title: A cardiovascular monitoring system in conscious cynomolgus monkeys for regulatory safety pharmacology. Part 1: Non-pharmacological validation.
abstract: BACKGROUND
  This project addresses the validation study design of a test system using a telemetered non-human primate model for cardiovascular safety pharmacology evaluation.
  
  
  METHODS
  The validation provided by the supplier evaluated installation (IQ) and operation (OQ) qualifications. This protocol was completed with tests evaluating electronic data management and accuracy and precision of transmitter (n=4) measurements for temperature and pressure criteria with a series of tested values. As part of performance qualification, physical activity (for 24 h) as well as cardiovascular, ECG (20 complexes for each animal) and systemic arterial blood pressure (SAP, 10 different measures), data were recorded simultaneously from the same animals (n=4) using certified equipment and the telemetry system. Reliability was evaluated over 60 days.
  
  
  RESULTS
  The IQ and OQ were completed successfully. The electronic data management was performed successfully. The ex-vivo evaluation for temperature and pressure showed high correlation (R(2)>0.99) but with a slight pressure shift, as expected, with this transmitter model. For physical activity, the correlation coefficients were good to excellent with high activity counts but the comparison demonstrated a limited sensitivity of the telemetry system with animal presenting low activity levels. ECG interval measurement using the telemetry software was considered at least equivalent to manual measurement, but with some limitations in the reading of the ECG. The comparison between both methods of SAP measurement showed adequate precision (R(2)=0.969) but no accuracy.
  
  
  CONCLUSIONS
  Reference monitoring methods are important to ensure proper test system validation. Monitoring with a reference methodology and the telemetry system is important in order to evaluate precision and accuracy of the test system. Computerized analysis may lack the capability to analyze ECG complexes with abnormal morphologies. This reinforces the need to have ECG evaluation prior to telemetry implantation along with visual evaluation of ECG tracing at standard speed (e.g. 50 mm/s) at all time points.
authors.affiliation: LAB Research Inc., 445 Armand Frappier, Laval, Quebec, Canada. authiers@labresearch.com
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauvin
authors.forename: Rocky
authors.initials: R
authors.lastname: Di Fruscia
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fournier
authors.forename: Fernando
authors.initials: F
authors.lastname: Chaurand
authors.forename: Eric
authors.initials: E
authors.lastname: Troncy
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000295:instrumentation / Q000379:methods; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003243:Consciousness; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000295:instrumentation / Q000379:methods; D001330:Electronic Data Processing / Q000379:methods / Q000592:standards; D004582:Electronics, Medical / Q000295:instrumentation / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods*; D009043:Motor Activity / Q000187:drug effects; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods / Q000592:standards; D012984:Software; D013686:Telemetry / Q000295:instrumentation / Q000379:methods; D013696:Temperature