Clinical Trials In Healthy Subjects Research Articles

Quantitative Performance of E‐Scribe Warehouse in Detecting Quality Issues With Digital Annotated ECG Data From Healthy Subjects

The US Food and Drug Administration recommends submission of digital electrocardiograms in the standard HL7 XML format into the electrocardiogram warehouse to support preapproval review of new drug applications. The Food and Drug Administration scrutinizes electrocardiogram quality by viewing the annotated waveforms and scoring electrocardiogram quality by the warehouse algorithms. Part of the Food and Drug Administration warehouse is commercially available to sponsors as the E-Scribe Warehouse. The authors tested the performance of E-Scribe Warehouse algorithms by quantifying electrocardiogram acquisition quality, adherence to QT annotation protocol, and T-wave signal strength in 2 data sets: "reference" (104 digital electrocardiograms from a phase I study with sotalol in 26 healthy subjects with QT annotations by computer-assisted manual adjustment) and "test" (the same electrocardiograms with an intentionally introduced predefined number of quality issues). The E-Scribe Warehouse correctly detected differences between the 2 sets expected from the number and pattern of errors in the "test" set (except for 1 subject with QT misannotated in different leads of serial electrocardiograms) and confirmed the absence of differences where none was expected. E-Scribe Warehouse scores below the threshold value identified individual electrocardiograms with questionable T-wave signal strength. The E-Scribe Warehouse showed satisfactory performance in detecting electrocardiogram quality issues that may impair reliability of QTc assessment in clinical trials in healthy subjects.

Vagal response varies with valsalva maneuver technique: A repeated-measures clinical trial in healthy subjects

Study objective Variable success rates of the Valsalva maneuver in treatment of paroxysmal supraventricular tachycardia may be due to variations in performance technique. This study aimed to compare the magnitude of the vagal reflexes initiated by 5 variations of the Valsalva maneuver technique (supine, supine with epigastric pressure, supine with leg raise, semirecumbent position, and sitting position). Methods This was a single-blinded, repeated-measures, clinical trial of 65 subjects in sinus rhythm. Subjects performed each Valsalva maneuver technique 5 times in random order. The means of the longest ECG R-R intervals during the relaxation phase (postmaneuver R-R interval) and the postmaneuver pulse rates for each technique were compared. The mean differences between the pre- and postmaneuver R-R intervals for each technique were also compared. Results The supine with epigastric pressure and supine techniques resulted in longer mean postmaneuver R-R intervals (1.082 seconds [95% confidence interval (CI) 1.045 to 1.119 seconds] and 1.075 seconds [95% CI 1.035 to 1.114 seconds], respectively) than the leg raise, semirecumbent, and sitting position techniques (1.053 seconds [95% CI 1.019 to 1.086 seconds], 1.044 seconds [95% CI 1.006 to 1.081 seconds], and 1.024 seconds [95% CI 0.990 to 1.059 seconds], respectively), which equates to slower mean postmaneuver pulse rates for the supine with epigastric pressure and supine techniques (55.5 and 55.8 beats/min, respectively) than the leg raise, semirecumbent, and sitting position techniques (57.0, 57.5, and 58.6 beats/min, respectively). The supine with epigastric pressure and supine techniques also resulted in the largest premaneuver versus postmaneuver differences. Conclusion For healthy subjects in sinus rhythm, the supine with epigastric pressure and supine techniques generated stronger vagal responses, as measured by R-R intervals and pulse rates, than the other techniques examined. However, the vagal responses of these 2 techniques were similar, and the addition of epigastric pressure may confer little advantage.