Abstract
When long-term follow up is required for a primary endpoint in a randomized clinical trial, a valid surrogate marker can help to estimate the treatment effect and accelerate the decision process. Several model-based methods have been developed to evaluate the proportion of the treatment effect that is explained by the treatment effect on the surrogate marker. More recently, a nonparametric approach has been proposed allowing for more flexibility by avoiding the restrictive parametric model assumptions required in the model-based methods. While the model-based approaches suffer from potential mis-specification of the models, the nonparametric method fails to give desirable estimates when the sample size is small, or when the range of the data does not follow certain conditions. In this paper, we propose a Bayesian model averaging approach to estimate the proportion of treatment effect explained by the surrogate marker. Our procedure offers a compromise between the model-based approach and the nonparametric approach by introducing model flexibility via averaging over several candidate models and maintains the strength of parametric models with respect to inference. We compare our approach with previous model-based methods and the nonparametric method. Simulation studies demonstrate the advantage of our method when surrogate supports are inconsistent and sample sizes are small. We illustrate our method using data from the Diabetes Prevention Program study to examine hemoglobin A1c as a surrogate marker for fasting glucose.