Top FDA leaders argued in The New England Journal of Medicine that a single well‑controlled clinical trial should be the new default basis for drug approvals, replacing the long‑standing expectation of two pivotal trials. Commissioner Marty Makary and CBER director Vinay Prasad outlined that additional “confirmative evidence” — mechanistic data, related‑indication results, animal models, or real‑world evidence — can bolster a single pivotal trial submission. The policy move formalizes what agency officials have sometimes practiced in recent years but marks a clear shift in regulatory expectations. Regulators will retain discretion to require additional trials when warranted, for example when mechanisms are unclear or endpoints are surrogate. Industry analysts and investors flagged the potential to lower late‑stage development costs and accelerate approvals, while trialists warned the change may shift emphasis onto complementary evidence standards and post‑market confirmation.