Delays of event adjudication in the TRITON trial

Area of Science:

• Cardiovascular Research
• Clinical Trial Methodology
• Pharmacology

Background:

• Central adjudication of clinical events in randomized controlled trials (RCTs) is debated due to increased costs, despite good data matching.
• Investigator-reported event rates are often comparable to adjudicated data, raising questions about the necessity of central review.

Purpose of the Study:

• To evaluate the timeliness of clinical event adjudication within the TRITON trial.
• To identify specific event types with delayed adjudications and assess their implications.

Main Methods:

• Review of the Food and Drug Administration (FDA) action package for prasugrel.
• Analysis of adjudication timing for various clinical events, including deaths, strokes, bleeding, myocardial infarction, and stent thrombosis.

Main Results:

• Adjudications for deaths and strokes were evenly distributed throughout the TRITON study.
• Bleeding event adjudications occurred mainly in the later study phases.
• Significant delays were observed in the adjudication of myocardial infarction and, notably, stent thrombosis events.

Conclusions:

• Deaths and strokes were the only events adjudicated without delays in the TRITON trial.
• While late adjudications for myocardial infarction and stent thrombosis may be explained by evolving definitions, delays in revascularization and bleeding event reporting lack clear justification.
• Regulatory authorities should consider independent audits for significant discrepancies between central adjudication and site-reported events impacting trial outcomes.