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Systematic adjudication of myocardial infarction end-points in an international clinical trial.

Mahaffey KW, Harrington RA, Akkerhuis M, Kleiman NS, Berdan LG, Crenshaw BS, Tardiff BE, Granger CB, DeJong I, Bhapkar M, Widimsky P, Corbalon R, Lee KL, Deckers JW, Simoons ML, Topol EJ, Califf RM, For the PURSUIT Investigato - Curr Control Trials Cardiovasc Med (2001)

Bottom Line: If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA. mahaf002@mc.duke.edu

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.

No MeSH data available.


Related in: MedlinePlus

Process for review of suspected clinical events in the PURSUIT trial. ECG, Electrocardiography.
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Figure 1: Process for review of suspected clinical events in the PURSUIT trial. ECG, Electrocardiography.

Mentions: A schematic diagram of the clinical event adjudication process is shown in Figure 1. Computer algorithms systematically identified key variables from the database that could indicate the occurrence of a post-enrolment (end-point) MI. These variables, which were determined from clinical expertise and trial experience, included elevated cardiac enzymes, ECG core laboratory identification of suspected MI, recurrent ischemic events, urgent revascularisations, or site investigator assessment of a post-enrolment MI. The system was designed for broad identification of all patients with possible MI after enrolment. A report of all patients with suspected end-point MI was generated according to 'hits' on the variables already listed.


Systematic adjudication of myocardial infarction end-points in an international clinical trial.

Mahaffey KW, Harrington RA, Akkerhuis M, Kleiman NS, Berdan LG, Crenshaw BS, Tardiff BE, Granger CB, DeJong I, Bhapkar M, Widimsky P, Corbalon R, Lee KL, Deckers JW, Simoons ML, Topol EJ, Califf RM, For the PURSUIT Investigato - Curr Control Trials Cardiovasc Med (2001)

Process for review of suspected clinical events in the PURSUIT trial. ECG, Electrocardiography.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC57749&req=5

Figure 1: Process for review of suspected clinical events in the PURSUIT trial. ECG, Electrocardiography.
Mentions: A schematic diagram of the clinical event adjudication process is shown in Figure 1. Computer algorithms systematically identified key variables from the database that could indicate the occurrence of a post-enrolment (end-point) MI. These variables, which were determined from clinical expertise and trial experience, included elevated cardiac enzymes, ECG core laboratory identification of suspected MI, recurrent ischemic events, urgent revascularisations, or site investigator assessment of a post-enrolment MI. The system was designed for broad identification of all patients with possible MI after enrolment. A report of all patients with suspected end-point MI was generated according to 'hits' on the variables already listed.

Bottom Line: If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA. mahaf002@mc.duke.edu

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.

No MeSH data available.


Related in: MedlinePlus