The FDA announced a policy shift that will generally require randomized controlled trials (RCTs) to support approvals of CAR‑T cell therapies, raising the evidentiary bar for developers. FDA Center for Biologics Evaluation and Research (CBER) leadership published the new guidance in JAMA and signaled preference for survival or other time‑to‑event endpoints over single‑arm response trials. The agency noted exceptions remain for ultra‑rare or heavily pretreated populations, but emphasized RCT evidence where feasible. Developers that built regulatory plans around single‑arm registrational data will need to reassess timelines, trial designs and commercialization strategies. The FDA said the move reflects its experience with seven CAR‑T approvals to date, several based on nonrandomized trials. The guidance is likely to increase late‑stage trial costs and shift competitive dynamics toward companies with resources to run large randomized studies. Clarification: An RCT (randomized controlled trial) randomly assigns patients to different treatments to reduce bias and strengthen causal inference. The FDA’s position echoes broader agency efforts to demand more robust comparative evidence for complex biologics. Stakeholders should expect longer development cycles for many CAR‑T programs unless clear exceptions apply.