Trial DesignCentral versus local adjudication of myocardial infarction in a cardiac biomarker trial
Section snippets
Study setting and population
This was a retrospective secondary analysis of data from the MIDAS, an 18-center (all centers in the United States) prospective study with enrollment, from December 19, 2006, to September 20, 2007, of patients with suspected ACS presenting to the emergency department within 8 hours after symptom onset and in whom serial cTn and objective cardiac perfusion testing was planned.6 All centers had institutional review board approval to conduct the MIDAS study, which was funded by Alere/Biosite and
Results
Overall, there were 1,107 cases (see Table I for study population); full demographics have been previously published.6 Excluding 11 deemed indeterminate by central adjudication, 1,096 cases were successfully adjudicated (see Table II). Local adjudication resulted in 104 AMI (9.5% of total) and 992 non-AMI; central adjudication resulted in 134 AMI (12.2%) and 962 non-AMI. In spite of excellent interrater reliability across central versus local methods, with a κ statistic = 0.79 (P < .001, 95% CI
Discussion
Acute myocardial infarction diagnosis may differ depending on the criteria for diagnosis,8, 9 but it may also differ based on central versus local adjudication. Adjudication is the mechanism in which the outcome measure is determined, and accuracy, or at least reproducibility, is essential when determining diagnostic characteristics of specific tests. Local adjudicators may be used to evaluate diagnostic tests, but there has been a recent push by the FDA to use a more central process. In this
Conclusion
We found that central and local diagnosis adjudication have a significant rate of diagnostic discordance independent of differences in criteria used to diagnosis myocardial infarction, due to possible human error and due to legitimately difficult cases. It is impossible to say with certainty which method is more accurate, but it is clearly important that one standard method be used to evaluate new biomarkers. Ideally, new methods would be outcome and risk based and not founded on such arbitrary
Disclosures
Presented at the Society for Academic Emergency Medicine, Chicago, May 2012.
Financial support: Alere/Biosite.
Potential conflict of interest: First author was paid as a central adjudicator.
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