ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1529923
Mining and evaluation of security alert signals of neuroprotective agents based on the Jinan adverse event reporting system database: a retrospective study
Provisionally accepted
- Shandong Provincial Third Hospital, Jinan, China
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Background: Pharmacologic agents with proposed neuroprotective properties are increasingly under investigation; however, limited regulation and heterogeneous evidence raise concerns about their safety profiles. To establish a foundation for its safe clinical use, data mining technology was used to investigate the safety warning signals of neuroprotective agent post-market approval.The Jinan adverse event (AE) reporting system database was searched for AEs related to neuroprotective agents within the timeframe from January 2000 to March 2022. Basic information pertaining to patients, reports, and common AEs was analyzed. Subgroup analyses were performed to examine the distribution of adverse (PRR), reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and the Medicines and Healthcare products Regulatory Agency (MHRA) were applied to obtain alert signals for this class of drugs. We further examined the presence of the detected signals on the labels of medicines in China and two developed countries (USA and Japan).Results: In total, 168,314 AEs were reported, of which 2094 were associated with neuroprotective agents. Risk signals demonstrated significant variations across age groups, gender strata, and analyses with/without concomitant medication adjustments. For the following medications -citicoline sodium, troxerutin and cerebroprotein hydrolysate, vinpocetine, extract of Ginkgo biloba leaves, and cerebroprotein hydrolysate injection -50% of AEs occurred before the median time point. Using the PRR, ROR, MHRA, and BCPNN methods, 81, 57, and 68 signals were detected, respectively. Among the 81 signals, 30 AEs were not included on the drug labels of China. Of these, 11 AEs were not included on the drug labels of Japan; two AEs were included on the drug labels used in China but not Japan.The Jinan AE reporting system database for warning signal mining can be used to analyze AEs after the marketing of neuroprotective agents, thereby reducing the risk associated with their clinical use.
Keywords: security alert signals, Neuroprotective agents., Data Mining, Adverse event, Stroke
Received: 18 Dec 2024; Accepted: 14 Jul 2025.
Copyright: © 2025 Zheng, Guan, Yang, Qi and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lei Zheng, Shandong Provincial Third Hospital, Jinan, China
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