Information borrowing in Bayesian clinical trials: choice of tuning parameters for the robust mixture prior

Abstract: Borrowing historical data for use in clinical trials has increased in recent years. This is accomplished in the Bayesian framework by specification of informative prior distributions. One such approach is the robust mixture prior arising as a weighted mixture of an informative prior and a robust prior inducing dynamic borrowing that allows to borrow most when the current and external data are observed to be similar. The robust mixture prior requires the choice of three additional quantities: the mixture weight, and the mean and dispersion of the robust component. Some general guidance is available, but a case-by-case study of the impact of these quantities on specific operating characteristics seems lacking. We focus on evaluating the impact of parameter choices for the robust component of the mixture prior in one-arm and hybrid-control trials. The results show that all three quantities can strongly impact the operating characteristics. In particular, as already known, variance of the robust component is linked to robustness. Less known, however, is that its location can have a strong impact on Type I error rate and MSE which can even become unbounded. Further, the impact of the weight choice is strongly linked with the robust component's location and variance. Recommendations are provided for the choice of the robust component parameters, prior weight, alternative functional form for this component as well as considerations to keep in mind when evaluating operating characteristics.