title: Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints.
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 perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer.
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors: Lindsay A
authors: LA
authors: Renfro
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic.
authors: Qian
authors: Q
authors: Shi
authors: Department of Statistics, University of Virginia.
authors: Yuan
authors: Y
authors: Xue
authors: Department of Biostatistics, Harvard School of Public Health.
authors: Junlong
authors: J
authors: Li
authors: HP Labs.
authors: Hongwei
authors: H
authors: Shang
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic.
authors: Daniel J
authors: DJ
authors: Sargent
keywords: clinical trials; meta-analysis; surrogate endpoints; survival analysis