The 33-page guidance, which finalizes a draft version released for comment in September 2018 and replaces an earlier guidance from 2010, sets out FDA’s recommendations on adaptive trial design principles and the information FDA will review from adaptive studies submitted as part of investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs) and supplemental applications.
While the final guidance is largely the same as the draft version, FDA says it has revised the guidance to clarify its recommendations for Bayesian adaptive designs and its expectations for the extent of pre-specification required for governing adaptations to studies in addition to minor editorial changes.
The final guidance also refers to sponsors to review FDA’s September 2019 draft guidance on complex innovative trial designs for more information on trial design proposals that use Bayesian inference.
Additionally, while FDA recommends that sponsors prespecify rules governing trial adaptations, the agency acknowledges that “monitoring committee recommendations might occasionally deviate from the anticipated algorithm based on the totality of the data.” The agency also says that if sponsors desire flexibility adjusting these deviations to their prespecified plan, they “should acknowledge the possibility of deviations from the anticipated algorithm, outline factors that may lead to such deviations, and propose testing and estimation methods that do not rely on strict adherence to the algorithm.”
In the Federal Register notice announcing the final guidance, FDA says it expects to see approximately 240 documented plans for clinical trials with an adaptive design and analysis plan from 40 sponsors annually.
FDA also says it expects to receive about 20 marketing applications for drugs and biologics from 15 sponsors that rely on data from an adaptive study each year.