A reflection on the causal interpretation of individual-level surrogacy

Area of Science:

• Biostatistics
• Clinical Epidemiology
• Medical Meta-Analysis

Background:

• Meta-analysis is key for evaluating surrogate endpoints.
• Existing paradigms assess surrogacy at trial and individual levels.
• Individual-level surrogacy lacks causal interpretation, limiting its utility.

Purpose of the Study:

• To propose an alternative definition of individual-level surrogacy.
• To establish a causal framework for individual-level surrogacy.
• To reconcile causal inference and meta-analytic schools of thought.

Main Methods:

• Introduced a new definition of individual-level surrogacy based on individual causal treatment effects.
• Utilized the maximum entropy principle to link definitions.
• Established a direct connection between meta-analytic and proposed individual-level surrogacy.

Main Results:

• The proposed definition provides a causal interpretation for individual-level surrogacy.
• A direct link was established between existing and new individual-level surrogacy definitions.
• The new perspective aligns individual-level surrogacy with trial-level surrogacy.

Conclusions:

• The revised individual-level surrogacy offers a more coherent framework.
• This work bridges the gap between causal inference and meta-analytic approaches.
• Enhances the evaluation of surrogate endpoints in clinical research and meta-analysis.