Two paradigms for the evaluation of surrogate markers in randomized clinical trials have been proposed: the causal effects paradigm and the causal association paradigm. Each of these paradigms rely on… Click to show full abstract
Two paradigms for the evaluation of surrogate markers in randomized clinical trials have been proposed: the causal effects paradigm and the causal association paradigm. Each of these paradigms rely on assumptions that must be made to proceed with estimation and to validate a candidate surrogate marker (S) for the true outcome of interest (T). We consider the setting in which S and T are Gaussian and are generated from structural models that include an unobserved confounder. Under the assumed structural models, we relate the quantities used to evaluate surrogacy within both the causal effects and causal association frameworks. We review some of the common assumptions made to aid in estimating these quantities and show that assumptions made within one framework can imply strong assumptions within the alternative framework. We demonstrate that there is a similarity, but not exact correspondence between the quantities used to evaluate surrogacy within each framework, and show that the conditions for identifiability of the surrogacy parameters are different from the conditions, which lead to a correspondence of these quantities.
               
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