The US Food and Drug Administration is preparing to move away from its long‑standing practice of routinely requiring two pivotal clinical trials to approve many new medicines, according to a perspective article by Commissioner Marty Makary, MD, and Deputy Commissioner Vinay Prasad, MD, MPH, in the New England Journal of Medicine. In the article, the officials say the agency will increasingly rely on a single “adequate and well‑controlled” study, supported by additional evidence such as dose‑finding data, biomarker results, and real‑world or observational findings, when appropriate.
News coverage of the shift reports that the change is intended to speed patient access to innovative treatments while maintaining evidentiary standards by focusing on the totality of data rather than a numeric trial threshold. The article emphasizes that the two‑study paradigm was never a legal requirement, but rather an historical convention that the agency now views as too rigid for certain modern drug development programs, particularly in areas like rare diseases and targeted oncology.
Makary and Prasad state that FDA will still expect more than one trial in many situations, including when effect sizes are modest, safety signals are uncertain, or trial conduct may raise questions that require confirmatory work. They also note that the agency will place greater weight on trial quality, clinical relevance, and reproducibility of endpoints, and that sponsors should engage early with FDA to discuss acceptable designs under the updated approach.
The authors describe the policy as an evolution of FDA’s existing flexibility under statutes like the Food and Drug Administration Modernization Act and subsequent reforms, which already allow approvals based on a single large, well‑designed trial. Legal and policy analysts commenting on the article say the move formalizes practices that have been applied case‑by‑case, and could influence how companies plan pivotal programs, timelines, and evidence packages for future marketing applications.
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