Imai Shungo, Takekuma Yoh, Kashiwagi Hitoshi, Miyai Takayuki, Kobayashi Masaki, Iseki Ken, Sugawara Mitsuru
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.
PLoS One. 2020 Jul 29;15(7):e0236789. doi: 10.1371/journal.pone.0236789. eCollection 2020.
Artificial neural networks are the main tools for data mining and were inspired by the human brain and nervous system. Studies have demonstrated their usefulness in medicine. However, no studies have used artificial neural networks for the prediction of adverse drug reactions. We aimed to validate the usefulness of artificial neural networks for the prediction of adverse drug reactions and focused on vancomycin -induced nephrotoxicity. For constructing an artificial neural network, a multilayer perceptron algorithm was employed. A 10-fold cross validation method was adopted for evaluating the resultant artificial neural network. In total, 1141 patients who received vancomycin at Hokkaido University Hospital from November 2011 to February 2019 were enrolled. Among these patients, 179 (15.7%) developed vancomycin -induced nephrotoxicity. The top three risk factors of vancomycin -induced nephrotoxicity which are relatively important in the artificial neural networks were average vancomycin trough concentration ≥ 13.0 mg/L and concomitant use of piperacillin-tazobactam and vasopressor drugs. The predictive accuracy of the artificial neural network was 86.3% and that of the multiple logistic regression model (conventional statistical method) was 85.1%. Moreover, area under the receiver operating characteristic curve (AUROC) of the artificial neural network was 0.83. In the 10-fold cross-validation, the accuracy obtained was 86.0% and AUROC was 0.82. The artificial neural network model predicting the vancomycin -induced nephrotoxicity showed good predictive performance. This appears to be the first report of the usefulness of artificial neural networks for an adverse drug reactions risk prediction model.
人工神经网络是数据挖掘的主要工具,其灵感来源于人类大脑和神经系统。研究已证明其在医学领域的实用性。然而,尚无研究将人工神经网络用于预测药物不良反应。我们旨在验证人工神经网络对药物不良反应预测的有效性,并聚焦于万古霉素诱导的肾毒性。为构建人工神经网络,采用了多层感知器算法。采用10折交叉验证法对所得人工神经网络进行评估。总共纳入了2011年11月至2019年2月在北海道大学医院接受万古霉素治疗的1141例患者。在这些患者中,179例(15.7%)发生了万古霉素诱导的肾毒性。在人工神经网络中相对重要的万古霉素诱导肾毒性的前三大危险因素是万古霉素平均谷浓度≥13.0mg/L、联合使用哌拉西林-他唑巴坦和血管升压药物。人工神经网络的预测准确率为86.3%,多重逻辑回归模型(传统统计方法)的预测准确率为85.1%。此外,人工神经网络的受试者工作特征曲线下面积(AUROC)为0.83。在10折交叉验证中,获得的准确率为86.0%,AUROC为0.82。预测万古霉素诱导肾毒性的人工神经网络模型显示出良好的预测性能。这似乎是关于人工神经网络用于药物不良反应风险预测模型有效性的首篇报道。