Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice
Abstract Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | BMC Medical Informatics and Decision Making |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12911-020-01181-3 |
| _version_ | 1819159843100950528 |
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| author | Florine A. Berger Heleen van der Sijs Matthijs L. Becker Teun van Gelder Patricia M. L. A. van den Bemt |
| author_facet | Florine A. Berger Heleen van der Sijs Matthijs L. Becker Teun van Gelder Patricia M. L. A. van den Bemt |
| author_sort | Florine A. Berger |
| collection | DOAJ |
| description | Abstract Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. Methods A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden’s index were calculated. Results The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51–0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54–0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. Conclusions A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs. Trial registration No trial registration, MEC-2015-368. |
| first_indexed | 2024-12-22T16:46:59Z |
| format | Article |
| id | doaj.art-510aaaa02493400f90fca56dde66c0eb |
| institution | Directory Open Access Journal |
| issn | 1472-6947 |
| language | English |
| last_indexed | 2024-12-22T16:46:59Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Informatics and Decision Making |
| spelling | doaj.art-510aaaa02493400f90fca56dde66c0eb2022-12-21T18:19:43ZengBMCBMC Medical Informatics and Decision Making1472-69472020-07-0120111210.1186/s12911-020-01181-3Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practiceFlorine A. Berger0Heleen van der Sijs1Matthijs L. Becker2Teun van Gelder3Patricia M. L. A. van den Bemt4Department of Hospital Pharmacy, Erasmus MC, University Medical Center RotterdamDepartment of Hospital Pharmacy, Erasmus MC, University Medical Center RotterdamPharmacy Foundation of Haarlem HospitalsDepartment of Hospital Pharmacy, Erasmus MC, University Medical Center RotterdamDepartment of Hospital Pharmacy, Erasmus MC, University Medical Center RotterdamAbstract Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. Methods A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden’s index were calculated. Results The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51–0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54–0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. Conclusions A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs. Trial registration No trial registration, MEC-2015-368.http://link.springer.com/article/10.1186/s12911-020-01181-3Risk factorsROC curveDecision support systems, clinicalDrug interactionsSensitivity and specificity |
| spellingShingle | Florine A. Berger Heleen van der Sijs Matthijs L. Becker Teun van Gelder Patricia M. L. A. van den Bemt Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice BMC Medical Informatics and Decision Making Risk factors ROC curve Decision support systems, clinical Drug interactions Sensitivity and specificity |
| title | Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice |
| title_full | Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice |
| title_fullStr | Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice |
| title_full_unstemmed | Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice |
| title_short | Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice |
| title_sort | development and validation of a tool to assess the risk of qt drug drug interactions in clinical practice |
| topic | Risk factors ROC curve Decision support systems, clinical Drug interactions Sensitivity and specificity |
| url | http://link.springer.com/article/10.1186/s12911-020-01181-3 |
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