Testing mediators of intervention effects in randomized controlled trials: An evaluation of three depression prevention programs.

Cognitive behavioral (CB) depression prevention programs, which focus on reducing negative cognitions and increasing pleasant activities, have reduced depressive symptoms and risk for future onset of major depression relative to assessment-only control conditions in randomized trials (Stice, Shaw, Bohon, Marti, & Rohde, 2009). Yet, few trials have investigated mediators that account for these effects, which provides a test of the theoretical mechanisms that putatively underlie program effects and can implicate components that are most effective, potentially aiding in program refinement (Kazdin & Nock, 2003). Although procedures for examining mediators that account for intervention effects have been proposed, they do not provided a rigorous test of all of the components necessary for mediation, particularly the temporal sequencing between changes in the mediator and the outcome. It has been noted it is vital to document that change in the mediator temporally precedes change in the outcome (Kazdin & Nock, 2003; Weersing & Weisz, 2002). Because a specific procedure for testing this temporal sequencing of change has not been offered, we proposed a 5-step procedure for testing mediation with data from randomized trials (Stice, Presnell, Gau, & Shaw, 2007) and suggested that the strongest case for mediation would be made when five conditions are satisfied: (1) intervention participants show greater decreases on the outcome than controls, (2) intervention participants show greater decreases on the mediator than controls, (3) change in the mediator predicts change in the outcome in the intervention condition,1 (4) the predictive effect of the intervention on change in the outcome is significantly reduced (for partial mediation) or eliminated (for full mediation) controlling for change in the mediator, and (5) meaningful change in the mediator occurs before meaningful change in the outcome more frequently than would be expected by chance in the intervention condition. We think this 5-step procedure provides a rigorous approach for testing mediation in randomized trials, yet this heuristic model may require refinement (e.g., the fifth criterion offers but one method for testing whether the mediator changes before the outcome) and these criteria involve assumptions that should be verified. Although trials have evaluated mediators that account for the effects of depression prevention programs, the most rigorous ones have only examined criteria 1 though 4 (Jaycox, Reivich, Gillham, & Seligman, 1994; Yu & Seligman, 2002), with mixed results. The purpose of the present report was to evaluate the 5-step method for testing the hypothesized mediators of depression prevention programs. In this indicated depression prevention program at-risk youth with elevated depressive symptoms were randomized to a CB group, a supportive expressive group, CB bibliotherapy, or an assessment-only control condition. We hypothesized that reductions in negative cognitions and increases in pleasant activities would mediate the effects of the group and bibliotherapy CB programs and that increases in emotional expression and reductions in loneliness would mediate the effects of the supportive expressive program on reductions in depressive symptoms. We tested for mediation during intervention delivery because this is typically when the most pronounced intervention effects occur and change is often linear during this period (Stice et al., 2009), making it easier to model change. As suggested by Kazdin and Nock (2003), we assessed changes in the mediator and outcome during the 6-week intervention delivery; at baseline, mid-way through, and after termination. Although we considered using weekly surveys, participants complained about the assessment burden in our prior trial that took this approach (Stice et al., 2007). A trial evaluating multiple programs also affords an opportunity to examine the specificity of intervention effects. Kazdin and Nock (2003) argued that it is important to test whether interventions affect mediators specific to that intervention, but not mediators specific to other interventions. Thus, we also tested whether each prevention program affects the theoretically specific mediators, but not mediators specific to the other programs.