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The estimation of controlled direct effects can be carried out by fitting a marginal structural model and using inverse probability of treatment weighting. To use marginal structural models to estimate natural direct and indirect effects, 2 marginal structural models can be used: 1 for the effects of the treatment and mediator on the outcome and 1 for the effect of the treatment on the mediator. Unlike marginal structural models typically used in epidemiologic research, the marginal structural models used to estimate natural direct and indirect effects are made conditional on the covariates.