dFDA: A Decentralized Framework for Drug Assessment Using Two-Stage Real-World Evidence Validation

We present the Predictor Impact Score (PIS), a novel composite metric operationalizing Bradford Hill causality criteria for automated signal detection from aggregated N-of-1 observational studies. Combined with pragmatic trial confirmation (based on evidence from 108+ embedded trials), this two-stage framework generates validated outcome labels at ~44x lower cost than traditional Phase III trials. This enables continuous, population-scale pharmacovigilance and precision dosing recommendations.