Endpoint adjudication in cardiovascular clinical trials

Area of Science:

• Cardiovascular Medicine
• Clinical Trials Methodology
• Biostatistics

Background:

• Endpoint adjudication (EA) by clinical endpoint committees (CECs) is common in cardiovascular randomized controlled trials (RCTs).
• EA aims to reduce misclassification, bias, and statistical noise by verifying investigator-identified endpoints against pre-specified definitions.
• However, EA significantly increases trial costs, time, and resources, prompting questions about its universal necessity.

Purpose of the Study:

• To compare summary estimates from adjudicated versus non-adjudicated endpoints in major cardiovascular RCTs.
• To develop a framework for determining when EA is warranted versus redundant in clinical trials.
• To identify trial characteristics that influence the value of EA.

Main Methods:

• Comparative analysis of summary estimates from adjudicated and non-adjudicated endpoints in published cardiovascular RCTs.
• Development of a risk-based framework to guide decisions on the necessity of EA.
• Identification of specific trial features (e.g., endpoint nuance, data quality, blinding) influencing EA utility.

Main Results:

• EA's value is higher for nuanced endpoints (e.g., myocardial infarction, bleeding, heart failure exacerbation) and in trials with poor data completeness or lack of blinding.
• EA may be redundant for simpler endpoints like all-cause death or hospitalization.
• A risk-based approach, involving partial adjudication, can optimize the balance between cost and accuracy.

Conclusions:

• Endpoint adjudication is not universally required in cardiovascular RCTs; its necessity depends on endpoint complexity and trial characteristics.
• A tailored, risk-based approach to EA can improve resource allocation without compromising trial integrity.
• Consideration of endpoint nuance, data quality, and blinding is crucial when deciding on the extent of endpoint adjudication.