Simulation-based sequential design.

We review some simulation-based methods to implement optimal decisions in sequential design problems as they naturally arise in clinical trial design. As a motivating example we use a stylized version of a dose-ranging design in the ASTIN trial. The approach can be characterized as constrained backward induction. The nature of the constraint is a restriction of the decisions to a set of actions that are functions of the current history only implicitly through a low-dimensional summary statistic. In addition, the action set is restricted to time-invariant policies. Time-dependence is only introduced indirectly through the change of the chosen summary statistic over time. This restriction allows computationally efficient solutions to the sequential decision problem. A further simplification is achieved by restricting optimal actions to be described by decision boundaries on the space of such summary statistics.