Makary says FDA will "end two-trial dogma" for approvals

The FDA plans to adopt a new policy that will do away with the default requirement to base regulatory filings for new medicines on two pivotal trials, according to Commissioner Marty Makary.

Rather, the intention is to move to a position where a single robust trial, backed up by confirmatory evidence, will be the new standard, according to an editorial written by Makary and Vinay Prasad, director of the FDA's Center for Biologics Evaluation and Research (CBER), and published in the New England Journal of Medicine.

The move is the latest in a series of initiatives designed to speed up the approval of new medicines and reduce red tape for drug developers, which some observers fear could undermine standards designed to make sure new therapeutics are safe and effective.

Others include the Commissioner's National Priority Voucher (CNPV) programme, which can reduce regulatory reviews to a few weeks from the usual standard of around 10 months, facilitated by the adoption of AI in agency decision-making to streamline tasks.

Critics of the CNPV have expressed concerns that the selection process is opaque, the scheme lacks statutory backing, and that recipients may be selected for political rather than clinical reasons.

At the moment, a single pivotal trial is already an option for some applications, for example, for cancer drugs or where it would be impractical to run two, so the agency has flexibility in this area. As a result, some experts have questioned the need for an initiative that could lead to a blanket reduction in standards for demonstrating safety and efficacy.

In 2020, more than half of approved drugs were supported by a single pivotal trial, according to a JAMA analysis published in 2022, but Makary and Prasad argue that there remains confusion among sponsors about the circumstances in which a single trial is sufficient.

Makary has previously told STAT – which revealed the plan in an article published towards the end of last year – that you can achieve the same statistical power with one trial as you would with two trials when it's designed and controlled appropriately.

In the JAMA editorial, Makary and Prasad say the change could actually enhance standards, as greater attention will be placed on the one trial. The new requirement will be rolled out synchronously with the agency's post-market initiative to collect robust data on all drugs, according to the two officials

The payoff will be a big increase in drug development and lower prices for new medicines, they promise, along with substantially reduced costs for drug developers.

Image by pudnbutch0 from Pixabay