Skip to main content
Targeted Maximum Likelihood Estimation for Dynamic Treatment Regimes in Sequential Randomized Controlled Trials
The International Journal of Biostatistics (2012)
  • Paul Chaffee
  • Mark J. van der Laan

Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, and thereby achieves important bias reduction in estimation of that parameter. As with the so-called Augmented Inverse Probability of Censoring Weight (A-IPCW) estimator, TMLE is double-robust and locally efficient. We report simulation results corresponding to two data-generating distributions from a longitudinal data structure.

  • sequential randomized controlled trials; targeted maximum likelihood estimation; semi-parametric estimation; efficient estimation; dynamic treatment regimes; longitudinal methods
Publication Date
June 22, 2012
Citation Information
Paul Chaffee and Mark J. van der Laan. 2011. "Targeted Maximum Likelihood Estimation for Dynamic Treatment Regimes in Sequential Randomized Controlled Trials" U.C. Berkeley Division of Biostatistics Working Paper Series Available at: