Abstract An instrumental variable can be used to test the causal null hypothesis that an exposure has no causal effect on the outcome, by assessing the association between the instrumental variable and the outcome. Under additional assumptions, an instrumental variable can be used to estimate...

In assessing the mechanism of treatment efficacy in randomized clinical trials, investigators often perform mediation analyses by analyzing if the significant intent-to-treat treatment effect on outcome occurs through or around a third intermediate or mediating variable: indirect and direct...