Predicting clinical trial outcomes using drug bioactivities through graph database integration and machine learning

Abstract The ability to estimate the probability of a drug to receive approval in clinical trials provides natural advantages to optimizing pharmaceutical research workflows. Success rates of clinical trials have deep implications for costs, duration of development, and under pressure due to stringent regulatory approval processes. We propose a machine learning approach that can predict the outcome of the trial with reliable accuracies, using biological activities, physicochemical properties of the compounds, target‐related features, and NLP‐based compound representation. In the above list, biological activities have never been used as an independent variable towards the prediction of clinical trial outcomes. We have extracted the drug–disease pair from clinical trials and mapped target(s) to that pair using multiple data sources. Empirical results demonstrate that ensemble learning outperforms independently trained, small‐data ML models. We report results and inferences derived from a Random forest classifier with an average accuracy of 93%, and an F1 score of 0.96 for the “Pass” class. “Pass” refers to one of the two classes (Pass/Fail) of all clinical trials, and the model performed well in predicting the “Pass” category. Through the analysis of feature contributions to predictive capability, we have demonstrated that bioactivity plays a statistically significant role in predicting clinical trial outcome. A significant effort has gone into the production of the dataset that, for the first time, integrates clinical trial information with protein targets. Cleaned, organized, integrated data and code to map these entities, created as a part of this work, are available open‐source. This reproducibility and the freely available code ensure that researchers with access to deep curated and proprietary clinical trial databases (we only use open‐source data in this study) can further expand the scope of the results.