Randomized clinical trials (RCTs) not only are the gold standard for evaluating the efficacy and effectiveness of psychiatric treatments but also can be valuable in revealing moderators and mediators of therapeutic change. Conceptually, moderators identify on whom and under what circumstances treatments have different effects. Mediators identify why and how treatments have effects. We describe an analytic framework to identify and distinguish between moderators and mediators in RCTs when outcomes are measured dimensionally. Rapid progress in identifying the most effective treatments and understanding on whom treatments work and do not work and why treatments work or do not work depends on efforts to identify moderators and mediators of treatment outcome. We recommend that RCTs routinely include and report such analyses.
Definitions of terms used in the linear model, with treatment coded +½ for those in the treatment group(T) and −½ for those in the control or comparison group (C), with the moderator or mediator (M) centered at the mean of M in T (MT), the mean of M in C (MC), and the midpoint of these two(M0).
A special case in which there is no main effect of treatment, no main effect of moderator or mediator (M), and no overall effect of treatment, but in which treatment may change not only the level but also the action of M on the outcome, a mediating effect. T indicates treatment group; C, control or comparison group; MC, the mean of M in C; MT, the mean of M in T; and M0, the midpoint of these two.
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