Concordance index: Surrogacy of progression-free survival for overall survival

Abstract

In oncology clinical trials, the primary endpoint is often time to an event of clinical interest, e.g., time to disease progression or time to death. As a result, progression-free survival (PFS: the time from initiation of treatment till disease progression or death whichever occurs first) and overall survival (OS: the time from initiation of treatment till death) are the focus of statistical analysis in comparison of two treatment arms. It is often argued that PFS may serve as a surrogate endpoint for OS, while the validity of such surrogacy is still under debates in different types of cancer. In practice, one may observe a significant difference in PFS but no significant difference in OS; or vice versa. We provide a concordance index (C-index) to measure the degree of concordance between PFS and OS, and elaborate on the PFS vs OS discrepancies using the C-index using simulation studies and real trial analysis.