The FDA’s Center for Biologics Evaluation and Research (CBER) signaled a policy shift: most chimeric antigen receptor (CAR‑T) cell therapy approvals will now be supported by randomized controlled trials (RCTs) rather than single‑arm studies. CBER Director Vinay Prasad and colleagues outlined the change in a JAMA commentary, citing the agency’s experience with prior approvals and the need for comparative survival or time‑to‑event endpoints. The agency noted exceptions for rare or heavily pretreated populations, but the default will favor superiority or meaningful clinical benefit demonstrated in RCTs. Developers should expect higher evidentiary demands for new CAR‑T programs, which may lengthen timelines and alter trial design and commercial planning. Clarification: Randomized controlled trials compare a new therapy against a control arm to demonstrate superiority or non‑inferiority on clinically meaningful endpoints like survival or progression.