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Updated: Jan 28, 2026

In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Comment on Iacobescu et al. Evaluating Binary Classifiers for Cardiovascular Disease Prediction: Enhancing Early
Mohamed Eltawil1, Laura Byham-Gray2, Yuane Jia3
1Department of Health Informatics, School of Health Professions, Rutgers University, Newark, NJ 07107, USA.
None:
Machine learning is increasingly applied to cardiovascular disease prediction yet reported performance metrics often appear implausibly high due to methodological errors. Recent work has reported nearly perfect predictive accuracy (≈99%) using a k-Nearest Neighbors (kNN) model on CDC heart-disease data. Such performance greatly exceeds typical BRFSS-based benchmarks and strongly indicates data leakage. In this commentary, we replicate and re-analyze the original workflow, showing that the authors applied the SMOTE-ENN resampling method prior to the train/test split, thereby allowing synthetic data generated from the full dataset to contaminate the test set. Combined with an excessively small neighborhood parameter (k = 2), this produced misleadingly high accuracy. It is noted that (1) with SMOTE-ENN performed globally, synthetic samples appear nearly identical to test points, leading to near-perfect classification, and (2) this kNN choice is unusually small for a dataset of this scale and further amplifies leakage bias. Correcting the workflow by restricting oversampling to the training data or using undersampling restores realistic results, reducing predictive accuracy to approximately 80%, confirming the inflation caused by pre-split resampling and aligning with literature norms. This case underscores the critical importance of rigorous validation, transparent reporting, and leakage-free pipelines in medical AI. We outline practical guidelines for avoiding such pitfalls and ensuring reproducible, realistic, and clinically reliable machine-learning studies.
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