Adapting Health Technology Assessment agency standards for surrogate outcomes in early stage cancer trials: what needs to happen?

Introduction: An avalanche of early stage cancer clinical trials is coming. The majority of these solely use surrogate outcomes that have not been validated against a target outcome of interest (e.g. overall survival). Current HTA guidance on surrogate outcome validation are not methodologically or practically conducive to this scenario.

Areas Covered: We provide a high-level overview of methods, approaches, and conceptual thinking for making better use of limited evidence within early stage cancer HTA submissions. We outline regulatory and HTA issues and emphasize how evidence transitions from one to another, what major gaps currently exist, and how these may be bridged. We summarize current methodologies and practices, their pros and cons. We outline how complementary measurements strengthen evaluations and address fallacies and biases of conventional statistical methods for surrogate outcomes validation. The value of real-world data to support some of the necessary validity components is discussed. Lastly, we address the importance of the patient voice for better understanding which surrogate outcomes may appropriately inform HTA.

Expert Opinion: Conventional surrogate outcome validation represents a fraught and sub-optimal framework for HTA purposes, particularly for early stage cancer. Tools for optimizing use of limited evidence exist. Education of stakeholders is highly needed.