ABSTRACT
In this chapter, we will discuss three methods for two-stage adaptive design
methods. The methods are differentiated in terms of the test statistics defined
at each stage, while the test statistic is evidence against the null hypothesis in
terms of cumulative information (data). The three methods are constructed
based on three different ways to combine the so-called stagewise p-values: (1)
the sum of p-values (MSP), (2) the product of p-values (MPP), and (3) the
inverse-normal p-values (MINP). The MINP is a generalization of the test
statistics used in the classical group sequential design. The operating charac-
teristics of MPP and MINP are very similar. The methods are very general,
meaning that they can be applied to broad adaptations and any number of
stages in the adaptive trials. However, we will focus on two-stage designs and
provide the closed forms for determination of stopping boundaries. We will
design different group sequential trials using these methods, while the appli-
cations of the methods to other types of adaptive designs will be discussed
later. Power and sample-size calculations for the adaptive designs are based
on computer simulations.
