Since I’m not familiar with the data for your example and the subject area I don’t want to comment specifically on it, but let me try a more general answer to your question. The natural indirect effect is interpreted as the effect the treatment has on the outcome through its effect on the mediator variable. So in the situation where the outcome is the risk of an event occurring, a negative NIE and positive NDE indicates (assuming all the necessary assumptions are satisfied) that the treatment’s effect on the mediator leads to a decreased risk of the outcome occurring, but the effect of treatment on the outcome through any remaining pathways (not through the mediator) increases the risk of the outcome occurring. One way this might occur is if the treatment has a positive effect on the outcome (directly), the mediator also has a positive effect on the outcome, but the treatment has a negative effect on the mediator leading to a negative NIE. Also, in some situations, it might be the case that both the NIE and NDE are significant, but the overall total effect is not. A formal definition of these effects in a counterfactual framework is provided in the “Conterfactual Framework for Defining Causal Mediation Effects” section of the PROC CAUSALMED documentation.
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