Analyzing Direct Effects in Randomized Trials with Secondary Interventions

Michael Rosenblum, Division of Biostatistics, School of Public Health, University of California,Berkeley
Nicholas P. Jewell, Division of Biostatistics, School of Public Health, University of California, Berkeley
Mark J. van dr Laan, Division of Biostatistics, School of Public Health, University of California,Berkeley
Stephen Shiboski, Department of Epidemiology & Biostatistics, University of California, San Francisco
Ariane van der Straten, Women's Global Health Imperative, Department of Obstretics, Gynecology, and Reproductive Services, University of California, San Francisco
Nancy Padian, Women's Global Health Imperative, Department of Obstretics, Gynecology, and Reproductive Services, University of California, San Francisco

Abstract

The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the “gold standard” HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the ”direct effects” of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed.