1. RFP : 백신 이상반응 연구 및 안정성, 유효성 품질평가 기술개발

2. 해당분과 : 3-2-1 과제

3. 과제명 : 국가예방접종 대상 백신의 한국형 능동감시 시스템 구축

4. 연구책임자 : 최남경(이화여자대학교)

[Abstract]

BACKGROUND: The importance of identifying and evaluating adverse drug reactions (ADRs) has been widely recognized. Many studies have developed algorithms for ADR signal detection using electronic health record (EHR) data. In this study, we propose a machine learning (ML) model that enables accurate ADR signal detection by integrating features from existing algorithms based on inpatient EHR laboratory results.

MATERIALS AND METHODS: To construct an ADR reference dataset, we extracted known drug-laboratory event pairs represented by a laboratory test from the EU-SPC and SIDER databases. All possible drug-laboratory event pairs, except known ones, are considered unknown. To detect a known drug-laboratory event pair, three existing algorithms-CERT, CLEAR, and PACE-were applied to 21-year inpatient EHR data. We also constructed ML models (based on random forest, L1 regularized logistic regression, support vector machine, and a neural network) that use the intermediate products of the CERT, CLEAR, and PACE algorithms as inputs and determine whether a drug-laboratory event pair is associated. For performance comparison, we evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1-measure, and area under receiver operating characteristic (AUROC).

RESULTS: All measures of ML models outperformed those of existing algorithms with sensitivity of 0.593-0.793, specificity of 0.619-0.796, NPV of 0.645-0.727, PPV of 0.680-0.777, F1-measure of 0.629-0.709, and AUROC of 0.737-0.816. Features related to change or distribution of shape were considered important for detecting ADR signals.

CONCLUSIONS: Improved performance of ML models indicated that applying our model to EHR data is feasible and promising for detecting more accurate and comprehensive ADR signals.