Group sequential design for historical control trials using error spending functions

ABSTRACT

Group sequential designs using Lan-DeMets error spending functions are proposed for historical control trials with time-to-event endpoints. Both O’Brien–Fleming and Gamma family types of sequential decision boundaries are derived based on sequential log-rank tests, which follow a Brownian motion in a transformed information time. Simulation results show that the proposed group sequential designs using historical controls preserve the overall type I error and power.

KEYWORDS:

• Error spending function
• group sequential design
• historical control
• information time
• decision boundaries

Acknowledgments

We thank the referees for their constructive comments that have lead to significant improvements in the article. The first author’s research was supported by the Biostatistics and Bioinformatics Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558) and the second author’s research was supported by the National Cancer Institute (NCI) support grant P30CA021765 and ALSAC.

Additional information

Funding

This work was supported by the National Cancer Institute [P30CA021765, P30CA177558].