The Food and Drug Administration is moving to loosen the evidence it expects for new drugs, with Commissioner Dr. Marty Makary and Dr. Vinay Prasad saying the agency will shift its “default position” to requiring one study rather than two for some new drug and novel health product approvals. In a Wednesday essay in the New England Journal of Medicine, the two FDA leaders described the change as part of an effort to speed access to medical products, arguing that modern drug research has become more precise.
In their argument for the change, Makary and Prasad wrote that “overreliance on two trials no longer makes sense” and pointed to “powerful alternative ways to feel assured that our products help people live longer or better than requiring manufacturers to test them yet again.” They also predicted that the policy shift would lead to “a surge in drug development,” framing the adjustment as aligned with evolving scientific methods rather than a retreat from evidence.
The FDA’s new approach contrasts with the agency’s stricter stance in other product categories described in the reporting. The FDA vaccine division, headed by Prasad, had refused to accept Moderna’s application for a new mRNA flu shot, saying its clinical trial was insufficient; the FDA later reversed course, agreeing to review the vaccine after Moderna agreed to conduct an additional study in older people. Separately, Prasad has rejected several experimental gene therapies and biotech drugs, according to the reporting, citing the need for additional studies or more definitive evidence.
Makary and Prasad’s announcement adds to a broader set of directives attributed to Makary since he took the role in April, including steps aimed at shortening FDA reviews, using artificial intelligence in staff work, and offering one-month assessments for some new medications described as serving “national interests.” The reporting also notes that those changes sit alongside FDA’s more restrictive approach to vaccines and other therapies.
A key part of the essay’s justification rests on how regulators have interpreted the underlying law requiring “adequate and well-controlled investigations.” The two-study standard for drug approvals has been traced to the early 1960s, when Congress adopted that requirement, and the reporting describes the agency’s long interpretation as meaning at least two studies—often with a large patient count and extended follow-up—to help confirm that trial results are not a fluke.
But the reporting also describes a shift that began in the 1990s, when the FDA increasingly accepted single studies for treatments for rare or fatal diseases where companies may struggle to test in larger populations. Over time, lawmakers directed regulators to be more flexible for serious or hard-to-treat conditions, and the reporting says that about 60% of first-of-a-kind drugs approved each year over the last five years were cleared based on a single study.
Dr. Woodcock, a former FDA drug director who retired in 2024 after leading the agency’s drug center for about 20 years, said the policy described Wednesday fits a longstanding scientific argument. She said 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,” and the reporting says her comments supported the general rationale for relying on one trial plus supporting evidence in some contexts, including cancer.
Woodcock also said the new policy announced Wednesday would mainly change how the FDA handles drugs for common diseases that previously were not eligible for reduced testing standards, adding that it would not primarily affect cancers and rare diseases because those categories were already being approved on a single trial approach. She also cautioned that the impact would depend on how the agency implements the policy across different cases, saying, “Implementation will be everything,” and that the drug industry would need clarity since the approach was unclear and companies were already “baffled.”