Statistics in Biopharmaceutical Research

Externally Controlled Trials: Tutorials, Reviews, and Practical Guidance

This Special Issue focuses on high-quality tutorials and review articles addressing the design, methodology, and implementation of externally controlled trials (ECTs), including single-arm trials and hybrid controlled trials. With rapid advancements in statistical, computational, and regulatory science, a wide range of innovative approaches for ECTs are emerging. However, a persistent gap remains between methodological development and practical implementation.

The Special Issue aims to bridge this gap by providing accessible, practice-oriented guidance that highlights methodological rigor, regulatory perspectives, and real-world applications. Contributions will support researchers, clinicians, and regulators in understanding state-of-the-art methods and their appropriate use.

Topics of Interest
Topics may include, but are not limited to:
• Target trial emulation for ECTs
• AI/ML methods and digital twins for external controls
• Bayesian/Frequentist methods and dynamic borrowing
• Causal inference frameworks
• Clinical trial design, conduct, and analysis
• Diagnostics, sensitivity analyses, and bias assessment
• Methodological and regulatory considerations for ECTs
• Case studies and implementation workflows (RWE, registries, etc.)
• User-friendly software