Ending the Two-Pivotal-Trials Default for Drug Approvals

Summary

In a February 2026 New England Journal of Medicine commentary, Dr. Vinay Prasad and FDA Commissioner Marty Makary announced that the FDA would drop its longstanding two-pivotal-trials standard for drug approvals. The new default, they wrote, would be one “adequate and well-controlled” study plus confirmatory evidence — which could include mechanistic data, related indications, animal models, same-class drug data, or real-world evidence. They called the two-trial standard “dogma” that “no longer makes sense” given modern precision in drug discovery, arguing that well-designed modern studies “tell a complete biologic story.”

The commentary laid out credibility factors reviewers would weigh — magnitude of effect, contemporary controls, pre-specified endpoints, blinding, and missing-data handling — and described cases where two trials would still be required. Industry reporting framed the change as part of a broader Prasad-era push to speed drug access while raising evidentiary discipline on endpoints, with BioSpace and Barchart covering the announcement as official policy.

Critics in the drug industry warned the new standard could lower the bar for approvals; Prasad’s own long record argued the opposite direction — that the change paired with stricter demands on appropriate endpoints would yield fewer but more meaningful approvals.

Timeline

• Feb 2026 — Makary and Prasad publish the NEJM commentary declaring the one-trial-plus-confirmatory-evidence default.
• Feb–Apr 2026 — Trade press (BioSpace, Barchart) reports the policy as official; industry debates the implications for development programs.
• April 30, 2026 — Prasad departs the FDA; the policy shift was announced as agency direction during his tenure.