Sensitivity Analyses Comparing Outcomes Only Existing in a Subset Selected Post‐Randomization, Conditional on Covariates, with Application to HIV Vaccine Trials

Abstract

In many experiments, researchers would like to compare between treatments and outcome that only exists in a subset of participants selected after randomization. For example, in preventive HIV vaccine efficacy trials it is of interest to determine whether randomization to vaccine causes lower HIV viral load, a quantity that only exists in participants who acquire HIV. To make a causal comparison and account for potential selection bias we propose a sensitivity analysis following the principal stratification framework set forth by Frangakis and Rubin (2002, Biometrics58, 21-29). Our goal is to assess the average causal effect of treatment assignment on viral load at a given baseline covariate level in the always infected principal stratum (those who would have been infected whether they had been assigned to vaccine or placebo). We assume stable unit treatment values (SUTVA), randomization, and that subjects randomized to the vaccine arm who became infected would also have become infected if randomized to the placebo arm (monotonicity). It is not known which of those subjects infected in the placebo arm are in the always infected principal stratum, but this can be modeled conditional on covariates, the observed viral load, and a specified sensitivity parameter. Under parametric regression models for viral load, we obtain maximum likelihood estimates of the average causal effect conditional on covariates and the sensitivity parameter. We apply our methods to the world's first phase III HIV vaccine trial.