Zmax test for delayed effect in immuno-oncology clinical trials. Issue 2 (3rd March 2020)

• Record Type: Journal Article
• Authors: Yang, Miao; Hua, Zhaowei; Xue, Lan; Hu, Mingxiu
• Is Part Of: Journal of biopharmaceutical statistics. Volume 30:Issue 2(2020)
• Page Start: 244
• Page End: 266
• Publication Date: 2020-03-03
• Subjects: Zmax test -- log-rank test -- weighted log-rank test -- Fleming-Harrington -- delayed effect -- immuno-oncology -- clinical trials; Pharmacy -- Statistical methods -- Periodicals; Drugs -- Testing -- Statistical methods -- Periodicals; Biometry -- Periodicals; Biopharmaceutics -- Periodicals; Pharmacokinetics -- Periodicals; 615.19
• DOI: 10.1080/10543406.2019.1632873
• Languages: English
• ISSNs: 1054-3406

Abstract

ABSTRACT: Delayed separation in survival curves has been observed in immuno-oncology clinical trials. Under this situation, the classic log-rank test may confront high power loss. In this paper, we consider a Zmax test, which is the maximum of the log-rank test and a Fleming–Harrington test. Simulation studies indicate that the Zmax test not only controls the Type I error rate but also maintains good power under different delayed effect models. The asymptotic properties of the Zmax test are also established, which further supports its robustness. We apply the Zmax test to two data sets reported in recent immuno-oncology clinical trials, in which Zmax has exhibited remarkable improvement over the conventional log-rank test.