FDA Will Require Only 1 Study to Approve New Drugs, Speeding Up Process

FDA Commissioner Martin Makary, MD, MPH, and his top deputy Vinay Prasad, MD, MPH, announced in a commentary published in The New England Journal of Medicine that the FDA will revamp its method of approving drugs for use in the US.¹ The commentary announced that the agency’s historic reliance on 2 clinical trials will end, with only 1 pivotal trial needed for a drug to be approved for use nationwide.

“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 had previously worked under guidelines stating that “adequate and well-controlled investigations” were needed before a drug could be approved for widespread use, which were interpreted as generally requiring 2 clinical investigations.² These guidelines had been in place since 1998, with only supplementary guidance published in 2019 and 2023. The newly announced shift marks the first substantial change in the methods of FDA approvals since the FDA obtained the authority to grant marketing authorizations.¹

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.

“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.”

This move is another step in Makary’s attempts to shorten FDA reviews, which started when he began his tenure last year.³ These include mandating the use of artificial intelligence for staffers and offering new medications a 1-month drug assessment if the FDA believes that the drug serves a national interest.

About 60% of first-of-a-kind drugs have been approved based on a single study in the past 5 years due to legislative initiatives that encouraged flexibility in reviewing drugs for conditions that were hard to treat. The drugs more likely to be affected by this new standard are for common diseases rather than those for rare diseases or cancers, which were already more often receiving approval based on a single trial.

This announcement comes a day after the FDA announced that it will now review Moderna’s seasonal mRNA flu vaccine application, which it had previously refused to look at due to perceived safety and efficacy concerns.⁴ The increased scrutiny of vaccines presents a contrast to the newly streamlined default standard for FDA approvals.

References

1. Prasad V, Makary MA. One pivotal trial, the new default option for FDA approval—ending the two-trial dogma. N Engl J Med. 2026;394(8):815-817. doi:10.1056/NEJMsb2517623
2. Demonstrating substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence. FDA. Updated November 30, 2023. Accessed February 19, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-one-adequate-and-well-controlled-clinical
3. Perrone M. FDA will drop two-study requirement for new drug approvals, aiming to speed access. AP News. Updated February 18, 2026. Accessed February 19, 2026. https://apnews.com/article/fda-drug-approval-studies-makary-prasad-a5aaa5501ae15f264bbd20d0dffa4dc4
4. Steinzor P. FDA reverses course, will review Moderna’s mRNA flu vaccine. AJMC^®. February 18, 2026. Accessed February 19, 2026. https://www.ajmc.com/view/fda-reverses-course-will-review-moderna-s-mrna-flu-vaccine