Statistical methods that leverage external trial information to help accelerate drug development are becoming increasingly popular. Bayesian methods facilitate dynamic borrowing, where the similarity of the response guides how much information is used. We have proposed a semiparametric Bayesian borrowing model for time-to-event data, with smoothing priors that allows the baseline hazard to take any form via an ensemble average \citep{Scott2024}. By accurately modelling the baseline hazard, rather than approximating its form via fixed piecewise intervals, power is improved and bias of the estimated treatment effect reduced when the borrowing assumption of parameter exchangeability holds. A ``lump-and-smear'' borrowing prior makes the model robust to non-exchangeable historical data by increasing the sensitivity of borrowing to the presence of prior-data conflict, reducing the potential for type I error inflation. We present BayesFBHborrow, an R package that implements our semiparametric Bayesian borrowing model with a historical control. We demonstrate how to select the optimal borrowing hyperparameters. The model supports covariate-adjusted borrowing, which can reduce prior-data conflict and improve power when differences in outcomes are attributable to changes in the covariate distribution. As the treatment effect estimator is non-collapsible, the marginal hazard ratio can be estimated via Bayesian G-computation, while still permitting an adjusted analysis to account for control group drift. We illustrate the Bayesian flexible baseline hazard model on a simulated and real dataset with a marginal estimand, for both an unadjusted and adjusted analyses.

翻译：暂无翻译