EXCERPT:
A New England Journal of Medicine perspective argues that the longstanding expectation of two adequate and well-controlled trials for FDA approval is due for reconsideration, particularly for rare diseases and confirmatory evidence scenarios.
CONTENT:
A perspective published in the New England Journal of Medicine is challenging one of drug development’s most entrenched assumptions: that FDA approval requires two independent pivotal trials demonstrating efficacy.
The authors argue that for many indications — particularly rare diseases with limited patient populations — a single well-designed, adequately powered trial with strong effect size and biological plausibility should be sufficient. The two-trial standard, they contend, was built for an era of smaller effect sizes and weaker statistical tools.
This has practical implications for how sponsors design development programs and allocate resources. A credible single-trial path could shorten timelines and reduce costs, particularly for programs where enrollment is inherently constrained. It also shifts the conversation toward trial design quality and pre-specified endpoints rather than replication as the primary standard of evidence.
Whether FDA moves formally in this direction remains to be seen, but the conversation at the regulatory level is clearly evolving.