The FDA issued a complete response letter to Biohaven's submission for troriluzole in a neurological indication, ruling that the real‑world evidence (RWE) and externally controlled analyses failed to meet standards for demonstrating substantial evidence of effectiveness. The agency cited risks intrinsic to RWE and external controls—bias, design limitations and unmeasured confounders—and advised further meetings to define acceptable evidence. The decision signals a tighter regulatory posture toward RWE as a primary basis for approval and forces companies that had hoped to shortcut costly randomized trials to re‑evaluate development strategies.