A group sequential approach to evaluation of bridging studies

Area of Science:

• Clinical Pharmacology
• Biostatistics
• Drug Development

Background:

• International Conference on Harmonization (ICH) E5 guideline defines bridging studies for extrapolating foreign clinical data.
• Bridging studies are typically conducted post-marketing approval in the original region.
• Analyzing bridging study data is challenging due to missing concurrent efficacy and safety data from the original region.

Purpose of the Study:

• To propose a group sequential approach for analyzing clinical data from bridging studies.
• To address the internal validity issues in extrapolating foreign clinical data to new regions.
• To present methods for sample size determination in new region bridging studies.

Main Methods:

• A group sequential design is proposed, using the region as a sequential group.
• Patients are enrolled sequentially: first from the original region, then from the new region.
• Methods for sample size calculation specific to bridging studies in the new region are developed.

Main Results:

• The proposed group sequential approach allows for the incorporation of data from the original region.
• This method enhances the ability to evaluate the similarity of foreign clinical data for extrapolation.
• Sample size determination methods are provided for bridging studies.

Conclusions:

• The group sequential approach offers a robust statistical framework for bridging study data analysis.
• This methodology facilitates more reliable extrapolation of foreign clinical data, supporting global drug registration.
• The proposed methods contribute to efficient and valid drug development across different regions.