In a move that updates one of the fundamental frameworks of US clinical trial regulation, the FDA has announced that a single pivotal clinical trial will now be the default requirement for the approval of novel medicines. The new standard is a shift away from the agency’s decades-old reliance on two adequate and well-controlled studies and marks a significant policy change under the leadership of Dr Marty Makary, Commissioner, FDA.
Detailed in a landmark article co-authored by Dr Makary and Prof Vinay Prasad, Director, Center for Biologics Evaluation and Research (CBER), the authors argue that the traditional two-trial requirement has become a legacy regulatory bottleneck that no longer aligns with modern R&D practices.
Slashing costs to lower prices
A primary driver for the policy shift is the escalating cost of drug development. By moving to a single-trial mandate, the FDA aims to remove the financial pressures that many sponsors cite when justifying high launch prices.
“Lowering capital costs for drug developers may remove a persistent argument in justification of lofty and rising drug prices for everyday Americans – the onerous cost of [R&D],” Dr Makary and Prof Prasadsaid in the article.
Historically, the FDA required two trials because drug development was a “black box”, i.e. if a drug worked twice in separate, identical tests, it proved the result was not just a statistical fluke. Today, the agency argues that advances in precision medicine and scientific discovery, including genomic sequencing and molecular modelling, allow researchers to understand drug–body interactions at a molecular level, providing biological evidence that can replace a second trial.
Internal friction and market impact
The transition has prompted shifts in the agency’s internal structure, notably the exit of FDA veteran Richard Pazdur, who reportedly objects to the proposal. Despite this friction, analysts foresee potential benefits for mid-stage biotech programmes in areas such as obesity and chronic disease, which are being researched widely. However, the agency maintains that the move focuses evidentiary standards rather than relaxing them.
“Going forward… one adequate and well-controlled study, combined with confirmatory evidence, will serve as the basis of marketing authorisation of novel products,” the authors state, noting that the reform will be rolled out synchronously with the agency’s post-market initiative to collect robust data on all drugs.
Ultimately, this pivot represents a gamble on the predictive power of modern science over traditional methods, betting that intensive scrutiny of a single study can accelerate innovation while lowering costs for patients.
