Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events
ABSTRACT Evaluating clinical relevance of potential drug–drug interactions is significant for managing safety risks. However, current approaches to the evaluation lack data on rare but serious adverse events. This study aims to develop an approach to assessing clinical relevance of potential drug–dr...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70253 |
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| author | Menghuan Song Hui Zhou Zhirong Yang Yunfeng Lai Carolina Oi Lam Ung Hao Hu |
| author_facet | Menghuan Song Hui Zhou Zhirong Yang Yunfeng Lai Carolina Oi Lam Ung Hao Hu |
| author_sort | Menghuan Song |
| collection | DOAJ |
| description | ABSTRACT Evaluating clinical relevance of potential drug–drug interactions is significant for managing safety risks. However, current approaches to the evaluation lack data on rare but serious adverse events. This study aims to develop an approach to assessing clinical relevance of potential drug–drug interactions that induce rare and serious adverse events, and test its performance. In the development, three key dimensions for evaluating clinical relevance were synthesized based on a literature review. A systematic five‐step approach was proposed through designated dimensions and discussions within the research team. Subsequently, the approach was applied to patients with depression to validate its ability of demonstrating the dimensions, and exacting data on rare but serious adverse events. The test results showed varying signal intensities among different drug combinations in relation to adverse events including serotonin syndrome, long QT syndrome, and Torsade de Pointes. Advanced age was identified as a confounding factor for the QT prolongation signal. These findings operationalize Dimension one: Probabilities and risk factors for the occurrence of rare and serious adverse events. Besides, in the test, fatality occurred in 22.01% of the cases having drug‐triggered QT prolongation. Advancing age was associated with the fatality (odds ratio = 1.03, 95% confidence interval = 1.01–1.07). The findings manifested Dimension two: Magnitude of adverse events and associated factors. Dimension three was achieved by findings of median time‐to‐onset of fatal serotonin syndrome and QT prolongation, which was one and 8 days, respectively. In summary, the proposed approach demonstrates effects in assessing the clinical relevance of potential drug–drug interactions. |
| format | Article |
| id | doaj-art-c23f4d594a5e4068bc2c6a8e81da96b1 |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-c23f4d594a5e4068bc2c6a8e81da96b12025-08-20T03:54:11ZengWileyClinical and Translational Science1752-80541752-80622025-05-01185n/an/a10.1111/cts.70253Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse EventsMenghuan Song0Hui Zhou1Zhirong Yang2Yunfeng Lai3Carolina Oi Lam Ung4Hao Hu5State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade Taipa Macao Special Administrative Region ChinaDepartment of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Computational Biology and Medical Big Data Shenzhen University of Advanced Technology Shenzhen ChinaSchool of Public Health and Management Guangzhou University of Chinese Medicine Guangzhou Guangdong ChinaState Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade Taipa Macao Special Administrative Region ChinaState Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade Taipa Macao Special Administrative Region ChinaABSTRACT Evaluating clinical relevance of potential drug–drug interactions is significant for managing safety risks. However, current approaches to the evaluation lack data on rare but serious adverse events. This study aims to develop an approach to assessing clinical relevance of potential drug–drug interactions that induce rare and serious adverse events, and test its performance. In the development, three key dimensions for evaluating clinical relevance were synthesized based on a literature review. A systematic five‐step approach was proposed through designated dimensions and discussions within the research team. Subsequently, the approach was applied to patients with depression to validate its ability of demonstrating the dimensions, and exacting data on rare but serious adverse events. The test results showed varying signal intensities among different drug combinations in relation to adverse events including serotonin syndrome, long QT syndrome, and Torsade de Pointes. Advanced age was identified as a confounding factor for the QT prolongation signal. These findings operationalize Dimension one: Probabilities and risk factors for the occurrence of rare and serious adverse events. Besides, in the test, fatality occurred in 22.01% of the cases having drug‐triggered QT prolongation. Advancing age was associated with the fatality (odds ratio = 1.03, 95% confidence interval = 1.01–1.07). The findings manifested Dimension two: Magnitude of adverse events and associated factors. Dimension three was achieved by findings of median time‐to‐onset of fatal serotonin syndrome and QT prolongation, which was one and 8 days, respectively. In summary, the proposed approach demonstrates effects in assessing the clinical relevance of potential drug–drug interactions.https://doi.org/10.1111/cts.70253a systematic approachclinical relevanceDDIdepressionpharmacoepidemiologypharmacovigilance |
| spellingShingle | Menghuan Song Hui Zhou Zhirong Yang Yunfeng Lai Carolina Oi Lam Ung Hao Hu Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events Clinical and Translational Science a systematic approach clinical relevance DDI depression pharmacoepidemiology pharmacovigilance |
| title | Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events |
| title_full | Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events |
| title_fullStr | Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events |
| title_full_unstemmed | Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events |
| title_short | Development and Validation of an Approach to Assessing Clinical Relevance of Potential Drug–Drug Interactions Inducing Rare but Serious Adverse Events |
| title_sort | development and validation of an approach to assessing clinical relevance of potential drug drug interactions inducing rare but serious adverse events |
| topic | a systematic approach clinical relevance DDI depression pharmacoepidemiology pharmacovigilance |
| url | https://doi.org/10.1111/cts.70253 |
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