  During the last twenty years there have been considerable methodological
developments in the design and analysis of Phase 1, Phase 2 and Phase 1/2
dose-finding studies. Many of these developments are related to the continual
reassessment method (CRM), first introduced by O'Quigley, Pepe and Fisher
(\citeyearQPF1990). CRM models have proven themselves to be of practical use
and, in this discussion, we investigate the basic approach, some connections to
other methods, some generalizations, as well as further applications of the
model. We obtain some new results which can provide guidance in practice.
