Prediction of Drug-Induced Long QT Syndrome Using Machine Learning Applied to Harmonized Electronic Health Record Data

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Abstract

Background:

Drug-induced QT prolongation is a potentially preventable cause of morbidity and mortality, however there are no widespread clinical tools utilized to predict which individuals are at greatest risk. Machine learning (ML) algorithms may provide a method for identifying these individuals, and could be automated to directly alert providers in real time.

Objective:

This study applies ML techniques to electronic health record (EHR) data to identify an integrated risk-prediction model that can be deployed to predict risk of drug-induced QT prolongation.

Methods:

We examined harmonized data from the UCHealth EHR and identified inpatients who had received a medication known to prolong the QT interval. Using a binary outcome of the development of a QTc interval >500 ms within 24 hours of medication initiation or no ECG with a QTc interval >500 ms, we compared multiple machine learning methods by classification accuracy and performed calibration and rescaling of the final model.

Results:

We identified 35,639 inpatients who received a known QT-prolonging medication and an ECG performed within 24 hours of administration. Of those, 4,558 patients developed a QTc > 500 ms and 31,081 patients did not. A deep neural network with random oversampling of controls was found to provide superior classification accuracy (F1 score 0.404; AUC 0.71) for the development of a long QT interval compared with other methods. The optimal cutpoint for prediction was determined and was reasonably accurate (sensitivity 71%; specificity 73%).

Conclusions:

We found that deep neural networks applied to EHR data provide reasonable prediction of which individuals are most susceptible to drug-induced QT prolongation. Future studies are needed to validate this model in novel EHRs and within the physician order entry system to assess the ability to improve patient safety.

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Most cited references 45

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Deep learning.

Yann LeCun, Yoshua Bengio, Geoffrey E Hinton (2015)

Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.

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SMOTE: Synthetic Minority Over-sampling Technique

N. Chawla, K. W. Bowyer, L Hall … (2002)

An approach to the construction of classifiers from imbalanced datasets is described. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ``normal'' examples with only a small percentage of ``abnormal'' or ``interesting'' examples. It is also the case that the cost of misclassifying an abnormal (interesting) example as a normal example is often much higher than the cost of the reverse error. Under-sampling of the majority (normal) class has been proposed as a good means of increasing the sensitivity of a classifier to the minority class. This paper shows that a combination of our method of over-sampling the minority (abnormal) class and under-sampling the majority (normal) class can achieve better classifier performance (in ROC space) than only under-sampling the majority class. This paper also shows that a combination of our method of over-sampling the minority class and under-sampling the majority class can achieve better classifier performance (in ROC space) than varying the loss ratios in Ripper or class priors in Naive Bayes. Our method of over-sampling the minority class involves creating synthetic minority class examples. Experiments are performed using C4.5, Ripper and a Naive Bayes classifier. The method is evaluated using the area under the Receiver Operating Characteristic curve (AUC) and the ROC convex hull strategy.