Supervised Machine Learning-Based Decision Support for Signal Validation Classification.

introductionSignal validation in pharmacovigilance is the process of evaluating data to decide whether evidence is sufficient to justify further assessment of a detected signal. During the signal validation process, safety experts in our organization are required to review signals of disproportionate reporting (SDRs) and classify them into one of six predefined categories.

objectiveThis experiment explored the extent to which predictive machine learning (ML) models can support the decision making of safety experts by accurately identifying the most appropriate predefined signal validation category.

methodsWe extracted cumulative data for six medicinal products, consisting of historic SDR validations and Individual Case Safety Reports, from the company's safety database for training and testing of the ML model. We implemented a decision tree-based supervised multiclass classifier model termed Gradient Boosted Trees followed by a SHapley Additive exPlanations (SHAP) analysis to mitigate the "black box" effect of the ensemble model by identifying the key predicting features in the model. Following a retrospective analysis, a prospective experiment was conducted to test the model accuracy and user acceptance in a real-life setting.

resultsThe prediction accuracy of our ML model ranged from 83 to 86% over 3 months for the six medicinal products. The applicability of the model was confirmed by the company's safety experts. Additionally, the systematic predictions provided valuable information to the safety experts and assisted them in reviewing the SDRs efficiently and consistently.

conclusionsThis experiment demonstrated that it is possible to train a multiclass classification model to accurately predict signal validation categories for SDRs. More importantly, the transparency of the predictions provided by the SHAP analysis led to high acceptance by the safety experts.