Replication of Randomized, Controlled Trials Using Real-World Data: What Could Go Wrong?

With the growing interest in using real-world evidence (RWE) for regulatory purposes, researchers and policy makers are considering how best to assess credibility of RWE. Because randomized controlled trial (RCT) has long been regarded as gold standard high-quality research, one approach being pursued is see what extent findings from RCTs can be replicated based on analyses nonrandomized data (RWD). If congruent, reasoning goes, this would bolster confidence underlying RWD sources validity RWE generated. But it well known that medical interventions perform differently experimental clinical trials versus practice, reflecting a phenomenon “efficacy-effectiveness gap.” So even with highest-quality strongest analytic methods, we should expect observe discrepancies between This calls into question objectives RCT replication efforts makes clear impugning methods failing align inappropriate and, worse, potentially harmful acceptance stakeholder decision making.