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FDA drug approval surrogate endpoints oncology drugs overall survival correlation clinical trials analysis drug approval guidelines

FDA validation of surrogate endpoints in oncology: 2005–2022


Summary

ere are summary bullets based on the provided text:

  • The FDA has increasingly approved oncologic drugs based on surrogate endpoints, which often lack a demonstrated correlation with clinically meaningful outcomes like overall survival.
  • A review of FDA analyses from 2005 to 2022 examined the validity of surrogate outcomes in relation to overall survival and other clinical benefits.
  • Out of 15 FDA surrogate analyses, only one showed a strong correlation between surrogate outcomes and overall survival.
  • Most analyses (87%) were based on clinical trials submitted to the FDA and were published from 2014 onwards.
  • The lack of strong correlations between surrogate outcomes and overall survival raises concerns about the reliability of these endpoints in clinical trials.
  • There is a need for further research to validate surrogate outcomes thoroughly before they are used in drug approval decisions, as unvalidated surrogates could lead to harmful patient outcomes.

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.

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FDA drug approval, surrogate endpoints, oncology drugs, overall survival correlation, clinical trials analysis, drug approval guidelines