Anomaly Detection Algorithm for Real-World Data and Evidence in Clinical Research: Implementation, Evaluation, and Validation Study

Background: Statistical analysis, which has become an integral part of evidence-based medicine, relies heavily on data quality that is of critical importance in modern clinical research. Input data are not only at risk of being falsified or fabricated, but also at risk of being mishandled by investigators. Objective: The urgent need to assure the highest data quality possible has led to the implementation of various auditing strategies designed to monitor clinical trials and detect errors of different origin that frequently occur in the field. The objective of this study was to describe a machine learning-based algorithm to detect anomalous patterns in data created as a consequence of carelessness, systematic error, or intentionally by entering fabricated values. Methods: A particular electronic data capture (EDC) system, which is used for data management in clinical registries, is presented including its architecture and data structure. This EDC system features an algorithm based on machine learning designed to detect anomalous patterns in quantitative data. The detection algorithm combines clustering with a series of 7 distance metrics that serve to determine the strength of an anomaly. For the detection process, the thresholds and combinations of the metrics were used and the detection performance was evaluated and validated in the experiments involving simulated anomalous data and real-world data. Results: Five different clinical registries related to neuroscience were presented-all of them running in the given EDC system. Two of the registries were selected for the evaluation experiments and served also to validate the detection performance on an independent data set. The best performing combination of the distance metrics was that of Canberra, Manhattan, and Mahalanobis, whereas Cosine and Chebyshev metrics had been excluded from further analysis due to the lowest performance when used as single distance metric-based classifiers. Conclusions: The experimental results demonstrate that the algorithm is universal in nature, and as such may be implemented in other EDC systems, and is capable of anomalous data detection with a sensitivity exceeding 85%.