Officials at FDA’s Center for Biologics Evaluation and Research told JAMA and industry stakeholders the agency will generally favor randomized controlled trials (RCTs) with survival or acceptable time‑to‑event endpoints to support approvals of CAR‑T therapies, except in narrowly defined rare or multiply refractory settings. CBER leadership reviewed the agency’s CAR‑T experience, noting many earlier approvals relied on single‑arm response data in relapsed/refractory indications. The new stance signals a shift toward more rigorous evidence standards for next‑generation cellular therapies and could lengthen development timelines or raise investment requirements for sponsors. Companies working on CAR‑T and in‑vivo approaches will need to weigh the regulatory preference for randomized evidence when designing registrational programs or arguing for accelerated pathways in rare populations.