  We propose a two-stage design for a clinical trial with an early stopping
rule for safety. We use different criteria to assess early stopping and
efficacy. The early stopping rule is based on a criteria that can be determined
more quickly than that of efficacy. These separate criteria are also nested in
the sense that efficacy is a special case of, but not identical to, the early
stopping criteria. The design readily allows for planning in terms of
statistical significance, power, and expected sample size necessary to assess
an early stopping rule. This method is illustrated with a Phase II design
comparing patients treated for lung cancer with a novel drug combination to
those treated using historical control. In this example, the early stopping
rule is based on the numbers of patients who exhibit progression-free survival
(PFS) at 2 months post treatment follow-up and efficacy is judged by the number
of patients who have PFS at 6 months.
