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Systematic adjudication of myocardial infarction end-points in an international clinical trial
Kenneth W Mahaffey1, Robert A Harrington, Martijn Akkerhuis
1Duke Clinical Research Institute, Durham, North Carolina, USA. mahaf002@mc.duke.edu
Insights
Clinical events committees (CECs) ensure unbiased assessment of myocardial infarction (MI) in cardiovascular trials. The PURSUIT trial demonstrated CECs provide standardized MI adjudication, crucial for accurate interpretation of treatment effects.
Area of Science:
- Cardiology
- Clinical Trials
- Medical Adjudication
Background:
- Clinical Events Committees (CECs) are integral to cardiovascular trials for endpoint adjudication.
- Limited published data exists on the diverse processes employed by CECs.
- This study examines the CEC process for myocardial infarction (MI) adjudication in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial.
Purpose of the Study:
- To review the effectiveness and outcomes of the CEC process for identifying and adjudicating suspected myocardial infarctions (MIs).
- To assess the impact of CEC-adjudicated MI rates on the interpretation of treatment effects in the PURSUIT trial.
Main Methods:
- Prospective central adjudication of suspected MIs in 10,948 patients from the PURSUIT trial.
- Systematic review of data collection forms, cardiac enzymes, and electrocardiograms to identify suspected MIs.
- Independent review by two physicians, with adjudication by a committee for disagreements.
Main Results:
- The CEC identified 5005 suspected MIs (46%), with 1415 (28%) confirmed as endpoint MIs.
- CEC-adjudicated MI rates were higher than those reported by site investigators.
- Discrepancies between site investigator reporting and CEC assessment occurred in 20% of cases, impacting treatment effect calculations.
Conclusions:
- CEC endpoint adjudication is vital for standardized, systematic, independent, and unbiased assessment in multicenter cardiovascular trials.
- Understanding the specific CEC process is essential for accurate interpretation of trial results and event rates.
- CEC review provides a more rigorous evaluation of myocardial infarction events compared to site investigator reporting alone.
Abstract:
BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.