In order to reduce the financial and human cost of clinical trial failure due to adverse events we have studied a method of using inexpensive bioassays to predict adverse event risks in clinical trials. The connection of hERG inhibition to cardiac risk is well known, but there may be other proteins with equal risk for other events. We used data from FDA submissions to classify each approved drug has having or not having each reported adverse event at the therapeutic dose. We then analyzed all bioactivities reported in journals and patents for each approved drug and classified each drug as binding or non-binding for each bioassay target. Finally, we created 2x2 contingency tables for each target/event combination and used statistical metrics of the association to find bioactivities strongly related to clinical events. Selected target/event relationships were then studied with pathway analysis to better understand the role of the target in the adverse event. This promises to be an efficient method to better understand pathways involved in toxicities, and better understand risks implied by specific bioactivities.

Towards the use of bioassays as predictors of adverse events in clinical trials

254th National Meeting (2017)

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