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Keywords:

  • thorough QT/QTc study;
  • electrocardiography;
  • reader variability;
  • quality assurance;
  • phase I studies;
  • drug-induced QT prolongation

Background: ECGs from thorough QT studies must be read in a central laboratory by trained experts. Standards of expertise are not presently defined. We, therefore, studied the use of Z-scores to define reader competence.

Methods: Two hundred ECGs were read by 24 experts and the mean and standard deviation (SD) of QT measurements calculated for each ECG. Z-scores ([QTreader– mean QTexperts]/ SDexperts) for each ECG and mean of absolute Z-scores of all ECGs read by a reader were calculated. The highest mean absolute Z-score of experts was considered the cutoff to define competence. Hundred of these standardized ECGs were used to assess performance of readers from the central laboratory.

Results: All experts had mean absolute Z-scores ≤ 1.5. Using this cutoff, one of 28 experienced readers and 7 of 15 trainees had unacceptable Z-scores. After re-training, all achieved Z-scores <1.5. Comparing histograms of actual Z-scores of the 100 ECGs of readers with unacceptable scores with that of the reader with the best Z-score showed two patterns. Readers with histograms having a peak and tails similar to that of the best reader, but with leftward or rightward shift, consistently made shorter or longer QT measurements, respectively. A histogram with a flatter peak and wider tails, suggested that measurements were long in some ECGs and short in others.

Conclusion: Mean absolute Z-score is useful to assess competence for measuring the QT interval on ECGs. Analysis of histograms can pinpoint problems in QT measurements.