[International collaborative trial: from the viewpoints of statistics and data management]

Area of Science:

• Clinical pharmacology
• Biostatistics
• Regulatory science

Context:

• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E5 guideline (1998) enabled use of foreign clinical trial data for Japanese drug approval.
• Bridging studies, designed to assess foreign data applicability in Japan, have been extensively discussed with limited focus on statistical methodologies.
• There is a growing preference for international collaborative studies over traditional bridging studies to expedite drug development.

Purpose:

• To review statistical methodologies for evaluating the similarity between bridging and bridged studies.
• To introduce novel statistical approaches, including the overlap coefficient and propensity-score matching, for assessing data distribution overlap and identifying comparable patient subpopulations from global databases.
• To propose a sample size determination method for Japanese clinical trials that minimizes the probability of detecting apparent heterogeneity.

Summary:

• The presentation critically examines statistical methods for assessing the similarity between bridging and bridged studies, incorporating new proposals such as the overlap coefficient for distribution comparison and propensity-score matching for patient subpopulation selection from global datasets.
• It highlights the increasing trend towards international collaborative studies as a more efficient alternative to bridging, citing the sentiment 'Best bridging is no bridging'.
• A statistical approach for determining Japanese sample sizes is presented to maintain a low probability (10-20%) of observing paradoxical treatment effects.

Impact:

• Provides advanced statistical tools for regulatory submissions relying on foreign clinical trial data.
• Offers strategies to accelerate global drug development through efficient study design and data utilization.
• Discusses critical success factors for international collaborative trials, including researcher incentives and robust data management, paving the way for more efficient pharmaceutical innovation.