Assessing Direct and Spillover Effects of Intervention Packages in Network-Randomized Studies.

Intervention packages may result in a greater public health impact than single interventions. Understanding the separate impact of each component in the overall package effectiveness can improve intervention delivery. We adapted an approach to evaluate the effects of a time-varying intervention package in a network-randomized study. In some network-randomized studies, only a subset of participants in exposed networks receive the intervention themselves. The spillover effect contrasts average potential outcomes if a person was not exposed themselves under intervention in the network versus no intervention in a control network. We estimated effects of components of the intervention package in HIV Prevention Trials Network 037, a Phase III network-randomized HIV prevention trial among people who inject drugs and their risk networks using Marginal Structural Models to adjust for time-varying confounding. The index participant in an intervention network received a peer education intervention initially at baseline, then boosters at 6 and 12 months. All participants were followed to ascertain HIV risk behaviors. There were 560 participants with at least one follow-up visit, 48% of whom were randomized to the intervention, and 1,598 participant-visits were observed. The spillover effect of the boosters in the presence of initial peer education training was a 39% rate reduction (Rate Ratio = 0.61; 95% confidence interval= 0.43, 0.87). These methods will be useful to evaluate intervention packages in studies with network features.