title: A new approach to correct the QT interval for changes in heart rate using a nonparametric regression model in beagle dogs.
abstract: BACKGROUND
  Over- and/or under-correction of QT intervals for changes in heart rate may lead to misleading conclusions and/or masking the potential of a drug to prolong the QT interval. This study examines a nonparametric regression model (Loess Smoother) to adjust the QT interval for differences in heart rate, with an improved fitness over a wide range of heart rates.
  
  
  METHODS
  240 sets of (QT, RR) observations collected from each of 8 conscious and non-treated beagle dogs were used as the materials for investigation. The fitness of the nonparametric regression model to the QT-RR relationship was compared with four models (individual linear regression, common linear regression, and Bazett's and Fridericia's correlation models) with reference to Akaike's Information Criterion (AIC). Residuals were visually assessed.
  
  
  RESULTS
  The bias-corrected AIC of the nonparametric regression model was the best of the models examined in this study. Although the parametric models did not fit, the nonparametric regression model improved the fitting at both fast and slow heart rates.
  
  
  CONCLUSIONS
  The nonparametric regression model is the more flexible method compared with the parametric method. The mathematical fit for linear regression models was unsatisfactory at both fast and slow heart rates, while the nonparametric regression model showed significant improvement at all heart rates in beagle dogs.
authors.affiliation: Biostatistics, Clinical Development Institute, Banyu Pharmaceutical Co., Ltd., AIG Kabutocho Building, 5-1, Nihombashi-Kabutocho, Chuo-ku, Tokyo 103-0026, Japan. hiroyuki_watanabe@merck.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Miyazaki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D016014:Linear Models; D008133:Long QT Syndrome / Q000503:physiopathology*; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000494:pharmacology; D008954:Models, Biological; D018709:Statistics, Nonparametric; D013686:Telemetry
chemical_list: D008747:Methylcellulose