Group sequential multi-arm multi-stage survival trial design with treatment selection

ABSTRACT

Multi-arm trials are increasingly of interest because for many diseases; there are multiple experimental treatments available for testing efficacy. Several novel multi-arm multi-stage (MAMS) clinical trial designs have been proposed. However, a major hurdle to adopting the group sequential MAMS routinely is the computational effort of obtaining stopping boundaries. For example, the method of Jaki and Magirr for time-to-event endpoint, implemented in R package MAMS, requires complicated computational efforts to obtain stopping boundaries. In this study, we develop a group sequential MAMS survival trial design based on the sequential conditional probability ratio test. The proposed method is an improvement of the Jaki and Magirr’s method in the following three directions. First, the proposed method provides explicit solutions for both futility and efficacy boundaries to an arbitrary number of stages and arms. Thus, it avoids complicated computational efforts for the trial design. Second, the proposed method provides an accurate number of events for the fixed sample and group sequential designs. Third, the proposed method uses a new procedure for interim analysis which preserves the study power.

KEYWORDS:

• Multi-arm multi-stage
• group sequential design
• log-rank test
• sequential conditional probability ratio test
• time-to-event

Acknowledgements

We thank an associate editor and two anonymous reviewers for their careful reading of our manuscript and their many insightful comments and suggestions. Dr. Wu’s research was supported by the University of New Mexico Comprehensive Cancer Center Support Grant National Cancer Institute (NCI) P30CA118100. Dr. Li’s research was supported by the Comprehensive Cancer Center at St. Jude Children’s Research Hospital and American Lebanese Syrian Associated Charities (ALSAC).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/10543406.2023.2235409.

Supporting information

Additional supplemental materials and R codes can be found online in the Supporting Information.

Additional information

Funding

The work was supported by the National Cancer In [P30CA118100].