title: Analyzing sequentially randomized trials based on causal effect models for realistic individualized treatment rules.
abstract: In this paper, we argue that causal effect models for realistic individualized treatment rules represent an attractive tool for analyzing sequentially randomized trials. Unlike a number of methods proposed previously, this approach does not rely on the assumption that intermediate outcomes are discrete or that models for the distributions of these intermediate outcomes given the observed past are correctly specified. In addition, it generalizes the methodology for performing pairwise comparisons between individualized treatment rules by allowing the user to posit a marginal structural model for all candidate treatment rules simultaneously. This is particularly useful if the number of such rules is large, in which case an approach based on individual pairwise comparisons would be likely to suffer from too much sampling variability to provide an informative answer. In addition, such causal effect models represent an interesting alternative to methods previously proposed for selecting an optimal individualized treatment rule in that they immediately give the user a sense of how the optimal outcome is estimated to change in the neighborhood of the identified optimum. We discuss an inverse-probability-of-treatment-weighted (IPTW) estimator for these causal effect models, which is straightforward to implement using standard statistical software, and develop an approach for constructing valid asymptotic confidence intervals based on the influence curve of this estimator. The methodology is illustrated in two simulation studies that are intended to mimic an HIV/AIDS trial.
authors.affiliation: Division of Biostatistics, University of California at Berkeley, CA, USA. bembom@berkeley.edu
authors.forename: Oliver
authors.initials: O
authors.lastname: Bembom
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van der Laan
mesh_terms: D015984:Causality; D003198:Computer Simulation; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D015233:Models, Statistical; D010597:Pharmacogenetics / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods*