Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

• Activity Number: 72
• Type: Contributed
• Date/Time: Sunday, August 3, 2014 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Lindsay Renfro and Yuan Xue and Daniel Sargent and Qian Shi
• Companies: Mayo Clinic and University of Virginia and Mayo Clinic and Mayo Clinic
• Keywords: clinical trials ; meta-analysis ; surrogate endpoints ; survival analysis

Abstract

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We derive some analytical results and perform a simulation study to identify such conditions, and we demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer.