Survival Analysis of Cancer Patients with Multiple Endpoints Using Global Score Test Methodology

摘要

Progression-free survival (PFS), time-to-progression (TTP) and overall survival (OS) are examples of multiple endpoints commonly used in clinical trials of cancer patients. PFS is increasingly used as a primary endpoint in evaluation of patients with solid tumors, while multiple endpoints are often analysed independently. These endpoints are indeed correlated and it is desirable to evaluate effectiveness of treatments by means of a single parameter. In this paper, a single overall treatment effect is provided by combining the univariate score statistics for comparing treatments with respect to each survival endpoint. This global score test methodology was applied in analysis of 330 patients with an aggressive cancer, each with two endpoints recorded, T1 and T2, relating to disease progression and death respectively. The values of score statistics obtained from the proposed method matched closely those from the logrank test. Meanwhile, the correlations between the two score test statistics were found to be similar to those computed using the established Wei, Lin and Weissfeld method. Simulations further confirmed the consistent performance of this new method in analysis of bivariate survival data.