practice settings, indicating that real-world data systems can be leveraged in this fashion to generate regulatory-grade evidence. Other organizations, including the NIH Collaboratory, the Clinical Trials Transformation Initiative (CTTI) and the Australian Clinical Trials Alliance, have workstreams devoted to advancing these objectives. Nirosha Lederer, the panel moderator, will set the stage for the discussion by outlining the key questions, including: What are the defining characteristics of embedded clinical trials? In what ways are embedded trials similar or different from pragmatic trials? Is embedding clinical trials in real-world practice a more practical way of improving their generalizability? David Thompson will highlight similarities and differences between embedded and pragmatic trials. Lindsay Kehoe will describe CTTI’s progress to date to identify practical issues associated with embedded clinical trials. Lou Fiori will provide an overview of case studies of embedded clinical trials undertaken in the US Veterans Administration system. The moderator will solicit audience interaction and feedback on the alternative viewpoints.