FDA Drops Two-Study Requirement for New Drug Approvals

The Food and Drug Administration plans to drop its longtime standard of requiring two rigorous studies to win approval for new drugs, the latest change from Trump administration officials vowing to speed up the availability of certain medical products. Going forward, the FDA's "default position" will be to require one study for new drugs and other novel health products, FDA Commissioner Dr. Marty Makary and a top deputy, Dr. Vinay Prasad, wrote in a New England Journal of Medicine piece published Wednesday.

The announcement is the latest example of Makary and his team changing longstanding FDA standards and procedures with the stated goal of slashing bureaucracy and accelerating the availability of new medicines. Since arriving at the agency last April, Makary has launched a series of directives that he says will shorten FDA reviews, including mandating the use of artificial intelligence by staffers and offering one-month drug assessments for new medications that serve "national interests."

In their piece published Wednesday, Makary and Prasad state that dropping the two-trial requirement reflects modern advances that have made drug research "increasingly precise and scientific." "Going forward, the FDA's default position is that 1 adequate and well-controlled study, combined with confirmatory evidence, will serve as the basis of marketing authorization of novel products," the FDA officials wrote in their commentary.

"The FDA's historical reliance on 2 clinical trials rather than 1 was intended to provide credible causal evidence that a therapy could improve clinical outcomes with acceptable safety in a world where biologic understanding was more limited than it is today," the FDA officials wrote. "Two trials should be seen as just 1 of many interlocking facets of clinical credibility, and in 2026 there are powerful alternative ways to feel assured that our products help people live longer or better than requiring manufacturers to test them yet again."

The FDA officials predicted the shift would lead to "a surge in drug development."

The two-study standard for drugs dates to the early 1960s, when Congress passed a law requiring the FDA to review data from "adequate and well-controlled investigations," before clearing new medications. For decades, the agency interpreted that requirement as meaning at least two studies, preferably with a large number of patients and significant follow-up time. The reason for requiring the second study was to confirm that the first trial's results weren't a fluke and could be reproduced.

But beginning in the 1990s, the FDA increasingly began accepting single studies for the approval of treatments for rare or fatal diseases that companies often struggle to test in large numbers of patients. Over the last five years, roughly 60% of first-of-a-kind drugs approved each year have been cleared based on a single study. The shift reflects laws passed by Congress that directed regulators to be more flexible when reviewing drugs for serious or hard-to-treat conditions.

Since 1997, the FDA has had explicit statutory authority to approve drugs on the basis of a single adequate and well-controlled study combined with confirmatory evidence. Such evidence can include mechanistic data, results in related indications, animal models, class effects, real-world evidence or, in some cases, a second trial.

The former FDA drug director said the change makes sense and reflects the FDA's decades-long move toward relying on one trial, combined with supporting evidence, for various life-threatening diseases, including cancer. "The scientific point is well taken that as we move toward greater understanding of biology and disease we don't need to do two trials all the time," said Dr. Janet Woodcock, who led the FDA's drug center for about 20 years before retiring in 2024.

Makary and Prasad noted that these guidelines had been flexible in the past—specifically in oncology, where 1 study was often enough for a drug approval—but were confusing to drug manufacturers seeking to understand when only 1 trial would be acceptable. Moving forward, the default of using only 1 trial to grant a drug approval should clear up questions surrounding the necessary number of trials.

Woodcock said the new policy announced Wednesday will mainly impact drugs for common diseases that previously weren't eligible for reduced testing standards. "It's not the cancers and the rare diseases that will be affected by this," she noted. "The agency has been approving those on a single trial already."

Rather than focusing on the number of trials, reviewers are expected to concentrate on trial quality, including magnitude of effect, appropriateness of control arms, endpoint selection, statistical power, blinding, handling of missing data, biological plausibility and alignment with intermediate biomarkers.

Makary and Prasad reject criticism that the new policy weakens standards. Both officials argue that two poorly designed trials do not guarantee valid conclusions, and that concentrating review resources on a single rigorous, well-designed study may actually strengthen regulatory scrutiny. "Without examination of the quality of a study, two trials may even provide a false assurance," they wrote.

The latest approach from FDA leadership contrasts with the agency's recent actions on vaccines, gene therapies and other treatments. Last week, the FDA's vaccine division, headed by Prasad, refused to accept Moderna's application for a new mRNA flu shot, saying its clinical trial was insufficient. Then on Wednesday the agency reversed course, saying it would review the vaccine after Moderna agreed to conduct an additional study in older people.

Separately, Prasad has rejected a string of experimental gene therapies and biotech drugs, citing the need for additional studies or more definitive evidence. The trend has weighed on the stocks of many biotech companies and clashed with Makary's public statements promoting the speed and flexibility of the FDA's reviews.

Woodcock said the drug industry will have to wait and see whether the FDA's approach to promising experimental therapies changes. "Implementation will be everything," she said. "Since the agency's approach is unclear, and the industry is already baffled, I don't think this adds any illumination."