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# FDA Officials Discuss One Trial Standard
- URL: https://www.fdaweb.com/fda-officials-discuss-one-trial-standard/
- Published: 2026-02-18T12:00:00.000Z
- Updated: 2026-09-14T13:33:59.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5160689

A newly published FDA [perspective](https://www.nejm.org/doi/full/10.1056/NEJMsb2517623?ref=fdaweb.com) in the *New England Journal of Medicine* outlines a significant shift in how the agency intends to evaluate new drug applications: moving from a longstanding default expectation of two pivotal trials to one.

In the article, FDA commissioner **Marty Makary** and CBER director **Vinay Prasad** write that the agency will formally adopt a “one adequate and well-controlled study” default standard for marketing authorization, provided that confirmatory evidence supports the findings. The change, they say, reflects modern scientific capabilities and will be paired with strengthened postmarket data collection requirements.

Although federal law has permitted approvals based on a single adequate and well-controlled study since 1997, the agency historically operated under what the authors describe as a de facto “two-trial dogma.” Requiring two trials was designed to reduce the probability of false-positive results in an era when biologic understanding was more limited.

From a statistical standpoint, they note, testing an inert product twice lowers the likelihood of a Type I error because a false-positive finding would need to occur in both trials. But in contemporary drug development, they contend, regulatory confidence rests on more than replication alone.

Mechanistic data, biomarker responses, intermediate endpoints, class effects, animal models, and real-world evidence now contribute to a more comprehensive assessment of causality. In many therapeutic areas — particularly oncology — approvals based on a single premarket study are already common practice.

“Two trials should be seen as just one of many interlocking facets of clinical credibility,” the authors write, emphasizing that trial quality, effect size, biologic plausibility, and statistical rigor often matter more than simple replication.

Under the new default, FDA reviewers will place heightened scrutiny on study architecture: the appropriateness of control arms, prespecified hypotheses, primary endpoints, blinding and concealment, statistical power, handling of missing data, and alignment between surrogate markers and biologic targets.

The agency also signals growing comfort with Bayesian interpretations of trial data, rather than relying exclusively on traditional frequentist thresholds.

Importantly, the shift does not eliminate the agency’s authority to require multiple trials. FDA says it will still demand additional studies when a drug’s mechanism of action is unclear, when outcomes are highly labile or surrogate-based, or when a trial’s design presents methodological limitations.