ISSUE: With the growing interest in using real world evidence (RWE) for regulatory purposes, researchers and policy makers are considering how best to assess the credibility of RWE. As the randomized controlled trial (RCT) has long been regarded as the gold standard, one approach being pursued is to see to what extent findings from RCTs can be replicated using real-world data (RWD). If findings are congruent, this would bolster confidence in the underlying RWD sources and validity of the RWE generated. But it is well known that products perform differently in clinical trials versus clinical practice, a phenomenon known as the “efficacy-effectiveness gap.” So even with the highest quality RWD and strongest analytic methods we can and should expect to observe discrepancies in findings between RCTs and real-world studies. Hence the panel question, what does good look like when we attempt to replicate RCTs using RWD?

OVERVIEW: Marc Berger, the panel moderator, will set the stage for the discussion by outlining the key questions, including: What are the methodologic issues in using RWD to replicate RCTs? How do we interpret any discrepancies we observe between RCTs and real-world studies in light of the efficacy-effectiveness gap? Is this approach appropriate to render judgements on the validity of RWD/RWE? David Martin will describe an ongoing FDA project involving the replication of 30 RCTs using RWD. Sebastian Schneeweiss, who is involved in the FDA project, will outline the study methodology and approaches for interpretation of findings as part of an overall argument supporting this approach. David Thompson will take a contrarian position that involves identifying the myriad reasons why study findings based on RWD might diverge from RCTs, even in instances in which the quality of the underlying data sources is high. The moderator will solicit audience interaction and feedback on the competing viewpoints.