Detecting drug-induced changes in ECG parameters using jacketed telemetry: Effect of different data reduction techniques

doi:10.1016/j.vascn.2016.12.004

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	Detecting drug-induced changes in ECG parameters using jacketed telemetry: Effect of different data reduction techniques
	Skinner, Matthew 3; Xing, Guozhen 1; Lu, Jing 1; Ren, Jin1 ; Oldman, Karen 2
刊名	JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
	2017-05
卷号	85 页码:38-48
关键词	Data reduction Electrocardiogram Heart rate Methods Moxifloxacin Non-human primate Non-invasive telemetry QT interval Safety pharmacology Super-interval
ISSN号	1056-8719
DOI	10.1016/j.vascn.2016.12.004
文献子类	Article
英文摘要	Introduction: Continuous cardiovascular data is routinely collected during preclinical safety assessment of new medicines. This generates large datasets, which must be summarised to analyse and interpret drug effects. We assessed four methods of data reduction of continuous electrocardiogram (ECG) data and examined the impact on the statistical power of the assay. Methods: Continuous ECG data were collected from a validation study in 6 cynomolgus monkeys using jacketed telemetry. Animals received either vehicle or vehicle followed by ascending doses of moxifloxacin each on a different dosing day. Recordings made for 25 h on each dosing day were reduced to discrete time-points using: 1-min average snapshots, 15-min average snapshots, large duration averages (0.5-4 h) or super-intervals (3.5-9 h averages). Results: There was no difference in the ability to detect moxifloxacin-induced QTc prolongation between the 1- and 15-min snapshots and the large duration averages data reduction methods (minimum detectable change in QTca of 20, 17 and 18 ms, respectively at 80% power). The super-intervals method detected slightly smaller changes in QTc (15 ms), but did not detect a statistically significant increase in QTc after the lowest dose of moxifloxacin, in contrast to the other methods. There were fewer statistically significant differences between dosing days in animals given vehicle when the large duration averages and super-interval reduction techniques were used. Discussion: There is no marked difference in the power of detection of drug-induced ECG changes in cynomolgus monkeys when using either small duration average or large duration average data reduction techniques. Use of larger duration averages or super-intervals may facilitate data interpretation by reducing the incidence of spurious significant differences that occur by chance between dosing days. (C) 2017 Elsevier Inc. All rights reserved.
WOS关键词	QT INTERVAL PROLONGATION ; SAFETY PHARMACOLOGY ; CYNOMOLGUS MONKEYS ; CONSORTIUM ; DOG
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000405993600004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272674]
专题	药物安全性评价中心
通讯作者	Skinner, Matthew
作者单位	1.Chinese Acad Sci, CDSER, State Key Lab New Drug Res, SIMM, Haike Rd 501, Shanghai 201203, Peoples R China; 2.AstraZeneca R&D, Discovery Sci Stat, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England 3.AstraZeneca R&D, Dept Safety & Metab, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England;
推荐引用方式 GB/T 7714	Skinner, Matthew,Xing, Guozhen,Lu, Jing,et al. Detecting drug-induced changes in ECG parameters using jacketed telemetry: Effect of different data reduction techniques[J]. JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS,2017,85:38-48.
APA	Skinner, Matthew,Xing, Guozhen,Lu, Jing,Ren, Jin,&Oldman, Karen.(2017).Detecting drug-induced changes in ECG parameters using jacketed telemetry: Effect of different data reduction techniques.JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS,85,38-48.
MLA	Skinner, Matthew,et al."Detecting drug-induced changes in ECG parameters using jacketed telemetry: Effect of different data reduction techniques".JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS 85(2017):38-48.