Charles River, Laval, Canada.
Lilly Corporate Center, Eli Lilly & Co, Indianapolis, IN, USA.
Int J Toxicol. 2020 Jul/Aug;39(4):274-293. doi: 10.1177/1091581820921338. Epub 2020 May 14.
The Safety Pharmacology Society (SPS) conducted a membership survey to examine industry practices related mainly to cardiovascular (CV) safety pharmacology (SP).
Questions addressed nonclinical study design, data analysis methods, drug-induced effects, and conventional and novel CV assays.
The most frequent therapeutic area targeted by drugs developed by the companies/institutions that employ survey responders was oncology. The most frequently observed drug-mediated effects included an increased heart rate, increased arterial blood pressure, hERG (I) block, decreased arterial blood pressure, decreased heart rate, QTc prolongation, and changes in body temperature. Broadly implemented study practices included Latin square crossover study design with n = 4 for nonrodent CV studies, statistical analysis of data (eg, analysis of variance), use of arrhythmia detection software, and the inclusion of data from all study animals when integrating SP studies into toxicology studies. Most responders frequently used individual animal housing conditions. Responders commonly evaluated drug effects on multiple ion channels, but in silico modeling methods were used much less frequently. Most responders rarely measured the J-T interval in CV studies. Uncertainties relative to Standard for Exchange of Nonclinical Data applications for data derived from CV SP studies were common. Although available, the use of human induced pluripotent stem cell cardiomyocytes remains rare. The respiratory SP study was rarely involved with identifying drug-induced functional issues. Responders indicated that the study-derived no observed effect level was more frequently determined than the no observed adverse effect level in CV SP studies; however, a large proportion of survey responders used neither.
安全药理学学会（SPS）进行了一次会员调查，以检查主要与心血管（CV）安全药理学（SP）相关的行业实践。
调查问题涉及非临床研究设计、数据分析方法、药物诱导作用以及常规和新型 CV 检测。
调查应答者所服务的公司/机构开发的药物针对的最常见治疗领域是肿瘤学。最常观察到的药物介导作用包括心率增加、动脉血压升高、hERG（I）阻断、动脉血压降低、心率降低、QTc 延长和体温变化。广泛实施的研究实践包括非啮齿类动物 CV 研究的 n = 4 拉丁方交叉研究设计、数据的统计分析（例如方差分析）、心律失常检测软件的使用以及将 SP 研究整合到毒理学研究中时整合所有研究动物的数据。大多数应答者经常使用单个动物饲养条件。应答者通常评估多种离子通道的药物作用，但很少使用计算建模方法。大多数应答者在 CV 研究中很少测量 J-T 间期。相对于从 CV SP 研究中获得的数据的非临床数据交换标准应用的不确定性很常见。尽管可用，但人类诱导多能干细胞心肌细胞的使用仍然很少。呼吸 SP 研究很少涉及识别药物诱导的功能问题。应答者表示，在 CV SP 研究中，更频繁地确定研究衍生的无观察效应水平，而不是无观察不良效应水平；然而，很大比例的调查应答者两者都不使用。
