FDA Commissioners Makary and Prasad publish NEJM commentary proposing single pivotal trial as drug approval default

FDA Commissioner Martin Makary and CBER Director Vinay Prasad published a perspective in the New England Journal of Medicine on February 18, 2026, announcing that a single adequate and well-controlled pivotal trial — supplemented by confirmatory evidence — would become the FDA's default standard for novel drug approvals. The piece ended what Makary and Prasad called the "two-trial dogma" established by the Kefauver-Harris Amendments, arguing that a single high-quality trial is scientifically sufficient when effect sizes are large and mechanisms plausible. Critics including patient advocates and biostatisticians noted the shift would reduce the statistical power to detect safety signals and could disproportionately harm populations underrepresented in trials.