The U.S. Food and Drug Administration (FDA) has officially changed its policy to require only one well-controlled and adequately-run clinical trial as the default standard for new drug approvals. This shift, formalized in 2026, marks a departure from the agency’s longstanding expectation of two pivotal studies.
FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research Director Vinay Prasad outlined the rationale behind the change in an article published in The New England Journal of Medicine. They described the previous two-trial requirement as “dogma” that had a “powerful theoretical basis to reduce false-positive conclusions.” However, they argued that it “no longer makes sense,” particularly as advances in drug development allow regulators to assess survival outcomes alongside biomarkers and other secondary measures to build a comprehensive understanding of a drug’s effects.
“Two trials should be seen as just one of many interlocking facets of clinical credibility,” Makary and Prasad wrote. “In 2026, there are powerful alternative ways to feel assured that our products help people live longer or better.”
Under the new policy, companies submitting drugs for approval must still provide certain types of confirmative evidence beyond a single trial. This can include data demonstrating how products work on a biological or mechanistic level, information from related indications or animal models, or results from other drugs in the same class. Real-world evidence will also be considered supportive by the FDA.
Analysts at RBC Capital Markets noted that this approach could benefit both companies and patients by improving the likelihood that drugs reach approval and potentially reducing late-stage development costs. However, they emphasized that exceptions remain: “The FDA will still retain discretion to require additional studies when warranted.” Such cases may involve drugs with unclear mechanisms or trials using short-term surrogate endpoints.
RBC concluded, “Overall, positive vibes, but likely more evolution than revolution.”
Some experts have voiced concerns about lowering requirements for drug approval. Steven Grossman, president of HPS Group, stated: “The agency’s new ‘one pivotal trial policy’ appears to undermine its commitment to patients,” adding that second studies can reveal important differences not apparent after initial trials. He said: “Second studies can be important. I know because I have worked on drugs and biologics that had a great first study and didn’t fare as well on the second. Shifting to one-trial is also inconsistent with recent FDA rejections citing a need for additional evidence and Dr. Prasad’s ongoing rhetoric about how many unsafe drugs are on the market.”
Richard Pazdur, former head of the Oncology Center of Excellence at FDA who was later appointed director of the Center for Drug Evaluation and Research in November 2025, expressed his reservations about endorsing this policy change publicly. According to Pazdur in an interview with The Wall Street Journal, he was asked shortly after his appointment to approve a press release regarding the single-trial standard—a position he was undecided about—and ultimately chose to retire in December 2025 rather than endorse it.
