The FDA is shifting to a default standard of one adequate and well-controlled pivotal trial, supported by confirmatory evidence, instead of two for new drug approvals, as announced by Commissioner Marty Makary and CBER Director Vinay Prasad in a New England Journal of Medicine paper.34
This change ends the 'two-trial dogma' from the 1960s, leveraging modern technology, statistical methods, and biologic inferences to ensure credibility without duplication.46
The single trial must emphasize strong controls, endpoints, effect size, and statistical protocols; two trials may still be required for nebulous mechanisms or surrogate outcomes.36
The policy aims to reduce sponsor costs (estimated $30m-$150m per trial), speed drugs to market, and lower drug prices, applying to traditional, breakthrough, accelerated, and priority reviews.34
US law has allowed single trials since 1997 with confirmatory evidence, but prior FDA practice created confusion; recent approvals often used one trial already.34
Critics argue it may undermine safety commitments, though proponents say it improves focus on high-quality design and addresses past approvals with safety issues despite two trials.36
Sources:
3. https://www.clinicaltrialsarena.com/news/fda-to-allow-one-pivotal-trial-instead-of-two-for-drug-approval/
4. https://www.biopharmadive.com/news/fda-makary-prasad0one-pivotal-trial-nejm/812557/
6. https://www.biospace.com/fda/its-official-fda-will-now-default-to-one-clinical-trial-for-drug-applications