Ji-Hwan Bae1, Yeon-Hee Baek1, Jeong-Eun Lee1, Inmyung Song2, Jee-Hyong Lee3, Ju-Young Shin1,4. 1. School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea. 2. Department of Health Administration, College of Nursing and Health, Kongju National University, Gongju-si, South Korea. 3. Department of Artificial Intelligence, Sungkyunkwan University, Suwon-si, South Korea. 4. Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Jongno-gu, South Korea.
Abstract
Introduction: Various methods have been implemented to detect adverse drug reaction (ADR) signals. However, the applicability of machine learning methods has not yet been fully evaluated. Objective: To evaluate the feasibility of machine learning algorithms in detecting ADR signals of nivolumab and docetaxel, new and old anticancer agents. Methods: We conducted a safety surveillance study of nivolumab and docetaxel using the Korea national spontaneous reporting database from 2009 to 2018. We constructed a novel input dataset for each study drug comprised of known ADRs that were listed in the drug labels and unknown ADRs. Given the known ADRs, we trained machine learning algorithms and evaluated predictive performance in generating safety signals of machine learning algorithms (gradient boosting machine [GBM] and random forest [RF]) compared with traditional disproportionality analysis methods (reporting odds ratio [ROR] and information component [IC]) by using the area under the curve (AUC). Each method then was implemented to detect new safety signals from the unknown ADR datasets. Results: Of all methods implemented, GBM achieved the best average predictive performance (AUC: 0.97 and 0.93 for nivolumab and docetaxel). The AUC achieved by each method was 0.95 and 0.92 (RF), 0.55 and 0.51 (ROR), and 0.49 and 0.48 (IC) for respective drug. GBM detected additional 24 and nine signals for nivolumab and 82 and 76 for docetaxel compared to ROR and IC, respectively, from the unknown ADR datasets. Conclusion: Machine learning algorithm based on GBM performed better and detected more new ADR signals than traditional disproportionality analysis methods.
Introduction: Various methods have been implemented to detect adverse drug reaction (ADR) signals. However, the applicability of machine learning methods has not yet been fully evaluated. Objective: To evaluate the feasibility of machine learning algorithms in detecting ADR signals of nivolumab and docetaxel, new and old anticancer agents. Methods: We conducted a safety surveillance study of nivolumab and docetaxel using the Korea national spontaneous reporting database from 2009 to 2018. We constructed a novel input dataset for each study drug comprised of known ADRs that were listed in the drug labels and unknown ADRs. Given the known ADRs, we trained machine learning algorithms and evaluated predictive performance in generating safety signals of machine learning algorithms (gradient boosting machine [GBM] and random forest [RF]) compared with traditional disproportionality analysis methods (reporting odds ratio [ROR] and information component [IC]) by using the area under the curve (AUC). Each method then was implemented to detect new safety signals from the unknown ADR datasets. Results: Of all methods implemented, GBM achieved the best average predictive performance (AUC: 0.97 and 0.93 for nivolumab and docetaxel). The AUC achieved by each method was 0.95 and 0.92 (RF), 0.55 and 0.51 (ROR), and 0.49 and 0.48 (IC) for respective drug. GBM detected additional 24 and nine signals for nivolumab and 82 and 76 for docetaxel compared to ROR and IC, respectively, from the unknown ADR datasets. Conclusion: Machine learning algorithm based on GBM performed better and detected more new ADR signals than traditional disproportionality analysis methods.
Authors: Muhammad Imran; Aasia Bhatti; David M King; Magnus Lerch; Jürgen Dietrich; Guy Doron; Katrin Manlik Journal: Drug Saf Date: 2022-05-17 Impact factor: 5.228