Applying Trial-Derived Treatment Effects to Real-World Populations: Generalizing Cost-Effectiveness Estimates When Modeling Complex Hazards.

Objectives: Generalizability of trial-based cost-effectiveness estimates to real-world target populations is important for decision making. In the context of independent aggregate time-to-event baseline and relative effects data, complex hazards can make modeling of data for use in economic evaluation challenging. Our article provides an overview of methods that can be used to apply trial-derived relative treatment effects to external real-world baselines when faced with complex hazards and follows with a motivating example.

Methods: Approaches for applying trial-derived relative effects to real-world baselines are presented in the context of complex hazards. Appropriate methods are applied in a cost-effectiveness analysis using data from a previously published study assessing the real-world cost-effectiveness of a treatment for carcinoma of the head and neck as a motivating example.

Results: Lack of common hazards between the trial and target real-world population, a complex baseline hazard function, and nonproportional relative effects made the use of flexible models necessary to adequately estimate survival. Assuming common distributions between trial and real-world reference survival substantially affected survival and cost-effectiveness estimates. Modeling time-dependent vs proportional relative effects affected estimates to a lesser extent, dependent on assumptions used in cost-effectiveness modeling.

Conclusions: Appropriately capturing reference treatment survival when attempting to generalize trial-derived relative treatment effects to real-world target populations can have important impacts on cost-effectiveness estimates. A balance between model complexity and adequacy for decision making should be considered where multiple data sources with complex hazards are being evaluated.