‘A one-trial requirement will be the FDA’s new default standard,’ agency leaders said.
The Food and Drug Administration (FDA) will approve many new drugs based on one trial moving forward, agency leaders have said.
The FDA has typically required two studies from companies seeking approval for most new drugs, although in recent years it has approved some drugs based on a single well-run trial.
“The FDA has demonstrated disease-by-disease flexibility and has granted approvals based on a single premarket study with confirmatory evidence. In some fields, such as oncology, single trials have supported the majority of drug approvals,” Dr. Marty Makary, the FDA’s commissioner, and Dr. Vinay Prasad, head of the FDA’s Center for Biologics Evaluation and Research, said in an article published on Feb. 18 by the New England Journal of Medicine.
“However, although we have exercised flexibility in the past, there remains confusion from manufacturers regarding settings in which a single trial will be accepted. Moving forward, we are announcing that a one-trial requirement will be the FDA’s new default standard. This reform is being rolled out synchronously with the agency’s postmarket initiative to collect robust data on all drugs and devices.”
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 second study would, in theory, confirm that the first trial’s results weren’t a fluke and could be reproduced.
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 past five years, roughly 60 percent of first-of-a-kind drugs approved each year have been cleared based on a single study.
Makary and Prasad said that the historical reliance on multiple studies “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.”
They later added: “In the modern world, as drug discovery becomes increasingly precise and scientific, the FDA considers not just effects on survival, but biochemical and intermediate changes that tell a complete biologic story: does this drug actually work? In this setting, overreliance on two trials no longer makes sense.”
The change will save drug developers money and reduce the time it takes to get drugs to market, the officials said. They expect more drug development in response.
