Background variability in standard clinical pathology biomarkers in beagle dogs instrumented with chronic indwelling telemetry devices

Introduction: Contemporary best practice recommendations in preclinical cardiovascular safety assessment promote 3Rs principles. This includes the employment of within-subjects experimental designs to evaluate discrete, acute doses of investigational new drugs, as well as themaintenance of stock colonies of appropriate large animal test systems. Such colony species are often tested repeatedly on independent studies with provision of appropriate recovery periods and requisite health status evaluations (e. g., physical examinations, electrocardiographic assessments, clinical pathology evaluations). Methods: To investigate the utility of the often reiterative process of pre-or inter-study clinical pathology testing to help ascertain health status of non-naive, telemetered canines (beagle dogs), the present study collated the results of a randomly selected set of animals approximately every three months for a period of three years. Results: Although occasionally a few routine hematology or clinical chemistry endpoints did demonstrate evidence of systematic trending over time, none of the observed fluctuations fell outside the range of expected biological variability, nor would have prevented assignment of any given animal to study. Discussion: The present findings illustrate a high degree of consistency in routinely assessed clinical pathology parameters during the course of chronic telemetry instrumentation in the canine, including relative to historical control data in healthy, experimentally naive animals of the same species and source, maintained under analogous laboratory conditions. The data suggest that routine assessment of such parameters for the purposes of facilitating judgments concerning suitability for study may represent a pursuit of little overall value, and which may be reasonably accomplished based on alternative, observation-based screening procedures. (C) 2014 Elsevier Inc. All rights reserved.