Searching for effect heterogeneity: The baseline target moderated mediator design

George Howe, Ph.D.
George Washington University

ABSTRACT:
We present and discuss a novel approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research.  We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets.  We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in the target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes.  We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials.  We use simulated data to illustrate a BTMM, and end with a discussion of some advantages and limitations of this approach.