title: A Data-Driven Approach to Predicting Successes and Failures of Clinical Trials.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA; Institute for Precision Medicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY 10021, USA; Tri-Institutional Graduate Program on Computational Biology and Medicine (Cornell University in Ithaca, Weill Medical College of Cornell University, and Memorial Sloan-Kettering Cancer Center), New York, NY 10065, USA.
authors.forename: Kaitlyn M
authors.initials: KM
authors.lastname: Gayvert
authors.affiliation: Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA; Institute for Precision Medicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY 10021, USA; Tri-Institutional Graduate Program on Computational Biology and Medicine (Cornell University in Ithaca, Weill Medical College of Cornell University, and Memorial Sloan-Kettering Cancer Center), New York, NY 10065, USA.
authors.forename: Neel S
authors.initials: NS
authors.lastname: Madhukar
authors.affiliation: Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA; Institute for Precision Medicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY 10021, USA. Electronic address: ole2001@med.cornell.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
mesh_terms: D002986:Clinical Trials as Topic; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology; D006801:Humans; D016013:Likelihood Functions; D008954:Models, Biological; D008958:Models, Molecular; D012984:Software