Mediation analysis in the presence of spillover in pragmatic cluster randomized trials

Music City Center 

Public health interventions may spill over to others in the network of those directly receiving the intervention. In the past, this phenomena has been termed 'contamination' or 'interference' and often considered undesirable. When it occurs, standard analysis methods need further refinement, but from a public health perspective, the phenomena is highly desirable. We present methods for the estimation of spillover effects in cluster randomized trials in the presence of non-adherence. In addition, we present methods for the evaluation of mediation of overall intervention effects and of individual and spillover effects, that are appropriate for cluster randomized trials. Finally, we present methods for evaluation of the total effect of interventions, including within-treated-cluster spillover as well as spillover between treated and untreated clusters, as may occur in practice. Methods are illustrated in the Botswana Community Prevention Program, a cluster-randomized trial of a HIV prevention package conducted in 16 villages between 2013-2020, focusing on the evaluation of the spillover and mediation effects of voluntary medical male circumcision, one of the package's components.

Donna Spiegelman, Melody Owen, Laura Forastiere, Fan Li
Center on Methods for Implementation and Prevention Science
Department of Biostatistics
Yale School of Public Health