Statistical issues for design and analysis of single-arm multi-stage phase II cancer clinical trials.

BACKGROUND: Phase II trials have been very widely conducted and published every year for cancer clinical research. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. Because of their small sample sizes, statistical methods based on large sample approximation are not appropriate for design and analysis of phase II trials.METHODS: As a prospective clinical research, the analysis method of a phase II trial is predetermined at the design stage and it is analyzed during and at the end of the trial as planned by the design. The analysis method of a trial should be matched with the design method. For two-stage single arm phase II trials, Simon's method has been the standards for choosing an optimal design, but the resulting data have been analyzed and published ignoring the two-stage design aspect with small sample sizes.CONCLUSIONS: In this article, we review analysis methods that exactly get along with the exact two-stage design method. We also discuss some statistical methods to improve the existing design and analysis methods for single-arm two-stage phase II trials.