Accelerated Approval addresses a fundamental tension in drug development: the imperative to thoroughly demonstrate clinical benefit through adequate and well-controlled trials versus the urgency of making promising treatments available to patients with serious conditions. Established in 1992 initially for HIV/AIDS therapies, this pathway permits approval based on evidence that falls short of demonstrating the ultimate clinical outcome but provides reasonable likelihood that the drug will provide meaningful benefit to patients.

The scientific foundation of Accelerated Approval rests on surrogate endpoints or intermediate clinical endpoints that are reasonably likely to predict clinical benefit. Surrogate endpoints are laboratory measurements or physical signs that substitute for clinically meaningful outcomes. Intermediate clinical endpoints are clinical outcomes that occur earlier than ultimate outcomes but are still clinically meaningful themselves. For example, tumor response rates may serve as a surrogate for survival, or HIV viral load reduction may predict prevention of AIDS progression. The relationship between the surrogate and clinical benefit must be supported by scientific evidence, though definitive validation is not required.

Accelerated Approval carries the obligation to conduct post-marketing studies confirming the predicted clinical benefit. These confirmatory trials must be underway at the time of approval and completed with due diligence. If confirmatory studies fail to verify clinical benefit, or if sponsors fail to conduct required studies with due diligence, FDA has authority to withdraw the approval through an expedited process. This conditional approval framework balances earlier patient access against the uncertainty inherent in approval based on surrogate endpoints, with the understanding that the ultimate clinical benefit must be demonstrated in the post-marketing setting.