Confounding of indirect effects: a sensitivity analysis exploring the range of bias due to a cause common to both the mediator and the outcome.

Several investigators have demonstrated that the assessment of indirect and direct effects is biased in the presence of a cause that is common to both the mediator and the outcome if one has not controlled for this variable in the analysis. However, little work has been done to quantify the bias caused by this type of unmeasured confounding and determine whether this bias will materially affect conclusions regarding mediation. The author developed a sensitivity analysis program to address this crucial issue. Data from 2 well-known studies in the methodological literature on mediation were reanalyzed using this program. The results of mediation analyses were found not to be as vulnerable to the impact of confounding as previously described; however, these findings varied sharply between the 2 studies. Although the indirect effect observed in one study could potentially be due to a cause common to both the mediator and the outcome, such confounding could not feasibly explain the results of the other study. These disparate results demonstrate the utility of the current sensitivity analysis when assessing mediation.