title: Computerized extraction of electrocardiograms from continuous 12-lead holter recordings reduces measurement variability in a thorough QT study.
abstract: Continuous Holter recordings are often used in thorough QT studies (TQTS), with multiple 10-second electrocardiograms (ECGs) visually selected around predesignated time points. The authors hypothesized that computer-automated ECG selection would reduce within-subject variability, improve study data precision, and increase study power. Using the moxifloxacin and placebo arms of a Holter-based crossover TQTS, the authors compared interval duration measurements (IDMs) from manually selected to computer-selected ECGs. All IDMs were made with a fully automated computer algorithm. Moxifloxacin-induced changes in baseline- and placebo-subtracted QT intervals were similar for manual and computer ECG selection. Mean 90% confidence intervals were narrower, and within-subject variability by mixed-model covariance was lower for computer-selected than for manual-selected ECGs. Computer ECG selection reduced the number of subjects needed to achieve 80% power by 40% to 50% over manual. Computer ECG selection returns accurate ddQTcF values with less measurement variability than manual ECG selection by a variety of metrics. This results in increased study power and reduces the number of subjects needed to achieve desired power, which represents a significant potential source cost savings in clinical drug trials.
authors.affiliation: NewCardio, Inc, 2350 Mission College Blvd, Suite 1175, Santa Clara, CA 95054, USA. sgeorge@newcardio.com
authors.forename: Samuel
authors.initials: S
authors.lastname: George
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rodriguez
authors.forename: David
authors.initials: D
authors.lastname: Ipe
authors.forename: Philip T
authors.initials: PT
authors.lastname: Sager
authors.forename: Ihor
authors.initials: I
authors.lastname: Gussak
authors.forename: Branislav
authors.initials: B
authors.lastname: Vajdic
mesh_terms: D000328:Adult; D000465:Algorithms; D000890:Anti-Infective Agents; D001372:Aza Compounds; D018592:Cross-Over Studies; D003936:Diagnosis, Computer-Assisted; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines; D012107:Research Design; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin