Monitoring liver safety in drug development: the GSK experience

Area of Science:

• Pharmacovigilance
• Clinical Drug Development
• Hepatotoxicity Monitoring

Background:

• Liver safety is critical in drug development due to potential hepatotoxicity.
• Existing systems may lack tailored criteria for different clinical trial phases.
• Improving patient safety and data integrity in global trials is paramount.

Purpose of the Study:

• To establish an evidence-based liver safety system for global Phase I-III clinical trials.
• To enhance clinical trial subject safety and improve data quality.
• To develop and implement distinct algorithms for liver injury stopping criteria.

Main Methods:

• Development of two distinct algorithms for liver stopping criteria.
• Application of stringent criteria for Phase I studies (healthy volunteers, no anticipated benefit).
• Slightly higher thresholds for Phase II-III studies to assess potential liver adaptation.

Main Results:

• Implementation of a structured liver safety system across trial phases.
• Tailored monitoring and stopping rules based on study objectives and participant populations.
• Enhanced ability to promptly identify and evaluate liver safety events.

Conclusions:

• The developed liver safety system effectively balances subject protection with the progression of drug development.
• Differentiated stopping criteria optimize risk management for liver injury in early and later phase trials.
• This system contributes to robust pharmacovigilance and reliable clinical trial data.