  Adaptive designs for clinical trials permit alterations to a study in
response to accumulating data in order to make trials more flexible, ethical
and efficient. These benefits are achieved while preserving the integrity and
validity of the trial, through the pre-specification and proper adjustment for
the possible alterations during the course of the trial. Despite much research
in the statistical literature highlighting the potential advantages of adaptive
designs over traditional fixed designs, the uptake of such methods in clinical
research has been slow. One major reason for this is that different adaptations
to trial designs, as well as their advantages and limitations, remain
unfamiliar to large parts of the clinical community. The aim of this paper is
to clarify where adaptive designs can be used to address specific questions of
scientific interest; we introduce the main features of adaptive designs and
commonly used terminology, highlighting their utility and pitfalls, and
illustrate their use through case studies of adaptive trials ranging from
early-phase dose escalation to confirmatory Phase III studies.
