OBJECTIVES: Many health technology assessment (HTA) agencies provide guidance on evidence standards for the use of surrogate outcomes. However, the level of detail varies, and there is limited guidance on considerations for economic models. With the increasing use of novel surrogate outcomes in clinical trials and consequently in economic models for HTA submissions, there is a need for further clarity around what to consider when utilizing these outcomes in economic models to inform decision-making.

METHODS: We conducted three scoping reviews; a review of regulatory standards for the validation of surrogate outcomes, a review of guidance from HTA agencies for the use and validation of surrogate outcomes and a review of statistical methods that have been proposed to validate surrogate outcomes. These reviews were supplemented with a qualitative study exploring how surrogate outcomes are dealt with in HTA evaluations by different HTA agencies and any lessons learned. The findings of these four strands of work were evaluated by the working group to inform the recommendations.

RESULTS: We developed recommendations outlining what should be considered alongside existing economic modelling guidance in HTA, when surrogate outcomes are used. This included considerations around their definition, justification, adoption, statistical validation, incorporation, reporting and approaches to quantify and present the uncertainty surrounding estimates based on their use.

CONCLUSIONS: The use of surrogate outcomes can pose a challenge for HTA agencies, because of the additional uncertainty in the relationship with longer term outcomes. Our recommendations can support economic modelers and decision makers especially for interventions in conditions where there are no long-term data available and when novel surrogate outcomes need to be used.