Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation

BackgroundMachine learning offers new solutions for predicting life-threatening, unpredictable amiodarone-induced thyroid dysfunction. Traditional regression approaches for adverse-effect prediction without time-series consideration of features have yielded suboptimal predict...

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Main Authors: Ya-Ting Lu, Horng-Jiun Chao, Yi-Chun Chiang, Hsiang-Yin Chen
Format: Article
Language:English
Published: JMIR Publications 2023-02-01
Series:Journal of Medical Internet Research
Online Access:https://www.jmir.org/2023/1/e43734
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author Ya-Ting Lu
Horng-Jiun Chao
Yi-Chun Chiang
Hsiang-Yin Chen
author_facet Ya-Ting Lu
Horng-Jiun Chao
Yi-Chun Chiang
Hsiang-Yin Chen
author_sort Ya-Ting Lu
collection DOAJ
description BackgroundMachine learning offers new solutions for predicting life-threatening, unpredictable amiodarone-induced thyroid dysfunction. Traditional regression approaches for adverse-effect prediction without time-series consideration of features have yielded suboptimal predictions. Machine learning algorithms with multiple data sets at different time points may generate better performance in predicting adverse effects. ObjectiveWe aimed to develop and validate machine learning models for forecasting individualized amiodarone-induced thyroid dysfunction risk and to optimize a machine learning–based risk stratification scheme with a resampling method and readjustment of the clinically derived decision thresholds. MethodsThis study developed machine learning models using multicenter, delinked electronic health records. It included patients receiving amiodarone from January 2013 to December 2017. The training set was composed of data from Taipei Medical University Hospital and Wan Fang Hospital, while data from Taipei Medical University Shuang Ho Hospital were used as the external test set. The study collected stationary features at baseline and dynamic features at the first, second, third, sixth, ninth, 12th, 15th, 18th, and 21st months after amiodarone initiation. We used 16 machine learning models, including extreme gradient boosting, adaptive boosting, k-nearest neighbor, and logistic regression models, along with an original resampling method and 3 other resampling methods, including oversampling with the borderline-synthesized minority oversampling technique, undersampling–edited nearest neighbor, and over- and undersampling hybrid methods. The model performance was compared based on accuracy; Precision, recall, F1-score, geometric mean, area under the curve of the receiver operating characteristic curve (AUROC), and the area under the precision-recall curve (AUPRC). Feature importance was determined by the best model. The decision threshold was readjusted to identify the best cutoff value and a Kaplan-Meier survival analysis was performed. ResultsThe training set contained 4075 patients from Taipei Medical University Hospital and Wan Fang Hospital, of whom 583 (14.3%) developed amiodarone-induced thyroid dysfunction, while the external test set included 2422 patients from Taipei Medical University Shuang Ho Hospital, of whom 275 (11.4%) developed amiodarone-induced thyroid dysfunction. The extreme gradient boosting oversampling machine learning model demonstrated the best predictive outcomes among all 16 models. The accuracy; Precision, recall, F1-score, G-mean, AUPRC, and AUROC were 0.923, 0.632, 0.756, 0.688, 0.845, 0.751, and 0.934, respectively. After readjusting the cutoff, the best value was 0.627, and the F1-score reached 0.699. The best threshold was able to classify 286 of 2422 patients (11.8%) as high-risk subjects, among which 275 were true-positive patients in the testing set. A shorter treatment duration; higher levels of thyroid-stimulating hormone and high-density lipoprotein cholesterol; and lower levels of free thyroxin, alkaline phosphatase, and low-density lipoprotein were the most important features. ConclusionsMachine learning models combined with resampling methods can predict amiodarone-induced thyroid dysfunction and serve as a support tool for individualized risk prediction and clinical decision support.
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spelling doaj.art-24e53ed86f854e6cabc2746bb5bcfe892023-08-28T23:42:51ZengJMIR PublicationsJournal of Medical Internet Research1438-88712023-02-0125e4373410.2196/43734Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External ValidationYa-Ting Luhttps://orcid.org/0000-0001-5206-8021Horng-Jiun Chaohttps://orcid.org/0000-0002-6151-6946Yi-Chun Chianghttps://orcid.org/0000-0002-0083-2312Hsiang-Yin Chenhttps://orcid.org/0000-0001-5535-7152 BackgroundMachine learning offers new solutions for predicting life-threatening, unpredictable amiodarone-induced thyroid dysfunction. Traditional regression approaches for adverse-effect prediction without time-series consideration of features have yielded suboptimal predictions. Machine learning algorithms with multiple data sets at different time points may generate better performance in predicting adverse effects. ObjectiveWe aimed to develop and validate machine learning models for forecasting individualized amiodarone-induced thyroid dysfunction risk and to optimize a machine learning–based risk stratification scheme with a resampling method and readjustment of the clinically derived decision thresholds. MethodsThis study developed machine learning models using multicenter, delinked electronic health records. It included patients receiving amiodarone from January 2013 to December 2017. The training set was composed of data from Taipei Medical University Hospital and Wan Fang Hospital, while data from Taipei Medical University Shuang Ho Hospital were used as the external test set. The study collected stationary features at baseline and dynamic features at the first, second, third, sixth, ninth, 12th, 15th, 18th, and 21st months after amiodarone initiation. We used 16 machine learning models, including extreme gradient boosting, adaptive boosting, k-nearest neighbor, and logistic regression models, along with an original resampling method and 3 other resampling methods, including oversampling with the borderline-synthesized minority oversampling technique, undersampling–edited nearest neighbor, and over- and undersampling hybrid methods. The model performance was compared based on accuracy; Precision, recall, F1-score, geometric mean, area under the curve of the receiver operating characteristic curve (AUROC), and the area under the precision-recall curve (AUPRC). Feature importance was determined by the best model. The decision threshold was readjusted to identify the best cutoff value and a Kaplan-Meier survival analysis was performed. ResultsThe training set contained 4075 patients from Taipei Medical University Hospital and Wan Fang Hospital, of whom 583 (14.3%) developed amiodarone-induced thyroid dysfunction, while the external test set included 2422 patients from Taipei Medical University Shuang Ho Hospital, of whom 275 (11.4%) developed amiodarone-induced thyroid dysfunction. The extreme gradient boosting oversampling machine learning model demonstrated the best predictive outcomes among all 16 models. The accuracy; Precision, recall, F1-score, G-mean, AUPRC, and AUROC were 0.923, 0.632, 0.756, 0.688, 0.845, 0.751, and 0.934, respectively. After readjusting the cutoff, the best value was 0.627, and the F1-score reached 0.699. The best threshold was able to classify 286 of 2422 patients (11.8%) as high-risk subjects, among which 275 were true-positive patients in the testing set. A shorter treatment duration; higher levels of thyroid-stimulating hormone and high-density lipoprotein cholesterol; and lower levels of free thyroxin, alkaline phosphatase, and low-density lipoprotein were the most important features. ConclusionsMachine learning models combined with resampling methods can predict amiodarone-induced thyroid dysfunction and serve as a support tool for individualized risk prediction and clinical decision support.https://www.jmir.org/2023/1/e43734
spellingShingle Ya-Ting Lu
Horng-Jiun Chao
Yi-Chun Chiang
Hsiang-Yin Chen
Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
Journal of Medical Internet Research
title Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
title_full Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
title_fullStr Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
title_full_unstemmed Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
title_short Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation
title_sort explainable machine learning techniques to predict amiodarone induced thyroid dysfunction risk multicenter retrospective study with external validation
url https://www.jmir.org/2023/1/e43734
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