Flexibly Monitoring Group Sequential Survival Trials When Testing is Based Upon a Weighted Log-Rank Statistic

Abstract

We consider the repeated group sequential testing of a survival endpoint with a time-varying treatment effect using a weighted log-rank statistic. The emphasis of this article is on the monitoring of this statistic where information growth is nonlinear. We propose using a constrained boundaries approach to maintain the planned operating characteristics of a group sequential design. A simulation study is presented to demonstrate the operating characteristics of the method together with a case study to illustrate the procedure. We show that when monitoring a weighted log-rank statistic, the entry and survival distribution needs to be estimated at interim analyses.

Keywords:

• Constrained boundaries
• Group sequential
• Information
• Monitoring
• Nonparametric
• Nonproportional hazards
• Survival
• Weighted log-rank

Subject Classifications:

• 62L05
• 62L10
• 62N03

ACKNOWLEDGMENTS

We thank the reviewer and editors for their time and helpful comments on this article. This research was supported in part by grant P30CA062203 from the National Cancer Institute (D.L.G.).

Notes

Bold values represent implemented decision boundaries that are constrained at future analyses.

Bolded values represent values where the model for the entry distribution is correctly specified

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