The clinical trials puzzle: How network effects limit drug discovery

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. ar X iv :2 30 1. 10 70 9v 1 [ qbi o. Q M ] 2 5 Ja n 20 23