WITHDRAWN Building a Hybrid External Control Arm Using a Fusion of Bayesian Borrowing and Causal Inference

Music City Center 

Hybrid external control arms (HECAs) are an innovative study design that augment a randomized control arm with data from a historical control arm. HECAs have the potential to reduce patient burden, trial costs, and improve early decision-making while maintaining the scientific rigor of randomized control arms. This presentation will explore the construction and analysis of HECAs. One possible approach for analyzing HECAs will be explored in depth, which leverages Bayesian borrowing and causal inference to address challenges in patient exchangeability and outcome heterogeneity. In particular, techniques such as inverse probability of treatment weighting (IPTW) and robust mixture priors are used to ensure doubly robust estimation. A case study will demonstrate the application of these methods using data from a phase II trial, validating the HECA approach against frequentist benchmarks. This innovative methodology holds significant promise for advancing precision and efficiency in clinical trial design and analysis.

hybrid external control arms (HECAs)

Bayesian borrowing

Causal inference

inverse probability of treatment weighting (IPTWs)

robust mixture priors

clinical trial design 

Biopharmaceutical Section