A Data-Driven Approach to Predicting Successes and Failures of Clinical Trials.

TitleA Data-Driven Approach to Predicting Successes and Failures of Clinical Trials.
Publication TypeJournal Article
Year of Publication2016
AuthorsGayvert KM, Madhukar NS, Elemento O
JournalCell Chem Biol
Date Published2016 Oct 20
KeywordsClinical Trials as Topic, Computational Biology, Drug Discovery, Drug-Related Side Effects and Adverse Reactions, Humans, Likelihood Functions, Models, Biological, Models, Molecular, Software

Over the past decade, the rate of drug attrition due to clinical trial failures has risen substantially. Unfortunately it is difficult to identify compounds that have unfavorable toxicity properties before conducting clinical trials. Inspired by the effective use of sabermetrics in predicting successful baseball players, we sought to use a similar "moneyball" approach that analyzes overlooked features to predict clinical toxicity. We introduce a new data-driven approach (PrOCTOR) that directly predicts the likelihood of toxicity in clinical trials. PrOCTOR integrates the properties of a compound's targets and its structure to provide a new measure, the PrOCTOR score. Drug target network connectivity and expression levels, along with molecular weight, were identified as important indicators of adverse clinical events. Our method provides a data-driven, broadly applicable strategy to identify drugs likely to possess manageable toxicity in clinical trials and will help drive the design of therapeutic agents with less toxicity.

Alternate JournalCell Chem Biol
PubMed ID27642066
PubMed Central IDPMC5074862
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 CA194547 / CA / NCI NIH HHS / United States