Bayesian statistics plays a pivotal role in advancing medical science by enabling healthcare companies, regulators, and stakeholders to assess the safety and efficacy of new treatments, interventions, and medical procedures. The Bayesian framework offers a unique advantage over the classical framework, especially when incorporating prior information into a new trial with quality external data, such as historical data or another source of co-data. In recent years, there has been a significant increase in regulatory submissions using Bayesian statistics due to its flexibility and ability to provide valuable insights for decision-making, addressing the modern complexity of clinical trials where frequentist trials are inadequate. For regulatory submissions, companies often need to consider the frequentist operating characteristics of the Bayesian analysis strategy, regardless of the design complexity. In particular, the focus is on the frequentist type I error rate and power for all realistic alternatives. This tutorial review aims to provide a comprehensive overview of the use of Bayesian statistics in sample size determination, control of type I error rate, multiplicity adjustments, external data borrowing, etc., in the regulatory environment of clinical trials. Fundamental concepts of Bayesian sample size determination and illustrative examples are provided to serve as a valuable resource for researchers, clinicians, and statisticians seeking to develop more complex and innovative designs.

Borrowing information from historical or external data to inform inference in a current trial is an expanding field in the era of precision medicine, where trials are often performed in small patient cohorts for practical or ethical reasons. Even though methods proposed for borrowing from external data are mainly based on Bayesian approaches that incorporate external information into the prior for the current analysis, frequentist operating characteristics of the analysis strategy are often of interest. In particular, type I error rate and power at a prespecified point alternative are the focus. We propose a procedure to investigate and report the frequentist operating characteristics in this context. The approach evaluates type I error rate of the test with borrowing from external data and calibrates the test without borrowing to this type I error rate. On this basis, a fair comparison of power between the test with and without borrowing is achieved. We show that no power gains are possible in one-sided one-arm and two-arm hybrid control trials with normal endpoint, a finding proven in general before. We prove that in one-arm fixed-borrowing situations, unconditional power (i.e., when external data is random) is reduced. The Empirical Bayes power prior approach that dynamically borrows information according to the similarity of current and external data avoids the exorbitant type I error inflation occurring with fixed borrowing. In the hybrid control two-arm trial we observe power reductions as compared to the test calibrated to borrowing that increase when considering unconditional power.