PURPOSE: The 21^st Century Cures Act in the US has intensified focus on the potential to generate clinical insights from real world data (RWD). Efforts are underway to replicate clinical trial findings with RWD as a means of assessing the credibility of the underlying sources. But it is well known that average treatment effects reported from trials often differ from individual patient experience in clinical practice, a phenomenon known as the “efficacy-effectiveness gap.” The objective of this workshop is to go beyond simple replication of average treatment effects from trials by demonstrating how analyses of RWD can be constructed to (1) shed light on the efficacy-effectiveness gap and (2) highlight differences in treatment effects by patient segment to inform treatment decisions in real-world practice.

DESCRIPTION: The workshop will begin with a 15-minute overview of the current policy context involving use of RWD for regulatory decisions. FDA has released its real-world evidence (RWE) framework, which describes specific regulatory use cases for RWD/RWE in postmarketing safety surveillance, label expansion, and new product approvals. Historically, label expansion and product approvals have been determined primarily based on data from randomized controlled trials (RCTs), and so FDA is currently undertaking a project to assess the extent to which analyses of RWD can reflect the RCT gold standard. The next 30 minutes will be devoted to describing methods for replicating RCTs using RWD (eg, matching study measures, patient selection criteria), assessing observed differences and their sources (eg, compliance with therapy), and conducting stratified analyses to identify relevant patient segments to evaluate heterogeneity of treatment effects. Case studies from the presenters’ work and the published literature will be considered. The final 15 minutes will solicit audience input on the current state of affairs and identify additional opportunities and challenges for use of RWD in regulatory decision making.