Search

Aims: Many clinical decision support systems trigger warning alerts for drug-drug interactions potentially leading to QT prolongation and torsades de pointes (QTDDIs). Unfortunately, there is overalerting and underalerting because stratification is only based on a fixed QT-DDI severity level. We aimed to improve QT-DDI alerting by developing and validating a risk prediction model considering patient- and drugrelated factors. Methods: We fitted 31 predictor candidates to a stepwise linear regression for 1000 bootstrap samples and selected the predictors present in 95% of the 1000 models. A final linear regression model with those variables was fitted on the original development sample (350 QT-DDIs). This model was validated on an external dataset (143 QT-DDIs). Both true QTc and predicted QTc were stratified into three risk levels (low, moderate and high). Stratification of QT-DDIs could be appropriate (predicted risk = true risk), acceptable (one risk level difference) or inappropriate (two risk levels difference). Results: The final model included 11 predictors with the three most important being use of antiarrhythmics, age and baseline QTc. Comparing current practice to the prediction model, appropriate stratification increased significantly from 37% to 54% appropriate QT-DDIs (increase of 17.5% on average [95% CI +5.4% to +29.6%], padj = 0.006) and inappropriate stratification decreased significantly from 13% to 1% inappropriate QT-DDIs (decrease of 11.2% on average [95% CI -17.7% to -4.7%], padj ≤ 0.001). Conclusion: The prediction model including patient- and drug-related factors outperformed QT alerting based on QT-DDI severity alone and therefore is a promising strategy to improve DDI alerting. [ABSTRACT FROM AUTHOR]

Ensemble modeling is an increasingly popular data science technique that combines the knowledge of multiple base learners to enhance predictive performance. In this paper, the idea was to increase predictive performance by holding out three algorithms when testing multiple classifiers: (a) the best overall performing algorithm (based on the harmonic mean of sensitivity and specificity (HMSS) of that algorithm); (b) the most sensitive model; and (c) the most specific model. This approach boils down to majority voting between the predictions of these three base learners. In this exemplary study, a case of identifying a prolonged QT interval after administering a drug-drug interaction with increased risk of QT prolongation (QT-DDI) is presented. Performance measures included accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Overall performance was measured by calculating the HMSS. Results show an increase in all performance measure characteristics compared to the original best performing algorithm, except for specificity where performance remained stable. The presented approach is fairly simple and shows potential to increase predictive performance, even without adjusting the default cut-offs to differentiate between high and low risk cases. Future research should look at a way of combining all tested algorithms, instead of using only three. Similarly, this approach should be tested on a multiclass prediction problem.