Do we need to adjudicate major clinical events?

Area of Science:

• Clinical Trials Methodology
• Evidence-Based Medicine
• Regulatory Science

Background:

• Centralized systems for clinical event adjudication are frequently used in large clinical trials.
• There is limited published literature justifying the rationale and necessity of central adjudication.
• The process aims to ensure systematic application of event definitions and protect against bias.

Purpose of the Study:

• To review the reasons for employing central adjudication in clinical trials.
• To discuss potential simplifications by limiting or streamlining the adjudication process.
• To evaluate the necessity and impact of central adjudication on trial validity and efficiency.

Main Methods:

• Literature review on central adjudication in clinical trials.
• Analysis of adjudication experiences in multiple clinical studies.
• Examination of regulatory perspectives (e.g., FDA) on central adjudication.

Main Results:

• Central adjudication helps ensure systematic application of definitions for subjective nonfatal events.
• Blinded adjudication in open-label trials can prevent differential misclassification.
• Regulatory bodies and the clinical community often expect central adjudication, influencing trial perception.

Conclusions:

• The demonstrable value of adjudication in improving treatment effect determination is difficult to quantify.
• Central adjudication may be overused and excessively complex in large simple trials.
• The optimal role, methodology, and application of central adjudication require further investigation and evidence.