Criteria for Surrogate end Points Based on Causal Distributions

Abstract

SummaryWhen a treatment has a positive average causal effect (ACE) on an intermediate variable or surrogate end point which in turn has a positive ACE on a true end point, the treatment may have a negative ACE on the true end point due to the presence of unobserved confounders, which is called the surrogate paradox. A criterion for surrogate end points based on ACEs has recently been proposed to avoid the surrogate paradox. For a continuous or ordinal discrete end point, the distributional causal effect (DCE) may be a more appropriate measure for a causal effect than the ACE. We discuss criteria for surrogate end points based on DCEs. We show that commonly used models, such as generalized linear models and Cox’s proportional hazard models, can make the sign of the DCE of the treatment on the true end point determinable by the sign of the DCE of the treatment on the surrogate even if the models include unobserved confounders. Furthermore, for a general distribution without any assumption of parametric models, we give a sufficient condition for a distributionally consistent surrogate and prove that it is almost necessary.