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BMC Medical Informatics and Decision Making
Published in: BMC Medical Informatics and Decision Making 1/2020

01-12-2020 | Research article

Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice

Authors: Florine A. Berger, Heleen van der Sijs, Matthijs L. Becker, Teun van Gelder, Patricia M. L. A. van den Bemt

Published in: BMC Medical Informatics and Decision Making | Issue 1/2020

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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.
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Metadata
Title
Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice
Authors
Florine A. Berger
Heleen van der Sijs
Matthijs L. Becker
Teun van Gelder
Patricia M. L. A. van den Bemt
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medical Informatics and Decision Making / Issue 1/2020
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-020-01181-3

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