Association between preapproval confirmatory trial initiation and conversion to traditional approval or withdrawal in the FDA accelerated approval pathway

The accelerated approval pathway allows the US Food and Drug Administration (FDA) to approve drugs that demonstrate an effect on a surrogate end point that is reasonably likely to predict clinical benefit. Following accelerated approval, manufacturers are required to verify clinical benefit in confirmatory trials. Delays in confirmatory trial completion have led to proposals for reforming the accelerated approval pathway.1 One proposal would require a confirmatory trial initiation prior to accelerated approval.2 An FDA analysis found an association between preapproval initiation and faster (from the date of accelerated approval) completion of confirmatory trials for oncology indications that ultimately received traditional approval or were withdrawn.3 We extended the FDA analysis by also including nononcology indications and evaluating whether preapproval initiation was associated with timelier conversion to traditional approval or withdrawal.