The use of simulation and bootstrap in information-based group sequential studies.

In this paper, we present an information-based design and monitoring procedure which applies to any type of model for any type of group sequential study provided there is a unique parameter of interest one can estimate efficiently. Simulation techniques are described to handle the design phase of this procedure. Since designs depend on potentially unreliable guesses of nuisance parameters, we propose a bootstrap method that uses the information available at the interim analysis times to generate projections and prediction intervals for the time at which the study will be fully powered. A monitoring board can use this information to decide whether a redesign of the trial is warranted. We also show how to use simulation to redesign studies in progress. We illustrate all of these techniques with data from AIDS Clinical Trial Group Protocol 021.