This article is devoted to the construction and asymptotic study of adaptive group sequential covariate-adjusted randomized clinical trials analyzed through the prism of the semiparametric methodology of targeted maximum likelihood estimation (TMLE). We show how to build, as the data accrue group-sequentially, a sampling design which targets a user-supplied optimal design. We also show how to carry out a sound TMLE statistical inference based on such an adaptive sampling scheme (therefore extending some results known in the i.i.d setting only so far), and how group-sequential testing applies on top of it. The procedure is robust (i.e., consistent even if the working model is misspecified). A simulation study confirms the theoretical results, and validates the conjecture that the procedure may also be efficient.
Biostatistics | Design of Experiments and Sample Surveys | Statistical Methodology | Statistical Theory
Chambaz, Antoine and van der Laan, Mark J., "Estimation and Testing in Targeted Group Sequential Covariate-adjusted Randomized Clinical Trials" (April 2011). U.C. Berkeley Division of Biostatistics Working Paper Series. Working Paper 278.