Approximately two-thirds of cancer drugs receive US Food and Drug Administration FDA marketing authorization based upon improvement in a surrogate endpoint, such as tumor shrinkage or progression-free survival. While surrogates may allow for earlier entry of drugs into the market, they are not always correlated with clinically meaningful outcomes like overall survival OS. Some drugs approved on the basis of surrogate endpoints alone have subsequently failed to demonstrate improvements in OS. These approvals add cost and toxicity for the patient without concomitant benefit.

Surrogate validation studies investigate the associations between surrogate markers and OS across multiple randomized controlled trials. Simply put, they allow regulators to differentiate which surrogates to have confidence in and which are unreliable for regulatory action. In recent years, the US FDA has embraced surrogates that historically have not been used for approval, raising questions as to the process by which they examine and validate surrogates. In some cases, the agency may support the choice of these surrogate approvals by leveraging surrogate validation studies they have conducted, using internal or external data. As such, we sought to examine surrogate validation studies conducted by the US FDA published between 2005 and 2022.