title: Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with substantial heterogeneity in its clinical presentation. This makes diagnosis and effective treatment difficult, so better tools for estimating disease progression are needed. Here, we report results from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. In this crowdsourcing competition, competitors developed algorithms for the prediction of disease progression of 1,822 ALS patients from standardized, anonymized phase 2/3 clinical trials. The two best algorithms outperformed a method designed by the challenge organizers as well as predictions by ALS clinicians. We estimate that using both winning algorithms in future trial designs could reduce the required number of patients by at least 20%. The DREAM-Phil Bowen ALS Prediction Prize4Life challenge also identified several potential nonstandard predictors of disease progression including uric acid, creatinine and surprisingly, blood pressure, shedding light on ALS pathobiology. This analysis reveals the potential of a crowdsourcing competition that uses clinical trial data for accelerating ALS research and development.
authors.affiliation: 1] Institute of Bioinformatics and Systems Biology, German Research Center for Environmental Health, Munich, Germany. [2] Department of Informatics, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Küffner
authors.affiliation: Prize4Life, Tel Aviv, Israel and Cambridge, Massachusetts, USA.
authors.forename: Neta
authors.initials: N
authors.lastname: Zach
authors.affiliation: IBM T.J. Watson Research Center, Yorktown Heights, New York, USA.
authors.forename: Raquel
authors.identifier: 0000000177374172
authors.initials: R
authors.lastname: Norel
authors.affiliation: Department of Informatics, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Hawe
authors.affiliation: 1] MGH Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.affiliation: Sentrana Inc., Washington, DC, USA.
authors.forename: Liuxia
authors.initials: L
authors.lastname: Wang
authors.affiliation: Sentrana Inc., Washington, DC, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.affiliation: Latham&Watkins LLP, Silicon Valley, California, USA.
authors.forename: Lilly
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, USA.
authors.forename: Lester
authors.initials: L
authors.lastname: Mackey
authors.affiliation: Department of Neuroscience, Beaumont Hospital and Trinity College Dublin, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.affiliation: Neurological Clinical Research Institute, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.affiliation: Neurological Clinical Research Institute, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sherman
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch/Alzette, Luxembourg.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Ertaylan
authors.affiliation: Max Planck Institute for Intelligent Systems, Tübingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Grosse-Wentrup
authors.affiliation: Institute of Social- and Preventive Medicine, University of Zürich, Zürich, Switzerland.
authors.forename: Torsten
authors.initials: T
authors.lastname: Hothorn
authors.affiliation: Orca XL Problem Solvers, Amsterdam, the Netherlands.
authors.forename: Jules
authors.initials: J
authors.lastname: van Ligtenberg
authors.affiliation: Max Planck Institute for Biological Cybernetics and Bernstein Center for Computational Neuroscience, Tübingen, Germany.
authors.forename: Jakob H
authors.initials: JH
authors.lastname: Macke
authors.affiliation: Max Planck Institute for Intelligent Systems, Tübingen, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Max Planck Institute for Intelligent Systems, Tübingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schölkopf
authors.affiliation: Berkeley School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Linh
authors.initials: L
authors.lastname: Tran
authors.affiliation: Orca XL Problem Solvers, Amsterdam, the Netherlands.
authors.forename: Rubio
authors.initials: R
authors.lastname: Vaughan
authors.affiliation: IBM T.J. Watson Research Center, Yorktown Heights, New York, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
authors.affiliation: 1] Prize4Life, Tel Aviv, Israel and Cambridge, Massachusetts, USA. [2] ALS Innovation Hub, Biogen Idec, Cambridge, Massachusetts, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Leitner
mesh_terms: D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D002986:Clinical Trials as Topic; D063045:Crowdsourcing; D018450:Disease Progression; D006801:Humans