FDA Shifts to One-Trial Drug Approval Standard

Critics warn the change risks public health for the sake of speed and innovation.

Mar. 1, 2026 at 1:47pm

Got story updates? Submit your updates here. ›

The FDA has announced a policy shift that will make one pivotal clinical trial, accompanied by "confirmatory evidence," the default standard for approving most new drugs. The agency argues this will reduce development costs, shorten time to market, and spur innovation. However, critics warn the change risks public health, as a single trial may not provide enough certainty about a drug's safety and efficacy, especially for drugs targeting common conditions where millions could be exposed.

Why it matters

The two-trial norm has long been seen as a safeguard to ensure reproducibility, a core scientific principle. Critics argue that relying on a single trial, even with supportive data, could lead to more false positives and unintended harm, especially for drugs targeting common conditions where the risk calculus is different than for rare diseases with limited treatment options.

The details

The FDA says modern science is more precise, mechanisms are better understood, and tools like biomarkers and Bayesian approaches can complement traditional replication. But the author argues mechanism is not outcome, and improvements in lab values or surrogate markers don't necessarily translate into better clinical outcomes for patients. The policy extends beyond rare diseases and advanced cancers, where single-trial approvals have been more common, to now potentially apply to drugs for common conditions like hypertension and diabetes.

  • The FDA announced the policy change via a "Sounding Board" in the New England Journal of Medicine in 2026.
  • The two-trial norm dates back to reforms in the early 1960s, when Congress required "adequate and well-controlled investigations" before drug approval.

The players

Marty Makary, MD, MPH

FDA Commissioner, co-author of the NEJM article announcing the policy change.

Vinay Prasad, MD, MPH

Top FDA deputy, co-author of the NEJM article announcing the policy change.

Arthur Lazarus, MD, MBA

Former Doximity Fellow, member of the editorial board of the American Association for Physician Leadership, and adjunct professor of psychiatry at the Lewis Katz School of Medicine at Temple University, author of the opinion piece criticizing the FDA's policy shift.

Got photos? Submit your photos here. ›

What they’re saying

“We've already been doing this. More than half of recent approvals have relied on a single pivotal trial plus supportive evidence, particularly in oncology and rare diseases.”

— Marty Makary, MD, MPH, FDA Commissioner (medpagetoday.com)

“Replication is not dogma. It is discipline. It is how science separates signal from chance -- particularly when millions of patients may ultimately be exposed.”

— Arthur Lazarus, MD, MBA, Former Doximity Fellow, member of the editorial board of the American Association for Physician Leadership, and adjunct professor of psychiatry at the Lewis Katz School of Medicine at Temple University (medpagetoday.com)

What’s next

The FDA has promised enhanced post-market surveillance and real-world data collection to help identify safety signals quickly, but critics argue post-market monitoring has been uneven in the past.

The takeaway

This policy shift represents a significant change in the FDA's evidentiary standards, moving from a default of two trials to one, which could speed up drug approvals but also increase the risk of false positives and unintended harm, especially for drugs targeting common conditions where millions could be exposed. Maintaining public trust in the safety and efficacy of approved drugs will be crucial.