Enhanced detection sensitivity in nonclinical cardiovascular telemetry studies: Impact of a characterized facility

Abstract

In the context of a cardiovascular telemetry study, test facility characterization refers to the comprehensive assessment and description of the laboratory environment, equipment, procedures, and other relevant factors that could influence the outcomes and interpretation of the study. The goal is to ensure the integrity, reproducibility, and validity of telemetry data collected from implanted animals. Model verification, particularly regarding sensitivity analysis, is fundamental for ensuring the validity of these studies. In this investigation, we assessed the influence of transitioning to a purpose-built telemetry facility on model sensitivity, focusing on dofetilide-induced QT prolongation. Beagle dogs previously implanted with Data Sciences International ™ implants were relocated into a new facility, purpose built for telemetry studies. Following ICH E14/S7B guidelines, animals were administered dofetilide to induce QT prolongation. Sensitivity analysis, including the minimum detectable difference (MDD) and least significant difference (LSD) for the corrected QT interval (QTcI), was performed at both the previous facility and the newly established purpose-built facility. During baseline data collection, persistent signal dropout was observed in all animals resulting in data loss of ~20 % of total data collected. Troubleshooting steps included internal hardware and software diagnostics, battery assessment, and environmental assessments. The Received Signal Strength Indicator (RSSI) feature within the telemetry software was leveraged to pinpoint the source of interference. Data analysis revealed a consistent source of interference with an average strength of 30 (RSSI relative strength), coinciding with the operation of the facility's wireless security system (900 MHz), the same frequency band used for transmission and reception of telemetry data. Replacement of the security system with hardware operating at 433 MHz resulted in a negligible interference signal, with RSSI values averaging below 8, similar to previous facility values. An improvement in sensitivity at the purpose-built facility was observed. The MDD for QTcI prolongation was reduced to 6.2 ms, surpassing findings at previous facility (10.8 ms). Additionally, the LSD demonstrated enhanced sensitivity at the new facility (QTcI, 4.5 ms). Transitioning to a purpose-built telemetry facility has demonstrated tangible benefits in enhancing sensitivity. The optimized and characterized environment minimizes extraneous variables, enhancing the detection of QTcI prolongation induced by dofetilide.