Analysis

Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression

  • Nature Biotechnology volume 33, pages 5157 (2015)
  • doi:10.1038/nbt.3051
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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.

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Acknowledgements

We are grateful to the following people for their important assistance with this manuscript: the pharmaceutical companies which provided data to the PRO-ACT data set that enabled this entire endeavor, the Bowen family and D. Lautman for their generous support for this project, R. Betensky from the Harvard School of Public Health for her statistical advice and contributions to the earliest stage of developing the challenge, L. Reinhold from InnoCentive for her support and management of the challenge, our challenge sponsors, Nature, The Economist and Popular Science, the clinicians who participated in the clinicians' assessment and follow-on discussions about the results, L.A. White and D. Kerr from Biogen Idec for their assistance with estimating the financial impact of the algorithms and, of course, the solvers who participated in the challenge and the patients who inspired this effort.

Author information

Author notes

    • Robert Küffner
    •  & Neta Zach

    These authors contributed equally to this work.

Affiliations

  1. Institute of Bioinformatics and Systems Biology, German Research Center for Environmental Health, Munich, Germany.

    • Robert Küffner
  2. Department of Informatics, Ludwig-Maximilians-University, Munich, Germany.

    • Robert Küffner
    •  & Johann Hawe
  3. Prize4Life, Tel Aviv, Israel and Cambridge, Massachusetts, USA.

    • Neta Zach
    •  & Melanie L Leitner
  4. IBM T.J. Watson Research Center, Yorktown Heights, New York, USA.

    • Raquel Norel
    •  & Gustavo Stolovitzky
  5. MGH Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • David Schoenfeld
  6. Harvard Medical School, Charlestown, Massachusetts, USA.

    • David Schoenfeld
  7. Sentrana Inc., Washington, DC, USA.

    • Liuxia Wang
    •  & Guang Li
  8. Latham&Watkins LLP, Silicon Valley, California, USA.

    • Lilly Fang
  9. Department of Statistics, Stanford University, Stanford, California, USA.

    • Lester Mackey
  10. Department of Neuroscience, Beaumont Hospital and Trinity College Dublin, Dublin, Ireland.

    • Orla Hardiman
  11. Neurological Clinical Research Institute, Massachusetts General Hospital, Charlestown, Massachusetts, USA.

    • Merit Cudkowicz
    •  & Alexander Sherman
  12. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch/Alzette, Luxembourg.

    • Gokhan Ertaylan
  13. Max Planck Institute for Intelligent Systems, Tübingen, Germany.

    • Moritz Grosse-Wentrup
    • , Timm Meyer
    •  & Bernhard Schölkopf
  14. Institute of Social- and Preventive Medicine, University of Zürich, Zürich, Switzerland.

    • Torsten Hothorn
  15. Orca XL Problem Solvers, Amsterdam, the Netherlands.

    • Jules van Ligtenberg
    •  & Rubio Vaughan
  16. Max Planck Institute for Biological Cybernetics and Bernstein Center for Computational Neuroscience, Tübingen, Germany.

    • Jakob H Macke
  17. Berkeley School of Public Health, University of California, Berkeley, California, USA.

    • Linh Tran
  18. ALS Innovation Hub, Biogen Idec, Cambridge, Massachusetts, USA.

    • Melanie L Leitner

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Contributions

R.K., N.Z., R.N., J.H., D.S., O.H., M.C., G.S. and M.L.L. designed the challenge. R.K. and J.H. prepared the data and baseline algorithm, A.S. helped with data preparation. N.Z. managed the challenge. L.W., G.L., L.F., L.M., G.E., M.G.-W., T.H., J.v.L., J.H.M., T.M., B.S., L.T. and R.V. submitted algorithms. D.S., L.W., G.L., L.F. and L.M. contributed further analysis on challenge performance. R.K. and N.Z. analyzed the results and wrote the paper.

Competing interests

R.N. and G.S. are employees of IBM; L.F. is an employee of Latham&Watkins; R.V. is an employee of Orca XL Problem Solvers; M.L.L. is an employee of Biogen Idec; L.W. and G.L. are employees of Sentrana.

Corresponding authors

Correspondence to Robert Küffner or Neta Zach.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–13, Supplementary Tables 1–10, Supplementary Notes 1–3, Supplementary Results 1–5 and Supplementary Data 1

Zip files

  1. 1.

    Supplementary Software

    Algorithms participating

  2. 2.

    Supplementary Predictions

    Predictions made by algorithms participating