The FDA’s Center for Biologics Evaluation and Research signaled a major policy shift: randomized controlled trials (RCTs) will generally be required to support approvals of CAR‑T cancer therapies, agency officials wrote in a JAMA article led by CBER director Vinay Prasad. The agency cited its experience approving seven CAR‑T products across 18 indications and flagged that single‑arm trials relying on response rates will no longer be the routine pathway. CBER officials specified narrow exceptions for rare diseases or heavily pretreated populations where RCTs are infeasible, but developers should expect superiority or time‑to‑event endpoints such as survival in registrational studies going forward. The move forces companies to redesign late‑stage programs, extend timelines and budget for head‑to‑head comparisons or add control arms. Investors and program teams must now weigh increased evidence requirements against the high commercial value of CAR‑T products. The change also raises strategic pressure on the growing in‑vivo and off‑the‑shelf CAR‑T field to generate comparative data that demonstrate meaningful benefit beyond existing therapies.