Abstract

The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome. If current patterns persist, it would take 170 years to target all druggable proteins. We uncover two network-based fundamental mechanisms that currently limit target discovery: preferential attachment, leading to the repeated exploration of previously targeted proteins; and local network effects, limiting exploration to proteins interacting with highly explored proteins. We build on these insights to develop a quantitative network-based model of drug discovery. We demonstrate that the model is able to accurately recreate the exploration patterns observed in clinical trials. Most importantly, we show that a network-based search strategy can widen the scope of drug discovery by guiding exploration to novel proteins that are part of under explored regions in the human interactome.

Citation

Vasan K, Gysi D, Barabasi AL. The Clinical Trials Puzzle: How Network Effects Limit Drug Discovery. arXiv preprint arXiv:2301.10709. 2023 Jan 25.