RegulatoryGlossary Term
An FDA pathway allowing approval of drugs for serious conditions based on a surrogate endpoint or intermediate clinical endpoint reasonably likely to predict clinical benefit, with post-marketing requirements to confirm the expected benefit.
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.
Oncology approval
"The checkpoint inhibitor received Accelerated Approval based on objective response rate, with the sponsor required to complete an ongoing randomized trial demonstrating improvement in overall survival as a condition of continued approval."
Post-marketing requirement
"Following Accelerated Approval based on viral load suppression, the confirmatory trial demonstrated that patients receiving the drug had significantly reduced rates of progression to AIDS, leading to full traditional approval."
A premarket submission to the FDA demonstrating that a medical device is substantially equivalent to a legally marketed predicate device and therefore does not require premarket approval.
A regulatory submission to the FDA requesting approval to market a biological product in the United States, demonstrating that the product meets standards for safety, purity, and potency.
An FDA program for drugs intended to treat serious conditions where preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoints.
An FDA program designed to expedite the development and review of drugs intended to treat serious conditions and fill an unmet medical need, providing increased communication with FDA and eligibility for Rolling Review.
An FDA approval that allows an investigational medical device to be used in a clinical study to collect safety and effectiveness data required to support a premarket approval application or 510(k) submission.
An FDA pathway allowing approval of drugs for serious conditions based on a surrogate endpoint or intermediate clinical endpoint reasonably likely to predict clinical benefit, with post-marketing requirements to confirm the expected benefit.
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.
Oncology approval
"The checkpoint inhibitor received Accelerated Approval based on objective response rate, with the sponsor required to complete an ongoing randomized trial demonstrating improvement in overall survival as a condition of continued approval."
Post-marketing requirement
"Following Accelerated Approval based on viral load suppression, the confirmatory trial demonstrated that patients receiving the drug had significantly reduced rates of progression to AIDS, leading to full traditional approval."
A premarket submission to the FDA demonstrating that a medical device is substantially equivalent to a legally marketed predicate device and therefore does not require premarket approval.
A regulatory submission to the FDA requesting approval to market a biological product in the United States, demonstrating that the product meets standards for safety, purity, and potency.
An FDA program for drugs intended to treat serious conditions where preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoints.
An FDA program designed to expedite the development and review of drugs intended to treat serious conditions and fill an unmet medical need, providing increased communication with FDA and eligibility for Rolling Review.
An FDA approval that allows an investigational medical device to be used in a clinical study to collect safety and effectiveness data required to support a premarket approval application or 510(k) submission.