Practical risk management in early phase clinical trials.

Area of Science:

• Clinical Trials
• Pharmacovigilance
• Regulatory Science

Background:

• Stopping rules are crucial for risk management in early phase clinical trials, ensuring participant safety.
• Regulatory requirements, such as the European Medicine Agency's guidelines, mandate robust risk management strategies.
• Increasing trial complexity necessitates standardized approaches to risk management, particularly for adverse reactions.

Purpose of the Study:

• To present template stopping rules for adverse reactions (ARs) in early phase clinical trials.
• To provide a standardized, adaptable framework that meets regulatory requirements.
• To address the challenges posed by complex trial designs like integrated trials.

Main Methods:

• Developed template AR rules using a systematic, objective, and consistent process.
• Incorporated severity (objective grading), seriousness, frequency, and reversibility of ARs.
• Created a single-page table for ease of use, guiding decisions on participant management, dosing, and dose escalation.

Main Results:

• Successfully applied template AR rules to numerous early phase adaptive integrated trials in the UK.
• Received regulatory authorization for trials utilizing these rules.
• Presented the template rule table and case studies of trial-specific adaptations.

Conclusions:

• A systematic, objective, and consistent approach to risk management in large integrated trials can be simple yet robust.
• Facilitates effective decision-making and trial progression.
• Effectively safeguards participant safety while managing adverse reactions.